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A novel engineered IL-21 receptor arms T-cell receptor-engineered T cells(TCR-T cells)against hepatocellular carcinoma

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2215-2230页

作者： Wei Zhu Zhiming Zhang Jinzhang Chen Xiaolan Chen Lei Huang Xiaoyong Zhang Xuan Huang Na Ma Weikang Xu Xuan Yi xinyu Lu xin Fu Siwei Li Guoheng Mo Yiyue Wang Guosheng Yuan Mengya Zang Qi Li Xiaotao Jiang Yajing He Sha Wu Yukai He Yongyin Li Jinlin Hou State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis ResearchDepartment of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhouChina Institute of Cellular Medicine Newcastle University Medical SchoolNewcastleUK Department of Pathology The First People’s Hospital of FoshanFoshanChina Dermatology Hospital Southern Medical UniversityGuangzhouChina Department of Immunology School of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina Microbiome Medicine Center Department of Laboratory MedicineZhujiang HospitalSouthern Medical UniversityGuangzhouChina Key Laboratory of Proteomics of Guangdong Province Demonstration Center for Experimental Education of Basic Medical Sciences of ChinaGuangzhouChina Medical College of Georgia Augusta University112015th StreetAugustaGAUSA

Strategies to improve T cell therapy efficacy in solid tumors such as hepatocellular carcinoma(HCC)are urgently *** common cytokine receptorγchain(γc)family cytokines such as IL-2,IL-7,IL-15 and IL-21 play fundamental roles in T cell development,differentiation and effector *** study aims to determine the combination effects of IL-21 in T cell therapy against HCC and investigate optimized strategies to utilize the effect of IL-21 signal in T cell *** antitumor function of AFP-specific T cell receptor-engineered T cells(TCR-T)was augmented by exogenous IL-21 in vitro and in ***-21 enhanced proliferation capacity,promoted memory differentiation,downregulated PD-1 expression and alleviated apoptosis in TCR-T after activation.A novel engineered IL-21 receptor was established,and TCR-T armed with the novel engineered IL-21 receptors(IL-21R-TCR-T)showed upregulated phosphorylated STAT3 expression without exogenous IL-21 ***-21R-TCR-T showed better proliferation upon activation and superior antitumor function in vitro and in ***-21R-TCR-T exhibited a less differentiated,exhausted and apoptotic phenotype than conventional TCR-T upon repetitive tumor antigen *** novel IL-21 receptor in our study programs powerful TCR-T and can avoid side effects induced by IL-21 systemic *** novel IL-21 receptor creates new opportunities for next-generation TCR-T against HCC.

关键词： hepatocellular TCR utilize

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Observation of maximal intrinsic chirality empowered by dual quasi-bound states in the continuum in a planar metasurface

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Photonics Research 2024年第2期12卷 244-252页

作者： xin QI JIAJU WU FENG WU SONG ZHAO CHAO WU YUEYANG MIN MINA REN YUFEI WANG HAITAO JIANG YUNHUI LI ZHIWEI GUO YAPING YANG WANHUA ZHENG HONG CHEN YONG SUN MOE Key Laboratory of Advanced Micro-Structured Materials School of Physics Science and EngineeringTongji UniversityShanghai 200092China School of Optoelectronic Engineering Guangdong Polytechnic Normal UniversityGuangzhou 510665China l3 Shanghai Key Laboratory of Special Artificial Microstructure Materials and Technology School of Physics Science and EngineeringTongji UniversityShanghai 200092China Department of Electrical Engineering Tongji UniversityShanghai 201804China State Key Laboratory on Integrated Optoelectronics Institute of SemiconductorsChinese Academy of SciencesBeijing 100083China

Metasurfaces with spin-selective transmission play an increasingly critical role in realizing optical chiral responses,especially for strong intrinsic chirality,which is limited to complex three-dimensional *** this paper,we propose a planar metasurface capable of generating maximal intrinsic chirality and achieving dual-band spinselective transmission utilizing dual quasi-bound states in the continuum(quasi-BICs)caused by the structural symmetry ***,the value of circular dichroism(CD)and the transmittance of two kinds of circular polarization states can be arbitrarily controlled by tuning the asymmetry *** CD approaching unity with the maximum transmittance up to 0.95 is experimentally achieved in the dual ***,assisted by chiral BICs,the application in polarization multiplexed near-field image display is also *** work provides a new avenue to flexibly control intrinsic chirality in planar structure and offers an alternative strategy to develop chiral sensing,multiband spin-selective transmission,and high-performance circularly polarized wave *** basic principle and design method of our experiments in the microwave regime can be extended to other bands,such as the terahertz and infrared wavelengths.

