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A multi-parameter-induced activation of gas therapeutic platform to remarkably amplify photodynamic therapy efficacy

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Science China Chemistry 2024年第7期67卷 2403-2411页

作者： Jie Sun Ziwen Zhang Hongyu Wu Xuemei Dong Chengjun Dong Lixin Sun Zhiqian Guo Yingchao Liu Xianfeng Gu Chunchang Zhao Key Laboratory for Advanced Materials and Feringa Nobel Prize Scientist Joint Research Center Institute of Fine ChemicalsSchool of Chemistry and Molecular EngineeringEast China University of Science and TechnologyShanghai 200237China Department of Medicinal Chemistry School of PharmacyFudan UniversityShanghai 201203China Shandong Provincial Hospital Affiliated to Shandong First medical university Shandong First Medical University&Shandong Academy of Medical ScienceJinan 250021China

Gas therapy(GT)combined with photodynamic therapy(PDT)is an effective strategy to compensate for the PDT limitation caused by the hypoxic tumor microenvironment,which can greatly improve PDT *** uncontrolled leakage of gas molecules during delivery seriously hinders its practical biological ***,we report a multifunction nanomedicine that enables precise gas therapy(including carbon monoxide(CO)release and H_(2)S depletion)using a multi-parameter-induced activation gas release strategy,enlarging the PDT *** nanomedicine uses a disulfide bond to covalently link a photosensitizer with the CO donor 3-hydroxyflavone(3-HF).The disulfide bond can be specifically consumed in H_(2)S-rich tumor areas,releasing the CO donor(3-HF),and also depleting H_(2)*** importantly,the photo-controlled production of^(1)O_(2)can induce 3-HF precise release of CO in the tumor *** H_(2)S,light,and^(1)O_(2)multi-parameter-induced activation of gas release strategy ensures the accuracy of GT to amplify PDT *** expected,in vitro and in vivo investigations show that GT makes up for the PDT limitation,exhibiting the highest tumor therapeutic *** multi-parameter-activated design strategy provides a new way to improve the precision and efficacy of multimodal synergistic therapy of tumors.

关键词： gas therapy precision gas release hydrogen sulfide depletion photodynamic therapy multimodal synergistic therapy

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Drinking water quality & health risk assessment of secondary water supply systems in residential neighborhoods

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Frontiers of Environmental Science & Engineering 2024年第2期18卷 47-62页

作者： Yating Wei Dong Hu Chengsong Ye Heng Zhang Haoran Li Xin Yu College of the Environment&Ecology Xiamen UniversityXiamen 361102China school of Public Health Shandong First Medical University&Shandong Academy of Medical SciencesJinan 250117China

Secondary water supply systems(SWSSs)are important components of the water supply infrastructure that ensure residents’drinking water *** are characterized by long detention time,warm temperature,and unreasonable management,which may trigger the deterioration of water quality and increase *** this study,drinking water quality index(DWQI)and health risk assessment(HRA)were selected and modified to quantitatively assess the water quality and health risks of SWSSs in residential *** total,121 seasonal water samples were *** was observed that the water quality was excellent with the DWQI of 0.14±0.04,excluding one sample,which was extremely poor owing to its excessive total bacterial *** HRA results revealed that the health risks were low:negligible non-carcinogenic risk for any population;negligible and acceptable carcinogenic risk for children aged 6–17 and ***,samples revealed higher carcinogenic risk(7.63×10−5±3.29×10−6)for children aged 0–5,and arsenic was the major *** samples had poor water quality and higher health risks,which called for *** further investigate the water quality and health risks of SWSSs,monthly sampling was conducted during *** 24 water samples were qualified in Chinese standard(GB 5749-2022)and characterized as excellent *** HRA results were consistent with the seasonal samples’and the health risks were mainly concentrated in ***,our study provides a suitable framework for water quality security,advice for managers,and references for administrators in other cities.

