首页 > 最新文献

Combinatorial chemistry & high throughput screening最新文献

英文 中文
The Association of Allergic Rhinitis with Chronic Adenotonsillar Diseases and Chronic Rhinosinusitis: A Mendelian Randomization Study. 变应性鼻炎与慢性腺扁桃体疾病和慢性鼻窦炎的关系:一项孟德尔随机研究。
IF 1.7 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-01-08 DOI: 10.2174/0113862073428198251103103134
Chao Wang, Zhipeng Yin, Xiao Han, Yufei Pan, Kai Sun, Yuanyuan Lu, Zhenkun Yu

Introduction: Allergic rhinitis (AR) has long been considered to be associated with chronic adenotonsillar disease (CATD). However, their causal relationship remains unclear. This study aims to investigate the causal relationship between AR and CATD and to examine the mediating role of chronic rhinosinusitis (CRS) in this association.

Methods: This study employed a two-sample Mendelian randomization (MR) design using genetic instrumental variable analysis. Data for allergic rhinitis (AR) were obtained from the MRC IEU OpenGWAS data infrastructure, data for chronic adenotonsillar disease (CATD) from the FinnGen biobank, and data for chronic rhinosinusitis (CRS) from the GWAS Catalog. Several MR methods were applied. In addition, a two-step MR approach was used to investigate the mediating role of CRS in the relationship between AR and CATD.

Results: MR analysis identified a positive correlation between AR and CATD. IVW and weighted median analyses showed significant causal effects (beta = 0.55, 95% CI: 0.26 to 0.84); p <0.001). No causal association was found between CATD and AR. AR and CRS showed a positive correlation (beta = 1.38, 95% CI: 0.78 to 1.98; p = 6.5 × 10-6). CRS had a beta value of 0.15 (95% CI: 0.06 to 0.24; p = 0.001) for CATD. CRS mediates 37.6% of the AR to CATD pathway (mediation effect = 0.20, 95% CI: 0.04 to 0.37; p = 0.013).

Discussion: These findings indicate that AR may contribute to CATD risk through CRS, highlighting the need for further research to explore underlying biological mechanisms and validate these findings.

Conclusions: This study suggests a positive causal relationship between AR and CATD, with CRS acting as a mediator.

