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Lymph node-biomimetic scaffold boosts CAR-T therapy against solid tumor

National Science Review 2024年第4期11卷 206-215页

作者： Ziyan Liao Jie Jiang Wei Wu Jiaqi Shi Yanfang Wang Yuejun Yao Tao Sheng Feng Liu Wei Liu Peng zhao Feifei Lv Jie Sun Hongjun Li Zhen Gu National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang University Liangzhu Laboratory Zhejiang University Bone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology Zhejiang University School of Medicine Department of Medical Oncology The First Affiliated Hospital School of Medicine Zhejiang University Department of Laboratory Medicine The First Affiliated Hospital Zhejiang University School of Medicine Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalSchool of MedicineZhejiang University Jinhua Institute of Zhejiang University MOE Key Laboratory of Macromolecular Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang University Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University

The limited infiltration and persistence of chimeric antigen receptor(CAR)-T cells is primarily responsible for their treatment deficits in solid tumors. Here, we present a three-dimensional scaffold, inspired by the physiological process of T-cell proliferation in lymph nodes. This scaffold gathers the function of loading,delivery, activation and expansion for CAR-T cells to enhance their therapeutic effects on solid tumors. This porous device is made from poly(lactic-co-glycolic acid) by a microfluidic technique with the modification of T-cell stimulatory signals, including anti-CD3, anti-CD28 antibodies, as well as cytokines. This scaffold fosters a 50-fold CAR-T cell expansion in vitro and a 15-fold cell expansion in vivo. Particularly, it maintains long-lasting expansion of CAR-T cells for up to 30 days in a cervical tumor model and significantly inhibits the tumor growth. This biomimetic delivery strategy provides a versatile platform of cell delivery and activation for CAR-T cells in treating solid tumors.

关键词： drug delivery cell therapy bioinspired biomaterials cancer immunotherapy

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Catalytic asymmetric dearomative azo-Diels–Alder reaction of 2-vinlyindoles

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Chinese Chemical Letters 2024年第4期35卷 357-362页

作者： Yu-Hang Miao Zheng-Xu Zhang Xu-Yi Huang Yuan-zhao Hua Shi-Kun Jia Xiao Xiao Min-Can Wang Li-Ping Xu Guang-Jian Mei Green Catalysis Center and College of ChemistryZhengzhou UniversityZhengzhou 450052China School of Chemistry and Chemical Engineering Shandong University of TechnologyZibo 255000China Institute of Pharmaceutical Science and Technology Zhejiang University of TechnologyHangzhou 310014China

Due to the high electrophilic nature of azo-dienophiles, azo-Diels–Alder proceeds rapidly even without the need of a catalyst and is therefore regarded as the “click reaction”. This spontaneity causes strong background reaction and poses a daunting challenge to chemists for developing the catalytic asymmetric version. Reported herein is the first catalytic asymmetric dearomative azo-Diels–Alder reaction between2-vinylindoles and triazoledione. This protocol makes use of the high energy barrier of dearomatization to avert the strong background reaction of azo-Diels–Alder reaction, allowing the implementation of the projected reaction at ambient temperature. Density functional theory calculations have been performed to gain insights into the reaction mechanism and the origins of the enantioselectivity. By using this method,a variety of tetracyclic indole derivatives have been readily prepared in good to excellent yields and with excellent diastereo-and enantio–selectivities(33 examples, up to 97% yield and >99% ee, >20:1 dr).

关键词： Catalytic asymmetric dearomatization Azo-Diels–Alder reaction 2-Vinylindoles Chiral phosphoric acid Tetracyclic indole derivatives

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HPLC法测定复方氨基酸注射液(3AA)中主成分及有关物质含量

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药物分析杂志 2024年第7期44卷 1161-1168页

作者：左利民茹仙古丽·依明郭鑫肖菁徐士婕赵婷连晓芳刘惠一周怡山广志中国医学科学院医药生物研究所北京100050 新疆维吾尔自治区药物研究所新疆维吾尔药重点实验室乌鲁木齐830004 湖南省药品检验检测研究院长沙410001 国家药典委员会北京100061

