首页 > 最新文献

Molecular and Cellular Endocrinology最新文献

英文 中文
Legumain-deficient macrophages regulate inflammation and lipid metabolism in adipose tissues to protect against diet-induced obesity 缺失豆豆蛋白酶的巨噬细胞能调节脂肪组织中的炎症和脂质代谢,从而防止饮食引起的肥胖。
IF 4.1 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-28 DOI: 10.1016/j.mce.2024.112283
Wanyu Zhang , Shuowen Wang , Zhuo Liu , Ping Qian , Yuanyuan Li , Jianxin Wu

Adipose tissue macrophages (ATMs) are key players in the development of obesity and associated metabolic inflammation, which contributes to systemic metabolic dysfunction, and understanding the interaction between macrophages and adipocytes is crucial for developing novel macrophage-based strategies against obesity. Here, we found that Legumain (Lgmn), a well-known lysosomal cysteine protease, is expressed mainly in the ATMs of obese mice. To further define the potential role of Lgmn-expressing macrophages in the generation of an aberrant metabolic state, LgmnF/F; LysMCre mice, which do not express Lgmn in macrophages, were maintained on a high-fat diet (HFD), and metabolic parameters were assessed. Macrophage-specific Lgmn deficiency protects mice against HFD-induced obesity, diminishes the quantity of proinflammatory macrophages in obese adipose tissues, and alleviates hepatic steatosis and insulin resistance. By analysing the transcriptome and proteome of murine visceral white adipose tissue (vWAT) after HFD feeding, we determined that macrophage Lgmn deficiency causes changes in lipid metabolism and the inflammatory response. Furthermore, the reciprocity of macrophage-derived Lgmn with integrin α5β1 in adipocytes was tested via colocalization analyses. It is further demonstrated in macrophage and adipocyte coculture system that macrophage derived Lgmn bound to integrin α5β1 in adipocytes, therefore attenuating PKA activation, downregulating lipolysis-related proteins and eventually exacerbating obesity development. Overall, our study identified Lgmn as a previously unrecognized regulator involved in the interaction between ATMs and adipocytes contributing to diet-induced obesity and suggested that Lgmn is a potential target for treating metabolic disorders.

脂肪组织巨噬细胞(ATMs)是肥胖症和相关代谢炎症发展过程中的关键角色,而肥胖症和相关代谢炎症会导致全身代谢功能障碍,因此了解巨噬细胞和脂肪细胞之间的相互作用对于开发基于巨噬细胞的新型肥胖症防治策略至关重要。在这里,我们发现著名的溶酶体半胱氨酸蛋白酶 Legumain (Lgmn) 主要在肥胖小鼠的 ATMs 中表达。为了进一步确定表达 Lgmn 的巨噬细胞在产生异常代谢状态中的潜在作用,我们将巨噬细胞中不表达 Lgmn 的 LgmnF/F; LysMCre 小鼠饲养在高脂饮食(HFD)中,并对代谢参数进行了评估。巨噬细胞特异性Lgmn的缺乏能保护小鼠免受饮食诱发的肥胖,减少肥胖脂肪组织中促炎巨噬细胞的数量,减轻肝脏脂肪变性和胰岛素抵抗。通过分析喂食高密度脂蛋白胆固醇(HFD)后小鼠内脏白色脂肪组织(vWAT)的转录组和蛋白质组,我们确定巨噬细胞 Lgmn 缺乏会引起脂质代谢和炎症反应的变化。此外,我们还通过共定位分析测试了巨噬细胞衍生的 Lgmn 与脂肪细胞中整合素 α5β1 的互作关系。在巨噬细胞和脂肪细胞共培养系统中进一步证实,巨噬细胞衍生的Lgmn与脂肪细胞中的整合素α5β1结合,从而减弱了PKA的激活,下调了脂肪分解相关蛋白,最终加剧了肥胖的发展。总之,我们的研究发现,Lgmn是一种以前未被发现的调节因子,它参与了ATMs与脂肪细胞之间的相互作用,导致饮食引起的肥胖,并表明Lgmn是治疗代谢紊乱的潜在靶点。
{"title":"Legumain-deficient macrophages regulate inflammation and lipid metabolism in adipose tissues to protect against diet-induced obesity","authors":"Wanyu Zhang ,&nbsp;Shuowen Wang ,&nbsp;Zhuo Liu ,&nbsp;Ping Qian ,&nbsp;Yuanyuan Li ,&nbsp;Jianxin Wu","doi":"10.1016/j.mce.2024.112283","DOIUrl":"10.1016/j.mce.2024.112283","url":null,"abstract":"<div><p>Adipose tissue macrophages (ATMs) are key players in the development of obesity and associated metabolic inflammation, which contributes to systemic metabolic dysfunction, and understanding the interaction between macrophages and adipocytes is crucial for developing novel macrophage-based strategies against obesity. Here, we found that Legumain (Lgmn), a well-known lysosomal cysteine protease, is expressed mainly in the ATMs of obese mice. To further define the potential role of Lgmn-expressing macrophages in the generation of an aberrant metabolic state, Lgmn<sup>F/F</sup>; LysM<sup>Cre</sup> mice, which do not express Lgmn in macrophages, were maintained on a high-fat diet (HFD), and metabolic parameters were assessed. Macrophage-specific Lgmn deficiency protects mice against HFD-induced obesity, diminishes the quantity of proinflammatory macrophages in obese adipose tissues, and alleviates hepatic steatosis and insulin resistance. By analysing the transcriptome and proteome of murine visceral white adipose tissue (vWAT) after HFD feeding, we determined that macrophage Lgmn deficiency causes changes in lipid metabolism and the inflammatory response. Furthermore, the reciprocity of macrophage-derived Lgmn with integrin α5β1 in adipocytes was tested via colocalization analyses. It is further demonstrated in macrophage and adipocyte coculture system that macrophage derived Lgmn bound to integrin α5β1 in adipocytes, therefore attenuating PKA activation, downregulating lipolysis-related proteins and eventually exacerbating obesity development. Overall, our study identified Lgmn as a previously unrecognized regulator involved in the interaction between ATMs and adipocytes contributing to diet-induced obesity and suggested that Lgmn is a potential target for treating metabolic disorders.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"592 ","pages":"Article 112283"},"PeriodicalIF":4.1,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reduced hepatic AdipoR2 by increased glucocorticoid mediates effect of psychosocial stress to elevate serum cholesterol 糖皮质激素增加导致肝脏 AdipoR2 减少,从而介导了社会心理压力对血清胆固醇升高的影响。
IF 4.1 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-28 DOI: 10.1016/j.mce.2024.112282
Qi Wei Guo , Jia Lin , Yi Lin Shen , Yan Jiang Zheng , Xu Chen , Mi Su , Ji Cheng Zhang , Jin Hua Wang , Hui Tang , Guo Ming Su , Zheng Ke Li , Ding Zhi Fang