关键词： planar intrinsic quasi

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Interactions of thymic stromal lymphopoietin with interleukin-4 in adaptive immunity during Aspergillus fumigatus keratitis

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International Journal of Ophthalmology(English edition) 2021年第10期14卷 1473-1483页

作者： Chen Chen Chen-Yang dai Fang Han Jia-Yin Wu Lin Sun xin-Yi Wu Department of Ophthalmology Clinical Medical College of Shandong UniversityJinan 250012Shandong ProvinceChina Department of Ophthalmology Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Key Laboratory of Cardiovascular Remodeling and Function Research Shandong UniversityJinan 250012Shandong ProvinceChina

AIM:To investigate the potential interactions of thymic stromal lymphopoietin(TSLP)with interleukin-4(IL-4)in adaptive immunity during fungal keratitis(FK).METHODS:An FK mouse model was induced with Aspergillus fumigatus(AF)hyphal *** were divided into several groups:untreated,phosphate buffer saline(PBS),infected with AF,and pretreated with a scrambled siRNA,a TSLP-specific siRNA(TSLP siRNA),murine recombinant TSLP(rTSLP),immunoglobulin G(IgG),murine recombinant IFN(rIFN-γ),murine recombinant IL-4(rI L-4),rIL-13,murine recombinant IL-17A(rIL-17A),and murine recombinant IL-17F(rIL-17F)*** realtime reverse transcription-polymerase chain reaction(qRTPCR)and enzyme-linked immunosorbent assay(ELISA)or Western blot were performed to determine mRNA and protein levels in the inflamed *** locations were observed by immunofluoresence staining after AF hyphal ***:Compared to those in the untreated group,TSLP and T helper type 1(Th1)cytokine levels in the AF group were upregulated at 24 h post infection(hpi),and those of T helper type 2(Th2)and T helper type 17(Th17)cytokines were increased at 5 d post infection(dpi).Th2 cytokine levels were decreased in the TSLP siRNA-pretreated group and increased in the rTSLP-pretreated group compared with the AF *** TSLP level was increased in the rIL-4-pretreated group,but there were no significant changes among the other *** staining showed cytokine locations after AF hyphal ***:TSLP induces a Th2 immune response and promots Th2 T cell differentiation in ***-4 promotes TSLP ***,TSLP with IL-4 regulates adaptive immunity in FK.

关键词： Aspergillus fumigatus keratitis thymic stromal lymphopoietin Th2 immune response interleukin-4

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Synchronous occurrence of extramedullary plasmacytoma and squamous cell carcinoma in situ in the larynx: a case report

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Chinese Journal of Cancer 2010年第12期29卷 1029-1034页

作者： Xiao-Li Zhang dai-Qiang Li Jing-Jia Li Shi-Sheng Li xin-Ming Yang Department of Otolaryngology-Head and Neck Surgery the Second Xiangya Hospital Central South University Changsha Hunan 410011 P. R. China Department of Pathology the Second Xiangya Hospital Central South University Changsha Hunan 410011 P. R. China

Extramedullary plasmacytoma of the larynx is rare, especially when coexisted with squamous cell carcinoma in situ. We report a 56-year-old woman with hoarseness for 6 months and dysphonia for a week. Fiberoptic laryngoscopic examination showed a red, smooth-surface swelling in the submucous region of the left ventricle and ventricular band of the larynx. The patient underwent vertical laryngectomy and modified left neck dissection. Postoperative pathologic examination revealed coexisting plasmacytoma and carcinoma in situ. Bone marrow biopsy and systemic radiogram showed no positive findings. The hepatic and renal functions were normal. Monoclonal immunoglobulin light chain of type kappa was detected in urine. Hence, a laryngeal extramedullary plasmacytoma with carcinoma in situ was diagnosed. No recurrence or progression was observed during a 2-year follow-up. Here, we discussed the risk factors, diagnosis, and therapy for this rare disease.

