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A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo

Protein & Cell 2023年第1期14卷 37-50页

作者： Daming Zuo Yu Chen Jian-piaoCai hao-yang yuan Jun-Qi Wu Yue Yin Jing-Wen Xie Jing-Min Lin Jia Luo yang Feng Long-Jiao Ge Jia Zhou Ronald JQuinn San-Jun Zhao Xing Tong Dong-Yan Jin Shuofeng yuan Shao-Xing Dai Min Xu Center for Pharmaceutical Sciences Faculty of Life Science and TechnologyKunming University of Science and TechnologyKunming 650500China Department of Medical Laboratory School of Laboratory Medicine and BiotechnologySouthern Medical UniversityGuangzhou 510515China State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming 650500China Department of Microbiology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong 999077China Department of Immunology School of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China Griffith Institute for Drug Discovery Griffith UniversityBrisbane 4111Australia School of Life Sciences Yunnan Normal UniversityKunming 650500China School of Biomedical Sciences Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong 999077China Microbiome Medicine Center Department of Laboratory medicineZhujiang HospitalSouthern Medical UniversityGuangzhou 510515China

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease,including the devastating *** effective antivirals with broad-spectrum coverage are urgently ***,we reported a novel broad-spectrum antiviral compound *** administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV ***,oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron(BA.1)infection significantly decreases viral loads and attenuates lung ***,PAC5 binds to a pocket near Asp49 in the RNA recognition motif of ***5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway,leading to the production of type I IFNs with antiviral *** results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1,which may have a role in dealing with emerging infectious diseases now and in the future.

关键词： hnRNPA2B1 PAC5 HBV SARS-CoV-2 omicron TBK1-IRF3 pathway type I IFNs

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BOD1 regulates the cerebellar IV/V lobe-fastigial nucleus circuit associated with motor coordination

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Signal Transduction and Targeted Therapy 2022年第7期7卷 2490-2503页

作者： Xiu-Xiu Liu Xing-Hui Chen Zhi-Wei Zheng Qin Jiang Chen Li Lin yang Xiang Chen Xing-Feng Mao hao-yang yuan Li-Li Feng Quan Jiang Wei-Xing Shi Takuya Sasaki Kohji Fukunaga Zhong Chen Feng Han Ying-Mei Lu Key Laboratory of Cardiovascular&Cerebrovascular Medicine Drug Target and Drug Discovery CenterSchool of PharmacyNanjing Medical University211166 NanjingChina Department of Physiology School of Basic Medical SciencesNanjing Medical University211166 NanjingChina Institute of Pharmacology and Toxicology College of Pharmaceutical SciencesZhejiang University310058 HangzhouChina Department of Pharmaceutical and Administrative Sciences Loma Linda University School of PharmacyLoma LindaCA 92350USA Department of Basic Sciences Loma Linda University School of MedicineLoma LindaCA 92350USA Department of Pharmacology Graduate School of Pharmaceutical SciencesTohoku UniversitySendai 980-8578Japan Institute of Brain Science the Affiliated Brain Hospital of Nanjing Medical University210029 NanjingChina Gusu School Nanjing Medical UniversitySuzhou Municipal HospitalThe Affiliated Suzhou Hospital of Nanjing Medical University215002 SuzhouChina

Cerebellar ataxias are characterized by a progressive decline in motor coordination,but the specific output circuits and underlying pathological mechanism remain poorly *** cell-type-specific manipulations,we discovered a novel GABAergic Purkinje cell(PC)circuit in the cerebellar IV/V lobe that projected to CaMKIIα+neurons in the fastigial nucleus(FN),which regulated sensorimotor ***,transcriptomics profiling analysis revealed various cerebellar neuronal identities,and we validated that biorientation defective 1(BOD1)played an important role in the circuit of IV/V lobe to ***1 deficit in PCs of IV/V lobe attenuated the excitability and spine density of PCs,accompany with ataxia ***,BOD1 enrichment in PCs of IV/V lobe reversed the hyperexcitability of CaMKIIα+neurons in the FN and ameliorated ataxia behaviors in L7-Cre;BOD1f/f ***,these findings further suggest that specific regulation of the cerebellar IV/V lobePCs→FNCaMKIIα+circuit might provide neuromodulatory targets for the treatment of ataxia behaviors.

