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Inonotus obliquus polysaccharides prevent UVB-induced skin photodamage by modulating Sirt3-activated Foxo3a/PINK1-Parkin pathway: an in vitro and in vivo study

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Food Science and Human Wellness 2024年

作者： Pei Lin Yin-ying Lu Hong-yu Shi Zhen-dong Chen Jun Lin school of life sciences and health engineering Jiangnan University

Inonotus obliquus， an edible and medicinal fungus， has proven to be beneficial for relieving body aging. Previous research has shown that Inonotus obliquus polysaccharide (IOP) can effectively reduce oxidative stress and alleviate photoaging in UVB-treated HaCaT cells. However， the underlying mechanism is still unclear. This study aimed to investigate the mechanism through which IOP mitigates skin photodamage by modulating mitochondrial autophagy through both in vivo and in vitro experiments. The results indicated that IOP alleviated the thickening of the stratum corneum and inflammatory infiltration caused by UVB radiation. Moreover， IOP effectively inhibited the mRNA expression of MMP1 and MMP3 to prevent collagen breakdown and decreased the expression of aging-related proteins (P53 and P21) and inflammatory factors (TNF-α and IFN-γ) in UVB-induced mice. Both in vitro and in vivo studies demonstrated that IOP increased Sirt3 expression， activated the Foxo3a/PINK1-Parkin pathway and enhanced mitochondrial autophagy to reduce photodamage. Additionally， IOP could regulate the gut microbes in photodamaged mice and increase the relative abundance of Clostridium＿XlVa， Desulfovibrio， and Barnesiella， which are important for protecting the intestinal barrier and alleviating intestinal dysfunction. These results provide a theoretical foundation for the use of IOP as a natural component to reduce skin photodamage.

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Transcriptional regulation in the development and dysfunction of neocortical projection neurons

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Neural Regeneration Research 2024年第2期19卷 246-254页

作者： Ningxin Wang Rong Wan Ke Tang Precise Genome engineering Center School of Life SciencesGuangzhou UniversityGuangzhouGuangdong ProvinceChina

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.

关键词： autism spectrum disorders cognition differentiation excitatory circuits intellectual disability neocortex neurodevelopmental disorders projection neuron specification transcriptional regulation

Physiological and pathological functions of circular RNAs in the nervous system

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Neural Regeneration Research 2024年第2期19卷 342-349页

作者： Min Zhou Shi Li Chuan Huang school of life sciences Chongqing UniversityChongqingChina

Circular RNAs(circRNAs)are a class of covalently closed single-stranded RNAs that are expressed during the development of specific cells and tissues.CircRNAs play crucial roles in physiological and pathological processes by sponging microRNAs,modulating gene transcription,controlling the activity of certain RNA-binding proteins,and producing functional peptides.A key focus of research at present is the functionality of circRNAs in the nervous system and several advances have emerged over the last 2 years.However,the precise role of circRNAs in the nervous system has yet to be comprehensively reviewed.In this review,we first summarize the recently described roles of circRNAs in brain development,maturity,and aging.Then,we focus on the involvement of circRNAs in various diseases of the central nervous system,such as brain cancer,chronic neurodegenerative diseases,acute injuries of the nervous system,and neuropathic pain.A better understanding of the functionality of circRNAs will help us to develop potential diagnostic,prognostic,and therapeutic strategies to treat diseases of the nervous system.

关键词： Alzheimer’s disease amyotrophic lateral sclerosis brain development circRNAs neuropathic pain Parkinson’s disease

Immune checkpoint inhibitors:breakthroughs in cancer treatment

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Cancer Biology & Medicine 2024年第6期21卷 451-472页

作者： Xueqing Kong Jinyi Zhang Shuwei Chen Xianyang Wang Qing Xi Han Shen Rongxin Zhang Laboratory of Immunology and Inflammation School of Life Sciences and Biopharmaceutics Guangdong Pharmaceutical University Department of Biology School of Life Sciences and Biopharmaceutics Guangdong Pharmaceutical University

Over the past two decades, immunotherapies have increasingly been considered as first-line treatments for most cancers. One such treatment is immune checkpoint blockade(ICB), which has demonstrated promising results against various solid tumors in clinical trials. Monoclonal antibodies(mAbs) are currently available as immune checkpoint inhibitors(ICIs). These ICIs target specific immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4(CTLA-4) and programmed cell death protein 1(PD-1). Clinical trial results strongly support the feasibility of this immunotherapeutic approach. However, a substantial proportion of patients with cancer develop resistance or tolerance to treatment, owing to tumor immune evasion mechanisms that counteract the host immune response.Consequently, substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1, anti-programmed cell death ligand 1(anti-PD-L1), and anti-CTLA-4 treatments. Recently, several immune checkpoint molecular targets have been identified, such as T cell immunoreceptor with Ig and ITIM domains(TIGIT), mucin domain containing-3(TIM-3), lymphocyte activation gene-3(LAG-3), V-domain immunoglobulin suppressor of T cell activation(VISTA), B and T lymphocyte attenuator(BTLA), and signal-regulatory protein α(SIRPα). Functional m Abs targeting these molecules are under development. CTLA-4, PD-1/PD-L1, and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of research. This review discusses these structures, as well as clinical progress in m Abs targeting these immune checkpoint molecules and their potential applications.

