Fundamental Research最新文献

{"title":"Controlled assembly of exogenous DNA-based materials in living cells","authors":"Sen Yang,&nbsp;Siqi Li,&nbsp;Chi Yao,&nbsp;Dayong Yang","doi":"10.1016/j.fmre.2023.12.009","DOIUrl":"10.1016/j.fmre.2023.12.009","url":null,"abstract":"<div><div>The self-assembly of artificial structures within living cells provides valuable insights into cellular mechanisms and control of cellular functions, thereby contributing to advancements in biomedicine and synthetic biology. To precisely control the intracellular assembly process, exogenous active substances have been introduced, which respond to the natural intracellular environments. Deoxyribonucleic acid (DNA) is a versatile biological macromolecule that has great potential as a building block to construct biomaterials in addition to as a genetic material. Through rational sequence design, DNA molecules can form a variety of functional structures, enabling precise and efficient intracellular assembly. These properties greatly enrich the forms of intracellular assembly and expand the applications of DNA molecules. In this review, we summarize the controlled assembly of exogenous DNA-based materials under various stimulating conditions. We highlight three main applications of intracellular assembly of exogenous DNA materials. First, DNA materials interact with intracellular molecules to alter the natural intracellular environment and influence cell behavior and fate. Second, DNA materials form assemblies that affect subcellular structures and interfere with cellular functions. Third, DNA functional modules enable precise diagnosis and treatment of cancers by recognizing intracellular molecules for efficient tumor detection, precise imaging, and controlled drug delivery. From assembly mechanisms to biological effects, this review comprehensively summarizes the dynamic and controlled assembly of exogenous DNA-based materials in living cells and envisages the challenges and future research prospects in this field.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"6 4","pages":"Pages 2189-2201"},"PeriodicalIF":6.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139636130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinetic fractionation of Mg isotopes during chemical diffusion in aqueous solutions: A reappraisal","authors":"Weiqiang Li,&nbsp;Xianglong Luo,&nbsp;Zhihan Ji,&nbsp;Chuan Liu","doi":"10.1016/j.fmre.2024.11.010","DOIUrl":"10.1016/j.fmre.2024.11.010","url":null,"abstract":"<div><div>Diffusion is a basic process that could result in isotopic variability in nature, and diffusion-driven Mg isotope fractionation has been widely reported in a variety of magmatic processes. Whether chemical diffusion of Mg aquo ions in aqueous solution is associated with significant isotope fractionation, however, had been contentious. Addressing this issue can advance our understanding of the molecular configuration and movement of cations in aqueous solutions. Here, we modified the recently reported “diffusion cell” method to investigate the isotopic effect of diffusion of aqueous Mg under various conditions, with emphasis on the effects of temperature and anions. The experimental results show that in aqueous solutions, lighter Mg isotopes diffuse faster than the heavier isotopes. The ratio of diffusion coefficients between ²⁶Mg and ²⁴Mg (D_26Mg/D_24Mg, or kinetic isotope fractionation factor α) ranges from 0.99990 ± 0.00003 (1σ) to 0.99982 ± 0.00003 (1σ), depending on the specific experimental conditions. Notably, the magnitude of diffusion-induced Mg isotope fractionation in aqueous solution increases with higher temperature, and is greater for MgCl₂ and Mg(NO₃)₂ than for MgSO₄. Based on these new findings and a comparison with published data on diffusion-driven isotope fractionation for other divalent elements, we suggest that the mass dependency of isotope fractionation during chemical diffusion in aqueous solutions is regulated by the strength of ion-water interactions. Stronger ion-water interactions result in more pronounced hydrodynamic behavior at a molecular level for the diffusing ions, leading to less significant isotope fractionation in aqueous fluids.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"6 4","pages":"Pages 2387-2397"},"PeriodicalIF":6.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148640467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small-molecule autophagy modulators: Mechanisms, therapeutic potential, and development challenges in pathological settings","authors":"Yongya Wu,&nbsp;Jiaxiang Luo,&nbsp;Haolin Tang,&nbsp;Aoxue Wang,&nbsp;Maolin Duan,&nbsp;Jie Liu,&nbsp;Guan Wang,&nbsp;Liang Ouyang","doi":"10.1016/j.fmre.2026.04.015","DOIUrl":"10.1016/j.fmre.2026.04.015","url":null,"abstract":"<div><div>Autophagy is an evolutionarily conserved process in eukaryotic cells that delivers intracellular components to lysosomes for degradation and recycling. Increasing evidence has elucidated the regulation of autophagy, highlighting its involvement in cellular metabolism, survival, and development, as well as its association with diverse physiological and pathological processes. There are often mutations in