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Thirteen years to get from b to a:one of the neglected isoforms of IL-37 enters the stage

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Cellular & Molecular Immunology 2024年第2期21卷 201-202页

作者： Steven X.Cho Ina Rudloff Andrew M.Ellisdon Claudia A.Nold-Petry Marcel F.Nold Ritchie Centre Hudson Institute of Medical ResearchMelbourneVICAustralia Department of Pediatrics Monash UniversityMelbourneVICAustralia Cancer program Biomedicine Discovery InstituteMonash UniversityMelbourneVICAustralia Monash Newborn Monash Children’s HospitalMelbourneVICAustralia

Interleukin(IL)-37 is one of the few anti-inflammatory members of the predominantly pro-inflammatory IL-1 cytokine ***-37 possesses alarmin-like properties[1]and exerts its activities via intracellular[2]as well as cell surface receptor-dependent mechanisms,and the latter involves IL-1R8 and IL-18Rα[3].Because of its powerful and broad-spectrum“peacemaking”[4]functions,considerable efforts have been invested in developing IL-37-based anti-inflammatory therapeutics[5,6].

关键词： Interleukin neglected cytokine

Platelet-based bioactive systems guided precision targeting and immune regulation for cancer therapy

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Nano Research 2024年第9期17卷 8269-8284页

作者： Xinyi Cai Long Qiu Zhenying Diao Lintao Cai Ting Yin Hong Pan Guangdong Key Laboratory of Nanomedicine CAS-HK Joint Lab of BiomaterialsCAS Key Laboratory of Biomedical Imaging Science and SystemInstitute of Biomedicine and BiotechnologyShenzhen Institute of Advanced Technology(SIAT)Chinese Academy of SciencesShenzhen 518055China School of pharmacy Guangdong Medical UniversityDongguan 523808China Sino-Euro Center of biomedicine and Health Shenzhen 518024China

The antitumor effects of conventional drug carriers are often attenuated and limited in application by biological barriers associated with tumor heterogeneity and resistance brought about by low tumor *** the rapid development of nanotechnology,naturally derived bioactive materials,and live cell carriers,a promising strategy emerges for targeting the tumor microenvironment(TME)for precision cancer *** unique injury-targeting properties of platelets can significantly extend functional activity,which cannot be achieved with conventional *** this review,three strategies based on platelet-engineered materials are systematically described,namely nanoparticles for platelet membrane camouflage,engineered activated platelets,and targeted-platelets ***-based nanomaterials can effectively coordinate local and distant tumor-host crosstalk with controlled active tumor site recognition and killing effects due to the presence of specific membrane proteins on the surface and the self-secretion of a large number of *** advances in platelets for effectively overcoming biological barriers and reducing immune resistance in cancer immunotherapy applications will be discussed in future clinical *** review provides an overview of recent research advances in platelet-based bioactive material-directed immunotherapy and chemotherapy to inform future antitumor combination therapies.

关键词： platelets bionic targeting immune modulation precision therapy deep penetration

Variant PRC1 subunit RYBP/YAF2 forms condensate with RING1B and promotes H2AK119ub deposition

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Science China Life Sciences 2024年第9期67卷 2036-2038页

作者： Yanjiang Liu Gongcheng Hu Shengxiong Yang Chenghong Yan Juehan Wang Guangjin Pan Hongjie Yao State Key Laboratory of Respiratory Disease Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Department of Basic Research Guangzhou National Laboratory CAS Key Laboratory of Regenerative Biology Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences University of Chinese Academy of Sciences

Dear Editor,Polycomb group(Pc G) proteins represent important roles in repressing gene expression throughout development. The Polycomb repressive complexes(PRCs)have been subdivided into two central protein complexes, PRC1 and ***1 catalyzes H2AK119ub and PRC2catalyzes H3K27me1/2/3(Fursova et al.,2019). PRC1 is further categorized as CBX-containing canonical PRC1(c PRC1)and RYBP/YAF2-containing variant PRC1(v PRC1)(Blackledge and Klose,2021).