关键词： CTLA-4 ICIs Immunotherapy PD-1 cancer

HUNK inhibits cargo uptake and lysosomal traffic in the caveolar pathway via the AGAP3/ARF6

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Science Bulletin 2024年第2期69卷 173-178页

作者： Siyuan Jiang Xiaoqi Han Tihui Liu Ying He Zidong Zhao Tongfeng Liu Shuwen Cheng Jihang Zhang Liqiang Duan Yajuan Liu Tianyou Cheng Yong Liu Qinong Ye Shan Gao Zhongda Hospital Medical SchoolAdvanced Institute for Life and HealthSoutheast UniversityNanjing 20096China Medical school of Guizhou University Guiyang 550025China Shanxi Academy of Advanced Research and Innovation Taiyuan 030032China Zhongda Hospital School of Life Sciences and TechnologyAdvanced Institute for Life and HealthSoutheast UniversityNanjing 210096China Nanjing University Medical school Nanjing 210046China Hubei Key Laboratory of Cell Homeostasis College of Life SciencesTaiKang Center for Life and Medical SciencesWuhan UniversityWuhan 430072China Department of Medical Molecular Biology Beijing Institute of BiotechnologyCollaborative Innovation Center for Cancer MedicineBeijing 100850China

Endocytosis is a crucial cellular process that takes up cargos by enclosing them in membrane-bound vesicles,and transports cargos to different parts of the cell,such as the lysosomes[1].Endocytosis is classified into several mechanistically and morphologically pathways,including clathrin-mediated endocytosis(CME)and caveolae-mediated endocytosis(CavME)[1,2].

关键词： endocytosis cargo uptake

PRRSV degrades MDA5 via dual autophagy receptors P62 and CCT2 to evade antiviral innate immunity

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Virologica Sinica 2024年第2期39卷 264-276页

作者： Ruiqi Sun Yanyu Guo Lilin Zhang Huixia Zhang Boxuan Yin Xiaoyang Li Changyan Li Liu Yang Lei Zhang Zexing Li Jinhai Huang school of life sciences Tianjin UniversityTianjin300072China

Porcine reproductive and respiratory syndrome virus(PRRSV)is a major economically devastating pathogen that has evolved various strategies to evade innate immunity.Downregulation of antiviral interferon largely promotes PRRSV immunoevasion by utilizing cytoplasmic melanoma differentiation-associated gene 5(MDA5),a receptor that senses viral RNA.In this study,the downregulated transcription and expression levels of porcine MDA5 in PRRSV infection were observed,and the detailed mechanisms were explored.We found that the interaction between P62 and MDA5 is enhanced due to two factors:the phosphorylation modification of the autophagic receptor P62 by the upregulated kinase CK2αand the K63 ubiquitination of porcine MDA5 catalyzed by the E3 ubiquitinase TRIM21 in PRRSV-infected cells.As a result of these modifications,the classic P62-mediated autophagy is triggered.Additionally,porcine MDA5 interacts with the chaperonin containing TCP1 subunit 2(CCT2),which is enhanced by PRRSV nsp3.This interaction promotes the aggregate formation and autophagic clearance of MDA5-CCT2-nsp3 independently of ubiquitination.In summary,enhanced MDA5 degradation occurs in PRRSV infection via two autophagic pathways:the binding of MDA5 with the autophagy receptor P62 and the aggrephagy receptor CCT2,leading to intense innate immune suppression.The research reveals a novel mechanism of immune evasion in PRRSV infection and provides fundamental insights for the development of new vaccines or therapeutic strategies.