autophagy-regulating genes or abnormal autophagy function in multiple diseases, such as cancer, immune system diseases, and neurodegenerative diseases. Additionally, the regulation of the autophagy process shows potential therapeutic effects for these diseases. Several small molecules have been developed as autophagy regulators based on traditional drug discovery strategies, such as high-throughput screening, structure-activity relationship (SAR) optimization, and computer-aided drug design. Mechanistically, these compounds that bind specifically to such autophagy-related proteins or kinases can act as agonists or antagonists, with downstream consequences on the autophagy process. Several pharmacologic agents that regulate the autophagy process with extraordinary potential in disease treatment have come into clinical use. But most of these molecules still suffer from many obstacles, including low efficacy, low selectivity, poor pharmacokinetic profile, drug resistance, and toxicity. Moreover, some inappropriate and undruggable autophagy-related targets, as well as ubiquitous protein aggregates in neurodegenerative diseases, also bring serious challenges to the identification of small-molecule drugs. In this review, we briefly introduce autophagy and summarize its function and regulatory role in various diseases and disorders, and discuss the possibility of autophagy-targeted therapy in these diseases. The present review highlights current developments regarding the fundamental molecular mechanisms and signaling cascades of autophagy, while also addressing strategies for small-molecule–based therapeutic intervention.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"6 4","pages":"Pages 2081-2123"},"PeriodicalIF":6.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148640633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatin regulator expression patterns predict prognosis and guide neoadjuvant therapy in esophageal squamous cell carcinoma","authors":"Jia Liu,&nbsp;Wenyan Sun,&nbsp;Jiangcong Ma,&nbsp;Chengxiang Han,&nbsp;Qinghao Zhu,&nbsp;Yang Li,&nbsp;Shuwen Zheng,&nbsp;Xin Sun,&nbsp;Yong Huang,&nbsp;Qiong Wu,&nbsp;Chenghao Li","doi":"10.1016/j.fmre.2026.03.016","DOIUrl":"10.1016/j.fmre.2026.03.016","url":null,"abstract":"<div><div>Chromatin regulators (CRs), as key components of the epigenetic machinery, participate in tumor progression and therapeutic resistance by modulating chromatin structure and gene expression. Nonetheless, the precise functions of CRs in cancer immunotherapy and the tumor microenvironment (TME) remain largely unexplored. Here, we integrated multi-omics data to characterize genomic alterations, transcriptomic profiles, and copy number variations (CNVs) of 215 CRs and identified survival-associated CRs using Cox regression analysis. Subsequently, based on CR expression patterns, esophageal squamous cell carcinoma (ESCC) patients were classified into CR-active and CR-silent subgroups, which exhibited distinct survival outcomes and TME characteristics. Importantly, the CR-Score developed here was associated with treatment response-related endpoints and post-treatment disease-free survival in patients receiving neoadjuvant PD-1 blockade therapy. In summary, we systematically characterized the molecular and immune features of CR clusters in ESCC and demonstrated that the CR-Score is a novel biomarker for prognostic prediction, with potential clinical utility and theoretical relevance for neoadjuvant immunotherapy.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"6 4","pages":"Pages 2355-2365"},"PeriodicalIF":6.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148640496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term influences of pipe materials on bacterial communities of matured biofilms (> 40 years’ old) in drinking water distribution systems","authors":"Anran Ren,&nbsp;Jun Li,&nbsp;Zhen Zhang,&nbsp;Ed van der Mark,&nbsp;Lihua Chen,&nbsp;Xiaoming Li,&nbsp;Walter van der Meer,&nbsp;Gang Liu","doi":"10.1016/j.fmre.2024.05.019","DOIUrl":"10.1016/j.fmre.2024.05.019","url":null,"abstract":"<div><div>Pipe materials appear to play an important role in the development of biofilms in drinking water distribution systems. However, there is controversy as to whether pipe materials shape the composition and diversity of bacterial communities in biofilms. To investigate the long-term effects of pipe materials on biofilms, triplicate samples of mature biofilms on unplasticized polyvinyl chloride (PVC-U), grey cast iron and asbestos cement (pipe age &gt; 40 years) were obtained from three areas of an unchlorinated drinking water distribution system in the Netherlands. Illumina sequencing was performed and 773 OTUs (730 OTUs-814 OTUs) were detected within the biofilms on the three pipe materials, all of which were dominated by Proteobacteria (36.2%-46.1%). Both the alpha and beta diversity results showed that the bacterial communities of the biofilms formed on different pipe materials were highly similar. The neutral community model revealed that the assembly of the biofilm communities was governed by environmental selection rather than neutral processes. Among the 142 shared OTUs between