关键词：鳞状细胞癌原位病例报告浆细胞同步病理检查免疫球蛋白危险因素

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橙皮素通过Nrf2-ARE通路对大鼠肾缺血再灌注损伤的保护作用

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中国临床药理学杂志 2024年第12期40卷 1803-1807页

作者：翟鑫铎金敏刘宇山西医科大学药理学教研室山西太原030001

目的研究橙皮素(HSP)对大鼠肾缺血再灌注损伤(RIRI)的作用,并探讨其作用机制。方法将50只雄性SD大鼠随机分为假手术组、模型组、HSP预处理组、全反式维甲酸(ATRA)预处理组(ATRA+I/R)、HSP+ATRA预处理组(HSP+ATRA+I/R),每组10只。假手术... 详细信息

目的研究橙皮素(HSP)对大鼠肾缺血再灌注损伤(RIRI)的作用,并探讨其作用机制。方法将50只雄性SD大鼠随机分为假手术组、模型组、HSP预处理组、全反式维甲酸(ATRA)预处理组(ATRA+I/R)、HSP+ATRA预处理组(HSP+ATRA+I/R),每组10只。假手术组仅打开腹腔暴露双肾。其余各组采用夹闭双侧肾蒂45 min,再用灌注24 h的方法建立RIRI模型。用苏木精-伊红(HE)染色法确定肾组织损伤水平;用微板法检测血清肌酸酐(Scr)水平;用脲酶法检测血清尿素氮(BUN)水平;用酶联免疫吸附测定(ELISA)法检测血清中白细胞介素-6(IL-6)、白细胞介素-1β(IL^(-1)β)和肿瘤坏死因子-α(TNF-α)的含量;用试剂盒法检测肾组织超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、丙二醛(MDA)和过氧化氢酶(CAT)水平;用蛋白质印迹法检测肾组织中核因子E2相关因子2(Nrf2)及其下游抗氧化蛋白血红素氧合酶-1(HO-1)和醌氧化物还原酶1(NQO1)的表达。结果假手术组、模型组、HSP预处理组肾小管损伤评分分别为(0.20±0.45)、(4.20±0.84)和(2.40±0.55)分;Scr含量分别为(55.52±11.23)、(207.10±19.22)和(105.60±18.11)μmol·L^(-1);IL-6含量分别为(33.66±6.83)、(172.50±8.09)和(105.40±10.03)pg·mL^(-1)。假手术组、模型组、HSP预处理组、ATRA预处理组和HSP+ATRA预处理组SOD水平分别为(57.04±3.44)、(37.29±3.60)、(51.61±9.41)、(32.55±5.58)和(37.40±3.66)U·mg·prot^(-1);Nrf2蛋白相对表达水平分别为0.37±0.24、0.57±0.28、1.31±0.34、0.44±0.17和0.77±0.25;HO-1蛋白相对表达水平分别为0.26±0.14、0.57±0.30、1.32±0.61、0.53±0.28和0.67±0.50。模型组与假手术组相比,肾小管损伤评分、Scr、IL-6、SOD指标比较,在统计学上差异均有统计学意义(P1);HSP预处理组与模型组相比,上述指标在统计学上差异均有统计学意义(P1)。结论HSP可能通过激活Nrf2-抗氧化反应元件(ARE)通路上调其下游抗氧化蛋白的表达,减轻氧化应激对肾的损伤,进而改善RIRI。

关键词：橙皮素肾缺血再灌注损伤炎症氧化应激

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NLRP3基因敲减对高脂高糖饮食诱导的非酒精性脂肪性肝炎小鼠模型的影响

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临床肝胆病杂志 2024年第5期40卷 952-960页

作者：黄倩王卓媛安梓铭辛鑫孙沁梅苟小军胡义扬冯琴上海中医药大学附属曙光医院肝病研究所上海201203 上海中医药大学附属曙光医院科技实验中心上海201203 上海市中医临床重点实验室上海201203 肝肾疾病病证教育部重点实验室上海20120 上海市宝山区中西医结合医院上海201900

目的探讨NOD样受体热蛋白结构域相关蛋白3(NLRP3)基因敲减对高脂高糖诱导的非酒精性脂肪性肝炎(NASH)小鼠模型的影响。方法将44只小鼠随机分为正常饮食组(CON)20只,高脂高糖造模组(HFHC)24只。造模14周末,随机选取4只HFHC组小鼠进行腺... 详细信息