关键词： Drinking water quality Water quality index Health risk assessment Secondary water supply systems Heavy metals

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A combined nanotherapeutic approach targeting farnesoid X receptor,ferroptosis,and fibrosis for nonalcoholic steatohepatitis treatment

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2228-2246页

作者： Jiangtao Fu Pingping Zhang Zhiguo Sun Guodong Lu Qi Cao Yiting Chen Wenbin Wu Jiabao Zhang Chunlin Zhuang Chunquan Sheng Jiajun Xu Ying Lu Pei Wang The Center for Basic Research and Innovation of Medicine and Pharmacy(MOE) School of PharmacyNaval Medical UniversityShanghai 200433China National Demonstration Center for Experimental Pharmaceutical Education Naval Medical University/Second Military Medical UniversityShanghai 200433China Department of Diving and Hyperbaric Medicine Naval Special Medical CenterNaval Medical UniversityShanghai 200433China

Obeticholic acid(OCA),a farnesoid X receptor(FXR)agonist with favorable effects on fatty and glucose metabolism,has been considered the leading candidate drug for nonalcoholic steatohepatitis(NASH)***,its limited effectiveness in resolving liver fibrosis and lipotoxicity-induced cell death remains a major ***,a newly recognized form of cell death characterized by uncontrolled lipid peroxidation,is involved in the progression of *** oxide(NO)is a versatile biological molecule that can degrade extracellular *** this study,we developed a PEGylated thiolated hollow mesoporous silica nanoparticles(MSN)loaded with OCA,as well as a ferroptosis inhibitor liproxsatin-1 and a NO donor S-nitrosothiol(ONL@MSN).Biochemical analyses,histology,multiplexed flow cytometry,bulk-tissue RNA sequencing,and fecal 16S ribosomal RNA sequencing were utilized to evaluate the effects of the combined nanoparticle(ONL@MSN)in a mouse NASH *** with the OCA-loaded nanoparticles(O@MSN),ONL@MSN not only protected against hepatic steatosis but also greatly ameliorated fibrosis and ***@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis,inhibition of immune response/lipid peroxidation,and correction of microbiota *** findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FXR,ferroptosis,and fibrosis.

关键词： Nonalcoholic steatohepatitis Nanotherapy Farnesoid X receptor Ferroptosis Fibrosis Obeticholic acid S-Nitrosothiol Liproxstatin-1

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In vivo imaging reveals a synchronized correlation among neurotransmitter dynamics during propofol and sevoflurane anesthesia

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Zoological Research 2024年第3期45卷 679-690页

作者： Gao-Lin Qiu Li-Jun Peng Peng Wang Zhi-Lai Yang Ji-Qian Zhang Hu Liu Xiao-Na Zhu Jin Rao Xue-Sheng Liu Department of Anesthesiology First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China school of Life Science and technology ShanghaiTech UniversityShanghai 201210China

General anesthesia is widely applied in clinical ***,the precise mechanism of loss of consciousness induced by general anesthetics remains ***,we measured the dynamics of five neurotransmitters,includingγ-aminobutyric acid,glutamate,norepinephrine,acetylcholine,and dopamine,in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter *** revealed that the concentrations of γ-aminobutyric acid,glutamate,norepinephrine,and acetylcholine increased in the cortex during propofol-induced loss of *** levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol ***,the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of ***,the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic *** findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.

关键词： General anesthesia Loss of consciousness In vivo neurotransmitter imaging Medial prefrontal cortex Primary visual cortex

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Tim4 deficiency reduces CD301b+macrophage and aggravates periodontitis bone loss

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International Journal of Oral Science 2024年第2期16卷 280-292页

作者： Ziming Wang Hao Zeng Can Wang Jiaolong Wang Jing Zhang Shuyuan Qu Yue Han Liu Yang Yueqi Ni Wenan Peng Huan Liu Hua Tang Qin Zhao Yufeng Zhang State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyTaikang Center for Life and Medical SciencesWuhan UniversityWuhanChina school of Stomatology Nanchang UniversityNanchangChina Institute of Infection and Immunity Science and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinanChina medical Research Institute School of MedicineWuhan UniversityWuhanChina

Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth *** the progression of periodontitis,the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone ***301b^(+)macrophages are specific to the osteoimmunology microenvironment,and are emerging as vital booster for conducting bone ***,the key upstream targets of CD301b^(+)macrophages and their potential mechanism in periodontitis remain *** this study,we concentrated on the role of Tim4,a latent upstream regulator of CD301b^(+)*** first demonstrated that the transcription level of Timd4(gene name of Tim4)in CD301b^(+)macrophages was significantly upregulated compared to CD301b^(-) macrophages via high-throughput RNA ***,several Tim4-related functions such as apoptotic cell clearance,phagocytosis and engulfment were positively regulated by CD301b^(+)*** single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in *** following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b^(+)macrophages as periodontitis ***,the deficiency of Tim4 in mice decreased CD301b^(+)macrophages and eventually magnified alveolar bone resorption in ***,Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b^(+)macrophages *** a word,Tim4 might regulate CD301b^(+)macrophages through p38 MAPK signaling pathway in periodontitis,which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.