导论:变应性鼻炎(AR)一直被认为与慢性腺扁桃体病(CATD)有关。然而,它们之间的因果关系尚不清楚。本研究旨在探讨AR和CATD之间的因果关系,并探讨慢性鼻窦炎(CRS)在这一关联中的中介作用。方法:本研究采用双样本孟德尔随机化设计,采用遗传工具变量分析。过敏性鼻炎(AR)的数据来自MRC IEU OpenGWAS数据基础设施,慢性腺扁桃体病(CATD)的数据来自FinnGen生物银行,慢性鼻窦炎(CRS)的数据来自GWAS目录。应用了几种核磁共振方法。此外,我们采用两步MR方法来研究CRS在AR和CATD之间的中介作用。结果:MR分析发现AR与CATD呈正相关。IVW和加权中位数分析显示显著的因果效应(β = 0.55, 95% CI: 0.26 ~ 0.84);p讨论:这些发现表明AR可能通过CRS增加CATD风险,强调需要进一步研究以探索潜在的生物学机制并验证这些发现。结论:本研究提示AR和CATD之间存在正因果关系,其中CRS起中介作用。
{"title":"The Association of Allergic Rhinitis with Chronic Adenotonsillar Diseases and Chronic Rhinosinusitis: A Mendelian Randomization Study.","authors":"Chao Wang, Zhipeng Yin, Xiao Han, Yufei Pan, Kai Sun, Yuanyuan Lu, Zhenkun Yu","doi":"10.2174/0113862073428198251103103134","DOIUrl":"https://doi.org/10.2174/0113862073428198251103103134","url":null,"abstract":"<p><strong>Introduction: </strong>Allergic rhinitis (AR) has long been considered to be associated with chronic adenotonsillar disease (CATD). However, their causal relationship remains unclear. This study aims to investigate the causal relationship between AR and CATD and to examine the mediating role of chronic rhinosinusitis (CRS) in this association.</p><p><strong>Methods: </strong>This study employed a two-sample Mendelian randomization (MR) design using genetic instrumental variable analysis. Data for allergic rhinitis (AR) were obtained from the MRC IEU OpenGWAS data infrastructure, data for chronic adenotonsillar disease (CATD) from the FinnGen biobank, and data for chronic rhinosinusitis (CRS) from the GWAS Catalog. Several MR methods were applied. In addition, a two-step MR approach was used to investigate the mediating role of CRS in the relationship between AR and CATD.</p><p><strong>Results: </strong>MR analysis identified a positive correlation between AR and CATD. IVW and weighted median analyses showed significant causal effects (beta = 0.55, 95% CI: 0.26 to 0.84); p <0.001). No causal association was found between CATD and AR. AR and CRS showed a positive correlation (beta = 1.38, 95% CI: 0.78 to 1.98; p = 6.5 × 10-6). CRS had a beta value of 0.15 (95% CI: 0.06 to 0.24; p = 0.001) for CATD. CRS mediates 37.6% of the AR to CATD pathway (mediation effect = 0.20, 95% CI: 0.04 to 0.37; p = 0.013).</p><p><strong>Discussion: </strong>These findings indicate that AR may contribute to CATD risk through CRS, highlighting the need for further research to explore underlying biological mechanisms and validate these findings.</p><p><strong>Conclusions: </strong>This study suggests a positive causal relationship between AR and CATD, with CRS acting as a mediator.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Potential Mechanism of Gumibao Decoction in Treating Glucocorticoidinduced Osteoporosis Based on Network Pharmacology and Experimental Verification. 骨蜜保汤治疗糖皮质激素性骨质疏松的潜在机制:基于网络药理学及实验验证。
IF 1.7 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-01-08 DOI: 10.2174/0113862073388008251008041439
Liang Wang, Dong Xiao, Ganqun Lu, Guoqiang Liang, Zhengfeng Gong, Pengfei Yu, Huanhuan Feng
<p><strong>Objective: </strong>Gumibao decoction, a traditional Chinese herbal prescription, has demonstrated promising effects in treating osteoporosis; however, the underlying mechanism remains unclear. We investigated the regulatory mechanisms of Gumibao decoction in osteoporosis through network pharmacology analysis and validated its therapeutic effects using animal experiments.</p><p><strong>Methods: </strong>The TCMSP database was used to screen the bioactive constituents of Gumibao decoction and identify their associated targets. Disease targets for osteoporosis were acquired through the Gene- Cards, PharmGKB, DrugBank, OMIM, and TTD databases. A Protein-Protein Interaction (PPI) network was generated. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were subsequently performed for the core targets identified in the PPI network. Moreover, a glucocorticoid-induced osteoporosis model was established in Sprague-Dawley (SD) rats by administering methylprednisolone and dexamethasone, and the regulatory effects of Gumibao decoction on osteoporosis were evaluated using bone mass detection and western blotting.</p><p><strong>Results: </strong>The network pharmacology analysis identified quercetin, (-)-Epigallocatechin-3-Gallate (EGCG), kaempferol, luteolin, and fisetin as the primary bioactive components of Gumibao decoction. Core target proteins included AKT1, TP53, JUN, CTNNB1, and IL1B. The KEGG pathway enrichment analysis revealed the significant involvement of the TGF-β signalling pathway, osteoclast differentiation, and the MAPK signalling pathway in mediating its anti-osteoporotic effects. In vivo validation demonstrated that Gumibao decoction significantly ameliorated glucocorticoid-induced reductions in Bone Mineral Density (BMD) and deterioration of bone microstructure. Furthermore, protein expression analysis revealed significantly reduced levels of Smad4, phospho-Smad2/3, and TGF-β1 in the model group compared with the blank control group. Notably, all Gumibao decoction treatment groups exhibited significant upregulation of Smad4, P-Smad2/3, and TGF-β1 expression compared with the model group, validating the network pharmacology predictions implicating the TGF-β pathway.</p><p><strong>Discussion: </strong>Research on the components of Gumibao decoction has shown that it can regulate homeostasis between osteoblasts and osteoclasts through multiple targeted pathways, thereby positively modulating bone density, bone microstructure, and bone markers. This ultimately inhibits osteoclast differentiation and stimulates osteoblast proliferation, effectively alleviating and preventing osteoporosis.</p><p><strong>Conclusion: </strong>Gumibao decoction effectively improves glucocorticoid-induced osteoporosis, potentially by upregulating the expression of TGF-β1, P-Smad2/3, and Smad4 through the TGF-Β/Smad pathway, promoting bone formation, and restoring bone metabolic balance
目的:中药奎米保汤对骨质疏松症的治疗效果良好;然而,其潜在机制尚不清楚。我们通过网络药理学分析探讨骨米宝汤对骨质疏松症的调节机制,并通过动物实验验证其治疗效果。方法:利用TCMSP数据库对骨肉保汤的活性成分进行筛选,并鉴定其相关靶点。通过Gene- Cards、PharmGKB、DrugBank、OMIM和TTD数据库获得骨质疏松症的疾病靶点。生成了蛋白质-蛋白质相互作用(PPI)网络。随后对在PPI网络中确定的核心靶点进行了基因本体(GO)功能注释和京都基因与基因组百科全书(KEGG)途径富集分析。采用甲基强的松龙和地塞米松分别建立SD大鼠糖皮质激素所致骨质疏松模型,采用骨量检测和免疫印迹法评价骨密保汤对骨质疏松的调节作用。结果:网络药理学分析鉴定出槲皮素、(-)-表没食子儿茶素-3-没食子酸酯(EGCG)、山奈酚、木犀草素和非瑟酮是骨肉宝汤的主要生物活性成分。核心靶蛋白包括AKT1、TP53、JUN、CTNNB1和IL1B。KEGG通路富集分析显示TGF-β信号通路、破骨细胞分化和MAPK信号通路参与了其抗骨质疏松作用。体内实验验证表明,骨糜保汤能显著改善糖皮质激素诱导的骨密度降低和骨微结构恶化。蛋白表达分析显示,与空白对照组相比,模型组Smad4、phospho-Smad2/3、TGF-β1水平明显降低。值得注意的是,与模型组相比,所有顾米保煎剂治疗组均显著上调Smad4、P-Smad2/3和TGF-β1的表达,验证了TGF-β通路的网络药理学预测。讨论:对骨米宝汤成分的研究表明,其可以通过多种靶向途径调节成骨细胞和破骨细胞之间的稳态,从而正向调节骨密度、骨微观结构和骨标志物。最终抑制破骨细胞分化,刺激成骨细胞增殖,有效缓解和预防骨质疏松。结论:骨蜜保汤有效改善糖皮质激素所致骨质疏松大鼠,其机制可能是通过TGF-Β/Smad通路上调TGF-Β 1、P-Smad2/3、Smad4的表达,促进骨形成,恢复骨代谢平衡。
{"title":"Potential Mechanism of Gumibao Decoction in Treating Glucocorticoidinduced Osteoporosis Based on Network Pharmacology and Experimental Verification.","authors":"Liang Wang, Dong Xiao, Ganqun Lu, Guoqiang Liang, Zhengfeng Gong, Pengfei Yu, Huanhuan Feng","doi":"10.2174/0113862073388008251008041439","DOIUrl":"https://doi.org/10.2174/0113862073388008251008041439","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Gumibao decoction, a traditional Chinese herbal prescription, has demonstrated promising effects in treating osteoporosis; however, the underlying mechanism remains unclear. We investigated the regulatory mechanisms of Gumibao decoction in osteoporosis through network pharmacology analysis and validated its therapeutic effects using animal experiments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The TCMSP database was used to screen the bioactive constituents of Gumibao decoction and identify their associated targets. Disease targets for osteoporosis were acquired through the Gene- Cards, PharmGKB, DrugBank, OMIM, and TTD databases. A Protein-Protein Interaction (PPI) network was generated. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were subsequently performed for the core targets identified in the PPI network. Moreover, a glucocorticoid-induced osteoporosis model was established in Sprague-Dawley (SD) rats by administering methylprednisolone and dexamethasone, and the regulatory effects of Gumibao decoction on osteoporosis were evaluated using bone mass detection and western blotting.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The network pharmacology analysis identified quercetin, (-)-Epigallocatechin-3-Gallate (EGCG), kaempferol, luteolin, and fisetin as the primary bioactive components of Gumibao decoction. Core target proteins included AKT1, TP53, JUN, CTNNB1, and IL1B. The KEGG pathway enrichment analysis revealed the significant involvement of the TGF-β signalling pathway, osteoclast differentiation, and the MAPK signalling pathway in mediating its anti-osteoporotic effects. In vivo validation demonstrated that Gumibao decoction significantly ameliorated glucocorticoid-induced reductions in Bone Mineral Density (BMD) and deterioration of bone microstructure. Furthermore, protein expression analysis revealed significantly reduced levels of Smad4, phospho-Smad2/3, and TGF-β1 in the model group compared with the blank control group. Notably, all Gumibao decoction treatment groups exhibited significant upregulation of Smad4, P-Smad2/3, and TGF-β1 expression compared with the model group, validating the network pharmacology predictions implicating the TGF-β pathway.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Research on the components of Gumibao decoction has shown that it can regulate homeostasis between osteoblasts and osteoclasts through multiple targeted pathways, thereby positively modulating bone density, bone microstructure, and bone markers. This ultimately inhibits osteoclast differentiation and stimulates osteoblast proliferation, effectively alleviating and preventing osteoporosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Gumibao decoction effectively improves glucocorticoid-induced osteoporosis, potentially by upregulating the expression of TGF-β1, P-Smad2/3, and Smad4 through the TGF-Β/Smad pathway, promoting bone formation, and restoring bone metabolic balance ","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
ACC Inhibition by Lanatoside C: A Repurposed MASH Therapy. lanat苷C抑制ACC:一种改良的MASH疗法。
IF 1.7 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-01-08 DOI: 10.2174/0113862073405993251117054929
Xianxiang Bai, Rubin Duan, Bin Xiao

Introduction: Metabolic Dysfunction-Associated Steatohepatitis (MASH) is a growing global health concern, with only one FDA-approved therapy currently available. Acetyl-CoA carboxylase (ACC) inhibition has emerged as a promising strategy, yet effective and clinically translatable inhibitors remain limited. This study aimed to identify potential ACC inhibitors for MASH via drug repurposing.

Methods: A small-molecule library was screened using structure-based virtual screening, and candidate compounds were validated in a free fatty acid-induced MASH cell model. Intracellular triglyceride (TG) and aspartate aminotransferase (AST) levels were measured, while quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate lipid metabolism- related gene expression. Molecular dynamics simulations were conducted to further evaluate binding stability.

Results: Lanatoside C was identified as the most potent candidate. In vitro studies revealed significant reductions in TG and AST levels, downregulation of lipogenesis-related genes (SREBP1, FASN, ACC), and upregulation of fatty acid oxidation genes (CPT1A, ACOX1, FABP1). Molecular dynamics simulations confirmed the stable binding of Lanatoside C to ACC.

Discussion: These findings indicate that Lanatoside C exerts dual regulatory effects on lipid metabolism by suppressing fatty acid synthesis and enhancing oxidation. As an FDA-approved cardiac glycoside, Lanatoside C's known pharmacological profile supports its potential repositioning for MASH, although further in vivo studies and mechanistic validation are warranted.

Conclusion: Lanatoside C demonstrates promise as a repurposed ACC inhibitor for MASH treatment, offering a cost-effective repurposing strategy to advance therapeutic options for MASH.

