首页 > 最新文献

Methods最新文献

英文 中文
A novel methodology for mapping interstitial fluid dynamics in murine brain tumors using DCE-MRI 利用 DCE-MRI 绘制小鼠脑肿瘤间质流体动力学图的新方法。
IF 4.2 3区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-09-14 DOI: 10.1016/j.ymeth.2024.09.008
Cora Carman-Esparza , Kathryn Kingsmore , Andrea Vaccari , Skylar Davis , Jessica Cunningham , Maosen Wang , Jennifer Munson
We present a comprehensive methodology for measuring heterogeneous interstitial fluid flow in murine brain tumors using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) coupled with the computational tool, Lymph4D. This four-part protocol encompasses glioma cell preparation, tumor inoculation, MRI imaging protocol, and histological verification using Evans Blue. While conventional DCE-MRI analysis primarily focuses on vascular perfusion, our methods reveal untapped potential to extract crucial information about interstitial fluid dynamics, including directions, velocities, and diffusion coefficients. This methodology extends beyond glioma research, with applicability to conditions routinely imaged with DCE-MRI, thereby offering a versatile tool for investigating interstitial fluid dynamics across a wide range of diseases and conditions. Our methodology holds promise for accelerating discoveries and advancements in biomedical research, ultimately enhancing diagnostic and therapeutic strategies for a wide range of diseases and conditions.
我们介绍了一种利用动态对比增强磁共振成像(DCE-MRI)和计算工具 Lymph4D 测量小鼠脑肿瘤异质性间质流的综合方法。该方案由四个部分组成,包括胶质瘤细胞制备、肿瘤接种、磁共振成像方案和使用伊文思蓝进行组织学验证。传统的 DCE-MRI 分析主要关注血管灌注,而我们的方法揭示了提取间质流体动力学关键信息(包括方向、速度和扩散系数)的未开发潜力。这种方法不仅适用于胶质瘤研究,还适用于 DCE-MRI 常规成像的病症,从而为研究各种疾病和病症的间质流体动力学提供了多功能工具。我们的方法有望加速生物医学研究的发现和进步,最终提高各种疾病和病症的诊断和治疗策略。
{"title":"A novel methodology for mapping interstitial fluid dynamics in murine brain tumors using DCE-MRI","authors":"Cora Carman-Esparza ,&nbsp;Kathryn Kingsmore ,&nbsp;Andrea Vaccari ,&nbsp;Skylar Davis ,&nbsp;Jessica Cunningham ,&nbsp;Maosen Wang ,&nbsp;Jennifer Munson","doi":"10.1016/j.ymeth.2024.09.008","DOIUrl":"10.1016/j.ymeth.2024.09.008","url":null,"abstract":"<div><div>We present a comprehensive methodology for measuring heterogeneous interstitial fluid flow in murine brain tumors using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) coupled with the computational tool, <em>Lymph4D</em>. This four-part protocol encompasses glioma cell preparation, tumor inoculation, MRI imaging protocol, and histological verification using Evans Blue. While conventional DCE-MRI analysis primarily focuses on vascular perfusion, our methods reveal untapped potential to extract crucial information about interstitial fluid dynamics, including directions, velocities, and diffusion coefficients. This methodology extends beyond glioma research, with applicability to conditions routinely imaged with DCE-MRI, thereby offering a versatile tool for investigating interstitial fluid dynamics across a wide range of diseases and conditions. Our methodology holds promise for accelerating discoveries and advancements in biomedical research, ultimately enhancing diagnostic and therapeutic strategies for a wide range of diseases and conditions.</div></div>","PeriodicalId":390,"journal":{"name":"Methods","volume":"231 ","pages":"Pages 78-93"},"PeriodicalIF":4.2,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Digital Intervention for behaviouR changE and Chronic disease prevenTION (DIRECTION): Study protocol for a randomized controlled trial of a web-based platform integrating nutrition, physical activity, and mindfulness for individuals with obesity 改变行为和预防慢性病的数字干预(DIRECTION):针对肥胖症患者的集营养、体育锻炼和正念于一体的网络平台随机对照试验研究方案
IF 4.2 3区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-09-13 DOI: 10.1016/j.ymeth.2024.09.009
Camila E. Orsso , Teresita Gormaz , Sabina Valentine , Claire F. Trottier , Iasmin Matias de Sousa , Martin Ferguson-Pell , Steven T. Johnson , Amy A. Kirkham , Douglas Klein , Nathanial Maeda , João F. Mota , Sarah E. Neil-Sztramko , Maira Quintanilha , Bukola Oladunni Salami , Carla M. Prado

Excess body weight, suboptimal diet, physical inactivity, alcohol consumption, sleep disruption, and elevated stress are modifiable risk factors associated with the development of chronic diseases. Digital behavioural interventions targeting these factors have shown promise in improving health and reducing chronic disease risk. The Digital Intervention for behaviouR changE and Chronic disease prevenTION (DIRECTION) study is a parallel group, two-arm, randomized controlled trial evaluating the effects of adding healthcare professional guidance and peer support via group-based sessions to a web-based wellness platform (experimental group, n = 90) compared to a self-guided use of the platform (active control group, n = 90) among individuals with a body mass index (BMI) of 30 to <35 kg/m2 and aged 40–65 years. Obesity is defined by a high BMI. The web-based wellness platform employed in this study is My Viva Plan (MVP)®, which holistically integrates nutrition, physical activity, and mindfulness programs. Over 16 weeks, the experimental group uses the web-based wellness platform daily and engages in weekly online support group sessions. The active control group exclusively uses the web-based wellness platform daily. Assessments are conducted at baseline and weeks 8 and 16. The primary outcome is between-group difference in weight loss (kg) at week 16, and secondary outcomes are BMI, percent weight change, proportion of participants achieving 5% or more weight loss, dietary intake, physical activity, alcohol consumption, sleep, and stress across the study. A web-based wellness platform may be a scalable approach to promote behavioural changes that positively impact health. This study will inform the development and implementation of interventions using web-based wellness platforms and personalized digital interventions to improve health outcomes and reduce chronic disease risk among individuals with obesity.

