iSciencePub Date : 2025-09-09DOI: 10.1016/j.isci.2025.113520
Yutong Chen , Yang Li , Zongzhu Liang , Zhao Yang , Haotian Ren , Wanqing Wei , Yuanjie Niu , Zhiqun Shang
{"title":"ALKBH5-IGF2BP2 axis mediates prostate cancer progression and docetaxel resistance via m6A-stabilized CLSPN RNA","authors":"Yutong Chen , Yang Li , Zongzhu Liang , Zhao Yang , Haotian Ren , Wanqing Wei , Yuanjie Niu , Zhiqun Shang","doi":"10.1016/j.isci.2025.113520","DOIUrl":"10.1016/j.isci.2025.113520","url":null,"abstract":"<div><div>Prostate cancer (PCa) often progresses to castration-resistant PCa (CRPC), where docetaxel (DTX) resistance is a major challenge. We investigated the role of the m6A demethylase ALKBH5 in this resistance. ALKBH5 expression was significantly reduced in CRPC clinical samples. Functionally, overexpressing ALKBH5 inhibited PCa cell proliferation and migration, while its knockdown enhanced these effects and increased DTX resistance. Conversely, restoring ALKBH5 or knocking down the m6A reader IGF2BP2 reversed resistance. Multi-omics analysis identified CLSPN, a DNA replication stress regulator, as a key downstream target. Mechanistically, ALKBH5-mediated m6A demethylation reduces CLSPN mRNA stability in an IGF2BP2-dependent manner. Low ALKBH5, therefore, stabilizes CLSPN via IGF2BP2, promoting resistance. These findings, validated in clinical samples and organoid models, demonstrate that the ALKBH5-IGF2BP2 axis modulates DTX resistance in metastatic CRPC through m6A-dependent regulation of CLSPN. Targeting this pathway represents a promising therapeutic strategy to overcome DTX resistance.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113520"},"PeriodicalIF":4.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The inbred newt genome unveils molecular mechanisms of behavior, development, and regeneration in urodele amphibians","authors":"Yuki Kimura , Miyuki Suzuki , Akinori Okumura , Masatoshi Matsunami , Hiroyo Nishide , Rima Mizuno , Kazuto Bou , Yoshinobu Uno , Tomoaki Nakada , Itaru Hasunuma , Yoshikazu Haramoto , Akimasa Fukui , Takeshi Inoue , Yuki Sato , Katsushi Yamaguchi , Zicong Zhang , Akane Chihara , Mai Takehara , Yuki Shibata , Masaaki Kitada , Ken-ichi T. Suzuki","doi":"10.1016/j.isci.2025.113535","DOIUrl":"10.1016/j.isci.2025.113535","url":null,"abstract":"<div><div>Salamanders provide excellent models for studying vertebrate evolution, development, and regeneration. To further advance the newt as a model organism in biology, we conducted draft genome sequencing of 20 Gb of an inbred newt (<em>Pleurodeles waltl</em>). As part of this study, the <em>Hoxd11–d13</em> intergenic region is expanded by over 1 Mb owing to the massive insertion of repetitive sequences including newt-specific satellite DNA. Interestingly, <em>Myod</em> and <em>Bmp4</em>, genes that are typically involved in vertebrate development, are absent in salamanders. Co-option of <em>Sodefrin Precursor-like Factor</em> genes, which encode sex pheromone ligands, suggests a diversification of reproductive behavior among salamanders. Moreover, a limb enhancer of <em>Shh</em>, MFCS1/ZRS, retains its function, even though it is positioned approximately 5 Mb away from the promoter. Furthermore, we have identified a functional <em>cis</em>-element potentially associated with limb regeneration in this enhancer. The newt genome yields crucial insights into amphibian evolution, behavior, development, and regeneration.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113535"},"PeriodicalIF":4.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2025-09-08DOI: 10.1016/j.isci.2025.113531
Jun Liu , Yaxing Feng , Peng Qu , Yunbo Luo , Jiao Shi , Cui Ma , Qi Liang , Long Zhao , Gang Li , Bo Yang , Panke Cheng
