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Relationships between blood chromium exposure and liver injury:Exploring the mediating role of systemic inflammation in a chromate-exposed population

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Journal of Environmental sciences 2024年第9期143卷 224-234页

作者： Zekang Su Yali Zhang Shiyi Hong Qiaojian Zhang Jiayu Xu Guiping Hu Xiaojun Zhu Fang Yuan Shanfa Yu Tianchen Wang Guang Jia Department of Occupational and Environmental health sciences School of Public HealthPeking UniversityBeijing 100191China School of Engineering medicine and Beijing Advanced Innovation Center for Big Data-Based Precision medicine Beihang UniversityBeijing 100191China National Center for Occupational Safety and health Beijing 102308China Department of Occupational health and Radiological health Chongqing Centers for Disease Control and PreventionChongqing 400042China Henan Institute for Occupational medicine Zhengzhou 450052China Department of Clinical Laboratory Third Hospital of Peking UniversityBeijing 100191China

Hexavalent chromium and its compounds are prevalent pollutants,especially in the work environment,pose a significant risk for multisystem toxicity and *** it is known that chromium accumulation in the liver can cause damage,the dose-response relationship between blood chromium(Cr)and liver injury,as well as the possible potential toxic mechanisms involved,remains poorly *** address this,we conducted a follow-up study of 590 visits from 305 participants to investigate the associations of blood Cr with biomarkers for liver injury,including serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),and direct bilirubin(DBIL),and to evaluate the mediating effects of systemic ***(PLT)and the platelet-to-lymphocyte ratio(PLR)were utilized as biomarkers of systemic *** the linear mixed-effects analyses,each 1-unit increase in blood Cr level was associated with estimated effect percentage increases of 0.82%(0.11%,1.53%)in TBIL,1.67%(0.06%,3.28%)in DBIL,0.73%(0.04%,1.43%)in ALT and 2.08%(0.29%,3.87%)in AST,***,PLT mediated 10.04%,11.35%,and 10.77%increases in TBIL,DBIL,and ALT levels induced by chromate,*** addition,PLR mediated 8.26%and 15.58%of the association between blood Cr and TBIL or *** findings shed light on the mechanisms underlying blood Cr-induced liver injury,which is partly due to worsening systemic inflammation.

关键词： Blood chromate Liver injury Systemic inflammation Mediation analysis

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Reductive lipid nanoparticles loaded with vinorelbine inhibit chemotherapy-induced invasion of cancer cells by modulating ENPP2

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Nano Research 2024年第4期17卷 2886-2898页

作者： Xiaoqi Zhao Xuemeng Guo Mei Pang Weigen Qiu Zhenyu Luo Qing Lin Yichao Lu Hang Yin Sijie Wang Huihui Liu Junlei Zhang Lihua Luo Jian You college of Pharmaceutical sciences Zhejiang University866 Yuhangtang RoadHangzhou 310058China Hangzhou Institute of Innovative medicine Zhejiang UniversityHangzhou 310058China

Cancer is a predominant culprit behind worldwide death and accounts for up to 10 million deaths every *** is the primary therapeutic method employed for cancer in clinical settings and is essential in controlling tumor *** the advances in this field,tumor invasion and metastasis during treatment remain a significant cause of treatment ***,the underlying mechanisms involving such a disappointing phenomenon are still not fully ***(VNB)extends the lifespan of many cancer patients in the clinic as an emerging chemotherapy drug approved by Food and Drug Administration(FDA).However,VNB-induced tumor metastasis is still an intractable problem,which may be closely related to the abnormal oxidative stress generated during VNB-mediated ***,the study aims to construct a reductive nanosystem loaded with VNB,called VNB-VNP,to improve cancer cure rates and reduce tumor *** the reductive component vitamin E,VNB-VNP can effectively reduce oxidative stress and significantly outperform free VNB in preventing tumor *** transcriptome analysis shows that VNB-VNP can alleviate the over-expression of ectonucleotide pyrophosphatase/phosphodiesterase 2(ENPP2),which may be the main reason why VNB-VNP can inhibit tumor invasion and ***,the research designs a new platform for VNB treatment,which demonstrates promising efficacy in inhibiting neoplastic progression and identifies a new mechanism associated with VNB-induced tumor metastasis,which may offer several valuable references for enhancing chemotherapy efficacy in clinical anti-tumor therapy.