目的:建立复方氨基酸注射液(3AA)的主成分和有关物质测定的高效液相色谱方法。方法:采用反相高效液相色谱法并结合二维柱切换LC/MSn法对制剂中主要杂质进行分离和结构鉴定,建立复方氨基酸注射液(3AA)中缬氨酸、异亮氨酸和亮氨酸及其有... 详细信息

目的:建立复方氨基酸注射液(3AA)的主成分和有关物质测定的高效液相色谱方法。方法:采用反相高效液相色谱法并结合二维柱切换LC/MSn法对制剂中主要杂质进行分离和结构鉴定,建立复方氨基酸注射液(3AA)中缬氨酸、异亮氨酸和亮氨酸及其有关物质含量检测方法。采用Capcell PAK AQ C_(18)(250 mm×4.6 mm,3μm)色谱柱,以0.2 mol·L^(-1)磷酸二氢钠溶液(用磷酸调pH至2.8)-乙腈(98∶2)为流动相,流速1.0 mL·min^(-1),柱温40℃,检测波长210 nm,进样量20μL。采用Thermo Accucore AQ C18(100 mm×4.6 mm,2.6μm)色谱柱,以0.1%甲酸溶液为流动相A,以0.1%甲酸溶液-乙腈为流动相B,流速0.4 mL·min^(-1),柱温40℃;质谱条件采用ESI电离源,正离子扫描模式,扫描范围为m/z 100~1000,二级质谱采用数据依赖型扫描开展。结果:主峰和相邻杂质峰分离度良好,缬氨酸的线性范围为1.263~5.050 mg·mL^(-1),平均回收率(n=9)为99.0%;异亮氨酸的线性范围为1.350~5.402 mg·mL^(-1),平均回收率(n=9)为99.4%;亮氨酸的线性范围为1.647~6.588 mg·mL^(-1),平均回收率(n=9)为99.5%。3批样品中主要杂质均为原料引入的工艺杂质,其中甲硫氨酸含量分别为4.344、3.751、4.503μg·mL^(-1),苯丙氨酸含量分别为4.636、4.889、4.753μg·mL^(-1)。其他单个未知杂质分别为0.01%、0.02%、0.01%。结论:经方法学验证,本方法可用于复方氨基酸注射液(3AA)的质量控制。

关键词：复方氨基酸注射液(3AA) 含量测定二维柱切换串联质谱法有关物质结构鉴定质量控制

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三株鸡传染性支气管炎病毒优势流行毒株全基因组分析及其致病性

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畜牧兽医学报 2024年第5期55卷 2109-2122页

作者：熊挺何献铭赵希雅庄婷婷黄美珍梁世金余传照梁雪静陈瑞爱岭南现代农业科学与技术广东省实验室肇庆分中心肇庆526238 华南农业大学兽医学院广州510642

为调查研究禽传染性支气管炎病毒(IBV)的流行及优势毒株致病特性,本研究对实验室分离的IBV毒株进行了遗传演化研究和致病性研究,旨在了解我国当下IBV流行毒株基因型、生物学特性以及为新疫苗的研制提供借鉴参考。首先对56株IBV分离毒株S... 详细信息

为调查研究禽传染性支气管炎病毒(IBV)的流行及优势毒株致病特性,本研究对实验室分离的IBV毒株进行了遗传演化研究和致病性研究,旨在了解我国当下IBV流行毒株基因型、生物学特性以及为新疫苗的研制提供借鉴参考。首先对56株IBV分离毒株S1全长核苷酸序列进行遗传演化分析,从中挑选了MH20、KC和JS96 3株优势基因型毒株进行全基因组测序分析,然后选取毒力较强的JS96毒株进行了SPF鸡致病性试验。结果表明:遗传演化分析结果显示GI-19是我国主要流行毒株,占比约53.57%,同时变异毒不断涌现,GVI(新基因型)明显的流行增多。3株优势基因型分离毒株的全长基因组与QX-like毒株相似性最高,达到97%以上,但与国内外疫苗株、经典毒株的相似性低,仅为77%左右。抗原表位分析同样表明了分离株与疫苗毒株、经典毒株的B细胞抗原表位数量和序列都存在差异。3株分离毒株均可导致SPF鸡胚矮化和致死,其中JS96对1日龄SPF鸡的致病率高于15日龄SPF鸡,1日龄SPF鸡100%死亡率,15日龄SPF鸡出现生长显著迟缓和个别鸡症状明显,发病鸡剖检均可见“花斑肾”。本研究表明,QX-like基因型IBV毒株是现下IBV的主要流行毒株,对低日龄鸡致病性强,易发生基因重组,与疫苗毒株、经典毒株S蛋白相似性低,适配性较差,急需选择合适疫苗及研发新型疫苗,才能控制当下IBV疫病流行,减少养禽业的损失。

