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Precore mutation enhances viral replication to facilitate persistent infection especially in HBeAg-negative patients

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Virologica Sinica 2024年第2期39卷 319-330页

作者： Guixin Li Danli Yang Xin Liu Ting Zhang Hui Liu Jun Zou Zimeng Xu Xiangmei Chen Lizhong Dai Hongsong Chen Fengmin Lu peking university People's Hospital Peking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijing International Cooperation Base for Science and Technology on NAFLD DiagnosisBeijing100044China Department of Microbiology and Infectious Disease Center School of Basic Medical SciencesPeking UniversityBeijing100191China Baruch S.Blumberg Institute DoylestownPA18901USA Shenzhen Sanyuansheng biotechnology Co. LtdShenzhen518000China Precision medicine Center of Zhengzhou university Academy of Medical SciencesZhengzhou UniversityZhengzhou450001China peking university-sansure biotech joint laboratory of molecular medicine Sansure Biotech Co.LtdChangsha410205China

Naturally occurred precore(PC,G1896A)and/or basal core promoter(BCP,A1762T/G1764A)mutations are prevalent in chronic HBV-infected patients,especially those under HBeAg-negative status.However,the replicative capacity of HBV with PC/BCP mutations remains ambiguous.Herein,meta-analysis showed that,only under HBeAg-negative status,the serum HBV DNA load in patients with PC mutation was 7.41-fold higher than those without the mutation.Both PC mutation alone and BCPþPC mutations promoted HBV replication in cell and hydrodynamic injection mouse models.In human hepatocyte chimeric mouse model,BCPþPC mutations led to elevated replicative capacity and intrahepatic core protein accumulation.Mechanistically,preC RNA harboring PC mutation could serve as mRNA to express core and P proteins,and such pgRNA-like function favored the maintenance of cccDNA pool under HBeAg-negative status.Additionally,BCPþPC mutations induced more extensive and severe human hepatocyte damage as well as activated endoplasmic reticulum stress and TNF signaling pathway in livers of chimeric mice.This study indicates that HBeAg-negative patients should be monitored on HBV mutations regularly and are expected to receive early antiviral treatment to prevent disease progression.

关键词： Hepatitis B virus Precore mutation Basal core promoter mutations Endoplasmic reticulum stress

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Catalysis by subsurface metal atoms in Al(001) through electron transfer

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National Science Review 2024年第4期11卷 12-13页

作者： Bo Sun Ding Ma Beijing National laboratory for molecular Science New Cornerstone Science Laboratory College of Chemistry and Molecular Engineering Peking University

Heterogeneous catalysis plays a crucial role in the chemical industry, which has evolved from the investigation of chemisorption to an electronic structure[1]. Diverse strategies, such as alloying,doping, and confining, have been applied to enhance the catalytic properties of active sites through electronic modulation. The electron transfer between active sites and substrates profoundly influences catalytic activity [2].

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Strong metal-support interactions between highly dispersed Cu^(+) species and ceria via mix-MOF pyrolysis toward promoted water-gas shift reaction

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Journal of Energy Chemistry 2024年第4期91卷 475-483页

作者： Xiao-Chen Sun Xing-Chi Li Ze-Wei Xie Chen-Yue Yuan De-Jiu Wang Qian Zhang Xiao-Yu Guo Hao Dong Hai-Chao Liu Ya-Wen Zhang Beijing National laboratory for molecular Sciences(BNLMS) State Key Laboratory of Rare Earth Materials Chemistry and ApplicationsPKU-HKU Joint Laboratory in Rare Earth Materials and Bioinorganic ChemistryCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China Beijing National laboratory for molecular Sciences(BNLMS) College of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China Beijing National laboratory for molecular Sciences(BNLMS) State Key Laboratory for Structural Chemistry of Stable and Unstable SpeciesCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China

