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Targeting adaptor protein SLP76 of RAGE as a therapeutic approach for lethal sepsis

NATURE COMMUNICATIONS 2021年第1期12卷 308页

作者： Yan, Zhengzheng Luo, Haihua Xie, Bingyao Tian, Tian Li, Shan chen, Zhixia Liu, Jinghua Zhao, xuwen Zhang, Liyong Deng, Yongqiang Billiar, Timothy R. Jiang, Yong Southern Med Univ State Key Lab Organ Failure Res Guangdong Prov Key Lab Prote Sch Basic Med SciDept Pathophysiol Guangzhou 510515 Peoples R China Univ Pittsburgh Sch Med Dept Surg Pittsburgh PA 15213 USA Southern Med Univ Nanfang Hosp Dept Anesthesiol Guangzhou 510515 Peoples R China

Accumulating evidence shows that RAGE has an important function in the pathogenesis of sepsis. However, the mechanisms by which RAGE transduces signals to downstream kinase cascades during septic shock are not clear. Here, we identify SLP76 as a binding partner for the cytosolic tail of RAGE both in vitro and in vivo and demonstrate that SLP76 binds RAGE through its sterile alpha motif (SAM) to mediate downstream signaling. Genetic deficiency of RAGE or SLP76 reduces AGE-induced phosphorylation of p38 MAPK, ERK1/2 and IKK alpha/beta, as well as cytokine release. Delivery of the SAM domain into macrophages via the TAT cell-penetrating peptide blocks proinflammatory cytokine production. Furthermore, administration of TAT-SAM attenuates inflammatory cytokine release and tissue damage in mice subjected to cecal ligation and puncture (CLP) and protects these mice from the lethality of sepsis. These findings reveal an important function for SLP76 in RAGE-mediated pro-inflammatory signaling and shed light on the development of SLP76-targeted therapeutics for sepsis.

关键词： Bacterial infection Cell signalling Monocytes and macrophages

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基于LoRa自组网的电能采集系统设计与实现

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计算机测量与控制 2023年第3期31卷 235-240,261页

作者：陈德富刘小湖周旭文邱宝象吴华君屈亮亮浙江工业大学信息工程学院杭州310023 万向钱潮股份有限公司杭州311215

为了实现用电设备运行状况的远程监测,需要对设备运行时的电能参数进行采集并上报至云平台;针对上述目的,本项目设计了一种基于LoRa自组网技术的电能采集系统,整个系统主要由数据采集节点和集中器组成;数据采集节点采用RN8209电能计量... 详细信息

为了实现用电设备运行状况的远程监测,需要对设备运行时的电能参数进行采集并上报至云平台;针对上述目的,本项目设计了一种基于LoRa自组网技术的电能采集系统,整个系统主要由数据采集节点和集中器组成;数据采集节点采用RN8209电能计量芯片实现负载电能数据的精确采集,并通过LoRa通信模块将数据发送至集中器;集中器采用了基于NB-IoT通信模块和LoRa通信模块的双模组设计,通过LoRa模块接收节点上报的数据,并通过NB-IoT模块转发至物联网云平台;本系统利用LoRa载波侦听技术设计了基于CSMA/CA的星型自组网络,实现了节点与集中器间的无线通信,适用于低成本、小规模的远程电能数据采集系统;通过实验验证,该方案的数据采集功能、LoRa自组网通信功能和NB-IoT通信功能均能够正常实现,达到了设计目标。

关键词：电能采集 RN8209 LoRa通信 CSMA/CA 载波侦听星型自组网

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Investigation of energetic ion losses induced by long-lived saturated internal mode with energetic particle diagnostics in the HL-2A tokamak

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NUCLEAR FUSION 2023年第8期63卷 086014-086014页

