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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

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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

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A historical review of hybrid rice breeding

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Journal of Integrative Plant Biology 2024年第3期66卷 532-545页

作者： Xiaoming Zheng Fei Wei Cheng Cheng qian qian State Key Laboratory of Crop Gene Resources and Breeding Institute of Crop SciencesChinese Academy of Agricultural SciencesBeijing 100081China Yazhouwan National Laboratory Sanya City 572024China

The development of germplasm resources and advances in breeding methods have led to steady increases in yield and quality of rice (Oryza sativa L.). Three milestones in the recent history of rice breeding have contributed to these increases: dwarf rice breeding, hybrid rice breeding, and super rice breeding. On the 50th anniversary of the success of three-line hybrid rice,we highlight important scientific discoveries in rice breeding that were made by Chinese scientists and summarize the broader history of the field. We discuss the strategies that could be used in the future to optimize rice breeding further in the hope that China will continue to play a leading role in international rice breeding.

关键词： Chinese experience dwarf breeding hybrid rice breeding super rice breeding

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Unveiling a half-century mystery of molecular bases for three-line hybrid rice breeding system

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Journal of Integrative Plant Biology 2024年第1期66卷 3-6页

作者： Xiaoming Zheng qian qian State Key Laboratory of Crop Gene Resources and Breeding Chinese Academy of Agricultural SciencesBeijing 100081China Yazhouwan National Laboratory No.8 Huanjin RoadYazhou DistrictSanya 572024China

Rice(Oryza sativa L.)isa staplecropforhalf theworld's Ipopulation and an important contributor to world food security.The discovery and application of cytoplasmic male sterility(CMS)and fertility restoration(Rf)genetic materials have allowed the production of three-line hybrid rice(Kim and Zhang,2018),successfully harnessing heterosis in crops.Three major CMS and/or Rf systems are commonly used to produce three-line hybrid rice:Wild Abortive(CMS-WA),Boroll(CMS-BT),and Honglian(CMS-HL).Among these,the CMS-WA system is the most widely employed(Sattari et al.,2007;Chen and Liu,2014;Huang et al.,2014).Several Rf genes from different CMS systems have been cloned in rice,including Rf4 for CMS-WA(Tang et al.,2014),Rf1a and Rf1b for CMS-BT(Wang et al.,2006),Rf5,and Rf6 for CMS-HL(Huet al.,2012;Huang et al.,2015),and Rf19for CMS-FA(Jiang et al.,2022).A molecular mechanism and evolutionary model for the CMS-WA gene WA352c have also been reported(Luo et al.,2013;Tang et al.,2017).

关键词： breeding fertility Wild

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Sn-doped BiOCl nanosheet with synergistic H^(+)/Zn^(2+)co-insertion for“rocking chair”zinc-ion battery

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Journal of Energy Chemistry 2023年第6期81卷 623-632,I0014页

作者： yuzhu qian Hongrui Wang Xinni Li Ting Song Yong Pei Li Liu Bei Long Xiongwei Wu Xianyou Wang School of Chemistry Xiangtan UniversityXiangtan 411105HunanChina School of Chemistry and Materials Science Hunan Agricultural UniversityChangsha 410128HunanChina

The development of insertion-type anodes is the key to designing“rocking chair”zinc-ion batteries.However,there is rare report on high mass loading anode with high performances.Here,{001}-oriented Bi OCl nanosheets with Sn doping are proposed as a promising insertion-type anode.The designs of cross-linked CNTs conductive network,{001}-oriented nanosheet,and Sn doping significantly enhance ion/electron transport,proved via experimental tests and theoretical calculations(density of states and diffusion barrier).The H^(+)/Zn^(2+)synergistic co-insertion mechanism is proved via ex situ XRD,Raman,XPS,and SEM tests.Accordingly,this optimized electrode delivers a high reversible capacity of 194 m A h g^(-1)at 0.1 A g^(-1)with a voltage of≈0.37 V and an impressive cyclability with 128 m A h g^(-1)over 2500 cycles at 1 A g^(-1).It also shows satisfactory performances at an ultrahigh mass loading of 10 mg cm^(-2).Moreover,the Sn-Bi OCl//MnO_(2)full cell displays a reversible capacity of 85 m A h g^(-1)at 0.2 A g^(-1)during cyclic test.

