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Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

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Science China Chemistry 2025年第1期 308-316页

作者： Sili Wang Jiancheng Huang Yanan Du Wei Huang Yufeng Xue Xiaokun Xu Guannan Zhong Yuanyuan Shi Bin Hong Xiaoying Bian Wen Liu State Key Laboratory of Chemical Biology Shanghai Institute of Organic Chemistry University of Chinese Academy of SciencesChinese Academy of Sciences State Key Laboratory of Microbial Technology Shandong University national Health Commission (NHC) Key Laboratory of Biotechnology for Microbial Drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College

Cobalamin(Cbl)-dependent radical S-adenosyl-L-methionine(SAM) proteins constitute the largest collection of the radical SAM superfamily that has hundreds of thousands of individual members. Many of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding reactions. In the biosynthetic pathway of chuangxinmycin(CXM), a unique indole alkaloid antibiotic with potent anti-infective activity, functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process, which, however, remained to be reconstituted biochemically. We here report the dissection of this enzymatic process, which requires the incorporation of Cxm8, a Cbl-dependent radical SAM protein, with Cxm9, a DUF5825family protein that shares no homology to any proteins of known functions. Cxm8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-S-hetero ring system in a successive manner, achieving CXM and a recently identified, C3-dimethylated congener. Detailed biochemical characterization,isotope labeling, structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the DUF5825 protein for C3-methylase activity. This is the first example that a Cbl-dependent protein acts with a partner to exhibit radical SAM activity.

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Dietary carbohydrate intake and risk of type 2 diabetes:a 16-year prospective cohort study

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Science China Life Sciences 2025年

作者： Lu Gan Yi Yang Bin Zhao Kai Yu Kehua Guo Fang Fang Zhiguang Zhou Demetrius Albanes Jiaqi Huang Key Laboratory of Diabetes Immunology Ministry of Education and Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University CSU-Sinocare Research Center for Nutrition and Metabolic Health Xiangya School of Public Health Central South UniversityFurong Laboratory Division of Cancer Epidemiology and Genetics National Cancer Institute NIH Department of Health and Human Services School of Computer Science and Engineering Central South University institute of Environmental Medicine Karolinska Institute national Clinical Research Center for Metabolic Diseases Key Laboratory of Diabetes Immunology Ministry of Education and Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University

Despite considerable research underscoring the importance of carbohydrate intake in relation to the risk of type 2 diabetes(T2D), a comprehensive assessment of this relationship is currently lacking. We aimed to examine the associations of various types and food sources of dietary carbohydrate intake with the risk of T2D, to evaluate potential effect modification by other factors, including genetic susceptibility,and to explore the potential mediators for such associations. The present study included 161,872 participants of the UK Biobank who were free of prevalent cancer, cardiovascular disease, or diabetes, and had at least one validated 24-h dietary recall assessment. Multivariableadjusted age-stratified Cox proportional hazard regression models were applied to estimate hazard ratios(HRs) and 95% confidence intervals(CI) for the associations of various types and food sources of dietary carbohydrate intake with risk of T2D. During a median follow-up of13.6 years, 4,176 incident cases of T2D were identified. In the multivariable-adjusted models, a greater intake of fiber, carbohydrates from whole grains, and carbohydrates from non-starchy vegetables was significantly associated with a lower risk of T2D(highest vs. lowest quantile, HR [95% CI]=0.70 [0.62–0.79], 0.74 [0.67–0.82], and 0.83 [0.75–0.92], respectively, all P for trend <0.005). In contrast, a higher intake of starch and carbohydrate from starchy vegetables was associated with an increased risk of T2D(highest vs. lowest quantile, HR [95%CI]=1.31 [1.16–1.48] and 1.19 [1.09–1.31], respectively, both P for trend <0.005). Replacing one serving of refined grains or starchy vegetables with an equal amount of whole grains or non-starchy vegetables was associated with 4% to 10% lower risk of T2D(all P values <0.001).The observed associations were generally similar across population subgroups, including individuals with different genetic susceptibility to T2D. Mediation analyses of the inverse association between T

