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Intraperitoneal injection but not oral administration of ellagic acid: A novel immunomodulator via targeting casein kinase 2 signaling pathway

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Food Science and Human Wellness 2024年

作者： Wen-Hui Qi Bing Han Ting-Ting Cui Pei-Xin Shen Zhuo-Hua Zhao Ya-Ping Yan li-Bin Wang Xin-Yu Lu Yuan Zhang xing li Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry (Shaanxi Normal University)， The Ministry of Education College of life Sciences， Shaanxi Normal University Department of Pharmacology， School of Pharmacy， Fourth Military Medical University The Nervous System Disease Diagnosis and Treatment Engineering Technology Research Center of Ningxia School of Medical Technology， Xi'an Medical University

Immunosuppressants currently approved for the treatment of autoimmune diseases and organ transplant rejection present diverse adverse effects that impair the life quality of patients. Therefore， the development of novel immunomodulators with high efficiency and low toxicity is essential. Ellagic acid (EA)， a natural polyphenol compound widely distributed in berries， is metabolically transformed by gut microbiome to exert systemic health benefits. Here， we identified that intraperitoneal administration of EA with no cytotoxicity， beyond its well-known oral metabolic fate， effectively decreased clinical severity and CNS inflammation/demyelination in experimental autoimmune encephalomyelitis (EAE)， a mouse model of an autoimmune disease multiple sclerosis (MS). Interestingly， intraperitoneal EA administration at incredibly low doses (0.1 mg/kg/d) is dose-sparing with fingolimod (FTY720)， the first FDA-approved oral drug for MS. In addition， intraperitoneal EA also ameliorated the brain damage in a neuromyelitis optica (NMO) model， and significantly prevented the immune rejection of allograft skin graft. Evidence from pharmacological studies combined with RNA-seq indicate that prototype EA functions by a mechanism that involves direct inhibition of casein kinase II (CKII) to suppress the expression of IL-17 and promote the expression of Cpt1a to regulate Th17 differentiation. In conclusion， our study demonstrates that the prototype EA entering the blood circulation acts as a novel therapeutic immunomodulator for the treatment of autoimmune diseases and transplant rejection through the CKⅡ-mediated JAK/STAT/Cpt1a signaling pathway.

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First-line camrelizumab(a PD-1 inhibitor)plus apatinib(an VEGFR-2 inhibitor)and chemotherapy for advanced gastric cancer(SPACE):a phase 1 study

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1760-1767页

作者： Xiaofeng Chen Hao Xu Xiaobing Chen Tongpeng Xu Yitong Tian Deqiang Wang Fen Guo Kangxin Wang Guangfu Jin Xiao li Rong Wang Fengyuan li Yongbin Ding Jie Tang Yueyu Fang Jing Zhao liang liu ling Ma lijuan Meng Zhiguo Hou Rongrong Zheng Yang liu Ni Guan Bei Zhang Shuang Tong Shiqing Chen xing li Yongqian Shu Department of Oncology The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Gusu School Nanjing medical UniversitySuzhouChina Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingChina Department of General surgery The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of Oncology Henan Cancer Hospital Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhouChina Henan Engineering Research Center of Precision Therapy of Gastrointestinal Cancer&Zhengzhou Key Laboratory for Precision Therapy of Gastrointestinal Cancer ZhengzhouChina Department of Oncology Digestive Disease Institute&Cancer Institute of Jiangsu UniversityAffiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Oncology Suzhou Hospital of Nanjing Medical UniversitySuzhouChina Department of Oncology Nanjing PuKou People’s HospitalNanjingChina Department of Epidemiology School of Public HealthNanjing Medical UniversityNanjingChina Department of Pathology The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of general surgery Jurong Branch hospital of Jiangsu Province People HospitalJurongChina Department of Medical Oncology Liyang People’s HospitalLiyangChina Department of radiology Nanjing PuKou People’s HospitalNanjingChina Jiangsu Hengrui Pharmaceuticals ShanghaiChina Department of Medical Affairs 3D Medicines Inc.ShanghaiChina Shanghai OrigiMed Co. Ltd.ShanghaiChina

Patients with advanced gastric cancer typically face a grim *** phase 1a(dose escalation)and phase 1b(dose expansion)study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapyfor advanced gastric or gastroesophageal junction *** primary endpoints included maximum tolerated dose(MTD)in phase 1a and objective response rate(ORR)across phase 1a and *** 1a tested three dose regimens of camrelizumab,apatinib,oxaliplatin,and *** regimen 1:camrelizumab 200 mg on day 1,apatinib 250 mg every other day,oxaliplatin 100 mg/m^(2) on day 1,and S-140 mg twice a day on days *** regimen 2:same as dose regimen 1,but oxaliplatin 130mg/*** regimen3:same as dose regimen 2,but apatinib 250 mg ***-four patients were included(9 in phase 1a,25 in phase 1b).No dose-limiting toxicities occurred so no MTD was *** 3 was set for the recommended phase 2 doses and administered in phase *** confrmed ORR was 76.5%(95%CI 58.8-89.3).The median progression-free survival was 8.4 months(95%CI 5.9-not evaluable[NE]),and the median overall survival(OS)was not mature(11.6-NE).Ten patients underwent surgery after treatment and the multidisciplinary team *** 24 patients without surgery,the median OS was 19.6 months(7.8-NE).Eighteen patients(52.9%)developed grade≥3 treatment-emergent adverse *** plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer(ChiCTR2000034109).