关键词： chemotherapy vinorelbine tumor Invasion lysophosphatidic acid ectonucleotide pyrophosphatase/phosphodiesterase 2(ENPP2)

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Dysregulated N6-methyladenosine modification in peripheral immune cells contributes to the pathogenesis of amyotrophic lateral sclerosis

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Frontiers of medicine 2024年第2期18卷 285-302页

作者： Di He Xunzhe Yang Liyang Liu Dongchao Shen Qing Liu Mingsheng Liu Xue Zhang Liying Cui Department of Neurology Peking Union Medical College Hospital(PUMCH)Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China Medical Doctor Program Chinese Academy of Medical Science and Peking Union Medical CollegeBeijing100730China McKusick-Zhang Center for Genetic medicine State Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing100730China Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China

Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain *** evidence implicates N6-methyladenosine(m6A)modification in ALS *** RNA immunoprecipitation sequencing(MeRIP-seq)and liquid chromatography–mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis,respectively,in patients with ALS(n=16)and controls(n=6).The single-cell transcriptomic dataset(GSE174332)of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication *** of peripheral immune cells revealed extensive RNA hypermethylation,highlighting candidate genes with differential m6A modification and expression,including C-X3-C motif chemokine receptor 1(CX3CR1).In RAW264.7 macrophages,disrupted CX3CR1 signaling affected chemotaxis,potentially influencing immune cell migration in *** proteome analysis demonstrated the role of dysregulated immune cell migration in *** type-specific expression variations of these genes in the central nervous system(CNS),particularly microglia,were *** communication between neurons and glial cells was selectively altered in ALS *** integrated approach underscores m6A dysregulation in immune cells as a potential ALS contributor.

关键词： amyotrophic lateral sclerosis N^(6)-methyladenosine epi-transcriptome proteome single cell RNA sequencing analysis CX3CR1

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health behavior outcomes in stroke survivors prescribed wearables for atrial fibrillation detection stratified by age

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Journal of Geriatric Cardiology 2024年第3期21卷 323-330页

作者： Joanne Mathew Jordy Mehawej Ziyue Wang Taylor Orwig Eric Ding Andreas Filippaios Syed Naeem Edith Mensah Otabil Alex Hamel Kamran Noorishirazi IrinaRadu Jane Saczynski David D.McManus Khanh-Van Tran Division of Cardiovascular medicine Department of MedicineUniversity of Massachusetts Chan Medical SchoolLake Avenue NorthWorcesterUSA Department of Internal medicine Central Michigan UniversityMount PleasantUSA Department of Pharmacy and health Systems sciences School of PharmacyNortheastern UniversityBostonUSA Department of Population and Quantitative health sciences University of Massachusetts Chan Medical SchoolLake Avenue NorthWorcesterUSA

BACKGROUND Smartwatches have become readily accessible tools for detecting atrial fibrillation(AF).There remains limited data on how they affect psychosocial outcomes and engagement in older *** examine the health behavior outcomes of stroke survivors prescribed smartwatches for AF detection stratified by *** We analyzed data from the Pulsewatch study,a randomized controlled trial that enrolled patients(≥50 years)with a history of stroke or transient ischemic attack and CHA2DS2-VASc≥*** participants were equipped with a cardiac patch monitor and a smartwatch-app dyad,while control participants wore the cardiac patch monitor for up to 44 *** evaluated health behavior parameters using standardized tools,including the Consumer health Activation Index,the Generalized Anxiety Disorder questionnaire,the 12-Item Short Form health Survey,and wear time of participants categorized into three age groups:Group 1(ages 50-60),Group 2(ages 61-69),and Group 3(ages 70-87).We performed statistical analysis using a mixedeffects repeated measures linear regression model to examine differences amongst age *** Comparative analysis between Groups 1,2 and 3 revealed no significant differences in anxiety,patient activation,perception of physical health and wear *** use of smartwatch technology was associated with a decrease in perception of mental health for Group 2 compared to Group 1(β=-3.29,P=0.046).CONCLUSION Stroke survivors demonstrated a willingness to use smartwatches for AF ***,among these study participants,the majority did not experience negative health behavior outcomes or decreased engagement as age increased.

关键词： prescribed stratified wear

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Host-guest cocrystals boost thermally activated delayed fluorescence materials

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Science China Chemistry 2024年第10期67卷 3179-3180页

作者： Wenzhi Yang Jiong Zhou Department of Chemistry College of SciencesNortheastern University

Organic light-emitting diodes(OLEDs) play an important role in organic display and lighting fields. Thermally activated delayed fluorescence(TADF) materials have shown great potential in the OLED field because they can theoretically achieve 100% utilization of excitons and avoid heavy metal pollution problems [1].

