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Bidirectional regulation of the brain-gut-microbiota axis following traumatic brain injury

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Neural Regeneration Research 2025年第8期20卷 2153-2168页

作者： Xinyu You Lin Niu Jiafeng Fu Shining Ge Jiangwei Shi Yanjun Zhang Pengwei Zhuang national Key laboratory of Chinese Medicine Modernization Tianjin University of Traditional Chinese MedicineTianjinChina Haihe laboratory of Modern Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjinChina First Teaching Hospital of Tianjin University of Traditional Chinese Medicine TianjinChina national Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion TianjinChina

Traumatic brain injury is a prevalent disorder of the central nervous *** addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are *** dysfunction is a significant consequence of traumatic brain *** the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous *** gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated *** comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut ***,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain *** review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effec

关键词： traumatic brain injury brain-gut-microbiome axis gut microbiota neuroimmune immunosuppression host defense vagal afferents bacterial infection dorsal root ganglia nociception neural circuitry

The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

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Neural Regeneration Research 2025年第5期20卷 1505-1512页

作者： Jieying Wu Shan Ye Xiangyi Liu Yingsheng Xu Dongsheng Fan Department of Neurology Peking University Third HospitalBeijingChina Beijing Municipal Key laboratory of Biomarker and Translational Research in Neurodegenerative Diseases BeijingChina Key laboratory for Neuroscience National Health Commission/Ministry of EducationPeking UniversityBeijingChina

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor *** bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to ***,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is *** address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral *** used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis *** factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb *** results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis *** findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

关键词： amyotrophic lateral sclerosis bilateral limb involvement Cox proportional hazards regression model horizontal spread restricted cubic spline analysis time interval upper motor neuron vertical spread

Proton transfer-mediated GPCR activation

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Protein & Cell 2015年第1期6卷 12-17页

作者： Xuejun C. Zhang Can Cao Ye Zhou Yan Zhao national laboratory of macromolecules National Center of Protein Science--Beijing Institute of Biophysics ChineseAcademy of Sciences Beijing 100101 China

G-protein coupled receptors （GPCRs） play essential roles in signal transduction from the environment into the cell. While many structural features have been elu- cidated in great detail, a common functional mechanism on how the ligand-binding signal is converted into a conformational change on the cytoplasmic face result- ing in subsequent activation of downstream effectors remain to be established. Based on available structural and functional data of the activation process in class-A GPCRs, we propose here that a change in protonation status, together with proton transfer via conserved structural elements located in the transmembrane region, are the key elements essential for signal trans- duction across the membrane.

关键词： GPCR activation protonation membranepotential

How does a β-barrel integral membrane protein insert into the membrane？

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Protein & Cell 2016年第7期7卷 471-477页

作者： Xuejun C. Zhang Lei Han national laboratory of macromolecules National Center of Protein Science- Beijing Institute of Biophysics Chinese Academyof Sciences Beijing 100101 China

Integral membrane proteins （MPs） are categorized into two major groups： transmembrane （TM） α-helical bundles and β-barrels （Cymer et al., 2014）. Both types of structures permit the backbones of their peptides to fulfill their hydro- gen-bonding potential in a lipid-bilayer environment. The thermal stability of a typical β-barrel MP is usually much higher than that of a helical MP. Thus, β-barrel MPs are able to withstand near boiling-temperatures during purification （Han et al., 2016）, compared with the typical melting tem- peratures of 50℃ or lower for a-helical TM proteins. In fact, unfolding a β-barrel MP in a single-molecule assay typically requires multiple steps, each of which requires a force of 100-300 pN （Thoma et al., 2015）. Considering the thickness of the membrane as well as the multiple steps, unfolding one mole of β-barrel MP molecules would require -103 kJ of energy （equivalent to 400 RT or energy from hydrolyzing 20-30 moles of ATP）. Such high thermal stability is consid- ered to be the sole source of the energy that drives the folding of β-barrel MPs （Fleming, 2015）.China

关键词： membrane proteins categorized

Thermodynamics of ABC transporters

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Protein & Cell 2016年第1期7卷 17-27页

作者： Xuejun C. Zhang Lei Han Yan Zhao national laboratory of macromolecules National Center of Protein Science-Beijing Institute of Biophysics Chinese Academyof Sciences Beijing 100101 China

ABC transporters form the largest of all transporter families, and their structural study has made tremen- dous progress over recent years. However, despite such advances, the precise mechanisms that determine the energy-coupling between ATP hydrolysis and the con- formational changes following substrate binding remain to be elucidated. Here, we present our thermodynamic analysis for both ABC importers and exporters, and introduce the two new concepts of differential-binding energy and elastic conformational energy into the dis- cussion. We hope that the structural analysis of ABC transporters will henceforth take thermodynamic aspects of transport mechanisms into account as well.