关键词： period upstream eventually

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Immune checkpoint inhibitor-associated gastritis:Patterns and management

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World Journal of Gastroenterology 2024年第14期30卷 1941-1948页

作者： Jing Lin Zhong-Qiao Lin Shi-Cheng Zheng Yu Chen Department of medical Oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350000Fujian ProvinceChina Phase I Clinical Trial Ward Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhou 350000Fujian ProvinceChina school of Basic medical Sciences Fujian Medical UniversityFuzhou 350000Fujian ProvinceChina

Immune checkpoint inhibitors(ICIs)are widely used due to their effectiveness in treating various ***-related adverse events(irAEs)are defined as adverse effects resulting from ICI *** irAEs are a common type of irAEs characterized by intestinal side effects,such as diarrhea and colitis,which may lead to the cessation of *** irAE gastritis is rarely reported,it may lead to serious complications such as ***,irAE gastritis is often difficult to identify early due to its diverse *** steroid hormones and immunosuppressants are commonly used to reverse irAEs,the best regimen and dosage for irAE gastritis remains *** addition,the risk of recurrence of irAE gastritis after the reuse of ICIs should be *** this editorial,strategies such as early identification,pathological diagnosis,mana-gement interventions,and immunotherapy rechallenge are discussed to enable clinicians to better manage irAE gastritis and improve the prognosis of these patients.

关键词： Immunotherapy Immune checkpoint inhibitor Immune-related adverse events Immune checkpoint inhibitor-related gastritis

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Clinical and genomic analysis of baseline and acquired MET fusions with an intact kinase domain in lung cancer patients

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Genes & Diseases 2024年第1期11卷 76-79页

作者： Bo Jin Yutong Ma Qian Wu Qiuxiang Ou Yang Shao Shun Xu Department of medical Oncology The First Hospital of China Medical UniversityShenyangLiaoning 110001China Geneseeq Research Institute Nanjing Geneseeq Technology Inc.NanjingJiangsu 210000China school of Public Health Nanjing Medical UniversityNanjingJiangsu 211166China Department of Thoracic Surgery The First Hospital of China Medical UniversityShenyangLiaoning110001China

MET gene alterations in lung cancer patients mainly include exon 14 skipping and gene amplification,which are the key therapeutic targets and drive resistance to tyrosine kinase inhibitors(TKls).1 However,the structural variants of MET,such as MET fusions,are much rarer(0.26%),as reported in a Chinese non-small cell lung cancer(NSCLC)cohort.2 Several recurrent MET fusions,such as KIF5B-MET and HLADRB1-MET,were reported as oncogenic drivers and showed favorable responses to crizotinib.

关键词： lung patients alterations

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Overcoming adaptive resistance in AML by synergistically targeting FOXO3A-GNG7-mTOR axis with FOXO3A inhibitor Gardenoside and rapamycin

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Genes & Diseases 2024年第1期11卷 397-412页

作者： Zhe Chen Qian Guo Shichen Huang Lei Li Feng Wu Zhilong Liu Zhigang Li Tao Chen Guanbin Song Shuangnian Xu Jieping Chen Yu Hou Department of Hematology Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Institute of Life Sciences Chongqing Medical UniversityChongqing 400016China Key Laboratory of Biorheological Science and technology Ministry of EducationCollege of BioengineeringChongqing UniversityChongqing 400044China Chongqing Foreign Language school Chongqing 400039China

Therapeutic targeting FOxO3A(a forkhead transcription factor)represents a prom-ising strategy to suppress acute myeloid leukemia(AML).However,the effective inhibitors that target FOXO3A are lacking and the adaptive response signaling weakens the cytotoxic effect of FOxO3A depletion on AML ***,we show that FOxO3A deficiency induces a compensa-tory response involved in the reactive activation of mTOR that leads to signaling rebound and adaptive *** metabolism acts downstream of mTOR to provoke activa-tion of JNK/c-JUN via reactive oxygen species(ROS).At the molecular level,FOXO3A directly binds to the promoter of G protein gamma subunit 7(GNG7)and preserves its expression,while GNG7 interacts with mTOR and restricts phosphorylated activation of ***,combinatorial inhibition of FOXO3A and mTOR show a synergistic cytotoxic effect on AML cells and prolongs survival in a mouse model of *** a structure-based virtual screening,we report one potent small-molecule FOxO3A inhibitor(Gardenoside)that exhibits a strong effect of anti-FOXO3A DNA *** synergizes with rapamycin to substantially reduce tumor burden and extend survival in AML patient-derived xenograft *** results demonstrate that mTOR can mediate adaptive resistance to FOxO3A inhibition and validate a combinatorial approach for treating AML.

