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Cdc2-like kinases:structure,biological function,and therapeutic targets for diseases

Signal Transduction and Targeted Therapy 2023年第5期8卷 2088-2112页

作者： Mengqiu Song luping pang Mengmeng Zhang Yingzi Qu Kyle Vaughn Laster Zigang Dong Department of Pathophysiology School of Basic Medical SciencesCollege of MedicineZhengzhou UniversityZhengzhouHenan450001China China-US(Henan)Hormel Cancer Institute No.127Dongming RoadJinshui DistrictZhengzhouHenan450008China State Key Laboratory of Esophageal Cancer Prevention and Treatment Zhengzhou UniversityZhengzhouHenanChina Academy of Medical Sciences College of MedicineZhengzhou UniversityZhengzhouHenan450001China Research Center of Basic Medicine Academy of Medical SciencesCollege of MedicineZhengzhou UniversityZhengzhouHenan450001China

The CLKs(Cdc2-like kinases)belong to the dual-specificity protein kinase family and play crucial roles in regulating transcript splicing via the phosphorylation of SR proteins(SRSF1–12),catalyzing spliceosome molecular machinery,and modulating the activities or expression of non-splicing proteins.The dysregulation of these processes is linked with various diseases,including neurodegenerative diseases,Duchenne muscular dystrophy,inflammatory diseases,viral replication,and cancer.Thus,CLKs have been considered as potential therapeutic targets,and significant efforts have been exerted to discover potent CLKs inhibitors.In particular,clinical trials aiming to assess the activities of the small molecules Lorecivivint on knee Osteoarthritis patients,and Cirtuvivint and Silmitasertib in different advanced tumors have been investigated for therapeutic usage.In this review,we comprehensively documented the structure and biological functions of CLKs in various human diseases and summarized the significance of related inhibitors in therapeutics.Our discussion highlights the most recent CLKs research,paving the way for the clinical treatment of various human diseases.

关键词： diseases therapeutic specificity

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Roles of endophytic fungi in medicinal plant abiotic stress response and TCM quality development

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Chinese Herbal Medicines 2024年第2期16卷 204-213页

作者： Jiahao Zhang Jiemiao Lu Yichun Zhu Xiaoxia Shen Bo Zhu luping Qin School of Pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Songyang Institute of Zhejiang Chinese Medical University Songyang 323400China

Medicinal plants,as medicinal materials and important drug components,have been used in traditional and folk medicine for ages.However,being sessile organisms,they are seriously affected by extreme environmental conditions and abiotic stresses such as salt,heavy metal,temperature,and water stresses.Medicinal plants usually produce specific secondary metabolites to survive such stresses,and these metabolites can often be used for treating human diseases.Recently,medicinal plants have been found to partner with endophytic fungi to form a long-term,stable,and win-win symbiotic relationship.Endophytic fungi can promote secondary metabolite accumulation in medicinal plants.The close relationship can improve host plant resistance to the abiotic stresses of soil salinity,drought,and extreme temperatures.Their symbiosis also sheds light on plant growth and active compound production.Here,we show that endophytic fungi can improve the host medicinal plant resistance to abiotic stress by regulating active compounds,reducing oxidative stress,and regulating the cell ion balance.We also identify the deficiencies and burning issues of available studies and present promising research topics for the future.This review provides guidance for endophytic fungi research to improve the ability of medicinal plants to resist abiotic stress.It also suggests ideas and methods for active compound accumulation in medicinal plants and medicinal material development during the response to abiotic stress.

关键词： abiotic stress active compounds endophytic fungus medicinal material development medicinal plant

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Detailed resume of RNA m^(6)A demethylases

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2193-2205页

作者： Dandan Shen Bo Wang Ya Gao Lijuan Zhao Yaping Bi Jinge Zhang Ning Wang Huiqin Kang Jingru pang Ying Liu luping pang Zhe-Sheng Chen Yi-Chao Zheng Hong-Min Liu Key Laboratory of Advanced Drug Preparation Technologies Ministry of Education of ChinaCollaborative Innovation Center of New Drug Research and Safety EvaluationZhengzhou UniversityZhengzhou 450052China Key Laboratory of Henan Province for Drug Quality and Evaluation Institute of Drug Discovery and DevelopmentSchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450052China State Key Laboratory of Esophageal Cancer Prevention&Treatment Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052China Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNY 11439USA The School of Chinese Medicine The University of Hong KongPokfulamHong KongChina

