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Targeting autophagy in dysfunctional tumor vasculature 功能失调肿瘤血管自噬的靶向研究

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-11-17 DOI: 10.1016/j.isci.2025.114084

Qian Lin , Beichen Cai , Ruonan Ke , Xuejun Ni , Xiaofen Wan , Lu Chen , Tao Huang , Xiuying Shan , Biao Wang

Tumor vasculature drives cancer progression and therapeutic resistance, with autophagy serving as a critical regulator of endothelial cell function. This review synthesizes current knowledge of autophagy in tumor vasculature, examining molecular mechanisms, cellular interactions, and therapeutic applications. Tumor endothelial cell autophagy is controlled through mTOR/AMPK signaling, VEGF-mediated pathways, and stress responses. Stromal components, particularly pericytes and proteoglycans, modulate these processes via direct interactions and paracrine signaling, while the interplay between vascular autophagy and immune responses shapes tumor microenvironment dynamics. Therapeutic strategies combining autophagy inhibitors with anti-angiogenic agents, immune checkpoint inhibitors, or chemotherapy demonstrate enhanced preclinical efficacy. However, clinical translation faces challenges including non-specific inhibition and context-dependent effects. Successful therapeutic development requires tumor endothelial cell (TEC)-specific modulators, robust biomarkers for patient stratification, and optimized dosing strategies. Understanding vascular autophagy’s dual roles—promoting both tumor survival and vulnerability—provides essential insights for developing effective cancer treatments.

肿瘤血管系统驱动癌症进展和治疗抵抗，自噬是内皮细胞功能的关键调节因子。本文综述了肿瘤血管中自噬的最新知识，探讨了自噬的分子机制、细胞相互作用和治疗应用。肿瘤内皮细胞的自噬是通过mTOR/AMPK信号、vegf介导的途径和应激反应来控制的。基质成分，特别是周细胞和蛋白聚糖，通过直接相互作用和旁分泌信号调节这些过程，而血管自噬和免疫反应之间的相互作用形成肿瘤微环境动力学。自噬抑制剂联合抗血管生成药物、免疫检查点抑制剂或化疗的治疗策略显示出增强的临床前疗效。然而，临床翻译面临着非特异性抑制和情境依赖效应等挑战。成功的治疗发展需要肿瘤内皮细胞（TEC）特异性调节剂、用于患者分层的强大生物标志物和优化的给药策略。了解血管自噬的双重作用——促进肿瘤生存和脆弱性——为开发有效的癌症治疗提供了重要的见解。

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引用次数: 0

Advances in fungal vaccine development: Progress in the face of emerging challenges 真菌疫苗开发的进展：面对新出现的挑战的进展

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-11-17 DOI: 10.1016/j.isci.2025.114091

Munika Moses , Xinhua Huang , Xinying Xue , Changbin Chen

Historically overshadowed by bacterial and viral infections, fungal diseases are resurging globally, fueled by rising antifungal resistance and the increasing vulnerability of immunocompromised populations in healthcare settings. The widespread misuse and overuse of antifungals have accelerated the emergence of resistant fungal pathogens, complicating clinical management. Despite significant progress in vaccine development, with candidates such as NDV-3A and PEV7 advancing to late-stage trials, none have received FDA approval. Consequently, novel, more effective, and tolerable antifungal therapies are urgently needed. This review consolidates data on the progress made in fungal vaccine development, emphasizing key obstacles to clinical realization. It further proposes innovative strategies, such as bioinformatics-driven antigen discovery, nanotechnology-based delivery systems, reverse vaccinology, and the exploration of probiotic-vaccine synergies, which hold exceptional promise in overcoming these challenges and advancing the fight against fungal infections.

真菌疾病历来被细菌和病毒感染所掩盖，但由于抗真菌药物耐药性上升和卫生保健机构中免疫功能低下人群日益脆弱，真菌疾病正在全球范围内死灰复燃。抗真菌药物的广泛误用和过度使用加速了耐药真菌病原体的出现，使临床管理复杂化。尽管疫苗开发取得了重大进展，NDV-3A和PEV7等候选疫苗已进入后期试验，但尚未获得FDA批准。因此，迫切需要新的、更有效的、可耐受的抗真菌疗法。这篇综述整合了真菌疫苗开发进展的数据，强调了临床实现的主要障碍。它进一步提出了创新策略，如生物信息学驱动的抗原发现、基于纳米技术的递送系统、反向疫苗学和益生菌疫苗协同作用的探索，这些策略在克服这些挑战和推进对抗真菌感染方面具有非凡的前景。

引用次数: 0

Artificial intelligence empowers gut microbiota research in neurodegenerative diseases molecular mechanisms and precision therapy 人工智能使肠道微生物群研究在神经退行性疾病的分子机制和精确治疗