作者： Zhang, Jie Zhang, Yipo chen, Wei cheng, Shikui Ogawa, Kunihiro He, Xiaofei Wang, Yongqin Liu, Yi Xu, Min Isobe, Mitsutaka Zhu, Yuxuan Zhan, xuwen Zhou, Jianhang Zhang, Jinglong Liu, Liang He, Xiaoxue Li, Dong Li, Yonggao Guo, Wenping Yu, Liming Hao, Guangzhou Li, Bo Shi, Zhongbing Ji, Xiaoquan Zhong, Wulv Southwestern Inst Phys POB 432 Chengdu 610041 Peoples R China Natl Inst Fus Sci Natl Inst Nat Sci Toki Japan SOKENDAI Grad Univ Adv Studies Toki Japan Chengdu Univ Technol Coll Nucl Technol & Automation Engn Chengdu 610059 Peoples R China

Several sets of energetic particle diagnostics, including a set of neutron flux monitoring systems, a solid-state neutral particle analyzer and a fast ion loss probe (FILP), have been used to investigate the energetic ion losses induced by the long-lived saturated internal mode (LLM) in the HL-2A tokamak. Clear experimental evidence for different levels of energetic ion losses induced by LLM, sawtooth and minor disruption has been observed. A numerical calculation for the evolution of neutron emissions was carried out with the FBURN code, and it shows that the neutron emission drop rate linearly increases with the LLM amplitude and no threshold perturbation amplitude exists, illustrating that the loss mechanism for LLM induced energetic ion loss is dominantly convective. In addition, measurement results of the FILP demonstrate that LLM tends to expel energetic ions with relatively low energy (E < 27 keV) and high pitch angle (? > 60(?)), and can suppress the prompt loss of energetic ions with high energy and low pitch angle to a certain degree. Furthermore, the physical process for LLM induced energetic ion loss can be explained by orbit calculations, which show that LLM induced lost energetic ions will transport from center to peripheral region first, and then get lost out of plasma. The experimental observations are successfully reproduced by calculations using the ORBIT code combined with both the NUBEAM code and the MARS-K code. The paper clearly describes the whole physical process of LLM induced energetic ion loss for the first time in the HL-2A tokamak.

关键词： energetic ion loss long-lived saturated internal mode neutron flux measurement neutral particle analyzer fast ion loss probe

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Identification of mechanisms conferring an enhanced immune response in mice induced by CVC1302-adjuvanted killed serotype O foot-and-mouth virus vaccine

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VACCINE 2019年第43期37卷 6362-6370页

作者： Du, Luping Yu, Xiaoming Hou, Liting Zhang, Dong Zhang, Yuanpeng Qiao, xuwen Hou, Jibo chen, Jin Zheng, Qisheng Jiangsu Acad Agr Sci Inst Vet Immunol & Engn Nanjing 210014 Jiangsu Peoples R China Jiangsu Acad Agr Sci Natl Res Ctr Engn & Technol Vet Biol Nanjing 210014 Jiangsu Peoples R China Jiangsu Coinnovat Ctr Prevent & Control Important Yangzhou 225009 Jiangsu Peoples R China Minist Sci & Technol Nanjing Jiangsu Key Lab Food Qual Nanjing 210014 Jiangsu Peoples R China Minist Sci & Technol Nanjing Safety State Key Lab Cultivat Base Nanjing 210014 Jiangsu Peoples R China Shandong Prov Ctr Anim Dis Control & Prevent Jinan 250022 Shandong Peoples R China

The adjuvant CVC1302 was previously shown to efficiently enhance the immunogenicity of killed footand-mouth disease virus (FMDV) in mice and piglets. However, the underlining mechanism of action of CVC1302 remains unclear, especially at local injection sites and draining lymph nodes. Since the FMDV vaccine is administrated intramuscularly in field settings, we studied local immune responses to FMDV following intramuscular injection in mice, and found that CVC1302-adjuvanted killed FMDV (KV-CVC1302) induced secretion of several chemokines in murine muscle tissues, including MCP-1, MIP-1 alpha, and mIP-1 beta. The number of monocytes recruited to the site of injection was significantly higher in mice immunized with KV-CVC1302 compared with mice immunized with killed FMDV alone (MV). iTAQ-based quantitative proteomic assays were additionally employed to explore the molecular mechanisms of CVC1302 action in the draining lymph nodes. A total of 35 proteins were identified as being differentially expressed among the control group, KV-immunized group and KV-CVC1302-immunized group at 10 days post immunization (dpi). Proteins exhibiting differential expression were mainly involved in signal transduction, apoptosis, endocytosis and innate immune responses. Pathway analysis demonstrated that AMPK, phospholipase D, cAMP, Rapt, and MAPK signaling pathways were potentially induced by the immunopotentiator CVC1302. Understanding the local mechanism of CVC1302 action at injection sites and draining lymph nodes will provide new insights into the development of FMDV vaccines. (C) 2019 Elsevier Ltd. All rights reserved.