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Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke

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Neural Regeneration Research 2025年第7期20卷 1944-1956页

作者： Julia Castillo-González Elena González-Rey Institute of Parasitology and biomedicine Lopez-Neyra(IPBLN) CSICPT SaludGranadaSpain

The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral *** tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain *** the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its ***,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be *** review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier *** moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier ***,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case *** this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.

关键词： blood–brain barrier disruption drug delivery ischemic stroke neuroinflammation tight-junctions

维普期刊数据库

Dynamic Measurement of Intracellular pH Based on Bioluminescent Bacteria

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Chemical Research in Chinese Universities 2024年第2期40卷 287-292页

作者： LI Yaohua WANG Wei State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringChemBIC(Chemistry and Biomedicine Innovation Center)Nanjing UniversityNanjing210023P.R.China

Intracellular pH(pHi)is a fundamental indicator of cellular physiological state,regulating cellular state and function,and has important research *** various probes for measuring intracellular pH were available,it is challenging to reflect pHi in real-time and reversible ***,we developed a whole-cell bioluminescent(BL)probe based on wild type BL bacteria,photobacterium phosphoreum(***),to determine and image *** dependence of BL intensity of *** on pH values of culture solutions was *** was found that BL intensity could respond to the change of pH values rapidly and *** further revealed that *** maintained pH homeostasis in the extracellular pH(pHe)within the range of 5.0–7.0,while intracellular pH homeostasis was destroyed at the alkaline *** method opens up the enormous potential of BL bacteria as an alternative to fluorescence for monitoring and imaging pHi.

关键词： Bioluminescence P.phosphoreum Intracellular pH Cell imaging

Inhibition mechanisms of CRISPR-Cas9 by Acr ⅡA25.1 and AcrⅡA32

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Science China Life Sciences 2024年第9期67卷 1781-1791页

作者： Jianlin Zheng Yuwei Zhu Tengjin Huang Wenbo Gao Jiale He Zhiwei Huang HIT Center for Life Sciences School of Life Science and Technology Harbin Institute of Technology Westlake Center for Genome Editing Westlake Laboratory of Life Sciences and Biomedicine School of Life Sciences Westlake University

In the ongoing arms race between bacteria and bacteriophages, bacteriophages have evolved anti-CRISPR proteins to counteract bacterial CRISPR-Cas systems. Recently, Acr ⅡA25.1 and Acr ⅡA32 have been found to effectively inhibit the activity of Spy Cas9 both in bacterial and human cells. However, their molecular mechanisms remain elusive. Here, we report the cryo-electron microscopy structures of ternary complexes formed by Acr ⅡA25.1 and Acr ⅡA32 bound to Spy Cas9-sg RNA. Using structural analysis and biochemical experiments, we revealed that Acr ⅡA25.1 and Acr ⅡA32 recognize a novel, previously-unidentified anti-CRISPR binding site on Spy Cas9. We found that both Acr ⅡA25.1 and Acr ⅡA32 directly interact with the WED domain, where they spatially obstruct conformational changes of the WED and PI domains, thereby inhibiting Spy Cas9 from recognizing protospacer adjacent motif(PAM) and unwinding double-stranded DNA. In addition,they may inhibit nuclease activity by blocking the dynamic conformational changes of the Spy Cas9 surveillance complex. In summary, our data elucidate the inhibition mechanisms of two new anti-CRISPR proteins, provide new strategies for the modulation of Spy Cas9 activity,and expand our understanding of the diversity of anti-CRISPR protein inhibition mechanisms.

