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Anti-osteosarcoma trimodal synergistic therapy using NiFe-LDH and MXene nanocomposite for enhanced biocompatibility and efficacy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1329-1344页

作者： Yani Xu Lan Yang Min li Haozhou Shu na jia Yunzhen Gao Rongying Shi Xiaojia Yang Zhirong Zhang ling Zhang Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041China Med-X Center for Materials College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China

Osteosarcoma is usually resistant to immunotherapy and,thus primarily relies on surgical resection and high-dosage chemotherapy.Unfortunately,less invasive or toxic therapies such as photothermal therapy(PTT)and chemodynamic therapy(CDT)generally failed to show satisfactory outcomes.Adequate multimodal therapies with proper safety profiles may provide better solutions for osteosarcoma.Herein,a simple nanocomposite that synergistically combines CDT,PTT,and chemotherapy for osteosarcoma treatment was fabricated.In this composite,small 2D Ni Fe-LDH flakes were processed into 3D hollow nanospheres via template methods to encapsulate 5-Fluorouracil(5-FU)with high loading capacity.The nanospheres were then adsorbed onto larger 2D Ti3C2MXene monolayers and finally shielded by bovine serum albumin(BSA)to form 5-FU@Ni Fe-LDH/Ti3C2/BSA nanoplatforms(5NiTiB).Both in vitro and in vivo data demonstrated that the 5-FU induced chemotherapy,Ni Fe-LDH driven chemodynamic effects,and MXene-based photothermal killing collectively exhibited a synergistic“all-in-one”anti-tumor effect.5NiTiB improved tumor suppression rate fromnanotherapeutic platform achieved higher therapeutic efficacy with a lower agent dose,thereby minimizing side effects.Moreover,the composite is simple to produce,enabling the fine-tuning of dosages to suit different requirements.Thus,the platform is versatile and efficient,with potential for further development.

关键词： Osteosarcoma NiFe-LDH MXene Chemodynamic therapy Photothermal therapy Chemotherapy 5-Fluorouracil nanocomposite

Anti-OX40 Antibody Combined with HBc VLPs Delays Tumor Growth in a Mouse Colon Cancer Model

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Biomedical and Environmental Sciences 2024年第2期37卷 187-195页

作者： liU jia jia SU Qiu Dong YI Yao SHEN li Ping BI Sheng li national Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206China

Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.

关键词： Anti-OX40 antibody Hepatitis B core virus-like particles Tumor Combination therapy

Structural engineered living materials

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nano Research 2024年第2期17卷 715-733页

作者： Yang Geng Zian jia ling li 635 Prices Fork Road Department of Mechanical EngineeringVirginia Polytechnic Institute and State UniversityBlacksburg VA24061USA

Biological structural materials not only exhibit remarkable mechanical properties but also often embody dynamic characteristics such as environmental responsiveness,autonomy,and self-healing,which are difficult to achieve in conventional engineering materials.By merging materials science,synthetic biology,and other disciplines,engineered living materials(ELMs)provide a promising solution to combine living organisms with abiotic components,thus facilitating the construction of functional“living”materials.like natural materials,ELMs possess vitality and hold immense application potential in areas such as medicine,electronics,and construction,captivating increasing research attention recently.As an emerging branch of ELMs,structural ELMs aim to mimic living biological structural materials by achieving desired mechanical performance while maintaining important“living”characteristics.Here we summarize the recent progress and provide our perspectives for this emerging research area.We first summarize the superiority of structural ELMs by reviewing biological structural materials and biomimetic material design strategies.Subsequently,we provide a systematic discussion on the definition and classifications of structural ELMs,their mechanical performance,and physiological behaviors.Finally,we summarize some critical challenges faced by structural ELMs and highlight directions of future development.We hope this review article can provide a timely summary of the state of the art and relevant perspectives for future development of structural ELMs.

关键词： structural materials engineered living materials(ELMs) structural ELMs composites mechanical properties

Constrained reinforcement learning with statewise projection: a control barrier function approach

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Science China(Information Sciences) 2024年第3期67卷 136-154页

作者： Xinze JIN Kuo li Qingshan jia Department of Automation Tsinghua University

Safety is a critical issue for reinforcement learning(RL), as it may be risky for some actual applications if the learning process involves unsafe exploration. Instead of formulating constraints as expectationbased in constrained RL, considering statewise safety in constrained RL is more meaningful. This work aims to address the issue of safe projection in RL by introducing a control barrier function that inherently learns a safe policy through a set certificate. We seek to analyze some theoretical properties of safe projection in the learning process, including convergence and performance bound, and extend the discussion into ensembles and guided controllers. Moreover, we approach analytical solutions for deterministic and stochastic system dynamics. Experimental results in different tasks show that the proposed method achieves better effects in terms of both performance and safety.

