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Aspirin suppresses hepatocellular carcinoma progression by inhibiting platelet activity

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2742-2756页

作者： Li-Jun Zhao Zhi-Yin Wang Wei-Ting Liu Li-Li Yu Hao-Nan Qi Jie Ren Chen-Guang Zhang Hematology Laboratory The First Affiliated Hospital of Xinxiang Medical UniversityXinxiang 453100Henan ProvinceChina xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy School of Medical TechnologyXinxiang Medical UniversityXinxiang 453003Henan ProvinceChina School of public health Xinxiang Medical UniversityXinxiang 453003Henan ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)is the most common malignant liver disease in the ***(PLTs)are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes of a variety of liver *** is the most classic antiplatelet ***,the molecular mechanism of platelet action and whether aspirin can affect HCC progression by inhibiting platelet activity need further *** To explore the impact of the antiplatelet effect of aspirin on the development of *** Platelet-rich plasma,platelet plasma,pure platelet,and platelet lysate were prepared,and a coculture model of PLTs and HCC cells was ***-8 analysis,apoptosis analysis,Transwell analysis,and real-time polymerase chain reaction(RT-PCR)were used to analyze the effects of PLTs on the growth,metastasis,and inflammatory microenvironment of ***-PCR and Western blot were used to detect the effects of platelet activation on tumor-related signaling *** was used to block the activation and aggregation of PLTs both in vitro and in vivo,and the effect of PLTs on the progression of HCC RESULTS PLTs significantly promoted the growth,invasion,epithelial-mesenchymal transition,and formation of an inflammatory microenvironment in HCC *** PLTs promoted HCC progression by activating the mitogenactivated protein kinase/protein kinase B/signal transducer and activator of transcription three(MAPK/AKT/STAT3)signaling ***,aspirin inhibited HCC progression in vitro and in vivo by inhibiting platelet *** PLTs play an important role in the pathogenesis of HCC,and aspirin can affect HCC progression by inhibiting platelet *** results suggest that antiplatelet therapy has promising application prospects in the treatment and combined treatment of HCC.

关键词： Platelets Antiplatelet therapy Hepatocellular carcinoma Aspirin Antitumor

Zinc finger protein 831 promotes apoptosis and enhances chemosensitivity in breast cancer by acting as a novel transcriptional repressor targeting the STAT3/Bcl2 signaling pathway

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Genes & Diseases 2024年第1期11卷 430-448页

作者： Jun Fan Zhe Zhang Hongqiang Chen Dongjiao Chen Wenbo Yuan Jingzhi Li Yong Zeng Shimeng Zhou Shu Zhang Gang Zhang Jiashen Xiong Lu Zhou Jing Xu Wenbin Liu Yan Xu Department of Breast and Thyroid Surgery Daping HospitalArmy Medical University(Third Military Medical University)Chongqing 400042China Institute of Toxicology College of Preventive MedicineArmy Medical University(Third Military Medical University)Chongqing 400038China Department of Environmental health College of Preventive MedicineArmy Medical University(Third Military Medical University)Chongqing 400038China Anesthesia and Intensive Care Chinese University of Hong KongHong Kong SAR 999077China School of public health Xinxiang Medical UniversityXinxiangHenan 453003China School of public health China Medical UniversityShenyangLiaoning 110122China

Emerging evidence suggested that zinc finger protein 831(ZNF831)was associated with immune activity and stem cell regulation in breast ***,the roles and molec-ular mechanisms of ZNF831 in oncogenesis remain ***831 expression was significantly diminished in breast cancer which was associated with promoter CpG methylation but not *** over-expression of ZNF831 suppressed breast cancer cell proliferation and col-ony formation and promoted apoptosis in vitro,while knockdown of ZNF831 resulted in an opposite ***-proliferation effect of ZNF831 was verified in *** analysis of public databases and transcriptome sequencing both showed that ZNF831 could enhance apoptosis through transcriptional regulation of the JAK/STAT *** and luciferase report assays demonstrated that ZNF831 could directly bind to one specific region of STAT3 promoter and induce the transcriptional inhibition of *** a result,the attenuation of STAT3 led to a restraint of the transcription of Bcl2 and thus accelerated the apoptotic *** of STAT3 diminished the apoptosis-promoting effect of ZNF831 in breast cancer cell ***,ZNF831 could ameliorate the anti-proliferation effect of capecitabine and gemcitabine in breast cancer cell *** findings demonstrate for the first time that ZNF831 is a novel transcriptional suppressor through inhibiting the expression of STAT3/Bcl2 and promoting the apoptosis process in breast cancer,suggesting ZNF831 as a novel biomarker and potential therapeutic target for breast cancer patients.

