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Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

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Science China Chemistry 2025年第1期68卷 308-316页

作者： Sili Wang Jiancheng Huang Yanan Du Wei Huang Yufeng Xue Xiaokun Xu Guannan Zhong Yuanyuan Shi Bin Hong Xiaoying Bian Wen Liu State key laboratory of Chemical Biology Shanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200032China State key laboratory of Microbial Technology Shandong UniversityQingdao 266237China national Health Commission(NHC)key laboratory of Biotechnology for Microbial Drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100050China

Cobalamin(Cbl)-dependent radical S-adenosyl-L-methionine(SAM)proteins constitute the largest collection of the radical SAM superfamily that has hundreds of thousands of individual *** of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding *** the biosynthetic pathway of chuangxinmycin(CXM),a unique indole alkaloid antibiotic with potent anti-infective activity,functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process,which,however,remained to be reconstituted *** here report the dissection of this enzymatic process,which requires the incorporation of Cxm8,a Cbl-dependent radical SAM protein,with Cxm9,a DUF5825family protein that shares no homology to any proteins of known ***8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-S-hetero ring system in a successive manner,achieving CXM and a recently identified,C3-dimethylated *** biochemical characterization,isotope labeling,structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the DUF5825 protein for C3-methylase *** is the first example that a Cbl-dependent protein acts with a partner to exhibit radical SAM activity.

关键词： cbl-dependent radical SAM protein biosynthesis chuangxinmycin stereoselective methylation

Transforming growth factor-beta 1 enhances discharge activity of cortical neurons

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Neural Regeneration Research 2025年第2期20卷 548-556页

作者： Zhihui Ren Tian Li Xueer Liu Zelin Zhang Xiaoxuan Chen Weiqiang Chen Kangsheng Li Jiangtao Sheng Department of Microbiology and immunology Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular ImmunopathologyShantou University Medical CollegeShantouGuangdong ProvinceChina Department of Neurosurgery First Affiliated Hospital of Shantou University Medical CollegeShantouGuangdong ProvinceChina

Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system *** neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types ***-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related ***,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain *** this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from *** found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 *** VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical *** findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological ***,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.

关键词： central nervous system cortical neurons ERK firing properties JNK Nav1.3 p38 transforming growth factor-beta 1 traumatic brain injury voltage-gated sodium currents

Improving regulatory T cell-based therapy:insights into post-translational modification regulation

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Journal of Genetics and Genomics 2025年第2期52卷 145-156页

作者： Aiting Wang Yanwen Wang Rui Liang Bin Li Fan Pan Center for Cancer immunology Research Institute of Biomedicine and BiotechnologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China Center for Immune-Related Diseases at Shanghai institute of immunology Department of Immunology and MicrobiologyShanghai Jiao Tong University School of MedicineShanghai 200025China

Regulatory T(Treg)cells are pivotal for maintaining immune homeostasis and play essential roles in various diseases,such as autoimmune diseases,graft-versus-host disease(GVHD),tumors,and infectious *** cells exert suppressive function via distinct mechanisms,including inhibitory cytokines,granzyme or perforin-mediated cytolysis,metabolic disruption,and suppression of dendritic *** Box P3(FOXP3),the characteristic transcription factor,is essential for Treg cell function and *** evidence has demonstrated that FOXP3 activity and Treg cell function are modulated by a variety of post-translational modifications(PTMs),including ubiquitination,acetylation,phosphorylation,methylation,glycosylation,poly(ADP-ribosyl)ation,and uncharacterized *** review describes Treg cell suppressive mechanisms and summarizes the current evidence on PTM regulation of FOXP3 and Treg cell *** the regulatory role of PTMs in Treg cell plasticity and function will be helpful in designing therapeutic strategies for autoimmune diseases,GVHD,tumors,and infectious diseases.

