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Cav3.2 channel regulates cerebral ischemia/reperfusion injury:a promising target for intervention

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Neural Regeneration Research 2024年第11期19卷 2480-2487页

作者： Feibiao Dai Chengyun Hu Xue Li Zhetao Zhang Hongtao Wang Wanjun Zhou Jiawu Wang Qingtian Geng Yongfei Dong Chaoliang Tang Graduate School Wannan Medical CollegeWuhuAnhui ProvinceChina Department of Anesthesiology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Core Facility Center for Medical sciences The First Affiliated Hospital of USTC(Anhui Provincial Hospital)HefeiAnhui ProvinceChina Department of Pharmacy The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Neurosurgery The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina

Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury.However,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear.Here,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons.The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons.We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury.Cav3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury.Additionally,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal apoptosis.In the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury.These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling.Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.

关键词： calcineurin Cav3.2 channel cerebral ischemia/reperfusion hippocampus hypoxia/reoxygenation inflammatory response nuclear factor of activated T cells 3 oxidative stress primary hippocampal neurons stroke

Aging-induced YTHDF aggregates impair mitochondrial function by trapping mitochondrial RNAs and suppressing their expression in the brain

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Protein & Cell 2024年第2期15卷 149-155页

作者： Juan Zhang Dingfeng Li Keqiang He Qiang Liu Zhongwen Xie School of Life sciences Anhui Agricultural UniversityHefei 230036China State Key Laboratory of Tea Plant Biology and Utilization School of Tea and Food Sciences and TechnologyAnhui Agricultural UniversityHefei230036China division of Life sciences and Medicine Hefei National Research Center for Physical Sciences at the MicroscaleUniversity of Science and Technology of ChinaHefei 230026China Department of Anesthesiology The First Affliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Anhui Province Key Laboratory of Biomedical Aging Research University of Science and Technology of ChinaHefei 230026China Center for Advanced Interdisciplinary science and Biomedicine of IHM Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China

DearEditor,Brain aging is associated with a decrease in cognitive function,which is often accompanied by defective changes in mitochondrial morphology and reduction in mitochondrial function(Faitg et al.,2021).The main function of mitochondria is to produce energy in the form of ATP,which is vital to fulfill high energy demand of neurons,mainly for synaptic processes(Lee et al.,2018).Mitochondrial dysfunction acts as a key factor for age-related cognitive decline(Grimm and Eckert,2017).

关键词： function trapping

Combinations of electron and proton donors in transition-metal complex mediated nitrogen reduction reactions

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science China Chemistry 2024年第7期67卷 2136-2154页

作者： Delong Han Li Yang Hao Huang Priyanka Chakraborty Shashikant U.Dighe Kuo-Wei Huang KAUST Catalysis Center and division of Physical science and Engineering King Abdullah University of Science and TechnologyThuwal 23955Saudi Arabia Agency for science Technologyand ResearchInstitute of Materials Research and Engineering and Institute of Sustainability for ChemicalsEnergy and EnvironmentSingapore 138634Singapore

Nitrogen fixation is a complex process involving the transfer of six electrons and protons.Diverging from the conventional Haber-Bosch process,which relies on hydrogen(H_(2))to provide both electrons and protons to reduce nitrogen(N_(2)),homogeneous transition metal complex-catalyzed N_(2)reduction reactions(NRR)employ an array of electron and proton donors or even electron donors combined with silanes.As the synthesis of diverse catalytic progress,the categories of donors have seen rapid expansion.However,existing literature only provides summaries regarding the metal,ligands,and mechanism.Despite the significance of electron and proton donor combinations in nitrogen reduction reactions,no literature has thoroughly reviewed this aspect.Therefore,we hereby compiled a comprehensive list of commonly used reagents in N_(2)reduction and classified them according to their specific donor combinations.This review presents clear and organized information about these combinations,along with a summary of their general performance trend in NRR with related catalysts.Finally,we conclude the discussion by highlighting key points for researchers to consider when selecting catalysts and donor combinations,with the ultimate goal of advancing the field of nitrogen fixation.

