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Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第2期14卷 854-868页

作者： Yunzhu Lin xiang Wang Shi He Zhongxin Duan Yunchu zhang Xiaodong Sun Yuzhu Hu Yuanyuan zhang Zhiyong qian xiang Gao Zhirong zhang Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of EducationWest China School of PharmacySichuan UniversityChengdu 610041China Department of Pharmacy Evidence-based Pharmacy CenterWest China Second University HospitalKey Laboratory of Birth Defects and Related Diseases of Women and ChildrenSichuan UniversityChengdu 610041China Department of Neurosurgery and Institute of Neurosurgery State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China Department of Radiation Oncology State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China West China School of Basic Medical Sciences&Forensic Medicine Sichuan UniversityChengdu 610041China

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor(i PDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of p IL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation,macrophage polarization and DC maturation. The F-DPC/p IL-12/i PDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/p IL-12/i PDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

关键词： IL-12encodinggene Checkpointblocker Nanoparticles Targeted delivery Tumormicroenvironment Immune escape Ovarian cancer Immunotherapy

Metal-organic framework hybrid materials of ZIF-8/RGO for immobilization of D-amino acid dehydrogenase

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Nano Research 2024年第1期17卷 290-296页

作者： Hangbin Lei qian zhang Xiaoyan xiang Liang Jiang Shiyan Wang Lingxuan Duan Shizhen Wang Department of Chemical and Biochemical Engineering College of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005China Xiamen Key Laboratory of Synthetic Biotechnology Xiamen UniversityXiamen 361005China

Immobilization of D-amino acid dehydrogenase(DAADH)by the assembly of peptide linker was studied for the biosynthesis of Dphenylalanine.Hybrid material of zeolitic imidazolate framework-8(ZIF-8)combined with reduced graphene oxide(RGO)was applied for the immobilization of DAADH from Ureibacillus thermosphaericus.The recovery rate of DAADH/ZIF-8/RGO was 165.6%.DAADH/ZIF-8/RGO remained 53.4%of its initial activity at 50°C for 10 h while the free enzyme was inactivated.DAADH/ZIF-8/RGO maintained 70.5%activity in hyperalkaline solution with pH 12.Kinetic parameters indicated that DAADH/ZIF-8/RGO had greater affinity of phenylpyruvate as V_(max)/K_(m)of DAADH/ZIF-8/RGO was 1.27-fold than free enzyme.After seven recycles,the activity of DAADH/ZIF-8/RGO remained 64.3%.Furthermore,one-step separation and in situ immobilization of DAADH by ZIF-8/RGO/Ni was carried out with 1.5-fold activity enhancement.Combining peptide linker and metal-organic framework(MOF)immobilization,thermostability and activity of the immobilized DAADH were significantly improved.

关键词： D-Amino acid dehydrogenase immobilization metal-organic frameworks zeolitic imidazolate framework-8(ZIF-8) reduced graphene oxide

Effects of traditional Chinese medicine on treatment outcomes in severe COVID-19 patients:a single-centre study

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Chinese Journal of Natural Medicines 2024年第1期22卷 89-96页

作者： XIAO Yongjiu LI Binbin LIU Chang HUANG Xiuyu MA Ling qian Zhirong zhang Xiaopeng zhang qian LI Dunqing CAI Xiaoqing YAN xiangyong LUO Shuping xiang Dawei XIAO Kun Emergency Department the 940th Hospital of Jiont Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Scientific Research Center the Seventh Affiliated HospitalSun Yat-sen UniversityShenzhen 518000China School of Medicine Nankai universityTianjin 300000China Department of Cardiology the 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Department of Radiation Oncology Fujian Medical University Union HospitalFuzhou 350000China Department of Traditional Chinese Medicine the 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Department of Geriatric Diseases the Seventh Medical Center of Chinese PLA General HospitalBeijing 100700China Health and Sport Administration Muskingum UniversityOhioanUSA Laboratory of Vaccine and Antibody Engineering Beijing Institute of BiotechnologyBeijing 100071China Department of Pulmonary and Critical Care Medicine the 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation ArmyLanzhou 730050China Center of Pulmonary&Critical Care Medicine Chinese People’s Liberation Army(PLA)General HospitalBeijing 100853China