关键词：禽传染性支气管炎病毒基因测序演化与相似性分析致病性

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高频红外碳硫仪测定镍、铜冶炼过程物料中的硫

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世界有色金属 2024年第15期 193-195页

作者：李婷梁玉霞于静赵一华文沅琦金川集团镍钴有限公司检测中心

本文采用高频红外碳硫仪测定镍、铜冶炼过程物料中的硫，方法测定范围在0.001%～80%之间，硫RSD在0.45%～6.56%之间，方法精密度和准确度较好，能够满足镍、铜冶炼过程物料中的硫分析要求。

关键词：高频红外碳硫仪镍、铜冶炼过程物料硫

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Structural variation(SV)-based pan-genome and GWAS reveal the impacts of SVs on the speciation and diversification of allotetraploid cottons

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Molecular Plant 2023年第4期16卷 678-693页

作者： Shangkun Jin Zegang Han Yan Hu Zhanfeng Si Fan Dai Lu He Yu Cheng Yiqjan Li ting zhao Lei Fang Tianzhen Zhang Zhejang Provincial Engineering Center for Crop Precision Breeding Advanced Seed InstitutePlant Precision Breeding AcademyCollege of Agriculture and BiotechnologyZhejiang UniversityHangzhouChina Hainan Institute of Zhejiang University Sanya 572025China

Structural variations(SVs)have long been described as being involved in the origin,adaption,and domes-tication of ***,the underlying genetic and genomic mechanisms are poorly ***,we report a high-quality genome assembly of Gossypium barbadense ***,a landrace that is closely related to formation of extra-long-staple(ELS)cultivated *** SV-based pan-genome(Pan-SV)was then constructed using a total of 182593 non-redundant SVs,including 2236 inversions,97398 insertions,and 82959 deletions from 11 assembled genomes of allopolyploid *** utility of this Pan-sV was then demonstrated through population structure analysis and genome-wide association studies(GWASs).Using segregation mapping populations produced through crossing ELS cotton and the landrace along with an Sv-based GWAs,certain SVs responsible for speciation,domestication,and improvement in tetraploid cottons were ***,some of the SVs presently identified as associated with the yield and fiber quality improvement had not been identified in previous SNP-based *** particular,a 9-bp insertion or deletion was found to associate with elimination of the interspecific reproductive isolation between Gossypium hirsutum and ***,this study provides new insights into genome-wide,gene-scale SVs linked to important agronomic traits in a major crop spe-cies and highlights the importance of sVs during the speciation,domestication,and improvement of culti-vated crop species.

关键词： genome assembly structural variations SV-based pan-genome GWAS introgression QTL mapping

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Clinical practice guideline for acupuncture and moxibustion:Allergic rhinitis

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Journal of Integrative Medicine 2024年第3期22卷 245-257页

作者： Shi-hao Du Sheng Chen Shan-ze Wang Guan-qun Wang Shuo Du Wei Guo Xiao-long Xie Bi-hui Peng Chao Yang Ji-ping zhao Institute of Acupuncture and Moxibustion China Academy of Chinese Medical SciencesBeijing 100700China Department of Acupuncture and Moxibustion Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China Department of Acupuncture and Moxibustion Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510120Guangdong ProvinceChina Department of Traditional Chinese Medicine Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China