目的探讨NOD样受体热蛋白结构域相关蛋白3(NLRP3)基因敲减对高脂高糖诱导的非酒精性脂肪性肝炎(NASH)小鼠模型的影响。方法将44只小鼠随机分为正常饮食组(CON)20只,高脂高糖造模组(HFHC)24只。造模14周末,随机选取4只HFHC组小鼠进行腺相关病毒9(AAV9)尾静脉注射预实验,4周后验证NLRP3敲减模型是否成功。18周末确认敲减成功后,对剩余40只小鼠进行AAV9一次性尾静脉注射,分为CON+NLRP3敲减阴性对照组(CON+NLRP3-NC)、CON+NLRP3敲减组(CON+NLRP3-KD)、HFHC+NLRP3-NC及HHFHC+NLRP3-KD组,每组10只,继续造模6周。24周末取材观察炎症小体活化效应,检测小鼠体质量、肝质量、肝指数及糖代谢(空腹血糖、空腹胰岛素及HOMA-IR指数)指标;检测小鼠肝脂质含量(肝组织TG及油红O染色)、肝脏炎症(血清ALT活性、HE染色及炎症相关基因)及肝纤维化(天狼星红染色及纤维化相关基因)指标。计量资料多组间比较使用单因素方差分析,进一步两两比较采用LSD-t检验。结果与CON+NLRP3-NC组相比,Western Blot结果提示,HFHC+NLRP3-NC组的NLRP3、pro-Caspase1、Caspase1、ASC及IL-1β蛋白水平均升高,HFHC+NLRP3-KD组均降低(P值均1);在肝脏炎症方面,HFHC+NLRP3-NC组血清ALT,非酒精性脂肪性肝病活动度(NAS)评分及炎症相关基因均较CON+NLRP3-NC组明显升高,HFHC+NLRP3-KD组均明显降低(P值均1);在肝纤维化方面,HFHC+NLRP3-NC组肝胶原纤维面积以及纤维化相关基因均较CON+NLRP3-NC组明显升高,HFHC+NLRP3-KD组纤维化相关基因均明显降低(P值均0.05)。结论NLRP3基因敲减可显著改善高脂高糖饮食诱导的NASH小鼠模型肝脂肪沉积及炎症。

关键词：非酒精性脂肪性肝病 NLR家族,热蛋白结构域包含蛋白3 膳食,高脂炎症小鼠,近交C57BL

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Acupuncture promotes functional recovery after cerebral hemorrhage by upregulating neurotrophic factor expression

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Neural Regeneration Research 2020年第8期15卷 1510-1517页

作者： Dan Li Qiu-xin Chen Wei Zou Xiao-Wei Sun Xue-Ping Yu Xiao-Hong dai Wei Teng Third Department of Acupuncture First Affiliated HospitalHeilongjiang University of Chinese MedicineHarbinHeilongjiang ProvinceChina Department of Acupuncture Third Affiliated HospitalBeijing University of Chinese MedicineBeijingChina

Acupuncture is widely used in the treatment of cerebral hemorrhage,and it improves outcomes in experimental animal models and ***,the mechanisms underlying the effectiveness of acupuncture treatment for cerebral hemorrhage are still *** this study,a model of intracerebral hemorrhage was produced by injecting 50μL autologous blood into the caudate nucleus in Wistar *** at Baihui(DU20)and Qubin(GB7)acupoints was performed at a depth of 1.0 inch,12 hours after blood injection,once every 24 *** needle was rotated at 200 r/min for 5 minutes,For each 30-minute session,needling at 200 r/min was performed for three sessions,each lasting 5 *** the positive control group,at 6 hours,and 1,2,3 and 7 days after induction of hemorrhage,the rats were intraperitoneally injected with 1 mL aniracetam(0.75 mg/mL),three times a *** Bederson behavioral test was used to assess palsy in the contralateral *** blot assay was used to examine the expression levels of Nestin and basic fibroblast growth factor in the basal *** was performed to count the number of Nestin-and glial cell line-derived neurotrophic factor-positive cells in the basal *** effectively reduced hemorrhage and brain edema,elevated the expression levels of Nestin and basic fibroblast growth factor in the basal ganglia,and increased the number of Nestin-and glial cell line-derived neurotrophic factor-positive cells in the basal ***,these findings suggest that acupuncture promotes functional recovery after cerebral hemorrhage by increasing the expression of neurotrophic *** study was approved by the Committee for Experimental Animals of Heilongjiang Medical Laboratory Animal Center(approval No.2017061001)on June 10,2017.