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High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

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Neural Regeneration Research 2025年第9期20卷 2611-2623页

作者： Mengshi Yang Miao Bai Yuan Zhuang Shenghua Lu Qianqian Ge Hao Li Yu Deng Hongbin Wu Xiaojian Xu Fei Niu Xinlong Dong Bin Zhang Baiyun Liu Beijing Tiantan Hospital Capital Medical UniversityBeijingChina Department of Neurology The First Hospital of Tsinghua UniversityBeijingChina Department of Neurotrauma and Beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Department of Critical Care Medicine Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Center for Nerve Injury and Repair Beijing Institute of Brain DisordersChina National Clinical Research Center for Neurological DiseasesBeijingChina

Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently *** potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet *** the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of *** vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial ***,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were ***-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of *** Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our ***-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain *** dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in *** receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain ***,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is th

关键词： apoptosis BV2 microglia dexamethasone glucocorticoid receptor glucocorticoids innate immune system microglial polarization neuroinflammation primary microglia traumatic brain injury

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Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

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Neural Regeneration Research 2025年第1期20卷 67-81页

作者： Yubo Wang Tingli Yuan Tianjie Lyu Ling Zhang Meng Wang Zhiying He Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China national Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Shanghai Engineering Research Center of Stem Cells Translational Medicine ShanghaiChina national Center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina institute for Regenerative Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina Chinese institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital Healthcare for Neurological Diseases BeijingChina

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger ***,in particular,bears a high burden of stroke *** recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its *** review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and ***,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell ***,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient *** cell therapy may potentially become an important component of ischemic stroke treatment.

关键词： cell therapy immune cell inflammatory ischemic stroke stem cell

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Trend in Observed and Projected Maximum and Minimum Temperature over N-W Himalayan Basin

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Journal of Mountain Science 2015年第2期12卷 417-433页

作者： Dharmaveer SINGH Sanjay K JAIN Rajan Dev GUPTA GIS Cell Motilal Nehru National Institute of Technology Allahabad water Resources Systems Division National Institute of Hydrology Department of Civil Engineering Motilal Nehru National Institute of Technology Allahabad

Recently, study in past trends of climate variables gained significant consideration because of its contribution in adaptions and mitigation strategies for potential future changes in climate, primarily in the area of water resource management. Future interannual and inter-seasonal variations in maximum and minimum temperature may bring significant changes in hydrological systems and affect regional water resources. The present study has been performed to observe past(1970-2010) as well as future(2011-2100)spatial and temporal variability in temperature(maximum and minimum) over selected stations of Sutlej basin located in North-Western Himalayan region in India. The generation of future time series of temperature data at different stations is done using statistical downscaling technique. The nonparametric test methods, modified Mann-Kendall test and Cumulative Sum chart are used for detecting monotonic trend and sequential shift in time series of maximum and minimum temperature. Sen's slope estimator test is used to detect the magnitude of change over a period of time on annual and seasonal basis. The cooling experienced in annual TMax and TMin at Kasol in past(1970-2010) would be replaced by warming in future as increasing trends are detected in TMax during 2020 s and 2050 s and in TMin during 2020 s, 2050 s and 2080 s under A1 B and A2 scenarios. Similar results of warming are also predicted at Sunnifor annual TMin in future under both scenarios which witnessed cooling during 1970-2010. The rise in TMin at Rampur is predicted to be continued in future as increasing trends are obtained under both the scenarios. Seasonal trend analysis reveals large variability in trends of TMax and TMin over these stations for the future periods.

