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gRK2 mediated degradation of SAV1 initiates hyperplasia of fibroblast-like synoviocytes in rheumatoid arthritis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1222-1240页

作者： Paipai guo Ji Jiang Rui chu Feng He Mingli ge Ruhong Fang Qiuyun guan Huijuan Cheng chunru Jiang Tiantian Su Zhenduo Zhu Hao Liu Wei Wei Shihao Zhang Qingtong Wang Institute of Clinical Pharmacology Anhui Medical UniversityKey Laboratory of Anti-inflammatory and Immune MedicineMinistry of EducationCollaborative Innovation Center of Anti-inflammatory and Immune MedicinesHefei 230032China School of Pharmacy Bengbu Medical CollegeBengbu 233030China The Third Affiliated Hospital of Anhui Medical University(the First People’s Hospital of Hefei) Hefei 230061China

Hyperplasia and migration of fibroblast-like synoviocytes(FLSs)are the key drivers in the pathogenesis of rheumatoid arthritis(RA)and joint *** Yes-associated protein(YAP),which is a powerful transcription co-activator for proliferative genes,was observed in the nucleus of inflammatory FLSs with unknown upstream *** gene Expression Omnibus database analysis,it was found that Salvador homolog-1(SAV1),the pivotal negative regulator of the Hippo-YAP pathway,was slightly downregulated in RA ***,SAV1 protein expression is extremely ***,it was revealed that SAV1 is phosphorylated,ubiquitinated,and degraded by interacting with an important serine-threonine kinase,g protein-coupled receptor(gPCR)kinase 2(gRK2),which was predominately upregulated by gPCR activation induced by ligands such as prostaglandin E2(PgE2)in *** process further contributes to the decreased phosphorylation,nuclear translocation,and transcriptional potency of YAP,and leads to aberrant FLSs *** depletion of gRK2 or inhibition of gRK2 by paroxetine rescued SAV1 expression and restored YAP phosphorylation and finally inhibited RA FLSs proliferation and ***,paroxetine treatment effectively reduced the abnormal proliferation of FLSs in a rat model of collagen-induced arthritis which was accompanied by a significant improvement in clinical ***,these results elucidate the significance of gRK2 regulation of Hippo-YAP signaling in FLSs proliferation and migration and the potential application of gRK2 inhibition in the treatment of FLSs-driven joint destruction in RA.

关键词： Rheumatoid arthritis Fibroblast-like synoviocytes g protein-coupled receptor kinase 2 Salvador homolog-1 Yes-associated protein

抵当陷胸汤调控PI3K/Akt信号通路对糖尿病大鼠足细胞凋亡的影响

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中国实验方剂学杂志 2024年第12期30卷 62-69页

作者：张可敬王悦琦储全根储俊安徽中医药大学中医学院新安医学教育部重点实验室合肥230038 安徽中医药大学新安医学与中医药现代化研究所合肥230012

目的:观察抵当陷胸汤对糖尿病大鼠肾脏的保护作用及其对磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路的调控作用与对足细胞凋亡的影响,探讨抵当陷胸汤改善糖尿病肾病的机制。方法:采用单次腹腔注射链脲佐菌素(STZ)溶液55 mg·kg^(-1... 详细信息

目的:观察抵当陷胸汤对糖尿病大鼠肾脏的保护作用及其对磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路的调控作用与对足细胞凋亡的影响,探讨抵当陷胸汤改善糖尿病肾病的机制。方法:采用单次腹腔注射链脲佐菌素(STZ)溶液55 mg·kg^(-1)的方法建立糖尿病模型,将模型复制成功的30只随机分为模型组、抵当陷胸汤组(8.10 g·kg^(-1))、小陷胸汤组(4.05 g·kg^(-1))、抵当汤组(4.05 g·kg^(-1))、阿拉氯胺(ALT-711)组(3 mg·kg^(-1)),每组6只,另设6只空白组大鼠。连续给药8周后,采用苏木素-伊红(HE)染色观察大鼠肾脏组织病理形态变化;马松(Masson)染色观察胶原沉积程度;高碘酸-席夫(PAS)染色观察基底膜病变;免疫组化法检测大鼠肾组织磷酸化(p)-PI3K、p-Akt蛋白表达;原位末端标记法(TUNEL)检测大鼠足细胞凋亡;实时荧光定量聚合酶链式反应(Real-time PCR)检测大鼠肾组织PI3K、Akt mRNA表达情况;蛋白免疫印迹法(Western blot)检测肾组织中PI3K、p-PI3K、Akt、p-Akt、B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、磷酸化糖原合成酶激酶-3β(p-gSK-3β)、胱天蛋白酶-3(Caspase-3)的蛋白表达。结果:与正常组比较,模型组大鼠肾小球代偿性膨胀,系膜细胞增殖,系膜间质大量胶原沉积,基底膜增厚,PI3K、Akt mRNA表达减少,PI3K、Akt蛋白磷酸化显著受到抑制(PgSK-3β、Caspase-3表达显著升高(PgSK-3β、Caspase-3表达显著降低(P<0.01),足细胞凋亡率显著降低(P<0.01)。结论:抵当陷胸汤可能通过促进PI3K/Akt信号通路活化,抑制足细胞凋亡,减缓糖尿病肾病的发展进程。

