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Difluoromethyl phenoxathiinium salt: A new general and versatile difluoromethylating reagent with divergent ·CF_(2)H, CF_(2)H^(+), and :CF_(2) reactivities

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Science China Chemistry 2024年第3期67卷 953-962页

作者： Yuan-Qing Gu Hong-Xin Long Dan-Dan Zhang Mei-Feng Ruan Guo-Kai Liu school of Pharmacy Shenzhen University Medical SchoolShenzhen UniversityShenzhen 518055China

Development of practical and versatile electrophilic difluoromethylating reagent is still a grand challenge so far due to its inherent instability or low ***,we report the design and synthesis of difluoromethyl phenoxathiinium tetrafluoroborate(PT-CF_(2)H^(+)BF_(4)^(-)) as a novel difluoromethylating reagent,which proves to be a bench-stable,general,powerful and versatile reagent with divergent·CF_(2)H,CF_(2)H^(+),and:CF_(2) *** use of this reagent,we demonstrated a vast array of difluoromethyl radical transfer reactions via diverse pathways involving photocatalyst-free visible-light induction,visible-light photoredox catalysis and visible-light mediation single electron transfer of EDA ***,the green and highly effective CF_(2)H^(+) and:CF_(2) transfer reactions were also readily accomplished.

关键词： difluoromethyl phenoxathiinium salt versatile difluoromethylating reagent difluoromethyl radical difluoromthyl cation difluorocarbene

TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells via Targeting Wnt/β-catenin Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 322-329页

作者： QIN Jing-jing NIU Meng-da CHA Zhe GENG Qing-hua LI Yu-lin REN Chun-guang David P.Molloy YU Hua-rong Research Center of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Laboratory of Developmental Biology Department of Cell Biology and GeneticsSchool of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Department of Biochemistry and Molecular Biology School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China

Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma *** Cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5µmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5µmol/L).Cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,*** reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 mol/L)and the mechanism for action of TCCT was *** Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(P<0.01).TCCT up-regulated the expression of GSK-3β and down-regulated the expression of β-catenin and its associated proteins(P<0.05 or P<0.01),including c-Myc,Cyclin-D1,and matrix metalloproteinase(MMP)-*** addition,LiCl,an activator of the Wnt signaling pathway,restored the inhibitory effects of TCCT on the expression of β-catenin and its downstream genes,as well as the migration and invasion of glioblastoma cells(P<0.05 or P<0.01).Conclusions Celastrol and TRAIL can synergistically suppress glioblastoma cell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin *** underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

关键词： celastrol Chinese medicine tumor necrosis factor-related apoptosis-induced ligand glioblastoma β-catenin Tripterygium wilfordii

Single-cell RNA sequencing to understand host-virus interactions

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Virologica Sinica 2024年第1期39卷 1-8页

作者： Jia-Tong Chang Li-Bo Liu Pei-Gang Wang Jing An Department of Microbiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Single-cell RNA sequencing(scRNA-seq)has allowed for the profiling of host and virus transcripts and host-virus interactions at single-cell *** review summarizes the existing scRNA-seq technologies together with their strengths and *** applications of scRNA-seq in various virological studies are discussed in depth,which broaden the understanding of the immune atlas,host-virus interactions,and immune ***-seq can be widely used for virology in the near future to better understand the pathogenic mechanisms and discover more effective therapeutic strategies.

关键词： Single-cell RNA sequencing(scRNA-seq) Host-virus interaction COVID-19 Flavivirus

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

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

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

Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice

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Neural Regeneration Research 2024年第3期19卷 636-641页

作者： Jiao Mu Liufang Hao Zijue Wang Xuyang Fu Yusen Li Fei Hao Hongmei Duan Zhaoyang Yang Xiaoguang Li 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

