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Geroprotection from ergothioneine treatment in Drosophila melanogaster by improving intestinal barrier and activation of intestinal autophagy

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Food Science and Human Wellness 2024年

作者： Hong-Yu Pan Na Wang Qian-Wang Zheng Yuan Zou Jing-Ru zhong Guo-Zhao Luo Ming-Zhen Tu Li-Qiong Guo jun-Fang Lin College of Food Science， South China Agricultural University.Guangzhou Research Center for Micro-Ecological Agent Engineering and Technology of Guangdong Province Faculty of Food Science and Engineering， Kunming University of Science and Technology Guangzhou Alchemy Biotechnology Co.， Ltd

Ergothioneine is a natural amino acid with powerful antioxidant activity. Previous studies have demonstrated that ergothioneine can increase the lifespan of Drosophila melanogaster and Caenorhabditis elegans， and enhance telomerase activity. In present study， the metagenomics sequencing and qRT-PCR analysis were employed to characterize the composition and diversity of gut microbiome in aging flies. And the alterations in the gut barrier， gut morphology， and other gut physiological indicators of aging flies were evaluated. Here， the results showed that EGT induced little variations in gut microbiota composition in flies at mid-life， and significant alterations in the gut microbiota populations were only observed in flies at late-life. And ergothioneine attenuated age-related gut injuries， including decreasing reactive oxygen species levels in intestinal enterocytes， reduction of intestinal cells death， and preservation of gut integrity in aging flies. Ergothioneine also improved the gut morphology by preserving the structure and shape of cell organelles and inducing the intestinal autophagy. And activation of intestinal autophagy also contributed to the longevity effect mediated by ergothioneine in an unidentified mechanism.

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奠定中华民族共同体学学科基础的垦拓力作——《中华民族共同体概论》评介

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中南民族大学学报（人文社会科学版） 2024年第7期44卷 18-21页

作者：范军钟准健华中师范大学文学院

尺寸教材,悠悠国事。党的十八大以来,为进一步推进习近平总书记关于加强和改进民族工作的重要思想,铸牢中华民族共同体意识,近年,围绕中华民族共同体的学术研讨、教育教学、教材出版等一系列工作受到广泛关注和持续推进。2021年,由国家... 详细信息

尺寸教材,悠悠国事。党的十八大以来,为进一步推进习近平总书记关于加强和改进民族工作的重要思想,铸牢中华民族共同体意识,近年,围绕中华民族共同体的学术研讨、教育教学、教材出版等一系列工作受到广泛关注和持续推进。2021年,由国家民族事务委员会筹划的《中华民族共同体概论》(以下简称《概论》)经过各方专家学者的多次改写、修订和完善后,最终凝聚成四十余万字的恢宏教材,并于2023年12月由高等教育出版社、民族出版社联合出版。

关键词：高等教育出版社民族出版社联合出版教材出版《概论》中华民族共同体学科基础党的十八大以来

基于方剂靶点谱效关系的中成药临床精准定位模式探索——以芪蛭通络胶囊为例

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中国实验方剂学杂志 2024年第3期30卷 98-104页

作者：于亚南李兵刘骏王忠中国中医科学院中医临床基础医学研究所北京100700 中国中医科学院中药研究所北京100700

中成药临床价值是中药产业发展的核心方向。“精准化”的临床定位决定了从哪个角度证明药物的价值,是凸显临床价值的关键环节。该文以中成药“芪蛭通络胶囊”临床定位研究为例,展示“方剂靶点谱效比较-方剂核心价值发现-临床定位试验确... 详细信息