Understanding the effects of psychosocial stress on serum cholesterol may offer valuable insights into the relationship between psychological disorders and endocrine diseases. However, these effects and their underlying mechanisms have not been elucidated yet. Here we show that serum corticosterone, total cholesterol and low-density lipoprotein cholesterol (LDL-C) are elevated in a mouse model of psychosocial stress. Furthermore, alterations occur in AdipoR2-mediated AMPK and PPARα signaling pathways in liver, accompanied by a decrease in LDL-C clearance and an increase in cholesterol synthesis. These changes are further verified in wild-type and AdipoR2 overexpression HepG2 cells incubated with cortisol and AdipoR agonist, and are finally confirmed by treating wild-type and hepatic-specific AdipoR2 overexpression mice with corticosterone. We conclude that increased glucocorticoid mediates the effects of psychosocial stress to elevate serum cholesterol by inhibiting AdipoR2-mediated AMPK and PPARα signaling to decrease LDL-C clearance and increase cholesterol synthesis in liver.

了解社会心理压力对血清胆固醇的影响可能会对心理障碍与内分泌疾病之间的关系提供有价值的见解。然而,这些影响及其内在机制尚未得到阐明。在这里,我们发现,在社会心理应激小鼠模型中,血清皮质酮、总胆固醇和低密度脂蛋白胆固醇(LDL-C)会升高。此外,肝脏中由 AdipoR2 介导的 AMPK 和 PPARα 信号通路也发生了改变,同时低密度脂蛋白胆固醇清除率降低,胆固醇合成增加。这些变化在用皮质醇和 AdipoR 激动剂培养的野生型和 AdipoR2 过表达 HepG2 细胞中得到了进一步验证,并最终通过用皮质酮处理野生型和肝特异性 AdipoR2 过表达小鼠得到了证实。我们的结论是,糖皮质激素的增加通过抑制 AdipoR2 介导的 AMPK 和 PPARα 信号传导来降低 LDL-C 的清除率并增加肝脏中胆固醇的合成,从而介导社会心理压力对血清胆固醇升高的影响。
{"title":"Reduced hepatic AdipoR2 by increased glucocorticoid mediates effect of psychosocial stress to elevate serum cholesterol","authors":"Qi Wei Guo ,&nbsp;Jia Lin ,&nbsp;Yi Lin Shen ,&nbsp;Yan Jiang Zheng ,&nbsp;Xu Chen ,&nbsp;Mi Su ,&nbsp;Ji Cheng Zhang ,&nbsp;Jin Hua Wang ,&nbsp;Hui Tang ,&nbsp;Guo Ming Su ,&nbsp;Zheng Ke Li ,&nbsp;Ding Zhi Fang","doi":"10.1016/j.mce.2024.112282","DOIUrl":"10.1016/j.mce.2024.112282","url":null,"abstract":"<div><p>Understanding the effects of psychosocial stress on serum cholesterol may offer valuable insights into the relationship between psychological disorders and endocrine diseases. However, these effects and their underlying mechanisms have not been elucidated yet. Here we show that serum corticosterone, total cholesterol and low-density lipoprotein cholesterol (LDL-C) are elevated in a mouse model of psychosocial stress. Furthermore, alterations occur in AdipoR2-mediated AMPK and PPARα signaling pathways in liver, accompanied by a decrease in LDL-C clearance and an increase in cholesterol synthesis. These changes are further verified in wild-type and <em>AdipoR2</em> overexpression HepG2 cells incubated with cortisol and AdipoR agonist, and are finally confirmed by treating wild-type and hepatic-specific <em>AdipoR2</em> overexpression mice with corticosterone. We conclude that increased glucocorticoid mediates the effects of psychosocial stress to elevate serum cholesterol by inhibiting AdipoR2-mediated AMPK and PPARα signaling to decrease LDL-C clearance and increase cholesterol synthesis in liver.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"592 ","pages":"Article 112282"},"PeriodicalIF":4.1,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microbial Endocrinology: Host metabolism and appetite hormones interaction with gut microbiome 微生物内分泌学:宿主新陈代谢和食欲激素与肠道微生物组的相互作用。
IF 4.1 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-27 DOI: 10.1016/j.mce.2024.112281
Anam Ashraf, Md. Imtaiyaz Hassan
{"title":"Microbial Endocrinology: Host metabolism and appetite hormones interaction with gut microbiome","authors":"Anam Ashraf,&nbsp;Md. Imtaiyaz Hassan","doi":"10.1016/j.mce.2024.112281","DOIUrl":"10.1016/j.mce.2024.112281","url":null,"abstract":"","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"592 ","pages":"Article 112281"},"PeriodicalIF":4.1,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Melatonin improves nitric oxide bioavailability in isoproterenol induced myocardial injury 褪黑素可提高一氧化氮在异丙肾上腺素诱导的心肌损伤中的生物利用率
IF 4.1 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-24 DOI: 10.1016/j.mce.2024.112279