体重超标、饮食结构不合理、缺乏运动、饮酒、睡眠紊乱和压力增大是与慢性疾病相关的可改变的风险因素。针对这些因素的数字化行为干预在改善健康状况和降低慢性病风险方面已显示出前景。行为改变和慢性病预防的数字干预(DIRECTION)研究是一项平行分组、双臂随机对照试验,旨在评估在基于网络的健康平台(实验组,n = 90)上通过小组会议增加医疗保健专业指导和同伴支持,与自我指导使用平台(主动对照组,n = 90)相比,对体重指数(BMI)在 30 至 35 kg/m2 之间、年龄在 40 至 65 岁之间的个人产生的影响。肥胖的定义是体重指数较高。本研究采用的网络健康平台是我的万岁计划(MVP)®,该平台全面整合了营养、体育锻炼和正念计划。在为期 16 周的时间里,实验组每天使用网络健康平台,每周参加在线支持小组会议。积极对照组每天只使用网络健康平台。评估在基线、第 8 周和第 16 周进行。主要结果是第 16 周时组间体重减轻的差异(千克),次要结果是体重指数、体重变化百分比、体重减轻 5% 或更多的参与者比例、整个研究期间的饮食摄入量、体力活动、饮酒量、睡眠和压力。基于网络的健康平台可能是促进行为改变、对健康产生积极影响的一种可扩展方法。这项研究将为利用网络健康平台和个性化数字干预来改善肥胖症患者的健康状况和降低慢性病风险的干预措施的开发和实施提供参考。
{"title":"Digital Intervention for behaviouR changE and Chronic disease prevenTION (DIRECTION): Study protocol for a randomized controlled trial of a web-based platform integrating nutrition, physical activity, and mindfulness for individuals with obesity","authors":"Camila E. Orsso ,&nbsp;Teresita Gormaz ,&nbsp;Sabina Valentine ,&nbsp;Claire F. Trottier ,&nbsp;Iasmin Matias de Sousa ,&nbsp;Martin Ferguson-Pell ,&nbsp;Steven T. Johnson ,&nbsp;Amy A. Kirkham ,&nbsp;Douglas Klein ,&nbsp;Nathanial Maeda ,&nbsp;João F. Mota ,&nbsp;Sarah E. Neil-Sztramko ,&nbsp;Maira Quintanilha ,&nbsp;Bukola Oladunni Salami ,&nbsp;Carla M. Prado","doi":"10.1016/j.ymeth.2024.09.009","DOIUrl":"10.1016/j.ymeth.2024.09.009","url":null,"abstract":"<div><p>Excess body weight, suboptimal diet, physical inactivity, alcohol consumption, sleep disruption, and elevated stress are modifiable risk factors associated with the development of chronic diseases. Digital behavioural interventions targeting these factors have shown promise in improving health and reducing chronic disease risk. The <em>Digital Intervention for behaviouR changE and Chronic disease prevenTION</em> (<em>DIRECTION</em>) study is a parallel group, two-arm, randomized controlled trial evaluating the effects of adding healthcare professional guidance and peer support via group-based sessions to a web-based wellness platform (experimental group, n = 90) compared to a self-guided use of the platform (active control group, n = 90) among individuals with a body mass index (BMI) of 30 to &lt;35 kg/m<sup>2</sup> and aged 40–65 years. Obesity is defined by a high BMI. The web-based wellness platform employed in this study is My Viva Plan (MVP)®, which holistically integrates nutrition, physical activity, and mindfulness programs. Over 16 weeks, the experimental group uses the web-based wellness platform daily and engages in weekly online support group sessions. The active control group exclusively uses the web-based wellness platform daily. Assessments are conducted at baseline and weeks 8 and 16. The primary outcome is between-group difference in weight loss (kg) at week 16, and secondary outcomes are BMI, percent weight change, proportion of participants achieving 5% or more weight loss, dietary intake, physical activity, alcohol consumption, sleep, and stress across the study. A web-based wellness platform may be a scalable approach to promote behavioural changes that positively impact health. This study will inform the development and implementation of interventions using web-based wellness platforms and personalized digital interventions to improve health outcomes and reduce chronic disease risk among individuals with obesity.</p></div>","PeriodicalId":390,"journal":{"name":"Methods","volume":"231 ","pages":"Pages 45-54"},"PeriodicalIF":4.2,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S104620232400207X/pdfft?md5=787b2ff333611543fa5dd8dde7ef9999&pid=1-s2.0-S104620232400207X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gluconeogenesis unraveled: A proteomic Odyssey with machine learning 揭开糖元生成的神秘面纱:利用机器学习的蛋白质组奥德赛。
IF 4.2 3区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-09-12 DOI: 10.1016/j.ymeth.2024.09.002
Seher Ansar Khawaja , Fahad Alturise , Tamim Alkhalifah , Sher Afzal Khan , Yaser Daanial Khan
The metabolic pathway known as gluconeogenesis, which produces glucose from non-carbohydrate substrates, is essential for maintaining balanced blood sugar levels while fasting. It's extremely important to anticipate gluconeogenesis rates accurately to recognize metabolic disorders and create efficient treatment strategies. The implementation of deep learning and machine learning methods to forecast complex biological processes has been gaining popularity in recent years. The recognition of both the regulation of the pathway and possible therapeutic applications of proteins depends on accurate identification associated with their gluconeogenesis patterns. This article analyzes the uses of machine learning and deep learning models, to predict gluconeogenesis efficiency. The study also discusses the challenges that come with restricted data availability and model interpretability, as well as