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TRIM66-HP1γ remodels the chromatin through phase separation

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Biophysics Reports 2025年第1期11卷 18-33页

作者： Siyuan Shen Feng Chen Yifan Zhang Fudong Li Xuebiao Yao Dan Liu Yunyu Shi Liang Zhang Center for Advanced Interdisciplinary science and Biomedicine of IHM Division of Life Sciences and MedicineUniversity of Science and Technology of China Ministry of Education Key laboratory for Membraneless Organelles and cellular Dynamics University of Science and Technology of China Hefei National Research Center for Cross disciplinary science University of Science and Technology of China

Chromatin contains not only heterochromatin(HC) and euchromatins(EC) but also facultative heterochromatin(f HC), which experience the dynamic remodeling between HCs and ECs by different regulators. The regulation of f HCs involves lots of different cell functions, like genomic stability and gene transcription. Heterochromatin protein 1(HP1) recognizes methylated H3K9 and reshapes the chromatin into the f HCs through liquid–liquid phase separation(LLPS). Among the three members of the HP1 family, HP1α can condensate by itself and HP1β forms granules with the help of TRIM28, while the HP1γ cannot phase separation alone either and the coordinator is still unclear. So, in this study, we investigated the molecular mechanism of how HP1γ interacts with TRIM66 through Px Vx L motif. Based on that, we examined the key regions that controlled the TRIM66-HP1γ co-phase separation behaviors both in vitro and in vivo. Furthermore, we proved that the liquid granules of TRIM66-HP1γ and chromatin highly correlated with H3K9me3 sites, which indicated the relationship with DNA damage response. Finally, combined with our previous study, we proposed the system for how TRIM66 remodeled the chromatin into compressed f HC through the TRIM66-HP1γ-H3K9me3 axis with liquid–liquid phase separation.

关键词： Chromatin TRIM66-HP1γ Facultative heterochromatin Phase separation

New aspects of a small GTPase RAB35 in brain development and function

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Neural Regeneration Research 2025年第7期20卷 1971-1980页

作者： Ikuko Maejima Ken Sato laboratory of Molecular Traffic Institute for Molecular and Cellular RegulationGunma UniversityMaebashiJapan

In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting the cargo of proteins,lipids,and other molecules to appropriate compartments via transport vesicles or *** processes are strictly regulated by various small GTPases such as the RAS-like in rat brain(RAB)protein family,which is the largest subfamily of the RAS *** of membrane trafficking affects tissue homeostasis and leads to a wide range of diseases,including neurological disorders and neurodegenerative ***,it is important to understand the physiological and pathological roles of RAB proteins in brain ***35,a member of the RAB family,is an evolutionarily conserved protein in metazoans.A wide range of studies using cultured mammalian cells and model organisms have revealed that RAB35 mediates various processes such as cytokinesis,endocytic recycling,actin bundling,and cell ***35 is also involved in neurite outgrowth and turnover of synaptic *** generated brain-specific Rab35 knockout mice to study the physiological roles of RAB35 in brain development and *** mice exhibited defects in anxiety-related behaviors and spatial ***,RAB35 is required for the precise positioning of pyramidal neurons during hippocampal development,and thereby for normal hippocampal *** contrast,layer formation in the cerebral cortex occurred superficially,even in the absence of RAB35,suggesting a predominant role for RAB35 in hippocampal development rather than in cerebral cortex *** studies have suggested an association between RAB35 and neurodegenerative diseases,including Parkinson's disease and Alzheimer's *** this review,we provide an overview of the current understanding of subcellular functions of *** also provide insights into the phys

关键词： endocytosis endosomes hippocampal development neurodegenerative diseases RAB35

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Influence of heat treatment on microstructure of a newβ-solidifyingγ-TiAl alloy

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Journal of Iron and Steel Research International 2025年第1期32卷 239-248页

作者： Li Quan Xiao-bing Li Peng Xue Jun-jie Hao Kun Qian Bo Chen Jian-zhong Li Kui Liu School of Metallurgy Northeastern UniversityShenyang110819LiaoningChina Department of Materials science and technology Ji Hua LaboratoryFoshan528200GuangdongChina

The high strength and stability of the full-lamellar structure guarantee the industrial application of theβ-solidifyingγ-TiAl ***,it is a huge challenge to design an alloy with good hot-deformability as well as the full-lamellar *** low-cost Ti-42.5Al-2Mn-0.4Mo-0.1B-0.1C(at.%)alloy was designed,which undergoes bothβandαsingle-phase region during the *** is found that the full-lamellar structure can be obtained by the solution heat treatment at 1230℃ for 20 min and then aging treatment at 800℃ for 3 ***,a new microstructure,namely,the pearlitic-like microstructure(PM)induced by theα_(2)/γ→βo+γcellular reaction was observed when the aging temperature is increased to above 800℃.The volume fraction of the PM is gradually increased from 0%to 25.5%,65%,and 94%according to elevated aging temperature from 800 to 900,1000,and 1050℃,*** mechanism of the reducedα_(2)/γlamellae and PM formation was discussed regarding the heterogeneous distribution ofβstabilizing elements and the interface energy stored inα_(2)/γlamellae.