The modulation of metal-support interfacial interaction is significant but challenging in the design of high-efficiency and high-stability supported catalysts.Here,we report a synthetic strategy to upgrade Cu-CeO_(2)interfacial interaction by the pyrolysis of mixed metal-organic framework(MOF)structure.The obtained highly dispersed Cu/CeO_(2)-MOF catalyst via this strategy was used to catalyze water-gas shift reaction(WGSR),which exhibited high activity of 40.5μmolCOgcat^(-1).s^(-1)at 300℃and high stability of about 120 h.Based on comprehensive studies of electronic structure,pyrolysis strategy has significant effect on enhancing metal-support interaction and then stabilizing interfacial Cu^(+)species under reaction conditions.Abundant Cu^(+)species and generated oxygen vacancies over Cu/CeO_(2)-MOF catalyst played a key role in CO molecule activation and H2O molecule dissociation,respectively.Both collaborated closely and then promoted WGSR catalytic performance in comparison with traditio nal supported catalysts.This study shall offer a robust approach to harvest highly dispersed catalysts with finely-tuned metal-support interactions for stabilizing the most interfacial active metal species in diverse heterogeneous catalytic reactions.

关键词： Cu-based catalyst MOF derivative Water-gas shift reaction Metal-support interaction

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Meningeal lymphatic vasculature,a general target for glioblastoma therapy?

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Fundamental Research 2024年第2期4卷 267-269页

作者： Changping Zhou Han Xu Jincai Luo laboratory of Vascular Biology Institute of Molecular MedicineCollege of Future TechnologyBeijing Key Laboratory of Cardiometabolic Molecular MedicinePeking UniversityBeijing 100871China

Glioblastoma(GBM)causes nearly universal mortality as a result of the failure of conventional therapies including surgical resection,targeted radiation therapy,and chemotherapy.An increasingly important treatment option is combining immunotherapy with other therapies in both preclinical and clinical studies.The central nervous system(CNS)has been historically considered an immune privileged area,but increasing evidence,including the recent rediscovery of meningeal lymphatic vessels(MLVs),has overturned this notion.MLVs are populated by multiple immune cells and connect the CNS to the periphery by draining cerebrospinal fluid with soluble CNS antigens and immune cells into cervical lymph nodes.In the past few years,more and more studies have indicated that MLVs are involved in the regulation of inflammation and the immune response in the pathogenesis of various CNS diseases including GBM.Here,we explore the critical interlinkages between MLVs and GBM therapies including chemotherapy,radiotherapy and immunotherapy,and propose the meningeal lymphatic vasculature as a general target for GBM therapy.

关键词： Meningeal lymphatic vessels Glioblastoma Immunity Vascular endothelial growth factor C Immune modulation

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Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

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Neural Regeneration Research 2024年第8期19卷 1822-1827页

作者： Yuhui Kou Yusong Yuan Qicheng Li Wenyong Xie Hailin Xu Na Han Department of Trauma and Orthopedics Peking University People’s HospitalBeijingChina National Center for Trauma medicine BeijingChina Key laboratory of Trauma and Neural Regeneration(peking university) Ministry of EducationBeijingChina Department of Orthopedics China-Japan Friendship HospitalBeijingChina Department of Central laboratory and Institute of Clinical molecular Biology Peking University People’s HospitalBeijingChina

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration.However,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear.This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury.The functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent assay.Axonal debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian degeneration.Macrophage inflammatory factor expression in different polarization states was detected using a protein chip.The results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 polarization.The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention.Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in vitro.Thus,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

关键词： axonal debris inflammatory factors macrophages neutrophil peptide 1 peripheral nerve injury peripheral nerve regeneration RAW 264.7 cells sciatic nerve Wallerian degeneration

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Ordered Bicontinuous Network Structures Regulated by Orientational Interactions in a Rod-Coil Block Copolymer

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Chinese Journal of Polymer Science 2024年第5期42卷 636-642,I0008页

作者： Xiao-Lin Lyu Shi-Chu Yang An-Qi Xiao Ping-Ping Hou Wei Zhang Hong-Bing Pan Zhi-Hao Shen Xing-He Fan Qi-Feng Zhou Beijing National laboratory for molecular Sciences Key Laboratory of Polymer Chemistry and Physics of Ministry of EducationCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing100871China Key laboratory of Advanced Materials Technologies International(HongKong Macao and Taiwan)Joint Laboratory on Advanced Materials TechnologiesCollege of Materials Science and EngineeringFuzhou UniversityFuzhou350108China