代谢功能障碍相关脂肪性肝炎(MASH)是一个日益增长的全球健康问题,目前只有一种fda批准的治疗方法可用。乙酰辅酶a羧化酶(ACC)抑制已成为一种有前途的策略,但有效和临床可翻译的抑制剂仍然有限。本研究旨在通过药物再利用来确定潜在的ACC抑制剂。方法:采用基于结构的虚拟筛选方法筛选小分子文库,并在游离脂肪酸诱导的MASH细胞模型中对候选化合物进行验证。检测细胞内甘油三酯(TG)和天冬氨酸转氨酶(AST)水平,定量反转录聚合酶链反应(qRT-PCR)检测脂质代谢相关基因表达。通过分子动力学模拟进一步评价其结合稳定性。结果:Lanatoside C被确定为最有效的候选者。体外研究显示TG和AST水平显著降低,脂肪生成相关基因(SREBP1、FASN、ACC)下调,脂肪酸氧化基因(CPT1A、ACOX1、FABP1)上调。分子动力学模拟证实了Lanatoside C与ACC的稳定结合。讨论:这些发现表明Lanatoside C通过抑制脂肪酸合成和促进氧化对脂质代谢具有双重调节作用。作为fda批准的心脏糖苷,Lanatoside C已知的药理学特征支持其用于MASH的潜在重新定位,尽管进一步的体内研究和机制验证是必要的。结论:Lanatoside C作为一种改良的ACC抑制剂有望用于MASH治疗,提供了一种具有成本效益的改良策略,以推进MASH的治疗选择。
{"title":"ACC Inhibition by Lanatoside C: A Repurposed MASH Therapy.","authors":"Xianxiang Bai, Rubin Duan, Bin Xiao","doi":"10.2174/0113862073405993251117054929","DOIUrl":"https://doi.org/10.2174/0113862073405993251117054929","url":null,"abstract":"<p><strong>Introduction: </strong>Metabolic Dysfunction-Associated Steatohepatitis (MASH) is a growing global health concern, with only one FDA-approved therapy currently available. Acetyl-CoA carboxylase (ACC) inhibition has emerged as a promising strategy, yet effective and clinically translatable inhibitors remain limited. This study aimed to identify potential ACC inhibitors for MASH via drug repurposing.</p><p><strong>Methods: </strong>A small-molecule library was screened using structure-based virtual screening, and candidate compounds were validated in a free fatty acid-induced MASH cell model. Intracellular triglyceride (TG) and aspartate aminotransferase (AST) levels were measured, while quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate lipid metabolism- related gene expression. Molecular dynamics simulations were conducted to further evaluate binding stability.</p><p><strong>Results: </strong>Lanatoside C was identified as the most potent candidate. In vitro studies revealed significant reductions in TG and AST levels, downregulation of lipogenesis-related genes (SREBP1, FASN, ACC), and upregulation of fatty acid oxidation genes (CPT1A, ACOX1, FABP1). Molecular dynamics simulations confirmed the stable binding of Lanatoside C to ACC.</p><p><strong>Discussion: </strong>These findings indicate that Lanatoside C exerts dual regulatory effects on lipid metabolism by suppressing fatty acid synthesis and enhancing oxidation. As an FDA-approved cardiac glycoside, Lanatoside C's known pharmacological profile supports its potential repositioning for MASH, although further in vivo studies and mechanistic validation are warranted.</p><p><strong>Conclusion: </strong>Lanatoside C demonstrates promise as a repurposed ACC inhibitor for MASH treatment, offering a cost-effective repurposing strategy to advance therapeutic options for MASH.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Nutritional Evaluation of Three Freshwater Gastropod Species Consumed in Assam, India. 印度阿萨姆邦食用的三种淡水腹足类动物的营养评价。
IF 1.7 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-01-06 DOI: 10.2174/0113862073419515251107132458
Karabi Kalita, Namram Sushindrajit Singh, Tarali Kalita, Akalesh Kumar Verma, Pooja Das, Priyanku Sarma, Najma Khatun, Arpita Sarkar, Richa Sharma, Devajit Basumatari

Introduction: The rising demand for sustainable, nutritionally rich food sources has sparked interest in non-traditional protein sources, including gastropods. In northeastern India, freshwater gastropod species are widely consumed, particularly by certain tribes and communities, both as a traditional delicacy and for their nutritional value. This study delves into the biochemical composition of three commonly consumed freshwater gastropod species in Assam, namely Pila globosa, Pila scutata, and Brotia costula, to evaluate their potential as alternative food sources, with a focus on nutritional value and palatability.

Methods: In the present study, proximate analysis was done by using standard methods given in the Association of Official Analytical Chemists (AOAC, 2015). Mineral analysis was carried out using the atomic absorption spectrophotometer (AAS). High Performance Liquid Chromatography (HPLC) (method QA.16.5.10/AOAC 19th edition) was employed for the determination of amino acid contents of the samples.

Results: Among the species analyzed, P. scutata and P. globosa displayed the highest protein content, whereas B. costula exhibited greater levels of ash and carbohydrates. Mineral analysis showed that P. globosa contained the highest concentrations of calcium (Ca), magnesium (Mg), iron (Fe), zinc (Zn), and copper (Cu). Amino acid profiling revealed lysine and serine as the key essential and non-essential amino acids, with P. globosa and P. scutata showing higher concentrations, respectively.

Discussion: This study highlights the nutritional richness of three freshwater gastropod species, with Pila globosa and Pila scutata showing high protein and mineral content, and Brotia costula contributing to energy and mineral intake. Their amino acid profiles further enhance their dietary value. Gastropods in local culture embody the use of snail meat as a part of traditional food source, highlighting different ethnomedicinal beliefs. Despite their benefits, these species remain underutilized, suggesting the need for broader awareness and integration into mainstream diets to support food security and nutrition in northeastern India.

Conclusion: Given the current scenario of food disparity, incorporating gastropods into human diets could provide a sustainable and reliable source of protein and micronutrients, particularly in areas where food security is a concern.