关键词： Statistical downscaling model Canadian Coupled Global Climate Model Temperature MannKendall test Sen’s slope estimator

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Research on flexible display at Ulsan national institute of Science and Technology

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npj Flexible Electronics 2017年第1期1卷 47-59页

作者： Jihun Park Sanghyun Heo Kibog Park Myoung Hoon Song Ju-Young Kim Gyouhyung Kyung Rodney Scott Ruoff Jang-Ung Park Franklin Bien School of Materials Science and Engineering Ulsan National Institute of Science and Technology(UNIST)Ulsan Metropolitan City 44919Republic of Korea School of Electrical and Computer Engineering Ulsan National Institute of Science and Technology(UNIST)Ulsan Metropolitan City 44919Republic of Korea Department of Physics Ulsan National Institute of Science and Technology(UNIST)Ulsan Metropolitan City 44919Republic of Korea School of Design and Human Engineering Ulsan National Institute of Science and Technology(UNIST)Ulsan Metropolitan City 44919Republic of Korea Center for Multidimensional Carbon Materials Institute for Basic Science(IBS)Ulsan 44919Republic of Korea Department of Chemistry Ulsan National Institute of Science and Technology(UNIST)Ulsan 44919Republic of Korea

Displays represent information visually,so they have become the fundamental building block to visualize the data of current electronics including ***,electronics have been advanced toward flexible and wearable electronics that can be bent,folded,or stretched while maintaining their performance under various ***,recent advances in research to demonstrate flexible and wearable displays are *** introduce these results by dividing them into several categories according to the components of the display:active-matrix backplane,touch screen panel,light sources,integrated circuit for fingerprint touch screen panel,and characterization tests;and we also present mechanical tests in nano-meter scale and visual ergonomics research.

关键词： dividing electronics panel

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Growth behavior and electronic regulation of Pt on various Mo-based supports for hydrogen evolution electrocatalysis

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Science China Chemistry 2025年

作者： Lulu Chen Yichao Huang Jiajun Wang Meihong Liao Zhiyuan Liu Meiqi Liu Hanqing Cai Lin Wang Lidong Gao Dawei Hu Lianming Zhao Ning Pu Zhuangjun Fan State Key Laboratory of Chemical Safety School of Materials Science and Engineering China University of Petroleum (East China) School of Mechanical and Electronic Engineering Qingdao Binhai University Qingdao Chuangqi New Energy Catalysis Technology Co.Ltd. Sinopec Research institute of Petroleum Processing Co.Ltd. institute of Energy Hefei Comprehensive National Science Center

Insight into the growth behavior and electronic regulation of platinum （Pt） on various transition metal supports is paramount in developing high-performing electrocatalysts for hydrogen evolution reactions （HER）.Herein,we studied the influence of molybdenum-based supports （MoX,X=C,N,P,and S） on the growth behavior and electronic regulation of *** found that the formation energy variations between Pt single atom and clusters on MoX supports play a pivotal role in the growth behavior of ***,the electronic regulation of Pt induced by metal-support interaction may reflect the valence changes of Pt in Pt-MoX/*** Pt-MoC/C catalyst with a moderate valence state of Pt exhibits the best HER activity with an overpotential of 12.0 mV at 10 mA cm-2and a mass activity of 27.1 A mgPt-1,12.3 times as high as that of commercial 20 wt% Pt/*** work provides constructive guidance for the design of high-performance HER catalysts.

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The detection, extraction and parameter estimation of extreme-mass-ratio inspirals with deep learning

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 86-96页

作者： Qianyun Yun Wen-Biao Han Yi-Yang Guo He Wang Minghui Du Hangzhou institute for Advanced Study University of Chinese Academy of Sciences Shanghai Astronomical Observatory Chinese Academy of Sciences School of Physics and Astronomy Shanghai Jiao Tong University School of Astronomy and Space Science University of Chinese Academy of Sciences Taiji Laboratory for Gravitational Wave Universe (Beijing/Hangzhou) University of Chinese Academy of Sciences Lanzhou Center for Theoretical Physics Key Laboratory of Theoretical Physics of Gansu Province Key Laboratory of Quantum Theory and Applications of MoE Lanzhou University institute of Theoretical Physics & Research Center of Gravitation Lanzhou University International Centre for Theoretical Physics Asia-Pacific (ICTP-AP) University of Chinese Academy of Sciences (UCAS) Center for Gravitational Wave Experiment National Microgravity Laboratory Institute of Mechanics Chinese Academy of Sciences