关键词： fastigial reversed Together

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Sex differences in aging and injured brain

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Neural Regeneration Research 2025年第10期20卷 2901-2902页

作者： Jordan N.Williamson yuan yang University of Illinois Urbana-Champaign Grainger College of EngineeringDepartment of BioengineeringUrbanaILUSA Carle Foundation Hospital Stephenson Family Clinical Research InstituteClinical Imaging Research CenterUrbanaILUSA University of Illinois Urbana-Champaign Beckman Institute for Advanced Science and TechnologyUrbanaILUSA Northwestern University Department of Physical Therapy and Human Movement SciencesChicagoILUSA

Background:The prevalence,age of onset,and symptomatology of traumatic brain injury,stroke,and neurodegenerative diseases(such as Alzheimer’s disease(AD),Parkinson’s disease,amyotrophic lateral sclerosis,and Huntington’s disease)differ substantially between males and *** higher prevalence of these brain disorders has been attributed to females having a greater longevity compared with *** one of the greatest risk factors of acquired brain injury(such as stroke,traumatic brain injury caused by fall)and neurodegenerative disease is age.

关键词： Huntington prevalence traumatic

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Striatal CDK5 Regulates Cholinergic Neuron Activation and Dyskinesia-like Behaviors through BK Channels

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Research 2023年第4期2023卷 739-753页

作者： Chu Tong Peng-Xiang Min Qian Zhang Ru-Xin Gu Yao-Hai Wen Yi Shi Yu-Huan Bao Xiang Chen Yi-Xuan Zhang Xing-Feng Mao hao-yang yuan Xiu-Xiu Liu Takuya Sasaki Li Zhang Feng Han Ying-Mei Lu Department of Physiology School of Basic Medical SciencesNanjing Medical UniversityNanjing211166China International Joint Laboratory for Drug Target of Critical Illnesses School of PharmacyNanjing Medical UniversityNanjing211166China Department of Geriatrics Nanjing Brain Hospital Affiliated to Nanjing Medical UniversityNanjing210029China Institute of Pharmacology and Toxicology College of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China Gusu School Nanjing Medical UniversitySuzhou Municipal HospitalThe Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou215002China Department of Pharmacology Graduate School of Pharmaceutical SciencesTohoku UniversitySendai980-8578Japan Institute of Brain Science the Affiliated Brain Hospital of Nanjing Medical UniversityNanjing211166China.

Disturbance of the cholinergic system plays a crucial role in the pathological progression of neurological diseases that cause dyskinesia-like ***,the molecular mechanisms underlying this disturbance remain ***,we showed that cyclin-dependent kinase 5(Cdk5)was reduced in cholinergic neurons of midbrain according to the single-nucleus RNA sequencing *** levels of CDK5 also decreased in patients with Parkinson’s disease accompanied by motor ***,Cdk5 deficiency in cholinergic neurons triggered paw tremors,abnormal motor coordination,and motor balance deficits in *** symptoms occurred along with cholinergic neuron hyperexcitability and increases in the current density of large-conductance Ca2+-activated K+channels(BK channels).Pharmacological inhibition of BK channels restrained the excessive intrinsic excitability of striatal cholinergic neurons in Cdk5-deficient ***,CDK5 interacted with BK channels and negatively regulated BK channel activity via phosphorylation of *** of CDK5 expression in striatal cholinergic neurons reduced dyskinesia-like behaviors in ChAT-Cre;Cdk5f/f ***,these findings indicate that CDK5-induced phosphorylation of BK channels involves in cholinergic-neuronmediated motor function,providing a potential new therapeutic target for treating dyskinesia-like behaviors arising from neurological diseases.