The rich phase behavior of block copolymers(BCPs)has drawn great attention in recent years.However,the double diamond(DD)phase is rarely obtained because of the competition between the minimization of interfacial energy and packing frustration.Here,a rod-coil BCP containing mesogen-jacketed liquid crystalline polymer is designed to acquire ordered bicontinuous network nanostructures.The reduction of internal energy originating from the orientational interaction among the rod blocks can compensate for the free energy penalty of packing frustration to stabilize the DD structure.The resulting BCP can also experience lamellae-to-DD and double gyroid-to-lamellae transitions by changing the annealing temperature.These results make the rod-coil BCP an excellent candidate for the self-assembly of ordered network structures,demonstrating great potential in nanopatterning and metamaterials.

关键词： Block copolymer Rod-coil Ordered bicontinuous phase Double diamond Double gyroid

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The spectrum of rare monogenic diseases in patients with premature coronary artery disease

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中华医学杂志(英文版) 2024年第10期137卷 1246-1248页

作者： Teng Yaqun Du Tian Feng Siqin Tian Ran Liu Yaping Guo Jian Wang Lei Zhang Zhiyu Luan Xiaodong He Shan Zhuang Shengsheng Wang Yifei Zhang Shuyuan Chen Shi Liu Zhenyu Zhang Shuyang Department of Cardiology State Key Laboratory of Complex Severe and Rare disease Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Internal medicine Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Basic Medical Sciences Tsinghua University School of Medicine Beijing China Department of Breast Oncology Sun Yat-sen University Cancer Center Guangzhou Guangdong China McKusick-Zhang Center for Genetic medicine State Key Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic Medicine Peking Union Medical College Beijing China Tsinghua university-peking university joint Center for Life Sciences Beijing China Department of Cardiology Beijing Tsinghua Changgung Hospital Tsinghua University Beijing China Department of Endocrinology Key Laboratory of Endocrinology of National Health Commission Peking Union Medical College Hospital Chinese Research Center for Behavior Medicine in Growth and Development Beijing China

The global burden of premature coronary artery disease (CAD) is increasing among the young population. Premature CAD generally refers to the occurrence of obstructive coronary atherothrombotic lesions in men and women aged <55 years and <65 years, respectively, and particularly in those aged <45 years.[1] The incidence of CAD in the younger population has remained stable or has increased, despite the declining incidence in older adults. Patients with premature CAD have a poor long-term prognosis, experiencing a high rate of recurrent ischemic events, rapid progression to multivessel disease, and frequent premature death.[1] Thus, it is crucial to identify the underlying causes of premature CAD that are distinct from those of age-related CAD and improve patient outcomes through precise diagnosis and treatment.

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Network Pharmacology-Based Dissection of the Bioactive Compounds and Pharmacological Mechanisms of Yiqi Fumai Lyophilized Injection for the Treatment of Heart Failure

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World Journal of Traditional Chinese medicine 2024年第1期10卷 75-82页

作者： Yu-Xi Huang Jing-Jing Fan Lu-Lu Xu Rong Yu Yi Kuang Yue Chai Rui Zheng Xiao-Yu Zhang Hong-Cai Shang Xue Qiao Min Ye State Key laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijingChina Key laboratory of Chinese Internal medicine of Ministry of Education Dongzhimen HospitalBeijing University of Chinese MedicineBeijingChina Yunnan Baiyao International Medical Research Center Peking UniversityBeijingChina Key laboratory of molecular Cardiovascular Sciences of Ministry of Education Peking UniversityBeijingChina