One of the primary goals of space-borne gravitational wave detectors is to detect and analyze extreme-mass-ratio inspirals(EMRIs). This task is particularly challenging because EMRI signals are complex, lengthy, and faint. In this work, we introduce a2-layer convolutional neural network(CNN) approach to detect EMRI signals for space-borne detectors, achieving a true positive rate(TPR) of 96.9% at a 1% false positive rate(FPR) for signal-to-noise ratio(SNR) from 50 to 100. Especially, the key intrinsic parameters of EMRIs such as the mass, spin of the supermassive black hole(SMBH) and the initial eccentricity of the orbit can also be inferred directly by employing a neural network. The mass and spin of the SMBH can be determined at 99% and 92% respectively. This will greatly reduce the parameter spaces and computing cost for the following Bayesian parameter *** model also has a low dependency on the accuracy of the waveform model. This study underscores the potential of deep learning methods in EMRI data analysis, enabling the rapid detection of EMRI signals and efficient parameter estimation.

关键词： gravitational wave EMRIs deep-learing

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Increased excitatory amino acid transporter 2 levels in basolateral amygdala astrocytes mediate chronic stress–induced anxiety-like behavior

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Neural Regeneration Research 2025年第6期20卷 1721-1734页

作者： Xirong Xu Shoumin Xuan Shuai Chen Dan Liu Qian Xiao Jie Tu Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases Shenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina CAS Key Laboratory of Brain Connectome and Manipulation Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina Guangdong Provincial Key Laboratory of Brain Connectome and Behavior the Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina University of Chinese of Academy of Sciences BeijingChina Faculty of Life and Health Sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina

The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with ***, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal *** knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was ob

关键词： anxiety astrocytes basolateral amygdala behavior dihydrokainic acid excitatory amino acid transporter 2 fiber photometry glutamate LDN-212320 transporter

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Interfacial Zn2+-solvation regulator towards reversible and stable Zn anode

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Journal of Energy Chemistry 2025年第1期100卷 684-692页

作者： Miao Zhou Xiongbin Luo Hang Li Shan Guo Zhuang Tong Xiaotao Zhou Xu Li Zhaohui Hou Shuquan Liang Guozhao Fang College of Mechanical Engineering Key Laboratory of Hunan Province for Advanced Carbon-based Functional Materials Hunan Institute of Science and Technology School of Materials Science and Engineering Key Laboratory of Electronic Packaging and Advanced Functional Materials of Hunan Province Central South University College of Materials and Metallurgy Guizhou University national Energy Metal Resources and New Materials Key Laboratory Central South University

Aqueous zinc-ion batteries （AZIBs） are fundamentally challenged by the instability of the electrode/electrolyte interface,predominantly due to irreversible zinc （Zn） deposition and hydrogen ***,the intricate mechanisms behind the electrochemical discrepancies induced by interfacial Zn2+-solvation and deposition behavior demand comprehensive *** molecules endowed with special functional groups （such as hydroxyl,carboxyl,etc.） have the potential to significantly optimize the solvation structure of Zn2+and regulate the interfacial electric double layer （EDL）.By increasing nucleation overpotential and decreasing interfacial free energy,these functional groups facilitate a lower critical nucleation radius,thereby forming an asymptotic nucleation model to promote uniform Zn ***,this study presents a pioneering approach by introducing trace amounts of n-butanol as solvation regulators to engineer the homogenized Zn （H-Zn） anode with a uniform and dense *** interfacial reaction and structure evolution are explored by in/ex-situ experimental techniques,indicating that the H-Zn anode exhibits dendrite-free growth,no by-products,and weak hydrogen evolution,in sharp contrast to the bare ***,the H-Zn anode achieves a remarkable Zn utilization rate of approximately 20% and simultaneously sustains a prolonged cycle life exceeding 500 ***,the H-Zn//NH4V4O10（NVO） full battery showcases exceptional cycle stability,retaining 95.04%capacity retention after 400 cycles at a large current density of 5 A *** study enlightens solvation-regulated additives to develop Zn anode with superior utilization efficiency and extended operational lifespan.

关键词： Solvation

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