Ramison Santos , Patrick Turck , Victor de Mello Palma , Fernanda Visioli , Vanessa Duarte Ortiz , Isabel Cristina Teixeira Proença , Tânia Regina G. Fernandes , Elissa Fernandes , Silvio Tasca , Cristina Campos Carraro , Adriane Belló-Klein , Alex Sander da Rosa Araujo , Neelam Khaper , Alexandre Luz de Castro

Isoproterenol administration is associated with cardiac inflammation and decreased NO availability. Melatonin has been reported to have cardioprotective effect. The aim of this study was to investigate the effect of melatonin on NO bioavailability and inflammation in myocardial injury induced by isoproterenol. Isoproterenol was administrated in male Wistar rats for 7 days to induce cardiac injury. The animals were divided into 3 groups: Control, Isoproterenol, Isoproterenol + Melatonin. Animals received melatonin for 7 days. Echocardiographic analysis was performed and the hearts were collected for molecular analysis. Animals that received isoproterenol demonstrated a reduction in left ventricle systolic and diastolic diameter, indicating the presence of concentric hypertrophy. Melatonin was able to attenuate this alteration. Melatonin also improved NO bioavailability and decreased NF-κβ, TNFα and IL-1β expression. In conclusion, melatonin exhibited a cardioprotective effect which was associated with improving NO bioavailability and decreasing the pro-inflammatory proteins.

异丙肾上腺素与心脏炎症和氮氧化物供应减少有关。据报道,褪黑素具有保护心脏的作用。本研究旨在探讨褪黑素对异丙托品醇诱导的心肌损伤中 NO 生物利用率和炎症的影响。给雄性 Wistar 大鼠注射异丙肾上腺素 7 天以诱导心肌损伤。动物被分为 3 组:对照组、异丙肾上腺素组、异丙肾上腺素+褪黑素组。动物接受褪黑素治疗 7 天。进行超声心动图分析,并收集心脏进行分子分析。接受异丙肾上腺素治疗的动物显示左心室收缩和舒张直径缩小,表明存在同心性肥厚。褪黑素能够减轻这种变化。褪黑激素还改善了氮氧化物的生物利用率,降低了 NF-κβ、TNFα 和 IL-1β 的表达。总之,褪黑素具有保护心脏的作用,这与改善氮氧化物生物利用率和减少促炎蛋白有关。
{"title":"Melatonin improves nitric oxide bioavailability in isoproterenol induced myocardial injury","authors":"Ramison Santos ,&nbsp;Patrick Turck ,&nbsp;Victor de Mello Palma ,&nbsp;Fernanda Visioli ,&nbsp;Vanessa Duarte Ortiz ,&nbsp;Isabel Cristina Teixeira Proença ,&nbsp;Tânia Regina G. Fernandes ,&nbsp;Elissa Fernandes ,&nbsp;Silvio Tasca ,&nbsp;Cristina Campos Carraro ,&nbsp;Adriane Belló-Klein ,&nbsp;Alex Sander da Rosa Araujo ,&nbsp;Neelam Khaper ,&nbsp;Alexandre Luz de Castro","doi":"10.1016/j.mce.2024.112279","DOIUrl":"10.1016/j.mce.2024.112279","url":null,"abstract":"<div><p>Isoproterenol administration is associated with cardiac inflammation and decreased NO availability. Melatonin has been reported to have cardioprotective effect. The aim of this study was to investigate the effect of melatonin on NO bioavailability and inflammation in myocardial injury induced by isoproterenol. Isoproterenol was administrated in male Wistar rats for 7 days to induce cardiac injury. The animals were divided into 3 groups: Control, Isoproterenol, Isoproterenol + Melatonin. Animals received melatonin for 7 days. Echocardiographic analysis was performed and the hearts were collected for molecular analysis. Animals that received isoproterenol demonstrated a reduction in left ventricle systolic and diastolic diameter, indicating the presence of concentric hypertrophy. Melatonin was able to attenuate this alteration. Melatonin also improved NO bioavailability and decreased NF-κβ, TNFα and IL-1β expression. In conclusion, melatonin exhibited a cardioprotective effect which was associated with improving NO bioavailability and decreasing the pro-inflammatory proteins.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"591 ","pages":"Article 112279"},"PeriodicalIF":4.1,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141133074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mesenchymal stem cells improve cardiac function in diabetic rats by reducing cardiac injury biomarkers and downregulating JAK/STAT/iNOS and iNOS/Apoptosis signaling pathways 间充质干细胞通过减少心脏损伤生物标志物和下调 JAK/STAT/iNOS 和 iNOS/Apoptosis 信号通路,改善糖尿病大鼠的心脏功能
IF 4.1 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-24 DOI: 10.1016/j.mce.2024.112280
Thoraya Mohamed Elhassan A-Elgadir , Ayed A. Shati , Saif Aboud Alqahtani , Hasnaa A. Ebrahim , Hailah M. Almohaimeed , Asmaa M. ShamsEldeeen , Mohamed A. Haidara , Samaa S. Kamar , Amal F. Dawood , Mahmoud H. El-Bidawy