关键词： dinitrogen reduction reaction reducing donor combination transition metal complexes homogeneous catalysis

Blockade of the deubiquitinating enzyme USP48 degrades oncogenic HMGA2 and inhibits colorectal cancer invasion and metastasis

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1624-1643页

作者： Can Cheng Hanhui Yao Heng Li Jingwen Liu Zhengyi Liu Yang Wu Liang Zhu Hejie Hu Zhengdong Fang Liang Wu Department of General Surgery the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Department of Comprehensive Surgery Anhui Provincial Cancer HospitalWest District of the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Anhui Provincial Hospital Health Management Center the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Department of Breast Surgery Henan Provincial People's HospitalPeople's Hospital of Zhengzhou UniversityPeople's Hospital of Henan UniversityZhengzhou 450003China

HMGA2,a pivotal transcription factor,functions as a versatile regulator implicated in the progression of diverse aggressive malignancies.In this study,mass spectrometry was employed to identify ubiquitin-specific proteases that potentially interact with HMGA2,and USP48 was identified as a deubiquitinating enzyme of HMGA2.The enforced expression of USP48 significantly increased HMGA2 protein levels by inhibiting its degradation,while the deprivation of USP48 promoted HMGA2 degradation,thereby suppressing tumor invasion and metastasis.We discovered that USP48 undergoes SUMOylation at lysine 258,which enhances its binding affinity to HMGA2.Through subsequent phenotypic screening of small molecules,we identified DUB-IN-2 as a remarkably potent pharmacological inhibitor of USP48.Interestingly,the small-molecule inhibitor targeting USP48 induces destabilization of HMGA2.Clinically,upregulation of USP48 or HMGA2 in cancerous tissues is indicative of poor prognosis for patients with colorectal cancer(CRC).Collectively,our study not only elucidates the regulatory mechanism of DUBs involved in HMGA2 stability and validates USP48 as a potential therapeutic target for CRC,but also identifies DUB-IN-2 as a potent inhibitor of USP48 and a promising candidate for CRC treatment.

关键词： Colorectal cancer Invasion and metastasis Post-translational modification Ubiquitination SUMOylation USP48 HMGA2 Specific inhibitors

The Application of Permanent Magnet Synchronous Motor with Small Electrical Time Constant in Fiber Positioner

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Research in Astronomy and Astrophysics 2024年第1期24卷 212-222页

作者： Shaoxiong Guo Yan Yang Yanbin Yin Yihu Tang Yang Tian Chao Zhai Department of Precision Machinery and Precision Instrumentation University of Science and Technology of ChinaHefei 230026China School of Biomedical Engineering Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China Experiment Center of Engineering and Material science University of Science and Technology of ChinaHefei 230026China

With the development of cutting-edge multi-object spectrographs,fiber positioners located in the focal plane are being scaled down in size,and miniature hollow-cup Permanent Magnet motors are now being considered as a suitable replacement for Faulhaber Precistep stepper motors.However,the small electrical time constant of such coreless motors poses a challenge,as the problem of severe commutation torque ripple in a fiber positioner running a position loop has been tricky.To overcome this challenge,it is advised to increase the Pulse Width Modulation(PWM)frequency as much as possible to mitigate the effects of the current fluctuation.This must be done while ensuring adequate resolution of the PWM generator.By employing a voltage open-loop field-oriented control based on a modulation frequency of 1 MHz,the drive current only costs 25 m A under a 3.3 V power supply.The sine degree of phase current is immaculate,and the repeat positioning accuracy can reach 2μm.Moreover,it is possible to further shrink the bill of devices and the layout area of the Printed Circuit Board,especially in sizesensitive applications.This device has been developed under the new generation of The Large Sky Area MultiObject Fiber Spectroscopic Telescope.

关键词： instrumentation:adaptive optics instrumentation:spectrographs proper motions reference systems

Challenges and opportunities in rare cancer research in China

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science China(Life sciences) 2024年第2期67卷 274-285页

作者： Jianxin Xue Qunyan Lyu division of Thoracic Tumor Multimodality Treatment Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China National Natural science Foundation of China Beijing 100085China

Cancer is one of the major public health challenges in China.Rare cancers collectively account for a considerable proportion of all malignancies.The lack of awareness of rare cancers among healthcare professionals and the general public,the typically complex and delayed diagnosis,and limited access to clinical trials are key challenges.Recent years have witnessed an increase in funding for research related to rare cancers in China.In this review,we provide a comprehensive overview of rare cancers and summarize the status of research on rare cancers in China and overseas,including the trends of funding and publications.We also highlight the challenges and perspectives regarding rare cancers in China.