导语:对可持续、营养丰富的食物来源的需求不断增长,引发了人们对非传统蛋白质来源的兴趣,包括腹足类动物。在印度东北部,淡水腹足类动物被广泛食用,特别是在某些部落和社区,既是一种传统美食,也是一种营养价值。本研究深入研究了阿萨姆邦三种常见的淡水腹足动物物种,即Pila globosa, Pila scutta和Brotia costula的生化组成,以评估它们作为替代食物来源的潜力,重点关注营养价值和美味性。方法:在本研究中,使用官方分析化学家协会(AOAC, 2015)给出的标准方法进行近似分析。采用原子吸收分光光度计(AAS)进行矿物分析。采用高效液相色谱法(HPLC)(方法QA.16.5.10/AOAC 19版)测定样品的氨基酸含量。结果:在所分析的种属中,木犀草和球犀草的蛋白质含量最高,木犀草的灰分和碳水化合物含量较高。矿物学分析表明,球藻中钙(Ca)、镁(Mg)、铁(Fe)、锌(Zn)和铜(Cu)含量最高。氨基酸分析表明,赖氨酸和丝氨酸是主要的必需氨基酸和非必需氨基酸,其中球形假体和鸡眼假体的氨基酸含量较高。讨论:本研究强调了三种淡水腹足动物的营养丰富程度,其中globosa和scutata的蛋白质和矿物质含量较高,而Brotia costula则有助于能量和矿物质的摄入。它们的氨基酸谱进一步提高了它们的膳食价值。当地文化中的腹足动物体现了将蜗牛肉作为传统食物来源的一部分,突出了不同的民族医学信仰。尽管这些物种有好处,但它们仍未得到充分利用,这表明需要更广泛的认识并将其纳入主流饮食,以支持印度东北部的粮食安全和营养。结论:鉴于目前粮食差距的情况,将腹足类动物纳入人类饮食可以提供可持续和可靠的蛋白质和微量营养素来源,特别是在粮食安全受到关注的地区。
{"title":"Nutritional Evaluation of Three Freshwater Gastropod Species Consumed in Assam, India.","authors":"Karabi Kalita, Namram Sushindrajit Singh, Tarali Kalita, Akalesh Kumar Verma, Pooja Das, Priyanku Sarma, Najma Khatun, Arpita Sarkar, Richa Sharma, Devajit Basumatari","doi":"10.2174/0113862073419515251107132458","DOIUrl":"https://doi.org/10.2174/0113862073419515251107132458","url":null,"abstract":"<p><strong>Introduction: </strong>The rising demand for sustainable, nutritionally rich food sources has sparked interest in non-traditional protein sources, including gastropods. In northeastern India, freshwater gastropod species are widely consumed, particularly by certain tribes and communities, both as a traditional delicacy and for their nutritional value. This study delves into the biochemical composition of three commonly consumed freshwater gastropod species in Assam, namely Pila globosa, Pila scutata, and Brotia costula, to evaluate their potential as alternative food sources, with a focus on nutritional value and palatability.</p><p><strong>Methods: </strong>In the present study, proximate analysis was done by using standard methods given in the Association of Official Analytical Chemists (AOAC, 2015). Mineral analysis was carried out using the atomic absorption spectrophotometer (AAS). High Performance Liquid Chromatography (HPLC) (method QA.16.5.10/AOAC 19th edition) was employed for the determination of amino acid contents of the samples.</p><p><strong>Results: </strong>Among the species analyzed, P. scutata and P. globosa displayed the highest protein content, whereas B. costula exhibited greater levels of ash and carbohydrates. Mineral analysis showed that P. globosa contained the highest concentrations of calcium (Ca), magnesium (Mg), iron (Fe), zinc (Zn), and copper (Cu). Amino acid profiling revealed lysine and serine as the key essential and non-essential amino acids, with P. globosa and P. scutata showing higher concentrations, respectively.</p><p><strong>Discussion: </strong>This study highlights the nutritional richness of three freshwater gastropod species, with Pila globosa and Pila scutata showing high protein and mineral content, and Brotia costula contributing to energy and mineral intake. Their amino acid profiles further enhance their dietary value. Gastropods in local culture embody the use of snail meat as a part of traditional food source, highlighting different ethnomedicinal beliefs. Despite their benefits, these species remain underutilized, suggesting the need for broader awareness and integration into mainstream diets to support food security and nutrition in northeastern India.</p><p><strong>Conclusion: </strong>Given the current scenario of food disparity, incorporating gastropods into human diets could provide a sustainable and reliable source of protein and micronutrients, particularly in areas where food security is a concern.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Gypenoside LI Inhibits Renal Cancer Proliferation by Affecting Lipid Metabolism through the Upregulation of Dual-Specificity Phosphatase 1. 绞股皂苷LI通过上调双特异性磷酸酶1影响脂质代谢抑制肾癌增殖。
IF 1.7 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-11-29 DOI: 10.2174/0113862073437377251103074331
Anxin Wang, Xiuming Li, Yujie Wei, Peixuan Sun, Shuai Li, Jiahui Yu, Chang Zhou, Hui Liu

Introduction: Gynostemma pentaphyllum is commonly used in southern China to treat hyperlipidemia and tumors, primarily due to its active saponin compounds. This study aimed to analyze the inhibitory effect of gypenoside LI (Gyp LI) on clear cell renal cell carcinoma (ccRCC), which is mediated through DUSP1-related lipid metabolism.

Materials and methods: The concentration of Gyp LI required to inhibit the ccRCC cell lines 769-P and ACHN was determined using a CCK8 assay, and DUSP1 upregulation was confirmed by transcriptomic sequencing, RT-qPCR, and Western blot analysis. The roles of DUSP1 and Gyp LI in regulating cell proliferation were further validated using CCK-8, colony formation, and flow cytometry assays. . Additionally, we established a nude mouse xenograft tumor model using ACHN cells that overexpress DUSP1. We assessed the effects of Gyp LI and DUSP1 on tumor growth through histopathological examinations. We employed untargeted tissue metabolomics to identify metabolic pathways influenced by Gyp LI via upregulation of DUSP1.

Results: CCK-8 experiments showed that Gyp LI inhibited the proliferation of ccRCC cells. Additionally, transcriptome sequencing revealed that DUSP1 expression increased following Gyp LI intervention. We transfected cells with siDUSP1 and ovDUSP1 and assessed cell proliferation using CCK8, colony formation, flow cytometry, and WB analyses of apoptosis-related proteins, confirming that both ovDUSP1 and Gyp LI inhibited ccRCC cell proliferation. Animal studies revealed that both ovDUSP1 and Gyp LI inhibited tumor growth. Non-targeted metabolomics analysis revealed that Gyp LI affected seven metabolites associated with ccRCC treatment by upregulating DUSP1.

Conclusion: Gyp LI upregulates DUSP1 to suppress the metabolism of choline, linoleic acid, and alpha-linolenic acid, ultimately suppressing the incidence and progression of ccRCC.

绞股蓝在中国南方常用来治疗高脂血症和肿瘤,主要是由于它的活性皂苷化合物。本研究旨在分析绞盘皂苷LI (Gyp LI)对透明细胞肾细胞癌(ccRCC)的抑制作用,该作用通过与dusp1相关的脂质代谢介导。材料和方法:采用CCK8法测定抑制ccRCC细胞系769-P和ACHN所需的Gyp LI浓度,并通过转录组测序、RT-qPCR和Western blot分析证实DUSP1上调。通过CCK-8、集落形成和流式细胞术进一步验证了DUSP1和Gyp LI在调节细胞增殖中的作用。此外,我们利用过表达DUSP1的ACHN细胞建立了裸鼠异种移植瘤模型。我们通过组织病理学检查评估Gyp LI和DUSP1对肿瘤生长的影响。我们采用非靶向组织代谢组学方法,通过上调DUSP1来鉴定受Gyp LI影响的代谢途径。结果:CCK-8实验显示,Gyp LI能抑制ccRCC细胞的增殖。此外,转录组测序显示,在Gyp LI干预后,DUSP1的表达增加。我们转染细胞siDUSP1和ovDUSP1,并通过CCK8、集落形成、流式细胞术和凋亡相关蛋白的WB分析评估细胞增殖,证实ovDUSP1和Gyp LI均抑制ccRCC细胞增殖。动物实验表明,ovDUSP1和Gyp LI均能抑制肿瘤生长。非靶向代谢组学分析显示,Gyp LI通过上调DUSP1影响与ccRCC治疗相关的7种代谢物。结论:Gyp LI上调DUSP1抑制胆碱、亚油酸和α -亚麻酸的代谢,最终抑制ccRCC的发生和进展。
{"title":"Gypenoside LI Inhibits Renal Cancer Proliferation by Affecting Lipid Metabolism through the Upregulation of Dual-Specificity Phosphatase 1.","authors":"Anxin Wang, Xiuming Li, Yujie Wei, Peixuan Sun, Shuai Li, Jiahui Yu, Chang Zhou, Hui Liu","doi":"10.2174/0113862073437377251103074331","DOIUrl":"https://doi.org/10.2174/0113862073437377251103074331","url":null,"abstract":"<p><strong>Introduction: </strong>Gynostemma pentaphyllum is commonly used in southern China to treat hyperlipidemia and tumors, primarily due to its active saponin compounds. This study aimed to analyze the inhibitory effect of gypenoside LI (Gyp LI) on clear cell renal cell carcinoma (ccRCC), which is mediated through DUSP1-related lipid metabolism.</p><p><strong>Materials and methods: </strong>The concentration of Gyp LI required to inhibit the ccRCC cell lines 769-P and ACHN was determined using a CCK8 assay, and DUSP1 upregulation was confirmed by transcriptomic sequencing, RT-qPCR, and Western blot analysis. The roles of DUSP1 and Gyp LI in regulating cell proliferation were further validated using CCK-8, colony formation, and flow cytometry assays. . Additionally, we established a nude mouse xenograft tumor model using ACHN cells that overexpress DUSP1. We assessed the effects of Gyp LI and DUSP1 on tumor growth through histopathological examinations. We employed untargeted tissue metabolomics to identify metabolic pathways influenced by Gyp LI via upregulation of DUSP1.</p><p><strong>Results: </strong>CCK-8 experiments showed that Gyp LI inhibited the proliferation of ccRCC cells. Additionally, transcriptome sequencing revealed that DUSP1 expression increased following Gyp LI intervention. We transfected cells with siDUSP1 and ovDUSP1 and assessed cell proliferation using CCK8, colony formation, flow cytometry, and WB analyses of apoptosis-related proteins, confirming that both ovDUSP1 and Gyp LI inhibited ccRCC cell proliferation. Animal studies revealed that both ovDUSP1 and Gyp LI inhibited tumor growth. Non-targeted metabolomics analysis revealed that Gyp LI affected seven metabolites associated with ccRCC treatment by upregulating DUSP1.</p><p><strong>Conclusion: </strong>Gyp LI upregulates DUSP1 to suppress the metabolism of choline, linoleic acid, and alpha-linolenic acid, ultimately suppressing the incidence and progression of ccRCC.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Network Pharmacology and Computational Study to Identify Active Components and Potential Targets of Polygonatum sibiricum for Hepatocellular Carcinoma Treatment. 鉴别黄精治疗肝癌的有效成分和潜在靶点的网络药理学和计算研究。
IF 1.7 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-11-17 DOI: 10.2174/0113862073439548251029051037
Yuan Pan, Xiaoyu Zhang, Chao Chen, Chunmei Hu