Cardiovascular complications are prevalent manifestations of type 2 diabetes mellitus (T2DM) and are usually the main cause of death. This study aims to show the underlying mechanisms of the potential therapeutic effect of mesenchymal stem cells (MSCs) on diabetic cardiac dysfunction. Twenty-four male Wistar rats were randomly assigned to one of three groups The control group received standard laboratory chow, and the groups with T2DM received a single dose of 45 mg/kg body weight of streptozotocin (STZ) after 3 weeks of pretreatment with a high-fat diet (HFD). Eight weeks after the diagnosis of T2DM, rats were divided into two groups: the T2DM model group and the T2DM + MSCs group. BM-MSCs were administered systemically at 2 × 106 cells/rat doses.

A Significant amelioration in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and dyslipidemia was noted 2 weeks post-administration of MSCs. Administration of MSCs improved dyslipidemia, the altered cardiac injury biomarkers (p ≤ 0.0001), downregulated Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)/inducible Nitric oxide synthase (iNOS) and iNOS/Apoptosis signaling pathways. This was associated with improved cardiac dysfunction (impaired left ventricular performance and decreased contractility index).

Our results show that MSCs ameliorate cardiac dysfunction associated with diabetic cardiomyopathy by lowering dyslipidemia and insulin resistance, inhibiting oxidative stress, and inflammation, downregulating JAK2/STAT3/iNOS and iNOS/Apoptosis signaling pathways.