{"title":"Application of biomaterials in vascularization of cardiac organoids","authors":"Jun Liu , Yaxing Feng , Peng Qu , Yunbo Luo , Jiao Shi , Cui Ma , Qi Liang , Long Zhao , Gang Li , Bo Yang , Panke Cheng","doi":"10.1016/j.isci.2025.113531","DOIUrl":"10.1016/j.isci.2025.113531","url":null,"abstract":"<div><div>Cardiac organoids (COs) are platforms for disease modeling and regenerative medicine, yet inadequate vascularization still limits their function and longevity. This review examines how biomaterial properties—porosity, elasticity, surface chemistry, and bioactivity—regulate endothelial cell behavior and vascular network formation, thereby shaping progress in organoid vascularization. We survey natural, synthetic, and composite systems (e.g., collagen, fibrin, polyethylene glycol [PEG] hydrogels, and poly(ε-caprolactone) [PCL] scaffolds) used to promote vascularization. We also summarize fabrication strategies to improve perfusion, including micro/nanopatterning, scaffold design, and delivery of pro-angiogenic factors, and we outline technical routes for spatially patterned vasculature such as three-dimensional (3D) bioprinting and microfluidics. Ongoing challenges include degradation mismatch and incomplete integration. Future work should emphasize stimuli-responsive and bioactive materials, as well as standardized, scalable scaffold platforms, to strengthen reproducibility and translational efficiency. These directions will help optimize the vascular microenvironment of organoids, enhance functional maturation, and broaden applications in disease modeling, drug evaluation, and regenerative repair.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113531"},"PeriodicalIF":4.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2025-09-08DOI: 10.1016/j.isci.2025.113522
Si-Ao Li , Jia-Rui Yu , Hai-Sheng Yuan
{"title":"Climate change impacts on the distribution of valuable Thelephora fungi in China","authors":"Si-Ao Li , Jia-Rui Yu , Hai-Sheng Yuan","doi":"10.1016/j.isci.2025.113522","DOIUrl":"10.1016/j.isci.2025.113522","url":null,"abstract":"<div><div><em>Thelephora</em> includes valuable edible ectomycorrhizal (ECM) fungi in East Asia threatened by overharvesting, climate change, and habitat loss. Using Biomod2 ensemble modeling with bioclimatic variables, elevation data, and occurrence records, this study predicted current and future distributions of four <em>Thelephora</em> species under climate scenarios SSP2-45 and SSP5-85 for the 2050s and 2090s. The results indicate that the potential distribution ranges of these four <em>Thelephora</em> species are primarily influenced by Bio18 (precipitation of the warmest quarter), Bio12 (annual precipitation), elevation, and Bio3 (isothermality), though the relative importance of these factors varies among species. High-emission scenarios predict habitat reduction by 2050, with potential range expansion by 2090. Warming will drive northward habitat shifts, with migration distances increasing under high-emission scenarios. Over half of potential distribution areas contain non-host vegetation. Conservation strategies should prioritize host plant cultivation to expand fungal habitats and mitigate climate impacts.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113522"},"PeriodicalIF":4.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2025-09-08DOI: 10.1016/j.isci.2025.113512
Céline Sérazin , Lisa Dugast , Léa Flippe , Mathias Streitz , Désirée-Jacqueline Wendering , Stephan Schlickeiser , Frederik Heinrich , Pawel Durek , Gabriela Maria Guerra , Katrin Lehmann , Mir-Farzin Mashreghi , Harald Wajant , Hans Dieter Volk , Ignacio Anegon , Laurent David , Séverine Bézie , Carole Guillonneau