关键词：糖尿病肾脏病变抵当陷胸汤痰瘀同治磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)通路足细胞凋亡

Naked-eye visualization of lymph nodes using fluorescence nanoprobes in non-human primate-animal models

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Nano Research 2024年第8期17卷 7404-7414页

作者： Xiaoyuan Ji Binbin chu Xiaofeng Wu Zhiming Xia Airui Jiang Chenyu Wang Zhiming Chen Danni Zhong Qiaolin Wei Bin Song Wanlin Li Yiling Zhong Houyu Wang Fenglin Dong Min Zhou Yao He Suzhou Key Laboratory of Nanotechnology and Biomedicine Jiangsu Key Laboratory for Carbon-Based Functional Materials&DevicesInstitute of Functional Nano and Soft Materials(FUNSOM)Soochow UniversitySuzhou 215123China School of Public Health Shanghai Jiao Tong University School of MedicineShanghai 200025China Zhejiang University-University of Edinburgh Institute(ZJU-UoE Institute) Zhejiang UniversityHaining 314400China Department of Ultrasound the First Affiliated Hospital of Soochow UniversitySuzhou 215006China State Key Laboratory(SKL)of Biobased Transportation Fuel Technology Zhejiang UniversityHangzhou 310027China School of Pharmacy Hangzhou Normal UniversityHangzhou 311121China Macao Translational Medicine Center Macao University of Science and TechnologyTaipa 999078MacaoChina Macao Institute of Materials Science and Engineering Macao University of Science and TechnologyTaipa 999078MacaoChina

Despite sufficient studies performed in non-primate animal models,there exists scanty information obtained from pilot trials in non-human primate animal models,severely hindering nanomaterials moving from basic research into clinical *** herein present a pioneering demonstration of nanomaterials based optical imaging-guided surgical operation by using macaques as a typical kind of non-human primate-animal ***,taking advantages of strong and stable fluorescence of the small-sized(diameter:~5 nm)silicon-based nanoparticles(SiNPs),lymphatic drainage patterns can be vividly visualized in a real-time manner,and lymph nodes(LN)are able to be sensitively detected and precisely excised from small animal models(e.g.,rats and rabbits)to non-human primate animal models(e.g.,cynomolgus macaque(Macaca fascicularis)and rhesus macaque(Macaca mulatta)).Compared to clinically used invisible near-infrared(NIR)lymphatic tracers(i.e.,indocyanine green(ICg);etc.),we fully indicate that the SiNPs feature unique advantages for naked-eye visible fluorescence-guided surgical operation in long-term *** toxicological analysis in macaque models further provides confirming evidence of favorable biocompatibility of the SiNPs *** expect that our findings would facilitate the translation of nanomaterials from the laboratory to the clinic,especially in the field of cancer treatment.

关键词： fluorescent silicon nanoparticles lymph node real-time naked-eye visualization macaque models

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元宇宙空间刑法规制的教义学立场

暨南学报（哲学社会科学版） 2024年第1期46卷 79-96页

作者：储陈城安徽大学法学院

元宇宙是当今人工智能、大数据、5g、区块链以及扩展现实等一系列技术发展集合的结果,本质上是互联网的升级版,其具有拟真性和虚实相融的特点,但是仍然依附于现实世界。元宇宙空间中隐藏着诸如侵犯人身权利、侵犯财产权利、妨害社会管... 详细信息

元宇宙是当今人工智能、大数据、5g、区块链以及扩展现实等一系列技术发展集合的结果,本质上是互联网的升级版,其具有拟真性和虚实相融的特点,但是仍然依附于现实世界。元宇宙空间中隐藏着诸如侵犯人身权利、侵犯财产权利、妨害社会管理秩序以及破坏经济秩序等刑事风险。刑法在规制上述风险时,尚没有增设新罪的必要,通过刑法解释可以实现规制的效果。刑法通过解释介入元宇宙空间领域,需以利益衡量原则为指导,坚持刑法最后介入和技术规制技术优先规则,防止前沿技术的发展受到刑法的不当干预。同时,元宇宙空间中不法的认定应以法益现实被侵害为基础,依循各个罪名的规范保护目的,对相应的行为进行客观解释。