As the search for effective treatments for COVID-19 continues,the high mortality rate among critically ill patients in Intensive Care Units(ICU)presents a profound challenge.This study explores the potential benefits of traditional Chinese medicine(TCM)as a supplementary treatment for severe COVID-19.A total of 110 critically ill COVID-19 patients at the Intensive Care Unit(ICU)of Vulcan Hill Hospital between Feb.,2020,and April,2020(Wuhan,China)participated in this observational study.All patients received standard supportive care protocols,with a subset of 81 also receiving TCM as an adjunct treatment.Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed.Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group(16 of 81 vs 24 of 29;0.3 vs 2.3 person/month).In the adjusted Cox proportional hazards models,TCM treatment was associated with improved survival odds(P<0.001).Furthermore,the analysis also revealed that TCM treatment could partially mitigate inflammatory responses,as evidenced by the reduced levels of proinflammatory cytokines,and contribute to the recovery of multiple organic functions,thereby potentially increasing the survival rate of critically ill COVID-19 patients.

关键词： COVID-19 Pneumonia Novel coronavirus Critically ill Traditional Chinese medicine Clinical outcome

Pre-combustion mercury removal with co-production of hydrogen via coal electrolysis

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Journal of Environmental Sciences 2024年第2期136卷 382-389页

作者： xiang Lyu Runming Tao Tianyu zhang Chemical and Biomolecular Engineering Department Ohio University165 Stocker CenterAthensOH45701USA Electrification and Energy Infrastructures Division Oak Ridge National LaboratoryOak RidgeTN37831USA Beijing Key Lab for Source Control Technology of Water Pollution College of Environmental Science and EngineeringBeijing Forestry UniversityBeijing 100083China Engineering Research Center for Water Pollution Source Control&Eco-remediation College of Environmental Science and EngineeringBeijing Forestry UniversityBeijing 100083China

Pre-combustion mercury removal via coal electrolysis was performed and investigated on a bench-scale coal electrolytic cell(CEC)systemically,and factorial design was used to determine the effect of different operating conditions(coal particle size,operating temperature,operating cell voltage,and flow rate of slurry)on the percentage of mercury removal,percentage of ash removal,and dry heating value change.The results showed that the operating cell voltage,as well as the interaction between operating cell voltage and coal particle size,are significant factors in the percentage of mercury removal.There is no significant factor in the percentage of ash removal and the dry heating value change,but the coal could be purified while keeping the dry heating value almost constant after electrolysis.A co-product of hydrogen could be produced during coal electrolysis with 50%lower energy consumption compared with water electrolysis.Meanwhile,a mechanism for mercury removal in coal was proposed.The facts indicate that coal electrolysis is a promising method for precombustion mercury removal.

关键词： Pre-combustion mercury removal Coal electrolysis Ash removal Dry heating value Hydrogen production

A novel algorithm for evaluating cement azimuthal density based on perturbation theory in horizontal well

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Petroleum Science 2024年第1期21卷 244-251页

作者： Ji-Lin Fan Feng zhang qian Chen Hao-Chen Song Lu-Yu Zhong Yue-xiang Dai National Key Laboratory of Deep Oil and Gas School of GeosciencesChina University of Petroleum(East China)Qingdao 266580ShandongChina China National Logging Corporation Xi'an 710076ShaanxiChina Sinopec Matrix Corporation Qingdao 266001ShandongChina

Cement density monitoring plays a vital role in evaluating the quality of cementing projects,which is of great significance to the development of oil and gas.However,the presence of inhomogeneous cement distribution and casing eccentricity in horizontal wells often complicates the accurate evaluation of cement azimuthal density.In this regard,this paper proposes an algorithm to calculate the cement azimuthal density in horizontal wells using a multi-detector gamma-ray detection system.The spatial dynamic response functions are simulated to obtain the influence of cement density on gamma-ray counts by the perturbation theory,and the contribution of cement density in six sectors to the gamma-ray recorded by different detectors is obtained by integrating the spatial dynamic response functions.Combined with the relationship between gamma-ray counts and cement density,a multi-parameter calculation equation system is established,and the regularized Newton iteration method is employed to invert casing eccentricity and cement azimuthal density.This approach ensures the stability of the inversion process while simultaneously achieving an accuracy of 0.05 g/cm^(3) for the cement azimuthal density.This accuracy level is ten times higher compared to density accuracy calculated using calibration equations.Overall,this algorithm enhances the accuracy of cement azimuthal density evaluation,provides valuable technical support for the monitoring of cement azimuthal density in the oil and gas industry.