心血管并发症是2型糖尿病(T2DM)的常见表现,通常是导致死亡的主要原因。本研究旨在揭示间充质干细胞(MSCs)对糖尿病心脏功能障碍的潜在治疗作用的内在机制。24只雄性Wistar大鼠被随机分配到三组中的一组。对照组接受标准实验室饲料,T2DM组在高脂饮食(HFD)预处理3周后接受单剂量45毫克/公斤体重的链脲佐菌素(STZ)。确诊 T2DM 八周后,大鼠被分为两组:T2DM 模型组和 T2DM + 间充质干细胞组。给药两周后,大鼠的胰岛素抵抗静态模型评估(HOMA-IR)和血脂异常明显改善。服用间叶干细胞可改善血脂异常、心脏损伤生物标志物的改变(p ≤ 0.0001)、Janus 激酶 2/信号转导和激活转录 3(JAK2/STAT3)/诱导一氧化氮合酶(iNOS)和 iNOS/细胞凋亡信号通路的下调。我们的研究结果表明,间充质干细胞可通过降低血脂异常和胰岛素抵抗、抑制氧化应激和炎症、下调 JAK2/STAT3/iNOS 和 iNOS/Aoptosis 信号通路,改善糖尿病心肌病相关的心脏功能障碍。
{"title":"Mesenchymal stem cells improve cardiac function in diabetic rats by reducing cardiac injury biomarkers and downregulating JAK/STAT/iNOS and iNOS/Apoptosis signaling pathways","authors":"Thoraya Mohamed Elhassan A-Elgadir ,&nbsp;Ayed A. Shati ,&nbsp;Saif Aboud Alqahtani ,&nbsp;Hasnaa A. Ebrahim ,&nbsp;Hailah M. Almohaimeed ,&nbsp;Asmaa M. ShamsEldeeen ,&nbsp;Mohamed A. Haidara ,&nbsp;Samaa S. Kamar ,&nbsp;Amal F. Dawood ,&nbsp;Mahmoud H. El-Bidawy","doi":"10.1016/j.mce.2024.112280","DOIUrl":"10.1016/j.mce.2024.112280","url":null,"abstract":"<div><p>Cardiovascular complications are prevalent manifestations of type 2 diabetes mellitus (T2DM) and are usually the main cause of death. This study aims to show the underlying mechanisms of the potential therapeutic effect of mesenchymal stem cells (MSCs) on diabetic cardiac dysfunction. Twenty-four male Wistar rats were randomly assigned to one of three groups The control group received standard laboratory chow, and the groups with T2DM received a single dose of 45 mg/kg body weight of streptozotocin (STZ) after 3 weeks of pretreatment with a high-fat diet (HFD). Eight weeks after the diagnosis of T2DM, rats were divided into two groups: the T2DM model group and the T2DM + MSCs group. BM-MSCs were administered systemically at 2 × 10<sup>6</sup> cells/rat doses.</p><p>A Significant amelioration in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and dyslipidemia was noted 2 weeks post-administration of MSCs. Administration of MSCs improved dyslipidemia, the altered cardiac injury biomarkers (p ≤ 0.0001), downregulated Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)/inducible Nitric oxide synthase (iNOS) and iNOS/Apoptosis signaling pathways. This was associated with improved cardiac dysfunction (impaired left ventricular performance and decreased contractility index).</p><p>Our results show that MSCs ameliorate cardiac dysfunction associated with diabetic cardiomyopathy by lowering dyslipidemia and insulin resistance, inhibiting oxidative stress, and inflammation, downregulating JAK2/STAT3/iNOS and iNOS/Apoptosis signaling pathways.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"591 ","pages":"Article 112280"},"PeriodicalIF":4.1,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141131510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
L(1)10Bb serves as a conservative determinant for soma-germline communications via cellular non-autonomous effects within the testicular stem cell niche L(1)10Bb通过睾丸干细胞龛内的细胞非自主效应,成为体细胞与胚系沟通的保守决定因素
IF 4.1 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-23 DOI: 10.1016/j.mce.2024.112278
Lei He , Feiteng Sun , Yunhao Wu , Zhiran Li , Yangbo Fu, Qiuru Huang, Jiaxin Li, Zihan Wang, Jiaying Cai, Chenrui Feng, Xiaonan Deng, Han Gu, Xuxin He, Jun Yu, Fei Sun

The testicular stem cell niche is the central regulator of spermatogenesis in Drosophila melanogaster. However, the underlying regulatory mechanisms are unclear. This study demonstrated the crucial role of lethal (1) 10Bb [l(1)10Bb] in regulating the testicular stem cell niche. Dysfunction of l(1)10Bb in early-stage cyst cells led to male fertility disorders and compromised cyst stem cell maintenance. Moreover, the dysfunction of l(1)10Bb in early-stage cyst cells exerted non-autonomous effects on germline stem cell differentiation, independently of hub signals. Notably, our study highlights the rescue of testicular defects through ectopic expression of L(1)10Bb and the human homologous protein BUD31 homolog (BUD31). In addition, l(1)10Bb dysfunction in early-stage cyst cells downregulated the expression of spliceosome subunits in the Sm and the precursor RNA processing complexes. Collectively, our findings established l(1)10Bb as a pivotal factor in the modulation of Drosophila soma-germline communications within the testicular stem cell niche.