possible applications in personalized healthcare, metabolic disease treatment, and the discovery of drugs. The predictor utilizes statistics moments on the structures of gluconeogenesis and their enzymes, while Random Forest is utilized as a classifier to ensure the accuracy of this model in identifying the best outcomes. The method was validated utilizing the independent test, self-consistency, 10k fold cross-validations, and jackknife test which achieved 92.33 %, 91.87%, 87.88%, and 87.02%. An accurate prediction of gluconeogenesis has significant implications for understanding metabolic disorders and developing targeted therapies. This study contributes to the rising field of predictive biology by mixing algorithms for deep learning, and machine learning, with metabolic pathways.
糖元生成是从非碳水化合物底物中产生葡萄糖的代谢途径,对于空腹时维持血糖平衡至关重要。准确预测葡萄糖生成率对于识别代谢紊乱和制定高效的治疗策略极为重要。近年来,采用深度学习和机器学习方法来预测复杂的生物过程越来越受欢迎。识别蛋白质的通路调控和可能的治疗应用都取决于与其糖元生成模式相关的准确识别。本文分析了机器学习和深度学习模型在预测葡萄糖生成效率方面的应用。研究还讨论了受限数据可用性和模型可解释性带来的挑战,以及在个性化医疗保健、代谢疾病治疗和药物发现方面的可能应用。该预测方法利用了葡萄糖生成结构及其酶的统计时刻,并使用随机森林作为分类器,以确保该模型在识别最佳结果方面的准确性。该方法通过独立测试、自一致性、10 k 倍交叉验证和千分比测试进行了验证,结果分别为 92.33 %、91.87 %、87.88 % 和 87.02 %。准确预测葡萄糖生成对了解代谢紊乱和开发靶向疗法具有重要意义。这项研究通过将深度学习和机器学习算法与代谢途径相结合,为正在崛起的预测生物学领域做出了贡献。
{"title":"Gluconeogenesis unraveled: A proteomic Odyssey with machine learning","authors":"Seher Ansar Khawaja ,&nbsp;Fahad Alturise ,&nbsp;Tamim Alkhalifah ,&nbsp;Sher Afzal Khan ,&nbsp;Yaser Daanial Khan","doi":"10.1016/j.ymeth.2024.09.002","DOIUrl":"10.1016/j.ymeth.2024.09.002","url":null,"abstract":"<div><div>The metabolic pathway known as gluconeogenesis, which produces glucose from non-carbohydrate substrates, is essential for maintaining balanced blood sugar levels while fasting. It's extremely important to anticipate gluconeogenesis rates accurately to recognize metabolic disorders and create efficient treatment strategies. The implementation of deep learning and machine learning methods to forecast complex biological processes has been gaining popularity in recent years. The recognition of both the regulation of the pathway and possible therapeutic applications of proteins depends on accurate identification associated with their gluconeogenesis patterns. This article analyzes the uses of machine learning and deep learning models, to predict gluconeogenesis efficiency. The study also discusses the challenges that come with restricted data availability and model interpretability, as well as possible applications in personalized healthcare, metabolic disease treatment, and the discovery of drugs. The predictor utilizes statistics moments on the structures of gluconeogenesis and their enzymes, while Random Forest is utilized as a classifier to ensure the accuracy of this model in identifying the best outcomes. The method was validated utilizing the independent test, self-consistency, 10k fold cross-validations, and jackknife test which achieved 92.33 %, 91.87%, 87.88%, and 87.02%. An accurate prediction of gluconeogenesis has significant implications for understanding metabolic disorders and developing targeted therapies. This study contributes to the rising field of predictive biology by mixing algorithms for deep learning, and machine learning, with metabolic pathways.</div></div>","PeriodicalId":390,"journal":{"name":"Methods","volume":"232 ","pages":"Pages 29-42"},"PeriodicalIF":4.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DeepDBS: Identification of DNA-binding sites in protein sequences by using deep representations and random forest DeepDBS:利用深度表征和随机森林识别蛋白质序列中的 DNA 结合位点
IF 4.2 3区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-09-11 DOI: 10.1016/j.ymeth.2024.09.004
Yaser Daanial Khan , Tamim Alkhalifah , Fahad Alturise , Ahmad Hassan Butt

Interactions of biological molecules in organisms are considered to be primary factors for the lifecycle of that organism. Various important biological functions are dependent on such interactions and among different kinds of interactions, the protein DNA interactions are very important for the processes of transcription, regulation of gene expression, DNA repairing and packaging. Thus, keeping the knowledge of such interactions and the sites of those interactions is necessary to study the mechanism of various biological processes. As experimental identification through biological assays is quite resource-demanding, costly and error-prone, scientists opt for the computational methods for efficient and accurate identification of such DNA-protein interaction sites. Thus, herein, we propose a novel and accurate method namely DeepDBS for the identification of DNA-binding sites in proteins, using primary amino acid sequences of proteins under study. From protein sequences, deep representations were computed through a one-dimensional convolution neural network (1D-CNN), recurrent neural network (RNN) and long short-term memory (LSTM) network and were further used to train a Random Forest classifier. Random Forest with LSTM-based features outperformed the other models, as well as the existing state-of-the-art methods with an accuracy score of 0.99 for self-consistency test, 10-fold cross-validation, 5-fold cross-validation, and jackknife validation while 0.92 for independent dataset testing. It is concluded based on results that the DeepDBS can help accurate and efficient identification of DNA binding sites (DBS) in proteins.