中成药临床价值是中药产业发展的核心方向。“精准化”的临床定位决定了从哪个角度证明药物的价值,是凸显临床价值的关键环节。该文以中成药“芪蛭通络胶囊”临床定位研究为例,展示“方剂靶点谱效比较-方剂核心价值发现-临床定位试验确证”的中成药临床精准定位关键技术框架。该技术框架靶向临床精准定位需要解决的系列问题,在临床试验开展前,基于方剂多组分、多靶点及临床适应证多表型数据的多组学网络分析技术,发现中药品种的核心价值,预测其可能的临床优势,继而再针对其预测的临床优势选择合理的疗效指标,结合动态灵活的创新性临床试验判断及验证其临床疗效,提高临床定位的成功率。该研究模式将“组学技术”与“循证”相结合,定位“精准循证”的理念,旨在为建立具有中医药特色的中成药上市后精准用药与定位提供一种新的策略与方法,也为中医学走向精准医学提供更多技术层面的思考。

关键词：方剂组学临床定位靶点谱效精准循证芪蛭通络胶囊

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白藜芦醇柔性脂质体的制备及其体外评价

中国新药杂志 2024年第2期33卷 187-193页

作者：钟玮王俊张玉洁王中彦沈阳药科大学中药学院沈阳110016 沈阳药科大学药学院沈阳110016

目的:制备白藜芦醇柔性脂质体,并考察其体外特性.方法:采用乙醇注入法制备脂质体,以包封率、粒径为指标,通过单因素考察和星点设计-响应面法优化白藜芦醇脂质体处方;以皮肤滞留量筛选表面活性剂的配比,制备白藜芦醇柔性脂质体;并对其表... 详细信息

目的:制备白藜芦醇柔性脂质体,并考察其体外特性.方法:采用乙醇注入法制备脂质体,以包封率、粒径为指标,通过单因素考察和星点设计-响应面法优化白藜芦醇脂质体处方;以皮肤滞留量筛选表面活性剂的配比,制备白藜芦醇柔性脂质体;并对其表面特征、粒径、Zeta电位、体外释放度及皮肤滞留进行考察.结果:最终处方:大豆卵磷脂量为7.5mg·mL-1,磷脂-胆固醇的质量比为3.16∶1,磷脂-白藜芦醇的质量比为30.28∶1,磷脂-吐温-80的质量比为3∶1.制得的白藜芦醇柔性脂质体的平均粒径为(143.70±1.74)nm,多分散系数(PDI)为(0.092±0.060),Zeta电位为-(9.65±0.61)mV.体外释放研究表明,白藜芦醇乙醇溶液在4h释放了80%,达到释放平衡;白藜芦醇柔性脂质体在8h时的累计释放度为54%,24h内持续缓慢释放,符合Higuchi动力学模型.皮肤滞留实验结果表明,其在2~6h时皮肤滞留量缓慢升高,证明其可以缓慢释放,且在6h时达到34.14μg·cm-2.结论:优选的柔性脂质体重现性好、包封率高、粒径小,具有明显的缓释效果,皮肤滞留量高,适合于局部给药.

关键词：白藜芦醇柔性脂质体体外释放离体经皮渗透试验滞留量

Multiomics analyses of two Leonurus species illuminate leonurine biosynthesis and its evolution

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Molecular Plant 2024年第1期17卷 158-177页

作者： Peng Li Meng-Xiao Yan Pan Liu Dan-Jie Yang Ze-Kun He Yun Gao Yan Jiang Yu Kong Xin zhong Sheng Wu jun Yang Hong-Xia Wang Yan-Bo Huang Le Wang Xiao-Ya Chen Yong-Hong Hu Qing Zhao Ping Xu shanghai Key Laboratory of Plant Functional Genomics and Resources Shanghai Chenshan Botanical GardenShanghai Chenshan Plant Science Research CenterChineseAcademy of SciencesShanghaiChina College of Life Sciences Shanghai Normal UniversityShanghai 200234China State Key Laboratory of Plant Molecular Genetics CAS Center for Excellence in Molecular Plant SciencesChinese Academy of SciencesShanghaiChina University of the Chinese Academy of Sciences Beijing 100049China The Research Center of Chiral Drugs Innovation Research Institute of Traditional Chinese MedicineShanghai University of Traditional Chinese Medicine1200 Cailun RoadShanghai 201203China College of Chemistry and Chemical Engineering Shanghai University of Engineering ScienceShanghai 201620China