关键词： acupuncture basic fibroblast growth factor brain cell protection cerebral hemorrhage electron microscope glial cell line-derived neurotrophic factor immunohistochemistry Nestin western blot assay

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沃茨联结感量表在中国大学生中的信效度检验

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中国临床心理学杂志 2024年第5期32卷 1111-1116页

作者：韩雨森方新赵丹杨丽天津大学教育学院天津市自杀心理与行为研究实验室天津大学应用心理研究所北京大学医院心理咨询与治疗中心

目的：在中国大学生群体中对沃茨联结感量表（Watts connectedness scale, WCS）进行信效度检验。方法：采用方便取样法对651名大学生进行测量，以简短经验性回避问卷、敬畏体验量表、五因素正念量表、社会联结量表、抑郁-焦虑-压力问... 详细信息

目的：在中国大学生群体中对沃茨联结感量表（Watts connectedness scale, WCS）进行信效度检验。方法：采用方便取样法对651名大学生进行测量，以简短经验性回避问卷、敬畏体验量表、五因素正念量表、社会联结量表、抑郁-焦虑-压力问卷和短式沃里克-爱丁堡积极心理健康量表为效标检验效标关联效度。间隔3周后随机抽取其中54人进行重测信度检验。结果：控制项目表述效应后，沃茨联结感量表中文版三因子修正模型拟合良好（χ2/df=2.663, IFI=0.893, CFI=0.892, RMESA=0.071, SRMR=0.067, AIC=447.418, ECVI=1.451）。总量表的合成信度系数为0.826,α系数为0.834，各分量表的合成信度系数在0.779～0.815之间，α系数在0.770～0.808之间。三周后，总量表重测信度为0.646，各分量表重测信度在0.592～0.704之间。总量表与负性情绪状态呈显著负相关，与积极心理健康水平呈显著正相关，各分量表与相应的效标均存在显著相关。结论：沃茨联结感量表中文版在大学生群体中具有良好的信效度，可作为测量大学生联结感的有效工具。

关键词：联结感大学生信度效度

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火力与制导资源联合分配的快速构造算法组合设计

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中国科学：信息科学 2024年第6期54卷 1458-1473页

作者：王加根辛斌李冠呈北京理工大学自动化学院北京100081 自主智能无人系统全国重点实验室北京理工大学北京100081 中国长峰机电技术研究设计院北京100854

火力与制导资源联合分配问题是军事运筹学研究中典型的NP完全问题,其求解具有较高的实时性要求.精确求解算法难以适用,而近来提出的构造算法的时间开销也相对较大,严重影响算法的实际应用.为了解决该问题,本文将其建模为多阶段传感器–... 详细信息

火力与制导资源联合分配问题是军事运筹学研究中典型的NP完全问题,其求解具有较高的实时性要求.精确求解算法难以适用,而近来提出的构造算法的时间开销也相对较大,严重影响算法的实际应用.为了解决该问题,本文将其建模为多阶段传感器–武器–目标分配(sensor-weapon-target assignment,S-WTA)问题,并分解成两类作战资源分配子问题.在武器分配阶段采用了一种基于威胁值确定分配优先级的快速构造算法,在传感器分配阶段提出了一种新的基于阶段顺序确定分配优先级的快速构造算法,该算法能充分利用约束条件,大幅度减小时间开销.本文在两种基本构造算法与基于边际损失的构造算法的基础上进一步提出了构造算法序列化组合,对多阶段S-WTA问题进行求解.计算实验验证了新提出的基本构造算法的快速性以及构造算法序列化组合相比于各种基本构造算法的性能优势.

关键词：异构资源联合分配传感器– 武器– 目标分配启发式算法构造算法协同作战

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基于博弈论与改进CRITIC-AHP的配电网线路脆弱性评估

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水电能源科学 2024年第9期42卷 208-211,129页

作者：鲁玲蒲秋平王敏龚康李欣张鑫三峡大学电气与新能源学院湖北宜昌443002 国网浙江省电力有限公司衢州供电公司浙江衢州324000 国网湖北省电力有限公司宜昌供电公司湖北宜昌443002

针对现有配电网线路脆弱性评估指标单一的问题,从配电网结构、运行状态和故障影响等三个方面出发,全面考虑网络拓扑结构、负荷类型、潮流分布、设备参数和线路故障等影响因素,提出了改进的线路介数、改进的线路度数、线路电压稳定性和... 详细信息

针对现有配电网线路脆弱性评估指标单一的问题,从配电网结构、运行状态和故障影响等三个方面出发,全面考虑网络拓扑结构、负荷类型、潮流分布、设备参数和线路故障等影响因素,提出了改进的线路介数、改进的线路度数、线路电压稳定性和线路潮流熵等脆弱性评估指标。为解决权重分配过程中出现的权重偏好问题,提出基于博弈论与改进CRITIC-AHP组合赋权法的综合评价模型。最后,通过在IEEE33节点系统上进行仿真,验证了所提方法的有效性。

关键词：线路脆弱性线路介数负荷类型博弈论组合赋权

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