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Cellular & Molecular Immunology 2024年第7期21卷 674-688页

作者： siping liang Jinyu Zhou Can Cao Yiting Liu Siqi Ming Xi Liu Yuqi Shang Juanfeng Lao Qin Peng Jiahui Yang Minhao Wu Zhongshan School of Medicine Sun Yat-sen UniversityGuangzhouChina Key Laboratory of Tropical Disease Control(Sun Yat-sen University) Ministry of EducationGuangzhouChina Department of Infectious Diseases The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhaiChina

The NLRP3 inflammasome functions as an inflammatory driver,but its relationship with lipid metabolic changes in early sepsis remains ***,we found that GITR expression in monocytes/macrophages was induced by lysophosphatidylcholine(LPC)and was positively correlated with the severity of *** is a costimulatory molecule that is mainly expressed on T cells,but its function in macrophages is largely *** in vitro data showed that GITR enhanced LPC uptake by macrophages and specifically enhanced NLRP3 inflammasome-mediated macrophage ***,in vivo studies using either cecal ligation and puncture(CLP)or LPS-induced sepsis models demonstrated that LPC exacerbated sepsis severity/lethality,while conditional knockout of GITR in myeloid cells or NLRP3/caspase-1/IL-1βdeficiency attenuated sepsis severity/***,GITR specifically enhanced inflammasome activation by regulating the posttranslational modification(PTM)of *** competes with NLRP3 for binding to the E3 ligase MARCH7 and recruits MARCH7 to induce deacetylase SIRT2 degradation,leading to decreasing ubiquitination but increasing acetylation of ***,these findings revealed a novel role of macrophage-derived GITR in regulating the PTM of NLRP3 and systemic inflammatory injury,suggesting that GITR may be a potential therapeutic target for sepsis and other inflammatory diseases.

关键词： GITR Macrophage NLRP3 inflammasome Sepsis Posttranslational modification

Tetrahedral DNA nanostructures synergize with MnO_(2) to enhance antitumor immunity via promoting STING activation and M1 polarization

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2494-2505页

作者： siping liang Jiaying Li Zhengyu Zou Miao Mao Siqi Ming Fan Lin Ziyan Zhang Can Cao Jinyu Zhou Yuanqing Zhang Jiaping Li Minhao Wu Zhongshan School of Medicine Sun Yat-sen UniversityGuangzhou 510080China Department of Laboratory Medicine Guangdong Second Provincial General HospitalGuangzhou 510317China Guangdong Key Laboratory of Chiral Molecule and Drug Discovery School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China Department of Interventional Oncology The First Afﬁliated HospitalSun Yat-sen UniversityGuangzhou 510080China

Stimulator of interferon genes(STING) is a cytosolic DNA sensor which is regarded as a potential target for antitumor immunotherapy. However, clinical trials of STING agonists display limited anti-tumor effects and dose-dependent side-effects like inflammatory damage and cell toxicity. Here,we showed that tetrahedral DNA nanostructures(TDNs) actively enter macrophages to promote STING activation and M1 polarization in a size-dependent manner, and synergized with Mn^(2+) to enhance the expressions of IFN-β and iNOS, as well as the co-stimulatory molecules for antigen presentation. Moreover, to reduce the cytotoxicity of Mn^(2+),we constructed a TDN-MnO_(2) complex and found that it displayed a much higher efficacy than TDN plus Mn^(2+) to initiate macrophage activation and anti-tumor response both in vitro and in vivo. Together, our studies explored a novel immune activation effect of TDN in cancer therapy and its synergistic therapeutic outcomes with MnO_(2).These findings provide new therapeutic opportunities for cancer therapy.

关键词： Tetrahedral DNA nanostructure Manganese MnO_(2) STING M1 polarization Antigen presentation Anti-tumor immunity Cancer therapy

TREM2/β-catenin attenuates macrophage pyroptosis to promote bacterial eradication of Pseudomonas aeruginosa

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TREM2/β-catenin attenuates macrophage pyroptosis to promote...