关键词： Apoptosis Breast cancer Chemosensitivity STAT3 ZNF831

Beyond 1,4-addition of in-situ generated(aza-)quinone methides and indole imine methides

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Chinese Chemical Letters 2024年第7期35卷 35-53页

作者： Yan-Li Li Zhi-Ming Li Kai-Kai Wang Xiao-Long He medical college Xinxiang UniversityXinxiang 453000China School of Pharmacy Xinxiang UniversityXinxiang 453000China School of Food and Bioengineering Xihua UniversityChengdu 610039China

The conjugate addition of in-situ generated(aza-)quinone methides(QMs)and indole imine methides(IIMs)emerged as a powerful protocol to access densely functionalized benzenes and *** alcohols,aminobenzhydryl alcohols,and varied indolylmethanols served as most effective precursors for the in-situ generation of such reactive species under acid *** relevant propargylic alcohol has proven to be an elegant precursor to generate the propargylic-QMs and-IIMs via the acid promoted dehydration process,thus enabling diverse challenging remote activation to proceed conjugate1,6-and 1,***,the heteroarene has proven to be workable to transfer the LUMO of the p-QMs and 2-IIMs,thus inducing the remote nucleophilic dearomative *** conjugate additions of(aza-)p-QMs and varied IIMs has made significant contribution in the field of remote activation chemistry in past *** review summarizes the latest advances of the remote conjugate additions of the in-situ generated QMs and IIMs.

关键词： Conjugate addition QMs IIMs LUMO Remote activation Dearomative addition

Independent and Combined Associations of Sleep Duration, Bedtime, and Polygenic Risk Score with the Risk of Hearing Loss among Middle-Aged and Old Chinese: The Dongfeng–Tongji Cohort Study

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Research 2024年第1期2023卷 721-733页

作者： Miao Liu Haiqing Zhang Zhichao Wang Tingting Mo Xuefeng Lai Yaling He Minghui Jiang Meian He Weijia Kong Tangchun Wu Xiaomin Zhang Department of Occupational and Environmental health Ministry of Education Key Laboratory of Environment and Healthand State Key Laboratory of Environmental Health(Incubating)School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina Department of Otorhinolaryngology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina Department of Epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina

Evidence available on the independent and combined associations of sleep duration,bedtime,and genetic predisposition with hearing loss was *** present study included 15,827 participants from the Dongfeng–Tongji cohort *** risk was characterized by polygenic risk score(PRS)based on 37 genetic loci related to hearing *** conducted multivariate logistic regression models to assess the odds ratio(OR)for hearing loss with sleep duration and bedtime,as well as the joint association and interaction with *** showed that hearing loss was independently associated with sleeping≥9 h/night compared to the recommended 7 to9:00 *** 10:00 *** to those with bedtime>10:00 *** 11:00 p.m.,with estimated ORs of 1.25,1.27,and 1.16,respectively.

关键词： Middle hearing fen

Secreted Frizzled-Related Protein 5 Mediates Wnt5a Expression in Microcystin-Leucine-Arginine-Induced Liver Lipid Metabolism Disorder in Mice

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Biomedical and Environmental Sciences 2024年第8期37卷 850-864页

作者： Meiyan Yang Furong Yu Qianqian Ji Huiying Zhang Jiaxiang Zhang Daojun Chen Department of Occupational health and Environmental health School of Public HealthAnhui Medical UniversityHefei 230032AnhuiChina School of medical Technology Anhui Medical CollegeHefei 230601AnhuiChina

Objective Microcystin-leucine-arginine(MC-LR)exposure induces lipid metabolism disorders in the *** frizzled-related protein 5(SFRP5)is a natural antagonist of winglesstype MMTV integration site family,member 5A(Wnt5a)and an anti-inflammatory *** this study,we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5,which has anti-inflammatory effects,can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase(JNK)*** We exposed mice to MC-LR in vivo to induce liver lipid metabolism ***,mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR,and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were *** MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent ***5 overexpression in AML12cells suppressed MC-LR-induced *** of SFRP5 also inhibited Wnt5a and phosphorylation of *** MC-LR can induce lipid metabolism disorders in mice,and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.

