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STING regulates BCR signaling in normal and malignant B cells

Cellular & Molecular Immunology 2021年第4期18卷 1016-1031页

作者： chih-Hang Anthony Tang Avery C.Lee Shiun Chang Qin Xu Andong Shao Yun Lo Walker T.Spalek Javier A.Pinilla-lbarz Juan R.Del Valle chih-chi andrew hu The Wistar Institute 3601 Spruce StreetPhiladelphiaPA 19104USA Department of Malignant Hematology H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA Department of Chemistry&Biochemistry University of Notre DameNotre DameIN 46556USA

STING is an endoplasmic reticulum(ER)-resident protein critical for sensing cytoplasmic DNA and promoting the production of type Ⅰ interferons;however,the role of STING in B cell receptor(BCR)signaling remains *** generated STING V154M knock-in mice and showed that B cells carrying constitutively activated STING specifically degraded membrane-bound IgM,Ig a and Igβ via SEL1L/HRD1-mediated ER-associated degradation(ERAD).B cells with activated STING were thus less capable of responding to BCR activation by phosphorylating Igα and Syk than those without activated *** immunized with T-independent antigens,STING V154M mice produced significantly fewer antigen-specific plasma cells and antibodies than immunized wild-type(WT)*** further generated B cell-specific STING^(KO) mice and showed that STING^(KO) B cells indeed responded to activation by transducing stronger BCR signals than their STING-proficient *** B cell-specific STING^(KO) mice were T-independently immunized,they produced significantly more antigen-specific plasma cells and antibodies than immunized STIN^(WT)*** both human and m ouse IGHV-unmutated malignant chronic lymphocytic leukemia(CLL)cells downregulated the expression of STING,we explored whether STING downregulation could contribute to the well-established robust BCR signaling phenotype in malignant CLL *** generated a STING-deficient CLL mouse model and showed that STING-deficient CLL cells were indeed more responsive to BCR activation than their STING-proficient *** results revealed a novel B cell-intrinsic role of STING in negatively regulating BCR signaling in both normal and malignant B cells.

关键词： STING BCR ER-associated degradation CLL Plasma cells

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STING negatively regulates allogeneic T-cell responses by constraining antigen-presenting cell function

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Cellular & Molecular Immunology 2021年第3期18卷 632-643页

作者： Hee-Jin ChoiTaylor Ticer Yongxia Wu chih-Hang Anthony Tang Corey Mealer David Bastian M.Hanief Sofi Linlu Tian Steven Schutt Hee-Jin Choi Taylor Ticer Mengmeng Zhang Xiaohui Sui Lei huang andrew L.Mellor chih-chi andrew hu Xue-Zhong Yu Microbiology&Immunology Medical University of South CarolinaCharlestonSCUSA Immunology Microenvironment&Metastasis ProgramThe Wistar InstitutePhiladelphiaPAUSA Translational and Clinical Research Institute Faculty of Medical SciencesNewcastle UniversityNewcastle upon TyneUK Department of Medicine Medical University of South CarolinaCharlestonSCUSA Hollings Cancer Center Medical University of South CarolinaCharlestonSCUSA

Stimulator of interferon genes(STING)-mediated innate immune activation plays a key role in tumor-and self-DNA-elicited antitumor immunity and ***,STING can also suppress tumor immunity and *** signaling In host nonhematopoietic cells was reported to either protect against or promote graft-versus-host disease(GVHD),a major complication of allogeneic hematopoietic cell transplantation(allo-HCT).Host hematopoietic antigen-presenting cells(APCs)play key roles in donor T-cell priming during GVHD ***,how STING regulates host hematopoietic APCs after allo-HCT remains *** utilized murine models of allo-HCT to assess the role of STING in hematopoietic ***-deficient recipients developed more severe GVHD after major histocompatibility complex-mismatched *** bone marrow chimeras,we found that STING deficiency in host hematopoietic cells was primarily responsible for exacerbating the ***,STING on host CD11c+cells played a dominant role in suppressing allogeneic T-cell ***,STING deficiency resulted in increased survival,activation,and function of APCs,including macrophages and dendritic ***,constitutive activation of STING attenuated the survival,activation,and function of APCs isolated from STING V154M knock-in ***-deficient APCs augmented donor T-cell expansion,chemokine receptor expression,and migration into intestinal tissues,resulting in accelerated/exacerbated *** pharmacologic approaches,we demonstrated that systemic administration of a STING agonist(bis-(3'-5')-cyclic dimeric guanosine monophosphate)to recipient mice before transplantation significantly reduced GVHD *** conclusion,we revealed a novel role of STING in APC activity that dictates T-cell allogeneic responses and validated STING as a potential therapeutic target for controlling GVHD after allo-HCT.

