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NIR-triggered on-site NO/ROS/RNS nanoreactor:Cascade-amplified photodynamic/photothermal therapy with local and systemic immune responses activation

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Opto-Electronic Advances 2024年第6期7卷 58-73页

作者： Ziqing Xu Yakun Kang Jie Zhang Jiajia Tang Hanyao Sun Yang Li Doudou He Xuan Sha Yuxia Tang Ziyi Fu Feiyun Wu Shouju Wang Laboratory of Molecular Imaging Department of RadiologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Breast Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Women&Children Research Center The First Affiliated HospitalNanjing Medical UniversityNanjing 210029China

Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune *** these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS *** not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor *** in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/*** such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.

关键词： photothermal therapy photodynamic therapy nitric oxide reactive nitrogen species triple-negative breast cancer immune response nanoreactor

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Why people should run after positive affective experiences instead of health benefits

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Journal of Sport and Health Science 2024年第4期13卷 445-450页

作者： Silvio Maltagliati Philippe Sarrazin Layan Fessler Mael Lebreton Boris Cheval University of Grenoble Alpes SENSGrenoble 38000France Paris School of Economics Paris 75014France Swiss Center for Affective Sciences University of GenevaGeneva 1202Switzerland Laboratory for Behavioral Neurology and Imaging of Cognition Department of Fundamental NeurosciencesUniversity of GenevaGeneva 1202Switzerland Laboratory for the Study of Emotion Elicitation and Expression(E3Lab) Department of PsychologyUniversity of GenevaGeneva 1202Switzerland

Over time,physical activity(PA)has shifted from being a necessity to being an *** a result,levels of PA have sharply decreased.1 Today,we are facing a worldwide pandemic of physical inactivity,with one death every 6 s attributed to insufficient PA.2 To counteract this trend,a tremendous effort is being made to promote regular PA across the lifespan,mainly through the dissemination of knowledge about the health benefits of accumulating sufficient PA.

关键词： sharply benefits attributed

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Updated prevalence of latent prostate cancer in Chinese population and comparison of biopsy results: An autopsy-based study

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The Innovation 2024年第1期5卷 80-87页

作者： Yuliang Chen Zhien Zhou Yi Zhou Zhipeng Mai Shijie Jin Zhen Liang Zhiyuan Shang Yuzhi Zuo Yu Xiao wenze Wang Haibo Wang weigang Yan Department of Urology Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100730China Department of Gynaecology and Obstetrics Beijing HospitalNational Centre of GerontologyBeijing 100730China Department of Pathology Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100730China Peking University Clinical Research Institute Peking University First HospitalBeijing 100034China

Prostate cancer detected by autopsy is named latent prostate *** the repertoire of clinical prostate cancer,latent cancer may better reflect the disease *** clinical prostate specimens,which are obtained exclusively from biopsy-positive cases,prostate specimens obtained through autopsy provide information on biopsy-negative cases,helping calculate the true sensitivity of prostate *** 2014 to 2021,we collected autopsy specimens of the prostate from body donors in China and performed transperineal and transrectal biopsies on specimens before step-sectioning and pathological *** found that the crude prevalence of latent prostate cancer in middle-aged and elderly men was 35.1%(81/231),which was higher than previous estimates for Chinese *** overall per-patient sensitivities of transperineal and transrectal biopsies were not significantly different(33.3%vs.32.1%,p=0.82),but the two approaches differed in preferential sampling area along the proximal-distal axis of the *** biopsy had a higher sensitivity for detecting clinically significant lesions in the distal third(34.7%vs.16.3%,p=0.02)and distal half(30.6%vs.18.1%,p=0.04),while transrectal biopsy had a higher sensitivity for lesions in the proximal half(25.0%vs.13.9%,p=0.046).Both transperineal and transrectal methods of biopsy missed most small lesions(0.5 mL).In conclusion,the prevalence of latent prostate cancer in China has increased over the past 2 *** transperineal and transrectal methods of biopsy had comparable sensitivities but had different preferential sampling *** approaches miss one-third of large lesions.

