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CD36 promotes tubular ferroptosis by regulating the ubiquitination of FSP1 in acute kidney injury

Genes & Diseases 2024年第1期11卷 449-463页

作者： Yixin Ma Lili Huang Zheng Zhang Pengfei Yang Qingsong Chen Xujia Zeng Fangyan Tan Chunxia Wang Xiongzhong Ruan Xiaohui Liao Department of Nephrology The Second Affiliated HospitalChongqing Medical UniversityChongqing 400010China Department of Cell Biology and Genetics Chongqing Medical UniversityChongqing 400016China Centre for Nephrology Royal Free and University College Medical SchoolUniversity College LondonRoyal Free CampusRowland Hill StreetLondon NW32PFUnited Kingdom Centre for Lipid Research Key Laboratory of Molecular Biology on Infectious DiseasesMinistry of EducationChongqing Medical UniversityChongqing 400016China Kuanren Laboratory of Translational Lipidology Centre for Lipid ResearchSecond Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

Reactive oxidative species(ROos)production-driven ferroptosis plays a role in acute kidney injury(Akl).However,its exact molecular mechanism is poorly *** receptor CD36 has important roles in oxidizing lipids,lipid accumulation,metabolic syndrome,and insulin resistance in chronic kidney disease,but its roles remain unexplored in *** present study investigated the role and mechanism of CD36 in regulating proximal tubular cell ferroptosis and *** expression of CD36 was found to be significantly up-regulated in AKI renal tissues and correlated with renal function,which might serve as an independent biomarker for AKl ***,in adult mice subjected to AKl,deletion of CD36(CD36-/-)induced tubular cell Ros accumulation,ferroptosis activation,and renal ***,combining LC-MS/MS,co-IP,and ubiquitination analyses revealed that CD36 could specifically bind to ferroptosis suppressor protein 1(FSP1)and regulate its ubiquitination at sites K16 and K24,leading to FSP1 degradation and progression of ferroptosis in *** present results emphasize a novel mechanism of CD36 in cisplatin-induced *** discovery of the special CD36 roles in promoting ferroptosis and AKI development by regulating the ubiquitination of FSP1 in proximal tubular cells may be potential therapeutic targets for ***,CD36 may play a key role in the progression of ***,targeting CD36 may provide a promising treatment option for AKI.

关键词： Acute kidney injury CD36 Ferroptosis FSP1 Ubiquitin-dependent degradation

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Differential expression of miRNAs and mRNAs in the livers of largemouth bass Micropterus salmoides under heat stress

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Journal of Oceanology and Limnology 2024年第2期42卷 594-608页

作者： Xuqian ZHAO Zijie LIN Caijuan LI Hao ZHU Lingling LI Wenjia MAO Qufei LING school of Biology and Basic medical Sciences Suzhou Medical College of Soochow UniversitySuzhou 215000China

Global warming threatens freshwater ecosystems and compromises fish *** elucidate the role of miRNAs in the livers of heat stressed largemouth bass,juvenile fish was subject to heat stress under 37°*** mRNA-seq and miRNA-seq were conducted on the liver tissues under control and heat stress *** gene expression analysis and enrichment analysis were performed on mRNA and miRNA expression profiles.A total of 406 differentially expressed genes(DEGs)were discovered,of which 212 were up-regulated and 194 were *** of the DEGs were significantly implicated in the regulation of“protein processing in endoplasmic reticulum”,“proteasome”,“steroid biosynthesis”,and“ornithine decarboxylase inhibitor activity”*** addition,47 differentially expressed miRNAs(DEMs)were identified in largemouth bass livers under heat stress,including 21 up-regulated and 25 down-regulated miRNAs.A negatively regulated miRNA-mRNA network including 12 miRNAs and 19 mRNAs was constructed with DEMs involved in“protein degradation”,“calcium ion regulation”,“cell apoptosis”,and“lipid metabolism”.Moreover,this study indicated novel-miR-144 activated the IRE1 signaling pathway by targeting txndc5 to induce liver apoptosis in largemouth bass under heat *** study revealed the involvement of miRNA regulation in largemouth bass in response to heat stress.

