Fundamental Research最新文献_第3页

Lenalidomide promotes melarsoprol-activated cGAS-STING-mediated immunotherapy for hepatocellular carcinoma via attenuating TNF-α activity 来那度胺通过降低TNF-α活性促进Melarsorol激活的cGAS-STING介导的肝癌免疫治疗

IF 6.2 3区综合性期刊

Fundamental Research Pub Date : 2025-05-01 DOI: 10.1016/j.fmre.2023.05.013

Zhuo Yu , Yifang Zou , Shulan Han , Dandan Sun , Lingzhi Wang , Leilei Yang , Yutong Li , Xuemei Zhang , Jianfeng Guo

{"title":"Lenalidomide promotes melarsoprol-activated cGAS-STING-mediated immunotherapy for hepatocellular carcinoma via attenuating TNF-α activity","authors":"Zhuo Yu , Yifang Zou , Shulan Han , Dandan Sun , Lingzhi Wang , Leilei Yang , Yutong Li , Xuemei Zhang , Jianfeng Guo","doi":"10.1016/j.fmre.2023.05.013","DOIUrl":"10.1016/j.fmre.2023.05.013","url":null,"abstract":"<div><div>Current immunotherapy has limited efficacy in hepatocellular carcinoma (HCC) due to the immunosuppressive tumor microenvironment (TME). The activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of the interferon genes (STING) pathway demonstrates great potential to unleash the immunosuppressive TME. The capacity of melarsoprol (MEL; an arsenic-containing drug) on activating the cGAS-STING pathway in HCC cells for antitumor immunotherapy was confirmed for the first time in this study. When MEL (particularly at high doses) activated the cGAS-STING pathway； however, HCC growth was not fully inhibited, mainly due to the hyperactivation of tumor necrosis factor α (TNF-α; a cytokine associated with the cGAS-STING pathway). Accordingly, lenalidomide (LEN; a clinically approved TNF-α inhibitor) was used to alleviate pro-tumorigenic effects of the MEL-activated cGAS-STING pathway while maintaining immunotherapeutic effects. To modulate the cGAS-STING pathway <em>in vivo</em>, a poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticle (NP) was used for co-delivery of MEL and LEN, and the co-loaded NP was coated with aminoethyl anisamide (AEAA, a ligand for Sigma-1 receptor)-modified erythrocyte membrane, forming a co-formulation. In this study, co-formulation was able to modulate the cGAS-STING-mediated efficacy and reverse the immunosuppressive TME in allograft and carcinogen-induced orthotopic HCC mouse models, respectively. Our study reveals an intrinsic hurdle to DNA damaging drug-mediated cGAS-STING monotherapy and provides a promising combination strategy to tackle immunosuppression in HCC.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 3","pages":"Pages 1298-1312"},"PeriodicalIF":6.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48726049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chemical closed-loop recycling of polymers realized by monomer design 通过单体设计实现聚合物的化学闭环再循环

IF 6.2 3区综合性期刊

Fundamental Research Pub Date : 2025-05-01 DOI: 10.1016/j.fmre.2024.05.015

Wuchao Zhao, Jianghua He, Yuetao Zhang

引用次数: 0

Human activities control the source of eroded organic carbon in lake sediments over the last 100 years: Evidence from stable isotope fingerprinting 近百年来，人类活动控制了湖泊沉积物中侵蚀有机碳的来源:来自稳定同位素指纹图谱的证据

IF 6.2 3区综合性期刊

Fundamental Research Pub Date : 2025-05-01 DOI: 10.1016/j.fmre.2023.04.015

Shilan Wang , Xiaodong Nie , Fengwei Ran , Wenfei Liao , Changrong Yang , Tao Xiao , Yi Liu , Yaojun Liu , Zhongwu Li