睾丸干细胞龛是黑腹果蝇精子发生的核心调节因子。然而,其潜在的调控机制尚不清楚。本研究证明了致死(1)10Bb [l(1)10Bb] 在调节睾丸干细胞龛中的关键作用。早期囊肿细胞中的l(1)10Bb功能失调会导致男性生育障碍,并影响囊肿干细胞的维持。此外,早期囊肿细胞中l(1)10Bb的功能障碍对生殖系干细胞分化产生非自主性影响,与中枢信号无关。值得注意的是,我们的研究强调了通过异位表达L(1)10Bb和人类同源蛋白BUD31同源物(BUD31)来挽救睾丸缺陷。此外,l(1)10Bb在早期囊肿细胞中的功能障碍下调了Sm和前体RNA加工复合物中剪接体亚基的表达。总之,我们的研究结果确定了l(1)10Bb是果蝇睾丸干细胞龛内调节体细胞与胚系沟通的关键因素。
{"title":"L(1)10Bb serves as a conservative determinant for soma-germline communications via cellular non-autonomous effects within the testicular stem cell niche","authors":"Lei He ,&nbsp;Feiteng Sun ,&nbsp;Yunhao Wu ,&nbsp;Zhiran Li ,&nbsp;Yangbo Fu,&nbsp;Qiuru Huang,&nbsp;Jiaxin Li,&nbsp;Zihan Wang,&nbsp;Jiaying Cai,&nbsp;Chenrui Feng,&nbsp;Xiaonan Deng,&nbsp;Han Gu,&nbsp;Xuxin He,&nbsp;Jun Yu,&nbsp;Fei Sun","doi":"10.1016/j.mce.2024.112278","DOIUrl":"https://doi.org/10.1016/j.mce.2024.112278","url":null,"abstract":"<div><p>The testicular stem cell niche is the central regulator of spermatogenesis in <em>Drosophila melanogaster</em>. However, the underlying regulatory mechanisms are unclear. This study demonstrated the crucial role of <em>lethal (1)</em> 10Bb [<em>l(1)</em>10Bb] in regulating the testicular stem cell niche. Dysfunction of <em>l(1)</em>10Bb in early-stage cyst cells led to male fertility disorders and compromised cyst stem cell maintenance. Moreover, the dysfunction of <em>l(1)</em>10Bb in early-stage cyst cells exerted non-autonomous effects on germline stem cell differentiation, independently of hub signals. Notably, our study highlights the rescue of testicular defects through ectopic expression of L(1)10Bb and the human homologous protein BUD31 homolog (BUD31). In addition, <em>l(1)</em>10Bb dysfunction in early-stage cyst cells downregulated the expression of spliceosome subunits in the Sm and the precursor RNA processing complexes. Collectively, our findings established <em>l(1)</em>10Bb as a pivotal factor in the modulation of <em>Drosophila</em> soma-germline communications within the testicular stem cell niche.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"591 ","pages":"Article 112278"},"PeriodicalIF":4.1,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TJP1 suppresses trophoblast cell invasion by expressing E2F8 in the human placenta TJP1 通过在人类胎盘中表达 E2F8 抑制滋养层细胞入侵
IF 4.1 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-23 DOI: 10.1016/j.mce.2024.112277
Rika Miki , Seiko Matsuo , Takafumi Ushida , Sho Tano , Kenji Imai , Akihiro Nawa , Hiroaki Kajiyama , Tomomi Kotani

Adequate extravillous trophoblast (EVT) invasion into the maternal decidua is important for human placental development. We identified that E2F transcription factor 8 (E2F8) suppresses EVT invasion, and that tight junction protein-1 (TJP1) is a potential downstream target gene of E2F8. We investigated the role of TJP1 in the human placenta and regulation of TJP1 expression by E2F8. TJP1 expression decreased in E2F8 knockdown HTR-8/SVneo cells. TJP1 and E2F8 were co-expressed in villi in the first-trimester placenta and in EVTs and villi in the third-trimester placenta. TJP1 was significantly increased in the pre-eclamptic compared with control placenta. TJP1 knockdown increased the invasion of HTR-8/SVneo cells, while TJP1 overexpression inhibited cell invasion. Halo-E2F8 overexpression significantly increased TJP1 expression and TJP1 transcription compared with control placenta. Our findings suggest that E2F8 promotes TJP1 transcription, and that TJP1 expression by E2F8 inhibits EVT invasion. TJP1 and E2F8 may be related to pre-eclampsia pathogenesis.

绒毛外滋养层细胞(EVT)充分侵入母体蜕膜对人类胎盘的发育非常重要。我们发现E2F转录因子8(E2F8)抑制EVT的侵入,而紧密连接蛋白-1(TJP1)是E2F8的潜在下游靶基因。我们研究了 TJP1 在人类胎盘中的作用以及 E2F8 对 TJP1 表达的调控。在 E2F8 敲除的 HTR-8/SVneo 细胞中,TJP1 的表达量减少。TJP1和E2F8在第一妊娠期胎盘的绒毛和第三妊娠期胎盘的EVT和绒毛中共同表达。与对照胎盘相比,子痫前期胎盘中的 TJP1 明显增加。敲除 TJP1 会增加 HTR-8/SVneo 细胞的侵袭,而过表达 TJP1 则会抑制细胞的侵袭。与对照胎盘相比,Halo-E2F8 过表达可显著增加 TJP1 的表达和 TJP1 的转录。我们的研究结果表明,E2F8能促进TJP1的转录,E2F8表达的TJP1能抑制EVT的侵袭。TJP1和E2F8可能与先兆子痫的发病机制有关。
{"title":"TJP1 suppresses trophoblast cell invasion by expressing E2F8 in the human placenta","authors":"Rika Miki ,&nbsp;Seiko Matsuo ,&nbsp;Takafumi Ushida ,&nbsp;Sho Tano ,&nbsp;Kenji Imai ,&nbsp;Akihiro Nawa ,&nbsp;Hiroaki Kajiyama ,&nbsp;Tomomi Kotani","doi":"10.1016/j.mce.2024.112277","DOIUrl":"https://doi.org/10.1016/j.mce.2024.112277","url":null,"abstract":"<div><p>Adequate extravillous trophoblast (EVT) invasion into the maternal decidua is important for human placental development. We identified that E2F transcription factor 8 (E2F8) suppresses EVT invasion, and that tight junction protein-1 (<em>TJP1</em>) is a potential downstream target gene of E2F8. We investigated the role of TJP1 in the human placenta and regulation of TJP1 expression by E2F8. <em>TJP1</em> expression decreased in <em>E2F8</em> knockdown HTR-8/SVneo cells. TJP1 and E2F8 were co-expressed in villi in the first-trimester placenta and in EVTs and villi in the third-trimester placenta. TJP1 was significantly increased in the pre-eclamptic compared with control placenta. <em>TJP1</em> knockdown increased the invasion of HTR-8/SVneo cells, while TJP1 overexpression inhibited cell invasion. Halo-E2F8 overexpression significantly increased <em>TJP1</em> expression and <em>TJP1</em> transcription compared with control placenta. Our findings suggest that E2F8 promotes <em>TJP1</em> transcription, and that TJP1 expression by E2F8 inhibits EVT invasion. TJP1 and E2F8 may be related to pre-eclampsia pathogenesis.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"591 ","pages":"Article 112277"},"PeriodicalIF":4.1,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Guillemin-Yen partnership: A bright light gone dark Guillemin-Yen 合作伙伴关系:黑暗中的曙光
IF 4.1 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-22 DOI: 10.1016/j.mce.2024.112276
Eli Y. Adashi MD, MS
{"title":"The Guillemin-Yen partnership: A bright light gone dark","authors":"Eli Y. Adashi MD, MS","doi":"10.1016/j.mce.2024.112276","DOIUrl":"10.1016/j.mce.2024.112276","url":null,"abstract":"","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"590 ","pages":"Article 112276"},"PeriodicalIF":4.1,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
AMPK inhibits voltage-gated calcium channel-current in rat chromaffin cells AMPK 可抑制大鼠绒毛膜细胞中的电压门控钙通道电流。
IF 4.1 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-20 DOI: 10.1016/j.mce.2024.112275
A.K. Fukumoto-Inukai , K. Bermeo , I. Arenas , M.J. Rosendo-Pineda , J.A. Pimentel-Cabrera , D.E. Garcia