关键词： heat stress largemouth bass miRNA-mRNA interaction

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Heat stress induced hepatocyte apoptosis in largemouth bass Micropterus salmoides via IRE1α/TRAF2/ASK1/JNK pathway

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Journal of Oceanology and Limnology 2024年第3期42卷 988-1000页

作者： Xuqian ZHAO Wenjia MAO Zijie LIN Qufei LING school of Biology and Basic medical Sciences Suzhou Medical College of Soochow UniversitySuzhou 215000China

Heat stress(HS)has been shown to adversely affect fish livers and can lead to extensive *** investigate the relationship between endoplasmic reticulum(ER)stress and HS-induced apoptosis in fish livers,we isolated and cultured primary hepatocytes of largemouth bass,Micropterus salmoides by trypsin method,then established an in-vitro model of liver cells under HS(35℃).The contents of lactic dehydrogenase(LDH)and hydrogen peroxide(H2O2)were determined to evaluate the effects of HS on hepatocyte injury and oxidative ***-qPCR was performed to discover the key genes in unfolded protein response(UPR)pathways involved at different HS *** inhibitor 4-PBA and IRE1αinhibitor 4μ8C were used to further investigate the effects of HS on IRE1αapoptosis pathway in *** show that HS led to significant increases in the release of LDH,the content of H2O2,and the expressions of oxidative protein folding genes(ero1αand pdi)under HS,suggesting severe hepatocyte injury and oxidative stress happened in heat-stressed largemouth bass *** continuous activation of IRE1αpathway genes(grp78,grp94,atf6,perk,eif2a,atf4,chop,ire1α,traf2,ask1,jnk1,and jnk2)indicated that HS led significantly to ER *** particular,the mRNA expression levels of ER stress-related genes(grp78,grp94,atf6,perk,ire1α,chop,jnk1,and jnk2)in the high temperature(HT)+4-PBA group and the HT+4μ8C group were significantly down-regulated under *** 4μ8C treatment,the expression levels of apoptosis-related genes(caspase-2,caspase-3,caspase-6,caspase-7,caspase-8,caspase-9,and caspase-10)and LDH content were significantly decreased,whereas the cell survival rate was significantly increased when given 4-PBA or 4μ8C *** findings demonstrate that HS could induce liver apoptosis of largemouth bass through the IRE1αpathway,which may act as a key switch mediating liver apoptosis of largemouth bass under HS.

关键词： heat stress Micropterus salmoides endoplasmic reticulum stress apoptosis oxidative stress

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Development of an experimental method for well-controlled blast induced traumatic limb fracture in rats

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Defence Technology（防务技术） 2024年第4期34卷 168-176页

作者： Luyang Xu Xiancheng Yu Clement DFavier Ibidumo Igah Thuy-Tien Nguyen Warren Macdonald Anthony MJ.Bull Centre for Blast Injury Studies Imperial College LondonLondonUnited Kingdom Department of Bioengineering Imperial College LondonLondonUnited Kingdom Dyson school of Design Engineering Imperial College LondonLondonUnited Kingdom Department of Trauma and Orthopaedics Royal Free London National Health Service Foundation TrustLondonUnited Kingdom

Heterotopic ossification(HO)is a consequence of traumatic bone and tissue damage,which occurs in 65%of military casualties with blast-associated ***,the mechanisms behind blast-induced HO remain *** models are used to study blast-induced HO,but developing such models is challenging,particularly in how to use a pure blast wave(primary blast)to induce limb fracture that then requires an *** studies,including our recent study,have developed platforms to induce limb fractures in rats with blast loading or a mixture of blast and impact ***,these models are limited by the survivability of the animal and repeatability of the *** this study,we developed an improved platform,aiming to improve the animal's survivability and injury repeatability as well as focusing on primary blast *** platform exposed only one limb of the rat to a blast wave while providing proper protection to the rest of the rat's *** obtained very consistent fracture outcome in the tibia(location and pattern)in cadaveric rats with a large range of size and ***,the rats did not obviously move during the test,where movement is a potential cause of uncontrolled *** further conducted parametric studies by varying the features of the design of the *** factors,such as how the limb is fixed and how the cavity through which the limb is placed is sealed,significantly affect the resulting *** platform and test setups enable well-controlled limb fracture induced directly by pure blast wave,which is the fundamental step towards a complete in vivo animal model for blast-induced HO induced by primary blast alone,excluding secondary and tertiary blast *** addition,the platform design and the findings presented here,particularly regarding the proper protection of the animal,have implications for future studies investigating localized blast injuries,such as blast induced brain and lung injuries.

