The Innovation最新文献

{"title":"Joint observations by Tianwen-1 and MAVEN: Ushering in a new era of rapid dynamical coupling in the Martian space environment.","authors":"Yuming Wang, Shiyong Huang, Rentong Lin, Zhigang Yuan","doi":"10.1016/j.xinn.2026.101366","DOIUrl":"10.1016/j.xinn.2026.101366","url":null,"abstract":"","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"7 6","pages":"101366"},"PeriodicalIF":39.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13237833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148200336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Metabolic circuitry of NADH buffering reveals a vulnerability in redox-adaptive cancer cells.","authors":"Xuexue Li, Pengjiao Hou, Xuewei Zhai, Lifang Li, Zihao Guo, Luxin Qiao, Yanxia Fu, Jing Niu, Ping Chen, Ronghui Yang, Binghui Li","doi":"10.1016/j.xinn.2026.101365","DOIUrl":"10.1016/j.xinn.2026.101365","url":null,"abstract":"<p><p>Mitochondrial dysfunction elevates cellular NADH/NAD⁺ ratios, inducing reductive stress that impairs biosynthesis and cell viability. However, the mechanisms by which cells buffer excess NADH to maintain redox homeostasis remain unclear. In this study, we identify a mitochondrial-cytosolic metabolic circuitry involving pyruvate carboxylase (PC), malate dehydrogenases (MDH1/2), and malic enzyme 1 (ME1) that mitigates NADH overload by coupling anaplerotic flux with NADH oxidation. Under reductive stress induced by electron transport chain (ETC) dysfunction, oxaloacetate derived from PC is converted to malate by MDH1/2, which is then oxidized by ME1, transforming both cytosolic and mitochondrial NADH into cytosolic NADPH. Although cellular NADPH is typically associated with antioxidant defense and biosynthesis, our experiments show that TPNOX, which can oxidase NADPH to NADP⁺, restores proliferation under ETC inhibition, and this rescue is entirely dependent on the mitochondrial-cytosolic metabolic circuitry. This finding highlights that the primary function of the circuit is to maintain NADH homeostasis rather than to generate NADPH. Notably, glucose-6-phosphate dehydrogenase (G6PD) enhances ME1 activity independently of its catalytic function by acting as a scaffold, thereby preventing net NADPH production while facilitating the conversion of NADH to NADPH. Disruption of the PC-MDH1/2-ME1 pathway through PC inhibition sensitizes cells to complex I inhibitors and/or glutaminase blockade, synergistically suppressing tumor growth both <i>in vitro</i> and <i>in vivo</i>. These findings uncover a redox-buffering strategy that redirects NADH into NADPH production, revealing a metabolic vulnerability in redox-adapted cancer cells.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"7 9","pages":"101365"},"PeriodicalIF":39.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Sodium-ion-responsive injectable supramolecular hydrogel delivers engineered <i>Salmonella</i> for safer and enhanced tumor immunotherapy.","authors":"Wenliang Yu, Wei Tang, Tao Zhang, Mengyue Gao, Lina Liu, Xiaoran Zhou, Zeyang Liu, Ziyi Tan, Yao Li, Yuning Meng, Siyu Li, Chenyang Li, Congrui Guo, Kaiting Zheng, Zichun Hua","doi":"10.1016/j.xinn.2026.101363","DOIUrl":"10.1016/j.xinn.2026.101363","url":null,"abstract":"<p><p>Live bacterial therapeutics (LBTs) based on attenuated <i>Salmonella</i> Typhimurium VNP20009 (VNP) show great promise for refractory cancer treatment. However, improvements in antitumor efficacy are often accompanied by increased systemic toxicity. To address this critical challenge of achieving both potent efficacy and acceptable safety, this study developed a sodium-ion-responsive, injectable supramolecular hydrogel suitable for VNP delivery, isosteviol-1,6-diester sodium sulfonate (1,6-DAS). By encapsulating engineered VNP (VNP-TNF-α nanobody [nb]) within this hydrogel for intraperitoneal delivery in murine melanoma models, not only was 78.8% of bacteria-induced body weight loss alleviated and VNP-associated hepatosplenomegaly, necrosis, tissue damage, and immune dysregulation completely prevented, but antitumor immune responses were also further enhanced. The findings indicate that the 1,6-DAS hydrogel achieves comprehensive attenuation of VNP through a dual mechanism whereby slow release lowers acute bacterial burden in the liver and spleen and binding of 1,6-DAS molecules to VNP flagellin attenuates its immunogenicity. In addition, delivery of the VNP-TNF-α nb via the 1,6-DAS hydrogel further enhances antitumor immunity by upregulating and activating dendritic cells (DCs) and CD8⁺ T cells in the tumor microenvironment. Overall, the 1,6-DAS hydrogel provides a promising approach to address the core challenge of balancing efficacy and safety in VNP-based therapies, with substantial potential to propel microbiome-driven cancer immunotherapy forward.