关键词： Sn-doped BiOCl nanosheet High mass loading anode Synergistic H^(+)/Zn^(2+)co-insertion Fast ionic/electronic diffusion “Rocking chair”zinc-ion battery

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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

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Current situation and prospect for the diagnosis and treatment of pediatric critical rare diseases in China

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儿科学研究(英文) 2024年第1期8卷 66-71页

作者： Liu Yingchao qian Suyun Pediatric Intensive Care Unit Beijing Children’s Hospital Capital Medical University National Center for Children’s Health Beijing China

The onset of critical rare diseases (RDs) in children is rapid and dangerous, accompanied by a high mortality rate, which brings a heavy burden to both families and society. Multiple malformations, neuromuscular diseases, metabolic diseases, and heart diseases are the most common types of RDs in children of China, often manifesting with multiple organ dysfunction. At present, the diagnosis and treatment of critical RDs in children face challenges such as prolonged diagnosis time, a high misdiagnosis rate, limited treatment modalities, and a significant disease burden. However, with the progress in genetic testing technology, the establishment of multidisciplinary diagnosis and treatment platforms, and the implementation of relevant RD policies in China, children with critical RDs will received enhanced medical services, experience improved prognoses, and reintegrate into social life.

关键词： Children Critical Current situation Prospect Rare diseases

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Reveal more mechanisms of precondition mesenchymal stem cells inhibiting inflammation

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World Journal of Stem Cells 2024年第4期16卷 459-461页

作者： Yi Li qian-qian Chen En-qiang Linghu Department of Gastroenterology First Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology and Hepatology First Medical Center of Chinese PLA General HospitalBeijing 100853China

Hypoxia can get more ability to inhibit inflammation.But how it impact on survival time of mesenchymal stem cells(MSCs)is confusing and how preconditioned MSCs inhibiting inflammation are partially known.Those issues ... 详细信息

关键词： Mesenchymal stem cell Hypoxia-inducible factor 1α Hypoxia Inflammation Macrophage

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Molecular Mechanism of Rice Necrotic Lesion for Optimized Yield and Disease Resistance

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Rice science 2024年第3期31卷 285-299页

作者： HOU Xinyue WANG Yuping qian qian REN Deyong State Key Laboratory of Rice Biology and Breeding China National Rice Research InstituteHangzhou 310006China State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China Rice Research InstituteSichuan Agricultural UniversityChengdu 611130China

How to balance rice resistance and yield is an important issue in rice breeding.Plants with mutated necrotic lesion genes often have persistent broad-spectrum resistance,but this broad-spectrum resistance usually comes at the expense of yield.Currently,many necrotic lesion mutants in rice have been identified,and these genes are involved in disease resistance pathways.This review provides a detailed introduction to the characteristics,classification,and molecular mechanisms of necrotic lesion formation.Additionally,we review the molecular regulatory pathways of genes involved in rice disease resistance.Concurrently,we summarize the relationship between resistance and yield in rice using newly developed gene editing methods.We discuss a rational and precise breeding strategy to better utilize molecular design technology for breeding disease-resistant and high-yield rice varieties.

关键词： rice necrotic lesion regulation mechanism high yield high resistance

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Epidemiological research, burden, and clinical advances of inflammatory bowel disease in China

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中华医学杂志(英文版) 2024年第9期137卷 1009-1011页

作者： Yang Hong qian Jiaming Department of Gastroenterology Peking Union Medical College Hospital Chinese Academy of Medical Sciences &amp Peking Union Medical College Beijing China

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