The 5 Browns bring classical music to life in Beaver Creek
Vail, CO, Colorado
One would think that in a family of five kids ” three sisters and two brothers ” that sibling rivalries would be a must. Not so, according to Desirae Brown, the eldest of the classical piano act known as The 5 Browns. There are no battles to prove who among them is the best piano player, she said during a phone interview with all five members of the group.
“We’re all kind of working together now so it’s kind of to our benefit to really support each other, but even growing up it kind of felt like we understood each other,” Desirae said. “We supported each other, we understood what it was like to have a disappointing performance or get discouraged. So we kind of supported and respected one another. Even if all five of us played the same piece, we would play it five different ways so it’s more like a mutual respect rather than a competition.”
The 5 Browns are Desirae (29), Deondra (28), Gregory (26), Melody (24) and Ryan (23). The children of Mormon parents, each child started playing piano around the age of three and all five eventually attended the Julliard School in New York. Trained in classical piano, their repertoire ranges from Rachmaninoff to Chopin to Debussy and well beyond. Both of their albums ” “Browns In Blue” and “No Boundaries” ” went to No. 1 on the Billboard Classical charts. They’ve appeared on Oprah, 60 Minutes and The Tonight Show with Jay Leno, as well as toured the world; they just returned from a tour in China.
Saturday night at the Vilar Performing Arts Center in Beaver Creek, The 5 Browns will return to the stage with five pianos. They last played at the Vilar in 2006.
Dawn Poff, a Gypsum resident and piano teacher, said she and her family attended the show the last time The 5 Browns played at the Vilar and plan on being there Saturday night as well. As a piano player and teacher she knows firsthand the level of talent it takes to do what The 5 Browns do, she said.
“We love The 5 Browns,” Poff said. “They’re amazing. They do a great show. They’re very talented, they’re very entertaining.”
And for anyone worried that an evening of classical piano music might put them to sleep, Poff said forget about it.
“It’s not your typical classical piano show so it’s really amazing how they interact with each other (during) the pieces,” she said. “It’s very cool. It’s very lively.”
Though classically trained, the siblings often include elements of rock, Latin and jazz music into their performances, said Ryan, the youngest Brown. They even draw on contemporary artists like Coldplay, who Ryan said they are all big fans of.
“The energy that Chris Martin (of Coldplay) is able to put out while he’s onstage is incredible and we kind of try to take some of that into our own concerts,” Ryan said.
The 5 Browns group was born roughly five years ago, when the siblings were finishing school at Julliard.
“We all kind of came to the conclusion what better way to go out and share what we love than by doing it together,” Gregory said. “Things just sort of worked out after that decision and it kind of just snowballed.”
Since then they’ve had many classical pieces written for a five-piece arrangement, which makes for a broad and big sound when in concert.
“With five pianos it’s almost like the sections of an orchestra ” your options are that much greater,” Desirae said. “It’s fun for us to be able to play some of this repertoire that solo pianists in the past maybe would not have had a chance to play.”
It does seem kind of weird that all five siblings would want to play the same instrument, but according to Deondra, they’ve tried playing the violin, guitar and even the flute, but they all ended up coming back to their first love.
“We all kind of just felt like we were meant to play the piano. It was where we felt most comfortable in our creative voice and so we all kind of just stuck with that,” Deondra said.
High Life writer Charlie Owen can be reached at 970-748-2939 or firstname.lastname@example.org.
What: Classic piano sensations The 5 Browns.
When: Saturday night at 6:30 p.m.
Where: Vilar Performing Arts Center in Beaver Creek.
Cost: $60 or $75 depending on seating.
More information: Call 888-920-2787 or visit http://www.vilarpac.com.