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"7 9","pages":"101363"},"PeriodicalIF":39.5,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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-channel automated programmable liquid exchange system enables high-quality sample preparation for super-resolution microscopy.","authors":"Bo Wang, Fen Hu, Mingxin Chen, Zhao Xie, Shuai Liu, Jiqiang Li, Dan Ding, Jingjun Xu, Leiting Pan","doi":"10.1016/j.xinn.2026.101361","DOIUrl":"10.1016/j.xinn.2026.101361","url":null,"abstract":"<p><p>The emergence of super-resolution microscopy (SRM) leads to increasing demands on sample quality to faithfully visualize cellular ultrastructure at the nanoscale. For SRM techniques relying on fixed samples, immunofluorescence (IF) labeling is the commonly employed approach. However, traditional manual IF preparation is labor intensive, time consuming, and highly operator dependent, limiting standardization and reproducibility. Here, we report a compact, cost-effective device termed Multi-Channel Automated Programmable Liquid Exchange System (MAPLES) for high-quality IF sample preparation. MAPLES integrates dual peristaltic pumps and multi-channel solenoid valves to enable precise, gentle liquid handling without reagent cross-contamination. Equipped with interchangeable adapters, it supports multiple open-format biological samples. The system exhibits high injection accuracy, low reagent residue, and effective waste removal, making it well suited for multi-step IF workflows. MAPLES-prepared IF samples consistently preserve ultrastructural integrity and fidelity across various biological contexts, satisfying the stringent requirements for stochastic optical reconstruction microscopy (STORM) super-resolution imaging. Furthermore, the flexible modular design of MAPLES allows seamless integration with microscopes for automated sequential drug exchange during live-cell experiments and <i>in situ</i> STORM sample processing. Collectively, MAPLES offers a robust, accessible, and versatile platform for high-quality sample preparation, advancing SRM workflows and enabling diverse extended applications.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"7 9","pages":"101361"},"PeriodicalIF":39.5,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Does petroleum resource extraction and oceanic heat transfer increase geothermal heat flux? A global multi-sensor study of oil basins.","authors":"Salih Muhammad Awadh, Zaher Mundher Yaseen","doi":"10.1016/j.xinn.2026.101362","DOIUrl":"10.1016/j.xinn.2026.101362","url":null,"abstract":"","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"7 5","pages":"101362"},"PeriodicalIF":39.5,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Toward interface-adaptive silicon anodes: From 3D SEI to dynamic coupled interphases.","authors":"Hong Yin, Yingqi Cao, Yaru Wang, Junlin Huang, Sitaramanjaneya Mouli Thalluri, Zhipeng Yu","doi":"10.1016/j.xinn.2026.101360","DOIUrl":"10.1016/j.xinn.2026.101360","url":null,"abstract":"<p><p>This review examines the development of silicon anodes in lithium-ion batteries, focusing on modifying the solid electrolyte interphase (SEI) to address issues arising from silicon's significant volume expansion. It promotes a transition from static, stabilizing strategies to dynamic, adaptive interfaces that evolve in accordance with silicon's behavior during cycling. The discussion highlights key advancements in the dimensional evolution of SEI layers, transitioning from brittle 3D structures to more stable, conductive 2D configurations. The significance of hierarchical chemical coupling, integrating rigid inorganic components such as LiF with flexible polymer matrices, is highlighted for its role in ensuring mechanical stability and ionic conductivity. The integration of self-healing strategies and dynamic chemical bonds and the system-level integration of electrolytes, electrodes, and interfaces are critical for developing intelligent silicon anodes capable of adapting to mechanical and electrochemical stresses. This novel approach has the potential to enhance the performance and longevity of silicon-based anodes in next-generation batteries.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"7 8","pages":"101360"},"PeriodicalIF":39.5,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13457186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Deciphering interventional dynamical causality from non-intervention complex systems.","authors":"Jifan Shi, Yang Li, Juan Zhao, Siyang Leng, Rui Bao, Kazuyuki Aihara, Luonan Chen, Wei Lin","doi":"10.1016/j.xinn.2026.101358","DOIUrl":"10.1016/j.xinn.2026.101358","url":null,"abstract":"<p><p>Detecting and quantifying causal influence is a focal topic in the fields of science, engineering, and interdisciplinary studies. However, causal studies on non-intervention systems attract much attention but remain extremely challenging. The delay-embedding technique provides a promising approach. In this study, we propose a framework named interventional dynamical causality (IntDC) in contrast to the traditional constructive dynamical causality (ConDC). ConDC, including Granger causality, transfer entropy, and convergence of cross-mapping, measures the causality by constructing a dynamical model without considering interventions. A computational criterion, interventional embedding entropy (IEE), is proposed to measure causal strengths in an interventional manner. IEE is an intervened causal information flow but in the delay-embedding space. Further, the IEE theoretically and numerically enables the deciphering of IntDC solely from observational (non-interventional) time-series data, without requiring any knowledge of dynamical models or real interventions in the considered system. In particular, IEE can be applied to rank causal effects according to their importance and construct causal networks from data. We conducted numerical experiments on logistic dynamics, coupled-Hénon maps, and chaotic neural networks to demonstrate that IEE can find causal edges accurately, eliminate effects of confounding, and quantify causal strength robustly over traditional indices. We also applied IEE to real-world tasks, including estimating neural connectomes of <i>Caenorhabditis elegans</i>, detecting COVID-19 transmission networks in Japan, and investigating regulatory networks surrounding key circadian genes. IEE performed as an accurate and robust tool for causal analyses solely from the observational data. Both the IntDC framework and the IEE algorithm proposed in this study provide an approach to understanding causal influence in diverse non-intervention complex systems.