the water and biofilm samples, there were 25 enriched OTUs (e.g., OTU7, assigned as <em>Nitrospira</em> spp.), which accounted for 62.6% of the total sequences, while 16 OTUs were disadvantaged (e.g., OTU14 and OTU40, assigned as Hyphomicrobiaceae), accounting for 2.2% of the sequences. Based on the findings, we propose and discuss a harmonisation process by which biofilms with significant differences due to the pipe material harmonize over time resulting in biofilms with similar bacterial communities. Our findings provide valuable insights into long-term biofilm development, bridging an essential gap in our current understanding of the influence of pipe materials on biofilm communities. These findings also highlight the importance of long-term studies and point to a potentially masked harmonizing process during biofilm development over years/decades.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"6 4","pages":"Pages 2369-2375"},"PeriodicalIF":6.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148640499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improvement of mechanical properties and mechanism analysis of FMLs by ultrasonic vibration assisted hot press forming","authors":"Yizhe Chen,&nbsp;Longyu Dai,&nbsp;Yusen Yang,&nbsp;Hui Wang,&nbsp;Shujian Li,&nbsp;Lin Hua","doi":"10.1016/j.fmre.2025.02.022","DOIUrl":"10.1016/j.fmre.2025.02.022","url":null,"abstract":"<div><div>The low forming quality of fiber metal laminates (FMLs) limits their application in the aerospace field. As a fundamental research, FMLs high-quality forming process provides key technical support for FMLs engineering applications. In this study, an advanced process of ultrasonic vibration assisted hot press forming (UAHPF) of FMLs is proposed. The specially forming mold of UAHPF was designed and manufactured. Mechanical properties of FMLs were tested. UAHPF increased the tensile strength, bending strength, and shear strength of the FMLs by 13.09%, 11.97%, and 49.51% under the optimal process parameters, respectively. In comparison to traditional forming, UAHPF markedly diminished internal defects in FMLs, augmented the metal-fiber contact area, and narrowed the width of the fiber-resin gap. This novel process is a convenient and effective way to enhance the mechanical properties of FMLs.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"6 4","pages":"Pages 2492-2502"},"PeriodicalIF":6.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148640522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of anionic redox reactions with vacancies in layered potassium manganese oxide","authors":"Quan Wu,&nbsp;Meng Ren,&nbsp;Jiarun Geng,&nbsp;Tong Zhang,&nbsp;Fei Li,&nbsp;Fujun Li","doi":"10.1016/j.fmre.2024.03.001","DOIUrl":"10.1016/j.fmre.2024.03.001","url":null,"abstract":"<div><div>Layered manganese-based oxides are promising cathode materials for potassium-ion batteries (PIBs) owing to the abundant K resources. However, their energy density is limited to the accessible redox centers. Herein, P'2-type K_0.51Mn_0.93Mn_□0.07O₂ (Mn_□ = Mn vacancy) is synthesized to activate anionic redox reactions (ARRs) by introducing native Mn vacancies into the transition-metal slabs. The vacant Mn sites facilitate the formation of non-bonding O 2p orbitals to trigger ARRs, owing to their high orbital energy close to the Fermi level, and provide additional capacity. The presence of ARRs suppresses phase transition and results in formation of O-O dimers for stable oxygen networks to mitigate oxygen loss. High specific capacity of 116 mAh g⁻¹ with long cycle stability can be obtained based on the successive redox of Mn^3.75+/Mn^3.88+ and O²⁻/O^n- (<em>n</em> &lt; 2). This work provides a new pathway to activate ARRs with vacancies for high specific capacities and stable cycling for PIBs.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"6 4","pages":"Pages 2221-2226"},"PeriodicalIF":6.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148640626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A brief guideline for the studies of structure-function relationship of ion channels using AlphaFold3","authors":"Yichen Ke,&nbsp;Ruijie Gong,&nbsp;Nan Liu,&nbsp;Yaxiong Yang","doi":"10.1016/j.fmre.2025.07.010","DOIUrl":"10.1016/j.fmre.2025.07.010","url":null,"abstract":"<div><div>Ion channels are crucial membrane proteins that regulate ion flux, thus affecting a broad range of physiological processes and disease mechanisms. Traditional approaches, such as X-ray crystallography and cryo-electron microscopy, often face significant challenges in resolving the structure-function relationships of ion channels due to the complex subunit assemblies, transient functional states, and high experimental costs. AlphaFold3 offers a major leap forward by accurately modeling multimeric channels, predicting ligand and ion interactions, and refining subunit interfaces. Building on AlphaFold2, it integrates diffusion-based algorithms and enhanced confidence metrics to explore gating, auxiliary subunits, disease-linked mutations, etc. This review outlines AlphaFold3’s key innovations and provides a step-by-step protocol for its use in predicting ion channel complexes. We discuss essential structural parameters, common software for basic analyses, and complementary techniques including molecular dynamics simulations, molecular docking, functional assays (electrophysiology and ion imaging) and structure biology techniques that extend and validate computational findings. Representative examples, including the P2X receptors and voltage-gated calcium channels, demonstrate AlphaFold3’s ability to clarify channel assembly, gating mechanisms, channelopathies, and therapeutic opportunities. Finally, we address AlphaFold3’s remaining limitations. Despite these hurdles, AlphaFold3 offers a transformative platform that, when integrated with established experimental methods, is poised to significantly advance ion channel research and drug discovery.