关键词： Stimulator of interferon genes antigen-presenting cells allogeneic hematopoietic cell transplantation graft-versushost diseases hematopoietic stem-cell transplantation T cells

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Photo‑Energized MoS_(2)/CNT Cathode for High‑Performance Li–CO_(2)Batteries in a Wide‑Temperature Range

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Nano-Micro Letters 2025年第1期17卷 160-175页

作者： Tingsong hu Wenyi Lian Kang hu Qiuju Li Xueliang Cui Tengyu Yao Laifa Shen Jiangsu Key Laboratory of Materials and Technologies for Energy Storage College of Materials Science and TechnologyNanjing University of Aeronautics and AstronauticsNanjing 210016People’s Republic of China

Li–CO_(2) batteries are considered promising energy storage systems in extreme environments such as Mars;however,severe performance degradation will occur at a subzero temperature owning to the sluggish reaction ***,a photo-energized strategy adopting sustainable solar energy in wide working temperature range Li–CO_(2) battery was achieved with a binder-free MoS_(2)/carbon nanotube(CNT)photo-electrode as *** unique layered structure and excellent photoelectric properties of MoS_(2) facilitate the abundant generation and rapid transfer of photo-excited carriers,which accelerate the CO_(2) reduction and Li_(2)CO_(3) decomposition upon *** illuminated battery at room temperature exhibited high discharge voltage of 2.95 V and mitigated charge voltage of 3.27 V,attaining superior energy efficiency of 90.2%and excellent cycling stability of over 120 *** at an extremely low temperature of−30℃,the battery with same electrolyte can still deliver a small polarization of 0.45 V by the photoelectric and photothermal synergistic mechanism of MoS_(2)/CNT *** work demonstrates the promising potential of the photo-energized wide working temperature range Li–CO_(2) battery in addressing the obstacle of charge overpotential and energy efficiency.

关键词： Li-CO_(2)batteries Photo-energized Wide operation-temperature Kinetics MoS_(2)

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Fabrication and Mechano-sensing Characteristics of Bending Polypyrrole Actuator

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Journal of Wuhan University of Technology(Materials Science) 2025年第1期40卷 240-245页

作者： CHEN Jinyou hu Wei School of Automotive Engineering Hunan Financial&Industrial Vocational-technical CollegeHengyang 421002China College of Mechanical and Electrical Engineering Hunan Agricultural UniversityChangsha 410128China

To prepare a conductive polymer actuator with decent performance,a self-built experimental platform for the preparation of polypyrrole film is *** of the essential goals is to examine the mechanical characteristics of the actuator in the presence of various combinations of process parameters,combined with the orthogonal test method of"four factors and three levels".The bending and sensing characteristics of actuators of various sizes are methodically examined using a self-made bending polypyrrole *** functional relationship between the bending displacement and the output voltage signal is established by studying the characteristics of the actuator sensor subjected to various degrees of *** experimental results reveal that the bending displacement of the actuator tip almost exhibits a linear variation as a function of length and *** the voltage reaches 0.8 V,the bending speed of the actuator tends to be ***,the mechanical properties of the self-assembled polypyrrole actuator are verified by the design and fabrication of the microgripper.