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Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death

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Biomedical and Environmental sciences 2024年第1期37卷 54-70页

作者： YU Jin Hai HU Guo Liang GUO Xiao Quan CAO Hua Bin XIA Zhao Fei AMIN Buhe Jiangxi Provincial Key Laboratory for Animal health Institute of Animal Population HealthCollege of Animal Science and TechnologyJiangxi Agricultural UniversityNanchang 330045JiangxiChina Internal medicine Laboratory Department of Veterinary Clinical MedicineCollege of Veterinary MedicineChina Agricultural UniversityBeijing 100091China Department of Cancer Surgery Beijing Shijitan Hospital Affiliated with Capital Medical UniversityBeijing 100038China

Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide(LPS)induced septic cardiac *** Specific pathogen-free chicken embryos(n=120)were allocated untreated control,phosphate buffer solution(PBS)vehicle,PBS with ethanol vehicle,LPS(500 ng/egg),LPS with quercetin treatment(10,20,or 40 nmol/egg,respectively),Quercetin groups(10,20,or 40 nmol/egg).Fifteenday-old embryonated eggs were inoculated with abovementioned solutions via the allantoic *** embryonic day 19,the hearts of the embryos were collected for histopathological examination,RNA extraction,real-time polymerase chain reaction,immunohistochemical investigations,and Western *** They demonstrated that the heart presented inflammatory responses after LPS *** LPS-induced higher mRNA expressions of inflammation-related factors(TLR4,TNFα,MYD88,NF-κB1,IFNγ,IL-1β,IL-8,IL-6,IL-10,p38,MMP3,and MMP9)were blocked by quercetin with three *** significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS *** significantly decreased protein expressions of TLR4,IFNγ,MMP3,and MMP9 when compared with the LPS *** treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1,and significantly decreased protein expression of claudin 1 when compared with the LPS *** significantly downregulated autophagyrelated gene expressions(PPARα,SGLT1,APOA4,AMPKα1,AMPKα2,ATG5,ATG7,Beclin-1,and LC3B)and programmed cell death(Fas,Bcl-2,CASP1,CASP12,CASP3,and RIPK1)after LPS *** significantly decreased immunopositivity to APOA4,AMPKα2,and LC3-II/LC3-I in the treatment group when compared with the LPS *** significantly decreased protein expressions of AMPKα1,LC3-I,and *** significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or

关键词： Quercetin Lipopolysaccharide Inflammation Autophagy Programmed cell death Myocardiocytes permeability

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Neurokinin-2 receptor antagonist SR48968 induced necroptosis of myeloid leukemia cells by calcium overload-driven reactive oxygen species accumulation

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Genes & Diseases 2024年第5期11卷 33-35页

作者： Zhibin Yan Xiangyu Hong Qihao Lin Leijie Wang Gang Shao Chentao Ge Ruilong Xia Caiyun Fu Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine College of Life Sciences and MedicineZhejiang Sci-Tech UniversityHangzhouZhejiang 310018China college of Life sciences China Jiliang UniversityHangzhouZhejiang 310018China

Increasing evidence highlight tachykinin receptors as a prominent player in hematological *** previously revealed the proto-oncogenic role of neurokinin-1 receptor(NK-1R)in acute myeloid leukemia(AML),1 whereas the role of neurokinin-2 receptor(NK-2R)has not been ***,we found NK-2R was significantly up-regulated in AML patients in The Cancer Genome Atlas *** result was further confirmed in blood from AML patients and a range of human leukemia ***,we verified that blocking NK-2R by SR48968 markedly promoted cell death in human myeloid leukemia without cytotoxicity to normal ***,we uncovered that SR48968 induced cytotoxicity through necroptosis mediated by calcium overload-driven reactive oxygen species(ROS)*** summary,our results propose that NK-2R antagonist SR48968 may be used as a new therapeutic approach for myeloid leukemia.

关键词： myeloid antagonist markedly

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Seco-cyclic phorbol derivatives and their anti-HIV-1 activities

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Chinese Journal of Natural medicines 2024年第4期22卷 365-374页

作者： HUANG Xiaolei HUANG Xusheng LI Qirun MA Mengdi CUI Yadong YANG Liumeng WANG Haibo LUO Ronghua CHEN Jinglei YANG Jingxuan LIN Jinrong LI Duxin ZHENG Yongtang ZHANG Jian college of Pharmaceutical Science Soochow UniversitySuzhou 215123China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of sciences/Key Laboratory of Bioactive Peptides of Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Kunming college of Life Science University of Chinese Academy of SciencesKunming 650204China college of Traditional Chinese medicine Yunnan University of Chinese MedicineKunming 650500China