关键词： biopsy prevalence latent

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High-throughput screening of novel TFEB agonists in protecting against acetaminopheninduced liver injury in mice

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Acta Pharmaceutica Sinica B 2024年第1期14卷 190-206页

作者： Xiaojuan Chao Mengwei Niu Shaogui Wang Xiaowen Ma Xiao Yang Hua Sun Xujia Hu Hua Wang Li Zhang Ruili Huang Menghang Xia Andrea Ballabio Hartmut Jaeschke Hong-Min Ni wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Oncology the First Affiliated Hospital of Anhui Medical UniversityAnhui Medical UniversityHefei 230032China national Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Telethon Institute of Genetics and Medicine TIGEMPozzuoliNaples 80131Italy medical Genetics Department of Translational MedicineFederico II UniversityNaples 80131Italy Department of Molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA Department of Internal Medicine Division of GastroenterologyHepatology&MotilityUniversity of Kansas Medical CenterKansas CityKS 66160USA

Macroautophagy(referred to as autophagy hereafter)is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and *** studies showed that autophagy protects against acetaminophen(APAP)-induced injury(AILI)via selective removal of damaged mitochondria and APAP protein *** lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with *** the present study,we showed that transcription factor EB(TFEB),a master transcription factor for lysosomal biogenesis,was impaired by APAP resulting in decreased lysosomal biogenesis in mouse *** loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI,***,overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2(NRF2)activation to protect against *** also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB *** these agonists,salinomycin,an anticoccidial and antibacterial agent,activated TFEB and protected against AILI in *** conclusion,genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

关键词： Autophagy DILI Drug screening Hepatotoxicity Lysosome Mitochondria Mitophagy NRF2

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Engineered extracellular vesicles for delivery of siRNA promoting targeted repair of traumatic spinal cord injury

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Bioactive Materials 2023年第5期23卷 328-342页

作者： Yuluo Rong Zhuanghui Wang Pengyu Tang Jiaxing Wang Chengyue Ji Jie Chang Yufeng Zhu Wu Ye Jianling Bai wei Liu Guoyong Yin Lipeng Yu Xuhui Zhou weihua Cai Department of Orthopedics The First Affiliated Hospital of Nanjing Medical UniversityNanjing210029JiangsuChina Department of Biostatistics School of Public HealthNanjing Medical UniversityNanjing210029JiangsuChina Department of Orthopedics Second Affiliated Hospital of Naval Medical UniversityShanghai200003China Department of Orthopedics Shanghai General Hospital(Shanghai First People’s Hospital)Shanghai Jiao Tong UniversityShanghai200003China

Spinal cord injury(SCI)is a severe disease of the nervous system that causes irreparable damage and loss of function,for which no effective treatments are available to *** extracellular vesicles(EVs)carrying therapeutic molecules hold promise as an alternative SCI therapy depending on the specific functionalized EVs and the appropriate engineering *** this study,we demonstrated the design of a drug delivery system of peptide CAQK-modified,siRNA-loaded EVs(C-EVs-siRNA)for SCI-targeted *** peptide CAQK was anchored through a chemical modification to the membranes of EVs isolated from induced neural stem cells(iNSCs).CCL2-siRNA was then loaded into the EVs through *** modified EVs still maintained the basic properties of EVs and showed favorable targeting and therapeutic effects in vitro and in vivo.C-EVs-siRNA specifically delivered siRNA to the SCI region and was taken up by target cells.C-EVs-siRNA used the inherent anti-inflammatory and neuroreparative functions of iNSCs-derived EVs in synergy with the loaded siRNA,thus enhancing the therapeutic effect against *** combination of targeted modified EVs and siRNA effectively regulated the microenvironmental disturbance after SCI,promoted the transformation of microglia/macrophages from M1 to M2 and limited the negative effects of the inflammatory response and neuronal injury on functional recovery in mice after ***,engineered EVs are a potentially feasible and efficacious treatment for SCI,and may also be used to develop targeted treatments for other diseases.