text: Author/s Andres Barbosa* (1#), Erli Schneider Costa (2#), Meagan Dewar (3#), Daniel González-Acuña (4#), Rachael Gray (5#), Michelle Power (6#), Ralph Eric Thijl Vanstreels (7) (1) Museo Nacional de Ciencias Naturales, CSIC, Spain (2) Universidade Estadual do Rio Grande do Sul and APECS-Brazil, Brazil (3) Deakin University, APECS-Oceania, IPECS (International Penguin Early Career Scientists), Australia (4) Universidad de Concepción, Chile (5) The University of Sydney, Australia (6) Macquarie University, Australia (7) Universidade de São Paulo, Brazil # Working Group of Health Monitoring of Antarctic Bird and Marine Mammals (EGBAMM-SCAR) Brief Overview There have been relatively few wildlife mass mortality events reported in Antarctica that can be conclusively attributed to infectious disease. Climate change and increasing human activity in the region may increase both the risk of pathogen transmission and the frequency of mortality events. Information on the presence of pathogens and diseases in birds and marine mammals is limited and fragmented, being based on relatively few species and locations. Despite concerns about the introduction of non-endemic pathogens, structured Antarctic wildlife health surveillance programs have not been established, making it difficult to assess the implications of disease for conservation actions. To achieve a sound health surveillance program, long-term investigations are essential to identify both host species and monitoring locations to detect emergent pathogens, as well as to better characterise the viral, microbial and parasitic communities, both native and introduced, in Antarctica and their effects on host physiology, fitness and survival. Detailed Overview Infectious disease is one of the main causes of mortality in wild animals worldwide. Moreover, pathogens and parasites can cause sub-lethal effects to hosts, such as the reduction in reproductive output by physiological changes, which can in turn contribute to population decline. Infections can also interact with toxins (such as persistent organic pollutants) (1) increasing the host vulnerability to secondary infections from other pathogens and parasites, or reduce the ability of animals to accommodate to extreme environmental changes. Emerging infectious disease also presents a significant threat to populations, particularly when a species is unable to mount an effective immune response to novel pathogens with which it did not co-evolve. Antarctica is relatively isolated from other regions of the world, and communities of microorganisms there may differ from those of other regions of the planet. As a result, vertebrate species that inhabit the Antarctic environment may not have been exposed for long periods to many microorganisms (including pathogens) and, having not co-evolved with them, may now fail to produce an effective immune response if exposed. Another factor increasing the risk of a disease outbreak in Antarctic wildlife is that many bird and mammals live in dense aggregations which increase the probability of infectious disease transmission. However, the environmental conditions, particularly in terms of temperature and humidity, may render it very difficult for introduced microorganisms (or their invertebrate vectors/hosts) to thrive in this region. As a result, many pathogens, particularly those transmitted by vectors and those that have temperature/moisture thresholds for effective transmission, could have limited capability to disperse and cause disease outbreaks. Investigation of the health of Antarctic wildlife is therefore crucial to assessing the risk of disease outbreaks and pathogen introduction. Information relating to disease in Antarctic species, including causative agents, pathogenicity, prevalence and geographic range, is both limited and fragmented (2, 3, 4). Data from zoo animals, especially penguins, has, however, established their susceptibility to a wide range of diseases (2). Moreover, climate change is predicted to shift the global distribution of some pathogens and parasites (5). Climate change has already affected the distribution of some bird species and can affect the life cycle patterns and physiology of Antarctic birds and marine mammals, which could facilitate the exposure to pathogens or reduce the effectiveness of the immune response to infectious disease. Current knowledge of infectious diseases in Antarctic birds and marine mammals has been the subject of several reviews (2, 3,4). Here we focus on viruses, bacteria and protozoa due to their greater potential for outbreaks and host switching when compared to macroparasites (living both externally and internally on the animals) that can have more complex life cycles. A broad variety of pathogens and infectious diseases has been reported in seabirds in Antarctica and the Sub-Antarctic, either through direct evidence of infection or through serological evidence (Table 1). Table 1: Pathogens, and potential pathogenic microorganisms recorded in seabirds from the Antarctic (above 60ºS)(A) or Sub-Antarctic (below 60ºS)(S). References in square brackets. Direct evidence Serological evidence Viral Infectious Bursal Disease Virus (A)) , Influenza virus A (Low Pathogenic strains) (A)(S), Newcastle Disease Virus (A), Petrelpox Virus (A), Paramyxoviridae (A)(S) (unidentified strains)) Infectious Bursal Disease Virus (A)(S) , Influenza virus A (Low Pathogenic strains) (A) , Murray Valley Encephalitis Virus (S)[2,4], Newcastle Disease Virus (S)(A) , Flaviviridae (Kemerovo group, Sakhalin group, other unidentified strains) (S), other Flavirirus not identified (A), Adenovirus (Egg Drop Syndrome) (A) Bacterial Alcaligenes faecalis (A), Bacillus spp. (A), Campylobacter lari (A), Campylobacter jejuni (S), Chlamydophylla spp (A)[], Edwardsiella tarda (A), Erysipelothrix rhusiopathiae (S), Escherichia spp. (A), Enterococcus faecalis (A), Micrococcus sp. (A)), Pasteurella multocida (A,S), Plesiomonas shigelloides (S), Salmonella sp. (A), Staphylococcus saprophyticus (A), Streptococcus fecalis (A), Rickettsia-like organism (S) Borrelia burgdorferi sensu lato (S), Salmonella sp. (A), Chlamydophylla spp. (S), Clostridium sp. (A), Mycoplasma gallisepticum (A), Mycoplasma synoviae (A) Protozoal Cryptosporidium sp. (A), Eimeria pygosceli (A), Isospora sp. (A), Sarcocystis sp. (A), Hepatozoon albatrossi (S), Plasmodium (Haemamoeba) sp. (S) Unknown etiology Penguin feather-loss disorder (A) [6,7] Knowledge of infectious diseases in marine mammals is less extensive than for seabirds and is restricted to pinnipeds (8), with no information on cetaceans in the Southern Ocean. Salmonella has been described in numerous Antarctic pinniped species (9, 10), Cryptosporidium was detected in a single elephant seal faecal sample (11), and Sealpox Virus has been reported in a Weddell seal (3). The presence of antibodies against several pathogens has been demonstrated in pinnipeds in Antarctica and the Sub-Antarctic (Table 2). Table 2: Pathogens and potential pathogenic microorganisms recorded in marine mammals from the Antarctic (above 60ºS) (A) or Sub-Antarctic (below 60ºS) (S). References in square brackets. Direct evidence Serological evidence Viral Sealpox Virus (A) Canine Distemper Virus (A), Phocine Distemper Virus (A), Phocine Herpesvirus 1 (A,S) Bacterial Campylobacter sp. (A) , Salmonella sp. (A)[9,10], E. coli (A) Acinetobacter calco (S), Bordetella bronchispectica (S), Brucella sp. (A), Corynebacterium sp. (S), Moraxella phylpiruvica (S), Neisseria elongate (S), Proteus sp. (S) Protozoal Cryptosporidium sp. (A)  – Figure 1. Adélie penguin chick showing feather loss disease. This is a recently reported emergent disease affecting Adélie penguin chicks in Antarctic Peninsula and Ross Island. It should be noted though that the presence of antibodies in wildlife means that the animal was exposed to a microorganism and developed an immune response. It does not necessarily indicate that the microorganism caused disease in that individual. Mass mortality events are apparently unusual in Antarctica, which suggests that: a) disease outbreaks and health problems have posed a very low risk to Antarctic wildlife, and/or b) the effects of infectious diseases have been underestimated due to the scarcity of studies and lack of a systematic long-term surveillance for mortality events. To date, only eight recorded mortality events probably caused by diseases have been reported, mainly involving seabirds (Table 3). Table 3: Mass mortality events recorded in Antarctica region in seabirds and marine mammals. Species Description of the event (likely pathogen or disease) Location Reference Gentoo penguin (Pygoscelis papua) Several hundred in the late’ 60 (probably by a virus) Signy Island (60º 43’S 45º 36’W) 14 Adélie penguin (Pygoscelis adeliae) 65% of chicks in 1972 by (unknown) disease Mawson Coast (67º 35’S 62º 45’E) 15 King penguin (Aptenodytes patagonicus) 250-300 in 1992/1993 by (unknown) disease Marion Island (46º 52’S 37º 51’E) 16 Macaroni penguin (Eudyptes chrysolophus) 5000-10000 in 1993 (by conjunctivitis) Marion Island (46º 52’S 37º 51’E) 16 Yellow nose albatross (Thalassarche chlororhynchos) 31 chicks in 1995/1996 and unknown number in 1999 and 2000 (by Erysipelothrix rhusiopathidae, Pasteurella multocida) Amsterdam Island (37º 49’S 77º 33’ E) 17 Adélie penguin, kelp gull (Larus dominicanus), and skua (Catharacta sSp.) 86 birds in 1999/2000 and 2000/2001 (due to avian cholera) Hope Bay (63º 23’S 57º 00’W 18 Amsterdam albatross (Diomediea amsterdamensis) 66% and 74% chicks in 2000 and 2001 respectively (unknown disease) Amsterdam Island (37º 49’S 77º 33’ E) 17 Macaroni penguin (Eudyptes chrysolophus) 2000 in 2004 (due to avian cholera) Marion Island (46º 52’S 37º 51’E) 16 Crabeater seals (Lobodon carcinophagus) 3000 in 1955 (suspected by a virus) Crown Prince Gustav Channel (64º 00’S 57º 45’W) 19 However, in some cases it is difficult to attribute mortality directly to disease, as in the majority of circumstances, limited or no diagnostic investigations have been undertaken. The introduction of pathogens to Antarctic wildlife may arise from two main sources: a) migratory species that disperse over great distances between the Antarctic and other areas (20, 21) (for example, albatrosses, polar skuas, giant petrels, Arctic terns, elephant seals, Antarctic fur seals); or b) through human activity (scientific and associated logistic activities and tourism). Multiple pathways for the introduction of non-endemic species, including direct transport and inadequate management of waste and sewage from ships, research stations and field camps, have the potential to introduce micro-organisms (22). Introduction of novel pathogens through human activities must be one of the principal concerns for long-term conservation of the Antarctic ecosystem. Human presence has increased in the last decades with recent data (2013-2014) from IAATO and COMNAP showing that 37,405 tourists visited Antarctica and at least 4462 researchers plus logistics staff worked in the region in one year. Given the higher density of activities in the Antarctic Peninsula and Ross Sea regions, these areas could have the higher risk of novel pathogens introduction if the pathways are similar to those for the introduction of invasive plant propagules (23). Special attention also needs to be paid to the risk of anthropogenic spread of potential pathogens between locations within Antarctica. Monitoring the health of Antarctic wildlife is a necessary part of good environmental stewardship. Parties have previously recognised the importance of wildlife disease research and the importance of establishing co-ordinated international programmes of research and monitoring, as yet without success. Current knowledge on Antarctic wildlife diseases is limited to only a few research groups studying organisms in their areas of expertise, without any overall framework. This results in a bias towards disease-related information from small geographical regions or on a limited number of species, for example penguins in the South Shetland Islands, with little known or observed data for much of the continent. To address knowledge gaps in Antarctic wildlife health and disease status a working group for health monitoring of Antarctic species has been created within the SCAR Expert Group of Birds and Marine Mammals (EGBAMM). While there are existing tools to assess disease risks for wildlife, for Antarctic wildlife the fragmented and limited nature of available disease information makes their use impossible. Effective health monitoring encompassing long-term studies on a broader number of species and populations at selected sites, including ecological information on Antarctic wildlife, their pathogens and parasites, and resident microbiome, are all required to understand potential risks. The establishment of tissue banks would allow material to be reanalysed in future with new methods whilst the application of genomic techniques could substantially change our understanding of the pathogen/host interactions. Key Events 1964 Agreed Measures for the Conservation of Antarctic Flora and Fauna –initial recognition of the possibility of the accidental introductions of pathogens 1991 Protocol on Environmental Protection to the Antarctic Treaty – Annex II Article 4 and Appendix C and Annex III Article 2 specifically provides prohibitions on introductions of non-native species including viruses, bacteria, yeasts and fungi as well as directions on the treatment of sewage and wastes. 1998 Workshop on diseases of Antarctic wildlife in Australia http://www.ats.aq/documents/SATCM12/att/SATCM12_att002_e.pdf 2000 Introduction by IAATO of mandatory boot washing protocol for tourists. 2001 Report of Open-ended Contact Group on diseases of Antarctic Wildlife- review and risk assessment http://www.ats.aq/documents/ATCM24/wp/ATCM24_wp010_e.pdf 2007-2008 International Polar Year project number 172 BIRDHEALTH: Health of Arctic and Antarctic bird populations. 2007 Symposia on Health of Arctic and Antarctic birds in the 6th European Ornithologists Union in Vienna 2009 Publication of book Health of Antarctic Wildlife edited by KR Kerry and MJ Riddle. 2011 Revised Guidelines for Visitors Resolution 10 www.ats.aq/documents/ATCM34/att/ATCM34_att050_e.doc 2015 Workshop on microbial/parasite impacts on Antarctic wildlife, Sydney, Australia.

domain: geography


text:
Burien Police say that two local men recently stole a small outboard motor off of a Burien resident’s boat, then immediately posted it for sale on the app “OfferUp.”
An observant community member saw the ad and contacted police.
“Our master police officer coordinated with an undercover detective, who presented himself as a buyer,” police said. “The thieves arrived right on time to sell the motor and unknowingly presented it to the Burien Police Department.”
They were then arrested for their caper and the boat motor is now back with the owner.
“Shout out to Master Police Officer Price, Detective Cueva and Officer Luther for their work on this case!”