{"title":"Human activities control the source of eroded organic carbon in lake sediments over the last 100 years: Evidence from stable isotope fingerprinting","authors":"Shilan Wang , Xiaodong Nie , Fengwei Ran , Wenfei Liao , Changrong Yang , Tao Xiao , Yi Liu , Yaojun Liu , Zhongwu Li","doi":"10.1016/j.fmre.2023.04.015","DOIUrl":"10.1016/j.fmre.2023.04.015","url":null,"abstract":"<div><div>Understanding the redistribution of soil organic carbon (OC) driven by erosion contributes to the global carbon budget and watershed management. Quantifying the sources of eroded OC in sediments provides new insights to addressing this issue. However, limited quantitative information on the factors influencing OC sources has constrained the behavior of regulating the OC exported from the watershed. Here, we explored the sources of OC in lake sediments over the last 100 years and quantified the effects of climate change and human activities on OC sources. Results from the stable isotope fingerprinting and MixSIAR model indicated that phragmites (30.34%) and croplands (21.48%) were consistently the main OC sources. Therefore, efforts should be concentrated on controlling soil erosion from cropland and managing the endogenous environment. In addition, the partial least squares pathways (PLS-PM) and random forests revealed that human activities (Path coefficients (r<sub>∂</sub>): 0.45 to 0.61) have controlled the OC sources over the last hundred years. Agricultural activities, urbanization, and land use change altered the quality of OC sources by affecting the vegetation productivity in source areas. The quantity of OC sources was also influenced by underlying surface and surface connectivity changes. The effects of climate change (temperature (r<sub>∂</sub>): −0.41 to 0.1; precipitation (r<sub>∂</sub>): 0.1 to 0.29) on OC sources have not been significant, but their long-term effects cannot be ignored. These findings provide a better insight into the origin and behavior of OC in lake sediments under global change, which is crucial for basin management and lake governance.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 3","pages":"Pages 1097-1106"},"PeriodicalIF":6.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45263736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A tetramethylpyrazine releasing hydrogel can potentiate CAR-T cell therapy against triple negative breast cancer by reprogramming tumor vasculatures 四甲基吡嗪释放水凝胶可通过重新编程肿瘤血管增强CAR-T细胞治疗三阴性乳腺癌症

IF 6.2 3区综合性期刊

Fundamental Research Pub Date : 2025-05-01 DOI: 10.1016/j.fmre.2023.05.016

Yan Liu , Yu Hao , Xiang Lv , Yefei Zhang , Jiahui Chen , Jia Tian , Xinxing Ma , Yehui Zhou , Liangzhu Feng

{"title":"A tetramethylpyrazine releasing hydrogel can potentiate CAR-T cell therapy against triple negative breast cancer by reprogramming tumor vasculatures","authors":"Yan Liu , Yu Hao , Xiang Lv , Yefei Zhang , Jiahui Chen , Jia Tian , Xinxing Ma , Yehui Zhou , Liangzhu Feng","doi":"10.1016/j.fmre.2023.05.016","DOIUrl":"10.1016/j.fmre.2023.05.016","url":null,"abstract":"<div><div>Irregular vasculature of solid tumors has proven to be a pivotal factor restricting their response to chimeric antigen receptor-T (CAR-T) cell therapy because it is tightly associated with hypoxia and other biological barriers. Herein, an injectable hydrogel composed of poly (ethylene glycol) dimethacrylate (PEGDMA) and ferrous chloride (FeCl<sub>2</sub>) responding to endogenous hydrogen peroxides (H<sub>2</sub>O<sub>2</sub>) is developed to enable sustained intratumoral release of Chinese herbal extracts tetramethylpyrazine (TMP). TMP is selected due to its potency in activating vascular endothelial growth factor (VEGF) expression and the endothelial nitric oxide synthase/nitric oxide (eNOS/NO) axis inside vascular endothelial cells. Upon being fixed inside tumors with the PEGDMA based hydrogel, TMP can remodel tumor vasculature by simultaneously promoting angiogenesis and dilating tumor vasculature and thus attenuate tumor hypoxia in two murine xenografts bearing human triple negative breast cancer (TNBC). Resultantly, treatment with TMP fixation potentiates the tumor suppression effect of intravenously injected epidermal growth factor receptor expressing CAR-T (HER1-CAR-T) cells toward two TNBC tumor xenografts by promoting their tumor infiltration, survival, and effector function. This study highlights a concise yet effective approach to reinforce the therapeutic potency of CAR-T cells towards targeted solid tumors by simply remodeling tumor vasculature.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 3","pages":"Pages 1288-1297"},"PeriodicalIF":6.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47617512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Apigenin alleviates osteoporosis by orchestrating SIRT1/HIF1α signaling in mesenchymal stem cells 芹菜素通过协调间充质干细胞中的 SIRT1/HIF1α 信号传递缓解骨质疏松症