关键词： Extracellular vesicles Spinal cord injury siRNA Microglia/macrophages polarization Induced neural stem cells

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Engineering immunosuppressive drug-resistant armored(IDRA)SARS-CoV-2 T cells for cell therapy

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Cellular & Molecular Immunology 2023年第11期20卷 1300-1312页

作者： Qi Chen Adeline Chia Shou Kit Hang Amy Lim wee Kun Koh Yanchun Peng Fei Gao Jili Chen Zack Ho Lu-En Wai Kamini Kunasegaran Anthony Tanoto Tan Nina Le Bert Chiew Yee Loh Yun Shan Goh Laurent Renia Tao Dong Anantharaman Vathsala Antonio Bertoletti Emerging Infectious Disease Program Duke-NUS Medical SchoolSingaporeSingapore national University Centre for Organ Transplantation National University HospitalSingaporeSingapore MRC Human Immunology Unit MRC Weatherall Institute of Molecular MedicineRadcliffe Department of MedicineUniversity of OxfordOxfordUK Lion TCR Pte Ltd SingaporeSingapore A*STAR ID labs Agency for ScienceTechnology and ResearchSingaporeSingapore Lee Kong Chian School of Medicine Nanyang Technological UniversitySingaporeSingapore Department of Medicine Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Singapore Immunology Network A*STARSingaporeSingapore

Solid organ transplant(SOT)recipients receive immunosuppressive drugs(ISDs)and are susceptible to developing severe ***,we analyze the Spike-specific T-cell response after 3 doses of mRNA vaccine in a group of SOT patients(n=136)treated with different *** demonstrate that a combination of a calcineurin inhibitor(CNI),mycophenolate mofetil(MMF),and prednisone(Pred)treatment regimen strongly suppressed the mRNA vaccine-induced Spike-specific cellular *** defects have clinical consequences because the magnitude of vaccine-induced Spike-specific T cells was directly proportional to the ability of SOT patients to rapidly clear SARS-CoV-2 after breakthrough *** then compensate for the T-cell defects induced by immunosuppressive treatment and to develop an alternative therapeutic strategy for SOT patients,we describe production of 6 distinct SARS-CoV-2 epitope-specific ISD-resistant T-cell receptor(TCR)-T cells engineered using the mRNA electroporation method with reactivity minimally affected by mutations occurring in Beta,Delta,Gamma,and Omicron *** strategy with transient expression characteristics marks an improvement in the immunotherapeutic field and provides an attractive and novel therapeutic possibility for immunosuppressed COVID-19 patients.

关键词： T cell therapy Transplantation SARS-CoV-2 Immunosuppressive drug resistant T cells

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Association of a genetic variant in AKT1 gene with features of the metabolic syndrome

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Genes & Diseases 2019年第3期6卷 290-295页

作者： Fateme Sadat Eshaghi Hamideh Ghazizadeh Sakine Kazami-Nooreini Ameneh Timar Habibollah Esmaeily Mehrane Mehramiz Amir Avan Majid Ghayour-Mobarhan Dept.Biology Faculty of Basic SciencesHakim Sabzevari UniversityP.O.Box:397SabzevarIran Student Research Committee Faculty of MedicineMashhad University of Medical SciencesMashhadIran Metabolic Syndrome Research Center Mashhad University of Medical SciencesMashhadIran Social Department of Health Research Center Mashhad University of Medical SciencesMashhadIran