关键词： Porcine reproductive and respiratory syndrome virus(PRRSV) nsp3 Autophagy MDA5

The influence of wing morphology upon intraspecific divergence in birds: A global study of subspecies richness

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Avian Research 2024年第2期15卷 196-201页

作者： Haiying Fan Weibin Guo Buge Lin Zhiqing Hu Changcao Wang Shaobin Li school of life sciences Jinggangshan UniversityJi’An343009China State Key Laboratory of Biocatalysis and Enzyme engineering School of Life SciencesHubei UniversityWuhan430062China College of life Science Yangtze UniversityJingzhou434023China

Since the time of Darwin,subspecies have been recognized as an initial stage in the evolution of species.However,the impact of dispersal on subspecies richness in birds globally has received little attention,despite dispersal being a key factor in determining the rate of evolution and playing a significant role in evolutionary divergence.Therefore,it is important to conduct a comprehensive study to address this issue.In this study,we aimed to assess the association between subspecies richness(measured by the number of subspecies)and dispersal ability(measured by the hand-wing index)on a global scale,using a dataset of over 7000 bird species.Our results revealed a negative correlation between dispersal ability and the number of subspecies,without any quadratic correlation.The wing is a crucial phenotypic trait for birds,and the concept of subspecies is important in speciation theory and conservation biology.Therefore,our findings not only enhance our understanding of the association between avian morphological traits and evolutionary divergence but also have implications for the conservation of avian species diversity.

关键词： Dispersal Gene flow Hand-wing index Subspecies richness

Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

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National Science Review 2024年第2期11卷 124-134页

作者： Jingyu Li Weibo Hou Qi Zhao Wei Han Hongdi Cui Songling Xiao Ling Zhu Jiadan Qu Xiaoyu Liu Weitao Cong Jingling Shen Yuzheng Zhao Shaorong Gao Guoning Huang Qingran Kong Chongqing Key Laboratory of Human Embryo engineering Center for Reproductive Medicine Chongqing Health Center for Women and ChildrenWomen and Children's Hospital of Chongqing Medical University Oujiang Laboratory Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life Sciences Wenzhou Medical University Frontier Science Center for Stem Cell Research School of Life Sciences and Technology Tongji University school of Pharmaceutical Science Wenzhou Medical University Institute of life sciences College of Life and Environmental Sciences Wenzhou University Optogenetics&Synthetic Biology Interdisciplinary Research Center State Key Laboratory of Bioreactor Engineering Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology

Lactate is present at a high level in the microenvironment of mammalian preimplantation embryos in vivo and in vitro. However, its role in preimplantation development is unclear. Here, we report that lactate is highly enriched in the nuclei of early embryos when major zygotic genome activation(ZGA) occurs in humans and mice. The inhibition of its production and uptake results in developmental arrest at the 2-cell stage, major ZGA failure, and loss of lactate-derived H3K18lac, which could be rescued by the addition of Lac-Co A and recapitulated by overexpression of H3K18R mutation. By profiling the landscape of H3K18lac during mouse preimplantation development, we show that H3K18lac is enriched on the promoter regions of most major ZGA genes and correlates with their expressions. In humans, H3K18lac is also enriched in ZGA markers and temporally concomitant with their expressions. Taken together, we profile the landscapes of H3K18lac in mouse and human preimplantation embryos, and demonstrate the important role for H3K18lac in major ZGA, showing that a conserved metabolic mechanism underlies preimplantation development of mammalian embryos.

关键词： mammalian preimplantation development lactate epigenetic remodeling histone lactylation zygotic genome activation

Tributyltin causes generational neurodevelopmental toxicity and the protective effect of folic acid in zebrafish

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Journal of Environmental sciences 2024年第3期137卷 615-625页

作者： Haoxing Cai Naying Zheng Chen Tang Yuxuan Zhang Zhenghong Zuo Chengyong He State Key Laboratory of Cellular Stress Biology School of Life SciencesFaculty of Medicine and Life SciencesXiang’an Hospital of Xiamen UniversityXiamen UniversityXiamen 361005China

Tributyltin(TBT),a common organotin environmental pollutant,may pose a threat to human development during critical early-life periods.We aimed to assess the neurodevelopmental intergenerational toxicity of early-life exposure to TBT and the protective effect of DNA methyl donor folic acid(FA).Specifically,after early-life exposure(1–21 days postfertilization,dpf)to TBT(0,1,10 and 100 ng/L),zebrafish(Danio rerio)were cultured in clean medium until sexual maturity.The exposed females were mated with unexposed males to produce embryos(F1).The F1 generation were cultured(4–120 hours post-fertilization,hpf)with and without 1 mmol/L FA.The neurotoxic effects of early-life TBT exposure for zebrafish and their offspring(F1)were significantly enhanced anxiety and reduced aggression,decreased gene expression of DNA methyltransferase in the brain and increased serotonin levels in the body.Moreover,the intergenerational neurodevelopmental toxicity,as manifested in the F1 generation,was attenuated by FA supplementation.In summary,early-life TBT exposure led to intergenerational neurodevelopmental deficits in zebrafish,and DNA methyl donors had a protective effect on F1 neurodevelopment,which can inform the prevention and treatment of intergenerational neurotoxicity due to organotin pollutants.

关键词： Tributyltin Neurodevelopment Intergeneration DNA methylation Folic acid Zebrafish