IF 6.2 3区综合性期刊

Fundamental Research Pub Date : 2025-05-01 DOI: 10.1016/j.fmre.2024.02.002

Xu He , Mimi Chen , Xiongjinfu Zhang , Xinyi Cheng , Yida Chen , Hao Shen , Huilin Yang , Qin Shi , Junjie Niu

{"title":"Apigenin alleviates osteoporosis by orchestrating SIRT1/HIF1α signaling in mesenchymal stem cells","authors":"Xu He , Mimi Chen , Xiongjinfu Zhang , Xinyi Cheng , Yida Chen , Hao Shen , Huilin Yang , Qin Shi , Junjie Niu","doi":"10.1016/j.fmre.2024.02.002","DOIUrl":"10.1016/j.fmre.2024.02.002","url":null,"abstract":"<div><div>Osteoporosis (OP) is a systemic skeletal disease characterized by reduced bone mass and a degenerative bone microarchitecture. Apigenin (API), a flavonoid derived mainly from celery, has been reported to be beneficial for the treatment of OP; however, the underlying mechanisms remain unclear. Moreover, the effects of API on bone-forming cells, including mesenchymal stem cells and osteoblasts, remain unclear. In the present study, we first determined that API treatment could promote bone formation, improve bone metabolism in ovariectomized (OVX) mice, and effectively ameliorate bone loss, as supported by micro-CT scanning and histological staining of mouse femurs. <em>In vitro</em> investigations have confirmed that API has a bidirectional regulatory effect on bone metabolism, promoteing osteogenic differentiation and inhibiting osteoclastogenesis. The further study displayed that the promotion of osteogenesis of bone marrow-derived mesenchymal stem cells from OVX mice mainly through regulating SIRT1 and its downstream HIF1α signaling. In summary, API treatment may be a novel and promising therapeutic strategy for the treatment of OP.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 3","pages":"Pages 1063-1072"},"PeriodicalIF":6.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139814403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring behavior patterns in human and machine interactions 探索人机交互的行为模式

IF 6.2 3区综合性期刊

Fundamental Research Pub Date : 2025-05-01 DOI: 10.1016/j.fmre.2023.12.021

Ping Zhao , Yunjie Wei , Shouyang Wang

{"title":"Exploring behavior patterns in human and machine interactions","authors":"Ping Zhao , Yunjie Wei , Shouyang Wang","doi":"10.1016/j.fmre.2023.12.021","DOIUrl":"10.1016/j.fmre.2023.12.021","url":null,"abstract":"<div><div>A framework based on response-dependence theory is proposed to analyze human and machine interaction patterns. The interaction is an information processing and exchanging system with agents responding to signals from the decision perspective on multiple channels. Agents' pattern differences may emerge via a multiple-input multiple-output model on the sequential machine data. The connectivity with different decision-making factors embodies the interactive narrative features. The magnitude of the frequency response is compared in a parallel analysis. The interaction relationship will emerge in frequency response comparison. In the empirical study, we compare AlphaGo and human professional players' behaviors in the game of Go. We find a similar connectivity structure in vertical analysis and coincidences with the interaction relationship in the game. However, the response magnitude interval differs between AlphaGo and human professional players in several stimulus-response pairs. Integrated with static comparison, we find AlphaGo is more sensitive to long-term payoff changes than human professional players. The framework and empirical studies indicate that theory and techniques from cross-disciplinary can provide a perceptive and objective explanation of behavior patterns in human and machine interaction. The proposed framework might benefit scientists in research on AI ethics and machine behavior interpretation with big data techniques.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 3","pages":"Pages 1246-1257"},"PeriodicalIF":6.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139880148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Chemically recyclable polythioesters prepared by ring-opening polymerization of dithiolactone and monothiodilactone monomers 通过二硫内酯和单碘内酯单体的开环聚合制备可化学回收的聚硫酯