domain: news


text:
Back to Journals » International Journal of Nanomedicine » Volume 18
Copperphosphotungstate Doped Polyanilines Nanorods for GSH-Depletion Enhanced Chemodynamic/NIR-II Photothermal Synergistic Therapy
Authors Ye S, Xiao H, Chen J , Zhang D, Qi L, Peng T, Gao Y, Zhang Q, Qu J, Wang L, Liu R
Received 1 December 2022
Accepted for publication 14 February 2023
Published 12 March 2023 Volume 2023:18 Pages 1245—1257
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Dr Farooq A. Shiekh
Sheng Ye,1 Huichun Xiao,1 Jian Chen,1 Di Zhang,1 Li Qi,1 Ting Peng,2 Yanyang Gao,2 Qianbing Zhang,3 Jinqing Qu,2 Lei Wang,4 Ruiyuan Liu1
1Guangdong Provincial Key Laboratory of Medical Image Processing, School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China; 3Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 4College of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, China Three Gorges University, Yichang, People’s Republic of China
Correspondence: Jinqing Qu; Ruiyuan Liu, Email [email protected]; [email protected]
Introduction: The high concentration of glutathione (GSH) and hydrogen peroxide (H2O2) levels within the tumor microenvironment (TME) are the major obstacle to induce the unsatisfactory anticancer treatment efficiency. The synergistic cancer therapy strategies of the combination the GSH depletion enhanced chemodynamic therapy (CDT) with photothermal therapy (PTT) have been proved to be the promising method to significantly improve the therapeutic efficacy.
Methods: The copperphosphotungstate was incorporated into polyanilines to design copperphosphotungstate doped polyaniline nanorods ([email protected] Nanorods) via chemical oxidant polymerization of aniline. The low long-term toxicity and biocompatibility were evaluated. Both in vitro and in vivo experiments were carried out to confirm the GSH depletion enhanced CDT/NIR-II PTT synergistic therapy.
Results: [email protected] Nanorods feature biosafety and biocompatibility, strong NIR-II absorbance, and high photothermal-conversion efficiency (45.14%) in NIR-II bio-window, making them highly applicable for photoacoustic imaging and NIR-II PTT. Moreover, [email protected] Nanorods could consume endogenous GSH to disrupt redox homeostasis and perform a Fenton-like reaction with H2O2 to produce cytotoxic •OH for the enhanced CDT. Furthermore, NIR-II photothermal-induced local hyperthermia accelerates •OH generation to enhance CDT, which realizes high therapeutic efficacy in vivo.
Conclusion: This study provides a proof of concept of GSH-depletion augmented chemodynamic/NIR-II photothermal therapy.
Keywords: copperphosphotungstate, NIR-II absorption nanorods, NIR-II photothermal therapy, GSH depletion, chemodynamic therapy, synergistic therapy
Redox homeostasis, the balance between the generation and consumption of reactive oxygen species (ROS) in cells, is one of the most important intracellular physiological equilibriums for cell survival.1–3 ROS, including hydroxyl radicals (•OH), superoxide anions (•O2−), and singlet oxygen (1O2), play an essential role in tumorigenesis, tumor progression, metastasis, and tumor therapy.4–6 ROS modulate various cell signaling pathways, which are primarily mediated through the transcription factors NF-κB and STAT3, hypoxia-inducible factor-1α, kinases, growth factors, cytokines and other proteins, and enzymes; these pathways have been linked to inflammation, tumor survival, proliferation, invasion, angiogenesis, and metastasis of cancer.7–9 Nowadays, efficiently breaking the redox homeostasis to boost ROS generation has become the promising strategy for the anticancer treatment. However, due to the abnormalities of tumor tissues, H2O2 was overproduced, which is one of the most important sources of ROS and promotes tumor growth and metastasis.10,11 Moreover, a high concentration of glutathione (GSH, up to 10 mM) is observed in the tumor tissues, which is an important intracellular antioxidant to scavenge the cytotoxic ROS and keep the redox homeostasis.12,13 As a result, boosting ROS generation or depletion of GSH is the main approach to break redox homeostasis. For promotion of ROS production, chemodynamic therapy (CDT) exploits Fenton or Fenton-like reaction to convert endogenous H2O2 into highly toxic •OH for the elimination of tumor cells.14–16 For depletion of GSH, direct GSH oxidation,17 enhancing GSH efflux,18,19 and inhibiting GSH synthesis20,21 are the main strategies to break the redox balance and enhance the therapeutic effect. Therefore, the design and preparation of novel CDT nanomaterials, which could improve intracellular ROS levels and reduce GSH concentration in tumor cells to break the redox homeostasis in tumor tissues, has emerged as optional for tumor-enhanced CDT.22–26
However, GSH depletion enhanced CDT is far from satisfactory due to their strict requirement of H2O2 level and overexpressed glutathione in tumor tissues. Therefore, exploitation of CDT enhancement strategy, such as laser-enhanced CDT performance, is still a challenge. For example, the increasing local temperature at the tumor site can improve the Fenton or Fenton-like reaction rate to augment the efficiency of CDT.27,28 Up to now, considerable efforts have been devoted to develop multifunction nanomaterials for combined CDT/PTT, including Mo2C-derived polyoxometalate,29 [email protected]2−xSe core-shell nanocrystals,30 Cu2MoS4 nanocomposites,31 Fe3O4@MIL-100 nanocomposite,32 and Copper-olsalazine MOF.33,34 Therefore, multimodal therapies based on •OH generation, GSH consumption, and photothermal therapy are imperative to maximize the tumor therapeutic effect.
Recently, the near-infrared II photothermal therapy (NIR-II PTT) based on NIR-II absorption nanomaterials has drawn much attention in tumor therapy, which exhibited low toxicity, precise spatiotemporal selectivity, small photonscattering, high specificity, and excellent maximum permissible exposure (MPE,1064 nm: 1 W/cm2).35–37 Previous investigation on NIR-II absorption nanomaterials dominantly focused on noble-metal nanoparticles,38,39 transition metal chalcogenide,40,41 nanocarbons,42,43 rare-earth doped nanoparticles,44,45 two-dimensional (2D) nanosheets,46,47 phosphorus phthalocyanine,48,49 and conducting polymer nanoparticles.50,51 Polyanilines (PANI), as one of conducting polymers, have outstanding potential applications in biomedicine, such as antimicrobial therapy, drug delivery, bone regeneration, nerve regeneration, wound healing, and biosensor, because of their high electrical conductivity and biocompatibility caused by the hydrophilic nature, low-toxicity, good environmental stability, and nanostructured morphology.52,53 Moreover, chemical-modified polyanilines exhibited strong NIR-II absorbance, desirable photothermal-conversion performance, and excellent photostability, which make them good candidates for applications in NIR-II photothermal therapy of tumor.54–57 PANI surely represent a promising, but not yet completely explored, area of NIR-II photothermal therapy of tumor which calls for opportunities of deeper studies and developed research.
Copperphosphotungstate (CuPW), an essential member of polyoxotungstates, has been explored as an excellent catalyst to degrade organic pollutants.58,59 Moreover, CuPW demonstrated the oxidation property for ROS generation and GSH depletion.60 However, the insufficient therapeutic efficiency of CuPW makes its clinical use impractical. Addressing the challenges, in this work, we rationally incorporated the copperphosphotungstate into polyanilines to design copperphosphotungstate doped polyaniline nanorods ([email protected] Nanorods) via chemical oxidant polymerization of aniline. [email protected] Nanorods demonstrate low long-term toxicity and satisfactory biocompatibility. Moreover, [email protected] Nanorods achieve effective NIR-II absorption to thermal ablation cells. Furthermore, by the virtue of Cu2+ ions, these nanorods exhibit the ability to deplete intracellular GSH and convert H2O2 into • OH by a Fenton-like reaction. Both in vitro and in vivo experiments have proven that GSH depletion enhanced CDT/NIR-II PTT synergistic therapy based on [email protected] Nanorods induces the effective ablation of tumors. Hence, this work provides an option to develop a simple and multifunctional nanomedicine to realize GSH depletion, • OH production, and NIR-II PTT for effective tumor ablation.
Materials and Methods
The Preparation of Copperphosphotungstate Doped Polyaniline Nanorods
In a typical synthesis procedure of [email protected] Nanorods: aniline (92μL), phosphotungstic acid (188mg), CuSO4 (16 mg), and PVP (200 mg) were added in 18 mL DI water to obtain solution A, which was kept at 5°C. (NH4)2S2O3 (228mg) was added into 10mL DI water to obtain solution B, which was kept at 5 °C. Solution B was drop added into solution A at 5°C and stirred in 5°C for 4 h at 400 rpm. The blue solution was centrifugated under 5600×g (3000 rpm) to remove large particles for 10 min at room temperature. [email protected] Nanorods were obtained via centrifugation under 18,600×g (11000 rpm) for 10 min at room temperature and extensively washed with DI water and ethanol for several times.
Examining Catalytic Activities of Copperphosphotungstate Doped Polyaniline Nanorods by Detecting ROS, ·OH and GSH Consumption Using DCFH, Methylene Blue or DTNB as Indicator
For all experiments, comparison was made without or with 1064 nm laser irradiation (1.0 W/cm2, 5 min). For detection of ·OH generation, [email protected] Nanorods (100 μg/mL) were added in 3 mL methylene blue solution (8 μg/mL), followed by stirring for 30 min. Next, 100 μL H2O2 (1 mM) was added. After different periods of time, the level of ·OH generation was evaluated based on the decrease of absorbance at 617 nm.
To test the ROS production activity of [email protected] Nanorods, DCFH was used as the probe to detect 1O2 production. Briefly, DCFH-DA (0.5 mL) in DMSO was mixed with NaOH (2mL, 0.01 M) for 30 min. Then PBS (10 mL, 25 mM, pH 7.2) was added to form a stock solution of DCFH-DA. [email protected] Nanorods solution (100μg/mL) was mixed with the stock solution of DCFH-DA (10 μM) with or without H2O2 (1 mM). The solutions were placed at room temperature for 2 h. Then the fluorescent spectra were measured to estimate the produced ROS (excitation at 485 nm and emission at 528 nm).
