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Small molecule conjugates with selective estrogen receptor β agonism promote anti-aging benefits in metabolism and skin recovery

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2137-2152页

作者： Tarik Zahr Vijay K.Boda Jian Ge lexiang yu Zhongzhi Wu Jianwen Que Wei Li Li Qiang Naomi Berrie Diabetes Center Columbia UniversityNew YorkNY 10032USA Department of Molecular Pharmacology and Therapeutics Columbia UniversityNew YorkNY 10032USA Department of Pharmaceutical Sciences College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN 38163USA Drug Discovery Center College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN 38163USA Division of Digestive and Liver Diseases Columbia UniversityNew YorkNY 10032USA Center for Human Development Columbia UniversityNew YorkNY 10027USA Department of Pathology and Cell Biology Columbia UniversityNew YorkNY 10032USA Department of Medicine Columbia UniversityNew YorkNY 10032USA

Estrogen is imperative to mammalian reproductivity,metabolism,and ***,the hormone activating estrogen receptor(ERs)αcan cause major safety concerns due to the enrichment of ERαin female tissues and certain *** contrast,ERβis more broadly expressed in metabolic tissues and the ***,it is desirable to generate selective ERβagonist conjugates for maximizing the therapeutic effects of ERs while minimizing the risks of ERα***,we report the design and production of small molecule conjugates containing selective non-steroid ERβagonists Gtx878 or *** of aged mice with our synthesized conjugates improved aging-associated declines in insulin sensitivity,visceral adipose integrity,skeletal muscle function,and skin health,with validation in *** further uncovered the benefits of ERβconjugates in the skin using two inducible skin injury mouse models,showing increased skin basal cell proliferation,epidermal thickness,and wound ***,our ERβ-selective agonist conjugates offer novel therapeutic potential to improve aging-associated conditions and aid in rejuvenating skin health.

关键词： Estrogen receptorβ Aging Metabolism Skin injury Muscle metabolism Small molecule conjugates Regeneration Adiposity

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肺炎患儿NSE、ESR及CRP水平测定及临床意义分析

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潍坊医学院学报 2024年第3期46卷 202-205页

作者：齐宁宁于乐香杨柳李田华潍坊市人民医院小儿内科山东潍坊261041

目的探讨特异性烯醇化酶(NSE)、血沉(ESR)及C反应蛋白(CRP)在儿童肺炎中的临床应用价值。方法选取2020年9月~2023年6月在潍坊市人民医院住院治疗的153例肺炎患儿作为实验组,其中肺炎支原体肺炎(MP+)79例,非支原体肺炎(MP-)74例;重度肺... 详细信息

目的探讨特异性烯醇化酶(NSE)、血沉(ESR)及C反应蛋白(CRP)在儿童肺炎中的临床应用价值。方法选取2020年9月~2023年6月在潍坊市人民医院住院治疗的153例肺炎患儿作为实验组,其中肺炎支原体肺炎(MP+)79例,非支原体肺炎(MP-)74例;重度肺炎22例,轻度肺炎131例。选取57例同期门诊健康查体儿童作为对照组。测定各组儿童血清NSE、ESR和CRP水平,采用SPSS25.0软件对实验数据进行分析。结果 (1)实验组血清NSE、ESR、CRP水平均高于对照组(P0.05),但均高于对照组(P0.05)。(3)重度肺炎组血清NSE、CRP高于轻度肺炎组(P<0.05)。(4)诊断肺炎的AUC值,NSE高于CRP和ESR。结论肺炎患儿NSE水平明显升高,相较于ESR和CRP,NSE对儿童肺炎的诊断以及病情评估具有更重要的临床意义。

关键词：血清特异性烯醇化酶血沉 C反应蛋白肺炎儿童

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D-ribose increases triglyceride via upregulation of DGAT in the liver

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Science China(Life Sciences) 2019年第6期62卷 858-861页

作者： Yao Chen lexiang yu Yan Wei Yang Long Yong Xu Tao He Rongqiao He School of Basic Medical Sciences of Southwest Medical University Luzhou 646000 China State Key Laboratory of Brain and Cognitive Science Institute of Biophysics University of Chinese Academy of Sciences Beijing 100101 China Affiliated Hospital of Southwest Medical University Luzhou 646000 China CAS Key Laboratory of Mental Health Institute of Psychology Chinese Academy of Sciences Beijing 100101 China

Dear Editor, Fatty liver disease or hepatic steatosis, recognized as the hepatic component of metabolic syndrome, can progress to cirrhosis and hepatocellular carcinoma (Youngwanichsetha, 2018).