关键词： Cement azimuthal density Perturbation theory Casing eccentricity Spatial dynamic response function Regularized Newton iteration

Dual-ion carrier storage through Mg^(2+) addition for high-energy and long-life zinc-ion hybrid capacitor

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International Journal of Minerals,Metallurgy and Materials 2024年第1期31卷 179-185页

作者： Junjie zhang xiang Wu School of Materials Science and Engineering Shenyang University of TechnologyShenyang 110870China

Cation additives can efficiently enhance the total electrochemical capabilities of zinc-ion hybrid capacitors (ZHCs).However their energy storage mechanisms in zinc-based systems are still under debate.Herein,we modulate the electrolyte and achieve dual-ion storage by adding magnesium ions.And we assemble several Zn//activated carbon devices with different electrolyte concentrations and investigate their electrochemical reaction dynamic behaviors.The zinc-ion capacitor with Mg^(2+)mixed solution delivers 82 mAh·g^(-1)capacity at 1 A·g^(-1) and maintains 91%of the original capacitance after 10000 cycling.It is superior to the other assembled zinc-ion devices in single-component electrolytes.The finding demonstrates that the double-ion storage mechanism enables the superior rate performance and long cycle lifetime of ZHCs.

关键词： zinc-ion hybrid capacitor MgSO_(4) electrolyte rate performance storage mechanism

Boron promoted Fe^(3+)/peracetic acid process for sulfamethazine degradation:Efficiency,role of boron,and identification of the reactive species

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Journal of Environmental Sciences 2024年第1期135卷 72-85页

作者： Yanhong zhang Guangbing Liu Yuzhu Xue Lichun Fu Yawei qian Minhui Hou xiang Li Chen Ling Ying zhang Yuwei Pan Jiangsu Provincial Key Laboratory of Environmental Engineering Jiangsu Provincial Academy of Environmental ScienceNanjing 210036China College of Biology and the Environment Nanjing Forestry UniversityNanjing 210037China School of Iron and Steel Soochow UniversitySuzhou 215000China School of the Environment Nanjing UniversityNanjing 210023China SUMEC Complete Equipment&Engineering Co. LTD.Nanjing 211500China Key Laboratory of Pollution Process and Environmental Criteria Ministry of EducationCollege of Environmental Science and EngineeringNankai UniversityTianjin 300350China School of Environment Key Laboratory for Yellow River and Huai River Water Environmental and Pollution ControlMinistry of EducationHenan Key Laboratory for Environmental Pollution ControlHenan Normal UniversityXinxiang 453007China

In this work,boron(B)was used to promote Fe^(3+)/peracetic acid(Fe^(3+)/PAA)for the degradation of sulfamethazine(SMT).An SMT degradation efficiency of 9.1%was observed in the Fe^(3+)/PAA system over 60 min,which was significantly increased to 99.3%in the B/Fe^(3+)/PAA system over 10 min.The B/Fe^(3+)/PAA process also exhibited superior resistance to natural substances,excellent adaptability to different harmful substances,and good removal of antibiotics in natural fresh water samples.The mechanism of action of boron for Fe^(3+)reduction was determined using scanning electron microscopy(SEM),X-ray photoelectron spectroscopy(XPS),Fourier transform infrared(FT-IR)spectroscopy,density functional theory(DFT)calculations,and electrochemical tests.The dominant role of^(·)OH was confirmed using quenching experiments,electron spin resonance(EPR)spectroscopy,and quantitative tests.Organic radicals(R-O^(·))and Fe(IV)also significantly contribute to the removal of SMT.DFT calculations on the reaction between Fe^(2+)and the PAA were conducted to further determine the contribution from ^(·)OH,R-O^(·),and Fe(IV)from the perspective of thermodynamics and the reaction pathways.Different boron dosages,Fe^(3+)dosages,and initial pH values were also investigated in the B/Fe^(3+)/PAA system to study their effect of SMT removal and the production of the reactive species.Fe(IV)production determined the k_(R-O·+Fe(IV))value suggesting that Fe(IV)may play a more important role than R-O^(·).A comparison of the results with other processes has also proved that the procedure described in this study(B/Fe^(3+)/PAA)is an effective method for the degradation of antibiotics.

