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Peri-centrosomal localization of small interfering RNAs in C. elegans

Science China life sciences 2025年

作者： Qile Jin Xuezhu Feng Minjie Hong Ke Wang Xiangyang Chen Jiewei Cheng Yan Kuang Xiaoyue Si Mingjing Xu Xinya Huang Shouhong Guang Chengming Zhu Department of Obstetrics and Gynecology The First Affiliated Hospital of USTC The USTC RNA Institute Hefei National Research Center for Physical Sciences at the Microscale School of Life Sciences Division of Life Sciences and Medicine Biomedical Sciences and Health Laboratory of Anhui Province University of Science and Technology of China School of Basic Medicine Anhui Medical University

The centrosome is the microtubule-organizing center and a crucial part of cell division. Centrosomal RNAs(cnRNAs) have been reported to enable precise spatiotemporal control of gene expression during cell division in many species. Whether and how cnRNAs exist in C. elegans are unclear. Here, using the nuclear RNAi Argonaute protein NRDE-3 as a reporter, we observed potential peri-centrosome localized small interfering(si)RNAs in C. elegans. NRDE-3 was previously shown to associate with pre-mRNAs and pre-rRNAs via a process involving the presence of complementary siRNAs. We generated a GFP-NRDE-3 knock-in transgene through CRISPR/Cas9 technology and observed that NRDE-3 formed peri-centrosomal foci neighboring the tubulin protein TBB-2, other centriole proteins and pericentriolar material(PCM)components in C. elegans embryos. The peri-centrosomal accumulation of NRDE-3 depends on RNA-dependent RNA polymerase(RdRP)-synthesized 22G siRNAs and the PAZ domain of NRDE-3, which is essential for siRNA binding. Mutation of eri-1, ergo-1, or drh-3 significantly increased the percentage of pericentrosome-enriched NRDE-3. At the metaphase of the cell cycle, NRDE-3 was enriched in both the peri-centrosomal region and the spindle. Moreover, the integrity of centriole proteins and pericentriolar material(PCM) components is also required for the peri-centrosomal accumulation of NRDE-3. Therefore, we concluded that siRNAs could accumulate in the pericentrosomal region in C. elegans and suggested that the peri-centrosomal region may also be a platform for RNAi-mediated gene regulation.

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Capsaicin(CAP) exerts a protective effect against ethanol-induced oxidative gastric mucosal injury by modulating the chemokine receptor 4 (CCR4)/Src/p47phox signaling pathway both in vitro and in vivo

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Chinese Journal of Natural Medicines 2025年第2期23卷 191-202页

作者： Zhiru Yang Haolin Guo Pengfei Zhang Kairui Liu Junli Ba Xue Bai Shiti Shama Bo Zhang Xiaoning Gao Jun Kang School of life sciences Tianjin University School of Traditional Chinese Medicine Beijing University of Chinese Medicine Tianjin Pharmaceutical and Cosmetic Evaluation and Inspection Center Institute for TCM-X MOE Key Laboratory of Bioinformatics Bioinformatics Division BNRist Department of Automation Tsinghua University Institute of biomedical Research Henan Academy of Sciences

Ethanol(EtOH) is a common trigger for gastric mucosal diseases, and mitigating oxidative stress is essential for attenuating gastric mucosal damage. Capsaicin(CAP) has been identified as a potential agent to counteract oxidative damage in the gastric mucosa; however, its precise mechanism remains unclear. This study demonstrates that CAP alleviates EtOH-induced gastric mucosal injuries through two primary pathways: by suppressing the chemokine receptor 4(CCR4)/Src/p47phox axis, thereby reducing oxidative stress, and by inhibiting the phosphorylation and nuclear translocation of nuclear factor-κB p65(NF-κB) p65, resulting in diminished inflammatory responses. These findings elucidate the mechanistic pathways of CAP and provide a theoretical foundation for its potential therapeutic application in the treatment of gastric mucosal injuries.