N6-Methyladenosine(m^(6)A) is the most abundant internal modification in eukaryotic mRNA,playing critical role in various bioprocesses. Like other epigenetic modifications, m^(6)A modification can be catalyzed by the methyltransferase complex and erased dynamically to maintain cells homeostasis. Up to now, only two m^(6)A demethylases have been reported, fat mass and obesity-associated protein(FTO)and alkylation protein AlkB homolog 5(ALKBH5), involving in a wide range of mRNA biological progress, including mRNA shearing, export, metabolism and stability. Furthermore, they participate in many significantly biological signaling pathway, and contribute to the progress and development of cancer along with other diseases. In this review, we focus on the studies about structure, inhibitors development and biological function of FTO and ALKBH5.

关键词： FTO ALKBH5 RNA demethylation Diseases Inhibitors Screening

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Salinity Acclimation Induces Reduced Energy Metabolism,Osmotic Pressure Regulation and Transcriptional Reprogramming in Hypotrichida Ciliate Gastrostyla setifera

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Journal of Ocean University of China 2024年第2期23卷 539-549页

作者： JI Xin BI luping ZOU Songbao LI Wenlu JI Daode ZHANG Qianqian School of Ocean Yantai UniversityYantai 264005China Key Laboratory of Coastal Environmental Processes and Ecological Remediation Yantai Institute of Coastal Zone ResearchChinese Academy of SciencesYantai 264003China Zhejiang Institute of Freshwater Fisheries Huzhou 313001China Muping Coastal Environment Research Station Yantai Institute of Coastal Zone ResearchChinese Academy of SciencesYantai 264117China

Coastal and estuarine protists are frequently exposed to salinity undulation.While the tolerance and stress responses of microalgae to salinity have been extensively studied,there have been scarce studies on the physiological response of heterotrophic protists to salinity stressing.In this study,we investigated the physiological response of the heterotrophic ciliate Gastrostyla setifera to a salinity of 3,via a transcriptomic approach.The first transcriptome of genus Gastrostyla was obtained utilizing a group of manually isolated ciliate individuals(cells)and RNA-seq technique.The completeness of the transcriptome was verified.Differentially expressed gene(DEG)analysis was performed among the transcriptomes of G.setifera acclimated in saline water(salinity 3)and those cultured in fresh water.The results demonstrated a significant alternation in gene transcription,in which the ciliate exhibits a transcripttomic acclimation in responding salinity stressing.The up-regulated DEGs were enriched in the pathways of cytoskeleton proteins,membrane trafficking,protein kinases and protein phosphatases.These may represent enhanced functions of ion transport,stress response and cell protections.Pathways involved in energy metabolism and biosynthesis were markedly down-regulated,reflecting decreased cell activity.Particularly,we detected significantly down-regulated genes involved in several pathways of amino acid catabolism,which may lead to accumulation of amino acids in the ciliate cell.Amino acid could act as compatible solutes in the cytoplasm to maintain the osmotic balance in saline water.Overall,this work is an initial exploration to the molecular basis of the heterotrophic protist responding to salinity stressing.The result sheds light on the mechanisms of enhancement of cell protection,reduction of cell activity,and osmotic pressure regulation in ciliates acclimated to salinity.

关键词： salinity stress heterotrophic protist ciliate Gastrostyla setifera transcriptome differentially expressed gene

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LSM14B coordinates protein component expression in the P-body and controls oocyte maturation

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Journal of Genetics and Genomics 2024年第1期51卷 48-60页

作者： Huiru Zhang Tao Zhang Xiang Wan Chang Chen Shu Wang Dongdong Qin Lufan Li luping Yu Xin Wu State Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical UniversityNanjingJiangsu 210029China Center for Reproductive Medicine and Obstetrics and Gynecology Nanjing Drum Tower HospitalNanjing University Medical SchoolNanjingJiangsu 210029China