关键词： Jun N-terminal kinase Secreted frizzled-related protein 5 Wnt5a Hepatic lipid metabolism disorder

Development of a Proof-of-Concept Multi-Method Computer Simulation to Support Rural healthcare Disaster Preparedness Planning

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International Journal of Disaster Risk Science 2024年第3期15卷 346-358页

作者： Thomas A.Berg Kristina W.Kintziger Julie Suzuki Crumly Scott A.Lawson Carole R.Myers Tracey T.Stansberry college of Nursing University of Tennessee Knoxville Department of Environmental Agricultural and Occupational Health University of Nebraska Medical Center public health and healthcare Oak Ridge Associated Universities

Due to a lack of resources, rural communities often face challenges when planning catastrophic events. This project involved applying systems thinking and model-based systems engineering to develop a proof-of-concept, multi-method computer simulation and then determining whether the simulation could be used to assess the efficacy of disaster planning approaches on health outcomes in rural communities, as a function of primary healthcare. The project focus was a rural or non-urban healthcare system experiencing a natural hazard. Both system dynamics and discrete event models were incorporated to represent subsystem operations, crucial disaster responses, as well as three key response systems: public health, emergency management, and healthcare. The subsystem models included several components: policies/procedures, communications,resources, exercises/drills/training, healthcare space and staff, and the flow of affected people into and through the *** combined simulation can serve as a first step to a more comprehensive approach to helping rural communities achieve more efficient and effective healthcare planning for disaster responses.

关键词： Computer simulation Disaster preparedness Model-based systems engineering Rural healthcare System dynamics model Systems thinking

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

MethylGenotyper:Accurate Estimation of SNP Genotypes and Genetic Relatedness from DNA Methylation Data

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Genomics, Proteomics & Bioinformatics 2024年第3期22卷 43-54页

作者： Yi Jiang Minghan Qu Minghui Jiang Xuan Jiang Shane Fernandez Tenielle Porter Simon M.Laws Colin L.Masters Huan Guo Shanshan Cheng Chaolong Wang Ministry of Education Key Laboratory of Environment and health School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Centre for Precision health Edith Cowan UniversityPerthWA 6027Australia Collaborative Genomics and Translation Group School of Medical and Health SciencesEdith Cowan UniversityPerthWA 6027Australia Curtin medical School BentleyWA 6102Australia The Florey Institute of Neuroscience and Mental health University of MelbourneMelbourneVIC 3052Australia Department of Occupational and Environmental health School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Epigenome-wide association studies(EWAS)are susceptible to widespread confounding caused by population structure and genetic ***,kinship estimation is challenging in EWAS without genotyping ***,we proposed MethylGenotyper,a method that for the first time enables accurate genotyping at thousands of single nucleotide polymorphisms(SNPs)directly from commercial DNA methylation *** modeled the intensities of methylation probes near SNPs with a mixture of three beta distributions corresponding to different genotypes and estimated parameters with an expectation-maximization *** conducted extensive simulations to demonstrate the performance of the *** applying MethylGenotyper to the Infinium EPIC array data of 4662 Chinese samples,we obtained genotypes at 4319 SNPs with a concordance rate of 98.26%,enabling the identification of 255 pairs of close ***,we showed that MethylGenotyper allows for the estimation of both population structure and cryptic relatedness among 702 Australians of diverse *** also implemented MethylGenotyper in a publicly available R package(https://***/Yi-Jiang/MethylGenotyper)to facilitate future large-scale EWAS.

关键词： DNA methylation Genotype calling Genetic relatedness Population structure Epigenome-wide association study

Elaidic acid-induced intestinal barrier damage led to gut-liver axis derangement and triggered NLRP3 inflammasome in the liver of SD rats

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Food Science and Human Wellness 2024年第3期13卷 1279-1291页

作者： Hui Liu Xuenan Li Lu Li Yucai Li Haiyang Yan Yong Pang Wenliang Li Yuan Yuan college of Food Science and Engineering Jilin UniversityChangchun 130062China School of public health Jining Medical UniversityJining 272067China

Previous studies have shown that trans fatty acids(TFA) are associated with several chronic diseases,the gut microbiota is directly influenced by dietary components and linked to chronic *** research investigated the effects of elaidic acid(EA),a typical TFA,on the gut microbiota to understand the underlying mechanisms of TFA-related chronic diseases.16S rDNA gene sequencing on faecal samples from Sprague-Dawley rats were performed to explore the composition change of the gut microbiota by EA gavage for 4 *** results showed that the intake of EA increased the abundance of well-documented harmful bacteria,such as Proteobacteria,Anaerotruncus,Oscillibacter and ***,EA induced translocation of lipopolysaccharides(LPS) and the above pathogenic bacteria,disrupted the intestinal barrier,led to gut-liver axis derangement and TLR4 pathway activation in the ***,EA induced intestinal barrier damage and regulated TLR4-MyD88-NF-κB/MAPK pathways in the liver of SD rats,leading to the activation of NLRP3 inflammasome and inflammatory liver damage.

关键词： Elaidic acid(EA) Gut microbiota Intestinal barrier Gut-liver axis TLR4-MyD88-NF-κB/MAPK pathways NLRP3 inflammasome