关键词： Blast injury Biomechanics Heterotopic ossification Limb fracture Blast wave Animal model

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Synergistic chemotherapy/PTT/oxygen enrichment by multifunctional liposomal polydopamine nanoparticles for rheumatoid arthritis treatment

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 86-102页

作者： Xiaoling Fu Yutong Song Xianquan Feng Zhihong Liu Wenhao Gao Hongtao Song Qian Zhang school of Pharmacy Fujian Medical UniversityFuzhou 350108China Fuzong Clinical medical college of Fujian medical university Fuzhou 350025China First school of clinical medicine Nanjing Medical UniversityNanjing 211166China

Amultifunctional liposomal polydopamine nanoparticle(MPM@Lipo)was designed in this study,to combine chemotherapy,photothermal therapy(PTT)and oxygen enrichment to clear hyperproliferating inflammatory cells and improve the hypoxic microenvironment for rheumatoid arthritis(RA)***@Lipo significantly scavenged intracellular reactive oxygen species and relieved joint hypoxia,thus contributing to the repolarization of M1 macrophages into M2 ***,MPM@Lipo could accumulate at inflammatory joints,inhibit the production of inflammatory factors,and protect cartilage in vivo,effectively alleviating RA progression in a rat adjuvant-induced arthritis ***,upon laser irradiation,MPM@Lipo can elevate the temperature to not only significantly obliterate excessively proliferating inflammatory cells but also accelerate the production of methotrexate and oxygen,resulting in excellent RA treatment ***,the use of synergistic chemotherapy/PTT/oxygen enrichment therapy to treat RA is a powerful potential strategy.

关键词： Polydopamine Thermosensitive liposomes Photothermal therapy Oxygen generation Rheumatoid arthritis

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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

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Multifunctional high-performance pressure/proximity/temperature sensors enabled by hybrid resistive-supercapacitive response

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Nano Research 2024年第6期17卷 5604-5613页

作者： Huijun Kong Zhongqian Song Meichun Ding Changxiang Shao Jiahui Yu Baolei Wang Weiyan Li Chenwei Li Li Niu school of Chemistry and Pharmaceutical Engineering Shandong First Medical University and Shandong Academy of Medical SciencesJinan 250117China college of Artificial Intelligence and Big Data for medical Sciences Shandong First Medical University and Shandong Academy of Medical SciencesJinan 250117China school of Chemical Engineering and Technology Sun Yat-sen UniversityZhuhai 519082China

The issue of sensitivity attenuation in high-pressure region has been a persistent concern for pressure-sensitive electronic *** order to tackle such trade-off between sensitivity and linear range,herein,a hybrid piezoresistive-supercapacitive(HRSC)strategy is proposed via introducing a piezoresistive porous aerogel layer between the charge collecting electrodes and iontronic films of the pressure ***,the HRSC-induced impedance regulation and supercapacitive behavior contribute to significant mitigation in sensitivity attenuation,achieving high sensitivity across wide linear range(44.58 kPa^(−1)from 0 to 3 kPa and 23.6 kPa^(−1)from 3 to 12 kPa).The HRSC pressure sensor exhibits a low detection limit of 1 Pa,fast responsiveness(~130 ms),and excellent cycling stability,allowing to detect tiny pressure of air flow,finger bending,and human ***,the HRSC sensor exhibits exceptional perception capabilities for proximity and temperature,broadening its application scenarios in prosthetic perception and electronic *** proposed HRSC strategy may boost the ongoing research on structural design of high-performance and multimodal electronic sensors.

关键词： multimodal sensor pressure sensor high sensitivity MXene/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)(PEDOT:PSS)aerogel structural design

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The advantages of multi-level omics research on stem cell-based therapies for ischemic stroke

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Neural Regeneration Research 2024年第9期19卷 1998-2003页

作者： Yiqing Wang Chuheng Chang Renzhi Wang Xiaoguang Li Xinjie Bao 4+4 Doctor medical Program Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina Department of Neurosurgery Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina

Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.

关键词： ischemic stroke mesenchymal stem cells metabolomics multilevel omics neural stem/progenitor cells neuroinflammation pathophysiology proteomics stem cell therapy transcriptomes

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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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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

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