关键词： Capsaicin Chemokine signaling Gastric mucosal damage NF-κB p65

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Insights from an academic endeavor into central nervous system drug discovery

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Neural Regeneration Research 2025年第6期20卷 1717-1718页

作者： Lieve van Veggel An M.Voets Tim Vanmierlo Rudy Schreiber BIOMED biomedical Research Institute Faculty of Medicine and Life SciencesHasselt UniversityHasseltBelgium Department of Psychiatry and Neuropsychology Division of Translational NeuroscienceEuropean Graduate School of NeuroscienceSchool for Mental Health and NeuroscienceMaastricht UniversityMaastrichtThe Netherlands Section of Psychopharmacology Neuropsychology and PsychopharmacologyFaculty of Psychology and NeuroscienceMaastricht UniversityMaastrichtThe Netherlands university MS Center(UMSC) Hasselt-PeltBelgium

Historically,"big pharma"did most central nervous system drug discovery R&D ***,in modern times their"management reductionism"resulted in disappointing pipelines and pharma resided to(late)development,regulatory approval,and marketing(Thong,2015).This had significant consequences for financing and executing research,resulting in a larger role for funding by governments and patient-organizations and a shift of research to academia(Mazzucato,2013).

关键词： academic approval consequences

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The discovery of tiny RNAs that have crucial roles

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Science China life sciences 2025年

作者： Shouhong Guang Mofang Liu Department of Obstetrics and Gynecology The First Affiliated Hospital of USTC The USTC RNA Institute Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics Hefei National Research Center for Physical Sciences at the Microscale Center for Advanced Interdisciplinary Science and Biomedicine of IHM School of Life Sciences Division of Life Sciences and Medicine Biomedical Sciences and Health Laboratory of Anhui Province University of Science and Technology of China New Cornerstone Science Laboratory Key Laboratory of Epigenetic Regulation and Intervention Shanghai Key Laboratory of Molecular Andrology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences-University of Chinese Academy of Sciences

On October 7, the Nobel Assembly at Sweden’s Karolinska Institute announced the awarding of the 2024 Nobel Prize in Physiology or Medicine to American scientists Victor Ambros and Gary Ruvkun for their discovery of m...

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Blocking the PD-1 signal transduction by occupying the phosphorylated ITSM recognition site of SHP-2

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Science China(life sciences) 2025年第1期68卷 189-203页

作者： Wenjie Li Wenyi Mei Hewei Jiang Jie Wang Xiaoli Li Lina Quan Yanyan Diao Yanni Ma Sisi Fan Zhuwei Xie Mengdie Gong Huan Zhu Dewen Bi Feng Zhang Lei Ma Jian Zhang Yufeng Gao Aris Paschalidis Honghuang Lin Fangfang Liu Kangdong Liu Mingliang Ye Zhenjiang Zhao Yajun Duan Zhuo Chen Yufang Xu Weilie Xiao Shengce Tao Lili Zhu Honglin Li Shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science&TechnologyShanghai 200237China Shanghai Center for Systems Biomedicine Key Laboratory of Systems Biomedicine(Ministry of Education)Shanghai Jiao Tong UniversityShanghai 200240China Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of EducationYunnan Characteristic Plant Extraction LaboratoryYunnan Provincial Center for Research&Development of Natural ProductsState Key Laboratory for Conservation and Utilization of Bio-Resources in YunnanSchool of Pharmacy and School of Chemical Science and TechnologyYunnan UniversityKunming650500China CAS Key Laboratory of Separation sciences for Analytical Chemistry National Chromatographic R&A CenterDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Department of Cardiology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China Department of Infectious Diseases The First Affiliated Hospital of Anhui Medical UniversityHefei 230022China Department of Medicine University of Massachusetts Chan Medical SchoolWorcester MA 01655USA Department of Pathophysiology School of Basic Medical SciencesAcademy of Medical ScienceCollege of MedicineZhengzhou UniversityZhengzhou 450001China Innovation Center for AI and Drug Discovery East China Normal UniversityShanghai 200062China Lingang Laboratory Shanghai 200031China

Targeting the PD-1/PD-L1 axis with small-molecular inhibitors is a promising approach for ***,we identify a natural pentacyclic triterpenoid,Pygenic Acid A(PA),as a PD-1 signaling *** exerts anti-tumor activity in hPD-1 knock-in C57BL/6 mice and enhances effector functions of T cells to promote immune responses by disrupting the PD-1 signaling ***,we identify SHP-2 as the direct molecular target of PA for inhibiting the PD-1 signaling ***,mechanistic studies suggest that PA binds to a new druggable site in the phosphorylated PD-1 ITSM recognition site of SHP-2,inhibiting the recruitment of SHP-2 by *** together,our findings demonstrate that PA has a potential application in cancer immunotherapy and occupying the phosphorylated ITSM recognition site of SHP-2 may serve as an alternative strategy to develop PD-1 signaling *** addition,our success in target recognition provides a paradigm of target identification and confirmation for natural products.