关键词： regimen cancer doses

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医保支付与医生薪酬的激励转化机制研究——DRG付费下的实验研究证据

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中国卫生政策研究 2024年第7期17卷 8-17页

作者：李星林兴刘文婷韩优莉首都医科大学公共卫生学院北京100069

目的:探究与DRG支付方式改革相适应的医生薪酬激励设计,为优化医保支付方式改革相关政策提供参考依据。方法:利用经济学实验,设计七种将DRG支付激励转化为薪酬激励的医生薪酬支付方式,招募210名医学生和65名医生作为被试人员,测试其在... 详细信息

目的:探究与DRG支付方式改革相适应的医生薪酬激励设计,为优化医保支付方式改革相关政策提供参考依据。方法:利用经济学实验,设计七种将DRG支付激励转化为薪酬激励的医生薪酬支付方式,招募210名医学生和65名医生作为被试人员,测试其在不同薪酬激励下为患者提供的医疗服务数量及相应患者健康效益。结果:向医生反馈DRG支付情况或将DRG支付结余与医生绩效工资挂钩均会将支付方式的激励传导给服务提供者,在此基础上,引入以质量为基础的按绩效支付,被试者提供的服务量与最优服务量之间的差值减小,患者健康效益损失比也降低。结论:在将DRG支付激励传导给服务提供者时,与以质量为基础的按绩效支付相结合的医生薪酬设计更有利于提高患者健康效益。

关键词：医保支付方式按疾病诊断相关分组付费医生行为实验研究

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俞樾《卦气直日考》《卦气续考》所涉历法问题之辨析

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周易研究 2024年第4期 81-86页

作者：黄黎星福建师范大学文学院福建福州350007 曲阜师范大学东亚易学研究中心山东曲阜273100

俞樾《卦气直日考》《卦气续考》所论有三点历法问题值得辨析。其一,他将四正卦值配节气之起点由“二至”“二分”改为“四立”,从而使四正卦分值四时之六节气,避免了“跨历两时”的问题。这种做法不仅于文献依据及考辨上欠妥,而且消解... 详细信息

俞樾《卦气直日考》《卦气续考》所论有三点历法问题值得辨析。其一,他将四正卦值配节气之起点由“二至”“二分”改为“四立”,从而使四正卦分值四时之六节气,避免了“跨历两时”的问题。这种做法不仅于文献依据及考辨上欠妥,而且消解了四正卦初爻配合天文历法之关键节点的蕴意。其二,俞樾以阴阳爻画数阐释卦气说中六十卦的排列次序,此说有学术价值,但不能作为“改正”四正卦配值节气的证据。其三,俞樾认为卦气值日“惟京房之说为最密”,或存在观念上的误区。评价卦气值日法,需要明晰学科定位、主体立场。京房的“卦气值日法”本质上是模拟天文历法数的“逆推求合”,尽力使六十卦之赋值精切合乎天文历法之数;僧一行的《卦议》则是在天文历法的主体立场上引用易学的卦气说。

关键词：俞樾卦气历法四正卦值日京房

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A novel immiscible high entropy alloy strengthened via L1_(2)-nanoprecipitate

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Journal of Central South University 2024年第6期31卷 1808-1822页

作者： WANG Zheng-qin FAN Ming-yu ZHANG Yang li Jun-peng liU li-yuan HAN Ji-hong li xing-hao ZHANG Zhong-wu Key Laboratory of Superlight Materials and Surface Technology Ministry of EducationCollege of Materials Science and Chemical EngineeringHarbin Engineering UniversityHarbin 150001China

The low-cost Fe-Cu,Fe-Ni,and Cu-based high-entropy alloys exhibit a widespread utilization ***,these potential applications have been limited by their low *** this study,a novel Fe_(31)Cu_(31)Ni_(28)Al_(4)Ti_(3)Co_(3) immiscible high-entropy alloy(HEA)was *** vacuum arc melting and copper mold suction casting,this HEA exhibits a unique phase separation microstructure,which consists of striped Cu-rich regions and Fe-rich *** magnification of the striped Cu-rich region reveals that it is composed of a Cu-rich dot-like phase and a Fe-rich *** aging alloy is further strengthened by a L1_(2)-Ni_(3)(AlTi)nanoprecipitates,achieving excellent yield strength(1185 MPa)and uniform ductility(~8.8%).The differential distribution of the L1_(2) nanoprecipitate in the striped Cu-rich region and the external Fe-rich region increased the strength difference between these two regions,which increased the strain gradient and thus improved hetero-deformation induced(HDI)*** work provides a new route to improve the HDI hardening of Fe-Cu alloys.