The Lamiaceae family is renowned for its terpenoid-based medicinal components,but Leonurus,which has traditional medicinal uses,stands out for its alkaloid-rich ***,the principal active compound found in Leonurus,has demonstrated promising effects in reducing blood lipids and treating ***,the biosynthetic pathway of leonurine remains largely ***,we present the chromosome-level genome sequence assemblies of Leonurus japonicus,known for its high leonurine production,and Leonurus sibiricus,characterized by very limited leonurine *** integrating genomics,RNA sequencing,metabolomics,and enzyme activity assay data,we constructed the leonurine biosynthesis pathway and identified the arginine decarboxylase(ADC),uridine diphosphate glucosyltransferase(UGT),and serine carboxypeptidase-like(SCPL)acyltransferase enzymes that catalyze key reactions in this *** analyses revealed that the UGT–SCPL gene cluster evolved by gene duplication in the ancestor of Leonurus and neofunctionalization of SCPL in ***,which contributed to the accumulation of leonurine specifically in ***,our comprehensive study illuminates leonurine biosynthesis and its evolution in Leonurus.

关键词： Lamiaceae Leonurus japonicus Leonurus sibiricus genome sequence alkaloids leonurine gene cluster biosynthetic pathway evolution

Caveolin‑1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease

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Military Medical Research 2024年第2期11卷 206-227页

作者： Guang-Hui Deng Chao-Feng Wu Yun-Jia Li Hao Shi Wei-Chao zhong Mu-Keng Hong jun-Jie Li Jia-Min Zhao Chang Liu Meng-Chen Qin Zhi-Yun Zeng Wei-Min Zhang Ken Kin Lam Yung Zhi-Ping Lv Lei Gao Department of Gastroenterology Integrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510315China School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou 510515China Department of Hepatology Cancer CenterIntegrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510315China Shenzhen Traditional Chinese Medicine Hospital Shenzhen 518033GuangdongChina Department of Biology Hong Kong Baptist UniversityKowloon TongKowloonHong Kong SAR 999077China

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron *** previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the *** study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in ***:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this ***-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in ***,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload ***,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,Western blotting,immunofluorescence staining,immunohistochemical staining and *** related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and ***:Significant disorder of lipid and iron metabolism occurred in *** expression of Cav-1 was decreased in NAFLD hepatocytes(P<0.05),accompanied by iron metabolism ***-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD,subsequently alleviating the oxidative stress induced by excess ferrous ions in the ***,CD68^(+) CD163^(+) macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver,which was contrary to the effect of Cav-1 in *** correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers(P<0.05).Conclusions:These findings confirm that Cav-1 is an essential target protein that reg

关键词： Caveolin-1 Nonalcoholic fatty liver disease Iron metabolism Ferritin Oxidative stress

Aptamers targeting SARS-CoV-2 nucleocapsid protein exhibit potential ant1ip1 an-coronavirus activity