生物体内生物分子的相互作用被认为是生物体生命周期的主要因素。在各种相互作用中,蛋白质 DNA 相互作用对于转录、基因表达调控、DNA 修复和包装过程非常重要。因此,要研究各种生物过程的机制,就必须了解这些相互作用和相互作用的位点。由于通过生物检测进行实验鉴定相当耗费资源、成本高且容易出错,科学家们选择了计算方法来高效、准确地鉴定此类 DNA 蛋白相互作用位点。因此,我们在本文中提出了一种新颖而准确的方法,即 DeepDBS,利用所研究蛋白质的原始氨基酸序列来识别蛋白质中的 DNA 结合位点。根据蛋白质序列,通过一维卷积神经网络(1D-CNN)、递归神经网络(RNN)和长短期记忆(LSTM)网络计算出深度表征,并进一步用于训练随机森林分类器。基于 LSTM 特征的随机森林分类器在自一致性测试、10 倍交叉验证、5 倍交叉验证和 jackknife 验证中的准确率为 0.99,在独立数据集测试中的准确率为 0.92,优于其他模型和现有的先进方法。根据这些结果可以得出结论:DeepDBS 可以帮助准确、高效地识别蛋白质中的 DNA 结合位点(DBS)。
{"title":"DeepDBS: Identification of DNA-binding sites in protein sequences by using deep representations and random forest","authors":"Yaser Daanial Khan ,&nbsp;Tamim Alkhalifah ,&nbsp;Fahad Alturise ,&nbsp;Ahmad Hassan Butt","doi":"10.1016/j.ymeth.2024.09.004","DOIUrl":"10.1016/j.ymeth.2024.09.004","url":null,"abstract":"<div><p>Interactions of biological molecules in organisms are considered to be primary factors for the lifecycle of that organism. Various important biological functions are dependent on such interactions and among different kinds of interactions, the protein DNA interactions are very important for the processes of transcription, regulation of gene expression, DNA repairing and packaging. Thus, keeping the knowledge of such interactions and the sites of those interactions is necessary to study the mechanism of various biological processes. As experimental identification through biological assays is quite resource-demanding, costly and error-prone, scientists opt for the computational methods for efficient and accurate identification of such DNA-protein interaction sites. Thus, herein, we propose a novel and accurate method namely DeepDBS for the identification of DNA-binding sites in proteins, using primary amino acid sequences of proteins under study. From protein sequences, deep representations were computed through a one-dimensional convolution neural network (1D-CNN), recurrent neural network (RNN) and long short-term memory (LSTM) network and were further used to train a Random Forest classifier. Random Forest with LSTM-based features outperformed the other models, as well as the existing state-of-the-art methods with an accuracy score of 0.99 for self-consistency test, 10-fold cross-validation, 5-fold cross-validation, and jackknife validation while 0.92 for independent dataset testing. It is concluded based on results that the DeepDBS can help accurate and efficient identification of DNA binding sites (DBS) in proteins.</p></div>","PeriodicalId":390,"journal":{"name":"Methods","volume":"231 ","pages":"Pages 26-36"},"PeriodicalIF":4.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New methods in biomolecular nuclear magnetic resonance spectroscopy II 生物分子核磁共振光谱新方法 II
IF 4.2 3区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-09-10 DOI: 10.1016/j.ymeth.2024.09.006
T. Michael Sabo
{"title":"New methods in biomolecular nuclear magnetic resonance spectroscopy II","authors":"T. Michael Sabo","doi":"10.1016/j.ymeth.2024.09.006","DOIUrl":"10.1016/j.ymeth.2024.09.006","url":null,"abstract":"","PeriodicalId":390,"journal":{"name":"Methods","volume":"231 ","pages":"Pages 57-60"},"PeriodicalIF":4.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142253897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Artificial intelligence and computer-aided drug discovery: Methods development and application 人工智能和计算机辅助药物发现:方法开发与应用
IF 4.2 3区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-09-10 DOI: 10.1016/j.ymeth.2024.09.005
Haiping Zhang, Yanjie Wei, Konda Mani Saravanan
{"title":"Artificial intelligence and computer-aided drug discovery: Methods development and application","authors":"Haiping Zhang,&nbsp;Yanjie Wei,&nbsp;Konda Mani Saravanan","doi":"10.1016/j.ymeth.2024.09.005","DOIUrl":"10.1016/j.ymeth.2024.09.005","url":null,"abstract":"","PeriodicalId":390,"journal":{"name":"Methods","volume":"231 ","pages":"Pages 55-56"},"PeriodicalIF":4.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the potential of epigenetic clocks in aging research 探索表观遗传时钟在衰老研究中的潜力。
IF 4.2 3区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-09-07 DOI: 10.1016/j.ymeth.2024.09.001
Yuduo Hao , Kaiyuan Han , Ting Wang , Junwen Yu , Hui Ding , Fuying Dao