关键词： heterogeneous microstructure precipitation strengthening high-entropy alloy phase separation mechanical property

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Physicochemical characterization of Dendrobium officinale polysaccharides and regulation of immunometabolic homeostasis in Sub-health mice based on the CD4-Th17/Treg immunity axis

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Food Science and Human Wellness 2024年

作者： Bo li Ze-Hua Zhang Hao-Ru Guan xing-li-Shang He Ning Wang Ying-Jie Dong Mei Rong Jiu-Jie Jia Ting-Ting Chen Zhi-Yuan li Gui-Yuan Lv lin-Nan Zhang Su-Hong Chen Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals， Zhejiang University of Technology Zhejiang Provincial Key Laboratory of TCM for Innovative R & D and Digital Intelligent Manufacturing of TCM Great Health Products.Huzhou College of Pharmaceutical Science， Zhejiang Chinese Medical University

The aim of this study was to investigate the role of DOPS and DOPS100 in attenuating immune dysfunction in subfertile mice. The results of the study revealed several noteworthy findings. First， DOPS and DOPS100 treatments led to significant improvement in weight gain and reversal of fatigue-related behaviors compared to the normal group. Second， both DOPS and DOPS100 showed effectiveness in reducing immune organ swelling， modulating immunoglobulin （IgA and IgM） levels， and restoring complement （C3c and C4） levels. In addition， they demonstrated a significant ability to enhance the integrity of the intestinal mechanical barrier by differentially upregulating the tight junction proteins Occludin and ZO-1. In addition， it was found that DOPS100 specifically enhanced the CD4+-Th17/Treg immune axis in the gut， as evidenced by increased expression of Foxp3 as well as decreased expression of RORγt， and further modulation of IL-10， IL-22， and IL-17A expression levels of inflammatory factors. These findings collectively suggest that DOPS100 holds significant potential in improving sub-healthy status by repairing the intestinal barrier， restoring local immune homeostasis， and activating the intestinal immune regulatory network. The study's outcomes provide valuable insights into the therapeutic implications of DOPS and DOPS100 in addressing immune dysfunction in sub-healthy conditions.

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超大城市低运量轨道交通线网规划布局方法——以成都市为例

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规划师 2024年第S01期40卷 194-199页

作者：李星谭月成都市规划设计研究院

在超大城市构建多层次轨道交通线网以满足多元交通需求的趋势下,低运量轨道交通将在超大城市轨道交通系统中发挥更加重要的作用。以成都市为例,基于超大城市的交通需求特征,结合低运量轨道交通的系统制式特点,按照“多网融合”的轨道交... 详细信息

在超大城市构建多层次轨道交通线网以满足多元交通需求的趋势下,低运量轨道交通将在超大城市轨道交通系统中发挥更加重要的作用。以成都市为例,基于超大城市的交通需求特征,结合低运量轨道交通的系统制式特点,按照“多网融合”的轨道交通系统构建思路,提出超大城市低运量轨道交通线网布局方法。

关键词：超大城市低运量轨道交通多网融合成都市

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考虑多类型时间依赖资源约束的敏捷卫星调度优化

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控制理论与应用 2024年第6期41卷 1038-1046页

作者：李君邢立宁彭观胜徐运保湖南工程学院管理学院湖南长沙410073 西安电子科技大学电子工程学院陕西西安710071 中国人民解放军军事科学院国防科技创新研究院北京100000

随着现代空间科技的迅猛发展,光学遥感图像数据的应用需求越来越广泛,大力推动了光学对地观测卫星的发展.然而,由于高昂的发射成本的约束,对地观测卫星的资源是有限的,远远无法满足各类数据需求.因此,提高对地观测卫星的使用效率,提高... 详细信息