关键词： pygenic acid A programmed death-1 immunoreceptor tyrosine-based switch motif SH2 domain-containing protein-tyrosine phosphatase-2 target identification site recognition

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Biodegradation of Crystal Violet by Agrobacterium radiobacter

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Journal of Environmental sciences 2011年第8期23卷 1384-1393页

作者： G.K.Parshetti S.G.Parshetti A.A.Telke D.C.Kalyani R.A.Doong S.P.Govindwar Department of biomedical Engineering and Environmental sciences National Tsinghua University division of Applied life sciences Gyeongsang National University division of Chemical Engineering Konkuk University Department of Biochemistry Shivaji University

Agrobacterium radiobacter MTCC 8161 completely decolorized the Crystal Violet with 8 hr （10 mg/L） at static anoxic conditions. The decreased decolorization capability by A. radiobacter was observed, when the Crystal Violet concentration was increased from 10 to 100 mg/L. Semi-synthetic medium containing 1% yeast extract and 0.1% NH4C1 has shown 100% decolorization of Crystal Violet within 5 hr. A complete degradation of Crystal Violet by A. radiobacter was observed up to 7 cycles of repeated addition （10 rag/L）. When the effect of increasing inoculum concentration on decolorization of Crystal Violet （100 mg/L） was studied, maximum decolorization was observed with 15% inoculum concentration. A significant increase in the activities of laccase （184%） and aminopyrine N-demethylase （300%） in cells obtained after decolorization indicated the involvement of these enzymes in decolorization process. The intermediates formed during the degradation of Crystal Violet were analyzed by gas chromatography and mass spectroscopy （GC/MS）. It was detected the presence of N,N,N＇,N＂-tetramethylpararosarfiline, IN, N-dimethylaminophenyl] [N-methylaminophenyl] benzophenone, N, N-dimethylaminobenzaldehyde, 4-methyl amino phenol and phenol. We proposed the hypothetical metabolic pathway of Crystal Violet biodegradation by A. radiobacter. Phytotoxicity and microbial toxicity study showed that Crystal Violet biodegradation metabolites were less toxic to bacteria （A. radiobacter, P. aurugenosa and A. vinelandii） contributing to soil fertility and for four kinds of plants （Sorghum bicolor, Vigna radiata, Lens culinaris and Triticum aestivum） which are most sensitive, fast growing and commonly used in Indian agriculture.

关键词： Agrobacterium radiobacter Crystal Violet biodegradation gas chromatography and mass spectroscopy toxicity study

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Interaction of the Arabidopsis UV-B-Specific Signaling Component UVR8 with Chromatin

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Molecular Plant 2008年第1期1卷 118-128页

作者： Catherine Cloix Gareth I. Jenkins Plant Science Group Division of Biochemistry and Molecular Biology Institute of Biomedical and Life Sciences Bower Building University of GlasgowGlasgow G12 BQQ UK

Arabidopsis UV RESISTANCE LOCUS8 （UVR8） is a UV-B-specific signaling component that regulates expression of a range of genes concerned with UV protection. Here, we investigate the interaction of UVR8 with chromatin. Using antibodies specific to UVR8 in chromatin immunoprecipitation （ChiP） assays with wild-type plants, we show that native UVR8 binds to chromatin in vivo. Similar experiments using an anti-GFP antibody with plants expressing a GFP-UVR8 fusion show that UVR8 associates with a relatively small region of chromatin containing the HY5 gene. UVR8 interacts with chromatin containing the promoter regions of other genes, but not with all the genes it regulates. UV-B is not required for the interaction of UVR8 with chromatin because association with several gene loci is observed in the absence of UV-B. Pulldown assays demonstrate that UVR8 associates with histones in vivo and competition experiments indicate that the interaction is preferentially with histone H2B. ChIP experiments using antibodies that recognize specific histone modifications indicate that the UV-B-stimulated transcription of some genes may be correlated with histone modification. In particular, the ELIP1 promoter showed a significant enrichment of diacetyl histone H3 （K9/K14） following UV-B exposure. These findings increase understanding of the interaction of the key UV-B-specific regulator UVR8 with chromatin.

