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The Era of Immune Checkpoint Therapy: From Cancer to Viral Infection——A Mini Comment on the 2018 Medicine Nobel Prize

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Virologica Sinica 2018年第6期33卷 467-471页

作者： Jia Liu Wen Pan dongliang yang Department of Infectious Diseases Union Hospital TongjiMedical College Huazhong University of Science and Technology

The 2018 Medicine Nobel Prize was awarded jointly to two immunologists, James P. Allison at the University of Texas MD Anderson Cancer Center in Houston and Tasuku Honjo at Kyoto University in Japan, who pioneered a n... 详细信息

关键词： PD In The Era of Immune Checkpoint Therapy A Mini Comment on the 2018 Medicine Nobel Prize

Contribution of Toll-like receptors to the control of hepatitis B virus infection by initiating antiviral innate responses and promoting specific adaptive immune responses

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Cellular & Molecular Immunology 2015年第3期12卷 273-282页

作者： Zhiyong Ma Ejuan Zhang dongliang yang Mengji Lu Institute of Virology University Hospital Essen University of Duisburg-Essen Essen Germany Department of Infectious Diseases Zhongnan Hospital ofWuhan University Wuhan China Wuhan Institute of Virology Chinese Academy of Sciences Wuhan China Department of Infectious Diseases Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

It is well accepted that adaptive immunity plays a key role in the control of hepatitis B virus （HBV） infection. In contrast, the contribution of innate immunity has only received attention in recent years. Toll-like receptors （TLRs） sense pathogen-associated molecule patterns and activate antiviral mechanisms, including intracellular antiviral pathways and the production of antiviral effector interferons （IFNs） and pro-inflammatory cytokines. Experimental results from in vitroand in vivo models have demonstrated that TLRs mediate the activation of cellular signaling pathways and the production of antiviral cytokines, resulting in a suppression of HBV replication. However, HBV infection is associated with downregulation of TLR expression on host cells and blockade of the activation of downstream signaling pathways. In primary HBV infection, TLRs may slow down HBV infection, but contribute only indirectly to viral clearance. Importantly, TLRs may modulate HBV-specific T- and B-cell responses in vivo, which are essential for the termination of HBV infection. Thus, TLR agonists are promising candidates to act as immunomodulators for the treatment of chronic HBV infection. Antiviral treatment may recover TLR expression and function in chronic HBV infection and may increase the efficacy of therapeutic approaches based on TLR activation. A combined therapeutic strategy with antiviral treatment and TLR activation could facilitate the restoration of HBV-specific immune responses and thereby, achieve viral clearance in chronically infected HBV patients.

关键词： Hepatitis B virus Toll like receptor Innate immune response Adaptive immune response

Rapid Recovery in COVID-19 Patients with Chronic Hepatitis B Virus Infection Treated with Tenofovir Disoproxil Fumarate

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Journal of Clinical and Translational Hepatology 2021年第2期9卷 269-273页

作者： Xiliu Chen Di Liu dongliang yang Xin Zheng Department of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina Joint International Laboratory of Infection and Immunity Huazhong University of Science and TechnologyWuhanHubeiChina Pritzker School of Medicine University of ChicagoChicagoILUSA

The coronavirus disease 2019(COVID-19)pandemic continues *** report here two cases of chronic hepatitis B patients with acute respiratory syndrome coronavirus 2 infection treated with tenofovir disoproxil fumarate who demonstrated a favorable *** report adds some evidence that concurrent HBV infection may not worsen COVID-19 infection and tenofovir disoproxil fumarate treatment may have partial positive effect on COVID-19 rapid recovery.

关键词： COVID-19 SARS-CoV-2 Chronic hepatitis B Tenofovir disoproxil fumarate

Diketopyrrolopyrrole-derived organic small molecular dyes for tumor phototheranostics

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Chinese Chemical Letters 2022年第4期33卷 1681-1692页

作者： Qianli Ma Xu Sun Weili Wang dongliang yang Cangjie yang Qian Shen Jinjun Shao Key Laboratory of Flexible Electronics(KLOFE)&Institute of Advanced Materials(IAM) Nanjing Tech University(NanjingTech)Nanjing 211800China Department of Chemistry Boston CollegeChestnut HillMassachusetts 02467United States

Cancer is one of the leading causes of human death around the world. Phototherapy, including photodynamic therapy(PDT) and photothermal therapy(PTT), is an emerging light-triggered cancer treatment and shows the advantages of non-invasiveness and low side effects. The design and preparation of efficient phototherapeutic agents are of great significance for phototherapy. Diketopyrrolopyrrole(DPP) is a small molecular organic dye featuring outstanding photophysical properties, facile tuning of structures and properties, and excellent photostability;thus, phototherapeutic agents based on organic small molecular DPP derivatives have attracted significant research attention for not only phototherapy but also photodiagnosis of fluorescence imaging(FLI) and photoacoustic imaging(PAI). This review summarizes the recent progress of various DPP-based organic small molecules on phototheranostics during the last five years. The molecular structure design and their phototheranostics performances are discussed in detail,as will be of great help for further creation of DPP-based phototheranostics.

