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Src inhibition rescues FUNDC1-mediated neuronal mitophagy in ischaemic stroke

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Stroke & Vascular Neurology 2024年第4期9卷 367-379,I0022-I0031页

作者： Tianchi Tang Li-bin Hu Chao ding Zhihua Zhang Ning Wang Tingting Wang Hang Zhou Siqi Xia Linfeng fan Xiong-jie Fu Feng yan Xiangnan Zhang Gao Chen Jianru Li Department of Neurosurgery Zhejiang University School of Medicine Second Affiliated HospitalHangzhouZhejiangChina 2NeurosurgeryZhejiang University School of Medicine Second Affiliated HospitalHangzhouZhejiangChina 3Zhejiang University School of MedicineHangzhouZhejiangChina 4Zhejiang University Department of PharmacologyHangzhouZhejiangChina

Background Ischaemic stroke triggers neuronal mitophagy,while the involvement of mitophagy receptors in ischaemia/reperfusion(I/R)injury-induced neuronal mitophagy remain not fully ***,we aimed to investigate the involvement of mitophagy receptor FUN14 domain-containing 1(FUNDC1)and its modulation in neuronal mitophagy induced by I/R *** Wild-type and FUNDC1 knockout mice were generated to establish models of neuronal I/R injury,including transient middle cerebral artery occlusion(tMCAO)in vivo and oxygen glucose deprivation/reperfusion in *** outcomes of mice with two genotypes were *** mitophagy was analysed both in vivo and in *** of FUNDC1 and its regulator Src were *** impact of Src on FUNDC1-mediated mitophagy was assessed through administration of Src antagonist *** To our surprise,FUNDC1 knockout mice subjected to tMCAO showed stroke outcomes comparable to those of their wild-type *** neuronal mitophagy could be activated by I/R injury,FUNDC1 deletion did not disrupt neuronal *** activation of FUNDC1,represented by dephosphorylation of Tyr18,was detected in the early stages(within 3hours)of neuronal I/R injury;however,phosphorylated Tyr18 reappeared and even surpassed baseline levels in later stages(after 6hours),accompanied by a decrease in FUNDC1-light chain 3 *** inactivation of FUNDC1 was associated with Src activation,represented by phosphorylation of Tyr416,which changed in parallel with the level of phosphorylated FUNDC1(Tyr18)during neuronal I/R ***,FUNDC1-mediated mitophagy in neurons under I/R conditions can be rescued by pharmacological inhibition of *** FUNDC1 is inactivated by Src during the later stage(after 6hours)of neuronal I/R injury,and rescue of FUNDC1-mediated mitophagy may serve as a potential therapeutic strategy for treating ischaemic stroke.

关键词： FUNDC1 involvement injury

Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice

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Zoological Research 2024年第3期45卷 551-566页

作者： Chen Ling Su-Su Liu Yu-Ya Wang Gui-Tao Huo yan-Wei yang Nan Xu Hong Wang Yong Wu Yu-Fa Miao Rui Fu Yu-Wei Zhao Chang-Fa fan College of Life Sciences Northwest UniversityProvincial Key Laboratory of Biotechnology of Shaanxi ProvinceXi’anShaanxi 710069China division of Animal Model Research Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control(NIFDC)Beijing 102629China National Center for Safety Evaluation of Drugs National Institutes for Food and Drug Control(NIFDC)Beijing 100176China division of HIV/AIDS and Sexually Transmitted Virus Vaccines Institute for Biological Products ControlNational Institutes for Food and Drug Control(NIFDC)Beijing 102629China division of Laboratory Animal Monitoring Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control(NIFDC)Beijing 102629China

Hepatocellular carcinoma(HCC),a prevalent solid carcinoma of significant concern,is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic *** etiology and pathological progression of non-alcoholic steatohepatitis(NASH)-related HCC is multifactorial and ***,no single animal model can accurately mimic the full NASH-related HCC pathological progression,posing considerable challenges to transition and mechanistic ***,a novel conditional inducible wild-type human HRAS overexpressed mouse model(HRAS-HCC)was established,demonstrating 100%morbidity and mortality within approximately one month under normal dietary and lifestyle *** symptoms of HCC such as ascites,thrombus,internal hemorrhage,jaundice,and lung metastasis were successfully replicated in ***-depth pathological features of NASH-related HCC were demonstrated by pathological staining,biochemical analyses,and typical marker gene *** murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival,further confirming the accuracy and reliability of the *** on protein-protein interaction(PPI)network and RNA sequencing analyses,we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis,with subsequent progression to ***,our study successfully duplicated natural sequential progression in a single murine model over a very short period,providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.