The generation of mature and healthy oocytes is the most critical event in the entire female reproductive process,and the mechanisms regulating this process remain to be studied.Here,we demonstrate that Smith-like(LSM)family member 14B(LSM14B)regulates oocyte maturation,and the loss of LSM14B in mouse ovaries leads to abnormal oocyte MII arrest and female infertility.Next,we find the aberrant transcriptional activation,indicated by abnormal non-surrounded nucleolus and surrounded nucleolus oocyte proportions,and abnormal chromosome assembly and segregation in Lsm14b-deficient mouse oocytes.The global transcriptome analysis suggests that many transcripts involved in cytoplasmic processing body(P-body)function are altered in Lsm14b-deficient mouse oocytes.Deletion of Lsm14b results in the expression and/or localization changes of P-body components(such as LSM14A,DCP1A,and 4E-T).Notably,DDX6,a key component of the P-body,is downregulated and accumulates in the nuclei in Lsm14b-deficient mouse oocytes.Taken together,our data suggest that LSM14B links mouse oocyte maturation to female fertility through the regulation of the P-body.

关键词： LSM14B P-body DDX6 MIl arrest Chromatin configuration

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Microbial interactions within Chinese traditional medicinal plants

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Chinese Herbal Medicines 2024年第2期16卷 169-171页

作者： Juan Chen luping Qin Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine Ministry of EducationInstitute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China School of Pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China

Plants harbor diverse microbes(including bacteria,fungi,archaea,protists,and viruses)both inside and outside their tissues,so called the plant-associated microbiome.Decades of research have demonstrated the importance of plant microbiome in promoting the productivity and health of the plant in natural environment because of their essential functions in improving plant nutrition and plant resistance to biotic and abiotic stresses(Trivedi,Leach,Tringe,Sa,&Singh,2020).Thus,a plant can be regarded as a holobiont comprising the host plant and the associated microbiota(Hassani,Durán,&Hacquard,2018).Within the plant microbiota,mutualistic fungal and bacterial symbionts(e.***.mycorrhizal fungi and Rhizobia)are striking examples of microorganisms playing crucial roles in nutrient acquisition(Martin&van der Heijden,2024)and non-symbitic plant growth-promoting rhizobacteria or fungi(PGPR or PGPF)also have drawn interest due to their ability to improve soil properties and confer stress tolerance in plants(Upadhyay et al.,2023).

关键词： mutual striking outside

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GRK2 inhibits Flt-1^(+)macrophage infiltration and its proangiogenic properties in rheumatoid arthritis

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Acta Pharmaceutica Sinica B 2024年第1期14卷 241-255页

作者： Xuezhi Yang Yingjie Zhao Qi Wei Xuemin Zhu luping Wang Wankang Zhang Xiaoyi Liu Jiajie Kuai Fengling Wang Wei Wei Institute of Clinical Pharmacology Anhui Medical UniversityKey Laboratory of Anti-Inflammatory and Immune MedicineAnhui Collaborative Innovation Center of Anti-Inflammatory and Immune MedicineMinistry of EducationHefei 230032China Department of Clinical Pharmacology the Second Affiliated Hospital of Anhui Medical UniversityHefei 230601China

Rheumatoid arthritis(RA)is an autoimmune disease with a complex etiology.Monocyte-derived macrophages(MDMs)infiltration are associated with RA severity.We have reported the deletion of G-protein-coupled receptor kinase 2(GRK2)reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling.However,as more GRK2-interacting proteins were discovered,the GRK2 interactome mechanisms in RA have been understudied.Thus,in the collagen-induced arthritis mouse model,we performed genetic GRK2 deletion using GRK2^(f/f)Lyz2-Cre^(+/−)mice.Synovial inflammation and M1 polarization were improved in GRK2^(f/f)Lyz2-Cre^(+/−)mice.Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptorγ(PPARγ)as a new GRK2-interacting protein.We further confirmed that fms-related tyrosine kinase 1(Flt-1),which promoted macrophage migration to induce angiogenesis,was inhibited by GRK2-PPARγsignaling.Mechanistically,excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγligand-binding domain and enhanced Flt-1 transcription.Furthermore,the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology,Flt-1^(+)macrophages induced-synovial inflammation,and angiogenesis.Altogether,we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling.Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration,affording a distinct way to control joint inflammation and angiogenesis of RA.

