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Cornus officinalis with high pressure wine steaming enhanced anti-hepatic fibrosis: Possible through SIRT3-AMPK axis

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Journal of Pharmaceutical Analysis 2024年第5期14卷 758-771页

作者： Xin Han Yan Ning Xinyue Dou Yiwen Wang Qiyuan Shan Kao Shi Zeping Wang Chuan Ding Min Hao Kuilong Wang Mengyun Peng Haodan Kuang Qiao Yang Xianan Sang Gang Cao school of Pharmacy Zhejiang Chinese Medical UniversityHangzhou311400China

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying *** vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-b(TGF-b).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated histopathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw *** ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)*** note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and *** interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through *** conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mechanism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

关键词： Liver fibrosis SIRT3 Cornus officinalis AMPK Caspase6

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Knockdown of neuronal DAF-15/Raptor promotes healthy aging in ***

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Journal of Genetics and Genomics 2024年第5期51卷 507-516页

作者： Xiao Zang Qi Wang Hanxin Zhang Yiyan Zhang Zi Wang Zixing Wu Di Chen Model Animal Research Center of medical school Nanjing UniversityNanjingJiangsu 210061China zhejiang university-university of Edinburgh Institute School of MedicineZhejiang UniversityHainingZhejiang 314400China Department of Colorectal Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310058China

The highly conserved target of rapamycin(TOR)pathway plays an important role in aging across *** studies have established that inhibition of the TOR complex 1(TORC1)significantly extends lifespan in Caenorhabditis ***,it has not been clear whether TORC1 perturbation affects aging in a spatiotemporal ***,we apply the auxin-inducible degradation tool to knock down endogenous DAF-15,the *** ortholog of regulatory associated protein of TOR(Raptor),to characterize its roles in *** or tissue-specific inhibition of DAF-15 during development results in various growth defects,whereas neuron-specific knockdown of DAF-15 during adulthood significantly extends lifespan and *** neuronal DAF-15 deficiency-induced longevity requires the intestinal activities of DAF-16/FOXO and PHA-4/FOXA transcription factors,as well as the AAK-2/AMP-activated protein kinaseαcatalytic *** profiling reveals that the neuronal DAF-15 knockdown promotes the expression of genes involved in *** findings define the tissue-specific roles of TORC1 in healthy aging and highlight the importance of neuronal modulation of aging.

关键词： Aging targetof rapamycin DAF-15 DAF-16 C.elegans

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Gene therapy for monogenic disorders: challenges, strategies, and perspectives

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Journal of Genetics and Genomics 2024年第2期51卷 133-143页

作者： Yi Zhang Zhi-Ying Wu Department of medical Genetics and Center for Rare Diseases Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Key Laboratory of medical Neurobiology of zhejiang Province HangzhouZhejiang 310009China

Monogenic disorders refer to a group of human diseases caused by mutations in single genes. While disease-modifying therapies have offered some relief from symptoms and delayed progression for some monogenic diseases, most of these diseases still lack effective treatments. In recent decades, gene therapy has emerged as a promising therapeutic strategy for genetic disorders. Researchers have developed various gene manipulation tools and gene delivery systems to treat monogenic diseases. Despite this progress, concerns about inefficient delivery, persistent expression, immunogenicity, toxicity, capacity limitation, genomic integration, and limited tissue specificity still need to be addressed. This review gives an overview of commonly used gene therapy and delivery tools, along with the challenges they face and potential strategies to counter them.