To test GSHOD activity of [email protected] Nanorods, GSH (10 mM, 30 μL) and [email protected] Nanorods (100 μg/mL) were added into PBS solution (1 mL) with or without H2O2 (1 mM) at room temperature. After incubation for 30 min at room temperature, DTNB (Ellman’s Reagent, (5,5-dithio-bis-(2-nitrobenzoic acid)) solution (3mg/mL, 200 μL) was added and further incubated for 10 min. Oxidation of GSH was quantified by the decrease of absorbance at 412 nm using UV-vis spectroscopy.
Detecting Intracellular ROS and GSH
ROS production was probed by a cell-permeable dye (2,7-dichlorofluorescin diacetate, DCFH-DA), which becomes green fluorescent upon being oxidized to DCF by intracellular ROS. Specifically, 4T1 cells were first seeded in 12-well plates (2 × 104 cells per well) and then cultured for 24 h. Subsequently, the culture medium was replenished and added with DCFH-DA (10 nM). After 20 min, cells were washed thrice with PBS to remove free dyes. Finally, the fluorescence was recorded at 545 nm under 485 nm excitation.
The intracellular GSH was measured by the GSH and GSSG Assay Kit (Beyotime). 4T1cells were seeded in 6-well plates (3 × 106 cells per well) and incubated for 24 h. Then, the culture media were replaced with media containing [email protected] Nanorods (100 μg/mL). After 4 h, each well was replaced with the fresh media containing 10% FBS and the cells were incubated for another 20 h. Then, the cells were collected for GSH and GSSG assay according to the manufacturer’s protocol.
Results and Discussion
Synthesis and Characterization of Copperphosphotungstate Doped Polyaniline Nanorods
[email protected] Nanorods were synthesized by oxidative chemical polymerization of aniline under phosphotungstic acid, copper (II) sulfate, and ammonium persulphate. In a typical synthetic process, CuSO4, phosphotungstic acid and aniline were mixed with PVP, then ammonium persulphate was added to initiate the polymerization. The reaction was carried out at 5°C for 4h. The mixtures were centrifugated to obtain small blue [email protected] Nanorods.
As exhibited in Figures 1A and S1, the rod-like morphology of [email protected] Nanorods with an axial length of about 180 nm was confirmed by the transmission electron microscopy (TEM) images. The hydrodynamic diameter of the as-designed [email protected] Nanorods was verified to be 185 nm, which was consistent with the TEM examination (Figure 1B). Furthermore, the zeta potential of [email protected] Nanorods was determined to be 36.3 mV. Moreover, negligible change in the particle size of [email protected] Nanorods was observed over 14 days (Figure S2). The biodegradation property of [email protected] Nanorods after incubation in various pH solutions (pH =5.0, 6.0, and 7.4) was evaluated by ICP-OES investigation. No apparent release of Cu and W could be observed after 7 days under neutral or acidic condition (Table S1). Apart from that, the morphological change of [email protected] Nanorods under acid milieus was also investigated. As demonstrated in Figure S3, [email protected] Nanorods still preserved the rod-like morphology under acid conditions for long-term. All these results confirmed the excellent stability of [email protected] Nanorods in the physiological medium.
Figure 1 Characterizations of [email protected] Nanorods. (A) The TEM of [email protected] Nanorods. (B) The DLS of [email protected] Nanorods. (C) The IR spectrum of CuPWO4, PANI, [email protected] Nanorods. (D) Elemental mapping of Cu, W, P, C, N, and O in [email protected] Nanorods. (E) The XPS of [email protected] Nanorods. (F) High-resolution XPS spectra of Cu 2p in [email protected] Nanorods. (G) High-resolution XPS spectra of W 4f in [email protected] Nanorods.
The formatted coordination bonds of [email protected] Nanorods were further investigated via Fourier transform infrared (FTIR) spectroscopy. As shown in Figure 1C, the peaks of [email protected] Nanorods which were located at 1537, 1371, 1200, and 544 cm−1 were attributed to the bonds from polyaniline. Besides, the band at 1077 and 989 cm−1 of [email protected] Nanorods were attributed to copperphosphotungstate. The chemical composition of [email protected] Nanorods was also verified via energy-dispersive X-ray spectroscopy (EDS) elemental mapping. As shown in Figure 1D and E, [email protected] Nanorods consisted of Cu, P, W, O, and N elements, proving the uniform distribution between CuPW and PANI. The atomic composition was also confirmed by X-ray photoelectron spectroscopy (XPS) (Figure 1F and G). According to the well-resolved peaks in Figure 1F, the peaks at 953.3 eV (Cu 2p1/2) and 932.4 eV (Cu 2p3/2) were ascribed to the chemical state of Cu (II). In addition, the two strong peaks at 35.1 eV (W 4f7/2) and 33.2 eV (W 4f5/2) were relevant with the W(VI) valence state. All these results strongly proved the successful fabrication of [email protected] Nanorods.
NIR-II Photothermal Conversion Performance of Copperphosphotungstate Doped Polyaniline Nanorods
The UV-vis-NIR spectra of [email protected] Nanorods in water at different concentrations were investigated. [email protected] Nanorods demonstrated the absorption arranged from 600 to 1100 nm (Figure 2A). The absorbance of [email protected] Nanorods exhibited a linear increase with the increment of concentration. The mass extinction coefficient at 1064 nm was determined to be 9.85 L/g.cm, which was much higher than those of TiO2−x (5.54 L/g.cm)61 and SrCuSi4O10 nanosheets (2.42 L/g.cm)62 (Figure 2B). It seems that [email protected] Nanorods could efficiently collect and convert NIR-II light energy into hyperthermia.
Figure 2 NIR-IIPhotothermal performance of [email protected] Nanorods. (A) UV-vis-NIR spectra of [email protected] Nanorods in water with various concentration. (B) Fitting curve of mass extinction coefficient of [email protected] Nanorods at 1064 nm. (C) Photothermal curves of [email protected] Nanorods with various concentrations (0~100 μg/mL) under 1064 nm laser irradiation (1.0 W/cm2). (D) Temperature elevation curves of [email protected] Nanorods (100 μg/mL) under 1064 nm laser irradiation with different power densities. (E) Temperature curves of [email protected] Nanorods after five heating/cooling cycles. (F) Linear time constant calculated from the cooling period.
To explore the photothermal-conversion capability of [email protected] Nanorods, the temperature variation and corresponding images of [email protected] Nanorods at different concentrations after exposure to 1064 nm laser were explored (Figures 2C and D and S4). For example, the temperature of [email protected] Nanorods aqueous solution (100 μg/mL) increased from room temperature to 55℃ after irradiation (1064 nm, 1.0 W/cm2, 5 min). On the contrary, a slight temperature elevation was observed in the water under the same condition, indicating that [email protected] Nanorods exhibited excellent capacity to transfer NIR-II light energy into thermal energy.
Moreover, the photothermal property of [email protected] Nanorods in water was nearly unchanged after five heating/cooling cycles (Figure 2E), confirming the excellent thermal stability of [email protected] Nanorods. Furthermore, to assess the photothermal stability of [email protected] Nanorods, the UV-vis-NIR spectra of [email protected] Nanorods aqueous solution were explored after continuous 1064 nm laser irradiation. As shown in Figure S5, the UV-vis-NIR spectra of [email protected] Nanorods remained unchanged after 1064 nm laser irradiation for 30 min. All these results confirmed the high photothermal stability of [email protected] Nanorods.
As shown in Figure 2F, the photothermal-conversion efficiency of [email protected] Nanorods was determined to be 45.14%, which is high compared with most of the other NIR-II PTT agents, such as the gold nanoframeworks (23.9%),63 semiconducting copolymer nanoparticles (43.4%),64 MoS2 nanomaterials (43.3%).43 Therefore, all these results verified that [email protected] Nanorods are optional for NIR-II photothermal therapy.
The GSH Depletion and ROS Generation of Copperphosphotungstate Doped Polyaniline Nanorods
The GSH depletion performance of [email protected] Nanorods was exploited using the DTNB as a GSH indicator. After incubation with [email protected] Nanorods, the GSH concentrations were investigated for various durations. As shown in Figure S6, the absorption of DNTB changed slightly, confirming the stability of GSH. As depicted in Figure 3A, the GSH concentrations decreased gradually as incubation time increased. XPS analysis was carried out to verify the oxidation-reduction reaction between [email protected] Nanorods and GSH (Figure 3B). The emergence of Cu+ and the weakening of Cu2+ in the valence state of Cu proved the reduction of copper. In addition, the valence state of W keeps stable (Figure S7). The existence of Cu2+/Cu+ couples endow [email protected] Nanorods with GSH depletion property (Figure 3F).
Figure 3 Characterizations of the redox and Fenton-like reaction of [email protected] Nanorods. (A) GSH depletion by [email protected] Nanorods with DTNB as indicator after different duration. (B) XPS spectrum of [email protected] Nanorods after reaction with GSH. (C) MB degradation by .OH generated by H2O2 and [email protected] Nanorods at different groups. (D) Fluorescent spectrum of DCF for ROS generation. (E) ESR spectrum after different treatment. (F) The illustration of the GSH depletion and Fenton-like performance of [email protected] Nanorods (Up red arrow means the generation of .OH, while the down red arrow means the depletion of GSH).
[email protected] Nanorods were speculated to catalyze H2O2 and generate •OH. Therefore, the Fenton-like reaction activity of [email protected] Nanorods was validated by using the 3,3,5,5-tetramethyl-benzidine (TMB) as indicator. As depicted in Figure S8, with the increment of [email protected] Nanorods concentration, the absorbance value of TMB at 652 nm significantly increases, indicating the production of •OH. In the presence of H2O2, the production of •OH by [email protected] Nanorods was also confirmed with the methylene blue (MB) discoloration experiment. Figure 3C shows the absorption changes of MB after different treatments. The absorbance intensity of MB treated with H2O2, [email protected] Nanorods or [email protected] Nanorods +1064nm was negligible. On the contrary, [email protected] Nanorods + H2O2 groups exhibited apparent absorbance at 617nm, indicating that [email protected] Nanorods have Fenton-like reaction activity. Moreover, the absorbance at 617 nm of [email protected] Nanorods + H2O2 after 1064 nm irradiation was stronger compare to that without 1064 nm irradiation, confirming that photothermal treatment could improve the Fenton-like reaction activity. Simultaneously, the Fenton-like reaction activity of [email protected] Nanorods increased with the increment of H2O2 concentration (Figure S9). It seems that higher H2O2 concentration results in faster MB degradation.