第十三届全国免疫学学术大会

作者： Minhao Wu Yi Wang Yiting Liu siping liang Qiaojuan Liu Sun Yat-sen University Zhongshan School of Medicine

Triggering receptors expressed on myeloid cells 2(TREM2) is a cell surface receptor mainly found on macrophages. It is reported that TREM2 inhibits inflammatory responses, but promotes bacterial clearance during in vivo and in vitro infections with Pseudomonas aeruginosa(PA). However, the underlying mechanism remains unclear. Our study demonstrated that TREM2 deficiency or knockdown significantly enhanced PA-induced macrophage pyroptosis, a novel form of pro-inflammatory programmed cell death, which is induced by infectious or inflammatory stimuli and characterized by the cleavage of Caspase-1 and gasdermin D(GSDMD). Blockage of pyroptosis by knocking out/down Caspase-1 or silencing GSDMD enhanced macrophage-mediated bacterial killing of PA. While treatment with Caspase-1 inhibitor(YVAD) relieved TREM2 deficiency-mediated suppression of PA clearance. In addition, we found that TREM2 activated β-catenin signaling pathway via promoting its phosphorylation at S675 and enhancing the protein stability. Moreover, silencing of β-catenin enhanced pyroptotic cell death but impaired macrophage-mediated clearance of PA, while overexpression of β-catenin inhibited Caspase-1-dependent pyroptosis, and thereby restored cell survival and bacterial elimination in TREM2-silenced macrophages. Notably, in vitro studies suggested that TREM2/β-catenin suppressed the activation of NLRP3 and NLRC4 inflammasomes in macrophages challenged with PA or specific inflammasome activators. Collectively, our study provides a novel mechanism of TREM2-mediated antibacterial immunity and explores the relationship between pyroptosis and bacterial eradication.

关键词： TREM2 β-catenin bacteria macrophage pyroptosis

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晚期甲状腺乳头状癌鞋钉亚型1例

中华耳鼻咽喉头颈外科杂志 2023年第1期58卷 72-74页

作者：张海东龚单春梁思萍印洪林于振坤东南大学医学院南京210096 南京医科大学附属南京明基医院耳鼻咽喉头颈外科南京210019 南京医科大学附属南京明基医院病理科南京210019

甲状腺乳头状癌(PTC)各亚型中80%为经典型,表现为一种惰性的病理生理过程。还有约20%为高侵袭性亚型,易出现被膜外侵犯、局部邻近组织受累、颈侧淋巴结转移以及远处转移等;其中鞋钉亚型是近年来发现的一类高侵袭性亚型,发病率极低,约占... 详细信息

甲状腺乳头状癌(PTC)各亚型中80%为经典型,表现为一种惰性的病理生理过程。还有约20%为高侵袭性亚型,易出现被膜外侵犯、局部邻近组织受累、颈侧淋巴结转移以及远处转移等;其中鞋钉亚型是近年来发现的一类高侵袭性亚型,发病率极低,约占PTC的1%,本文介绍1例晚期复发PTC鞋钉亚型(hobnail variant of papillary thyroid carcinoma,HVPTC),患者老年女性,诊断为PTC并行根治性切除后仍多次复发,并出现脑转移,回顾多次手术后的病理结果,明确诊断为HVPTC。目前我院随访30个月,带瘤生存中。

关键词：甲状腺乳头状癌脑转移带瘤生存病理结果老年女性根治性切除多次手术侵袭性

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IGBT功率模块的一次性焊接工艺研究

台州学院学报 2018年第6期40卷 45-49页

作者：管功湖梁思平台州学院电子与信息工程学院浙江临海317000 临海市志鼎电子科技有限公司浙江临海317000

在焊接式IGBT功率模块封装过程中,通常采用键合引线进行互联,采取两次真空焊接工艺,先进行芯片与DBC陶瓷板的焊接,再进行母排端子与DBC陶瓷板的焊接以及DBC陶瓷板和基板的焊接,焊接质量直接影响IGBT功率模块的可靠性。结合现有国内外IGB... 详细信息

在焊接式IGBT功率模块封装过程中,通常采用键合引线进行互联,采取两次真空焊接工艺,先进行芯片与DBC陶瓷板的焊接,再进行母排端子与DBC陶瓷板的焊接以及DBC陶瓷板和基板的焊接,焊接质量直接影响IGBT功率模块的可靠性。结合现有国内外IGBT功率模块的封装技术,研发IGBT功率模块的焊接前倒装工艺和一次性焊接工艺,可降低芯片热应力,减少模块热阻抗,焊接无空洞,提高可靠性;同时简化焊接工艺复杂度,实现IGBT功率模块的工业化批量生产,进一步降低产品成本。

关键词： IGBT功率模块封装技术倒装工艺一次性焊接工艺

阶梯治疗儿童侵袭性复发性呼吸道乳头状瘤病1例

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中华耳鼻咽喉头颈外科杂志 2024年第8期59卷 867-871页

作者：鲁媛媛于振坤张永辉张庆宇胡慧英梁思萍周玉洁赵腾潘宇飞南京医科大学附属明基医院耳鼻咽喉头颈外科南京210019 南京医科大学附属明基医院影像科南京210019