关键词： AML Combinatorial inhibition FOXO3A GNG7 mTOR

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Distinguished biological adaptation architecture aggravated population differentiation of Tibeto-Burman-speaking people

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Journal of Genetics and Genomics 2024年第5期51卷 517-530页

作者： Yuntao Sun Mengge Wang Qiuxia Sun Yan Liu Shuhan Duan Zhiyong Wang Yunyu Zhou Jun Zhong Yuguo Huang Xinyu Huang Qingxin Yang Xiangping Li Haoran Su Yan Cai Xiucheng Jiang Jing Chen Jiangwei Yan Shengjie Nie Liping Hu Junbao Yang Renkuan Tang Chuan-Chao Wang Chao Liu Xiaohui Deng Libing Yun Guanglin He West China school of Basic Science&Forensic Medicine Sichuan UniversityChengduSichuan 610041China Institute of Rare Diseases West China Hospital of Sichuan UniversitySichuan UniversityChengduSichuan 610000China Center for Archaeological Science Sichuan UniversityChengduSichuan 610000China Faculty of Forensic Medicine Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510275China Guangzhou Forensic Science Institute GuangzhouGuangdong 510055China Department of Forensic Medicine College of Basic MedicineChongqing Medical UniversityChongqing 400331China school of Clinical medical Sciences North Sichuan Medical CollegeNanchongSichuan 637100China school of Basic medical Sciences North Sichuan Medical CollegeNanchongSichuan 637100China school of Forensic Medicine Kunming Medical UniversityKunmingYunnan 650500China school of Stomatology North Sichuan Medical CollegeNanchongSichuan 637100China Department of medical Laboratory North Sichuan Medical CollegeNanchongSichuan 637007China school of Life Sciences Xiamen UniversityXiamenFujian 361005China Anti-Drug technology Center of Guangdong Province GuangzhouGuangdong 510230China school of Forensic Medicine Shanxi Medical UniversityJinzhongShanxi030600China

Tibeto-Burman(TB)people have endeavored to adapt to the hypoxic,cold,and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic ***,the full landscape of genetic history and biological adaptation of geographically diverse TB-speaking people,as well as their interaction mechanism,remain ***,we generate a whole-genome meta-database of 500 individuals from 39 TB-speaking populations and present a comprehensive landscape of genetic diversity,admixture history,and differentiated adaptative features of geographically different TB-speaking *** identify genetic differentiation related to geography and language among TB-speaking people,consistent with their differentiated admixture process with incoming or indigenous ancestral source populations.A robust genetic connection between the Tibetan-Yi corridor and the ancient Yellow River people supports their Northern China origin *** finally report substructure-related differentiated biological adaptative signatures between highland Tibetans and Loloish *** signatures associated with the physical pigmentation(EDAR and SLC24A5)and metabolism(ALDH9A1)are identified in Loloish people,which differed from the high-altitude adaptative genetic architecture in ***-related genomic resources provide new insights into the genetic basis of biological adaptation and better reference for the anthropologically informed sampling design in biomedical and genomic cohort research.

关键词： Tibeto-Burman people Genetic profile Natural selection Genetic diversity Biological adaptation

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APTAnet: an atom-level peptide-TCR interaction affinity prediction model

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Biophysics Reports 2024年第1期10卷 1-14页

作者： Peng Xiong Anyi Liang Xunhui Cai Tian Xia school of Artificial Intelligence and Automation Huazhong University of Science and Technology Institute of Pathology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

The prediction of affinity between TCRs and peptides is crucial for the further development of TIL(Tumor-Infiltrating Lymphocytes) immunotherapy. Inspired by the broader research of drug-protein interaction(DPI), we propose an atom-level peptide-TCR interaction(PTI) affinity prediction model APTAnet using natural language processing methods. APTAnet model achieved an average ROC-AUC and PR-AUC of 0.893 and 0.877, respectively, in ten-fold cross-validation on 25,675 pairs of PTI ***, experimental results on an independent test set from the McPAS database showed that APTAnet outperformed the current mainstream models. Finally, through the validation on 11 cases of real tumor patient data, we found that the APTAnet model can effectively identify tumor peptides and screen tumor-specific TCRs.

关键词： Immunotherapy TCR Antigen Natural language processing Transfer learning

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