关键词： Treg cell FOXP3 Ubiquitination Acetylation Phosphorylation Methylation Glycosylation Post-translational modification

Advances in genotypic antimicrobialresistance testing: a comprehensive review

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Science China(Life Sciences) 2025年第1期68卷 130-143页

作者： Boheng Duan Xianjun Zeng Junping Peng Huan Kui College of Nanchang University Nanchang 330031China Department of Imaging The Second Affiliated Hospital of Nanchang UniversityNanchang 330038China NHC key laboratory of Systems Biology of Pathogens National Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 102629China key laboratory of Respiratory Disease Pathogenomics Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 102629China key laboratory of Pathogen Infection Prevention and Control(Ministry of Education) State Key Laboratory of Respiratory Health and MultimorbidityNational Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 102629China

Antimicrobial resistance(AMR)represents a substantial threat to global public health,complicating the treatment of common infections and leading to prolonged illness and escalated healthcare *** effectively combat AMR,timely and accurate detection is crucial for AMR surveillance and individual-based *** antibiotic resistance testing(AST)has long been considered the gold standard in clinical applications,serving as the foundation for clinical AMR diagnosis and optimized *** has significantly contributed to ensuring patients′health and the development of novel *** advancements in automated culture-based AST technologies,inherent limitations impede the widespread use of phenotypic AST in AMR *** AST technologies offer a promising alternative option,exhibiting advantages of rapidity,high sensitivity,and *** the continuous advancement and expanding applications of genotypic AST technologies,such as microfluidics,mass spectrometry,and high-resolution melting curve analysis,new vigor has been injected into the development and clinical implementation of genotypic AST *** this narrative review,we discuss the principles,applications,and advancements of emerging genotypic AST methods in clinical *** comprehensive review aims to highlight the significant scientific potential of emerging genotypic AST technologies in clinical AMR diagnosis,providing insights to enhance existing methods and explore novel approaches.

关键词： antimicrobial resistance(AMR) genotypic antibiotic resistance testing(AST) AST technologies review

Catatonia induced by antipsychotics in an adolescent male patient with systemic lupus erythematosus:A case report

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World Journal of Psychiatry 2025年第2期15卷 257-263页

作者： Wen-Qi Geng Xiao-Xi Yang Jin-Ya Cao Jing Wei Department of Psychological Medicine Chinese Academy of Medical Sciences and Peking Union Medical CollegePeking Union Medical College HospitalBeijing 100730China Department of Rheumatology and Clinical immunology Peking Union Medical College HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100730China national Clinical Research Center for Dermatologic and Immunologic Diseases(NCRC-DID) Ministry of Science&TechnologyBeijing 100730China State key laboratory of Complex Severe and Rare Diseases Peking Union Medical College HospitalBeijing 100730China key laboratory of Rheumatology and Clinical immunology Ministry of EducationBeijing 100730China

BACKGROUND Systemic lupus erythematosus(SLE)can affect multiple organs or *** involvement of the central nervous system can result in the manifestation of epilepsy,an acute confusional state,and other rare neuropsychiatric presentations,such as *** SUMMARY We present a case of an adolescent male patient with first-onset SLE who presented with neuropsychiatric symptoms including epilepsy and *** initial utilization of olanzapine to alleviate symptoms of agitation precipitated the emergence of catatonia,which was mitigated by discontinuing olanzapine and supplementing with *** this case,whether the catatonia was secondary to the utilization of antipsychotics or to an organic disease is a question that warrants differential *** Multidisciplinary collaborative management is the cornerstone for the successful management of severe cases of SLE.

关键词： Catatonia Systemic lupus erythematosus Referral consultation Antipsychotics Benzodiazepines Case report

Integrated Medicine Treatment of Rare Bone Marrow Tuberculosis in Systemic Lupus Erythematosus and Potentiating and Detoxifying Effects of Chinese Medicine:A Case Report

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Chinese Journal of Integrative Medicine 2025年第2期31卷 153-156页

作者： CHEN Wu HUANG Lin SHI Wei-man MA Ke WEN Cheng-ping DAI Qiao-ding School of Basic medical Science Zhejiang Chinese Medical UniversityHangzhou(310000)China The key laboratory of Chinese Medicine Rheumatology of Zhejiang Province Hangzhou(310000)China Department of Rheumatology and immunology The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)Hangzhou(310000)China

Systemic lupus erythematosus(SLE)is an autoimmune disease that affects multiple organ systems.(1,2)Patients with SLE who undergo long-term immunosuppressive and glucocorticoids therapy are at an elevated risk of devel... 详细信息

关键词： Systemic tuberculosis erythematosus

Liquid-liquid phase separation of TRAF6 promotes anti-TB immunity

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Science Bulletin 2025年第3期70卷 338-341页