随着现代空间科技的迅猛发展,光学遥感图像数据的应用需求越来越广泛,大力推动了光学对地观测卫星的发展.然而,由于高昂的发射成本的约束,对地观测卫星的资源是有限的,远远无法满足各类数据需求.因此,提高对地观测卫星的使用效率,提高其任务执行率,具有非常重要的应用价值.本文聚焦于敏捷对地观测卫星的任务调度问题,即在给定的调度周期内,对有限的卫星资源制定合理的任务调度方案,在满足一定星上资源约束下,最大化观测任务收益.该问题难点在于星上的资源是非常有限的,例如存储图像数据的固存资源、用于采集数据和卫星姿态切换的能量资源及执行任务活动耗费的时间资源.需要注意的是,能量消耗量和时间消耗量依赖于任务的执行时间,这是敏捷卫星相对传统的非敏捷卫星独有的特性.不同任务场景对不同类型资源的需求不同,多种资源约束互相耦合,资源约束具有时间依赖特性,这些难点无疑极大地增加了卫星调度的求解难度.为高效地求解该问题,本文构建了多类型时间依赖资源约束的敏捷卫星调度整数规划模型,并针对问题特性提出了一种基于自适应选择因子的迭代局部搜索启发式算法.自适应选择因子综合考虑了目标收益、资源消耗量、资源约束的松弛量,采用动态变化的资源重要度,能快速自适应地根据当前场景下各种类型的资源数据使用量来确定最佳局部搜索方向,从而在有限时间内找到高质量的解.实验结果证明,本文所提出的算法在多种情况下相比当前最好算法求解效果显著更优.此外,算法独有的自适应选择因子相比传统的选择因子的求解质量更高,这是因为所设计的自适应选择因子兼顾了目标收益和资源消耗量之间权衡关系的同时,采用动态变化的资源重要度准确捕捉了资源需求的迫切程度.

关键词：卫星调度迭代局部搜索动态规划时间依赖性数据验证

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金属微粒影响三电极气体火花开关击穿过程的仿真研究

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物理学报 2024年第1期73卷 248-257页

作者：周鑫淼张博雅陈立李兴文西安交通大学电工材料电气绝缘全国重点实验室西安710049

气体火花开关在脉冲功率技术中得到了大量应用,但由于脉冲功率技术大电流高电压的特点,气体火花开关在使用过程中很容易对电极表面造成烧蚀,烧蚀产生的金属微粒会显著影响开关的稳定性和可靠性.本文首先针对大气压氮气环境下的三电极气... 详细信息

气体火花开关在脉冲功率技术中得到了大量应用,但由于脉冲功率技术大电流高电压的特点,气体火花开关在使用过程中很容易对电极表面造成烧蚀,烧蚀产生的金属微粒会显著影响开关的稳定性和可靠性.本文首先针对大气压氮气环境下的三电极气体火花开关放电过程进行建模,对触发极边缘高场强区域的电离系数进行修正,使用场致电子发射电流模拟初始电子产生的过程,深入探究开关导通的物理机理,详细叙述开关击穿过程各阶段的放电形态.接着研究了金属微粒对于击穿过程的影响,研究表明金属微粒的存在增强了触发极附近的电场,加速了初始电子云的产生,同时金属微粒与触发极之间会率先击穿,并成为后续流注发展的源头.除此之外,金属微粒对于流注的传播具有阻碍作用,使放电通道产生分支.最后本文讨论了不同形状以及尺寸的金属微粒对于放电过程的影响,这些都为进一步研究三电极气体火花开关放电过程以及金属微粒诱发开关击穿的物理机理提供了理论支撑.

关键词：流注放电气体火花开关金属微粒场致发射

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Three-dimensional/one-dimensional perovskite heterostructures for stable tri-state synaptic memristors

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Science China Materials 2024年第9期67卷 2848-2855页

作者： Jiaqi Gong Shilei Ji Jintian li Hudie Wei Weiwei Mao Jing Hu Wen Huang Xuemin He xing’ao li liang Chu School of Science&School of Electronic and Optical Engineering Nanjing University of Posts and TelecommunicationsNanjing210023China Institute of Carbon Neutrality and New Energy&School of Electronics and Information Hangzhou Dianzi UniversityHangzhou310018China

Memristors have great potential in neural network *** memristors exhibit excellent resistive-switching(RS)properties between high resistance state(HRS)and low resistance state(LRS)state under applied voltage due to the extraordinary ion migration and superior charge ***,the stability issue of traditional three-dimensional(3D)perovskites is still ***,one-dimensional(1D)(CH_(3))_(3)SPbI_(3)perovskite passivation layer was in-situ formed on 3D perovskite film,which was further applied in stable synaptic *** memristor was provided with three resistance states due to the heterojunction electric field coupled with ion *** on/off ratio of memristors was obviously improved from 10 to over *** RS characteristics of 3D/1D perovskite memristor remained unchanged after 10^(3)s read and 300 switching *** 3D/1D perovskite memristor effectively exhibited versatile synaptic plasticity behaviors including long-term potentiation,long-term depression and paired-pulse facilitation by controlling the input ***,the novel device provides a new candidate for next-generation neuromorphic computing.

关键词： memristor perovskite heterojunction one-dimension (CH_3)_3SPbI_3 synaptic function

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