Figure 3D shows the fluorescent changes of DCF after different treatments. As can be seen in Figure 3D, different fluorescent intensity after various treatments were observed. The fluorescent signal in the group treated with H2O2, [email protected] Nanorods or [email protected] Nanorods +1064nm was negligible. On the contrary, the [email protected] Nanorods + H2O2 groups exhibited a fluorescent signal at 450nm, indicating that [email protected] Nanorods have Fenton-like reaction activity. Moreover, the enhanced fluorescent signal was observed in the [email protected] Nanorods + H2O2 with a 1064nm irradiation group, confirming that photothermal treatment could improve the Fenton-like reaction efficacy.
The generation of •OH was further exploited by electron spinning resonance (ESR) spectra with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as •OH trapping agent. As demonstrated in Figure 3E, [email protected] Nanorods alone, H2O2 alone, and [email protected] Nanorods plus 1064 nm irradiation could not lead to the production of •OH. After combination [email protected] Nanorods with H2O2, an apparent ESR signal was monitored. Moreover, the ESR signal intensity after 1064 nm irradiation was enhanced, which was consistent with the MB degradation experiments. Therefore, all the results confirmed that [email protected] Nanorods could produce toxic •OH to kill tumor cells (Figure 3F).
In a word, we designed copperphosphotungstate doped polyaniline nanorods to induce the GSH consumption enhanced Fenton-like reaction and NIR-II PTT, having the great potential to augment tumor therapy.
In vitro Therapeutic Efficacy Assessment of Copperphosphotungstate Doped Polyaniline Nanorods
Encouraged by the physicochemical properties and functions of [email protected] Nanorods, in vitro experiments were carried out to investigate the therapeutic efficacy. [email protected] Nanorods exhibited no apparent toxicity to normal cells (L929) whereas they were cytotoxic to tumor cells (4T1) with the increment of concentration (Figure 4A), due to the higher endogenous H2O2 in tumor cells than that in normal cells. The anti-tumor effect was greatly improved by 1064 nm irradiation or the addition of H2O2 incorporation with [email protected] Nanorods (Figures 4B and S10). For example, after treatment with [email protected] Nanorods (100 μg/mL) and H2O2 (200 μM), the enhancement of cytotoxicity was observed and more than 50% death of 4T1 cells was recorded. Moreover, with 100 μg/mL [email protected] Nanorods, 1064 nm irradiation (0.75 W/cm2, 3 min) plus 200μM extracellular H2O2, essentially 94% 4T1 cells were killed. This was ascribed to the GSH depletion by [email protected] Nanorods, the abundant generation of •OH via the Fenton-like reaction incorporated with NIR-II photothermal therapy.
Figure 4 Intracellular investigation of [email protected] Nanorods. (A) Cytotoxicity of L929 and 4T1 cells after incubation with [email protected] Nanorods for 24h. (B) 4T1 cells viability after treatment with [email protected] Nanorods for 4h, then in presence or absence of H2O2 (100 μM) with or without 1064nm irradiation (0.75 W/cm2, 5 min). (C) GSH depletion in cells after incubation with [email protected] Nanorods (0 to 200 μg/mL). (D) Fluorescence images of 4T1 cells after different treatment stained by DCFH-DA. (E) Fluorescence images of 4T1 cells after different treatment stained by JC-1. (F) Fluorescent images of 4T1 cells after different treatment and then stained by PI and Ca-AM. (G) Flow cytometry using Annexin-V-FTIC/PI assay of 4T1 cells after different treatment. In the (D–G), 1. 4T1 cells treated with PBS, 2. 4T1 cells treated with [email protected] Nanorods (100μg/mL), 3. 4T1 cells treated with [email protected] Nanorods (100μg/mL) and H2O2(100μM), 4. 4T1 cells treated with [email protected] Nanorods (100μg/mL) plus NIR-II irradiation (1064 nm laser, 0.75 W/cm2, 5 min), 5. 4T1 cells treated with [email protected] Nanorods (100μg/mL) and H2O2(100μM) plus NIR-II irradiation (1064 nm laser, 0.75 W/cm2, 5 min).
Owing to copperphosphotungstate which could oxidize GSH, it is supposed that intracellular GSH could be consumed by [email protected] Nanorods. Hence, the GSH level in tumor cells after treatment with [email protected] Nanorods was further investigated. As demonstrated in Figure 4C, the reduction of GSH level in 4T1 cells was observed after incubation with [email protected] Nanorods, which could be attributed to the copperphosphotungstate-mediated oxidation.
To explore ROS production in vitro, DCFH-DA was utilized as the probe. As displayed in Figure 4D, a negligible green fluorescence was observed from the PBS or [email protected] Nanorods alone group. 4T1 cells treated with [email protected] Nanorods plus 1064 nm irradiation exhibited weak green fluorescence due to the finite •OH production. Interestingly, in the presence of H2O2, strong green fluorescence was observed in [email protected] Nanorods group, implying the generation of •OH. Notably, 4T1 cells presented conspicuous green fluorescence image after treated with [email protected] and H2O2 under 1064 nm irradiation. It seems that the hydroxyl radical generation ability of [email protected] Nanorods could be enhanced with NIR-II laser-induced hyperthermia.
To investigate the dysfunction of mitochondria after different treatment, the JC-1 staining experiment was carried out to explore the mitochondrial membrane potential. As demonstrated in Figure 4E, only the red fluorescence could be detected in the PBS group, confirming the no change in mitochondrial membrane potential. Only a slightly enhanced green fluorescence was observed in 4T1 cells after treatment with [email protected] Nanorods, whereas the modest fluorescent ratio between the green with red could be detected in the group ([email protected] Nanorods plus 1064 nm irradiation) and group ([email protected] Nanorods and H2O2), confirming the damage of mitochondria. To our surprise, only the green fluorescence was observed in the group ([email protected] Nanorods+ H2O2 + 1064 nm laser), indicating the damage of abundant mitochondria. These results evidently prove that the local hyperthermia generated from [email protected] Nanorods with 1064 nm irradiation plus the CDT might kill efficiently tumor cell.
Next, the Calcein-AM and PI assay was used to investigate the cell apoptosis. As demonstrated in Figure 4F, only [email protected] Nanorods could not result in noticeable cell death. However, after treatment with [email protected] Nanorods and H2O2, evident cell death was observed through the depletion of GSH and chemodynamic combination therapy. Moreover, [email protected] Nanorods plus 1064nm irradiation could also result in cell death, which was ascribed to the NIR-II laser-induced hyperthermia. As expected, after [email protected] Nanorods and H2O2 plus 1064nm irradiation, the optimal therapeutic effect was achieved through the GSH depletion, •OH generation, and hyperthermia combination therapy.
The quantitative analysis based on flow cytometry further demonstrated that the proportions of apoptotic cells were 1.4%, 6.8%, 17.4%, 10.4%, and 83.3% in the cells after being treated by PBS, [email protected] Nanorods, [email protected] Nanorods + 1064 nm laser, [email protected] Nanorods +H2O2, and [email protected] Nanorods +H2O2 +1064 nm laser, respectively (Figure 4G). This result was in accordance with the Calcein-AM/PI and CCK-8 results and confirmed the interaction between [email protected] Nanorods and tumor cells. All these results confirmed that [email protected] Nanorods own outstanding GSH depletion enhanced CDT/NIR-II PTT for tumor elimination.
In vivo Biocompatibility and Biodistribution Assessment of Copperphosphotungstate Doped Polyaniline Nanorods
The biocompatibility of [email protected] Nanorods was investigated for latent therapeutic application. The BALB/C mice were intravenously injected with various doses of [email protected] Nanorods (0, 10, 20, and 40 mg/kg). The body weights of all the mice were recorded every 4 days, and negligible weight change was observed in all groups (Figure S11). Moreover, routine blood chemistry analysis was carried out postinjection of [email protected] Nanorods. As depicted in Figure S12, no significant difference in blood indexes of the mice in all groups was detected. Furthermore, hematoxylin and eosin (H&E) staining experiments of the main organs in all groups were performed to assess the histocompatibility of [email protected] Nanorods. As demonstrated in Figure S13, there are no significant pathological abnormalities or inflammatory lesions in all groups. All these results proved that [email protected] Nanorods possess satisfactory biocompatibility for further therapeutic utility.
Inspired by the desirable NIR-II absorption, the potential of [email protected] Nanorods as photoacoustic (PA) imaging agents was evaluated. The PA signals and imaging of [email protected] Nanorods in water with various concentrations were recorded. As displayed in Figure 5A, the PA signal intensity enhanced with the increment of [email protected] Nanorods concentrations in the range of 0~200μg/mL. Moreover, the enhanced PA signal was detected in the 4T1 cells after incubation with [email protected] Nanorods (Figure 5B). Furthermore, after intravenous injection of [email protected] Nanorods, PA imaging of 4T1 breast tumor-bearing mice were carried out (Figure 5C and D). The maximum PA signal at tumor region at 12 h after injection was recorded. Therefore, [email protected] Nanorods featured high potential for PA imaging-guided CDT/NIR-II PTT.