Acupuncture is one of the most effective complementary therapies for allergic rhinitis(AR)and has been recommended by several clinical practice guidelines(CPGs)for ***,these CPGs mentioned acupuncture without making recommendations for clinical implementation and therapeutic protocols,therefore limiting the applicability of acupuncture therapies for ***,for the benefit of acupuncture practitioners around the world,the World Federation of Acupuncture-moxibustion Societies have initiated a project to develop the CPG for the use of acupuncture and moxibustion to treat *** CPG was developed according to the Grading of Recommendations Assessment,Development,and Evaluation(GRADE)methodology,referring to the principles of the World Health Organization Handbook for Guideline *** the development of the CPG,the guideline development group(GDG)played an important *** clinical questions,recommendations and therapeutic protocols were all formulated by the GDG using the modified Delphi *** CPG contains recommendations for 15 clinical questions about the use of acupuncture and moxibustion *** include one strong recommendation for the intervention based on high-quality evidence,three conditional recommendations for either the intervention or standard care,and 11 conditional recommendations for the intervention based on very low quality of *** CPG also provides one filiform needle acupuncture protocol and five moxibustion protocols extracted based on the protocols presented in randomized controlled trials reviewed by the GDG.

关键词： Clinical practice guideline Allergic rhinitis Acupuncture Moxibustion GRADE

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Clinical practice guideline for acupuncture and moxibustion: Female urinary incontinence

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Journal of Integrative Medicine 2024年第3期22卷 258-269页

作者： Chao Yang Shan-ze Wang Sheng Chen Shuo Du Guan-qun Wang Wei Guo Xiao-long Xie Bi-hui Peng Shi-hao Du Ji-ping zhao Department of Acupuncture and Moxibustion Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China Department of Acupuncture and Moxibustion Guangdong provincial hospital of Chinese MedicineGuangzhou 510120Guangdong ProvinceChina Shanghai Ninth People’s Hospital Shanghai Jiao Tong University School of MedicineShanghai 200011China Institute of Acupuncture and Moxibustion China Academy of Chinese Medical SciencesBeijing 100700China

Urinary incontinence (UI) is a common problem *** has a major impact on physical and social activities and interpersonal *** is common in women,but is under-reported and *** affects the quality of life of female patients *** and moxibustion have been proposed as potentially effective interventions for female ***,for the benefit of acupuncture practitioners around the world,the World Federation of Acupuncture-moxibustion Societies initiated a project to develop a clinical practice guideline (CPG) for the use of acupuncture and moxibustion to treat female *** CPG was developed according to the Grading of Recommendations Assessment,Development,and Evaluation (GRADE) methodology,referring to the principles of the World Health Organization Handbook for Guideline *** the development of the CPG,the guideline development group (GDG) played an important *** clinical questions,recommendations and therapeutic protocols were all formulated by GDG using the modified Delphi *** CPG contains ten recommendations about the use of acupuncture and moxibustion interventions for ten clinical questions,which include nine conditional recommendations for the intervention and one conditional recommendation for either the intervention or the *** CPG also provides one protocol for conventional filiform needle therapy,two therapy protocols for deep needling stimulation on lumbosacral acupoints,and four moxibustion therapy protocols,based on the protocols presented in randomized controlled trials reviewed by the GDG.

关键词： Acupuncture Clinical practice guideline Female urinary incontinence Moxibustion GRADE

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Single-atom Pd anchored in the porphyrin-center of ultrathin 2D-MOFs as the active center to enhance photocatalytic hydrogen-evolution and NO-removal

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Chinese Chemical Letters 2024年第9期35卷 364-368页

作者： Xingyan Liu Chaogang Jia Guangmei Jiang Chenghua Zhang Mingzuo Chen Xiaofei zhao Xiaocheng Zhang Min Fu Siqi Li Jie Wu Yiming Jia Youzhou He Chongqing Key Laboratory of Catalysis and New Environmental Materials College of Environment and ResourcesChongqing Technology and Business UniversityChongqing 400067China School of Pharmacy North Sichuan Medical CollegeNanchong 637100China Carbon Neutrality Technology Application Research Center College of River and Ocean EngineeringChongqing Jiaotong UniversityChongqing 400074China State Key Joint Laboratory of Environment Simulation and Pollution Control School of EnvironmentTsinghua UniversityBeijing 100084China National Local Joint Engineering Research Center for Road Engineering and Disaster Prevention and Reduction Technology in Mountainous Areas China Merchants Chongqing Communications Technology Research and Design Institute Co.Ltd.Chongqing 400067China Chongqing Culture Relics and Archaeology Research Institute Chongqing 400013China