Metabolic changes are critical in the regulation of Ca2+ influx in central and peripheral neuroendocrine cells. To study the regulation of L-type Ca2+ channels by AMPK we used biochemical reagents and ATP/glucose-concentration manipulations in rat chromaffin cells. AICAR and Compound-C, at low concentration, significantly induce changes in L-type Ca2+ channel-current amplitude and voltage dependence. Remarkably, an overlasting decrease in the channel-current density can be induced by lowering the intracellular level of ATP. Accordingly, Ca2+ channel-current density gradually diminishes by decreasing the extracellular glucose concentration. By using immunofluorescence, a decrease in the expression of CaV1.2 is observed while decreasing extracellular glucose, suggesting that AMPK reduces the number of functional Ca2+ channels into the plasma membrane. Together, these results support for the first time the dependence of metabolic changes in the maintenance of Ca2+ channel-current by AMPK. They reveal a key step in Ca2+ influx in secretory cells.

代谢变化对中枢和外周神经内分泌细胞的 Ca2+ 流入调节至关重要。为了研究 AMPK 对 L 型 Ca2+ 通道的调控,我们在大鼠绒毛膜细胞中使用了生化试剂和 ATP/葡萄糖浓度操作。低浓度的 AICAR 和化合物-C 能显著诱导 L 型 Ca2+ 通道电流振幅和电压依赖性的变化。值得注意的是,降低细胞内的 ATP 水平可诱导通道电流密度的重叠下降。相应地,随着细胞外葡萄糖浓度的降低,Ca2+ 通道电流密度也会逐渐降低。通过免疫荧光法,在降低细胞外葡萄糖浓度的同时,观察到 CaV1.2 的表达减少,这表明 AMPK 减少了进入质膜的功能性 Ca2+ 通道的数量。这些结果首次证明了 AMPK 在维持 Ca2+ 通道电流时对代谢变化的依赖性。它们揭示了分泌细胞中 Ca2+ 流入的一个关键步骤。
{"title":"AMPK inhibits voltage-gated calcium channel-current in rat chromaffin cells","authors":"A.K. Fukumoto-Inukai ,&nbsp;K. Bermeo ,&nbsp;I. Arenas ,&nbsp;M.J. Rosendo-Pineda ,&nbsp;J.A. Pimentel-Cabrera ,&nbsp;D.E. Garcia","doi":"10.1016/j.mce.2024.112275","DOIUrl":"10.1016/j.mce.2024.112275","url":null,"abstract":"<div><p>Metabolic changes are critical in the regulation of Ca<sup>2+</sup> influx in central and peripheral neuroendocrine cells. To study the regulation of L-type Ca<sup>2+</sup> channels by AMPK we used biochemical reagents and ATP/glucose-concentration manipulations in rat chromaffin cells. AICAR and Compound-C, at low concentration, significantly induce changes in L-type Ca<sup>2+</sup> channel-current amplitude and voltage dependence. Remarkably, an overlasting decrease in the channel-current density can be induced by lowering the intracellular level of ATP. Accordingly, Ca<sup>2+</sup> channel-current density gradually diminishes by decreasing the extracellular glucose concentration. By using immunofluorescence, a decrease in the expression of Ca<sub>V</sub>1.2 is observed while decreasing extracellular glucose, suggesting that AMPK reduces the number of functional Ca<sup>2+</sup> channels into the plasma membrane. Together, these results support for the first time the dependence of metabolic changes in the maintenance of Ca<sup>2+</sup> channel-current by AMPK. They reveal a key step in Ca<sup>2+</sup> influx in secretory cells.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"591 ","pages":"Article 112275"},"PeriodicalIF":4.1,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interleukin-1 increases SERPINE1 expression in human granulosa-lutein cell via P50/P52 signaling pathways 白细胞介素-1 通过 P50/P52 信号通路增加人 Granulosa-Lutein 细胞中 SERPINE1 的表达。
IF 4.1 3区 医学 Q2 CELL BIOLOGY Pub Date : 2024-05-20 DOI: 10.1016/j.mce.2024.112274
Yu Xiang , Shuangying Liu , Shan Wan , Qingqing Chen , Yang Song , Guofang Feng , Xinyue Zhang , Long Bai , Yimin Zhu