关键词： Boron Peracetic acid Sulfamethazine DFT Reactive species

Global patterns and ecological drivers of taxonomic and phylogenetic endemism in angiosperm genera

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Plant Diversity 2024年第2期46卷 149-157页

作者： Hong qian Brent D.Mishler Jian zhang Shenhua qian Research and Collections Center Illinois State Museum1011 East Ash StreetSpringfieldIL 62703USA University and Jepson Herbaria Department of Integrative BiologyUniversity of CaliforniaBerkeleyCA 94720-2465USA Center for Global Change and Complex Ecosystems Zhejiang Tiantong Forest Ecosystem National Observation and Research StationSchool of Ecological and Environmental SciencesEast China Normal UniversityShanghai 200241China Shanghai Institute of Pollution Control and Ecological Security Shanghai 200092China Key Laboratory of the Three Gorges Reservoir Region's Eco-Environment Ministry of EducationChongqing UniversityChongqing 400045China

Endemism of lineages lies at the core of understanding variation in community composition among geographic regions because it reflects how speciation,extinction,and dispersal have influenced current distributions.Here,we investigated geographic patterns and ecological drivers of taxonomic and phylogenetic endemism of angiosperm genera across the world.We identify centers of paleo-endemism and neo-endemism of angiosperm genera,and show that they are mostly located in the Southern Hemisphere in tropical and subtropical regions,particularly in Asia and Australia.Different categories of phylogenetic endemism centers can be differentiated using current climate conditions.Current climate,historical climate change,and geographic variables together explained~80%of global variation in taxonomic and phylogenetic endemism,while 42-46%,1%,and 15%were independently explained by these three types of variables,respectively.Thus our findings show that past climate change,current climate,and geography act together in shaping endemism,which are consistent with the findings of previous studies that higher temperature and topographic heterogeneity promote endemism.Our study showed that many centers of phylogenetic endemism of angiosperms,including regions in Amazonia,Venezuela,and west-central tropical Africa that have not previously been identified as biodiversity hotspots,are missed by taxon-based measures of endemism,indicating the importance of including evolutionary history in biodiversity assessment.

关键词： Angiosperm Current climate Endemism Historical climate change Topographic heterogeneity

Autophagy receptor ZmNBR1 promotes the autophagic degradation of ZmBRI1a and enhances drought tolerance in maize

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Journal of Integrative Plant Biology 2024年第6期66卷 1068-1086页

作者： Yang xiang Guangdong Li qian Li Yingxue Niu Yitian Pan Yuan Cheng xiangli Bian Chongyang Zhao Yuanhong Wang Aying zhang College of Life Sciences Nanjing Agricultural University State Key Laboratory of Crop Genetics & Germplasm Enhancement and Utilization Nanjing Agricultural University Sanya Institute of Nanjing Agricultural University Nanjing Agricultural University

Drought stress is a crucial environmental factor that limits plant growth, development, and productivity.Autophagy of misfolded proteins can help alleviate the damage caused in plants experiencing drought.However, the mechanism of autophagy-mediated drought tolerance in plants remains largely unknown.Here, we cloned the gene for a maize(Zea mays)selective autophagy receptor, NEXT TO BRCA1GENE 1(ZmNBR1), and identified its role in the response to drought stress. We observed that drought stress increased the accumulation of autophagosomes. RNA sequencing and reverse transcriptionquantitative polymerase chain reaction showed that ZmNBR1 is markedly induced by drought stress. ZmNBR1 overexpression enhanced drought tolerance, while its knockdown reduced drought tolerance in maize. Our results established that ZmNBR1 mediates the increase in autophagosomes and autophagic activity under drought stress.ZmNBR1 also affects the expression of genes related to autophagy under drought stress. Moreover, we determined that BRASSINOSTEROID INSENSITIVE1A(ZmBRI1a), a brassinosteroid receptor of the BRI1-like family, interacts with ZmNBR1. Phenotype analysis showed that ZmBRI1a negatively regulates drought tolerance in maize, and genetic analysis indicated that ZmNBR1 acts upstream of ZmBRI1a in regulating drought tolerance. Furthermore, ZmNBR1facilitates the autophagic degradation of ZmBRI1a under drought stress. Taken together, our results reveal that ZmNBR1 regulates the expression of autophagy-related genes, thereby increasing autophagic activity and promoting the autophagic degradation of ZmBRI1a under drought stress, thus enhancing drought tolerance in maize. These findings provide new insights into the autophagy degradation of brassinosteroid signaling components by the autophagy receptor NBR1 under drought stress.

关键词： autophagy receptor drought tolerance Zea mays ZmBRI1a ZmNBR1