关键词： Dear Editor hepatic steatosis progress to cirrhosis

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Acetylation of PPARγin macrophages promotes visceral fat degeneration in obesity

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Life Metabolism 2022年第3期1卷 258-269页

作者： Nicole Aaron Tarik Zahr Ying He lexiang yu Brent Mayfield Utpal BPajvani Li Qiang Naomi Berrie Diabetes Center Columbia UniversityNew YorkNYUSA Department of Pharmacology Columbia UniversityNew YorkNYUSA Department of Pathology and Cell Biology Columbia UniversityNew YorkNYUSA Department of Genetics and Development Columbia UniversityNew YorkNYUSA Department of Medicine Columbia UniversityNew YorkNYUSA

Obesity is characterized by chronic,low-grade inflammation,which is driven by macrophage infiltration of adipose ***γ is well established to have an anti-inflammatory function in macrophages,but the mechanism that regulates its function in these cells remains to be fully ***γundergoes post-translational modifications(PTMs),including acetylation,to mediate ligand responses,including on metabolic ***,we report that PPARγacetylation in macrophages promotes their infiltration into adipose tissue,exacerbating metabolic *** generated a mouse line that expresses a macrophage-specific,constitutive acetylation-mimetic form of PPARγ(K293Q^(flox/flox):LysM-cre,mK293Q)to dissect the role of PPARγacetylation in *** highfat diet feeding to stimulate macrophage infiltration into adipose tissue,we assessed the overall metabolic profile and tissue-specific phenotype of the mutant mice,including responses to the PPARγagonist ***-specific PPARγK293Q expression promotes proinflammatory macrophage infiltration and fibrosis in epididymal white adipose tissue,but not in subcutaneous or brown adipose tissue,leading to decreased energy expenditure,insulin sensitivity,glucose tolerance,and adipose tissue ***,mK293Q mice are resistant to Rosiglitazone-induced improvements in adipose tissue *** study reveals that acetylation is a new layer of PPARγregulation in macrophage activation,and highlights the importance and potential therapeutic implications of such PTMs in regulating metabolism.

关键词： PPARγacetylation adipose tissue remodeling macrophage inflammation fibrosis

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Decomposition of D-Ribose Producing Formaldehyde

Decomposition of D-Ribose Producing Formaldehyde

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： lexiang yu yujing Wang Yao Chen Yan Wei Rongqiao He State Key Laboratory of Brain and Cognitive Science Institute of BiophysicsUniversity of Chinese Academy of Sciences Southwest Medical University Alzheimer's Disease Center Beijing Institute for Brain DisordersCapital Medical University

Although D-ribose is reputedly a key "anti-aging nutrient" and provided as a supplement to elderly people to improve their health,no laboratories have reported that D-ribose is involved in the production of formaldehyde(FA) under the physiological pH *** is toxic and has been implicated in the pathologies of various diseases,such as neurodegenerative diseases and ***,to improve the safety of D-ribose supplementation,we show that formaldehyde can be produced from decomposition of D-ribose in solution.D-ribose first decomposed into glyceraldehyde(GA),followed by production of formaldehyde under neutral and alkaline *** experiments showed that formaldehyde was produced in the presence of D-ribose in a lysine *** formaldehyde is produced in the presence of norleucine(containing an α-amino group) compared with 6-aminocaproic acid(containing an ε-amino group),which indicates that the α-amino group of amino acids plays an active role in the decomposition of *** with glycine further confirmed this *** work suggests the concentration of formaldehyde produced during administration of D-ribose should be carefully monitored in the elderly who are receiving D-ribose as an anti-aging supplement.

关键词： D-ribose formaldehyde anti-aging nutrient glyceraldehyde

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D-ribose induces the synthesis of triglyceride in liver through increase of DGAT

D-ribose induces the synthesis of triglyceride in liver thro...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2018年全国学术会议

作者： Yao Chen lexiang yu Yan Wei Yang Long Yong Xu Rongqiao He Southwest Medical University Institute of Biophysics University of Chinese Academy of Sciences Affiliated Hospital of Southwest Medical University

Glucotoxicity and lipotoxicity are the key characteristics of type 2 diabetes mellitus(T2 DM) in early *** reports demonstrated that patients of T2 DM suffered from abnormal high levels not only of D-glucose but also of ***(TG) is the main lipid molecule involved in hyperlipidaemia,atherosclerosis,coronary heart disease and T2 ***,we aimed to investigate the relationship of D-ribose and lipid metabolism in liver-target *** O-acyltransferase(DGAT) is the key enzyme in esterification reaction,playing an important role in the last process of triglyceride synthesis in *** this study,SD rats were intraperitoneally injected with D-ribose(4 g/kg),D-glucose(4.8 g/kg) or normal saline once daily for two *** results showed that rats of D-ribose group got a significant increase in liver TG and DGAT levels compared with the normal saline *** staining of liver revealed that the structure of hepatic lobules was disordered and even disappeared,and hepatocytes were extensively edematous accompanied with steatosis in D-ribose treated ***,there were no significant biochemical and pathologic changes in D-glucose injected ***,seventy volunteers were recruited to participate a double-blind trial including laboratorial assays and color dopplar ultrasound *** results showed that urine D-ribose and serum TG levels of participants with fatty liver were significantly higher than those of non-fatty liver.D-ribose levels was significantly positive correlated with serum *** suggest that D-ribose might induce the over-production of TG in liver through increase of *** work could help with the exploring of abnormal lipids metabolism and may propose a novel research idea for the lipid dysmetabolism in T2 DM.