关键词： Gene therapy Monogenic diseases Geneediting Genedelivery Challenges

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Satellite glial cells in sensory ganglia play a wider role in chronic pain via multiple mechanisms

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Neural Regeneration Research 2024年第5期19卷 1056-1063页

作者： Xiaoyun Qiu Yuanzhi Yang Xiaoli Da Yi Wang Zhong Chen Cenglin Xu Key Laboratory of Neuropharmacology and Translational Medicine of zhejiang Province School of Pharmaceutical ScienceZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina

Satellite glial cells are unique glial cells that surround the cell body of primary sensory *** increasing body of evidence suggests that in the presence of inflammation and nerve damage,a significant number of satellite glial cells become activated,thus triggering a series of functional *** suggests that satellite glial cells are closely related to the occurrence of chronic *** this review,we first summarize the morphological structure,molecular markers,and physiological functions of satellite glial ***,we clarify the multiple key roles of satellite glial cells in chronic pain,including gap junction hemichannel Cx43,membrane channel Pannexin1,K channel subunit 4.1,ATP,purinergic P2 receptors,and a series of additional factors and their receptors,including tumor necrosis factor,glutamate,endothelin,and ***,we propose that future research should focus on the specific sorting of satellite glial cells,and identify genomic differences between physiological and pathological *** review provides an important perspective for clarifying mechanisms underlying the peripheral regulation of chronic pain and will facilitate the formulation of new treatment plans for chronic pain.

关键词： chronic pain primary sensory neurons satellite glial cells sensory ganglia

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Local coordination and electronic interactions of Pd/MXene via dual‐atom codoping with superior durability for efficient electrocatalytic ethanol oxidation

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Carbon Energy 2024年第8期6卷 166-177页

作者： Zhangxin Chen Fan Jing Minghui Luo Xiaohui Wu Haichang Fu Shengwei Xiao Binbin Yu Dan Chen Xianqiang Xiong Yanxian Jin school of Pharmaceutical and Chemical Engineering Taizhou UniversityTaizhouZhejiangChina school of Sciences Zhejiang Sci‐Tech UniversityHangzhouZhejiangChina

Catalyst design relies heavily on electronic metal‐support interactions,but the metal‐support interface with an uncontrollable electronic or coordination environment makes it ***,we outline a promising approach for the rational design of catalysts involving heteroatoms as anchors for Pd nanoparticles for ethanol oxidation reaction(EOR)*** doped B and N atoms from dimethylamine borane(DB)occupy the position of the Ti_(3)C_(2)lattice to anchor the supported Pd *** electrons transfer from the support to B atoms,and then to the metal Pd to form a stable electronic center.A strong electronic interaction can be produced and the d‐band center can be shifted down,driving Pd into the dominant metallic state and making Pd nanoparticles deposit uniformly on the ***‐obtained Pd/DB–Ti_(3)C_(2)exhibits superior durability to its counterpart(∼14.6%retention)with 91.1%retention after 2000 cycles,placing it among the top single metal anodic ***,in situ Raman and density functional theory computations confirm that Pd/DB–Ti_(3)C_(2)is capable of dehydrogenating ethanol at low reaction energies.

关键词： durability electronic interactions ethanol oxidation heteroatom codoping Pd/MXene

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Raising New Hope for Controlling Seizures in Focal Cortical Dysplasia with Gene Therapy

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Neuroscience Bulletin 2024年第7期40卷 1028-1030页

作者： Yuanzhi Yang Yang Zheng Zhong Chen Cenglin Xu Key Laboratory of Neuropharmacology and Translational Medicine of zhejiang Province School of Pharmaceutical SciencesXinhua Hospital of Zhejiang ProvinceThe Second Affiliated Hospital of Zhejiang Chinese Medical UniversityZhejiang Chinese Medical UniversityHangzhou310053China

Focal cortical dysplasia(FCD)is characterized by abnormal cortical development and pharmacoresistant epilepsy,often accompanied by cognitive and behavioral malfunctions[1].According to the International League against Epilepsy(ILAE)classification proposed by Najm,Imad et *** 2022,FCD can be further divided into isolated forms(FCD type Ⅰ and Ⅱ)and another type associated with a principal lesion(FCD type Ⅲ)[2].