关键词： rare cancers basic research clinical research preclinical model funding scheme

Regulatory role of peroxynitrite in advanced glycation end products mediated diabetic cardiovascular complications

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World Journal of Diabetes 2024年第3期15卷 572-574页

作者： Asis Bala Pharmacology and Drug Discovery Research Laboratory Division of Life SciencesInstitute of Advanced Study in Science and TechnologyGuwahati 781035AssamIndia

The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling mediators.The effect of superoxide(O2-)and O2-mediated ROS and reactive nitrogen species depends on their concentration and location of formation.Nitric oxide(NO)has anti-inflammatory and anticoagulant properties and a vasodilation effect,but NO can be deactivated by reacting with O_(2)^(-).This reaction between NO and O2-produces the potent oxidant ONOO−.Therefore,ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.

关键词： Diabetes Cardiovascular complication Advanced glycation end products Reactive oxygen species Reactive nitrogen species Peroxynitrite

Anticipating the lifespan: Predicting the durability of an anode-supported solid oxide fuel cell short stack over 50,000 h

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Progress in Natural science:Materials International 2024年第3期34卷 606-613页

作者： Muhammad Zubair Khan Amjad Hussain Seung-Bok Lee Tak-Hyoung Lim Rak-Hyun Song Department of Materials science & Engineering Pak-Austria Fachhochschule: Institute of Applied Sciences and Technology Mang Haripur Hydrogen Energy Research division Korea Institute of Energy Research Department of Advanced Energy and System Engineering Korea University of Science and Technology (UST)

In the present study, the operational lifetime of a solid oxide fuel(SOFC) short stack is predicted by investigating the performance degradation of both the short stack and its cells throughout 1000 h at 800°C. The short stack and integral cell voltages are continuously measured during the long-term test, with electrochemical impedance spectroscopy(EIS) conducted every 200 h. The short stack voltage decreased rapidly for the initial 200–300 h and afterwards, it decreased at a slow rate due to the increase in the Ohmic and polarization resistances in the same manner. Scanning electron microscopy results show that there is no delamination or cracking among constituent layers of the short-stack cells. The single degradation effects of the Ni coarsening in the anode, cation migration and surface segregation in cathode and oxide scale growth in metallic interconnect mesh are successfully integrated into a comprehensive lifetime prediction model. The experimentally measured voltage degradation data of the short stack fits well with the developed mathematical model and allows the successful prediction of the lifetime up to 50,000 h.

关键词： Degradation Impedance Lifetime SOFC Stack

A multiple flame-retardant,early fire-warning,and highly sensitive thread-shaped all-fabric-based piezoresistive sensor

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science China(Technological sciences) 2024年第4期67卷 1151-1159页

作者： LI WeiBiao ZHANG Shuai MA ShuQi WANG JiaCheng WANG Huan YANG QiRong SONG YongTao ZHU Jie North China Institute of Aerospace Engineering Langfang 065000China Langfang Fire and Rescue division of Hebei Province Langfang 065000China School of Information science and Engineering Xinjiang College of Science and TechnologyKorla 841000China

In the artificial intelligence age,multifunctional and intelligent fireproof fabric-based electronics are urgently needed.Herein,a novel thread-shaped all-fabric-based piezoresistive sensor(denoted as TAFPS)with properties such as flame retardancy,firewarning,and piezoresistivity is proposed,which is composed of an inner nickel-plated fabric electrode,a multifunctional double helix fabric,and an external flame-retardant encapsulation fabric.Owing to the multiple flame-retardant properties of glass fiber tubular fabric,aminated carbon nanotubes(ACNTs),and ammonium polyphosphate,the char residue of the TAFPS reaches40.3 wt%at 800℃.In addition,the heat-sensitive effect of ACNTs during combustion causes a rapid decrease in the TAFPS resistance,triggering the fire alarm system within 2 s.Additionally,benefiting from the force-sensitive behavior of the double helix layer and tightly wrapped pattern of the external heat-shrinkable tubular fabric,TAFPS demonstrated a high sensitivity of4.40 kPa^(-1)(0–5.81 k Pa)and good stability for 10000 s.Considering its excellent flame resistance,high sensitivity,and agreeable stability,the developed TAFPS can be integrated into fire suits to monitor the exercise training process and the external fire environment.This work offers a novel approach for fabricating all-fabric-based piezoresistive sensors in the future for fire prevention and fire alarms,with promising applications in fire protection,the Internet of Things,and smart apparel.

关键词： all-fabric piezoresistive sensor multiple flame retardancy agile fire-warning high sensitivity