It has been reported that immune factors are associated with the occurrence of polycystic ovary syndrome (PCOS). Interleukin-1 (IL-1) is a member of the interleukin family that widely participates in the regulation of the inflammatory response in the immune system. In addition, it has been reported that aberrant IL-1 accumulation in serum is associated with the occurrence of PCOS. However, little is known about how IL-1 participates in the pathogenesis of PCOS. In the present study, we demonstrated that the immune microenvironment was altered in follicular fluid from PCOS patients and that the expression levels of two IL-1 cytokines, IL-1α and IL-1β were increased. Transcriptome analysis revealed that IL-1α and IL-1β treatment induced primary human granulosa-lutein (hGL) cell inflammatory response and increased the expression of serpin family E member 1 (SERPINE1). Mechanistically, we demonstrated that IL-1α and IL-1β upregulated SERPINE1 expression through IL-1R1-mediated activation of downstream P50 and P52 signaling pathways in human granulosa cells. Our study highlighted the role of immune state changes in the occurrence of PCOS and provided new insight into the treatment of patients with IL-1-induced ovarian function disorders.

据报道,免疫因素与多囊卵巢综合征(PCOS)的发生有关。白细胞介素-1(IL-1)是白细胞介素家族的一员,广泛参与调节免疫系统的炎症反应。此外,据报道,血清中 IL-1 的异常积累与多囊卵巢综合症的发生有关。然而,人们对 IL-1 如何参与 PCOS 的发病机制知之甚少。本研究表明,PCOS 患者卵泡液中的免疫微环境发生了改变,两种 IL-1 细胞因子(IL-1α 和 IL-1β)的表达水平升高。转录组分析表明,IL-1α和IL-1β可诱导原代人颗粒-黄体(hGL)细胞炎症反应,并增加丝氨酸蛋白家族E成员1(SERPINE1)的表达。从机理上讲,我们证明了IL-1α和IL-1β通过IL-1R1介导的下游P50和P52信号通路激活人颗粒细胞中SERPINE1的表达。我们的研究强调了免疫状态变化在多囊卵巢综合征发生中的作用,并为治疗IL-1诱导的卵巢功能紊乱患者提供了新的见解。
{"title":"Interleukin-1 increases SERPINE1 expression in human granulosa-lutein cell via P50/P52 signaling pathways","authors":"Yu Xiang ,&nbsp;Shuangying Liu ,&nbsp;Shan Wan ,&nbsp;Qingqing Chen ,&nbsp;Yang Song ,&nbsp;Guofang Feng ,&nbsp;Xinyue Zhang ,&nbsp;Long Bai ,&nbsp;Yimin Zhu","doi":"10.1016/j.mce.2024.112274","DOIUrl":"10.1016/j.mce.2024.112274","url":null,"abstract":"<div><p>It has been reported that immune factors are associated with the occurrence of polycystic ovary syndrome (PCOS). Interleukin-1 (IL-1) is a member of the interleukin family that widely participates in the regulation of the inflammatory response in the immune system. In addition, it has been reported that aberrant IL-1 accumulation in serum is associated with the occurrence of PCOS. However, little is known about how IL-1 participates in the pathogenesis of PCOS. In the present study, we demonstrated that the immune microenvironment was altered in follicular fluid from PCOS patients and that the expression levels of two IL-1 cytokines, IL-1α and IL-1β were increased. Transcriptome analysis revealed that IL-1α and IL-1β treatment induced primary human granulosa-lutein (hGL) cell inflammatory response and increased the expression of serpin family E member 1 (SERPINE1). Mechanistically, we demonstrated that IL-1α and IL-1β upregulated SERPINE1 expression through IL-1R1-mediated activation of downstream P50 and P52 signaling pathways in human granulosa cells. Our study highlighted the role of immune state changes in the occurrence of PCOS and provided new insight into the treatment of patients with IL-1-induced ovarian function disorders.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"591 ","pages":"Article 112274"},"PeriodicalIF":4.1,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Molecular and Cellular Endocrinology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1