关键词： epilepsy al. Therapy

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Prediction of cell-cell communication patierns of dorsal root ganglion cells: single-cell RNA sequencing data analysis

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Neural Regeneration Research 2024年第6期19卷 1367-1374页

作者： Yanna Lian Cheng Wu Li Liu Xiangyao Li National Health Commission and Chinese Academy of medical Sciences Key Laboratory of medical Neurobiology Ministry of Education Frontier Science Center for Brain Research and Brain-Machine Integration School of Brain Science and Brain Medicine Zhejiang University International Institutes of Medicine the Fourth Affiliated Hospital of Zhejiang University School of Medicine zhejiang university-university of Edinburgh Institute Zhejiang University School of Medicine Zhejiang University 4. Biomedical Sciences College of Medicine and Veterinary Medicine The University of Edinburgh Core Facilities of the school of Medicine Zhejiang University

Dorsal root ganglion neurons transmit peripheral somatic information to the central nervous system, and dorsal root ganglion neuron excitability affects pain perception. Dorsal root ganglion stimulation is a new approach for managing pain sensation. Knowledge of the cell-cell communication among dorsal root ganglion cells may help in the development of new pain and itch management strategies. Here, we used the single-cell RNA-sequencing(scRNA-seq) database to investigate intercellular communication networks among dorsal root ganglion cells. We collected scRNA-seq data from six samples from three studies, yielding data on a total of 17,766 cells. Based on genetic profiles, we identified satellite glial cells, Schwann cells, neurons, vascular endothelial cells, immune cells, fibroblasts, and vascular smooth muscle cells. Further analysis revealed that eight types of dorsal root ganglion neurons mediated proprioceptive, itch, touch, mechanical, heat, and cold sensations. Moreover, we predicted several distinct forms of intercellular communication among dorsal root ganglion cells, including cell-cell contact, secreted signals, extracellular matrix, and neurotransmitter-mediated signals. The data mining predicted that Mrgpra3-positive neurons robustly express the genes encoding the adenosine Adora2b(A2B) receptor and glial cell line-derived neurotrophic factor family receptor alpha 1(GFRα-1). Our immunohistochemistry results confirmed the coexpression of the A2B receptor and GFRα-1. Intrathecal injection of the A2B receptor antagonist PSB-603 effectively prevented histamine-induced scratching behaviour in a dose-dependent manner. Our results demonstrate the involvement of the A2B receptor in the modulation of itch sensation. Furthermore, our findings provide insight into dorsal root ganglion cell-cell communication patterns and mechanisms. Our results should contribute to the development of new strategies for the regulation of dorsal root ganglion excitability.

关键词： cell-cell communications CellChat dorsal root ganglion scRNA-Seq database

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Meiotic transcriptional reprogramming mediated by cell-cell communications in humans and mice revealed by scATACseq and scRNA-seq

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Zoological Research 2024年第3期45卷 601-616页

作者： Hai-Quan Wang Xiao-Long Wu Jing Zhang Si-Ting Wang Yong-Juan Sang Kang Li Chao-Fan Yang Fei Sun Chao-Jun Li State Key Laboratory of Reproductive Medicine and Offspring Health Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China medical school Nanjing UniversityNanjingJiangsu 210093China zhejiang university school of Medicine HangzhouZhejiang 310016China Department of Urology and Andrology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhouZhejiang 310000China Model Animal Research Center of medical school Nanjing UniversityNanjingNanjingJiangsu 210093China Liangzhu Laboratory Zhejiang UniversityHangzhouZhejiang 311121China

Meiosis is a highly complex process significantly influenced by transcriptional ***,studies on the mechanisms that govern transcriptomic changes during meiosis,especially in prophase I,are ***,we performed single-cell ATAC-seq of human testis tissues and observed reprogramming during the transition from zygotene to pachytene *** event,conserved in mice,involved the deactivation of genes associated with meiosis after reprogramming and the activation of those related to spermatogenesis before their functional ***,we identified 282 transcriptional regulators(TRs)that underwent activation or deactivation subsequent to this *** suggested that physical contact signals from Sertoli cells may regulate these TRs in spermatocytes,while secreted ENHO signals may alter metabolic patterns in these *** results further indicated that defective transcriptional reprogramming may be associated with non-obstructive azoospermia(NOA).This study revealed the importance of both physical contact and secreted signals between Sertoli cells and germ cells in meiotic progression.