Figure 5 The Biodistribution of [email protected] Nanorods (A) The PA intensity and imaging of [email protected] Nanorods with different concentration. (B) The PA intensity and imaging of 4T1 cells incubated with or without [email protected] Nanorods. (C) The PA imaging of 4T1-bearing mice after injection of [email protected] Nanorods (The tumor area was marked with pink circle). (D) The quantity analysis of PA intensity in tumor after injection of [email protected] Nanorods. (E) The Cu concentration in different organic tissues after injection of [email protected] Nanorods.
Before assessing the therapeutic effect in vivo, the biodistribution of [email protected] Nanorods in 4T1 tumor-bearing mice was evaluated. The major organs and tumor tissues were gathered at 3, 6, 12, and 24 h after intravenous injection of [email protected] Nanorods, and the content of the Cu element was determined. As displayed in Figure 5E, the highest tumor accumulation of the composite was observed at 12 h postinjection in consonance with the PA imaging experiment. Moreover, obvious distribution was also observed in liver, spleen, and kidney due to the blood circulation and the capture of reticuloendothelial system. Based on the consequences of PA imaging and the biodistribution examination, the NIR-II photothermal therapy was carried out at 12h after injection of [email protected] Nanorods via the tail vein.
In vivo Synergistic CDT/NIR-II PTT Performance of Copperphosphotungstate Doped Polyaniline Nanorods
To further explore the in vivo therapeutic effect of [email protected] Nanorods, thirty mice bearing 4T1 tumor were randomly divided into five groups (PBS, [email protected] Nanorods, [email protected] Nanorods +1064 nm laser, [email protected] Nanorods+H2O2, and [email protected] Nanorods +H2O2+1064 nm laser). The tumor regions were irradiated by the 1064 nm laser at 12h after intravenous injection of [email protected] Nanorods. The temperature and thermal images of the tumor sites were recorded by a thermal imaging camera (Figure 6A and B). The temperature at the tumor site in the group treated by [email protected] Nanorods + 1064 nm laser elevated quickly and reached 50.5°C within 5 min, confirming the high photothermal capability of [email protected] Nanorods. On the contrary, a slight temperature increase (3°C) in the tumor region was detected in the control groups (PBS+1064 nm laser).
Figure 6 The therapeutic effect of [email protected] Nanorods. (A) Photothermal images of 4T1 tumor-bearing mice administration with PBS (control) or [email protected] Nanorods after 1064 nm laser irradiation (0.75 W/cm2) for different durations. (B) The temperature of tumor sites change. (C) The body weight of mice after different treatments. (D) Growth curves of tumors in 4T1 tumor-bearing mice after different treatments. (E) Tumor weight after different treatments. (F) The photo of tumor after different treatments. (G) H&E and Tunnel staining of tumors with different treatments.
After various treatments, the tumor volumes and body weights of mice in all groups were recorded every 2 days. There are no significant weight loss in all groups, suggesting the high biosafety of [email protected] Nanorods (Figure 6C). As shown in Figure 6D, little tumor inhibition could be observed in the PBS group or [email protected] Nanorods group. To our surprise, the [email protected] Nanorods +1064nm group or [email protected] Nanorods +H2O2 group exhibited moderate tumor suppression, suggesting NIR-II PTT or CDT alone cannot efficiently inhibit tumor. Furthermore, synergistic therapy of NIR-II PTT and CDT significantly inhibited tumor, confirming the superior therapeutic effect of CDT/NIR-II PTT combination therapy compared to NIR-II PTT or CDT alone. Moreover, the digital photography and tumor weights also proved the most tumor suppression in “combination therapy” group (Figure 6E and F). All these results confirmed the higher therapeutic effect of NIR-II PTT plus CDT, compare to NIR-II PTT or CDT alone.
H&E staining of tumor tissues were also carried out to assess the therapeutic efficacy in all groups (Figure 6G). There is modesty necrosis with deformed nuclei in the [email protected] Nanorods + 1064 nm or [email protected] Nanorods +H2O2 group, compared to the PBS group. Moreover, most serious necrosis with distorted nuclei was detected in the [email protected] Nanorods + 1064 nm +H2O2 group. Then, the Tunnel staining of tumor tissues in all groups were performed to evaluate apoptosis of tumor cells after different treatment (Figure 6G). The proportion of proliferation tumor cells in the [email protected] Nanorods + 1064 nm group or [email protected] Nanorods +H2O2 group decreased, respectively, while the percentage of apoptotic cells increased after administration of [email protected] Nanorods + 1064 nm +H2O2. These results proved that CDT/NIR-II PTT combination therapy could inhibit tumor and induce tumor cell apoptosis.
In general, we fabricated a novel copperphosphotungstate doped polyanilines nanorods ([email protected] Nanorods) to disrupt the redox homeostasis in tumor cells. [email protected] Nanorods featured strong NIR-II absorbance and high photothermal-conversion efficiency (45.14%). Moreover, [email protected] Nanorods were characterized to consume GSH and convert H2O2 into • OH by a Fenton-like reaction. Both in vitro and in vivo experiments have confirmed that GSH depletion enhanced CDT/NIR-II PTT synergistic therapy based on [email protected] Nanorods could effectively ablate tumors. Consequently, this work provides an alternative but efficient avenue to surmount the drawbacks of GSH depletion enhanced CDT via combination NIR-II PTT for effective cancer treatment.
CuPW, CopperPhosphotungstate; [email protected], CopperPhosphotungstate doped Polyanilines; H2O2, Hydrogen Peroxide; CDT, ChemodynamicTherapy; PPT, Photothermal Therapy; PANI, Polyanilines; TME, Tumor Microenvironment; ROS, Reactive Oxygen Species; MPE, Maximum Permissible Exposure; TMB, 3,3,5,5-Tetramethyl-Benzidine; TEM, Transmission Electron Microscopy; FTIR, Fourier Transform Infrared; XPS, X-ray Photoelectron Spectroscopy; ESR, Electron Spinning Resonance.
Ethics Approval and Consent to Participate
Animal experiment is in accordance with the regulations of the Animal Ethical and Welfare Committee of Southern Medical University (SYXK2016-0167).
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
We gratefully acknowledge the National Natural Science Foundation of China (81671749) for financial support.
The authors declare no competing interests in the paper.
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41. Ling X, Jin ZK, Jiang Q, et al. Engineering biocompatible TeSexnano-alloys as a versatile theranostic nanoplatform. Natl Sci Rev. 2021;8(6):nwaa156.
42. Liu ZW, Zhao XY, Yu BR, Zhao NN, Zhang C, Xu FJ. Rough carbon-iron oxide nanohybrids for near-infrared-II light-responsive synergistic antibacterial therapy. ACS Nano. 2021;15(4):7482–7490.
43. Han Y, Liu HM, Fan M, et al. Near-infrared-II photothermal ultra-small carbon dots promoting anticancer efficiency by enhancing tumor penetration. J Colloid Interface Sci. 2022;616:595–604.
44. Lv RC, Yang PP, He F, et al. A yolk-like multifunctional platform for multimodal imaging and synergistic therapy triggered by a single near-infrared light. ACS Nano. 2015;9(2):1630–1647.
45. Dong LL, Li K, Wen D, Gao X, Feng J, Zhang HJ. Engineering gadolinium-integrated tellurium nanorods for theory-oriented photonic hyperthermia in the NIR-II biowindow. Small. 2020;16(42):2003508.
46. Cheng L, Wang XW, Gong F, Liu T, Liu Z. 2D nanomaterials for cancer theranostic applications. Adv Mater. 2020;32(13):1902333.
47. An D, Fu JY, Zhang B, et al. NIR-II responsive inorganic 2D nanomaterials for cancer photothermal therapy: recent advances and future challenges. Adv Funct Mater. 2021;31(32):2101625.
48. Du LH, Qin H, Ma T, Zhang T, Xing D. In vivo imaging-guided photothermal/photoacoustic synergistic therapy with bioorthogonal metabolic glycoengineering-activated tumor targeting nanoparticles. ACS Nano. 2017;11(9):8930–8943.
49. Pan HH, Li SK, Kan JL, et al. A cruciform phthalocyanine pentad-based NIR-II photothermal agent for highly efficient tumor ablation. Chem Sci. 2019;10(35):8246–8252.
50. Yin C, Li XZ, Wang Y, et al. Organic semiconducting macromolecular dyes for NIR-II photoacoustic imaging and photothermal therapy. Adv Funct Mater. 2021;31(37):2104650.
51. Jiang YY, Huang JG, Xu C, Pu KY. Activatable polymer nanoagonist for second near-infrared photothermal immunotherapy of cancer. Nat Commun. 2021;12(1):1–14.
52. Zare EN, Makvandi P, Ashtari B, Rossi F, Motahari A, Perale G. Progress in conductive polyaniline-based nanocomposites for biomedical applications: a review. J Med Chem. 2020;63(1):1–22.
53. Pina CD, Falletta E. Advances in polyaniline for biomedical applications. Curr Med Chem. 2022;29(2):329–357.
54. Zhang Y, Wang YJ, Yang XQ, Yang QL, Li J, Tan WH. Polyaniline nanovesicles for photoacoustic imaging-guided photothermal-chemo synergistic therapy in the second near-infrared window. Small. 2020;16(35):2001177.
55. Wang SL, Zhang LL, Zhao JJ, He M, Huang Y, Zhao SL. A tumor microenvironment-induced absorption red-shifted polymer nanoparticle for simultaneously activated photoacoustic imaging and photothermal therapy. Sci Adv. 2021;7(12):eabe3588.
56. Kuang YL, Liu NB, Ye S, et al. Ce doped polyaniline nanoparticles for absorption and photoacoustic imaging response to GSH in vitro and in vivo. Bioact Mater. 2022;17:197–203.
57. Tian C, Xue XL, Chen Y, et al. Phosphotungstate acid doped polyanilines nanorods for in situ NIR-II photothermal therapy of orthotopic hepatocellular carcinoma in rabbit. Int J Nanomedicine. 2022;17:5565–5579.
58. Sadasivan R, Patel A. Mono-copper substituted phosphotungstate supported on to neutral alumina: synthesis, characterization and detailed studies for oxidation of styrene. Inorganica Chim Acta. 2021;522:120357.
59. Yao FF, Fu WZ, Ge XH, Wang LS, Wang JH, Zhong WZ. Preparation and characterization of a copper phosphotungstate/titanium dioxide (Cu-H3PW12O40/TiO2) composite and the photocatalytic oxidation of high-concentration ammonia nitrogen. Sci Total Environ. 2020;727:138425.
60. Xie F, Li X, Li YJ, Jiang XS, Rui Q, Sha JQ. Assembly of polyoxometalate-templated metal-organic framework with effective peroxidase-like catalytic activity. J Coord Chem. 2019;72(2):272–282.
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© 2023 The Author(s). This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