关键词： Diketopyrrolopyrrole Phototherapy Photodynamic Photothermal NIR dye

Near-infrared Aza-BODIPY Dyes Through Molecular Surgery for Enhanced Photothermal and Photodynamic Antibacterial Therapy

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Chemical Research in Chinese Universities 2021年第4期37卷 951-959页

作者： YU Qing HUANG Xuan ZHANG Tian WANG Weili yang dongliang SHAO Jinjun DONG Xiaochen Key Laboratory of Flexible Electronics(KLOFE)&Institute of Advanced Materials(IAM) Nanjing Tech UniversityNanjing210009P.R.China

The widespread use of high-dose antibiotics will not only lead to the rapid acquisition of antibiotic resistance and increased incidence of drug-resistant bacterial infections, but also produce toxic side effects on normal tissues. Herein, two near-infrared dyes BDP-4PTZ and BDP-4DPA were synthesized, and the electron donors of diphenylamine and phenothiazine with the only difference of sulphur(S)-lock between the two phenyl rings were introduced onto the electron acceptor aza-dipyrromethene boron difluoride(aza-BODIPY) through molecular surgery. Through co-precipitation into nanoparticles(NPs), BDP-4PTZ NPs and BDP-4DPA NPs were fabricated with good biocompatibility. Upon 660 nm photoirradiation, BDP-4PTZ NPs and BDP-4DPA NPs showed excellent photothermal conversion efficiency(43% and 50%, respectively) and reactive oxygen species(ROS) production performance(ca. 3.6 and 6 times higher than that of indocyanine green, respectively). In vitro antibacterial experiments indicated that both NPs could effectively destroy the bacteria’s membrane to eradicate drug-resistant bacteria. Furthermore, the bacterial abscess was effectively eliminated after treatment with BDP-4DPA NPs under 660 nm photoirradiation without adverse effects. Thus, through molecular surgery, BDP-4DPA without the S-lock demonstrates synergistic photothermal and photodynamic antimicrobial activities, which is promising for further molecular design towards effective neo-antimicrobial phototherapy.

关键词： Aza-dipyrromethene boron difluoride(aza-BODIPY) Photothermal therapy Photodynamic therapy Photosensitizer Antibacterial therapy

Gut Microbiota Dysbiosis Strengthens Kupffer Cell-mediated Hepatitis B Virus Persistence through Inducing Endotoxemia in Mice

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Journal of Clinical and Translational Hepatology 2022年第1期10卷 17-25页

作者： Wenqing Zhou Jinzhuo Luo Xiaohong Xie Shangqing yang Dan Zhu Hongming Huang dongliang yang Jia Liu Department of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina

Background and Aims:Change of gut microbiota com-position is associated with the outcome of hepatitis B virus(HBV)infection,yet the related mechanisms are not fully *** objective of this study was to investigate the immune mechanism associated with HBV persistence induced by gut microbiota ***:C57BL/6 mice were sterilized for gut-microbiota by using an antibi-otic(ABX)mixture protocol,and were monitored for their serum endotoxin(lipopolysaccharide[LPS])*** HBV-replicating mouse model was established by performing HBV-expressing plasmid pAAV/HBV1.2 hydrodynamic injec-tion(HDI)with or without LPS,and was monitored for se-rum hepatitis B surface antigen,hepatitis B e antigen,HBV DNA,and cytokine *** cells(KCs)were purified from antibiotic-treated mice and HBV-replicating mice and analyzed for IL-10 production and T cell suppression ***:ABX treatment resulted in increased serum LPS levels in *** KCs separated from both ABX-treated and LPS-treated HBV-replicating mice showed significantly increased IL-10 production and enhanced ability to suppress IFN-γproduction of TCR-activated T cells than the KCs sep-arated from their counterpart *** of pAAV/HBV1.2 in combination with LPS in mice led to a delayed HBV clear-ance and early elevation of serum IL-10 levels compared to pAAV/HBV1.2 HDI ***,IL-10 function blockade or KC depletion led to accelerated HBV clearance in LPS-treated HBV-replicating ***:Our results suggest that dysbiosis of the gut microbiota in mice leads to endotoxemia,which induces KC IL-10 production and strengthens KC-mediated T cell suppression,and thus fa-cilitates HBV persistence.