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"6 4","pages":"Pages 2273-2288"},"PeriodicalIF":6.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148640628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-trait genetic analysis identifies novel pleiotropic loci for stroke and hematological traits or risk factors","authors":"Yue Jiang,&nbsp;Yingchao Song,&nbsp;Yaqi Li,&nbsp;Yuhao Tong,&nbsp;Huanxin Ding,&nbsp;Linzehao Li,&nbsp;Ziyue Yang,&nbsp;Ziang Meng,&nbsp;Miao Guo,&nbsp;Steven Weidong Su,&nbsp;Xiao Chang","doi":"10.1016/j.fmre.2024.05.004","DOIUrl":"10.1016/j.fmre.2024.05.004","url":null,"abstract":"<div><div>Accumulating evidence suggests a correlation between stroke and hematological traits along with their associated risk factors, yet the precise shared genetic basis remains elusive. We collected GWAS summary statistics of stroke and potentially related hematological traits or risk factors from the GWAS Catalog and used LDSC to estimate genetic correlations and heritabilities. For trait pairs with significant correlations, we performed a comprehensive multi-trait GWAS analysis to identify pleiotropic loci shared by stroke and genetically correlated hematological traits or risk factors in both Europeans and East Asians. Our MTAG analysis identified 59 pleiotropic loci associated with both stroke and hypertension in Europeans, along with 17 such loci in East Asians. Among these loci, 33 were previously unknown in Europeans, and six were previously unknown in East Asians, suggesting potential new insights into the genetic basis of these traits. In the MTAG analysis of ischemic stroke and venous thromboembolism, we found six known loci and two novel loci. Notably, the 10q22.1 locus (rs12242391) was identified as an eQTL for the nearby gene TSPAN15 in multiple tissues, including whole blood. Furthermore, the 12q13.13 locus (rs4759076), which had not been reported in association with ischemic stroke or venous thromboembolism previously, exhibited a strong cis-eQTL effect with the nearby gene NFE2, a crucial regulator of megakaryocyte biogenesis and platelet production. Our study provided valuable insights into the shared genetic architecture of stroke and hematological traits or risk factors, highlighting potential avenues for future research and clinical applications.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"6 4","pages":"Pages 2701-2710"},"PeriodicalIF":6.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141142329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress and application of solid-state nanopore fabrication based on wet etching","authors":"Liang Cheng,&nbsp;Yun Chen,&nbsp;Bin Xie,&nbsp;Hengxu Wu,&nbsp;Chuhao Cai,&nbsp;Wenxuan Wu,&nbsp;Yuanhui Guo,&nbsp;Maoxiang Hou,&nbsp;Li Ma,&nbsp;Huilong Liu,&nbsp;Xin Chen","doi":"10.1016/j.fmre.2025.03.009","DOIUrl":"10.1016/j.fmre.2025.03.009","url":null,"abstract":"<div><div>Solid-state nanopores have the potential to revolutionise biomedical and molecular detection, particularly in the fields of gene sequencing, protein analysis, and ion screening, owing to their exceptional mechanical strength, stability, and tunability of pore structure. Among various techniques for fabricating solid-state nanopores, wet etching stands out for its low cost, high efficiency, batch production capability, and compatibility with a wide range of substrate materials, including silicon, silicon nitrides, silicon oxides, and metals. This paper systematically reviews recent advancements in the fabrication of solid-state nanopores using wet etching, encompassing key technologies such as anisotropic wet etching, metal-assisted chemical etching, and electrochemical etching. Additionally, this paper details representative applications of solid-state nanopores, such as gene sequencing, protein detection, energy conversion and storage, seawater desalination, and haemodialysis. Furthermore, this paper offers a prospective analysis of enhancing the size consistency of solid-state nanopores fabricated by wet etching and explores future applications, aiming to foster the ongoing advancement of solid-state nanopore fabrication technology and its applications.</div></div>","PeriodicalId":34602,"journal":{"name":"Fundamental Research","volume":"6 4","pages":"Pages 2449-2462"},"PeriodicalIF":6.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148640567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}