Stroke can cause Wallerian degeneration in regions outside of the brain,particularly in the corticospinal *** investigate the fate of major glial cells and axons within affected areas of the corticospinal tract following stroke,we induced photochemical infarction of the sensorimotor cortex leading to Wallerian degeneration along the full extent of the corticospinal *** first used a routine,sensitive marker of axonal injury,amyloid precursor protein,to examine Wallerian degeneration of the corticospinal *** antibody to amyloid precursor protein mapped exclusively to proximal axonal segments within the ischemic cortex,with no positive signal in distal parts of the corticospinal tract,at all time *** improve visualization of Wallerian degeneration,we next utilized an orthograde virus that expresses green fluorescent protein to label the corticospinal tract and then quantitatively evaluated green fluorescent protein-expressing *** this approach,we found that axonal degeneration began on day 3 post-stroke and was almost complete by 7 days after *** addition,microglia mobilized and activated early,from day 7 after stroke,but did not maintain a phagocytic state over ***,astrocytes showed relatively delayed mobilization and a moderate response to Wallerian ***,no anterograde degeneration of spinal anterior horn cells was observed in response to Wallerian degeneration of the corticospinal *** conclusion,our data provide evidence for dynamic,pathogenic spatiotemporal changes in major cellular components of the corticospinal tract during Wallerian degeneration.

关键词： corticospinal tract green fluorescent protein microglia spinal anterior horn cells stroke virus trace Wallerian degeneration

Early diagnostic strategies for colorectal cancer

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World Journal of Gastroenterology 2024年第33期30卷 3818-3822页

作者： Shi-Cai Liu Han Zhang school of medical Information Wannan Medical CollegeWuhu 241002Anhui ProvinceChina school of Basic medical Sciences Wannan Medical CollegeWuhu 241002Anhui ProvinceChina

At present,cancer is still an important factor threatening human *** cancer(CRC)is one of the top three most common cancers worldwide and one of the deadliest malignancies in *** latest data showed that CRC incidence and mortality rank third and second,respectively,among global *** and accurate diagnosis is crucial to reduce the morbidity,mortality and improve survival of patients with CRC,but the current early diagnostic methods have *** effectiveness and compliance of diagnostic methods have a certain impact on whether people choose *** this editorial,we explore strategies for the early diagnosis of CRC,including stool-based,blood-based,direct visualization,and imaging examinations.

关键词： Colorectal cancer Diagnostic markers Colonoscopy Fecal immunochemical test Fecal occult blood test Circulating tumor cells Circulating tumor DNA

Reperfusion and cytoprotective agents are a mutually beneficial pair in ischaemic stroke therapy:an overview of pathophysiology,pharmacological targets and candidate drugs focusing on excitotoxicity and free radical

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Stroke & Vascular Neurology 2024年第4期9卷 351-359页

作者： Xiumei Xu Mingyu Chen Dongya Zhu school of Pharmacy Nanjing Medical UniversityNanjingJiangsuChina

Stroke is the second-leading cause of death and the leading cause of disability in much of the *** particular,China faces the greatest challenge from stroke,since the population is aged *** decades of clinical trials,no neuroprotectant has had reproducible efficacy on primary clinical end points,because reperfusion is probably a necessity for neuroprotection to be clinically ***,the success of thrombolysis and endovascular thrombectomy has taken us into a reperfusion era of acute ischaemic stroke(AIS)*** cytoprotective agents can prevent detrimental effects of ischaemia,and therefore‘freeze’ischaemic penumbra before reperfusion,extend the time window for reperfusion *** reperfusion often leads to reperfusion injury,including haemorrhagic transformation,brain oedema,infarct progression and neurological worsening,cytoprotective agents will enhance the efficacy and safety of reperfusion therapy by preventing or reducing reperfusion ***,reperfusion and cytoprotective agents are a mutually beneficial pair in AIS *** this review,we outline critical pathophysiological events causing cell death within the penumbra after ischaemia or ischaemia/reperfusion in the acute phase of AIS,focusing on excitotoxicity and free *** discuss key pharmacological targets for cytoprotective therapy and evaluate the recent advances of cytoprotective agents going through clinical trials,highlighting multitarget cytoprotective agents that intervene at multiple levels of the ischaemic and reperfusion cascade.

关键词： protective injuries drugs