{"title":"Two subsets of regulatory CD8+ T cells with differential transcriptome revealed by single cell analysis","authors":"Céline Sérazin , Lisa Dugast , Léa Flippe , Mathias Streitz , Désirée-Jacqueline Wendering , Stephan Schlickeiser , Frederik Heinrich , Pawel Durek , Gabriela Maria Guerra , Katrin Lehmann , Mir-Farzin Mashreghi , Harald Wajant , Hans Dieter Volk , Ignacio Anegon , Laurent David , Séverine Bézie , Carole Guillonneau","doi":"10.1016/j.isci.2025.113512","DOIUrl":"10.1016/j.isci.2025.113512","url":null,"abstract":"<div><div>Although CD8<sup>+</sup> regulatory T cells (Tregs) were described in the 1970’s, they remain poorly defined compared to CD4<sup>+</sup> Tregs. Their phenotypic heterogeneity and lack of consensus markers have hindered mechanistic studies and slowed clinical development despite their therapeutic potential. In this study, we performed single-cell RNA sequencing coupled with CITE-seq and TCR-seq on peripheral blood CD8<sup>+</sup> T cells from four healthy donors, including the CD45RC marker to distinguish pro-inflammatory from pro-regulatory subsets. We analyzed ∼7000 freshly isolated, non-stimulated CD8<sup>+</sup> T cells and identified two distincts CD8<sup>+</sup> Tregs subsets, defined by HELIOS or TNFR2 expression, with unique transcriptional and surface marker profiles. Functional assays revealed potent suppressive capacity of the TNFR2<sup>+</sup>CD29<sup>low</sup>CD45RC<sup>low/-</sup> subset. These findings were independently validated using a publicly available single-cell dataset from four additional individuals. This work provides the most comprehensive profiling of human CD8<sup>+</sup> Tregs to date and supports their translation to clinical application.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113512"},"PeriodicalIF":4.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Influences of genetic factors for educational attainment and cognitive functions on current dietary consumption","authors":"Daisuke Fujikane , Kazutaka Ohi , Daisuke Nishizawa , Junko Hasegawa , Naomi Sato , Fumihiko Tanioka , Haruhiko Sugimura , Kazutaka Ikeda , Toshiki Shioiri","doi":"10.1016/j.isci.2025.113530","DOIUrl":"10.1016/j.isci.2025.113530","url":null,"abstract":"<div><div>Dietary habits are critical for the prevention and management of physical and mental disorders and may also be influenced by genetic factors for educational attainment (EA) and cognitions. This study examined the effects of polygenic scores (PGSs) associated with EA and cognitions on current dietary consumption among older patients with lifestyle-related diseases. Dietary habits were assessed across eight categories in 730 older adult outpatients diagnosed with or suspected of having lifestyle-related diseases. Six PGSs associated with EA and cognitions were calculated using large-scale genome-wide association study (GWAS) datasets, and their correlations with dietary consumption patterns were investigated. Higher PGSs associated with EA and cognitions were commonly correlated with increased consumption of fruits. Moreover, we found positive genetic correlations between fruit consumption with EA and cognitive functions in an independent cohort. Our findings suggest that genetic factors related to educational and cognitive phenotypes may shape dietary habits that promote physical and mental health and longevity.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113530"},"PeriodicalIF":4.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2025-09-07DOI: 10.1016/j.isci.2025.113515
Dalin Zhang , Chun-Lung Chiu , Ru Wen , Zhengyuan Qiu , Fernando Garcia-Marques , Abel Bermudez , Man Zhao , Hongjuan Zhao , Scott J. Dixon , Donna M. Peehl , Erinn B. Rankin , Sharon Pitteri , James D. Brooks
{"title":"FTO inhibition attenuates renal fibrosis by downregulating ferroptosis activator ACSL4 and profibrotic factor TGFBI","authors":"Dalin Zhang , Chun-Lung Chiu , Ru Wen , Zhengyuan Qiu , Fernando Garcia-Marques , Abel Bermudez , Man Zhao , Hongjuan Zhao , Scott J. Dixon , Donna M. Peehl , Erinn B. Rankin , Sharon Pitteri , James D. Brooks","doi":"10.1016/j.isci.2025.113515","DOIUrl":"10.1016/j.isci.2025.113515","url":null,"abstract":"<div><div>Renal fibrosis (RF) is the main pathological feature and a potential therapeutic target of chronic kidney disease (CKD), a prevalent health problem causing a high economic burden to the health care system. Fat mass and obesity-associated (FTO) inhibition, either genetically or pharmacologically, significantly reduced collagen deposition, lipid peroxidation, and ferroptosis marker expression after unilateral