关键词：元宇宙刑事风险利益衡量法益侵害客观解释

Tomato CYP94C1 inactivates bioactive JA-lle to attenuate jasmonate-mediated defense during fruit ripening

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Molecular Plant 2024年第4期17卷 509-512页

作者： Tianxia Yang Lei Deng Qinyang Wang chuanlong Sun Muhammad Ali Fangming Wu Huawei Zhaj Qian Xu Peiyong Xin Shujing Cheng Jinfang chu Tingting Huang Chang-Bao Li chuanyou Li Key Laboratory of Seed Innovation Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China College of Life Sciences Shandong Agricultural UniversityTai'an 271018China Taishan Academy of Tomato Innovation Tai'an 271018China CAS Center for Excellence in Biotic Interactions University of Chinese Academy of SciencesBeijing 100049China College of Horticulture Science and Engineering Shandong Agricultural UniversityTaian 271018China Institute of Vegetable Qingdao Academy of Agricultural SciencesQingdao 266100China Key Laboratory of Biology and genetic Improvement of Horticultural Crops(North China) Ministry of AgricultureBeijing Vegetable Research CenterBeijing Academy of Agriculture and Forestry SciencesBejing 100097China Frontiers Science Center for Molecular Design Breeding(MOE) Department of Plant Genetics and BreedingChina Agricultural UniversityBeijing 100193China

Dear Editor,Fruit rot caused by necrotrophic pathogens results in substantial reductions in fruit yield and revenues worldwide(Petrasch et al.,2019).A widespread phenomenon in fleshy fruit species is the susceptibility of ripe fruits to necrotrophs(Silva et al.,2021),which facilitates seed dispersal(Forlani et al.,2019)but causes severe post-harvest losses in *** most of the nutritional and sensory qualities of fruits are elaborated at the ripening stage(Liu et al.,2015),balancing fruit ripening and pathogen resistance to maintain fruit quality has proven to be challenging.A deeper understanding of the mechanisms underlying the increased susceptibility of fruits to necrotrophs during ripening could lead to new strategies for producing necrotrophy-resistant fruits without compromising ripening-relatedquality.

关键词： susceptibility maintain fruit

文化记忆与非虚构写作:以利季娅·金兹堡为例

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学术月刊 2024年第6期56卷 124-127,112,131页

作者：初金一耶鲁大学斯拉夫语言文学系

一、问题的缘起我想从两则引文谈起,“真正的作者并不是我,而是我焦躁不安的记忆”(forthe real author is notI,but my impatient memory),“记忆是一位诗人,别把他当成历史学家”(le souvenir est un poete,n'en fais pas un histori... 详细信息

一、问题的缘起我想从两则引文谈起,“真正的作者并不是我,而是我焦躁不安的记忆”(forthe real author is notI,but my impatient memory),“记忆是一位诗人,别把他当成历史学家”(le souvenir est un poete,n'en fais pas un historien)。前者出自弗拉基米尔·纳博科夫的小说《绝望》(Despair);后者出自法国诗人保罗·热拉迪(Paul géraldy)的《你和我》(Toi et moi)。这两句话都指向了记忆和写作的关系。在纳博科夫那里,写作并不是指作家的创造性、想象性的劳动,而是在记忆的迫切要求下发生的。对纳博科夫而言,与其说作者记录下了记忆,不如说记忆指挥着笔,让自己得以显现。

关键词：文化记忆焦躁不安法国诗人纳博科夫非虚构写作 Paul 引文想象性

响应面优化黄姜花根多糖提取工艺及其抗氧化活性分析

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饲料研究 2024年第11期47卷 109-113页

作者：黎楚楚徐霖林长松贵州理工学院食品药品制造工程学院贵州贵阳550005 贵阳学院生物与环境工程学院贵州贵阳550005

试验旨在探究黄姜花根多糖的最佳提取工艺及其体外抗氧化活性,以黄姜花根为原料,探究液料比、提取温度、提取时间对黄姜花根多糖得率的影响,并结合响应面法优化黄姜花根多糖提取工艺,通过测定1,1-二苯基-2-苦肼基(DPPH)自由基和2,2-联氮... 详细信息