关键词： conductive polymer polypyrrole mechanical characteristics actuators sensing characteristics

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Optimizing Fine-Tuning in Quantized Language Models:An In-Depth Analysis of Key Variables

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Computers, Materials & Continua 2025年第1期82卷 307-325页

作者： Ao Shen Zhiquan Lai Dongsheng Li Xiaoyu hu National Key Laboratory of Parallel and Distributed Computing National University of Defense TechnologyChangsha410073China Strategic Assessments and Consultation Institute Academy of Military ScienceBeijing100091China

Large-scale Language Models(LLMs)have achieved significant breakthroughs in Natural Language Processing(NLP),driven by the pre-training and fine-tuning *** this approach allows models to specialize in specific tasks with reduced training costs,the substantial memory requirements during fine-tuning present a barrier to broader ***-Efficient Fine-Tuning(PEFT)techniques,such as Low-Rank Adaptation(LoRA),and parameter quantization methods have emerged as solutions to address these challenges by optimizing memory usage and computational *** these,QLoRA,which combines PEFT and quantization,has demonstrated notable success in reducing memory footprints during fine-tuning,prompting the development of various QLoRA *** these advancements,the quantitative impact of key variables on the fine-tuning performance of quantized LLMs remains *** study presents a comprehensive analysis of these key variables,focusing on their influence across different layer types and depths within LLM *** investigation uncovers several critical findings:(1)Larger layers,such as MLP layers,can maintain performance despite reductions in adapter rank,while smaller layers,like self-attention layers,aremore sensitive to such changes;(2)The effectiveness of balancing factors depends more on specific values rather than layer type or depth;(3)In quantization-aware fine-tuning,larger layers can effectively utilize smaller adapters,whereas smaller layers struggle to do *** insights suggest that layer type is a more significant determinant of fine-tuning success than layer depth when optimizing quantized ***,for the same discount of trainable parameters,reducing the trainable parameters in a larger layer is more effective in preserving fine-tuning accuracy than in a smaller *** study provides valuable guidance for more efficient fine-tuning strategies and opens avenues for further research into optimizing LLM

关键词： Large-scale Language Model Parameter-Efficient Fine-Tuning parameter quantization key variable trainable parameters experimental analysis

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Repetitive transcranial magnetic stimulation in Alzheimer’s disease:effects on neural and synaptic rehabilitation

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Neural Regeneration Research 2025年第2期20卷 326-342页

作者： Yi Ji Chaoyi Yang Xuerui Pang Yibing Yan Yue Wu Zhi Geng Wenjie hu Panpan hu Xingqi Wu Kai Wang Department of Neurology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui ProvinceChina Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders HefeiAnhui ProvinceChina Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health HefeiAnhui ProvinceChina Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina Department of Psychology and Sleep Medicine The Second Affiliated Hospital of Anhui Medical UniversityHefeiAnhui ProvinceChina

Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and *** Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life,leaving patients *** transcranial magnetic stimulation is a cost-effective,neuro-modulatory technique used for multiple neurological *** the past two decades,it has been widely used to predict cognitive decline;identify pathophysiological markers;promote neuroplasticity;and assess brain excitability,plasticity,and *** has also been applied to patients with dementia,because it can yield facilitatory effects on cognition and promote brain recovery after a neurological ***,its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of *** study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment,evaluate its effects on synaptic plasticity,and identify the associated *** review essentially focuses on changes in the pathology,amyloidogenesis,and clearance pathways,given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer’s *** mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription,which are closely related to the neural regeneration process,are also ***,we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation,with the aim to highlight future directions for better clinical translations.

关键词： Alzheimer’s disease amyloid deposition apoptotic mechanisms biomarker neural regeneration neurodegeneration repetitive transcranial magnetic stimulation synaptic plasticity

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Potential role of tanycyte-derived neurogenesis in Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1599-1612页

作者： Guibo Qi Han Tang Jianian hu Siying Kang Song Qin Department of Anatomy Histologyand EmbryologySchool of Basic Medical SciencesFudan UniversityShanghaiChina State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan UniversityShanghaiChina

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier ***, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could pro

关键词： Alzheimer's disease blood–brain barrier ependymoglial cells hypothalamus metabolic diseases neural stem cells neurogenesis neuroinflammatory diseases neurons tanycyte