关键词： Cdk5 Neuron CDK5

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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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Stochastic Augmented-Based Dual-Teaching for Semi-Supervised Medical Image Segmentation

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Computers, Materials & Continua 2025年第1期82卷 543-560页

作者： Hengyang Liu yang yuan Pengcheng Ren Chengyun Song Fen Luo School of Computer Science and Engineering Chongqing University of TechnologyChongqing400054China College of Artificial Intelligence Chongqing Technology and Business UniversityChongqing400067China

Existing semi-supervisedmedical image segmentation algorithms use copy-paste data augmentation to correct the labeled-unlabeled data distribution ***,current copy-paste methods have three limitations:(1)training the model solely with copy-paste mixed pictures from labeled and unlabeled input loses a lot of labeled information;(2)low-quality pseudo-labels can cause confirmation bias in pseudo-supervised learning on unlabeled data;(3)the segmentation performance in low-contrast and local regions is less than *** design a Stochastic Augmentation-Based Dual-Teaching Auxiliary Training Strategy(SADT),which enhances feature diversity and learns high-quality features to overcome these *** be more precise,SADT trains the Student Network by using pseudo-label-based training from Teacher Network 1 and supervised learning with labeled data,which prevents the loss of rare labeled *** introduce a bi-directional copy-pastemask with progressive high-entropy filtering to reduce data distribution disparities and mitigate confirmation bias in *** the mixed images,Deep-Shallow Spatial Contrastive Learning(DSSCL)is proposed in the feature spaces of Teacher Network 2 and the Student Network to improve the segmentation capabilities in low-contrast and local *** this procedure,the features retrieved by the Student Network are subjected to a random feature perturbation *** two openly available datasets,extensive trials show that our proposed SADT performs much better than the state-ofthe-art semi-supervised medical segmentation *** only 10%of the labeled data for training,SADT was able to acquire a Dice score of 90.10%on the ACDC(Automatic Cardiac Diagnosis Challenge)dataset.

关键词： Semi-supervised medical image segmentation contrastive learning stochastic augmented

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“Zero‑Strain” NiNb_(2)O_(6) Fibers for All‑Climate Lithium Storage

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Nano-Micro Letters 2025年第1期17卷 348-360页

作者： Yan Zhao Qiang yuan Liting yang Guisheng Liang Yifeng Cheng Limin Wu Chunfu Lin Renchao Che College of Physics Donghua UniversityShanghai 201620People’s Republic of China School of Materials Science and Engineering Institute of Materials for Energy and EnvironmentQingdao UniversityQingdao 266071People’s Republic of China Laboratory of Advanced Materials Shanghai Key Laboratory of Molecular Catalysis and Innovative MaterialsAcademy for Engineering&TechnologyFudan UniversityShanghai 200438People’s Republic of China Zhejiang Laboratory Hangzhou 311100People’s Republic of China Inner Mongolia University Hohhot 010021People’s Republic of China

Niobates are promising all-climate Li^(+)-storage anode material due to their fast charge transport,large specific capacities,and resistance to electrolyte ***,their moderate unit-cellvolume expansion(generally 5%–10%)during Li^(+)storage causes unsatisfactory long-term ***,“zero-strain”NiNb_(2)O_(6) fibers are explored as a new anode material with comprehensively good electrochemical *** Li^(+)storage,the expansion of electrochemical inactive NiO_(6) octahedra almost fully offsets the shrinkage of active NbO_(6) octahedra through reversible O *** superior volume-accommodation capability of the NiO_(6) layers guarantees the“zero-strain”behavior of NiNb_(2)O_(6) in a broad temperature range(0.53%//0.51%//0.74%at 25//−10//60℃),leading to the excellent cyclability of the NiNb_(2)O_(6) fibers(92.8%//99.2%//91.1%capacity retention after 1000//2000//1000 cycles at 10C and 25//−10//60℃).This NiNb_(2)O_(6) material further exhibits a large reversible capacity(300//184//318 mAh g−1 at 0.1C and 25//−10//60℃)and outstanding rate performance(10 to 0.5C capacity percentage of 64.3%//50.0%//65.4%at 25//−10//60℃).Therefore,the NiNb_(2)O_(6) fibers are especially suitable for large-capacity,fast-charging,long-life,and all-climate lithium-ion batteries.