The process of aging is a notable risk factor for numerous age-related illnesses. Hence, a reliable technique for evaluating biological age or the pace of aging is crucial for understanding the aging process and its influence on the progression of disease. Epigenetic alterations are recognized as a prominent biomarker of aging, and epigenetic clocks formulated on this basis have been shown to provide precise estimations of chronological age. Extensive research has validated the effectiveness of epigenetic clocks in determining aging rates, identifying risk factors for aging, evaluating the impact of anti-aging interventions, and predicting the emergence of age-related diseases. This review provides a detailed overview of the theoretical principles underlying the development of epigenetic clocks and their utility in aging research. Furthermore, it explores the existing obstacles and possibilities linked to epigenetic clocks and proposes potential avenues for future studies in this field.

衰老过程是许多老年相关疾病的一个显著风险因素。因此,评估生物年龄或衰老速度的可靠技术对于了解衰老过程及其对疾病进展的影响至关重要。表观遗传学改变被认为是衰老的一个重要生物标志物,在此基础上制定的表观遗传学时钟已被证明可以精确地估算计时年龄。广泛的研究已经验证了表观遗传时钟在确定衰老率、识别衰老风险因素、评估抗衰老干预措施的影响以及预测老年相关疾病的出现方面的有效性。本综述详细概述了表观遗传时钟发展的理论基础及其在衰老研究中的应用。此外,它还探讨了与表观遗传时钟相关的现有障碍和可能性,并提出了该领域未来研究的潜在途径。
{"title":"Exploring the potential of epigenetic clocks in aging research","authors":"Yuduo Hao ,&nbsp;Kaiyuan Han ,&nbsp;Ting Wang ,&nbsp;Junwen Yu ,&nbsp;Hui Ding ,&nbsp;Fuying Dao","doi":"10.1016/j.ymeth.2024.09.001","DOIUrl":"10.1016/j.ymeth.2024.09.001","url":null,"abstract":"<div><p>The process of aging is a notable risk factor for numerous age-related illnesses. Hence, a reliable technique for evaluating biological age or the pace of aging is crucial for understanding the aging process and its influence on the progression of disease. Epigenetic alterations are recognized as a prominent biomarker of aging, and epigenetic clocks formulated on this basis have been shown to provide precise estimations of chronological age. Extensive research has validated the effectiveness of epigenetic clocks in determining aging rates, identifying risk factors for aging, evaluating the impact of anti-aging interventions, and predicting the emergence of age-related diseases. This review provides a detailed overview of the theoretical principles underlying the development of epigenetic clocks and their utility in aging research. Furthermore, it explores the existing obstacles and possibilities linked to epigenetic clocks and proposes potential avenues for future studies in this field.</p></div>","PeriodicalId":390,"journal":{"name":"Methods","volume":"231 ","pages":"Pages 37-44"},"PeriodicalIF":4.2,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142196501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biomedical event causal relation extraction with deep knowledge fusion and Roberta-based data augmentation 利用深度知识融合和基于罗伯塔的数据增强技术提取生物医学事件因果关系。
IF 4.2 3区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-09-04 DOI: 10.1016/j.ymeth.2024.08.007
Lishuang Li, Yi Xiang, Jing Hao

Biomedical event causal relation extraction (BECRE), as a subtask of biomedical information extraction, aims to extract event causal relation facts from unstructured biomedical texts and plays an essential role in many downstream tasks. The existing works have two main problems: i) Only shallow features are limited in helping the model establish potential relationships between biomedical events. ii) Using the traditional oversampling method to solve the data imbalance problem of the BECRE tasks ignores the requirements for data diversifying. This paper proposes a novel biomedical event causal relation extraction method to solve the above problems using deep knowledge fusion and Roberta-based data augmentation. To address the first problem, we fuse deep knowledge, including structural event representation and entity relation path, for establishing potential semantic connections between biomedical events. We use the Graph Convolutional Neural network (GCN) and the predicated tensor model to acquire structural event representation, and entity relation paths are encoded based on the external knowledge bases (GTD, CDR, CHR, GDA and UMLS). We introduce the triplet attention mechanism to fuse structural event representation and entity relation path information. Besides, this paper proposes the Roberta-based data augmentation method to address the second problem, some words of biomedical text, except biomedical events, are masked proportionally and randomly, and then pre-trained Roberta generates data instances for the imbalance BECRE dataset. Extensive experimental results on Hahn-Powell's and BioCause datasets confirm that the proposed method achieves state-of-the-art performance compared to current advances.