domain: literature


6mm Multiwall H-Channel 96"
This H-channel is used to used to vertically join two 6mm multiwall sheets, with each sheet sliding into either side of the H-channel. The H-channel will give glazing projects a more professional look.
- Connector used to join two sheets
- Use vertically
- Clear polycarbonate
- Can be used with aluminum tape
|Country of Origin||United States|


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Elaboration of a short summary (300 words) based on a controversial clinical article researched in the medical literature, published in the current year, in which a potential evidence-based medical error, originating from the biostatistical approach, is identified. Assessment targets: Ability to identify a problem, critically analyze a controversy, and apply knowledge of biostatistics in valuing medical evidence. The biostatistical tests must be one of the following: ANOVA, linear regression, multiple regression, general linear model or logistic regression.
19 pekerja bebas membida secara purata €622 untuk pekerjaan ini
Sir Share more details about your project. I was seeing your project & I thought i am the suitable person for it.I will complete your project on given time [login to view URL] me. Thank you!
HI I am experienced in Research Statistics Research Writing etc I can start right now but i have few doubts and questions lets have a quick chat and get it started waiting for your reply

domain: medical


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Our aerosol generators are already used by a large number of transport and logistics companies in the UK and abroad. The RSL Fire extinguishing systems can be used to protect the engine compartment, electrical components and lithium batteries. Our automatic fire suppression systems provide reliable protection against class A, B, C and F fires. Retrofitting is possible without any problems. Our extremely compact extinguishing systems can also be accommodated in very narrow spaces including engine rooms and electrical cabinets. Our fire suppression systems work completely autonomously, from fire detection to extinguishing. Our aerosol extinguishing agent also prevents re-ignition and minimizes fire damage. Discover the advantages of our solutions for transport and logistics. Contact us for more information, we are happy to answer all your questions.
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GM Pressing Hard to Get 4-Gen Bolt AV’s On The Road – Miami Lakes Automall Chevrolet
General Motors Petition
In 2018 General Motors revealed the first images of the upcoming GM Cruise AV, a fourth-generation Bolt AV-based-autonomous vehicle. This new self-driving model will be the first of its kind without a steering wheel or petal.
Since then, GM has been petitioning for permission to test new Bolts “without a human driver and without human driver controls.” They’ve requested to permit 2,500 vehicles to run on public roads citing this is meant to advance safety and low-emission technology.
For the past two weeks, top GM executives have discussed the electric hatch as a self-driving platform. According to Reuters, an international news organization, CEO Mary Barra met with US Transportation Secretary Elaine Chao last week in order to discuss getting the 4-Gen AV’s onto the city streets.
“I expect we’re going to be able to move forward with these petitions soon — as soon as we can. There’s a lot of back and forth between us and the companies. We’re sharing with them thoughts and ideas and concerns. They come back to us with additional information.” Said, James Owens, National Highway Traffic Safety Administration (NHTSA) administrator.
Additionally, Owens mentioned that he expects that a decision will be made in 2020. He also said that the primary concern for NHTSA is to make sure any driverless vehicles on public roads are as safe as those driven by people.
GM’s 100-page petition made it more than clear that they mean business; It goes into detail as to how autonomous vehicles will be a huge benefit to the public.
The company wrote “Because human error or behavior leads to 94 percent of vehicle crashes, technology that eliminates the human driver has the potential to save tens of thousands of lives and to avoid or mitigate hundreds of thousands of vehicle crashes every year in the United States alone…Every day in the United States, more than 100 lives are lost in car crashes. Every day of delay in getting autonomous vehicles safely on American roads is a day in which we are losing lives that could be saved.”
GM states that by introducing this program it will gain a wider acceptance to the use of electric and zero-emission vehicles. If the NHTSA permits GM’s request, the company’s deployment plan will include a ride-share program that GM will bring public exposure to. The ride-sharing system would operate in urban areas and users would interact with it by the use of his or her phone.
2019 Chevrolet Bolt EV
Though autonomous vehicles have ways to go, Miami Lakes Automall currently has 2019 electric models starting at $29,000 , (plus destination fee) against the retail price of about $43,000.
The highlight of this 2019 EV is its battery back of course! The 60-kWh battery can take the Bolt up to 238 miles. On top of this, just 30 minutes at the DC Fast Charging station will give the vehicle another 90 miles of range. The engine also has 266 lb-ft of torque with a horsepower of about 200.
_ Those interested in any 2019 Chevy EV models can search our electric vehicle online inventory or call us: (305) 455-3540. Representatives are standing by! _


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Dayo Amusa leaves many talking as she shares a letter from her serial lover
Nollywood star Dayo Amusa stirred conversation among her fans when she unveiled a letter from her devoted nephew, marking a notable departure from her usual posts.
In honor of Valentine’s Day, her nephew penned a heartfelt message to her, affectionately dubbing her his Adufe. In his letter, he struggled to encapsulate the depth of his affection for her.
He acknowledged her multifaceted role in his life, recognizing her not only as an aunt but also as a nurturing maternal figure and, significantly, as his beloved. He highlighted her unwavering love and attentive care towards him.
Timzy, her nephew and recurrent paramour, expressed gratitude for the unique connection they share, praising her for consistently making him feel cherished and valued.
He made her know that she had a special place in his heart as he agreed to be her Val.
Read the heartwarming letter below,

domain: celebrity


text:
Pucker is a collaborative photo project by David Wile and April Maciborka that documents the always epic first taste of lemon for children. Most of us have had that camera ready just waiting to see what kind of reaction our own kids give to their first lemon. As the project shows, there’s such a range of reactions but not one is lacking in cuteness.
Admit it, if you haven’t already given that first taste of lemon you’re going to tonight.
Photo Credit to David Wile and April Maciborka

domain: artistic


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Insider Selling: Craig L. Christensen Sells 20,000 Shares of Tetra Tech Stock (TTEK)
Tetra Tech (NASDAQ:TTEK) SVP Craig L. Christensen sold 20,000 shares of the stock on the open market in a transaction dated Friday, January 17th. The stock was sold at an average price of $30.00, for a total value of $600,000.00. Following the completion of the sale, the senior vice president now directly owns 29,509 shares in the company, valued at approximately $885,270. The transaction was disclosed in a document filed with the Securities & Exchange Commission, which is available at this link.
Tetra Tech (NASDAQ:TTEK) traded up 0.77% on Tuesday, hitting $30.14. 534,052 shares of the company’s stock traded hands. Tetra Tech has a 52-week low of $22.21 and a 52-week high of $31.49. The stock’s 50-day moving average is $27.97 and its 200-day moving average is $25.76. The company’s market cap is $1.934 billion.
Tetra Tech (NASDAQ:TTEK) last issued its quarterly earnings data on Thursday, November 14th. The company reported $0.39 earnings per share (EPS) for the quarter, beating the consensus estimate of $0.36 by $0.03. The company had revenue of $531.50 million for the quarter, compared to the consensus estimate of $521.54 million. During the same quarter in the previous year, the company posted $0.48 earnings per share. The company’s revenue for the quarter was down .9% on a year-over-year basis. Analysts expect that Tetra Tech will post $1.75 EPS for the current fiscal year.
A number of analysts have recently weighed in on TTEK shares. Analysts at Stephens upgraded shares of Tetra Tech from an “equal weight” rating to an “overweight” rating in a research note to investors on Friday. They now have a $36.00 price target on the stock. Separately, analysts at KeyCorp upgraded shares of Tetra Tech from a “hold” rating to a “buy” rating in a research note to investors on Thursday, January 16th. They now have a $33.00 price target on the stock. Five equities research analysts have rated the stock with a hold rating and eight have given a buy rating to the stock. Tetra Tech presently has a consensus rating of “Buy” and a consensus price target of $29.27.
Tetra Tech, Inc is a provider of consulting, engineering, program management, construction management and technical services focusing on natural resource management, infrastructure, energy and the environment.
Get Analysts' Upgrades and Downgrades via Email - Stay on top of analysts' coverage with Analyst Ratings Network's FREE daily email newsletter that provides a concise list of analysts' upgrades and downgrades. Click here to register now.