Single-atom catalysts were widely used to treat atmospheric pollution and alleviate energy crises through ***,how to prevent the aggregation of single atoms during the preparation and catalytic processes remained a great ***,a novel ultrathin two-dimensional porphyrin-based single-atom photocatalyst Ti-MOF(abbreviated as TMPd)obtained through a simple hydrothermal synthesis strategy was used for photocatalytic hydrogen evolution and NO removal,in which the singleatom Pd tightly anchored in the center of porphyrin to ensure single-atom Pd stable *** with most reported MOFs-based photocatalysts,the TMPd showed an excellent hydrogen evolution rate(1.32 mmol g^(-1)h^(-1))and the NO removal efficiency(62%)under visible light *** high-angle annular dark-field scanning transmission electron microscope(HAADF-STEM)and synchrotron-radiation-based X-ray absorption fine-structure spectroscopy(XAFS)proved that pd in TMPd existed in an isolated state,and the atomic force microscope(AFM)proved the ultrathin morphology of *** calculations had demonstrated that single-atom Pd could serve as the active center and more effectively achieve electron transfer,indicating that single-atom Pd played a vital role in photocatalytic hydrogen *** addition,a possible photocatalytic pathway of NO removal was proposed based on ESR and in-situ infrared spectra,in which the catalysts anchored with single-atom Pd could produce more active substances and more effectively oxidize NO to NO_(2)^(-)or NO_(3)^(-).The results suggested that coordinating single-atom metal species as the active site in the center of porphyrin could be a feasible strategy to obtain various ultrathin porphyrin-based single-atom photocatalysts to acquire excellent photocatalytic performance further.

关键词： Porphyrin-based MOFs Single-atom Pd Ultrathin 2D nanosheets Hydrogen evolution NO removal

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男性2型糖尿病患者血清白蛋白水平与骨密度关系的研究

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中华骨质疏松和骨矿盐疾病杂志 2024年第3期17卷 203-212页

作者：韩梅昝晓晖马邓荣郭馨远赵阳婷李凯陈重阳王亚雯刘靖芳兰州大学第一临床医学院兰州730000 兰州大学第一医院内分泌科兰州730000

目的探讨50岁以上男性2型糖尿病(diabetes mellitus type 2,T2DM)患者血清白蛋白(albumin,ALB)水平与骨密度(bone mineral density,BMD)的相关性。方法选取2021年7月~2022年3月兰州大学第一医院内分泌科住院的202例50岁以上男性T2DM患... 详细信息

目的探讨50岁以上男性2型糖尿病(diabetes mellitus type 2,T2DM)患者血清白蛋白(albumin,ALB)水平与骨密度(bone mineral density,BMD)的相关性。方法选取2021年7月~2022年3月兰州大学第一医院内分泌科住院的202例50岁以上男性T2DM患者及体检中心的30名男性健康对照者,根据血清ALB水平将T2DM患者分为3组:低ALB水平组(T1组,ting hormone,TSH)、γ-谷氨酰转移酶(γ-glutamyl transferase,GGT)、乳酸脱氢酶(lactate dehydrogenase,LDH)、肌酸激酶(creatine kinase,CK)、天冬氨酸转氨酶(aspartate transaminase,AST)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、钙(calcium,Ca)、磷(phosphorus,P)、尿酸(uric acid,UA)及尿白蛋白排泄率(urinary albumin excretion rates,UAER)等混杂因素后,血清ALB水平与全髋的BMD水平独立正相关(β=0.229,95%CI:0.000~0.019)。结论50岁以上男性T2DM患者血清ALB水平与BMD密切相关,中老年男性T2DM患者应该早期关注血清ALB水平的变化,为OP的防治提供线索。

关键词： 2型糖尿病骨质疏松血清白蛋白骨密度

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