Phorbol esters are recognized for their dual role as anti-HIV-1 agents and as activators of protein kinase C(PKC).The efficacy of phorbol esters in binding with PKC is attributed to the presence of oxygen groups at positions C20,C3/C4,and C9 of ***,the lipids located at positions C12/C13 are essential for both the anti-HIV-1 activity and the formation of the PKC-ligand *** influence of the cyclopropane ring at positions C13 and C14 in phorbol derivatives on their anti-HIV-1 activity requires further *** research entailed the hydrolysis of phorbol,producing seco-cyclic phorbol *** anti-HIV-1 efficacy of these derivatives was assessed,and the affinity constant(Kd)for PKC-δprotein of selected seco-cyclic phorbol derivatives was determined through isothermal titration *** findings suggest that the chemical modification of cyclopropanols could affect both the anti-HIV-1 activity and the PKC binding ***,compound S11,with an EC_(50) of 0.27μmol·L^(−1) and a CC_(50) of 153.92μmol·L^(−1),demonstrated a potent inhibitory effect on the intermediate products of HIV-1 reverse transcription(ssDNA and 2LTR),likely acting at the viral entry stage,yet showed no affinity for the PKC-δ*** results position compound S11 as a potential candidate for further preclinical investigation and for studies aimed at elucidating the pharmacological mechanism underlying its anti-HIV-1 activity.

关键词： seco-Cyclic phorbol derivatives Hydrolysis reaction Cyclopropane ring Esterification Anti-HIV-1 agent

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Influencing Factors of healthy Aging Risk Assessed Using Biomarkers:A Life Course Perspective

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China CDC weekly 2024年第11期6卷 219-224,I0014-I0017页

作者： Cedric Zhang Bo Lua Yajie Gao Jinming Li Xingqi Cao Xinwei Lyu Yinuo Tu Shuyi Jin Zuyun Liu Center for Clinical Big Data and Analytics of the Second Affiliated Hospital and Department of Big Data in Health Science School of Public Healththe Key Laboratory of Intelligent Preventive Medicine of Zhejiang ProvinceZhejiang University School of MedicineHangzhou CityZhejiang ProvinceChina Institute of Epidemiology and health Care University College LondonLondonUK college of Chemical and Biological Engineering Zhejiang UniversityHangzhou CityZhejiang ProvinceChina

Assessing individual risks of healthy aging using biomarkers and identifying associated factors have become important areas of *** this study,we conducted a literature review of relevant publications between 2018 and 2023 in both Chinese and English *** studies have predominantly used single biomarkers,such as C-reactive protein,or focused on specific life course stages and factors such as socioeconomic status,mental health,educational levels,and unhealthy *** summarizing the progress in this field,our study provides valuable insights and future directions for promoting healthy aging from a life course perspective.

关键词： such insight directions

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Inhalable metal–organic framework-mediated cuproptosis combined with PD-L1 checkpoint blockade for lung metastasis synergistic immunotherapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2281-2297页

作者： Chongzheng Yan Ying Liu Guozhi Zhao Huatian Yang Huaiyou Lv Genju Li Yuhan Li Yaqing Fu Fengqin Sun Yafei Feng Yizhe Li Zhongxi Zhao Department of Pharmaceutics Key Laboratory of Chemical Biology of Ministry of EducationSchool of Pharmaceutical SciencesCheelloo College of MedicineShandong UniversityJinan 250012China Key University Laboratory of Pharmaceutics&Drug Delivery Systems of Shandong Province School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China

Cuproptosis shows enormous application prospects in lung metastasis ***,the glycolysis,Cu^(+)efflux mechanisms,and insufficient lung drug accumulation severely restrict cuproptosis ***,an inhalable poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate)(OPDEA)-coated copper-based metal–organic framework encapsulating pyruvate dehydrogenase kinase 1 siRNA(siPDK)is constructed for mediating cuproptosis and subsequently promoting lung metastasis immunotherapy,namely *** inhalation,OMP shows highly efficient lung accumulation and long-term retention,ascribing to the OPDEA-mediated pulmonary mucosa *** tumor cells,OMP is degraded to release Cu2+under acidic condition,which will be reduced to toxic Cu^(+)to induce cuproptosis under glutathione(GSH)***,siPDK released from OMP inhibits intracellular glycolysis and adenosine-5ʹ-triphosphate(ATP)production,then blocking the Cu^(+)efflux protein ATP7B,thereby rendering tumor cells more sensitive to OMP-mediated ***,OMP-mediated cuproptosis triggers immunogenic cell death(ICD)to promote dendritic cells(DCs)maturation and CD8^(+)T cells ***,OMP-induced cuproptosis up-regulates membrane-associated programmed cell death-ligand 1(PD-L1)expression and induces soluble PD-L1 secretion,and thus synergizes with anti-PD-L1 antibodies(aPD-L1)to reprogram immunosuppressive tumor microenvironment,finally yielding improved immunotherapy ***,OMP may serve as an efficient inhalable nanoplatform and afford preferable efficacy against lung metastasis through inducing cuproptosis and combining with aPD-L1.

关键词： Cuproptosis Immunogenic cell death PD-L1 checkpoint blockade Copper-based metal-organic framework Immunotherapy Tumor microenvironment Transmucosal deliveryLung metastasis

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