ureteral obstruction (UUO) compared with sham-operated controls in mice. In murine and human kidney epithelial cells as well as in human embryonic stem cell-derived kidney organoids, FTO inhibition reduced erastin-induced ferroptosis by decreasing lipid peroxidation and reactive oxygen species production by downregulating the ferroptosis driver ACSL4. Moreover, FTO inhibition directly downregulated <em>TGFBI,</em> which was strongly associated with reduced M2 macrophage accumulation after UUO. Our results provide a strong rationale for targeting FTO to alleviate RF in patients subjected to obstruction-related kidney injury, thereby reducing the prevalence of CKD and associated treatment costs and improving the quality of life.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113515"},"PeriodicalIF":4.1,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2025-09-07DOI: 10.1016/j.isci.2025.113480
Aqsa Abid , XiaoYing Sun , Yuqing Tang , Yi Xiao , Bo Li
{"title":"Tailoring the catalytic performance of MXenes in propane dehydrogenation by layer substitution from microkinetic simulations","authors":"Aqsa Abid , XiaoYing Sun , Yuqing Tang , Yi Xiao , Bo Li","doi":"10.1016/j.isci.2025.113480","DOIUrl":"10.1016/j.isci.2025.113480","url":null,"abstract":"<div><div>The reactivity and catalytic performance of MXenes in propane dehydrogenation (PDH) are highly dependent on their composition. This study explores modifying MXenes by substituting their X-layers with carbon, nitrogen, or a mix of both. Density functional theory (DFT) and microkinetic simulations show that these substitutions substantially alter the catalytic mechanism. Nitrogen substitution shifts the <em>p</em>-band center of oxygen active sites closer to the Fermi level, significantly lowering the energy barrier for the first C−H bond activation. Microkinetic analysis further confirms that nitrogen-substituted MXenes exhibit the highest turnover frequency (TOF) for propane conversion and propylene formation. The findings demonstrate that PDH reactivity can be precisely tuned by X-layer substitution, offering a strategy for optimizing MXene-based catalysts.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113480"},"PeriodicalIF":4.1,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
iSciencePub Date : 2025-09-07DOI: 10.1016/j.isci.2025.113476
Hao-Qin Xiong , Jia-Zhuo Qu , Zhe-Xi Luan , Xiao-Long Sun , Xiang-Yang Mei
{"title":"Wet catalytic oxidation upcycling semi-dry flue gas desulfurization ash to sustainable gypsum","authors":"Hao-Qin Xiong , Jia-Zhuo Qu , Zhe-Xi Luan , Xiao-Long Sun , Xiang-Yang Mei","doi":"10.1016/j.isci.2025.113476","DOIUrl":"10.1016/j.isci.2025.113476","url":null,"abstract":"<div><div>Semi-dry flue gas desulfurization ash (SFGDA), rich in calcium sulfite (CaSO<sub>3</sub>) and highly alkaline, poses challenges for direct reuse due to its instability and slow oxidation. This review synthesizes recent advances in wet catalytic oxidation (WCO) that transform CaSO<sub>3</sub> into construction-grade calcium sulfate (CaSO<sub>4</sub>). We frame homogeneous and heterogeneous radical-chain routes and lattice-defect activation, underscoring how Mn/Co/Fe redox cycles and oxygen-vacancy engineering accelerate conversion. Performance comparisons span conventional salts, metal-organic frameworks (MOFs), perovskites, and nanostructured catalysts, with Co-MOFs achieving 96% oxidation in 3 h and MnTiO<sub>3</sub> lowering activation energy by 40%. Process optimizations ultrasound assisted nanobubbles, micro-scale mass-transfer intensification, and pH control at 5–6 address diffusional and alkaline limitations, while layered double hydroxides and anti-scaling surfaces mitigate chloride poisoning and fouling. By merging mechanistic insights with technological progress, this work maps out a sustainable pathway for SFGDA management.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 10","pages":"Article 113476"},"PeriodicalIF":4.1,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}