试验旨在探究黄姜花根多糖的最佳提取工艺及其体外抗氧化活性,以黄姜花根为原料,探究液料比、提取温度、提取时间对黄姜花根多糖得率的影响,并结合响应面法优化黄姜花根多糖提取工艺,通过测定1,1-二苯基-2-苦肼基(DPPH)自由基和2,2-联氮-二(3-乙基-苯并噻唑-6-磺酸)二铵盐(ABTS^(+))自由基的清除能力研究黄姜花根的抗氧化活性。结果表明:在提取温度83℃、液料比30 mL/g、提取时间172 min的条件下,黄姜花根多糖得率最高,可达9.32%。在一定范围内,黄姜花根多糖清除自由基能力与多糖的浓度呈量效关系,黄姜花根多糖溶液对DPPH自由基和ABTS^(+)自由基的清除率分别为92.58%和91.80%。研究表明,黄姜花根多糖的抗氧化活性较强,可为今后黄姜花根多糖的进一步开发与应用提供参考。

关键词：黄姜花根多糖响应面热水浸提抗氧化活性

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非极大部分对偶平面图的刻画与平面三角剖分图的部分对偶最大亏格

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数学学报（中文版） 2024年第3期67卷 531-538页

作者：秦楚陈仪朝苏州科技大学数学科学学院苏州215009

图嵌入g的部分对偶g^(A)是选择g的部分边集A做对偶,它是经典的庞加莱对偶g^(*)的推广.与经典的庞加莱对偶不同的是,部分对偶g^(A)的亏格往往不等于g的亏格.类似于黄-刘图的非上可嵌入性刻画定理,对平面图我们先证明了非极大部分对偶平... 详细信息

图嵌入g的部分对偶g^(A)是选择g的部分边集A做对偶,它是经典的庞加莱对偶g^(*)的推广.与经典的庞加莱对偶不同的是,部分对偶g^(A)的亏格往往不等于g的亏格.类似于黄-刘图的非上可嵌入性刻画定理,对平面图我们先证明了非极大部分对偶平面图结构定理,并由此确定了平面三角剖分图g的部分对偶最大亏格,即当g为3-圈时,g的部分对偶最大亏格为1;否则g的部分对偶最大亏格为其顶点数减1.

关键词：部分对偶极大部分对偶平面图平面三角剖分图部分对偶最大亏格

Causal relationships between gut microbiota and dementia:A twosample,bidirectional,Mendelian randomization study

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World Journal of Clinical Cases 2024年第16期12卷 2780-2788页

作者： Zhao-Lin Ren Hai-Hong Zhou chu-Pei Chen Hao He Duo-Lao Wang Zhou Liu Department of Neurology The Affiliated Hospital of Guangdong Medical UniversityZhanjiang 524000Guangdong ProvinceChina Department of Clinical Medicine Guangdong Medical UniversityZhanjiang 524000Guangdong ProvinceChina Department of Clinical Sciences Liverpool School of Tropical MedicineLiverpool L693BXUnited Kingdom

BACKgROUND Existing evidence suggests that gut microbiota represent a significant environmental risk factor for various forms of dementia,including Alzheimer's dementia,vascular dementia,and dementia in other diseases classified ***,the exact causal relationships between gut microbiota and the different forms of dementia or their subtypes remain *** To investigate putative causal relationships between gut microbiota and dementia or its subtypes using Mendelian randomization(MR)*** A bidirectional,two-sample,MR analysis was conducted utilizing publicly available gut microbiota-related genome-wide association study(gWAS)summary data from the MiBiogen consortium alongside gWAS summary statistics for dementia and its subtypes from the Finngen *** variables were selected according to the fundamental tenets of MR and their strengths were evaluated using the *** MR methods were employed,and the robustness of our findings was *** account for multiple comparisons,we applied the Bonferroni method for P-value *** We identified several gut microbiota taxa exhibiting putative causal relationships with dementia or its subtypes,potentially serving as risk or protective factors for the *** addition,reverse MR analysis indicated that the relative abundance of several gut microbiota taxa might be influenced by dementia or its *** exhaustive sensitivity analysis confirmed the absence of heterogeneity and horizontal *** applying correction for multiple testing,we observed that the order Bacillales(odds ratio:0.830,95%confidence interval:0.740-0.932,P=0.00155,Padjust=0.0311)exhibited a strong association with Alzheimer’s disease-related *** The results suggest that gut microbiota is causally associated with *** findings provide novel insights into the pathophysiology of dementia and have important implications for its treatment and prevention.

关键词： Mendelian randomization Finngen MiBiogen gut microbiota Dementia Alzheimer’s disease Vascular dementia