关键词： reinforcement learning safe projection control barrier function

Interconnection of cellular autophagy and endosomal vesicle trafficking and its role in hepatitis B virus replication and release

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Virologica Sinica 2024年第1期39卷 24-30页

作者： jia li Yong lin Xueyu Wang Mengji Lu Institute for Virology University Hospital EssenUniversity of Duisburg-EssenEssen45122Germany Key Laboratory of Molecular Biology of Infectious Diseases(Chinese Ministry of Education) Chongqing Medical UniversityChongqing400016China The Key Laboratory for Diagnosis and Treatment of Infectious Diseases The First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310000China

Hepatitis B virus(HBV)produces and releases various particle types,including complete virions,subviral particles with envelope proteins,and naked capsids.Recent studies demonstrate that HBV exploits distinct intracellular membrane trafficking pathways,including the endosomal vesicle trafficking and autophagy pathway,to assemble and release viral and subviral particles.Herein,we summarize the findings about the distinct roles of autophagy and endosomal membrane trafficking and the interaction of both pathways in HBV replication,assembly,and release.

关键词： Amphisome Autophagy Endosomal vesicle Hepatitis B virus(HBV)

Novel heterozygous USH1C mutation impacts hair cell mechanotransduction and causes progressive hearing loss

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Science Bulletin 2024年第2期69卷 167-172页

作者： Yanyan jia Gaogan jia Luo Guo nan Song Yu-Meng Wang Luoying jiang Yilai Shu Yan Chen Shujia Zhu Huawei li Wenyan li ENT Institute and Otorhinolaryngology Department of Eye&ENT Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceFudan UniversityShanghai 200031China Institutes of Biomedical Sciences Fudan UniversityShanghai 200032China NHC Key Laboratory of Hearing Medicine(Fudan University) Shanghai 200031China The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science Fudan UniversityShanghai 200032China Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology Shanghai 201210China Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China Department of Cardiology and Institute for Developmental and Regenerative Cardiovascular MedicineXinhua Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200092China

Hearing loss is one of the most common sensory disorders worldwide,affecting approximately 466 million people,including 34 million children[1].Genetic mutations accounts for approximately 60%of inherited hearing loss cases[2,3].These genetic changes result in a wide variety of clinical manifestations,ranging from nonsyndromic hearing loss(NSHL)to over 400 syndromes involving hearing loss and from mild adult-onset hearing loss to profound congenital deafness,covering the entire spectrum of Mendelian inheritance.

关键词： mec hearing approximate

Impact of next-generation sequencing on antimicrobial treatment in immunocompromised adults with suspected infections

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World Journal of Emergency Medicine 2024年第2期15卷 105-110页

作者： jia li jiazhen Luo Tao Hu ling Cheng Weiwei Shang li Yan Department of Intensive Care Unit Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Emergency Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Tongji Medical College Huazhong University of Science and TechnologyWuhan 430030China Department of Geriatrics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

BACKGROUND:Prompt pathogen identification can have a substantial impact on the optimization of antimicrobial treatment.The objective of the study was to assess the diagnostic value of next-generation sequencing(NGS)for identifying pathogen and its clinical impact on antimicrobial intervention in immunocompromised patients with suspected infections.METHODS:This was a retrospective study.Between January and August 2020,47 adult immunocompromised patients underwent NGS testing under the following clinical conditions:1)prolonged fever and negative conventional cultures;2)new-onset fever despite empiric antimicrobial treatment;and 3)afebrile with suspected infections on imaging.Clinical data,including conventional microbial test results and antimicrobial treatment before and after NGS,were collected.Data were analyzed according to documented changes in antimicrobial treatment(escalated,no change,or deescalated)after the NGS results.RESULTS:The median time from hospitalization to NGS sampling was 19 d.Clinically relevant pathogens were detected via NGS in 61.7% of patients(29/47),more than half of whom suffered from fungemia(n=17),resulting in an antimicrobial escalation in 53.2% of patients(25/47)and antimicrobial de-escalation in 0.2% of patients(1/47).Antimicrobial changes were mostly due to the identification of fastidious organisms such as Legionella,Pneumocystis jirovecii,and Candida.In the remaining three cases,NGS detected clinically relevant pathogens also detected by conventional cultures a few days later.The antimicrobial treatment was subsequently adjusted according to the susceptibility test results.Overall,NGS changed antimicrobial management in 55.3%(26/47)of patients,and conventional culture detected clinically relevant pathogens in 14.9% of the patients(7/47).CONCLUSION:With its rapid identification and high sensitivity,NGS could be a promising tool for identifying relevant pathogens and enabling rapid appropriate treatment in immunocompromised patients with suspected infections.