生物医学事件因果关系提取(BECRE)作为生物医学信息提取的一个子任务,旨在从非结构化的生物医学文本中提取事件因果关系事实,在许多下游任务中发挥着至关重要的作用。现有研究存在两个主要问题:i) 局限于浅层特征,无法帮助模型建立生物医学事件之间的潜在关系;ii) 使用传统的超采样方法解决 BECRE 任务的数据不平衡问题,忽视了数据多样化的要求。本文提出了一种新颖的生物医学事件因果关系提取方法,利用深度知识融合和基于 Roberta 的数据增强来解决上述问题。针对第一个问题,我们融合了深度知识,包括结构事件表示和实体关系路径,以建立生物医学事件之间的潜在语义联系。我们使用图卷积神经网络(GCN)和预言张量模型来获取结构事件表示,并基于外部知识库(GTD、CDR、CHR、GDA 和 UMLS)对实体关系路径进行编码。我们引入了三元组关注机制来融合结构事件表示和实体关系路径信息。此外,针对第二个问题,本文提出了基于 Roberta 的数据增强方法,即对生物医学文本中除生物医学事件外的部分词语进行按比例的随机屏蔽,然后由预先训练好的 Roberta 为不平衡的 BECRE 数据集生成数据实例。在 Hahn-Powell's 和 BioCause 数据集上的大量实验结果证实,与目前的先进方法相比,所提出的方法达到了最先进的性能。
{"title":"Biomedical event causal relation extraction with deep knowledge fusion and Roberta-based data augmentation","authors":"Lishuang Li,&nbsp;Yi Xiang,&nbsp;Jing Hao","doi":"10.1016/j.ymeth.2024.08.007","DOIUrl":"10.1016/j.ymeth.2024.08.007","url":null,"abstract":"<div><p>Biomedical event causal relation extraction (BECRE), as a subtask of biomedical information extraction, aims to extract event causal relation facts from unstructured biomedical texts and plays an essential role in many downstream tasks. The existing works have two main problems: i) Only shallow features are limited in helping the model establish potential relationships between biomedical events. ii) Using the traditional oversampling method to solve the data imbalance problem of the BECRE tasks ignores the requirements for data diversifying. This paper proposes a novel biomedical event causal relation extraction method to solve the above problems using deep knowledge fusion and Roberta-based data augmentation. To address the first problem, we fuse deep knowledge, including structural event representation and entity relation path, for establishing potential semantic connections between biomedical events. We use the Graph Convolutional Neural network (GCN) and the predicated tensor model to acquire structural event representation, and entity relation paths are encoded based on the external knowledge bases (GTD, CDR, CHR, GDA and UMLS). We introduce the triplet attention mechanism to fuse structural event representation and entity relation path information. Besides, this paper proposes the Roberta-based data augmentation method to address the second problem, some words of biomedical text, except biomedical events, are masked proportionally and randomly, and then pre-trained Roberta generates data instances for the imbalance BECRE dataset. Extensive experimental results on Hahn-Powell's and BioCause datasets confirm that the proposed method achieves state-of-the-art performance compared to current advances.</p></div>","PeriodicalId":390,"journal":{"name":"Methods","volume":"231 ","pages":"Pages 8-14"},"PeriodicalIF":4.2,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Godanti bhasma (anhydrous CaSO4) induces massive cytoplasmic vacuolation in mammalian cells: A model for phagocytosis assay Godanti bhasma(无水硫酸钙)可诱导哺乳动物细胞出现大量细胞质空泡:吞噬作用检测模型
IF 4.2 3区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-08-30 DOI: 10.1016/j.ymeth.2024.08.006
Subrata K. Das , Alpana Joshi , Laxmi Bisht , Vishakha Goswami , Abul Faiz , Gaurav Dutt , Shiva Sharma

Phagocytosis is an essential physiological mechanism; its impairment is associated with many diseases. A highly smart particle is required for understanding detailed sequential cellular events in phagocytosis. Recently, we identified an Indian traditional medicine named Godanti Bhasma (GB), a bioactive calcium sulfate particle prepared by thermo-transformation of gypsum. Thermal processing of the gypsum transforms its native physicochemical properties by removing water molecules into the anhydrous GB, which was confirmed by Raman and FT-IR spectroscopy. GB particle showed a 0.5–5 µm size range and a neutral surface charge. Exposure of mammalian cells to GB particles showed a rapid cellular uptake through phagocytosis and induced massive cytoplasmic vacuolation in cells. Interestingly, no cellular uptake and cytoplasmic vacuolation were observed with the parent gypsum particle. The presence of the GB particles in intra-vacuolar space was confirmed using FESEM coupled with EDX. Flow