关键词： β-γ-TiAl Alloy design Two-step heat treatment Full-lamellar structure cellular reaction

The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons

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Neural Regeneration Research 2025年第1期20卷 209-223页

作者： Shi-Yan Sun Lingyun Nie Jing Zhang Xue Fang Hongmei Luo Chuanhai Fu Zhiyi Wei Ai-Hui Tang Hefei National Research Center for Physical sciences at the Microscale CAS Key Laboratory of Brain Function and DiseaseMinistry of Education Key Laboratory for Membrane-less Organelles and Cellular DynamicsDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina CAS Center for Excellence in Molecular Cell sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Neurobiology School of Life SciencesSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina Brain Research Center Southern University of Science and TechnologyShenzhenGuangdong ProvinceChina

Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and ***-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains *** this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative ***,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic *** of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and *** down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive *** together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

关键词： actin cytoskeleton dendrite KANK1 KIF21A microtubule spine morphology spine synaptic plasticity talin1

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Nanoparticle Induces Membrane Fusion in a State-wise and Property-sensitive Mode

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高分子科学（英文版） 2025年第1期43卷 235-244页

作者： Chi-Yun Ma Xue-Wei Dong Xue-Mei Lu Bing Yuan Kai Yang Center for Soft Condensed Matter Physics and Interdisciplinary Research & School of Physical science and technology Soochow UniversitySuzhou 215006China Center for Soft Condensed Matter Physics and Interdisciplinary Research & School of Physical science and technology Soochow UniversitySuzhou 215006China State Key laboratory of Surface Physics and Department of Physics Fudan UniversityShanghai 200433China School of Optical and Electronic Information Suzhou City UniversitySuzhou 215104China School of Physical science and technology Jiangsu Key Laboratory of Thin FilmsSoochow UniversitySuzhou 215006China Songshan Lake Materials laboratory Dongguan 523808China Center for Soft Condensed Matter Physics and Interdisciplinary Research & School of Physical science and technology Soochow UniversitySuzhou 215006China Songshan Lake Materials laboratory Dongguan 523808China

Membrane fusion is essential for many cellular physiological functions,which is modulated by highly precise molecular mechanism in-volving multiple energy ***(NPs),which exhibit immense potential in the field of biomedical applications,can act as fusogen proteins to initiate and regulate membrane ***,the underlying mechanisms of NP-induced membrane fusion and the molecular de-tails involved remain largely ***,using coarse-grained molecular dynamics simulations,we systematically investigate the NP-induced membrane fusion behaviors and the influences of NP properties(size,hydrophobicity and hydrophilicity).Our results show that the vesicle-bilay-er fusion induced by a hydrophobic NP is an intricately state-wise process,involving the approach and local deformation of the vesicle and bilay-er bridging by the NP,the flip-flop of lipids from proximal leaflets and the formation of a fusion stalk,as well as further lipid interactions between distal leaflets and complete ***,we find that NP properties have distinct effects on membrane fusion and thus the optimal NP con-ditions for facilitating membrane fusion are *** work provides a mechanistic understanding of NP-induced membrane fusion and of-fers useful insights for efficient and controlled regulation of membrane fusion.

关键词： Nanoparticle Membrane fusion Molecular dynamics simulation Coarse-grained model

MoS2 synaptic transistor with one-step manufacture

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science China(Information sciences) 2025年第1期68卷 357-365页

作者： Yihao GUO Yang WANG Wenjie DENG Yi WU Jingtao LI Kexin LI Yuehui ZHAO Songlin YU Xiaoting WANG Yongzhe ZHANG Hui YAN Key laboratory of Optoelectronics technology of Education Ministry of China Faculty of Information TechnologyBeijing University of Technology Key laboratory of Advanced Functional Materials Ministry of Education Faculty of Materials and ManufacturingBeijing University of Technology The 11th Research Institute of Electronics technology Group Corporation

The synaptic transistor,which is a neuromorphic device with brain-like functions,has garnered significant attention due to characteristics such as low energy consumption,high integration,multiple functions,and high computational ***,the current synaptic transistor possesses a complicated structure and involves complex manufacturing steps,which is not conducive to low-cost,large-scale bionic ***,we introduce a simple MoS2synaptic transistor exhibiting robust synaptic *** transistor utilizes magnetron sputtering manufacture to combine the process of device metal electrode deposition and the introduction of defect states,which helps streamline the manufacturing process into a single *** long-term potentiation and long-term depression in photoelectric coordination are initially ***,biological functions,such as double pulse facilitation and the transformation behavior of short-term memory to long-term memory,are thoroughly evaluated,along with learning-forgetting-relearning ***,the device exhibits robust synaptic plasticity until incident light angles down to 30° to imitate the multi-to-one axon-cellular ***,a classical simulation of Pavlov's dog conditioned reflex is demonstrated along with the multiview extraction *** experimental results demonstrate a promising synaptic transistor with a simple structure,manufacturing technique,and excellent *** further indicates the potential for large-scale integration of bionic neuromorphic systems.