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"7 10","pages":"101358"},"PeriodicalIF":39.5,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Current landscape and future directions of neoantigen vaccines: A new era of personalized cancer immunotherapy.","authors":"Xinyue Wang, Shu Su, Siyi Tan, Xiaosu Chen, Lifeng Wang, Shuan Wang, Fangjun Chen","doi":"10.1016/j.xinn.2026.101357","DOIUrl":"10.1016/j.xinn.2026.101357","url":null,"abstract":"<p><p>At the forefront of cancer immunotherapy, neoantigens are tumor specific and highly immunogenic, and they have emerged as the key target for personalized oncology. Neoantigen vaccines have demonstrated promising immunologic responses and survival benefit in clinical trials with the combination of chemoradiotherapy and immune checkpoint therapy. This review provides a comprehensive synthesis of biological mechanisms and the next-generation screening approach of cancer neoantigens. We evaluate the current vaccine platforms and the design and vector of cancer neoantigen vaccines, and we additionally analyze strategies to overcome immunosuppressive tumor microenvironment challenges. We conducted a detailed analysis of ongoing and preliminary neoantigen vaccine clinical trials, summarizing existing challenges and areas requiring further improvement. Through an in-depth analysis of the latest research advances, we propose current optimization strategies for neoantigen vaccines, including novel screening models and innovative delivery approaches. Future directions for personalized cancer immunotherapy are outlined, with neoantigen vaccines positioned as pivotal enabling platforms.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"7 9","pages":"101357"},"PeriodicalIF":39.5,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"Terahertz spectroscopy for probing free carriers in perovskite solar cells.","authors":"Yinong Xie, Bosen Zou, Zarifi Masri, Hieng Kiat Jun, Guohua Xie, Wei Huang","doi":"10.1016/j.xinn.2026.101356","DOIUrl":"10.1016/j.xinn.2026.101356","url":null,"abstract":"","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"7 5","pages":"101356"},"PeriodicalIF":39.5,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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":"PROTAC-mediated regulation of programmed cell death: From molecular mechanisms to therapeutic breakthroughs.","authors":"Hangqi Huang, Aoli Deng, Feifan Pan, Yajuan Lu, Lulu Chen, Jinghao Cao, Qin Tang, Yingchao Liu, Yunyi Wu, Jing Du, Yanchun Li, Xiangmin Tong","doi":"10.1016/j.xinn.2026.101359","DOIUrl":"10.1016/j.xinn.2026.101359","url":null,"abstract":"<p><p>Proteolysis-targeting chimeras (PROTACs) represent a revolutionary therapeutic strategy that achieves selective protein degradation through the ubiquitin-proteasome system, offering transformative potential for modulating programmed cell death (PCD) pathways. This review comprehensively examines the central role of PROTACs in regulating critical PCD mechanisms, including ferroptosis induction via GPX4 degradation, pyroptosis regulation through stimulator of interferon genes (STING) targeting, necroptosis modulation by MLKL/RIPK1 degradation, apoptosis activation through BCL-2/MDM2 elimination, and autophagy regulation via dual ubiquitin-proteasome and lysosomal pathways. These approaches effectively address the limitations of traditionally \"undruggable\" targets while demonstrating unique mechanistic properties and clinical promise. Currently, over 30 PROTAC candidates have entered clinical trials, including the estrogen receptor (ER) degrader ARV-471 for breast cancer and the IRAK4 degrader KT-474 for inflammatory diseases, both showing remarkable efficacy in overcoming drug resistance. While challenges remain in delivery systems, E3 ligase selectivity, and toxicity management, innovative technologies, such as nanocarriers, covalent PROTACs, and novel E3 ligases (e.g., RNF114) are advancing PROTAC applications in oncology, neurodegenerative disorders, and immune-related diseases. Future research will focus on optimizing molecular design, expanding the E3 ligase repertoire, and developing combination therapies. These efforts will establish PROTACs as groundbreaking solutions for intractable diseases, with their precise control of PCD pathways opening new therapeutic avenues. The technology's ability to selectively modulate cell death mechanisms positions it as a transformative approach in precision medicine.</p>","PeriodicalId":36121,"journal":{"name":"The Innovation","volume":"7 7","pages":"101359"},"PeriodicalIF":39.5,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148413161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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}