Metabolic syndrome(MetS)is a clustering of metabolic abnormalities that is associated with increased risk of developing cardiovascular disease and type 2 *** is growing body of data showing the associations of genetic variants of the genes involved in the PI3K/AKT/mTOR pathway with diabetes and *** aimed to investigate the association between MetS and its components with the genetic polymorphism in AKT1,rs1130233(T>C).Total of 618 participants,recruited from Mashhad stroke and heart atherosclerosis disorder cohort(MASHAD study).Patients with MetS were defined by using international diabetes federation(IDF)criteria(n Z 326)and those without MetS(n Z 261)were *** and biochemical parameters were measured in all *** analysis for the rs1130233 polymorphism was performed,using the ABI-StepOne instruments with SDS version-2.0 *** with MetS had a significantly higher levels of BMI,waistcircumference,total cholesterol,triglyceride,high sensitivity-c reactive protein(hs-CRP)and blood-pressure,and lower concentrations of high density lipoprotein(HDL-C),compared to non-MetS individuals(Pween the rs1130233 and MetS was not *** with a CC or CT genotypes had a significantly higher serum hs-CRP-level(OR:1.5;95%CI(1.05e2.1),P Z 0.02).Additionally,subjects who carried the TC genotype had a higher BMI compared to the CC genotype(p value Z 0.045).Our findings demonstrated that AKT1,rs1130233(T>C)polymorphism was associated with major components of MetS such as hs-CRP,and BMI,indicating further investigation in a multi-center setting to explore its value as an emerging biomarker of risk stratification marker.

关键词： AKT1 CRP Genetic variant MetS PI3K/AKT/mTOR pathway rs1130233

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Aggregation-induced emission luminogens for highly effective microwave dynamic therapy

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Bioactive Materials 2022年第1期7卷 112-125页

作者： Nil Kanatha Pandey wei Xiong Lingyun Wang wei Chen Brian Bui Jian Yang Eric Amador Mingli Chen Christina Xing Aseem Atul Athavale Yaowu Hao Wirya Feizi Lloyd Lumata Department of Physics The University of Texas at ArlingtonArlingtonTX 76019USA Key Laboratory of Functional Molecular Engineering of Guangdong Province School of Chemistry and Chemical EngineeringSouth China University of TechnologyGuangzhou510640China Department of Biomedical Engineering The Pennsylvania State UniversityUniversity ParkPA16802USA Department of Chemistry College of SciencesNortheastern UniversityBox 332Shenyang 110819China Department of Materials Science and Engineering The University of Texas at ArlingtonArlingtonTX 76019USA Department of Physics The University of Texas at Dallas800 West Campbell RoadRichardsonTX 75080USA

Aggregation-induced emission luminogens(AIEgens)exhibit efficient cytotoxic reactive oxygen species(ROS)generation capability and unique light-up features in the aggregated state,which have been well explored in image-guided photodynamic therapy(PDT).However,the limited penetration depth of light in tissue severely hinders AIEgens as a candidate for primary or adjunctive therapy for clinical ***,microwaves(MWs)show a distinct advantage for deeper penetration depth in tissues than ***,for the first time,we report AIEgen-mediated microwave dynamic therapy(MWDT)for cancer *** found that two AIEgens(TPEPy-I and TPEPy-PF6)served as a new type of microwave(MW)sensitizers to produce ROS,including singlet oxygen(1O2),resulting in efficient destructions of cancer *** results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and live/dead assays reveal that the two AIEgens when activated by MW irradiation can effectively kill cancer cells with average IC-50 values of 2.73 and 3.22μM,***,the ability of the two AIEgens to be activated by MW not only overcomes the limitations of conventional PDT,but also helps to improve existing MW ablation therapy by reducing the MW dose required to achieve the same therapeutic outcome,thus reducing the occurrence of side-effects of MW radiation.

关键词： AIEgens Microwaves Photodynamic therapy Reactive oxygen species Microwave ablation Cancer treatment Singlet oxygen

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Programmable dual responsive system reconstructing nerve interaction with small-diameter tissue-engineered vascular grafts and inhibiting intimal hyperplasia in diabetes

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Bioactive Materials 2022年第1期7卷 466-477页