Introduction: Polygonatum sibiricum (P. sibiricum) possesses antioxidant and antiinflammatory activities. We explored the multi-target mechanisms of P. sibiricum against hepatocellular carcinoma (HCC), aiming to improve its poor prognosis.

Materials and methods: Active compounds and disease targets of P. sibiricum were retrieved from the TCMSP and CTD databases. A PROTEIN-PROTEIN INTERACTION (PPI) network was constructed using the STRING database, and functional enrichment was performed with the clusterProfiler package. A compound-target-pathway network was developed in Cytoscape. Immune infiltration was assessed via CIBERSORT and ESTIMATE algorithms, while ligand-target binding was evaluated by molecular docking and 100-ns molecular dynamics (MD) simulations. In vitro experiments were performed to explore the expression and functions of the key genes.

Results: We screened 9 active components, 87 putative targets, and 240 HCC-related genes. Twenty overlapping targets were used to construct a PPI network. Network analysis identified baicalein and five core targets (FOS, MMP9, AKT1, TP53, and PTGS2). Molecular docking and 100-ns MD simulations confirmed stable ligand-protein binding. Immune profiling showed that higher expression of the core targets was related to higher StromalScore, ImmuneScore, and lower tumor purity. Enrichment analysis revealed that these genes were involved in critical pathways, including angiogenesis, EMT, and inflammation response. Functionally, MMP9 knockdown suppressed HCC cell proliferation, migration, and invasion.

Discussion: P. sibiricum, particularly through baicalein targeting FOS/MMP9/AKT1/ TP53/PTGS2, inhibited HCC development by modulating EMT/angiogenesis pathways and immune milieu. However, these findings required further verification.

Conclusion: Baicalein was identified as an active compound targeting five crucial genes to suppress HCC progression, uncovering a new anti-HCC mechanism of P. sibiricum.

简介:西伯利亚黄精具有抗氧化和抗炎活性。为了改善肝细胞癌(HCC)的不良预后,我们探讨了sibiricum治疗HCC的多靶点机制。材料与方法:从TCMSP和CTD数据库中检索西伯利亚野檀的有效成分和疾病靶点。利用STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,并利用clusterProfiler包进行功能富集。在Cytoscape中建立了一个化合物-靶标-通路网络。通过CIBERSORT和ESTIMATE算法评估免疫浸润,通过分子对接和100-ns分子动力学(MD)模拟评估配体-靶标结合。通过体外实验探讨关键基因的表达和功能。结果:我们筛选了9种有效成分、87种推定靶点和240种hcc相关基因。使用20个重叠的目标构建PPI网络。网络分析鉴定出黄芩素和5个核心靶点(FOS、MMP9、AKT1、TP53和PTGS2)。分子对接和100-ns MD模拟证实了稳定的配体-蛋白结合。免疫分析显示,核心靶点的高表达与较高的StromalScore、ImmuneScore和较低的肿瘤纯度有关。富集分析显示,这些基因参与了血管生成、EMT和炎症反应等关键途径。功能上,MMP9敲低抑制HCC细胞的增殖、迁移和侵袭。讨论:sibiricum,特别是通过黄黄素靶向FOS/MMP9/AKT1/ TP53/PTGS2,通过调节EMT/血管生成途径和免疫环境来抑制HCC的发展。然而,这些发现需要进一步核实。结论:黄芩苷是一种靶向5个关键基因抑制肝癌进展的活性化合物,揭示了黄芩抗肝癌的新机制。
{"title":"Network Pharmacology and Computational Study to Identify Active Components and Potential Targets of Polygonatum sibiricum for Hepatocellular Carcinoma Treatment.","authors":"Yuan Pan, Xiaoyu Zhang, Chao Chen, Chunmei Hu","doi":"10.2174/0113862073439548251029051037","DOIUrl":"https://doi.org/10.2174/0113862073439548251029051037","url":null,"abstract":"<p><p><p>Introduction: Polygonatum sibiricum (P. sibiricum) possesses antioxidant and antiinflammatory activities. We explored the multi-target mechanisms of P. sibiricum against hepatocellular carcinoma (HCC), aiming to improve its poor prognosis.</p><p><strong>Materials and methods: </strong>Active compounds and disease targets of P. sibiricum were retrieved from the TCMSP and CTD databases. A PROTEIN-PROTEIN INTERACTION (PPI) network was constructed using the STRING database, and functional enrichment was performed with the clusterProfiler package. A compound-target-pathway network was developed in Cytoscape. Immune infiltration was assessed via CIBERSORT and ESTIMATE algorithms, while ligand-target binding was evaluated by molecular docking and 100-ns molecular dynamics (MD) simulations. In vitro experiments were performed to explore the expression and functions of the key genes.</p><p><strong>Results: </strong>We screened 9 active components, 87 putative targets, and 240 HCC-related genes. Twenty overlapping targets were used to construct a PPI network. Network analysis identified baicalein and five core targets (FOS, MMP9, AKT1, TP53, and PTGS2). Molecular docking and 100-ns MD simulations confirmed stable ligand-protein binding. Immune profiling showed that higher expression of the core targets was related to higher StromalScore, ImmuneScore, and lower tumor purity. Enrichment analysis revealed that these genes were involved in critical pathways, including angiogenesis, EMT, and inflammation response. Functionally, MMP9 knockdown suppressed HCC cell proliferation, migration, and invasion.</p><p><strong>Discussion: </strong>P. sibiricum, particularly through baicalein targeting FOS/MMP9/AKT1/ TP53/PTGS2, inhibited HCC development by modulating EMT/angiogenesis pathways and immune milieu. However, these findings required further verification.</p><p><strong>Conclusion: </strong>Baicalein was identified as an active compound targeting five crucial genes to suppress HCC progression, uncovering a new anti-HCC mechanism of P. sibiricum.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Network Pharmacology Analysis and Experimental Validation Reveal the Mechanism of Action of Longlutong Decoction in the Treatment of Coronary Heart Disease. 网络药理学分析及实验验证揭示龙骨通汤治疗冠心病的作用机制。
IF 1.7 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-11-14 DOI: 10.2174/0113862073426600251020060402
Xiaocong Ma, Yang Zhai, Cong Tian, Wenhui Shao, Guangshan Zheng, Guihua Yue

Introduction: Longlutong Decoction (LLTD) is a Chinese traditional prescription used for coronary heart disease (CHD). The present study aimed to illuminate the mechanisms of LLTD treatment on CHD.