关键词： .Wild-type Regulates Interacts Histones Arabidopsis UV Signaling Component UVR interaction of UVR native UVR anti-GFP UVR associates chromatin containing

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A novel homozygous frameshift variant in DNAH8 causes multiple morphological abnormalities of the sperm flagella in a consanguineous Pakistani family

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Asian Journal of Andrology 2023年第3期25卷 350-355页

作者： Sobia Dil Asad Khan Ahsanullah Unar Meng-Lei Yang Imtiaz Ali Aurang Zeb Huan Zhang Jian-Teng Zhou Muhammad Zubair Khalid Khan Shun Bai Qing-Hua Shi division of Reproduction and Genetics The First Affiliated Hospital of University of Science and Technology of ChinaSchool of Basic Medical SciencesDivision of Life Sciences and MedicineBiomedical Sciences and Health Laboratory of Anhui ProvinceUniversity of Science and Technology of ChinaHefei 230027China

Multiple morphological abnormalities of the sperm flagella(MMAF)is a severe form of asthenozoospermia categorized by immotile spermatozoa with abnormal flagella in ***-exome sequencing(WES)is used to detect pathogenic variants in patients with *** this study,a novel homozygous frameshift variant(c.6158_6159insT)in dynein axonemal heavy chain 8(DNAH8)from two infertile brothers with MMAF in a consanguineous Pakistani family was identified by *** transcription-polymerase chain reaction(RT-PCR)confirmed DNAH8 mRNA decay in these patients with the DNAH8 ***–eosin staining and transmission electron microscopy revealed highly divergent morphology and ultrastructure of sperm flagella in these ***,an immunofluorescence assay showed the absence of DNAH8 and a reduction in its associated protein DNAH17 in the patients'***,our study expands the phenotypic spectrum of patients with DNAH8-related MMAF worldwide.

关键词： DNAH8 gene mutation male infertility multiple morphological abnormalities of the sperm flagella

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Redox physiology in animal function:The struggle of living in an oxidant environment

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Current Zoology 2010年第6期56卷 687-702页

作者： David COSTANTINI division of Ecology and Evolutionary Biology Faculty of Biomedical and Life SciencesUniversity of Glasgow

A strong focus of ecological research for several decades has been to understand the factors underlying the variation in animal life-histories. In recent times, ecological studies have begun to show that oxidative stress may represent another important modulator of competitive trade-offs among fitness traits or of positively integrated patterns of traits. Therefore, incorporating mechanisms underlying oxidative physiology into evolutionary ecology has the potential to help understand variation in life-history strategies. In this review, I provide a general overview of oxidative stress physiology, and subsequently focus on topics that have been neglected in previous ecological reviews on oxidative stress. Specifically, I introduce and discuss the adaptations that animals have evolved to cope with oxidative stress; the environmental stressors that can generate changes in oxidative balance; the role of reactive species in transduction of environmental stimuli and cell signaling; and the range of hormetic responses to oxidative stress [Current Zoology 56 （6）： 687-702, 2010].

关键词： Antioxidants Free radicals life-history Oxidative stress Stress response Vertebrates

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Multifaceted roles of centrosomes in development,health,and disease

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Journal of Molecular Cell Biology 2021年第9期13卷 611-621页

作者： Feifei Qi Jun Zhou Institute of biomedical sciences College of Life SciencesShandong Normal UniversityJinan 250014China State Key Laboratory of Medicinal Chemical Biology College of Life SciencesNankai UniversityTianjin 300071China

The centrosome is a membrane-less organelle consisting of a pair of barrel-shaped centrioles and pericentriolar material and functions as the major microtubule-organizing center and signaling hub in animal *** past decades have witnessed the functional complexity and importance of centrosomes in various cellular processes such as cell shaping,division,and *** addition,centrosome abnormalities are linked to a wide range of human diseases and pathological states,such as cancer,reproductive disorder,brain disease,and ***,we discuss various functions of centrosomes in development and health,with an emphasis on their roles in germ cells,stem cells,and immune *** also discuss how centrosome dysfunctions are involved in diseases.A better understanding of the mechanisms regulating centrosome functions may lead the way to potential therapeutic targeting of this organelle in disease treatment.

关键词： centrosome germ cell stem cell immunity ciliopathy Introduction

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