关键词： D-ribose triglyceride DGAT lipid liver T2DM

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新井初产油和老井含水的经济极限研究

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石油钻采工艺 2000年第6期22卷 39-41页

作者：于乐香王星石油大学石油工程系山东东营257062 胜利石油管理局地质科学院山东东营257000

针对胜利油田目前高含水和特高含水的现状 ,为适应市场经济对油田开发的要求 ,确定了极限初产油量的表达式 ,并讨论了井深、投资、经营成本、油价的变化对它的影响 ,同时考虑税金、成本上涨率等因素建立了经济极限含水的定量关系式 ,并... 详细信息

针对胜利油田目前高含水和特高含水的现状 ,为适应市场经济对油田开发的要求 ,确定了极限初产油量的表达式 ,并讨论了井深、投资、经营成本、油价的变化对它的影响 ,同时考虑税金、成本上涨率等因素建立了经济极限含水的定量关系式 ,并对胜利油田老区分高渗透和低渗透两大类对经济极限初产油和经济极限含水进行了测算验证 ,为油田开发决策和生产运行提供可靠的科学依据。

关键词：油田形成高含水期经济评价投资油井初产油

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氟吡酰草胺的合成及发展前景

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云南化工 2018年第1期45卷 7-8页

作者：李源于乐祥王兴国山东省农药科学研究院山东济南250100

作为农药行业的重要角色,氟吡酰草胺因为其对大多数麦类作物中的一年生阔叶杂草表现出优异防除功效,而广受农民朋友的青睐。氟吡酰草胺属于吡啶酰胺结构化合物的除草剂,它的合成过程比较简单,反应条件温和,而且合成原料试剂易得,而且进... 详细信息

作为农药行业的重要角色,氟吡酰草胺因为其对大多数麦类作物中的一年生阔叶杂草表现出优异防除功效,而广受农民朋友的青睐。氟吡酰草胺属于吡啶酰胺结构化合物的除草剂,它的合成过程比较简单,反应条件温和,而且合成原料试剂易得,而且进一步讨论了氟吡酰草胺的合成过程,首先将6-氯吡啶-2-羧酸和间三氟甲基苯酚醚化反应,再和4-氟苯胺发生酰基化反应,即可得到最终的氟吡酰草胺产品,反应收率较高,易于工业化的生产。氟吡酰草胺至今依然保持良好的销售额,未来研制加工出不同剂型多种复配剂的推出,还可以将方向延伸到杀虫杀菌剂类的开发,必将更加拓宽氟吡酰草胺的应用前景。

关键词：氟吡酰草胺合成优化

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气相色谱-质谱法测定二甲戊灵在棉花中的残留量

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农药科学与管理 2015年第5期36卷 35-38页

作者：于乐祥梁林张爱娟翟淑华刘伟山东省农药科学研究院山东济南250033

建立了气相色谱-质谱法检测二甲戊灵在棉花中残留量的方法。棉籽,棉花植株及土壤样品经乙腈提取,PSA和C18固相分散吸附剂净化,应用气相色谱-质谱联用仪检测,外标法定量,结果显示,在0.01~0.5mg/kg添加水平范围内,二甲戊灵在棉籽,棉花植... 详细信息

建立了气相色谱-质谱法检测二甲戊灵在棉花中残留量的方法。棉籽,棉花植株及土壤样品经乙腈提取,PSA和C18固相分散吸附剂净化,应用气相色谱-质谱联用仪检测,外标法定量,结果显示,在0.01~0.5mg/kg添加水平范围内,二甲戊灵在棉籽,棉花植株及土壤中的平均回收率分别为91.1%~97.1%,86.4%~95.2%和85.6%~94.0%,相对标准偏差(RSD)分别为4.6%~6.1%,3.7%~8.2%和2.0%~8.0%,最低检测浓度(LOQ)均为0.01mg/kg。

关键词：二甲戊灵气相色谱-质谱法棉花

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浅谈农药产品爆炸性初步筛选试验

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农药科学与管理 2019年第8期40卷 46-52页

作者：朱明伟石凯威于乐祥张晓菲吴进龙山东省农药科学研究院山东济南250100 农业农村部农药检定所北京100125 北京颖泰嘉和分析技术有限公司北京102206

爆炸性是农药登记试验中一项重要的试验,文中描述了农药产品爆炸性的判断依据,阐述了爆炸性初步筛选试验,使用TGA/DSC同步热分析仪对常见农药原药、母药、固体制剂和液体制剂进行了热分析试验,并进行了谱图解析和结果判断,对比说明了TGA... 详细信息

爆炸性是农药登记试验中一项重要的试验,文中描述了农药产品爆炸性的判断依据,阐述了爆炸性初步筛选试验,使用TGA/DSC同步热分析仪对常见农药原药、母药、固体制剂和液体制剂进行了热分析试验,并进行了谱图解析和结果判断,对比说明了TGA/DSC同步热分析仪在农药产品爆炸性初步筛选试验中相比DSC分析仪的优势.

关键词：农药爆炸性 DSC TGA/DSC

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