关键词： Chronic hepatitis B Gut microbiota Kupffer cells T cell IL-10

Van der Waals materials-based floating gate memory for neuromorphic computing

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Chip 2023年第4期2卷 27-44页

作者： Qianyu Zhang Zirui Zhang Ce Li Renjing Xu dongliang yang Linfeng Sun Centre for Quantum Physics Key Laboratory of Advanced Optoelectronic Quan-tum Architecture and Measurement(MOE)School of PhysicsBeijing Institute of TechnologyBeijing 100081China Beijing Key Lab of Nanophotonics&Ultra-fine Optoelectronic Systems School of PhysicsBeijing Institute of TechnologyBeijing 100081China Thrust of Microelectronics of Function Hub The Hong Kong University of Science and Technology(Guangzhou)Guangzhou 511400China

With the advent of the“Big Data Era”,improving data storage density and computation speed has become more and more urgent due to the rapid growth in different types of *** memory with a floating gate(FG)structure is attracting great attention owing to its advantages of miniaturization,low power consumption and reli-able data storage,which is very effective in solving the problems of large data capacity and high integration ***,the FG memory with charge storage principle can simulate synaptic plasticity perfectly,breaking the traditional von Neumann computing ar-chitecture and can be used as an artificial synapse for neuromorphic computations inspired by the human *** many candidate materials for manufacturing devices,van der Waals(vdW)materials have attracted widespread attention due to their atomic thickness,high mobility,and sustainable miniaturization *** to the arbitrary stacking ability,vdW heterostructure combines rich physics and potential 3D integration,opening up various possibilities for new functional integrated devices with low power consumption and flexible *** paper provides a comprehensive review of memory devices based on vdW materials with FG structure,including the working principles and typical structures of FG structure devices,with a focus on the introduction of various highperformance FG memories and their versatile applications in neuro-morphic ***,the challenges of neuromorphic devices based on FG structures are also *** review will shed light on the design and fabrication of vdW material-based memory devices with FG engineering,helping to promote the development of practical and promising neuromorphic computing.

关键词： Van der Waals materials Floating gate memory Memristor Neuromorphic computing

A Crowned Killer’s Ré sumeé: Genome, Structure, Receptors, and Origin of SARS-CoV-2

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Virologica Sinica 2020年第6期35卷 673-684页

作者： Shichuan Wang Mirko Trilling Kathrin Sutter Ulf Dittmer Mengji Lu Xin Zheng dongliang yang Jia Liu Department of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Institute for Virology University Hospital of EssenUniversity of Duisburg-EssenEssen 45147Germany Joint International Laboratory of Infection and Immunity Huazhong University of Science and TechnologyWuhan 430022China

The recent emergence and rapid global spread of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) pose an unprecedented medical and socioeconomic crisis, and the disease caused by it, Coronavirus disease 2019(COVID-19),was declared a pandemic by the World Health Organization(WHO) on March 11, 2020. Chinese scientists and physicians rapidly identified the causative pathogen, which turned out to be a novel betacoronavirus with high sequence similarities to bat and pangolin coronaviruses. The scientific community has ignited tremendous efforts to unravel the biological underpinning of SARS-CoV-2, which constitutes the foundation for therapy and vaccine development strategies. Here, we summarize the current state of knowledge on the genome, structure, receptor, and origin of SARS-CoV-2.

关键词： Coronavirus Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) Coronavirus disease 2019(COVID-19) Genome Structure Receptor Origin

Orthogonal Aza-BODIPY–BODIPY dyad as heavy-atom free photosensitizer for photo-initiated antibacterial therapy

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Journal of Innovative Optical Health Sciences 2022年第1期15卷 128-140页

作者： dongliang yang Liguo Sun Lei Xue Xiaorui Wang Yanling Hu Jinjun Shao Ling Fu Xiaochen Dong Key Laboratory of Flexible Electronics(KLOFE)and Institute of Advanced Materials(IAM)School of Physical and Mathematical Sciences Nanjing Tech University(NanjingTech)Nanjing 211816 P.R.China Department of Radiology Binzhou Medical University Hospital Yantai 264100 P.R.China

Photodynamic antibacterial therapy shows great potential in bacterial infection and the reactive oxygen species(ROS)production of the photosensitizers is crucial for the therapeutic e®*** heavy atoms is a common strategy to enhance photodynamic performance,while dark toxicity can be induced to impede further clinical ***,a novel halogen-free photosensitizer Aza-BODIPY-BODIPY dyad NDB with an orthogonal molecular conguration was synthesized for photodynamic antibacterial *** absorption and emission peaks of NDB photosensitizer in toluene were observed at 703 nm and 744 nm,***°uorescence(FL)lifetime was measured to be 2.8 ns in *** 730 nm laser illumination,the ROS generation capability of NDB was 3-fold higher than that of the commercial *** nanoprecipitation,NDB NPs presented the advantages of high photothermal conversion e±ciency(39.1%),good photostability,and excellent *** importantly,in vitro antibacterial assay conrmed that the ROS and the heat generated by NDB NPs could extirpate methicillin-resistant *** e®ectively upon exposure to 730 nm laser,suggesting the potential application of NDB NPs in photo-initiated antibacterial therapy.

关键词： Photosensitizer photodynamic therapy antibacterial therapy.