Objective:Yiqi Fumai Lyophilized Injection(YQFM),a Chinese medicine injection,has been widely used for the treatment of cardiovascular diseases,especially heart failure(HF).However,bioactive compounds and underlying mechanisms of YQFM in treating HF remain poorly understood.Materials and Methods:Network pharmacology was employed to investigate the bioactive compounds and mechanisms of YQFM.A compound-target network was constructed to screen bioactive compounds based on contribution index calculation.Then,an adriamycin-induced HF rat model was established to evaluate the cardio-protective effects of YQFM by hematoxylin and eosin staining and enzyme-linked immunosorbent assays.Results:Network pharmacology indicated that YQFM may alleviate HF through 36 compounds and 109 targets.Particularly,ginsenosides Rb1,Rg1,Re,Rf,Rb2,Rh1,schisandrin,and ginsenoside Rc were indicated as the top contributors of YQFM in treating HF.YQFM was predicted to act on multiple targets such as vascular endothelial growth factor A,interleukin-2(IL-2),IL-6,and IL-1β,as well as to regulate signaling pathways such as hypoxia-inducible factor 1,tumor necrosis factor,VEGF,and PI3K-Akt.The pharmacological study suggested that YQFM could attenuate cardiac injury and up-regulate plasma concentrations of VEGFR-1 and NO in HF rats.Ginsenoside Rb1,as the major contributor from network pharmacology analysis,also showed a cardioprotective effect and up-regulation of VEGFR-1 in plasma.Conclusions:Ginsenosides and schisandrin were predicted as the most important contributors to the cardioprotective effect of YQMF.Ginsenoside Rb1 was proved to alleviate HF and increase the plasma concentration of VEGFR-1.

关键词： Contribution index heart failure network pharmacology traditional Chinese medicine yiqi fumai lyophilized injection

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Bionic immunoactivator copresenting autophagy promoting and costimulatory molecules for synergistic cancer immunotherapy

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Nano Research 2024年第3期17卷 1710-1724页

作者： Yiwei Peng Yiliang Yang Zhenzhen Yang Datong Gao Jiajia Li Qi Sun Yitian Du Meng Lin Xianrong Qi Beijing Key laboratory of molecular Pharmaceutics and New Drug Delivery System School of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Immunotherapy has great promise in improving malignant tumor treatment.However,the efficacy of existing strategies is often limited by the immunosuppressive environment.Here,we demonstrate an in situ bionic immunoactivator,PLT-Bec1/DTA-1,with possessed natural advantages of platelets for tumor recruitment and activation,on which DTA-1(CD357 monoclonal antibody)and Bec1 were tethered as combined immune boosters.PLT-Bec1/DTA-1,as a self-triggered release repository,can deliver the pre-tethered Bec1 and DTA-1 deeply through the secretion of platelet microparticles(PMPs),thereby cooperate tacitly and exhibit superiority in immune activation of dendritic cells(DCs)and T cells via autophagy inducibility,coupled with glucocorticoid-induced tumor necrosis factor receptor(GITR)-triggered T_(Reg) suppression,remodeled the immunosuppressive network of tumor microenvironment.PLT-Bec1/DTA-1 promoted antigen presentation and T cell proliferation,and alleviated the low activity state of bone marrow-derived dendritic cells(BMDCs)in tumor suppressive environment.PLT-Bec1/DTA-1 inhibited tumor recurrence(5-and 13-fold lower of control group in tumor volume)and CD8^(+)T/T_(Reg) ratio(6.3-and 8.8-fold vs.control group)in mouse tumor model after intravenous or subcutaneous administration.Also,PLT-Bec1/DTA-1 prevented tumor colonization in lung through in situ immune activation,and was slightly superior to the combined of Bec1 and PD-L1.Our findings highlight the promise of delivering immunostimulatory payloads via bionic carriers,eliciting automatic in situ activation of effector immune cells in tumor microenvironment for tumor eradication.All these results provide promising prospects into the application of immunoactivator in improving cancer synergistic immunotherapy to overcome the bottlenecks in clinic.

关键词： in situ bionic immunoactivator autophagy glucocorticoid-induced tumor necrosis factor receptor(GITR)agonist platelets and platelet microparticles cancer immunotherapy

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Capturing metal clusters at the strong-interaction region to reverse Ostwald ripening

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Science China Materials 2024年第4期67卷 1363-1364页

作者： Shuheng Tian Ding Ma Beijing National laboratory for molecular Sciences New Cornerstone Science LaboratoryCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing 100871China

High-temperature interactions induce sintering of metal nanoparticles(NPs) on heterogeneous catalyst surfaces, leading to reduced surface area and active site loss through Ostwald ripening [1]. This irreversible deactivation necessitates costly catalyst replacement, notably impacting metals like copper in hydrogenation and reforming reactions [2].

关键词： catalyst reforming irreversible

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