关键词： HRAS THBS1 HCC driver factor NASH Fibrosis Cirrhosis HCC Treatment evaluation

Impacts of gravitational-wave background from supermassive black hole binaries on the detection of compact binaries by LISA

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Chinese Physics C 2024年第6期48卷 198-203页

作者：黄帆毕研晨曹周键黄庆国 CAS Key Laboratory of Theoretical Physics Institute of Theoretical PhysicsChinese Academy of SciencesBeijing 100190China School of Physical Sciences University of Chinese Academy of SciencesBeijing 100049China Institute of Applied Mathematics Academy of Mathematics and Systems ScienceChinese Academy of SciencesBeijing 100190China School of Fundamental Physics and Mathematical Sciences Hangzhou Institute for Advanced StudyUCASHangzhou 310024China

In the frequency band of the Laser Interferometer Space Antenna(LISA),extensive research has been conducted on the impact of foreground confusion noise generated by galactic binaries within the Milky Way ***,recent evidence of a stochastic signal,announced by the NANOGrav,EPTA,PPTA,CPTA,and InPTA,indicates that the stochastic gravitational-wave background(SGWB)generated by supermassive black hole binaries(SMBHBs)can contribute strong background noise within the LISA *** the presence of such strong noise,it is expected to have significant impacts on LISA's scientific *** this study,we investigate the impacts of the SGWB generated by SMBHBs on the detection of individual massive black hole binaries,verified galactic binaries,and extreme mass ratio inspirals in the context of *** find it essential to resolve and eliminate the excess noise from the SGWB to guarantee the success of LISA's missions.

关键词： gravitational-wave background supermassive black hole binaries LISA

Effect of cytochrome P4502C19(CYP2C19)gene polymorphism and clopidogrel reactivity on long term prognosis of patients with coronary heart disease after PCI

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Journal of Geriatric Cardiology 2024年第1期21卷 90-103页

作者： Cheng-yan HU yan-Ling WANG Zhen-Xing fan Xi-Peng SUN Shuai WANG Zhi LIU Department of Geriatrics Fu Xing HospitalCapital Medical UniversityBeijingChina Department of Cardiology Xuanwu Hospital Capital Medical UniversityBeijingChina Emergency Department of Xuanwu Hospital Capital Medical UniversityBeijingChina

Objective To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with longterm clinical outcome in patients with coronary heart disease(CHD)undergoing percutaneous coronary intervention(PCI).Methods In total,675 patients were *** on the platelet inhibition rate,patients were categorized into two groups:clopidogrel low responsiveness(CLR)and normal clopidogrel responsiveness(NCR).The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up *** were classified into three groups(normal metabolizer,intermediate metabolizer,and poor metabolizer)based on the CYP2C19 *** aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel *** cumulative rates of 12-month all-cause deaths,major adverse cardiovascular events(MACCEs),and bleeding events were *** CLR was observed in 44.4%of the overall *** differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes(Pdied and 96 patients(14.2%)experienced *** with CLR(9.6%vs.11.7%vs.22.1%,Pdifference between the group with a score of one and the occurrence of MACCEs(P>0.05).Conclusions Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene ***2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI,which is better than either test alone.

关键词： CYP2C19 drugs PCI

GHz photon-number resolving detection with high detection efficiency and low noise by ultra-narrowband interference circuits

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Journal of Semiconductors 2024年第3期45卷 71-75页

作者： Tingting Shi Yuanbin fan Zhengyu yan Lai Zhou yang Ji Zhiliang Yuan Beijing Academy of Quantum Information Sciences Beijing 100193China Institute of Semiconductors Chinese Academy of SciencesBeijing 100083China College of Materials Science and Opto-Electronic Technology University of Chinese Academy of SciencesBeijing 100049China

We demonstrate the photon-number resolution(PNR)capability of a 1.25 GHz gated InGaAs single-photon avalanche photodiode(APD)that is equipped with a simple,low-distortion ultra-narrowband interference circuit for the rejection of its background capacitive *** discriminating the avalanche current amplitude,we are able to resolve up to four detected photons in a single detection gate with a detection efficiency as high as 45%.The PNR capability is limited by the avalanche current saturation,and can be increased to five photons at a lower detection efficiency of 34%.The PNR capability,combined with high efficiency and low noise,will find applications in quantum information processing technique based on photonic qubits.

关键词： single photon avalanche diode(APD) photon number resolution(PNR) detection efficiency

Comparison on the Origin and Development of Sophora flavescens in China and Japan

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Agricultural Biotechnology 2024年第2期13卷 58-63页

作者： Jing yan Zheng fan Yuling XU Chenyu ZHOU Rongchun HAN School of pharmacy Anhui University of Chinese MedicineHefei 230012China Antagen Pharmaceutics IncMassachusetts Canton 02021USA The Affiliated Taihe Hospital of Traditional Chinese Medicine Anhui University of Chinese MedicineTaihe 236600China

Sophora flavescens , which was first recorded in Shen Nong s Herbal Classic , has the functions of clearing away heat, drying dampness, killing parasites and promoting urination. In its long-term application, traditional Chinese medicine has gradually deepened its understanding of the origin and efficacy of S. flavescens . In order to explore changes in the origin and efficacy of traditional Chinese herb S. flavescens in the history of China and Japan, in this paper, the origin and development of S. flavescens in China and Japan were compared from three aspects: the origin, medicinal efficacy, and processing methods of S. flavescens in China and Japan, hoping to provide clear understanding of the medicinal plant S. flavescens .