Methods: The therapeutic effect of LLTD on CHD was investigated using a CHD rat model. The chemical components of LLTD were identified, following which network pharmacology approaches were utilized to identify active components and disease-related targets. GO and KEGG analyses were conducted to explore potential molecular mechanisms. Finally, the molecular mechanism of LLTD treatment of CHD was verified.

Results: Histopathological assessment revealed markedly attenuated myocardial injury severity in the medicated groups when compared to the model group. Moreover, 81 potential active ingredients were identified in LLTD, with 645 overlapping targets between component targets and disease targets. Network analysis identified Pinocembrin, Magnoflorine, Jatrorrhizine as key active ingredients, and AKT1, TNF, IL-6, STAT3, and Bcl-2 as primary core targets. A total of 1792 biological processes were affected according to GO analysis, and 187 pathways were identified through KEGG analysis. Finally, molecular docking and experimental results validated that LLTD could alleviate cardiomyocyte injury in CHD by regulating the primary core targets.

Discussion: This study indicates that LLTD may achieve systematic modulating of the signaling network through a "network pharmacology" model, which provides valuable insights for the development of multi-target therapies targeting the complex pathological mechanism underlying CHD.

Conclusion: LLTD may exert cardioprotective effects by regulating inflammatory responses, apoptosis, and oxidative stress.

龙骨通汤是一种用于治疗冠心病(CHD)的中药方剂。本研究旨在阐明LLTD治疗冠心病的机制。方法:采用冠心病大鼠模型,观察枳实对冠心病的治疗作用。鉴定了LLTD的化学成分,随后利用网络药理学方法鉴定了活性成分和疾病相关靶点。通过GO和KEGG分析来探索潜在的分子机制。最后,验证了LLTD治疗冠心病的分子机制。结果:与模型组比较,给药组心肌损伤程度明显减轻。此外,在LLTD中鉴定出81种潜在的有效成分,其中645种成分靶点与疾病靶点重叠。网络分析发现,匹诺诺啡、magnnoflorine、Jatrorrhizine是关键活性成分,AKT1、TNF、IL-6、STAT3和Bcl-2是主要核心靶点。根据GO分析,共有1792个生物过程受到影响,通过KEGG分析确定了187个途径。最后,分子对接和实验结果验证了LLTD通过调节主要核心靶点来减轻冠心病心肌细胞损伤。讨论:本研究表明,LLTD可能通过“网络药理学”模型实现信号网络的系统性调节,这为开发针对冠心病复杂病理机制的多靶点治疗方法提供了有价值的见解。结论:LLTD可能通过调节炎症反应、细胞凋亡和氧化应激发挥心脏保护作用。
{"title":"Network Pharmacology Analysis and Experimental Validation Reveal the Mechanism of Action of Longlutong Decoction in the Treatment of Coronary Heart Disease.","authors":"Xiaocong Ma, Yang Zhai, Cong Tian, Wenhui Shao, Guangshan Zheng, Guihua Yue","doi":"10.2174/0113862073426600251020060402","DOIUrl":"https://doi.org/10.2174/0113862073426600251020060402","url":null,"abstract":"<p><strong>Introduction: </strong>Longlutong Decoction (LLTD) is a Chinese traditional prescription used for coronary heart disease (CHD). The present study aimed to illuminate the mechanisms of LLTD treatment on CHD.</p><p><strong>Methods: </strong>The therapeutic effect of LLTD on CHD was investigated using a CHD rat model. The chemical components of LLTD were identified, following which network pharmacology approaches were utilized to identify active components and disease-related targets. GO and KEGG analyses were conducted to explore potential molecular mechanisms. Finally, the molecular mechanism of LLTD treatment of CHD was verified.</p><p><strong>Results: </strong>Histopathological assessment revealed markedly attenuated myocardial injury severity in the medicated groups when compared to the model group. Moreover, 81 potential active ingredients were identified in LLTD, with 645 overlapping targets between component targets and disease targets. Network analysis identified Pinocembrin, Magnoflorine, Jatrorrhizine as key active ingredients, and AKT1, TNF, IL-6, STAT3, and Bcl-2 as primary core targets. A total of 1792 biological processes were affected according to GO analysis, and 187 pathways were identified through KEGG analysis. Finally, molecular docking and experimental results validated that LLTD could alleviate cardiomyocyte injury in CHD by regulating the primary core targets.</p><p><strong>Discussion: </strong>This study indicates that LLTD may achieve systematic modulating of the signaling network through a \"network pharmacology\" model, which provides valuable insights for the development of multi-target therapies targeting the complex pathological mechanism underlying CHD.</p><p><strong>Conclusion: </strong>LLTD may exert cardioprotective effects by regulating inflammatory responses, apoptosis, and oxidative stress.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
MiR-509-3p Targets YAP1 to Regulate Inflammatory Cytokines Against Hyperglycemia-Induced Renal Tubular Cell Damage in Diabetic Kidney Disease. MiR-509-3p靶向YAP1调节炎症因子对抗高血糖诱导的糖尿病肾病肾小管细胞损伤
IF 1.7 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-11-14 DOI: 10.2174/0113862073446094251111052119
Xiaoyu Wang, Linlin Li, Bowen Tian, Hongdong Li, Xiaodong Zhu, Shumei Shi

Introduction: Hyperglycemia-induced renal inflammation and the subsequent activation of inflammatory cytokines play critical roles in Diabetic Kidney Disease (DKD) progression. However, the underlying molecular mechanisms, particularly those involving microRNAs, remain poorly understood.

Methods: Serum samples from DKD patients (n = 10) and healthy controls (n = 10) were subjected to microRNA transcriptome profiling. An in vitro DKD model was established by treating Human Renal Tubular Epithelial Cells (RTECs and HK-2) with High Glucose (HG). The levels of pro-inflammatory cytokines, Interleukin (IL)-1β, IL-6, and Tumor Necrosis Factor (TNF)-α, were assessed using quantitative reverse transcription-PCR and enzyme-linked immunosorbent assay. Dual-luciferase reporter assays evaluated the relationship between miR-509-3p and Yesassociated protein 1 (YAP1). In situ hybridization and immunohistochemistry were performed to validate the expressions of miR-509-3p and YAP1 in kidney tissues from DKD patients (n = 38) and controls (n = 38).

Results: MiR-509-3p was identified as one of the most significantly dysregulated microRNAs in the serum of DKD patients. Its expression was significantly downregulated in a dose-dependent manner in HG-induced RTECs and HK-2 cells (p <0.01). Overexpression of miR-509-3p significantly suppressed HG-induced pro-inflammatory cytokine expression (p <0.01). Suppression of miR-509-3p further enhanced HG-induced IL-1β, TNF-α, and IL-6 expression, whereas this effect was reversed by silencing YAP1 (p <0.01). Mechanistically, miR-509-3p directly targeted the 3'-UTR of YAP1 mRNA. Consistently, DKD renal tissues exhibited reduced miR-509-3p and elevated YAP1 expression, with a significant negative correlation (p = 0.002). Furthermore, miR-509-3p and YAP1 were significantly correlated with estimated glomerular filtration rate and urine albumin-creatinine ratio (p <0.001).

Conclusion: The study preliminarily suggests that miR-509-3p/YAP1 axis may act as a crucial regulator of hyperglycemia-induced tubular inflammation, offering a potential therapeutic target for DKD.