关键词： Immunocompromised patients Next-generation sequencing Antimicrobial management

Electrochemical reconstruction of non-noble metal-based heterostructure nanorod arrays electrodes for highly stable anion exchange membrane seawater electrolysis

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Journal of Energy Chemistry 2024年第4期91卷 370-382页

作者： Jingchen na Hongmei Yu Senyuan jia Jun Chi Kaiqiu Lv Tongzhou li Yun Zhao Yutong Zhao Haitao Zhang Zhigang Shao Fuel Cell System and Engineering Laboratory Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023LiaoningChina University of Chinese Academy of Sciences Beijing 100049China

Direct seawater electrolysis for hydrogen production has been regarded as a viable route to utilize surplus renewable energy and address the climate crisis.However,the harsh electrochemical environment of seawater,particularly the presence of aggressive Cl^(-),has been proven to be prone to parasitic chloride ion oxidation and corrosion reactions,thus restricting seawater electrolyzer lifetime.Herein,hierarchical structure(Ni,Fe)O(OH)@NiCoS nanorod arrays(nas)catalysts with heterointerfaces and localized oxygen vacancies were synthesized at nickel foam substrates via the combination of hydrothermal and annealing methods to boost seawater dissociation.The hiera rchical nanostructure of NiCoS nas enhanced electrode charge transfer rate and active surface area to accelerate oxygen evolution reaction(OER)and generated sulfate gradient layers to repulsive aggressive Cl^(-).The fabricated heterostructure and vacancies of(Ni,Fe)O(OH)tuned catalyst electronic structure into an electrophilic state to enhance the binding affinity of hydroxyl intermediates and facilitate the structural transformation into amorphousγ-NiFeOOH for promoting OER.Furthermore,through operando electrochemistry techniques,we found that theγ-NiFeOOH possessing an unsaturated coordination environment and lattice-oxygen-participated OER mechanism can minimize electrode Cl^(-)corrosion enabled by stabilizing the adsorption of OH*intermediates,making it one of the best OER catalysts in the seawater medium reported to date.Consequently,these catalysts can deliver current densities of 100 and 500 mA cm-2for boosting OER at minimal overpotentials of 245and 316 mV,respectively,and thus prevent chloride ion oxidation simultaneously.Impressively,a highly stable anion exchange membrane(AEM)seawater electrolyzer based on the non-noble metal heterostructure electrodes reached a record low degradation rate under 100μV h-1at constant industrial current densities of 400 and 600 mA cm-2over 300 h,which exhibits a promising future for the nonprecious and stable AEMWE

关键词： Direct seawater electrolysis Anion exchange membrane water electrolysis Oxygen evolution reaction Oxygen vacancies Operando electrochemistry techniques

A Review on Flow Boiling of the Fluid with Lower Boiling Point in Micro-Channels

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Journal of Thermal Science 2024年第1期33卷 1-17页

作者： ZHANG Zhiqiang jia li DANG Chao Beijing Key Laboratory of Flow and Heat Transfer of Phase Changing in Micro and Small Scale School of MechanicalElectronic and Control EngineeringBeijing Jiaotong UniversityBeijing 100044China

With the advancement of micro machining technology,the high-heat-flux removal from miniature electronic devices and components has become an attractive topic.Flow boiling in micro-channels is an optimal form of heat transfer and has been widely employed in high-heat-flux cooling applications.This comprehensively-reviewed article focused on the available recent literatures of experimental investigation regarding the flow boiling heat transfer and unstable behaviors of the fluid with lower boiling point in micro-channels.The thermal-fluid characteristics and potential heat transfer mechanisms of low-boiling-point fluids flow boiling in different narrow passages were summarized and discussed.The literatures regarding the pressure drop and occurrence of the unstable phenomena existing in two-phase flow boiling process were also discussed.The emphasis was given to the heat transfer enhancement methods as well as instability elimination,and various methods such as modification of surface and channel flow geometries were considered.Some future researches in the field of micro-scale flow boiling were suggested.

关键词： flow boiling lower boiling point fluids mini/micro-channels instabilities enhancement suppression