关键词： process optimization artificial synaptic device one-stepmanufacture synaptic plasticity bionic simulation

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Stepwise activated probe for cell surface glycan imaging

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science China Chemistry 2025年

作者： Chunyi Zhang Jing Chen Xiaoyao Bai Shengnan Fu Xin Su State Key laboratory of Organic-Inorganic Composites Beijing Key Laboratory of Bioprocess Beijing Advanced Innovation Center for Soft Matter Science and Engineering College of Life Science and Technology Beijing University of Chemical Technology

Fluorescent DNA probes commonly used for in situ imaging of cell surface glycans are “always-on” probes(AOPs), which produce high background noise and lack spatial specificity. Molecular dynamics simulations indicate that single-stranded DNA(ssDNA) can stably associate with the cell membrane, contributing to persistent background signals in AOPs. To overcome this challenge, a stepwise activated probe(SAP) is developed for in situ imaging of cell surface glycans. In SAP, the cell surface glycan is labeled by rolling circle amplification product through metabolic glycan labeling strategies. The product hybridizes a fluorophore and quencher-labeled ssDNA reporter to form a double strand producing primary enhancement of fluorescence signal. Nicking enzyme(***) cleaves the double strand and releases the quencher, further enhancing the signal. Nonspecific absorption of the reporter on the cellular membrane does not increase the fluorophore-quencher distance in SAP or trigger *** cleavage. As a result, only the glycan sites are illuminated. SAP not only exhibits high imaging specificity but also greatly simplifies the imaging procedure by reducing the washing steps. SAP offers a considerable improvement in detection specificity and sensitivity by employing a two-step activation and amplification process, making it a powerful method for in situ fluorescence imaging.

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Evaluating the scope of human leukocyte antigen polymorphisms influencing hepatitis B virus-related liver cancer and cirrhosis through multi-clustering analysis

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World Journal of Gastroenterology 2025年第7期31卷 156-159页

作者： Shi Li Yue Xi Xue-Ying Dong Wen-Bin Yuan Jing-Feng Tang Ce-Fan Zhou School of Life and Health sciences Institute of Biomedical ResearchNational“111”Center for Cellular Regulation and Molecular PharmaceuticsKey Laboratory of Fermentation Engineering(Ministry of Education)Hubei University of TechnologyWuhan 430068Hubei ProvinceChina

Hepatitis B virus remains a major cause of cirrhosis and hepatocellular carcinoma,with genetic polymorphisms and mutations influencing immune responses and disease *** et al present novel findings on specific human leukocyte antigen(HLA)alleles,including rs2856718 of HLA-DQ and rs3077 and rs9277535 of HLA-DP,which may predispose individuals to cirrhosis and liver cancer,based on multi-clustering ***,we discuss the feasibility of this approach and identify key areas for further investigation,aiming to offer insights for advancing clinical practice and research in liver disease and related cancers.

关键词： Hepatitis B virus Gene polymorphisms Multi-clustering analysis Genetic markers Personalized medicine Clinical implications

Lung-targeted polyzwitterionic lipid nanoparticles for effective treatment of lung inflammation

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science China Chemistry 2025年第3期 1107-1116页

作者： Wen Zhang Jiaxin Li Nan Wang Muzi Li Chen Peng Xinyue Zhang Guanghui Ouyang Yan Li Beijing Key laboratory for Bioengineering and Sensing technology School of Chemistry and Biological EngineeringUniversity of Science and Technology Beijing CAS Key laboratory of Colloid Interface and Chemical ThermodynamicsInstitute of ChemistryChinese Academy of Sciences

Lipid nanoparticles(LNPs) are non-viral nucleic acid delivery systems that show great potential in vaccine development and disease *** LNPs are particularly advantageous for in vivo delivery,the wide application of LNPs is impeded as their systemic delivery of nucleic acid drugs to extrahepatic tissues remains highly *** address this issue,we developed lung-targeted polyzwitterionic LNPs with zwitterionic polymer poly(2-methyacryloyloxyethyl phosphorylcholine)(PMPC) modified 1,2-dimyristoyl-sn-glycerol lipid for the delivery of small interfering RNA(si RNA).Three libraries with 90PMPC-LNPs@siRNA were *** polyzwitterionic PMPC-LNPs had high siRNA encapsulation efficiency of about 90%.The findings revealed that polyzwitterionic PMPC-LNPs@siRNA absorbed protein corona with the main component of Vitronectin,mediating lung-targeted delivery of *** good cellular uptake and endo/lysosomal escape ability,in vitro and in vivo studies demonstrated that polyzwitterionic PMPC-LNPs with siRNA against tumor necrosis factor-α(TNF-α) could significantly down-regulate the TNF-α in mRNA and protein levels,and improved the pathological features of lung *** PMPC-LNPs@siRNA achieved safe and efficient treatment of lung ***,this work offered a promising siRNA therapeutic approach for lung diseases.

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