关键词： Sophora flavescens Japan Herbalogical study Processing

Spatio-temporal evolution of the coordinated development of high-tech industry agglomeration and resource-environmental carrying capacity in the Yellow River Basin

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Ecological Economy 2024年第3期20卷 219-236页

作者： LI yan REN Ai-lian LI Meng-yu SUN fan School of Business Administration Henan University of Economics and LawZhengzhou 450046CHINA School of Management and Economics North China University of Water Resources and Electric PowerZhengzhou 450046CHINA Postdoctoral Research Station in Business Administration at Business School Henan University Kaifeng 475000CHINA

Under the background of new infrastructure,the Yellow River Basin’s superior growth cannot be separated originating with the synergistic effect of scientific and technological inventiveness and ecological civilization *** light of the coupling coordination analysis of the coordination effect of provincial high-tech industry agglomeration and resource carrying capacity in the Yellow River Basin from 2009 to 2021,The evolution of the geographical and temporal pattern of development was investigated using the Moran index and kernel density *** results show that the agglomeration of high-tech industries in the Yellow River Basin presents a development trend of seek improvement in stability,and there is a good coupling and coordination throughout the progression of scientific and technological innovation and the loading capacity of the resource,from the viewpoint of a time *** the perspective of spatial pattern distribution,the whole basin aims at the lower reaches,accelerates the optimization of digital industry and promotes Yellow River Basin development of superior quality through innovation support and increase of input,and based on policy guidance.

关键词： Yellow River Basin high-tech industrial agglomeration resource carrying capacity coupling coordination space-time evolution

Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2726-2737页

作者： Bo Liu Honghui Liu Pu Han Xiaoyun Wang Chunmei Wang Xinxin yan Wenwen Lei Ke Xu Jianjie Zhou Jianxun Qi Ruiwen fan Guizhen Wu Wen-xia Tian George F.Gao Qihui Wang College of Veterinary Medicine Shanxi Agricultural University030801 JinzhongChina CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences(CAS)100101 BeijingChina School of Life Sciences Yunnan University650504 KunmingYunnan ProvinceChina NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and Prevention(China CDC)102206 BeijingChina Savaid Medical School University of Chinese Academy of Sciences101408 BeijingChina

Almost all the neutralizing antibodies targeting the receptor-binding domain(RBD)of spike(S)protein show weakened or lost efficacy against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)emerged or emerging variants,such as Omicron and its *** suggests that highly conserved epitopes are crucial for the development of neutralizing ***,we present one nanobody,N235,displaying broad neutralization against the SARS-CoV-2 prototype and multiple variants,including the newly emerged Omicron and its ***-electron microscopy demonstrates N235 binds a novel,conserved,cryptic epitope in the N-terminal domain(NTD)of the S protein,which interferes with the RBD in the neighboring S *** neutralization mechanism interpreted via flow cytometry and Western blot shows that N235 appears to induce the S1 subunit shedding from the trimeric S ***,a nano-IgM construct(MN235),engineered by fusing N235 with the human IgM Fc region,displays prevention via inducing S1 shedding and cross-linking virus *** to N235,MN235 exhibits varied enhancement in neutralization against pseudotyped and authentic viruses in *** intranasal administration of MN235 in low doses can effectively prevent the infection of Omicron sub-variant BA.1 and XBB in vivo,suggesting that it can be developed as a promising prophylactic antibody to cope with the ongoing and future infection.

关键词： doses prevention conserved

Extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis through the transport of microRNA-29a

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World Journal of Stem Cells 2024年第2期16卷 191-206页

作者： fan yang Wan-Qi Xiong Chen-Zhi Li Ming-Jian Wu Xiu-Zhi Zhang Chun-Xiao Ran Zhen-Hao Li yan Cui Bao-Yi Liu De-Wei Zhao Department of Orthopedics Affiliated Zhongshan Hospital of Dalian UniversityDalian 116001Liaoning ProvinceChina

BACKGROUND Knee osteoarthritis(KOA)is a common orthopedic condition with an uncertain etiology,possibly involving genetics and *** like changes in chondrocyte microenvironment,oxidative stress,inflammation,and immune responses affect KOA ***-stage treatment options primarily target symptom *** stem cells(MSCs)show promise for treatment,despite *** research highlights microRNAs(miRNAs)within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA *** suggests exosomes(Exos)as a promising avenue for future *** these findings emphasize the need for effective KOA progression management,further safety and efficacy validation for Exos is *** To explore miR-29a’s role in KOA,we’ll create miR-29a-loaded vesicles,testing for early treatment in rat *** Extraction of bone marrow MSC-derived extracellular vesicles,preparation of engineered vesicles loaded with miR-29a using ultrasonication,and identification using quantitative reverse transcription polymerase chain reaction;after establi-shing a rat model of KOA,rats were randomly divided into three groups:Blank control group injected with saline,normal extracellular vesicle group injected with normal extracellular vesicle suspension,and engineered extrace-llular vesicle group injected with engineered extracellular vesicle *** three groups evaluation,histological detection,and immunohistochemical detection to compare and evaluate the progress of various forms of *** General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain,gait,joint mobility,and swelling compared to the blank control ***,the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the nor

关键词： Exosomes Osteoarthritis Mesenchymal stem cells MicroRNA-29a Intra-articular injection