关键词： FMDV CVC1302 Local mechanism Injection sites Draining lymph nodes Mice

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猪XCR1/FMDV双特异纳米抗体融合蛋白的制备与鉴定

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中国农业大学学报 2025年第1期30卷 131-141页

作者：杨利杜露平侯立婷张浩明于晓明李兰乔绪稳张元鹏秦竹王义伟郑其升陈瑾程海卫江苏省农业科学院动物免疫工程研究所/国家兽用生物制品工程技术研究中心/江苏省食品质量与安全重点实验室南京210014 兽用生物制品(泰州)国泰技术创新中心江苏泰州225300

为通过将FMDV抗原靶向提呈至猪DC细胞进而提高疫苗免疫效力,本研究利用原核系统表达了猪XCR1目的蛋白,以该蛋白为免疫原免疫羊驼,提取其外周血淋巴细胞的总mRNA并反转录为cDNA,构建噬菌体展示纳米抗体文库,经过3轮亲和筛选获得猪XCR1特... 详细信息

为通过将FMDV抗原靶向提呈至猪DC细胞进而提高疫苗免疫效力,本研究利用原核系统表达了猪XCR1目的蛋白,以该蛋白为免疫原免疫羊驼,提取其外周血淋巴细胞的总mRNA并反转录为cDNA,构建噬菌体展示纳米抗体文库,经过3轮亲和筛选获得猪XCR1特异性纳米抗体;利用SOE-PCR技术将该纳米抗体和猪O型FMDV特异性纳米抗体Nb205连接,构建XCR1/FMDV双特异纳米抗体融合蛋白。结果表明:1)成功原核表达猪XCR1目的蛋白,SDS-PAGE和Western blot结果显示,其相对分子量大小约35 ku,符合预期。2)羊驼血清效价为1∶64000,满足建库要求;构建的噬菌体展示文库库容量约为1.91×10^(8)CFU/mL,插入率为91.3%,多样性好;经3轮亲和筛选成功获得了纳米抗体Nb75,间接ELISA结果显示该纳米抗体能特异性与XCR1结合。3)利用SOE-PCR技术成功构建XCR1/FMDV双特异纳米抗体融合蛋白Nb75-205;SDS-PAGE和Western blot显示,该蛋白在大肠杆菌中可溶性表达,且呈现二聚体结构,间接ELISA结果显示Nb75-205能同时与XCR1目的蛋白和FMDV抗原结合。综上,本研究采用噬菌体展示技术成功获得猪XCR1特异性纳米抗体,并构建XCR1/FMDV双特异纳米抗体融合蛋白Nb75-205,且该蛋白为天然二聚体结构,与XCR1目的蛋白和FMDV抗原均具有较好的结合活性,为进一步开展FMDV抗原的猪XCR1靶向提呈研究奠定基础。

关键词：趋化因子受体1 双特异纳米抗体二聚体 FMDV

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Macrophage-Disguised Manganese Dioxide Nanoparticles for Neuroprotection by Reducing Oxidative Stress and Modulating Inflammatory Microenvironment in Acute Ischemic Stroke

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ADVANCED SCIENCE 2021年第20期8卷 e2101526页