关键词： NiNb_(2)O_(6)porous fiber “Zero-strain”mechanism Electrochemical property Harsh-temperature operation Operando characterization

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Study on the hydrogen absorption properties of a YGdTbDyHo rare-earth high-entropy alloy

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 127-135页

作者： Tongyue Li Ziliang Xie Wenjiao Zhou Huan Tong Dawen yang Anjia Zhang yuan Wu Xiping Song State Key Laboratory for Advanced Metals and Materials University of Science and Technology BeijingBeijing 100083China Whole Win(Beijing)Materials Sci.&Tech.Co. Ltd.Beijing 100083China

This study investigated the microstructure and hydrogen absorption properties of a rare-earth high-entropy alloy(HEA),*** indicated that the YGdTbDyHo alloy had a microstructure of equiaxed grains,with the alloy elements distributed *** hydrogen absorption,the phase structure of the HEA changed from a solid solution with an hexagonal-close-packed(HCP)structure to a high-entropy hydride with an faced-centered-cubic(FCC)structure without any secondary phase *** alloy demonstrated a maximum hydrogen storage capacity of 2.33 H/M(hydrogen atom/metal atom)at 723 K,with an enthalpy change(ΔH)of-141.09 kJ·mol^(-1)and an entropy change(ΔS)of-119.14 J·mol^(-1)·K^(-1).The kinetic mechanism of hydrogen absorption was hydride nucleation and growth,with an apparent activation energy(E_(a))of 20.90 kJ·mol^(-1).Without any activation,the YGdTbDyHo alloy could absorb hydrogen quickly(180 s at 923 K)with nearly no incubation period *** reason for the obtained value of 2.33 H/M was that the hydrogen atoms occupied both tetrahedral and octahedral *** results demonstrate the potential application of HEAs as a high-capacity hydrogen storage material with a large H/M ratio,which can be used in the deuterium storage field.

关键词： rare-earth high-entropy alloy hydrogen absorption capacity pressure–composition–temperature curves kinetics

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RECENT VERIFICATION FOR CERENKOV LINE RADIATION

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Chinese Science Bulletin 1989年第9期34卷 716-721页

作者：奚富云徐克尊郝禄原杨炳忻 University of Science and Technology of China Hefei

I. TNTRODUCTIONSince You and Cheng proposed the theory of Cerenkov line spectrum, we have studied the radiation experimentally and theoretically. By an electron beam made

关键词： Cerenkov line spectrum radiation fluorescence radiation delay coincidence measurement isotropic polarization.

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粒子群优化算法实现仿射不变性形状识别

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重庆大学学报（自然科学版） 2010年第3期33卷 65-71页

作者：毛玉星韩倍涛冯莲王豪徐少志郝远洋重庆大学输配电装备及系统安全与新技术国家重点实验室重庆400044

针对形状识别过程中,轮廓图像会因为视点改变发生仿射变换的问题,提出了一种新的仿射不变特征提取方法及匹配策略。首先,对所有边界点计算其与质心的距离及方向角,并在给定的角度邻域内进行平均以消除噪声干扰;然后,计算方向角相差180... 详细信息

针对形状识别过程中,轮廓图像会因为视点改变发生仿射变换的问题,提出了一种新的仿射不变特征提取方法及匹配策略。首先,对所有边界点计算其与质心的距离及方向角,并在给定的角度邻域内进行平均以消除噪声干扰;然后,计算方向角相差180°的边界点质心距离之比作为形状特征,该特征具有仿射不变性。由于仿射变换图像间各轮廓点的方向角具有非线性变化特征,质心距离比需要重采样以建立对应关系,笔者将其转化为一个路径规划问题,并用粒子群优化算法得以解决。实验表明该方法对形状识别中的平移、旋转、缩放、拉伸和噪声干扰具有良好的效果。

关键词：形状识别仿射变换质心距离比粒子群优化

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