cytometry analysis and live tracking of GB-treated cells showed particle internalization, vacuole formation, particle dissolution, and later vacuolar turnover. Quantification of GB-induced vacuolation was done using neutral red uptake assay in cells. Treatment of lysosomal inhibitors (BFA1 or CQ) with GB could not induce vacuolation, suggesting the requirement of an acidic environment for the vacuolation. In the mimicking experiment, GB particle dissolution in acidic cell-free solution suggested that degradation of GB occurs by acidic pH inside the cell vacuole. Vacuole formation generally accompanies with cell death, whereas GB-induced massive vacuolation does not cause cell death. Moreover, the cell divides and proliferates with the vacuolar process, intra-vacuolar cargo degradation, and eventually vacuolar turnover. Taken together, the sequential cellular events in this study suggest that GB can be used as a smart particle for phagocytosis assay development in animal cells.

吞噬是一种重要的生理机制,其功能受损与许多疾病有关。要了解吞噬过程中细胞事件的详细顺序,需要一种高度智能的颗粒。最近,我们发现了一种名为 "Godanti Bhasma"(GB)的印度传统药物,这是一种通过石膏热转化制备的生物活性硫酸钙颗粒。对石膏进行热加工后,通过去除水分子,将其转化为无水的 GB,从而改变了其原有的物理化学特性,拉曼光谱和傅立叶变换红外光谱证实了这一点。GB 颗粒的大小范围为 0.5-5 µm,表面电荷呈中性。哺乳动物细胞暴露于 GB 粒子后,会通过吞噬作用迅速被细胞吸收,并诱导细胞出现大量胞质空泡。有趣的是,在母体石膏颗粒中没有观察到细胞摄取和细胞质空泡化现象。利用 FESEM 和 EDX 技术证实了 GB 粒子存在于泡内空间。流式细胞仪分析和对 GB 处理过的细胞的活体追踪显示了颗粒的内化、空泡形成、颗粒溶解和随后的空泡周转。利用细胞中性红吸收测定法对 GB 诱导的空泡化进行了定量。用 GB 处理溶酶体抑制剂(BFA1 或 CQ)不能诱导空泡化,这表明空泡化需要酸性环境。在模拟实验中,GB 颗粒在酸性无细胞溶液中的溶解表明,GB 的降解是在细胞空泡内的酸性 pH 值作用下发生的。空泡的形成通常伴随着细胞死亡,而 GB 诱导的大量空泡化不会导致细胞死亡。此外,细胞分裂和增殖与空泡过程、空泡内货物降解以及最终的空泡周转同时进行。综上所述,本研究中的连续细胞事件表明,GB 可作为一种智能颗粒用于动物细胞中吞噬检测的开发。
{"title":"Godanti bhasma (anhydrous CaSO4) induces massive cytoplasmic vacuolation in mammalian cells: A model for phagocytosis assay","authors":"Subrata K. Das ,&nbsp;Alpana Joshi ,&nbsp;Laxmi Bisht ,&nbsp;Vishakha Goswami ,&nbsp;Abul Faiz ,&nbsp;Gaurav Dutt ,&nbsp;Shiva Sharma","doi":"10.1016/j.ymeth.2024.08.006","DOIUrl":"10.1016/j.ymeth.2024.08.006","url":null,"abstract":"<div><p>Phagocytosis is an essential physiological mechanism; its impairment is associated with many diseases. A highly smart particle is required for understanding detailed sequential cellular events in phagocytosis. Recently, we identified an Indian traditional medicine named Godanti Bhasma (GB), a bioactive calcium sulfate particle prepared by thermo-transformation of<!--> <!-->gypsum. Thermal processing of the gypsum transforms its native physicochemical properties by removing water molecules into the anhydrous GB, which was confirmed by Raman and FT-IR spectroscopy. GB particle showed a 0.5–5 µm size range and a neutral surface charge. Exposure of mammalian cells to GB particles showed a rapid cellular uptake through phagocytosis and induced massive cytoplasmic vacuolation in cells. Interestingly, no cellular uptake and cytoplasmic vacuolation were observed with the parent gypsum particle. The presence of the GB particles in intra-vacuolar space was confirmed using FESEM coupled with EDX. Flow cytometry analysis and live tracking of GB-treated cells showed particle internalization, vacuole formation, particle dissolution, and later vacuolar turnover. Quantification of GB-induced vacuolation was done using neutral red uptake assay in cells. Treatment of lysosomal inhibitors (BFA1 or CQ) with GB could not induce vacuolation, suggesting the requirement of an acidic environment for the vacuolation. In the mimicking experiment, GB particle dissolution in acidic cell-free solution suggested that degradation of GB occurs by acidic pH inside the cell vacuole. Vacuole formation generally accompanies with cell death, whereas GB-induced massive vacuolation does not cause cell death. Moreover, the cell divides and proliferates with the vacuolar process, intra-vacuolar cargo degradation, and eventually vacuolar turnover. Taken together, the sequential cellular events in this study suggest that GB can be used as a smart particle for phagocytosis assay development in animal cells.</p></div>","PeriodicalId":390,"journal":{"name":"Methods","volume":"230 ","pages":"Pages 158-168"},"PeriodicalIF":4.2,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MFF-DTA: Multi-scale feature fusion for drug-target affinity prediction MFF-DTA:药物-靶点亲和力预测的多尺度特征融合。