作者： Li, Chao Zhao, Zhenhao Luo, Yifan Ning, Tingting Liu, Peixin chen, Qinjun Chu, Yongchao Guo, Qin Zhang, Yiwen Zhou, Wenxi chen, Hongyi Zhou, Zheng Wang, Yu Su, Boyu You, Haoyu Zhang, Tongyu Li, xuwen Song, Haolin Li, Chufeng Sun, Tao Jiang, chen Fudan Univ Sch Pharm Dept PharmaceutState Key Lab Med Neurobiol Key Lab Smart Drug DeliveryMinist EducInst Brai Shanghai 201203 Peoples R China Fudan Univ Sch Pharm Inst Brain Sci MOE Frontiers Ctr Brain SciDept Pharmaceut Shanghai 201203 Peoples R China

Reperfusion injury is still a major challenge that impedes neuronal survival in ischemic stroke. However, the current clinical treatments are remained on single pathological process, which are due to lack of comprehensive neuroprotective effects. Herein, a macrophage-disguised honeycomb manganese dioxide (MnO2) nanosphere loaded with fingolimod (FTY) is developed to salvage the ischemic penumbra. In particular, the biomimetic nanoparticles can accumulate actively in the damaged brain via macrophage-membrane protein-mediated recognition with cell adhesion molecules that are overexpressed on the damaged vascular endothelium. MnO2 nanosphere can consume excess hydrogen peroxide (H2O2) and convert it into desiderated oxygen (O-2), and can be decomposed in acidic lysosome for cargo release, so as to reduce oxidative stress and promote the transition of M1 microglia to M2 type, eventually reversing the proinflammatory microenvironment and reinforcing the survival of damaged neuron. This biomimetic nanomedicine raises new strategy for multitargeted combined treatment of ischemic stroke.

关键词： biomimetic nanoparticles inflammatory microenvironment microglia polarization neuroprotection O-2 generation reperfusion injury reactive oxygen species (ROS) consumption

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CONVERGENCE TO EQUILIBRIUM OF A BODY MOVING IN A KINETIC SEA

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SIAM JOURNAL ON MATHEMATICAL ANALYSIS 2015年第6期47卷 4630-4651页

作者： chen, xuwen Strauss, Walter A. Univ Rochester Dept Math Rochester NY 14627 USA Brown Univ Dept Math Providence RI 02912 USA Brown Univ Lefschetz Ctr Dynam Syst Providence RI 02912 USA

We consider a continuum of particles that are acted upon by an external force G(t, x) and that collide with a rigid body. The body itself is subject to a constant force E as well as to the collective force of interaction with the particles. We assume that the particles that collide with the body reflect probabilistically with some probablility distribution K(v, u). Under certain conditions on G(t, x) and K(v, u), we identify an equilibrium velocity V-infinity of the body and we prove that this equilibrium is asymptotically stable.

关键词： kinetic free boundary stability

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A novel two-stage partial-nitritation/anammox (PN/A) process based on zeolite biological fixed bed reactor for low-strength ammonium wastewater treatment

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IOP Conference Series: Earth and Environmental Science 2021年第1期787卷

作者： Xiaoyang Gu xuwen Zheng Yongxing chen Zhenguo chen Qingbo Meng Hualu Environmental Technology Co. Ltd. Guangzhou 510700 China School of Environment and Energy South China University of Technology Guangzhou 510006 China School of Chemistry and Chemical Engineering South China University of Technology 510641 China Institute of Resources Comprehensive Utilization Guangdong Academy of Sciences Guangzhou 510650 China

A novel two-stage partial nitritation/anammox (PN/A) process coupled by a zeolite biological fixed bed reactor (ZBFB) and an anammox reactor were proposed for wastewater containing 30 mg/L NH4+-N by long-term operation. The cycle operational results by adsorption and biological desorption in ZBFB showed adsorption effluent NH4+-N maintained at 3.0-4.0 mg/L and the average biological desorption effluent NO2--N was 42.2 mg/L. In ZBFB, free ammonia inhibition on nitrite oxidizing bacteria was the main reason for stable nitrite accumulation performance with nitrite accumulation ratio as 88.70% during biological desorption step. Total nitrogen in the mixture of influent and biological desorption effluent of ZBFB could be removed to less than 15 mg/L by the subsequent anammox reactor. High-throughput sequencing analysis results presented the enrichment of Nitrosomonas and inhibition of Nitrobactor and Nitrospira in ZBFB, and dominance of Candidatua Kuenenia in anammox reactor. All results revealed desirable feasibility for nitrogen removal from low-strength ammonium wastewater by ZBFB combined with anammox reactor.