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Aspiring actress and writer
Theater and movie nerd
"Thank you for your consideration." - Katniss Everdeen
"I get emails from a raccoon. So, nothing sounds crazy anymore." - Natasha Romanoff
Hello! I love acting, singing, performing, and obviously writing. I love any books in the historical fiction and mystery genres and some dystopian (well I mean I'm open to any genre). As for movies and shows, I'll really watch anything with romance, comedy, drama, or action.
I constantly start stories, though I rarely finish them.
Just_A_Memory and I are collaborating on a series called "Hate Me, Push Me, Break Me". We hope you enjoy it!! :)
Currently reading Breathe by Sarah Crossan, but I'm always open to book suggestions!
Hope you're having a great day :)
Written By: katnissromanoff
October 31, 2020


text:
For over 20 years, distinguished scholars and professionals have been visiting the School of Architecture and Planning to teach and inspire, all made possible by the generous support of Will and Nan Clarkson.
When civic leaders Will and Nan Clarkson founded the Clarkson Visiting Chair program in the School of Architecture and Planning in 1991, their vision was to engage students, faculty, practitioners and members of the public in knowledge-sharing and scholarship on critical issues in architecture, planning and design. Since then, over 30 Clarkson Visiting Chairs from across the world have joined the School of Architecture and Planning as scholars-inresidence, spurring rich dialogue and debate through a week-long series of public lectures and seminars.
Dedicated to the Buffalo community, the Clarksons have a particularly deep passion for Buffalo architecture. In 2011, they donated a Frank Lloyd Wright-designed art glass window to the Martin House Restoration Corporation for display in the reconstructed carriage house of the Martin House complex. The window was only one of two to survive after the original carriage house was demolished in 1962. Will Clarkson was also instrumental in the 1981 publishing of “Buffalo Architecture: A Guide,” the first national publication to describe the city’s architectural treasures.

domain: history


text:
Make sure Nasco Education is on your preferred vendor and bid lists! Send inquiries to: [email protected]
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text:
Fast Food Lowry City
Seas the moment!
THIS LOCATION IS CLOSED. Real seafood should be sourced from real sea-places, like, you know, oceans. So that's exactly where we source ours from. We're no one trick sea pony. Sure, we've got the classic fried fish and chips you love, but now we've got delicious new grilled seafood options to add to our menu of delica-seas.
Long John Silver's - CLOSED can be found at 303 South Hwy. 13 . The following is offered: Fast Food - In Lowry City there are 1 other Fast Food. An overview can be found here.

domain: food


Galaxy Note 8 vs iPhone 8: Specs Comparison
Samsung has already firmly switched its attention to its upcoming Galaxy Note 8. This is undoubtedly a hugely significant flagship for the Korean giant after the disaster of the exploding Galaxy Note 7. Recent reports from Korea indicate that Samsung will soon announce the Galaxy Note 8 at a special "Unpacked" event and that it'll basically be a bigger version of Galaxy S8 and will offer a few extra tricks, which includes a stylus and a dual lens camera on the back. While this year will be the 10th anniversary of the iPhone, and everyone is anticipating that Apple will unveil a phone that has been widely dubbed the iPhone 8 and could be the "revolutionary" iPhone Apple fans have been waiting for.
Samsung Galaxy Note 8
The Galaxy Note 8 reports claim that the device may come and feature a dual-camera system and a rear-facing fingerprint scanner placement, similar to what was placed on the Galaxy S8. Samsung may introduce an optical fingerprint sensor, embedded into the Galaxy Note 8 display. Interestingly, the latest report of Note 8 news indicates the phablet will feature a dual speaker setup and will come with an upgraded version of Qualcomm's Snapdragon 835 chip, in the form of the Snapdragon 836, to ship and backed up with 6GB of RAM memory and with 64 and 128GB versions.
The Galaxy Note 8 is expected to come with fast and wireless charging, with an improved S Pen stylus. More so, Since the Note 7 was about $50 pricier than the Galaxy S7 Edge at their respective releases, more likely this year's Galaxy Note 8 will cost around $900.
Apple iPhone 8
The next-gen iPhone will have a larger 5.8in display, "edge-to-edge" and slightly curved. The iPhone 8 will have the Touch ID sensor embedded into the screen. Reports suggest there will be a "function area" at the bottom of the screen that acts like the Touch Bar on the MacBook Pro. Apple will use USB-C instead of Lightning on the iPhone 8 in order to feature fast charging. Another report claims that the iPhone 8 will offer only two capacities, the 64GB and 256GB and will also have 3GB of RAM.
The iPhone 8 is expected to use Apple A11 processor built on a 10nm process to match the Qualcomm Snapdragon 835. The next iPhone will come with heftier price than this year's release, and reports suggest that the highest-spec model will be the first iPhone to cost more than $1,000.
iPad Pro 10.5 Review: A Surprisingly Powerful Tablet
At its recent WWDC conference, Apple announced a new 10.5in iPad Pro, complete with new features and a revamped screen, making it undoubtedly one of the most powerful tablets.
OnePlus 5 News: Official Look, Price And Release Date Revealed
OnePlus has now revealed a detailed image of what its new flagship OnePlus 5 smartphone actually looks like.
iPhone 8 Will Be Larger Than The iPhone 7
Reports claim that the iPhone 8 will be bigger in size than the iPhone 7, but smaller than the iPhone 7 Plus.
iPhone 8: 5G Wireless Internet Speed And New Design Leaks
New iPhone 8 leaks have surfaced online ahead of its release date. The latest leaked images purport to show the final design of the upcoming phone and to come with 5G internet speed.
Apple to Completely Be Carbon Neutral by 2030
Apple promised to go completely carbon neutral in the next 10 years, with every device sold having a net-zero climate impact.
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Buildots Raises $16 Million as It Brings AI Computer Vision to Construction Management
Buildots uses hardhat-mounted 360° cameras to seamlessly determine the exact status of an ongoing project and provides invaluable insight to contractors.
2 NASA Astronauts Are Home from ISS, Proving SpaceX Can Safely Bring People to and from Space
After a two-month mission, SpaceX brings back home 2 astronauts, proving that it could transport people to and from space safely.
Something is Surely Brewing Within Destiny 2
How are you keeping on? There's a whole lot of content in the game and even though some of it is going away, the great variety won't go anywhere. On top of that, new stuff will be added and the huge add-on announced not that long ago kind of gives you hint about that. If you've played this game long enough, then you know you can't have everything, but what if there was a way? Of course, we're talking about Destiny 2 boosting. But it's not just good for herding some items. Our services can be used for any in-game goal, small or big.


Primarily based mostly on earlier leaks, along with Samsung’s official bulletins in regards to the cellphone , the images by Dutch publication LetsGoDigital reveal what to probably rely on on 20 February. Navigate your iPad Web browser to this net page and click on the icon to obtain the iBook to your iBooks Library. The e-e book is designed for landscape mode.
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With Apple’s A10 Fusion chip in-constructed, the model new iPod contact is optimized for gaming, together with what Apple calls, “immersive augmented actuality (AR) experiences”. Samsung CEO DJ Koh holding up the Galaxy Fold. Phrase the spotlight on the ridge in the middle and one of the best ways the two halves of the display do not utterly cohere into one.
Testing carried out by Apple in February 2019 using preproduction three.2GHz 6-core Intel Core i7-based totally 21.5-inch iMac methods with 32GB of RAM, and preproduction three.6GHz 8-core Intel Core i9-based totally 27-inch iMac methods with 64GB of RAM; and transport three.6GHz quad-core Intel Core i7-based 21.5-inch iMac programs with 32GB of RAM, as well as transport 4.2GHz quad-core Intel Core i7-based totally 27-inch iMac methods with 64GB of RAM. Examined with Xcode 10.1 (10B61). Performance assessments are performed utilizing particular computer techniques and mirror the approximate performance of iMac.
The first video, from DetroitBorg , covers the current iPod contact sixth Gen, and the second video, from Insanely Nice , covers the last word iPod nano seventh Gen. You additionally could also be fascinated inside the complete written critiques listed above. Starting at $199 with 32GB of storage, the iPod contact is probably the most value efficient machine Apple sells that has its personal show. You’ll be able to bump up the system’s storage, with a 128GB mannequin costing $299 and a brand new-for-2019 256GB mannequin working you $399.
Though it might not have a headphone jack, the Razer Phone 2’s use of Android Pie has given it all of the Bluetooth options of the Google Pixel 2. As a result of it has significantly higher audio system, and Dolby Atmos assist by its dongle, this cellphone edges out the Pixel three and takes a spot on top-of-the-line 5 handsets.


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Cell migration is an important process involved in wound healing, tissue development, and so on. Many studies have been conducted to explore how certain chemicals and electric fields induce cell movements in specific directions, which are phenomena termed chemotaxis and electrotaxis, respectively. However, phototaxis, the directional migration of cells or organisms toward or away from light, is rarely investigated due to the difficulty of generating a precise and controllable light gradient. In this study, we designed and fabricated a microfluidic chip for simultaneously culturing cells and generating a blue light gradient for guiding cell migration. A concentration gradient was first established inside this chip, and by illuminating it with a blue light-emitting diode (LED), a blue light gradient was generated underneath. Cell migration in response to this light stimulus was observed. It was found that lung cancer cells migrated to the dark side of the gradient, and the intracellular reactive oxygen species (ROS) was proportional to the intensity of the blue light.
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domain: biology