作者： Yanzhao Li Yeqin Wang Fangchao Xue Xuli Feng Zhaojing Ba Junjie Chen Zhenhua Zhou Yanhong Wang Ge Guan Guanyuan Yang Ziwei Xi Hao Tian Yong Liu Ju Tan Gang Li Xiewan Chen Mingcan Yang wen Chen Chuhong Zhu wen Zeng Department of Anatomy National and Regional Engineering Laboratory of Tissue EngineeringState and Local Joint Engineering Laboratory for Vascular ImplantsKey Lab for Biomechanics and Tissue Engineering of ChongqingThird Military Medical UniversityChongqing400038China Department of Cell Biology Third Military Army Medical UniversityChongqing400038China Innovative Drug Research Centre of Chongqing University Chongqing401331China Departments of Neurology Southwest HospitalThird Military Medical UniversityChongqingChina medical English Department Third Military Medical UniversityChongqing400038China The 8th medical Center of Chinese PLA General Hospital Beijing100091China Department of Plastic and Aesthetic Surgery Southwest HospitalThird Military Medical UniversityChongqingChina State Key Laboratory of Trauma Burn and Combined InjuryChongqingChina

Small-diameter tissue-engineered vascular grafts(sdTEVGs)with hyperglycemia resistance have not been *** intimal hyperplasia caused by hyperglycemia remains problem to hinder the patency of ***,inspired by bionic regulation of nerve on vascular,we found the released neural exosomes could inhibit the abnormal phenotype transformation of vascular smooth muscle cells(VSMCs).The transformation was a prime culprit causing the intimal hyperplasia of *** address this concern,sdTEVGs were modified with an on-demand programmable dual-responsive system of ultrathin *** external primary Reactive Oxygen Species(ROS)-responsive Netrin-1 system was initially triggered by local inflammation to induce nerve remolding of the sdTEVGs overcoming the difficulty of nerve regeneration under ***,the internal secondary ATP-responsive DENND1A(guanine nucleotide exchange factor)system was turned on by the neurotransmitter ATP from the immigrated nerve fibers to stimulate effective release of neural *** results showed nerve fibers grow into the sdTEVGs in diabetic rats 30 days after *** day 90,the abnormal VSMCs phenotype was not detected in the sdTEVGs,which maintained long-time patency without intima *** study provides new insights to construct vascular grafts resisting hyperglycemia damage.

关键词： sdTEVGs On-demand programmed responsive systems Neural exosomes Nerve reconstruction Intimal hyperplasia

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ACOUSTIC MEASUREMENTS BUBBLES IN BIOLOGICAL TIESSURE

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Journal of Hydrodynamics 2009年第1期21卷 47-64页

作者： CHAHINE Georges L. TANGUAY Michel LORAINE Greg DYNAFLOW INC. 10621-J Iron Bridge Road Jessup Maryland 20794 USA

An acoustic based instrument, the ABS Acoustic Bubble Spectrometer@@（ABS）, was investigated for the detection and quantification of bubbles in biological media. These include viscoelastic media （blood）, materials of varying density （bone in tissue）, non-homogenous distribution of bubbles （intravenous bubbly flow）, and bubbles migrating in tissue （decompression sickness, DCS）. The performance of the ABS was demonstrated in a series of laboratory experiments. Validation of the code was performed using a viscoelastic polymer solution, Polyox, in which the bubble size distribution and void fraction were determined by ABS measurements and with image analysis of high speed videos. These tests showed that the accuracy of the ABS was not significantly affected by viscoelasticity for bubbles smaller than 200 microns. The ABS detection and measurement of non-homogenous bubble distributions was demonstrated using a bubbly flow through a simulated vein surrounded by tissue. The scatter of acoustic signals due to bones in the acoustic pathway was also investigated. These in-vitro experiments were done using meat （beef） as a tissue simulant. Decompression experiments were done using beef meat which was held underwater at high pressure （9.9 atm） then rapidly decompressed. Bubble size distributions and void fraction calculations in these experiments were then validated using image analysis of high speed video. In addition, preliminary experiments were performed with the US Navy medical Research Center, demonstrating the utility of the modified ABS system in detecting the evolution of bubbles in swine undergoing decompression sickness （DCS）. These results indicate that the ABS may be used to detect and quantify the evolution of bubbles in-vivo and aid in the monitoring of DCS.

关键词： ABS Acoustic Bubble Spectrometer@@ (ABS) biological tissue decompression sickness (DCS)

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