患者,女,16岁,因“进行性声嘶加重、呼吸道乳头状瘤反复复发15年”入院。患者自1岁时出现声嘶外院就诊,喉镜示:喉肿物(复发性喉乳头状瘤?),遂行支撑喉镜下喉肿物切除术(具体术式不详),术后病理:喉乳头状瘤。术后4个月余复发,再次手术治... 详细信息

患者,女,16岁,因“进行性声嘶加重、呼吸道乳头状瘤反复复发15年”入院。患者自1岁时出现声嘶外院就诊,喉镜示:喉肿物(复发性喉乳头状瘤?),遂行支撑喉镜下喉肿物切除术(具体术式不详),术后病理:喉乳头状瘤。术后4个月余复发,再次手术治疗;后每间隔1~4个月复发并给予手术治疗,直至10岁;10~12岁手术间隔为1年;12~14岁时手术间隔约半年;14~15岁时手术间隔约3个月;共计接受手术40余次。15岁后乳头状瘤病变范围逐渐扩大,于2022年5月我院就诊。查体:喉部多发乳头状瘤,声带黏连,喉狭窄,肺内乳头状瘤播散。入院后,为患者制订阶梯治疗方案:先行全身贝伐珠单抗治疗(4次),喉部及肺内乳头状瘤病灶均明显缩小;后行经支撑喉镜CO 2激光喉乳头状瘤切除术+光动力治疗(3次),至今术后19个月喉部乳头状瘤未复发。目前进一步定期随访中。

关键词：乳头状瘤病喉乳头状瘤贝伐珠单抗肿物切除术支撑喉镜阶梯治疗喉狭窄光动力治疗

GITR调控巨噬细胞自噬在铜绿假单胞菌感染中的作用

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热带医学杂志 2019年第9期19卷 1065-1069,1191页

作者：刘依婷梁斯平朱思颖刘俏娟李嘉颖吴敏昊中山大学中山医学院广东广州510080 中山大学热带病防治研究教育部重点实验室广东广州510080

目的探讨糖皮质激素诱导的肿瘤坏死因子受体(GITR)在铜绿假单胞菌(PA)感染中的作用。方法在小鼠巨噬细胞系RAW264.7细胞中过表达PSG5-GITR,PA感染、异硫氰酸荧光素标记的葡聚糖(FITC-Dextran)或Alexa Fluor 488荧光素标记的酵母多糖生... 详细信息

目的探讨糖皮质激素诱导的肿瘤坏死因子受体(GITR)在铜绿假单胞菌(PA)感染中的作用。方法在小鼠巨噬细胞系RAW264.7细胞中过表达PSG5-GITR,PA感染、异硫氰酸荧光素标记的葡聚糖(FITC-Dextran)或Alexa Fluor 488荧光素标记的酵母多糖生物微粒处理。免疫荧光和蛋白印迹检测PA感染细胞中自噬相关蛋白微管相关蛋白1轻链3(LC3)的表达,免疫荧光、平板计数试验或流式细胞术检测细胞吞噬能力。结果过表达PSG5-GITR促进PA感染后RAW264.7细胞LC3Ⅱ的表达,上调LC3斑点数量;抑制细胞对PA和FITC-Dextran的吞噬作用,下调吞噬溶酶体的数量;3-甲基腺嘌呤抑制自噬后,GITR抑制的RAW264.7细胞吞噬作用被有效回复。结论 GITR通过促进PA诱导的小鼠巨噬细胞RAW264.7自噬,从而抑制其吞噬功能。

关键词：铜绿假单胞菌自噬吞噬

2型糖尿病患者骨密度与代谢相关脂肪性肝病相关性的研究

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中国糖尿病杂志 2024年第6期32卷 437-442页

作者：何思萍梁瑜祯广西医科大学第二附属医院内分泌科南宁530000

目的探讨T2DM患者骨密度(BMD)与代谢相关脂肪性肝病(MAFLD)的相关性。方法选取2021年5月至2022年2月于我院内分泌科住院治疗的T2DM患者300例,根据肝脏超声脂肪受控衰减参数(CAP)分为单纯T2DM组(n=138)及合并MAFLD组(T2DM+MAFLD,n=162)... 详细信息