导读:高血糖诱导的肾脏炎症和随后的炎症细胞因子的激活在糖尿病肾病(DKD)的进展中起着关键作用。然而,潜在的分子机制,特别是那些涉及microrna的机制,仍然知之甚少。方法:对DKD患者(n = 10)和健康对照(n = 10)的血清样本进行microRNA转录组分析。采用高糖(HG)处理人肾小管上皮细胞(RTECs和HK-2),建立体外DKD模型。采用定量逆转录pcr和酶联免疫吸附法检测促炎细胞因子、白细胞介素(IL)-1β、IL-6和肿瘤坏死因子(TNF)-α的水平。双荧光素酶报告基因检测评估了miR-509-3p与Yesassociated protein 1 (YAP1)之间的关系。采用原位杂交和免疫组织化学方法验证miR-509-3p和YAP1在DKD患者(n = 38)和对照组(n = 38)肾脏组织中的表达。结果:MiR-509-3p被鉴定为DKD患者血清中最显著失调的microrna之一。在hg诱导的RTECs和HK-2细胞中,其表达呈剂量依赖性显著下调(p)。结论:本研究初步提示miR-509-3p/YAP1轴可能是高血糖诱导的小管炎症的重要调节因子,为DKD提供了潜在的治疗靶点。
{"title":"MiR-509-3p Targets YAP1 to Regulate Inflammatory Cytokines Against Hyperglycemia-Induced Renal Tubular Cell Damage in Diabetic Kidney Disease.","authors":"Xiaoyu Wang, Linlin Li, Bowen Tian, Hongdong Li, Xiaodong Zhu, Shumei Shi","doi":"10.2174/0113862073446094251111052119","DOIUrl":"https://doi.org/10.2174/0113862073446094251111052119","url":null,"abstract":"<p><strong>Introduction: </strong>Hyperglycemia-induced renal inflammation and the subsequent activation of inflammatory cytokines play critical roles in Diabetic Kidney Disease (DKD) progression. However, the underlying molecular mechanisms, particularly those involving microRNAs, remain poorly understood.</p><p><strong>Methods: </strong>Serum samples from DKD patients (n = 10) and healthy controls (n = 10) were subjected to microRNA transcriptome profiling. An in vitro DKD model was established by treating Human Renal Tubular Epithelial Cells (RTECs and HK-2) with High Glucose (HG). The levels of pro-inflammatory cytokines, Interleukin (IL)-1β, IL-6, and Tumor Necrosis Factor (TNF)-α, were assessed using quantitative reverse transcription-PCR and enzyme-linked immunosorbent assay. Dual-luciferase reporter assays evaluated the relationship between miR-509-3p and Yesassociated protein 1 (YAP1). In situ hybridization and immunohistochemistry were performed to validate the expressions of miR-509-3p and YAP1 in kidney tissues from DKD patients (n = 38) and controls (n = 38).</p><p><strong>Results: </strong>MiR-509-3p was identified as one of the most significantly dysregulated microRNAs in the serum of DKD patients. Its expression was significantly downregulated in a dose-dependent manner in HG-induced RTECs and HK-2 cells (p <0.01). Overexpression of miR-509-3p significantly suppressed HG-induced pro-inflammatory cytokine expression (p <0.01). Suppression of miR-509-3p further enhanced HG-induced IL-1β, TNF-α, and IL-6 expression, whereas this effect was reversed by silencing YAP1 (p <0.01). Mechanistically, miR-509-3p directly targeted the 3'-UTR of YAP1 mRNA. Consistently, DKD renal tissues exhibited reduced miR-509-3p and elevated YAP1 expression, with a significant negative correlation (p = 0.002). Furthermore, miR-509-3p and YAP1 were significantly correlated with estimated glomerular filtration rate and urine albumin-creatinine ratio (p <0.001).</p><p><strong>Conclusion: </strong>The study preliminarily suggests that miR-509-3p/YAP1 axis may act as a crucial regulator of hyperglycemia-induced tubular inflammation, offering a potential therapeutic target for DKD.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Exploring Endoplasmic Reticulum Stress-Related Genes in Cartilage Defects: Implications for Diagnosis and Therapy. 探索软骨缺损内质网应力相关基因:对诊断和治疗的意义。
IF 1.7 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-11-14 DOI: 10.2174/0113862073441646251107115725
Haoqi Cai, Cong Li, Kai Luo, Xiaoyang Zhang, Bozhong Shi, Bo Chen, Guowei Zeng, Longming Huang, Jinghao Zheng, Xiaomin He

Introduction: Cartilage defects (CDs) are orthopedic conditions with limited regenerative potential. This study aimed to identify endoplasmic reticulum (ER) stress-related biomarkers and construct a diagnostic model to enhance the early detection of CD.

Methods: This study analyzed the transcriptomic dataset GSE129147 to identify ER stressrelated differentially expressed genes (ERSRDEGs) between CD and control tissues using the limma package (version 3.58.1). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were employed for functional enrichment. Immune infiltration was assessed using cell-type identification, which involved estimating the relative subsets of RNA transcripts and single-sample gene set enrichment analysis. Diagnostic models were constructed using logistic regression, support vector machine, and least absolute shrinkage and selection operator regression.

Results: Twenty ERSRDEGs were identified, with CYBB, ATP6V1A, and TNFRSF12A significantly upregulated in CD samples. GO and KEGG analyses highlighted oxidative stress response and extracellular matrix remodeling as key mechanisms in CD pathogenesis. Immune analysis revealed an increase in regulatory T cells and a reduction in CD8⁺ T cells. TNFRSF12A showed strong immune associations and, together with TWIST1 and ATP6V1A, formed the final preliminary diagnostic model. The preliminary LASSO model achieved satisfactory predictive accuracy (AUC: 0.7-0.9).

Discussion: These findings suggest that ER stress and immune imbalance jointly contribute to cartilage degeneration. The identified genes, particularly TNFRSF12A, TWIST1, and ATP6V1A, not only serve as potential biomarkers but also provide preliminary evidence for new mechanistic insights into stress-immune crosstalk in CD.

Conclusion: This study reveals the key roles of ER stress and immune dysregulation in CDs. Moreover, the ERSRDEG-based diagnostic model provides preliminary bioinformatics evidence and potential molecular indicators for targeted diagnostics and therapies.