关键词： ABC transporters differential-bindingenergy energy-coupling elastic conformational energy

How does transmembrane electrochemical potential drive the rotation of Fo motor in an ATP synthase？

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Protein & Cell 2015年第11期6卷 784-791页

作者： Xuejun C. Zhang Min Liu Yan Zhao national laboratory of macromolecules National Center of Protein Science-Beijing Institute of Biophysics Chinese Academyof Sciences Beijing 100101 China

ATP synthesis via Fi/Fo-like ATP synthases is a universal energy An essential step of this process is to Utilize the free energy of the transmembrane electrochemical potential of cations, such as protons or sodium ion... 详细信息

关键词： synthase research history filled landmark discoveries

GPCR activation:protonation and membrane potential

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Protein & Cell 2013年第10期4卷 747-760页

作者： Xuejun C.Zhang Kening Sun Laixing Zhang Xuemei Li Can Cao national laboratory of macromolecules National Center for Protein Science-BeijingInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China

GPCR proteins represent the largest family of signaling membrane proteins in eukaryotic *** importance to basic cell biology,human diseases,and pharma-ceutical interventions is well *** crystal structures of GPCR proteins have been reported in both active and inactive *** data indicate that agonist binding alone is not suffi cient to trigger the conformational change of GPCRs necessary for binding of downstream G-proteins,yet other essential factors re-main *** on analysis of available GPCR crystal structures,we identifi ed a potential conformational switch around the conserved Asp2.50,which consistently shows distinct conformations between inactive and active *** the structural information with the current literature,we propose an energy-coupling mechanism,in which the interaction between a charge change of the GPCR protein and the membrane potential of the living cell plays a key role for GPCR activation.

关键词： GPCR membrane potential protonation ac-tivation

Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

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Neural Regeneration Research 2025年第1期20卷 93-106页

作者： Yujie Yang Xinyi Li Jiaying Lu Jingjie Ge Mingjia Chen Ruixin Yao Mei Tian Jian Wang Fengtao Liu Chuantao Zuo Key laboratory of Arrhythmias Ministry of EducationDepartment of Medical GeneticsShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Department of Neurology National Research Center for Aging and MedicineNational Center for Neurological Disordersand State Key Laboratory of Medical NeurobiologyHuashan HospitalFudan UniversityShanghaiChina Department of Nuclear Medicine&PET Center National Center for Neurological Disordersand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghaiChina International Human Phenome Institutes(Shanghai) ShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of *** review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest *** conducted a thorough literature search using reputable databases such as PubMed and Web of *** criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical *** findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting ***,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo *** validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic *** summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

关键词： aromatic amino acid decarboxylase brain imaging dopamine transporter Parkinson’s disease parkinsonism positron emission tomography presynaptic dopaminergic function vesicle monoamine transporter type 2

Highly mass activity electrocatalysts with ultralow Pt loading on carbon black for hydrogen evolution reaction

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 182-190页

作者： Shaorou Ke Yajing Zhao Xin Min Yanghong Li Ruiyu Mi Yangai Liu Xiaowen Wu Minghao Fang Zhaohui Huang Engineering Research Center of Ministry of Education for Geological Carbon Storage and Low Carbon Utilization of Resources Beijing Key Laboratory of Materials Utilization of Nonmetallic Minerals and Solid WastersNational Laboratory of Mineral MaterialsSchool of Materials Science and TechnologyChina University of Geosciences(Beijing)Beijing 100083China

Pt-based nanocatalysts offer excellent prospects for various ***,the low loading of Pt with excellent performance for efficient and stable nanocatalysts still presents a considerable *** this study,nanocatalysts with ultralow Pt content,excellent performance,and carbon black as support were prepared through in-situ ***~2-nm particles uniformly and stably dispersed on carbon black because of the strong s-p-d orbital hybridizations between carbon black and Pt,which suppressed the agglomeration of Pt *** unique structure is beneficial for the hydrogen evolution *** catalysts exhibited remarkable catalytic activity for hydrogen evolution reaction,exhibiting a potential of 100 mV at 100 mA·cm^(-2),which is comparable to those of commercial Pt/C *** activity(1.61 A/mg)was four times that of a commercial Pt/C catalyst(0.37 A/mg).The ultralow Pt loading(6.84wt%)paves the way for the development of next-generation electrocatalysts.

关键词： hydrogen evolution reaction ultralow platinum in-situ synthesis ultrasound