IF 4.2 3区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-08-30 DOI: 10.1016/j.ymeth.2024.08.008
Xiwei Tang , Wanjun Ma , Mengyun Yang , Wenjun Li

Accurately predicting drug-target affinity is crucial in expediting the discovery and development of new drugs, which is a complex and risky process. Identifying these interactions not only aids in screening potential compounds but also guides further optimization. To address this, we propose a multi-perspective feature fusion model, MFF-DTA, which integrates chemical structure, biological sequence, and other data to comprehensively capture drug-target affinity features. The MFF-DTA model incorporates multiple feature learning components, each of which is capable of extracting drug molecular features and protein target information, respectively. These components are able to obtain key information from both global and local perspectives. Then, these features from different perspectives are efficiently combined using specific splicing strategies to create a comprehensive representation. Finally, the model uses the fused features to predict drug-target affinity. Comparative experiments show that MFF-DTA performs optimally on the Davis and KIBA data sets. Ablation experiments demonstrate that removing specific components results in the loss of unique information, thus confirming the effectiveness of the MFF-DTA design. Improvements in DTA prediction methods will decrease costs and time in drug development, enhancing industry efficiency and ultimately benefiting patients.

准确预测药物与靶点的亲和力对于加快新药的发现和开发至关重要,而这是一个复杂而又充满风险的过程。识别这些相互作用不仅有助于筛选潜在化合物,还能指导进一步优化。为此,我们提出了一种多视角特征融合模型 MFF-DTA,它整合了化学结构、生物序列和其他数据,以全面捕捉药物-靶点亲和力特征。MFF-DTA 模型包含多个特征学习组件,每个组件都能分别提取药物分子特征和蛋白质靶标信息。这些组件能够从全局和局部两个角度获取关键信息。然后,利用特定的拼接策略将这些来自不同角度的特征有效地结合起来,以创建一个全面的表征。最后,该模型利用融合后的特征来预测药物与靶标的亲和力。对比实验表明,MFF-DTA 在戴维斯和 KIBA 数据集上的表现最佳。消融实验表明,去除特定成分会导致独特信息的丢失,从而证实了 MFF-DTA 设计的有效性。DTA 预测方法的改进将减少药物开发的成本和时间,提高行业效率,最终造福患者。
{"title":"MFF-DTA: Multi-scale feature fusion for drug-target affinity prediction","authors":"Xiwei Tang ,&nbsp;Wanjun Ma ,&nbsp;Mengyun Yang ,&nbsp;Wenjun Li","doi":"10.1016/j.ymeth.2024.08.008","DOIUrl":"10.1016/j.ymeth.2024.08.008","url":null,"abstract":"<div><p>Accurately predicting drug-target affinity is crucial in expediting the discovery and development of new drugs, which is a complex and risky process. Identifying these interactions not only aids in screening potential compounds but also guides further optimization. To address this, we propose a multi-perspective feature fusion model, MFF-DTA, which integrates chemical structure, biological sequence, and other data to comprehensively capture drug-target affinity features. The MFF-DTA model incorporates multiple feature learning components, each of which is capable of extracting drug molecular features and protein target information, respectively. These components are able to obtain key information from both global and local perspectives. Then, these features from different perspectives are efficiently combined using specific splicing strategies to create a comprehensive representation. Finally, the model uses the fused features to predict drug-target affinity. Comparative experiments show that MFF-DTA performs optimally on the Davis and KIBA data sets. Ablation experiments demonstrate that removing specific components results in the loss of unique information, thus confirming the effectiveness of the MFF-DTA design. Improvements in DTA prediction methods will decrease costs and time in drug development, enhancing industry efficiency and ultimately benefiting patients.</p></div>","PeriodicalId":390,"journal":{"name":"Methods","volume":"231 ","pages":"Pages 1-7"},"PeriodicalIF":4.2,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1046202324001890/pdfft?md5=a691264b50021b10f091a9d3d57ce863&pid=1-s2.0-S1046202324001890-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Methods
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