关键词： anti-CRISPR cryo-EM SpyCas9 AcrIIA25.1 AcrIIA32 inhibiton

Combining cisplatin and a STING agonist into one molecule for metalloimmunotherapy of cancer

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National Science Review 2024年第1期11卷 107-119页

作者： Shuren Zhang Dongfan Song Wenhao Yu Ji Li Xiaoyu Wang Yachao Li Zihan Zhao Qi Xue Jing Zhao Jie P.Li Zijian Guo State Key Laboratory of Coordination Chemistry School of Chemistry and Chemical EngineeringChemistry and Biomedicine Innovation Center (ChemBIC) Nanjing University Department of Urology Afflliated Drum Tower HospitalMedical SchoolNanjing University Nanchuang (Jiangsu)Institute of Chemistry and Health

Mounting evidence suggests that strategies combining DNA-damaging agents and stimulator of interferon genes(STING) agonists are promising cancer therapeutic regimens because they can amplify STING activation and remodel the immunosuppressive tumor microenvironment. However, a single molecular entity comprising both agents has not yet been developed. Herein, we designed two PtIV-MSA-2 conjugates(Ⅰand Ⅱ) containing the DNA-damaging chemotherapeutic drug cisplatin and the innate immuneactivating STING agonist MSA-2; these conjugates showed great potential as multispecific small-molecule drugs against pancreatic cancer. Mechanistic studies revealed that conjugate Ⅰ upregulated the expression of transcripts associated with innate immunity and metabolism in cancer cells, significantly differing from cisplatin and MSA-2. An analysis of the tumor microenvironment demonstrated that conjugate I could enhance the infiltration of natural killer(NK) cells into tumors and promote the activation of T cells, NK cells and dendritic cells in tumor tissues. These findings indicated that conjugate I, which was created by incorporating a Pt chemotherapeutic drug and STING agonist into one molecule, is a promising and potent anticancer drug candidate, opening new avenues for small-molecule-based cancer metalloimmunotherapy.

关键词： platinum drug STING agonist single-molecule multitarget metalloimmunology

RNA m6A dynamic modification mediated by nucleuslocalized FTO is involved in follicular reserve

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Zoological Research 2024年第2期45卷 415-428页

作者： Jiao-Na Zhang Rui-Ting Wang Francesca-Gioia Klinger Shun-Feng Cheng Wei Shen Xiao-Feng Sun College of Life Sciences Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of ShandongQingdao Agricultural UniversityQingdaoShandong 266109China Department of biomedicine and Prevention University of Rome Tor VergataRome 00133Italy

In eukaryotic organisms,the most common internal modification of messenger RNA(m RNA)is N6-methyladenosine(m6A).This modification can be dynamically and reversibly controlled by specific enzymes known as m6A writers and *** fat-mass and obesity-associated protein(FTO)catalyzes RNA demethylation and plays a critical role in various physiological and pathological *** research identified dynamic alterations in both m6A and FTO during the assembly of primordial follicles,with an inverse relationship observed for m6A levels and nuclear-localized FTO *** of Fto small interfering RNA(si RNA)altered the expression of genes related to cell proliferation,hormone regulation,and cell chemotaxis,and affected RNA alternative *** of the full-length Fto gene led to changes in m6A levels,alternative splicing of Cdk5,cell proliferation,cell cycle progression,and proportion of primordial ***,overexpression of Fto lacking a nuclear localization signal(NLS)did not significantly alter m6A levels or primordial follicle *** findings suggest that FTO,localized in the nucleus but not in the cytoplasm,regulates RNA m6A demethylation and plays a role in cell proliferation,cell cycle progression,and primordial follicle *** results highlight the potential of m6A and its eraser FTO as possible biomarkers and therapeutic targets.

关键词： m6A FTO Ovary Primordial follicle assembly Alternative splicing

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Genetic mapping of plasma proteome on brain structure

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Journal of Genetics and Genomics 2024年第7期51卷 774-777页

作者： Shengyi Ma Fengzhe Xu Yuanqing Fu Ju-Sheng Zheng Fudan University Shanghai 200433China School of Life Sciences Westlake UniversityHangzhouZhejiang 310030China Westlake Center for Intelligent Proteomics Westlake Laboratory of Life Sciences and BiomedicineHangzhouZhejiang 310030China

The emergence of high-throughput techniques for proteomics measurement has led to an increasing number of proteogenomic studies that aim to reveal protein quantitative trait loci(pQTL)based on large cohorts(Suhre et a... 详细信息

关键词： mapping structure throughput