关键词： Single-cell RNA-seq Single-cell ATAC-seq Spermatogenesis Meiosis Transcriptional reprogramming Cell-cell communication

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Brain Pathology in COVID-19:Clinical Manifestations and Potential Mechanisms

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Neuroscience Bulletin 2024年第3期40卷 383-400页

作者： Zhixing Xu Hui Wang Siya Jiang Jiao Teng Dongxu Zhou Zhong Chen Chengping Wen Zhenghao Xu First school of Clinical Medicine Zhejiang Chinese Medical UniversityHangzhou 310053China school of Pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Second school of Clinical Medicine Zhejiang Chinese Medical UniversityHangzhou 310053China Afliated Lin’an People’s Hospital of Hangzhou medical College First People’s Hospital of Hangzhou Lin’an DistrictLin’anHangzhou 311300China school of Life Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Key Laboratory of Neuropharmacology and Translational Medicine of zhejiang Province College of Pharmaceutical ScienceZhejiang Chinese Medical UniversityHangzhou 310053China Laboratory of Rheumatology and Institute of TCM Clinical Basic Medicine College of Basic Medical ScienceZhejiang Chinese Medical UniversityHangzhou 310053China

Neurological manifestations of coronavirus disease 2019(COVID-19)are less noticeable than the respiratory symptoms,but they may be associated with disability and mortality in *** though Omicron caused less severe disease than Delta,the incidence of neurological manifestations is *** than 30%of patients experienced“brain fog”,delirium,stroke,and cognitive impairment,and over half of these patients presented abnormal neuroimaging *** this review,we summarize current advances in the clinical findings of neurological manifestations in COVID-19 patients and compare them with those in patients with influenza *** also illustrate the structure and cellular invasion mechanisms of SARS-CoV-2 and describe the pathway for central SARS-CoV-2 *** addition,we discuss direct damage and other pathological conditions caused by SARS-CoV-2,such as an aberrant interferon response,cytokine storm,lymphopenia,and hypercoagulation,to provide treatment *** review may offer new insights into preventing or treating brain damage in COVID-19.

关键词： COVID-19 SARS-CoV-2 Brain Neurological pathology

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CRISPR/Cas9 system and its applications in nervous system diseases

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Genes & Diseases 2024年第2期11卷 675-686页

作者： Haibin Jiang Mengyan Tang Zidi Xu Yanan Wang Mopu Li Shuyin Zheng Jianghu Zhu Zhenlang Lin Min Zhang The Second school of Medicine Wenzhou Medical UniversityWenzhouZhejiang 325035China The First school of Medicine Wenzhou Medical UniversityWenzhouZhejiang 325035China Department of Pediatrics The Second School of MedicineThe Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325027China Key Laboratory of Perinatal Medicine of Wenzhou WenzhouZhejiang 325027China Key Laboratory of Structural Malformations in Children of zhejiang Province WenzhouZhejiang 325000China zhejiang Provincial Clinical Research Center for Pediatric Disease WenzhouZhejiang 325027China

The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system is an acquired immune system of many bacteria and archaea,comprising CRISPR loci,Cas genes,and its associated *** system can recognize exogenous DNA and utilize the Cas9 protein's nuclease activity to break DNA double-strand and to achieve base insertion or deletion by subsequent DNA *** recent years,multiple laboratory and clinical studies have revealed the therapeutic role of the CRISPR/Cas9 system in neurological *** article reviews the CRISPR/Cas9-mediated gene editing technology and its potential for clinical application against neurological diseases.

关键词： CRISPR/Cas9 Gene editing Mutation Neurological diseases Therapeutics

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