IF 6.2 3区综合性期刊

Fundamental Research Pub Date : 2025-05-01 DOI: 10.1016/j.fmre.2024.01.022

Wenxiu Lv , Maosheng Li , Jinlong Chen , Youhua Tao

引用次数: 0

Atmospheric impacts and regulation framework of shipping emissions: Achievements, challenges and frontiers 航运排放对大气的影响和监管框架：成就、挑战和前沿

IF 6.2 3区综合性期刊

Fundamental Research Pub Date : 2025-05-01 DOI: 10.1016/j.fmre.2024.02.013

Huan Liu , Wen Yi , Jukka-Pekka Jalkanen , Zhenyu Luo , Elisa Majamäki , Volker Matthias , Jana Moldanová , Zongbo Shi , Kebin He

{"title":"Atmospheric impacts and regulation framework of shipping emissions: Achievements, challenges and frontiers","authors":"Huan Liu , Wen Yi , Jukka-Pekka Jalkanen , Zhenyu Luo , Elisa Majamäki , Volker Matthias , Jana Moldanová , Zongbo Shi , Kebin He","doi":"10.1016/j.fmre.2024.02.013","DOIUrl":"10.1016/j.fmre.2024.02.013","url":null,"abstract":"<div><div>Currently, over 80% of the international trade volume is carried by sea. Marked by persistent growth, evident atmospheric impacts, intricate mitigation challenges, international shipping has been recognized as one of the most “hard-to-abate” sectors gathering increasing attention from both academic community and governmental sectors in recent years. Against the backdrop of the ambitious climate and clean air objectives, the quantitative shipping emission characterization, impact assessment and policy effectiveness research are not only fundamental to understand the status quo and ramifications of shipping emissions but also beneficial for future emission regulations. Here, we summarized the achievements in shipping emission modelling and impact research in the past two decades, and identified the challenges lying in the transition pathway towards a clean and carbon-neutral shipping. To address the pressing demand for this, we proposed an innovative framework which aims to facilitate emission abatement. Finally, promising directions for future work were delineated, including the indirect effects of shipping emitted aerosols on the climate, the emissions and impacts of novel contaminants, synergies and conflicts among different emission reduction measures, projections on future shipping emission inventories, Arctic shipping emissions, etc.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 3","pages":"Pages 1073-1076"},"PeriodicalIF":6.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140282800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of artificial intelligence in revolutionizing drug discovery 人工智能在药物发现革命中的作用

IF 6.2 3区综合性期刊

Fundamental Research Pub Date : 2025-05-01 DOI: 10.1016/j.fmre.2024.04.021

Ashfaq Ur Rehman , Mingyu Li , Binjian Wu , Yasir Ali , Salman Rasheed , Sana Shaheen , Xinyi Liu , Ray Luo , Jian Zhang