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Velocity Reversal Criterion of a Body Immersed in a Sea of Particles

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COMMUNICATIONS IN MATHEMATICAL PHYSICS 2015年第1期338卷 139-168页

作者： chen, xuwen Strauss, Walter Brown Univ Dept Math Providence RI 02912 USA Brown Univ Dept Math Lefschetz Ctr Dynam Syst Providence RI 02912 USA

We consider a rigid body colliding with a continuum of particles. We assume that the body is moving at a velocity close to an equilibrium velocity V-infinity and that the particles colliding with the body reflect diffusely, that is, probabilistically with some probability distribution K. We find a condition that is sufficient and almost necessary that the collective force of the colliding particles reverses the relative velocity V(t) of the body, that is, changes the sign of V(t) - V-infinity, before the body approaches equilibrium. Examples of both reversal and irreversal are given. This is in strong contrast with the pure specular reflection case in which only reversal happens.

关键词： PARTICLES VELOCITY PROBABILITY theory EQUILIBRIUM COLLIDING-beam accelerators

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基于影像学特征对骨质疏松性椎体压缩骨折病人经皮椎体成形术后同椎体再发骨折的预测研究

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国际医学放射学杂志 2022年第4期45卷 407-413页

作者：吴丽梁治平熊玉超何洁贾妩懿吴迪朗曾旭文陈松广州市红十字会医院放射科广州510220

目的探讨基于影像学特征对骨质疏松性椎体压缩骨折(OVCF)病人经皮椎体成形术(PVP)后的列线图模型预测术椎椎体再发骨折的价值。方法回顾性纳入急性OVCF并行PVP后的病人93例。所有病人均行X线及MRI检查,根据椎体再发骨折诊断标准将病人... 详细信息

目的探讨基于影像学特征对骨质疏松性椎体压缩骨折(OVCF)病人经皮椎体成形术(PVP)后的列线图模型预测术椎椎体再发骨折的价值。方法回顾性纳入急性OVCF并行PVP后的病人93例。所有病人均行X线及MRI检查,根据椎体再发骨折诊断标准将病人分为再发骨折组(48例)和无再发骨折组(45例)。采用t检验和卡方检验比较2组间临床资料及影像特征的差异,对差异有统计学意义的指标进行多因素Logistic回归分析,获取再发骨折的独立危险因素,采用R软件建立列线图模型并绘制其校准曲线。采用受试者操作特征(ROC)曲线评估模型的预测效能,计算ROC曲线下面积(AUC)。应用校准曲线对列线图模型进行验证。结果再发骨折组的椎体高度恢复率、延伸至终板的骨折线、椎体内裂隙(IVC)、骨水泥周围积液及骨水泥-终板未接触(NPEC)与无再发骨折组的差异均有统计学意义(均P<0.05);多因素Logistic回归分析显示延伸至终板的骨折线[优势比(OR)=3.232]、存在IVC(OR=27.117)和NPEC(OR=1.993)及较高的椎体高度恢复率(OR=2.943)为同椎体再发骨折的独立危险因素(均P<0.05)。存在延伸至终板的骨折线的椎体骨质前份前移距离[(3.12±2.62)mm]大于无延伸者[(1.67±2.18)mm](P<0.05)。与不存在IVC病人相比,存在IVC病人的椎体高度恢复率(分别为7.19%±8.60%和12.63%±11.81%)和NPEC发生率[78.38%(58/74)和94.74%(18/19)]均更高(P<0.05)。列线图模型预测再发骨折的AUC为0.860,敏感度0.792,特异度0.844。校准曲线显示列线图预测概率与实际概率一致性尚可。结论基于影像学特征建立的列线图模型能够预测术椎椎体再发骨折。

关键词：骨质疏松性椎体压缩骨折经皮椎体成形术再发骨折列线图磁共振成像数字X线摄影

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