软骨缺损(cd)是一种再生潜力有限的骨科疾病。本研究旨在鉴定内质网(ER)应激相关生物标志物,构建诊断模型,提高CD的早期检测。方法:利用limma软件包(版本3.58.1)对转录组学数据集GSE129147进行分析,鉴定CD与对照组织内质网应激相关差异表达基因(ERSRDEGs)。使用京都基因与基因组百科全书(KEGG)和基因本体(GO)分析进行功能富集。利用细胞类型鉴定评估免疫浸润,包括估计RNA转录物的相对亚群和单样本基因集富集分析。使用逻辑回归、支持向量机、最小绝对收缩和选择算子回归构建诊断模型。结果:鉴定出20个ersrdeg,其中CYBB、ATP6V1A和TNFRSF12A在CD样品中显著上调。GO和KEGG分析强调氧化应激反应和细胞外基质重塑是CD发病的关键机制。免疫分析显示调节性T细胞增加,CD8 + T细胞减少。TNFRSF12A表现出很强的免疫关联,并与TWIST1和ATP6V1A共同形成最终的初步诊断模型。初步LASSO模型获得了满意的预测精度(AUC: 0.7 ~ 0.9)。讨论:这些发现提示内质网应激和免疫失衡共同导致软骨退变。这些鉴定出的基因,尤其是TNFRSF12A、TWIST1和ATP6V1A,不仅可以作为潜在的生物标志物,而且为cd中应激-免疫串扰机制的新见解提供了初步证据。结论:本研究揭示了内质网应激和免疫失调在cd中的关键作用。此外,基于ersrdeg的诊断模型为靶向诊断和治疗提供了初步的生物信息学证据和潜在的分子指标。
{"title":"Exploring Endoplasmic Reticulum Stress-Related Genes in Cartilage Defects: Implications for Diagnosis and Therapy.","authors":"Haoqi Cai, Cong Li, Kai Luo, Xiaoyang Zhang, Bozhong Shi, Bo Chen, Guowei Zeng, Longming Huang, Jinghao Zheng, Xiaomin He","doi":"10.2174/0113862073441646251107115725","DOIUrl":"https://doi.org/10.2174/0113862073441646251107115725","url":null,"abstract":"<p><strong>Introduction: </strong>Cartilage defects (CDs) are orthopedic conditions with limited regenerative potential. This study aimed to identify endoplasmic reticulum (ER) stress-related biomarkers and construct a diagnostic model to enhance the early detection of CD.</p><p><strong>Methods: </strong>This study analyzed the transcriptomic dataset GSE129147 to identify ER stressrelated differentially expressed genes (ERSRDEGs) between CD and control tissues using the limma package (version 3.58.1). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were employed for functional enrichment. Immune infiltration was assessed using cell-type identification, which involved estimating the relative subsets of RNA transcripts and single-sample gene set enrichment analysis. Diagnostic models were constructed using logistic regression, support vector machine, and least absolute shrinkage and selection operator regression.</p><p><strong>Results: </strong>Twenty ERSRDEGs were identified, with CYBB, ATP6V1A, and TNFRSF12A significantly upregulated in CD samples. GO and KEGG analyses highlighted oxidative stress response and extracellular matrix remodeling as key mechanisms in CD pathogenesis. Immune analysis revealed an increase in regulatory T cells and a reduction in CD8⁺ T cells. TNFRSF12A showed strong immune associations and, together with TWIST1 and ATP6V1A, formed the final preliminary diagnostic model. The preliminary LASSO model achieved satisfactory predictive accuracy (AUC: 0.7-0.9).</p><p><strong>Discussion: </strong>These findings suggest that ER stress and immune imbalance jointly contribute to cartilage degeneration. The identified genes, particularly TNFRSF12A, TWIST1, and ATP6V1A, not only serve as potential biomarkers but also provide preliminary evidence for new mechanistic insights into stress-immune crosstalk in CD.</p><p><strong>Conclusion: </strong>This study reveals the key roles of ER stress and immune dysregulation in CDs. Moreover, the ERSRDEG-based diagnostic model provides preliminary bioinformatics evidence and potential molecular indicators for targeted diagnostics and therapies.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Impact of All-trans Retinoic Acid on Skeletal Development: Mechanisms of Growth Plate Closure. 全反式维甲酸对骨骼发育的影响:生长板闭合的机制。
IF 1.7 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Pub Date : 2025-11-14 DOI: 10.2174/0113862073424590251103061707
Fan Xuan, Yutong Xing, Zuyan Mei, Yanan Zhang, YaLei Pi, Xiaoli Wu, Huifeng Zhang

Introduction: All-trans retinoic acid (ATRA), a therapeutic mainstay for acute promyelocytic leukemia, is associated with off-target effects on skeletal development, including premature growth plate closure. However, the molecular mechanisms underlying ATRA-induced growth plate senescence remain poorly understood.

Methods: Using Sprague-Dawley rats, ADTC5 chondrocyte cell lines, and integrated multiomics approaches (transcriptome sequencing, weighted gene co-expression network analysis, molecular docking, and functional assays), we investigated how ATRA modulates growth plate development. Animal models were treated with graded ATRA doses, while in vitro studies included cell viability assays, RNA interference, and Western blot analysis to validate interactions in the signaling pathway.

Results: ATRA induced dose-dependent growth plate thinning (high-dose: 59.79 μm vs. control: 511.35 μm) and skeletal growth retardation in rats. Transcriptomic analysis identified ITGB2 as a pivotal gene, with molecular docking revealing a strong binding interaction (-240.25 kcal/mol) between ITGB2 and YAP mediated by hydrogen bonds/salt bridges. Functional experiments revealed that ATRA upregulated ITGB2, which activated YAP, a Hippo pathway effector, thereby suppressing Wnt/β-catenin signaling by inhibiting β-catenin. This led to downregulation of osteogenic markers (Runx2/SOX9) and enhanced growth plate closure. YAP knockdown reversed these effects, restoring β-catenin and downstream target gene expression (c-myc, cyclin D).

Conclusion: ATRA accelerates growth plate closure through the ITGB2-YAP axis, disrupting Wnt/β-catenin signaling. These findings establish a mechanistic framework for developing therapeutic strategies targeting ITGB2 or YAP to delay premature growth plate senescence in pediatric disorders.

全反式维甲酸(ATRA)是治疗急性早幼粒细胞白血病的主要药物,与骨骼发育脱靶效应相关,包括过早生长板闭合。然而,atra诱导生长板衰老的分子机制仍然知之甚少。方法:利用Sprague-Dawley大鼠、ADTC5软骨细胞系和综合多组学方法(转录组测序、加权基因共表达网络分析、分子对接和功能分析),研究ATRA如何调节生长板的发育。动物模型用分级ATRA剂量处理,而体外研究包括细胞活力测定、RNA干扰和Western blot分析,以验证信号通路中的相互作用。结果:ATRA诱导大鼠生长板变薄(高剂量为59.79 μm,对照组为511.35 μm)和骨骼生长迟缓。转录组学分析发现ITGB2是关键基因,分子对接显示ITGB2与YAP之间通过氢键/盐桥介导的强结合相互作用(-240.25 kcal/mol)。功能实验显示,ATRA上调ITGB2,激活Hippo通路效应因子YAP,从而通过抑制β-catenin抑制Wnt/β-catenin信号传导。这导致成骨标志物(Runx2/SOX9)下调,生长板闭合增强。YAP敲除逆转了这些作用,恢复了β-catenin和下游靶基因(c-myc, cyclin D)的表达。结论:ATRA通过ITGB2-YAP轴加速生长板闭合,破坏Wnt/β-catenin信号通路。这些发现为制定针对ITGB2或YAP的治疗策略以延缓儿科疾病中生长板过早衰老建立了机制框架。
{"title":"Impact of All-trans Retinoic Acid on Skeletal Development: Mechanisms of Growth Plate Closure.","authors":"Fan Xuan, Yutong Xing, Zuyan Mei, Yanan Zhang, YaLei Pi, Xiaoli Wu, Huifeng Zhang","doi":"10.2174/0113862073424590251103061707","DOIUrl":"https://doi.org/10.2174/0113862073424590251103061707","url":null,"abstract":"<p><strong>Introduction: </strong>All-trans retinoic acid (ATRA), a therapeutic mainstay for acute promyelocytic leukemia, is associated with off-target effects on skeletal development, including premature growth plate closure. However, the molecular mechanisms underlying ATRA-induced growth plate senescence remain poorly understood.</p><p><strong>Methods: </strong>Using Sprague-Dawley rats, ADTC5 chondrocyte cell lines, and integrated multiomics approaches (transcriptome sequencing, weighted gene co-expression network analysis, molecular docking, and functional assays), we investigated how ATRA modulates growth plate development. Animal models were treated with graded ATRA doses, while in vitro studies included cell viability assays, RNA interference, and Western blot analysis to validate interactions in the signaling pathway.</p><p><strong>Results: </strong>ATRA induced dose-dependent growth plate thinning (high-dose: 59.79 μm vs. control: 511.35 μm) and skeletal growth retardation in rats. Transcriptomic analysis identified ITGB2 as a pivotal gene, with molecular docking revealing a strong binding interaction (-240.25 kcal/mol) between ITGB2 and YAP mediated by hydrogen bonds/salt bridges. Functional experiments revealed that ATRA upregulated ITGB2, which activated YAP, a Hippo pathway effector, thereby suppressing Wnt/β-catenin signaling by inhibiting β-catenin. This led to downregulation of osteogenic markers (Runx2/SOX9) and enhanced growth plate closure. YAP knockdown reversed these effects, restoring β-catenin and downstream target gene expression (c-myc, cyclin D).</p><p><strong>Conclusion: </strong>ATRA accelerates growth plate closure through the ITGB2-YAP axis, disrupting Wnt/β-catenin signaling. These findings establish a mechanistic framework for developing therapeutic strategies targeting ITGB2 or YAP to delay premature growth plate senescence in pediatric disorders.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Combinatorial chemistry & high throughput screening
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:604180095
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