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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

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Boosting Oxygen Evolution Reaction Performance on NiFe‑Based Catalysts Through d‑Orbital Hybridization

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Nano-Micro Letters 2025年第1期17卷 281-292页

作者： Xing Wang Wei Pi Sheng hu Haifeng Bao Na Yao Wei Luo State Key Laboratory of New Textile Materials and Advanced Processing Technology Key Laboratory of New Textile Materials and Applications of Hubei ProvinceSchool of Materials Science and EngineeringWuhan Textile UniversityWuhan 430200People’s Republic of China College of Chemistry and Molecular Sciences Wuhan UniversityWuhan 430072People’s Republic of China

Anion-exchange membrane water electrolyzers(AEMWEs)for green hydrogen production have received intensive attention due to their feasibility of using earth-abundant NiFe-based *** introducing a third metal into NiFe-based catalysts to construct asymmetrical M-NiFe units,the d-orbital and electronic structures can be adjusted,which is an important strategy to achieve sufficient oxygen evolution reaction(OER)performance in ***,the ternary NiFeM(M:La,Mo)catalysts featured with distinct M-NiFe units and varying d-orbitals are reported in this *** and theoretical calculation results reveal that the doping of La leads to optimized hybridization between d orbital in NiFeM and 2p in oxygen,resulting in enhanced adsorption strength of oxygen intermediates,and reduced rate-determining step energy barrier,which is responsible for the enhanced OER *** critically,the obtained NiFeLa catalyst only requires 1.58 V to reach 1 A cm^(−2) in an anion exchange membrane electrolyzer and demonstrates excellent long-term stability of up to 600 h.

关键词： NiFe-based catalysts d-orbital coupling Oxygen evolution reaction Anion exchange membrane electrolyzer

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Wave effect of gravitational waves intersected with a microlens field Ⅱ:An adaptive hierarchical tree algorithm and population study

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Science china(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 241-254页

作者： Xikai Shan Guoliang Li Xuechun Chen Wen Zhao Bin hu Shude Mao Department of Astronomy Tsinghua University Purple Mountain Observatory Chinese Academy of Sciences Institute for Frontier in Astronomy and Astrophysics Beijing Normal University School of Physics and Astronomy Beijing Normal University School of Astronomy and Space Science University of Science and Technology of China CAS Key Laboratory for Researches in Galaxies and Cosmology Department of Astronomy University of Science and Technology of ChinaChinese Academy of Sciences

The gravitational lensing wave effect generated by a microlensing field embedded in a lens galaxy is an inevitable phenomenon in strong lensed gravitational waves （SLGWs）.This effect presents both challenges and opportunities for the detection and application of ***,investigating this wave effect requires computing a complete diffraction integral over each microlens in the *** is extremely time-consuming due to the large number of microlenses （10～3-10～6）.Therefore,simply adding all the microlenses is ***,the complexity of the time delay surface makes the lens plane resolution a crucial factor in controlling numerical *** this paper,we propose a trapezoid approximation-based adaptive hierarchical tree algorithm to meet the challenges of calculation speed and *** find that this algorithm accelerates the calculation by four orders of magnitude compared to the simple adding method and is one order of magnitude faster than the fixed hierarchical tree algorithm proposed for electromagnetic *** importantly,our algorithm ensures controllable numerical errors,increasing confidence in the *** with our previous work （***.66,239511,2023）,this paper addresses all numerical issues,including integral convergence,precision,and computational time1).Finally,we conducted a population study on the microlensing wave effect of SLGWs using this algorithm and found that the microlensing wave effect cannot be ignored,especially for Type II SLGWs （from saddle position of the time delay surface） due to their intrinsic geometric structures and their typical intersection with a denser microlensing ***,more than 33%（11%） of SLGWs have a mismatch larger than 1%（3%） compared to the unlensed ***,we found that the mismatch between signal pairs in a doubly imaged GW is generally larger than 10-3,and 61%（25%） of signal pairs have a mismatch larger than 1%（3%）.Therefo

关键词： gravitational lensing diffractional integral algorithm gravitational wave

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