关键词： GRK2 Monocyte-derived macrophages Rheumatoid arthritis PPARg Flt-1

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唯物史观的历史叙事:基于《资本论》的考察

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厦门大学学报（哲学社会科学版） 2024年第1期74卷 1-11页

作者：周露平上海交通大学马克思主义学院上海212003

传统的历史叙事以抽象的精神反思或批判历史进程,不能真正呈现历史进程背后的物质性的生产方式与矛盾化的社会关系,基本上从属于唯心史观的考察方式。马克思则从唯物史观的新世界观视角,提出了历史进程的社会动力机制。以此为基础,《资... 详细信息

传统的历史叙事以抽象的精神反思或批判历史进程,不能真正呈现历史进程背后的物质性的生产方式与矛盾化的社会关系,基本上从属于唯心史观的考察方式。马克思则从唯物史观的新世界观视角,提出了历史进程的社会动力机制。以此为基础,《资本论》研究全面揭示出现代资本发展的历史内容与超越方式,展示出历史叙事中超越资本逻辑、实现无产阶级革命的人类解放的历史路标。《资本论》通过政治经济学批判,科学剖析资本主义社会的历史情境、发展机制与历史趋势等,形成了以无产阶级解放为革命形式的主体语境。

关键词：《资本论》唯物史观历史叙事

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人文经济学的思想叙事与中国践行

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南京社会科学 2024年第5期 1-9,19页

作者：周露平上海交通大学马克思主义学院经济哲学研究院上海200240

人文经济学激活了我们对中国经济的未来想象:民生进步的经济财富与社会文明的人文精神可以深度融合。古典经济学(包括哲学)有一定的人文精神内容,但这种人文内容是服务于现代资本增殖的合理化论证的,体现为财富增长满足私人利益的资本... 详细信息

人文经济学激活了我们对中国经济的未来想象:民生进步的经济财富与社会文明的人文精神可以深度融合。古典经济学(包括哲学)有一定的人文精神内容,但这种人文内容是服务于现代资本增殖的合理化论证的,体现为财富增长满足私人利益的资本生产积累。与之相对,人文经济学是中国特色社会主义市场经济的科学理论与实践指导,满足全体人民的利益诉求;同时,它为中国特色社会主义市场经济提供独特的人文价值,提升中国式现代化的人文内涵,推动以人类解放为中心的人文归宿。深度挖掘人文经济学与中国式现代化之间的内容联系,有助于人文经济学以人文形式打开经济世界的理解视域,为中国式现代化提供科学的理论支撑与实践指引,谱写具有中国人文精神密码的新型经济学科学理论。

关键词：人文经济学思想叙事中国践行资本批判经济哲学

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从“洛克问题”到“蒲鲁东悖论”:马克思对所有权问题的求解

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哲学动态 2024年第2期 11-21页

作者：周露平上海交通大学马克思主义学院

就学术思想史而言,假如没有提升到所有权批判的理论高度,那么现代性批判及其超越就难以实现。这容易引发两种理论后果:要么是认同维度上的“洛克问题”即所有权与占有权的统一问题,要么是否定维度上的“蒲鲁东悖论”即否定所有权、实现... 详细信息

就学术思想史而言,假如没有提升到所有权批判的理论高度,那么现代性批判及其超越就难以实现。这容易引发两种理论后果:要么是认同维度上的“洛克问题”即所有权与占有权的统一问题,要么是否定维度上的“蒲鲁东悖论”即否定所有权、实现占有权的扩张议题。马克思思想贯通着对现代所有权的批判,决定着唯物史观如何科学化为《资本论》的批判主题:一方面是从唯物史观视角澄清所有权在场的可能性,为《资本论》批判提供新哲学与新世界观;另一方面从《资本论》的维度提出如何超越资本所有权制度,完成超越现代所有权的论证。思想史中的“洛克问题”与“蒲鲁东悖论”在马克思这里得以终结,因为马克思不仅对所有权或占有权展开外部批判,而且聚焦对现代资本的内部批判,从根本上破解了所有权问题。

关键词：所有权占有权洛克问题蒲鲁东悖论资本批判

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