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1186-1198页

作者： Minghui Yang Chunhui Li Guoguo Ye Chenguang Shen Huiping Shi Liping zhong Yuxin Tian Mengyuan Zhao Pengfei Wu Abid Hussain Tian Zhang Haiyin Yang jun Yang Yuhua Weng Xinyue Liu Zhimin Wang Lu Gan Qianyu Zhang Yingxia Liu Ge Yang Yuanyu Huang Yongxiang Zhao School of Life Science Advanced Research Institute of Multidisciplinary ScienceKey Laboratory of Molecular Medicine and BiotherapyBeijing Institute of TechnologyBeijing 100081China National Clinical Research Center for infectious disease Shenzhen Third People’s HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhen 518112China Guangdong Provincial Key Laboratory of Tropical Disease Research School of Public HealthSouthern Medical UniversityGuangzhou 510515China State Key Laboratory of Targeting Oncology National Center for International Research of Biotargeting TheranosticsGuangxi Key Laboratory of Biotargeting TheranosticsCollaborative Innovation Center for Targeting Tumor Diagnosis and TherapyGuangxi Medical UniversityNanning 530021China CAMS Key Laboratory of Antiviral Drug Research Beijing Key Laboratory of Antimicrobial AgentsInstitute of Medicinal BiotechnologyChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Emerging and recurrent infectious diseases caused by human coronaviruses(HCoVs)continue to pose a significant threat to global public health *** light of this ongoing threat,the development of a broad-spectrum drug to combat HCoVs is an urgently ***,we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment(SELEX).These aptamers have nanomolar affinity with the nucleocapsid protein(NP)of Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and also show excellent binding efficiency to the N proteins of both SARS,MERS,HCoV-OC43 and-NL63 with affinity KD values of 1.31 to 135.36 *** aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant(BA.5)with EC50 values at 2.00 nM and 41.08 nM,*** protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs(−229E and-HKU1).In conclusion,we have identified six aptamers with a high pan-coronavirus antiviral activity,which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.

关键词： acute threat conclusion

GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines

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World Journal of Stem Cells 2024年第5期16卷 538-550页

作者： Yang-Zhou Jiang Lan-Yue Hu Mao-Shan Chen Xiao-Jie Wang Cheng-Ning Tan Pei-Pei Xue Teng Yu Xiao-Yan He Li-Xin Xiang Yan-Ni Xiao Xiao-Liang Li Qian Ran zhong-jun Li Li Chen Laboratory of Radiation Biology Department of Blood TransfusionLaboratory Medicine CenterThe Second Affiliated HospitalThird Military Medical UniversityChongqing 400037China Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation Center Ministry of Education of the People’s Republic of ChinaChongqing 400037China

BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1)have been identified as negative regulators of ***,the positive regulators of ANKRD26 are still *** To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 *** Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family *** to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activi

关键词： Ankyrin repeat domain containing 26 GATA binding protein 2 Thrombocytopenia 2 Transcriptional regulation Myeloid-derived cell lines

目标跟踪中基于IoU和中心点距离预测的尺度估计

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自动化学报 2024年第8期50卷 1646-1659页

作者：李绍明储珺冷璐涂序继南昌航空大学软件学院南昌330063 江西省图像处理与模式识别重点实验室南昌330063

通过分析基于交并比(Intersection over union,IoU)预测的尺度估计模型的梯度更新过程,发现其在训练和推理过程仅将IoU作为度量,缺乏对预测框和真实目标框中心点距离的约束,导致外观模型更新过程中模板受到污染,前景和背景分类时定位出... 详细信息

通过分析基于交并比(Intersection over union,IoU)预测的尺度估计模型的梯度更新过程,发现其在训练和推理过程仅将IoU作为度量,缺乏对预测框和真实目标框中心点距离的约束,导致外观模型更新过程中模板受到污染,前景和背景分类时定位出现偏差.基于此发现,构建了一种结合IoU和中心点距离的新度量NDIoU(Normalization distance IoU),在此基础上提出一种新的尺度估计方法,并将其嵌入判别式跟踪框架.即在训练阶段以NDIoU为标签,设计了具有中心点距离约束的损失函数监督网络的学习,在线推理期间通过最大化NDIoU微调目标尺度,以帮助外观模型更新时获得更加准确的样本.在七个数据集上与相关主流方法进行对比,所提方法的综合性能优于所有对比算法.特别是在GOT-10k数据集上,所提方法的AO、SR_(0.50)和SR_(0.75)三个指标达到了65.4%、78.7%和53.4%,分别超过基线模型4.3%、7.0%和4.2%.

关键词：目标跟踪交并比尺度估计中心点距离