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Neuroscience Bulletin 2024年第7期40卷 1012-1016页

作者： Qianhui Xia Xi Kuang Wei Meng Fei Yin Chenchen Ma Yupeng Yang center for Advanced Interdisciplinary Science and biomedicine of IHM Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China

Dear Editor,Stress initiates a cascade of hormonal and behavioral responses that enable an organism to adapt to new environmental *** unbalanced stress response can lead to dysregulation of the hypothalamic-pituitary-... 详细信息

关键词： Corti Receptor Cortex

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

Dynamic transcriptional programs define distinct mammalian cortical lineages

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Neural Regeneration Research 2024年第2期19卷 387-389页

作者： Tanzila Mukhtar Verdon Taylor Department of biomedicine University of BaselBaselSwitzerland Eli and Edythe Broad center of Regeneration Medicine and Stem Cell Research University of CaliforniaSan FranciscoCAUSA

The cerebral cortex is composed of billions of neurons and glia that are generated sequentially during *** cells are generated in an organized fashion during *** early stages of brain development,neural stem cells(NSC... 详细信息

关键词： cortex cerebral development

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

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

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

Photoredox-catalyzed C-glycosylation of peptides with glycosyl bromides

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Chinese Chemical Letters 2024年第6期35卷 263-267页

作者： Chen Li Ziyuan Zhao Shouyun Yu State Key Laboratory of Analytical Chemistry for Life Science Jiangsu Key Laboratory of Advanced Organic MaterialsChemistry and Biomedicine Innovation Center(ChemBIC)School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China

Glycosyl radicals,produced under mild photoredox conditions,show unique utility in the preparation of C-linked *** herein report the construction of C-glycosidic bonds on α,β-dehydroalanine(DHA)of peptides with easily available glycosyl bromides as glycosyl radical precursors under highly anomeric control,leading to C-glycosylation modifications of *** method not only has outstanding functional group compatibility,but also is feasible in near-physiological conditions(pH~7 and temperature T≤37℃ in aqueous media).

关键词： Glycosylation C-Glycosides Glycopeptides Dehydroalanine Photoredox catalysis

Different bactericidal abilities of plasma-activated saline with various reactive species prepared by surface plasma-activated air and plasma jet combinations

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Plasma Science and Technology 2024年第1期26卷 50-61页

作者：贾怡康李甜会张瑞赵鹏瑜王子丰陈旻郭莉刘定新 State Key Laboratory of Electrical Insulation and Power Equipment Center for Plasma BiomedicineXi’an Jiaotong UniversityXi’an 710049People’s Republic of China School of Life Science and Technology Xi’an Jiaotong UniversityXi’an 710049People’s Republic of China

Plasma-activated water(PAW),as an extended form of cold atmospheric-pressure plasma,greatly expands the application of plasma-based *** biological effects of PAW are closely related to the aqueous reactive species,which can be regulated by the activation *** this study,surface plasma-activated air(SAA)and a He+O_(2)plasma jet(Jet)were parallelly combined(the SAA+Jet combination)or sequentially combined(the SAA→Jet combination and the Jet→SAA combination)to prepare plasma-activated saline(PAS).The PAS activated by the combinations exhibited stronger bactericidal effects than that activated by the SAA or the Jet *** concentrations of H_(2)O_(2)and NO_(2)^(-)were higher in the PAS activated by the Jet→SAA combination,while ONOO^(-)concentrations were close in the three kinds of PAS and^(1)O_(2)concentrations were higher in the PAS activated by the SAA+Jet *** analysis of scavengers also demonstrated that H_(2)O_(2),^(1)O_(2),and ONOO^(-)in the PAS activated by the SAA+Jet combination,and^(1)O_(2)in the PAS activated by the Jet→SAA combination played critical roles in bactericidal ***,the effective placement time of the three PAS varied,and the PAS activated by the Jet→SAA combination could also inactivate 2.6-log_(10)of MRSA cells after placement for more than 60 *** regulation of reactive species in plasma-activated water via different combinations of plasma devices could improve the directional application of plasma-activated water in the biomedical field.

关键词： plasma-activated water surface plasma-activated air plasma jet bactericidal effect reactive species

Decarboxylative Amination with Nitroarenes via Synergistic Catalysis

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Chinese Journal of Chemistry 2024年第4期42卷 351-355页

作者： Meiling Ding Sitian Zhou Shunruo Yao Chengjian Zhu Weipeng Li Jin Xie State Key Laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic MaterialsChemistry and Biomedicine Innovation Center(ChemBIC)School of Chemistry and Chemical EngineeringNanjing UniversityNanjingJiangsu210023 China Green Catalysis center and College of ChemistryZhengzhou UniversityZhengzhouHenan450001 China

In this paper,we have developed a decarboxylative amination of carboxylic acids with nitroarenes for the synthesis of secondary *** protocol is performed at mild conditions without the use of noble metals as catalysts.A wide range of structurally diverse secondary amines could be obtained in good yields(up to 94%)with good functional group *** transformation shows good to excellent selectivity,avoiding the generation of over alkylated byproducts.

关键词： Nitroarenes Amines Synergistic catalysis Carboxylic acids Radical alkylation Amination Photocatalysis Steric hindrance

Mechanism by which Rab5 promotes regeneration and functional recovery of zebrafish Mauthner axons

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Neural Regeneration Research 2025年第6期20卷 1816-1824页

作者： Jiantao Cui Yueru Shen Zheng Song Dinggang Fan Bing Hu center for Advanced Interdisciplinary Science and biomedicine of IHM Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina

Rab5 is a GTPase protein that is involved in intracellular membrane trafficking. It functions by binding to various effector proteins and regulating cellular responses, including the formation of transport vesicles and their fusion with the cellular membrane. Rab5 has been reported to play an important role in the development of the zebrafish embryo;however, its role in axonal regeneration in the central nervous system remains unclear. In this study, we established a zebrafish Mauthner cell model of axonal injury using single-cell electroporation and two-photon axotomy techniques. We found that overexpression of Rab5 in single Mauthner cells promoted marked axonal regeneration and increased the number of intra-axonal transport vesicles. In contrast, treatment of zebrafish larvae with the Rab kinase inhibitor CID-1067700markedly inhibited axonal regeneration in Mauthner cells. We also found that Rab5 activated phosphatidylinositol 3-kinase(PI3K) during axonal repair of Mauthner cells and promoted the recovery of zebrafish locomotor function. Additionally, rapamycin, an inhibitor of the mechanistic target of rapamycin downstream of PI3K, markedly hindered axonal regeneration. These findings suggest that Rab5 promotes the axonal regeneration of injured zebrafish Mauthner cells by activating the PI3K signaling pathway.

关键词： axonal regeneration Mauthner cell nerve regeneration Rab5 zebrafish