{"title":"Role of artificial intelligence in revolutionizing drug discovery","authors":"Ashfaq Ur Rehman , Mingyu Li , Binjian Wu , Yasir Ali , Salman Rasheed , Sana Shaheen , Xinyi Liu , Ray Luo , Jian Zhang","doi":"10.1016/j.fmre.2024.04.021","DOIUrl":"10.1016/j.fmre.2024.04.021","url":null,"abstract":"<div><div>The application of artificial intelligence (AI) in medicine, particularly through machine learning (ML), marked a significant progression in drug discovery. AI acts as a powerful catalyst in narrowing the gap between disease understanding and the identification of potential therapeutic agents. This review provides an inclusive summary of the latest advancements in AI and its application in drug discovery. We examine the various stages of the drug discovery process, starting from disease identification and encompassing diagnosis, target identification, screening, and lead discovery. AI's capability to analyze extensive datasets and discern patterns is essential in these stages, enhancing predictions and efficiencies in disease identification, drug discovery, and clinical trial management. The role of AI in expediting drug development is emphasized, highlighting its potential to analyze vast data volumes, thus reducing the time and costs associated with new drug market introduction. The importance of data quality, algorithm training, and ethical considerations, especially in patient data handling during clinical trials, is addressed. By considering these factors, AI promises to transform drug development, offering significant benefits to patients and society.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 3","pages":"Pages 1273-1287"},"PeriodicalIF":6.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141034957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Machine learning-based prediction models for atopic dermatitis diagnosis and evaluation 基于机器学习的特应性皮炎诊断与评估预测模型

IF 6.2 3区综合性期刊

Fundamental Research Pub Date : 2025-05-01 DOI: 10.1016/j.fmre.2023.02.021

Songjiang Wu, Li Lei, Yibo Hu, Ling Jiang, Chuhan Fu, Yushan Zhang, Lu Zhu, Jinhua Huang, Jing Chen, Qinghai Zeng

{"title":"Machine learning-based prediction models for atopic dermatitis diagnosis and evaluation","authors":"Songjiang Wu, Li Lei, Yibo Hu, Ling Jiang, Chuhan Fu, Yushan Zhang, Lu Zhu, Jinhua Huang, Jing Chen, Qinghai Zeng","doi":"10.1016/j.fmre.2023.02.021","DOIUrl":"10.1016/j.fmre.2023.02.021","url":null,"abstract":"<div><div>Atopic dermatitis (AD) is the most common chronic inflammatory skin disease seriously affecting the quality of life of patients. Reliable and accurate evaluation methods are necessary for early diagnosis and effective AD treatment. Thus, this study used machine learning (ML) to explore a novel diagnostic and therapeutic effect evaluation model for AD. Firstly, candidate model genes were screened from an integrated data set of four AD-related microarray datasets: GSE133477, GSE32924, GSE58558, and GSE107361, using Robust Rank Aggregation (RRA), and protein-protein interaction network (PPI). Next, three recognized models (REC) and three AD-associated gene models (AAG) established with LASSO, Logistic linear regression (LR), and random forest (RF) were developed and tested separately using GSE130588 and GSE99802 datasets. The results revealed that REC model of LASSO (model genes including <em>IL7R, KRT16, CCL2, CD53, CCL18</em> and <em>CCL22</em>), REC model of LR(including <em>IL7R, KRT16, CCL18</em>) and AAG model of LR (including <em>MX1, CCNB1, SERPINB13, ADAM19, CEP55, VMP1, TTC39A, and FCHSD1</em>) accurately classified AD lesions and non-lesions based on the good AUCs (LASSO (REC):0.8761, and LR (REC and AAG):0.8302 in GSE130588; LASSO (REC): 0.7761, and LR (REC and AAG):0.8783 in GSE99802). In Dupilumab, Crisaborole, and fezakinumab-treated samples, the LASSO (REC) and LR(AAG) models were positively correlated with SCORD (Pearson correlation coefficients of 0.55 and 0.69, respectively) and negatively correlated with the treatment length. In addition, the two models also accurately predicted the infiltration of immune cells in the skin lesions and non-lesions. Therefore, the ML-based predictive model provides a new approach to predicting AD diagnosis and the therapeutic effect of AD treatment options.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"5 3","pages":"Pages 1313-1322"},"PeriodicalIF":6.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45369805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0