作者： Yongjia Duan Yuanna Cheng Mingtong Ma Liru Li Shanshan Liu Liru Guan Jie Wang Hongjie Liu Xiaochen Huang Jianxia Chen Hua Yang Baoxue Ge Lin Wang Shanghai key laboratory of Tuberculosis Shanghai Pulmonary HospitalTongji University School of MedicineShanghai 200433China Department of Microbiology and immunology Tongji University School of MedicineShanghai 200433China Clinic and Research Center of Tuberculosis Shanghai Pulmonary HospitalTongji University School of MedicineShanghai 200433China key laboratory of Pathogen-Host Interaction Ministry of EducationDepartment of Microbiology and ImmunologyTongji University School of MedicineShanghai 200049China

Tumor necrosis factor receptor(TNFR)-associated factor 6(TRAF6)is a key regulator of the innate immune system,activating NF-κB and AP-1 signaling[1].TRAF6 participates in the immune regulation of many diseases,especially in chronic infections caused by pathogenic bacteria,such as Mycobacterium tuberculosis(Mtb)-induced tuberculosis(TB)[2].

关键词： immunity tuberculosis TRAF6

Single-cell sequencing reveals the features of adaptive immune responses in the liver of a mouse model of dengue fever

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Animal Models and Experimental Medicine 2025年第1期8卷 30-43页

作者： Yizhen Yuan Qian Chen Zhe Li Fangzhou Cai Dan Li Wei Wang national Center of Technology Innovation for Animal Model State Key Laboratory of Respiratory Health and MultimorbidityKey Laboratory of Pathogen Infection Prevention and Control(Peking Union Medical College)Ministry of EducationNHC Key Laboratory of Comparative MedicineInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences(CAMS)&Peking Union Medical College(PUMC)BeijingChina

Background:Dengue fever,an acute insect-borne infectious disease caused by the dengue virus(DENV),poses a great challenge to global public *** involve-ment is the most common complication of severe dengue and is closely related to the occurrence and development of ***,the features of adaptive immune responses associated with liver injury in severe dengue are not ***:We used single-cell sequencing to examine the liver tissues of mild or se-vere dengue mice model to analyze the changes in immune response of T cells in the liver after dengue virus infection,and the immune interaction between macrophages and T *** cytometry was used to detect T cells and macrophages in mouse liver and blood to verify the single-cell sequencing ***:Our result showed CTLs were significantly activated in the severe liver injury group but the immune function-related signal pathway was *** rea-son may be that the excessive immune response in the severe group at the late stage of DENV infection induces the polarization of macrophages into M2 type,and the macrophages then inhibit T cell immunity through the TGF-βsignaling *** ad-dition,the increased proportion of Treg cells suggested that Th17/Treg homeostasis was disrupted in the livers of severe liver injury ***:In this study,single-cell sequencing and flow cytometry revealed the characteristic changes of T cell immune response and the role of macrophages in the liver of severe dengue fever *** study provides a better understanding of the pathogenesis of liver injury in dengue fever patients.

关键词： adaptive immunity dengue fever model liver injury single-cell sequencing

Impulsive thrust strategy for orbital pursuit-evasion games based on impulse-like constraint

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Chinese Journal of Aeronautics 2025年第1期38卷 520-536页

作者： Hongbo WANG Yao ZHANG Hao LIU Kunpeng ZHANG School of Aerospace Engineering Beijing Institute of TechnologyBeijing 100081China national key laboratory of Space Intelligent Control Beijing Institute of Control EngineeringBeijing 100094China

This paper proposes a novel impulsive thrust strategy guided by optimal continuous thrust strategy to address two-player orbital pursuit-evasion game under impulsive thrust *** strategy seeks to enhance the interpretability of impulsive thrust strategy by integrating it within the framework of differential game in traditional continuous ***,this paper introduces an impulse-like constraint,with periodical changes in thrust amplitude,to characterize the impulsive thrust ***,the game with the impulse-like constraint is converted into the two-point boundary value problem,which is solved by the combined shooting and deep learning method proposed in this *** learning and numerical optimization are employed to obtain the guesses for unknown terminal adjoint variables and the game terminal ***,the accurate values are solved by the shooting method to yield the optimal continuous thrust strategy with the impulse-like ***,the shooting method is iteratively employed at each impulse decision moment to derive the impulsive thrust strategy guided by the optimal continuous thrust *** examples demonstrate the convergence of the combined shooting and deep learning method,even if the strongly nonlinear impulse-like constraint is *** effect of the impulsive thrust strategy guided by the optimal continuous thrust strategy is also discussed.

关键词： Orbital pursuit-evasion game Differential game Impulsive thrust Deep learning Shooting method