目的探讨T2DM患者骨密度(BMD)与代谢相关脂肪性肝病(MAFLD)的相关性。方法选取2021年5月至2022年2月于我院内分泌科住院治疗的T2DM患者300例,根据肝脏超声脂肪受控衰减参数(CAP)分为单纯T2DM组(n=138)及合并MAFLD组(T2DM+MAFLD,n=162),采用双能X射线骨密度仪测定BMD。结果与T2DM组比较,T2DM+MAFLD组BMI、腹围(AC)、FIns、FC-P、TG、胰岛素抵抗指数(HOMA-IR)、血清白蛋白、肝脏硬度值(LSM)、CAP、L1-L4 BMD、腰椎整体BMD、大转子BMD、髋部整体BMD升高(P<0.05或P<0.01),HDL-C降低(P<0.01)。Spearman相关分析显示,男性腰椎整体BMD与吸烟史、AC、BMI、CAP、FIns、FC-P、HOMA-IR呈正相关(P<0.05或P<0.01),与碱性磷酸酶(ALP)呈负相关(P<0.01);髋部整体BMD与吸烟史、AC、BMI、CAP、FC-P呈正相关(P<0.05或P<0.01)。女性腰椎整体BMD与BMI、CAP呈正相关(P<0.05或P<0.01),与年龄、ALP呈负相关(P<0.05或P<0.01);髋部整体BMD与BMI、CAP呈正相关(P<0.05),与年龄、ALP呈负相关(P<0.05或P<0.01)。多元线性回归分析显示,CAP是腰椎整体BMD的影响因素,BMI是髋部整体BMD的影响因素。结论 CAP是腰椎整体BMD的影响因素,BMI是髋部整体BMD的影响因素。

关键词：糖尿病,2型代谢相关脂肪性肝病骨密度

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先秦时期的历政文化

史学集刊 2004年第3期 29-33页

作者：梁韦弦吉林师范大学中国思想文化研究所吉林四平136000

中国古代自尧制新历起形成了实质上与巫史文化对立的历政文化,这标志着中国古人对最基本的自然规律开始有了比较明确的认识,从而对以农业为主的社会生产发生了重大的积极作用,并孕育了中国古代的唯物主义天人哲学,故历政文化是中国古代... 详细信息

中国古代自尧制新历起形成了实质上与巫史文化对立的历政文化,这标志着中国古人对最基本的自然规律开始有了比较明确的认识,从而对以农业为主的社会生产发生了重大的积极作用,并孕育了中国古代的唯物主义天人哲学,故历政文化是中国古代最重要的优良传统文化之一。在先秦学术中,真正继承历政文化精髓并使之升华的是儒家之学,渊源于历政文化的阴阳五行之学则最终沦为一种“舍人事而任鬼神”的“小数”。

关键词：历政文化天人哲学阴阳五行先秦儒家

A confinement strategy to in-situ prepare a peanut-like N-doped, C-wrapped TiO_(2) electrode with an enhanced desalination capacity and rate for capacitive deionization

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Nano Research 2021年第3期14卷 684-691页

作者： Mingxing liang Xueting Bai Fei Yu Jie Ma College of Marine Ecology and Environment Shanghai Ocean UniversityShanghai201306China State Key Laboratory of Pollution Control and Resource Reuse College of Environmental Science and EngineeringTongji UniversityShanghai200092China Research Center for Environmental Functional Materials College of Environmental Science and EngineeringTongji University1239 Siping RoadShanghai200092China Shanghai Institute of Pollution Control and Ecological Security Shanghai200092China

Capacitive deionization(CDI)technology has been considered a promising desalination technique,especially for brackish water,because of its relatively low energy consumption,facile operation,and easy regeneration of ***,the desalination capacity,cost,fabrication method,electrochemical stability,and environmental unfriendliness of the electrodes have restricted the practical application of the CDI ***,we reported the one-step in situ preparation of nitrogen-doped and carbon-decorated MXene-derived TiO_(2)(termed N-TiO_(2−x)/C)through the confinement-growth *** small particle size(∼25 nm)and uniform distribution of a peanut-like N-TiO_(2−x)/C material could be ascribed to the confined growth space created by the nanoporous structure of melamine *** defects produced by N doping provide an enhanced electrical conductivity and more adsorption sites,while wrapping with a carbon shell layer increases the conductivity and offers protection for N-TiO_(2−x) to achieve an excellent electrochemical *** prepared N-TiO_(2−x)/C electrode is hydrophilic due to the abundant oxygen-containing functional groups(e.g.,C-O,N-Ti-O,-NO_(x),and-OH)and exhibits a high salt removal capacity(33.4 mg·g^(−1)),desalination rate(1.5 mg·g^(−1)·min^(−1)),and remarkable cycling stability(without declining after 100 cycles),which might be ascribed to the synergistic effects of the short ion diffusion path,more active adsorption sites,enhanced conductivity,pseudocapacitive behavior,and protection of the carbon shell *** work provides a confined-growth strategy to develop MXene-derived oxide electrodes for electrochemical desalination.

关键词： capacitive deionization confinement growth MXene-derived N-doped pseudocapacitive behavior