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-11-17 DOI: 10.1016/j.isci.2025.114044

Hanyu Zhu , Haijun He , Ming Yang , Hanbing Zhu , Akifumi Hagiwara , Liting Shu , Jiangxingzi Xu , Yufang Miao , Xiaowei Han , Chuanliu Wang

Neurodegenerative diseases (NDs) are a type of chronic and complex diseases that seriously affect the quality of human life. Their pathogenesis involves aspects such as genetics, environment, and metabolism. In recent years, the close relationship between gut microbiota and host health has gradually attracted attention, especially with the promotion of the concept of “gut-brain axis,” and the role of gut microbiota in nervous system diseases has become a research focus. At the same time, the rapid development of AI technology has provided powerful tools for modeling and data analysis of complex biological systems. This paper reviews the molecular mechanism and therapeutic approaches of gut microbiota in NDs and discusses the application potential of AI in this field, aiming to provide new ideas for the molecular mechanism research and precise treatment of NDs.

神经退行性疾病（NDs）是一类严重影响人类生活质量的慢性复杂疾病。其发病机制涉及遗传、环境、代谢等方面。近年来，肠道菌群与宿主健康的密切关系逐渐引起人们的关注，特别是随着“肠脑轴”概念的推广，肠道菌群在神经系统疾病中的作用成为研究热点。与此同时，人工智能技术的快速发展为复杂生物系统的建模和数据分析提供了强大的工具。本文综述了NDs中肠道菌群的分子机制和治疗途径，并探讨了人工智能在该领域的应用潜力，旨在为NDs的分子机制研究和精准治疗提供新的思路。

引用次数: 0

Challenges and strategies in developing high-performance n-type polycrystalline SnSe thermoelectric materials 开发高性能n型多晶SnSe热电材料的挑战与对策

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-11-14 DOI: 10.1016/j.isci.2025.114025

Adeel Abbas , Habib Khan , Ch Asad Abbas , Syed Irfan , Hamedalneel B.A. Hamid , Jamal N.A. Hassan , Farhan Mudasar , Tianjun Ma , Yue-Xing Chen , Muhammad Shahid Rafique

This review comprehensively examines recent advances in n-type SnSe thermoelectric materials, addressing the critical performance gap with their p-type counterparts. We analyze the fundamental challenges imposed by intrinsic defect chemistry, anisotropic transport, and doping limitations that have historically constrained n-type SnSe development. The discussion systematically evaluates synthesis approaches spanning bulk crystal growth to nanostructured thin films, highlighting how processing conditions influence microstructural evolution and thermoelectric properties. A central focus is placed on doping strategies, including halogen-based and transition metal systems that enable carrier concentration optimization and phonon scattering enhancement. By synthesizing theoretical insights with experimental breakthroughs, this review identifies key knowledge gaps and proposes actionable research directions to realize high-performance n-type SnSe materials, ultimately enabling the development of efficient SnSe thermoelectric devices.

本文全面研究了n型SnSe热电材料的最新进展，解决了与p型热电材料的关键性能差距。我们分析了固有缺陷化学、各向异性输运和掺杂限制所带来的基本挑战，这些限制历来限制了n型SnSe的发展。讨论系统地评估了从体晶体生长到纳米结构薄膜的合成方法，强调了加工条件如何影响微观结构演变和热电性能。中心重点放在掺杂策略，包括卤素和过渡金属系统，使载流子浓度优化和声子散射增强。本文将理论见解与实验突破相结合，找出关键的知识空白，提出可操作的研究方向，以实现高性能n型SnSe材料，最终实现高效SnSe热电器件的发展。

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引用次数: 0

Nuclear receptors as therapeutic targets in metabolic and cardiovascular disorders 核受体作为代谢和心血管疾病的治疗靶点

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-11-14 DOI: 10.1016/j.isci.2025.114042

Feifei Li , Qiujing Chen , Yang Dai , Lin Lu

Nuclear receptors (NRs) are ligand-dependent transcription factors that play essential roles in maintaining metabolic homeostasis and regulating disease progression through the control of metabolism, inflammation, and cellular differentiation. Due to their central position in these pathways, NRs have emerged as critical therapeutic targets in a range of metabolic and cardiovascular disorders, including diabetes, metabolic dysfunction-associated steatotic liver disease ([MASLD]; previously termed non-alcoholic fatty liver disease [NAFLD]), and atherosclerosis. This review summarizes current understanding of the molecular mechanisms by which NRs regulate metabolic function, with particular emphasis on their contributions to disease pathogenesis. We further outline recent advances from preclinical and clinical studies that explore NR-targeted therapeutic strategies. A deeper understanding of NR biology in metabolic and cardiovascular contexts holds promise for the development of more effective and selective interventions.

核受体（NRs）是一种依赖配体的转录因子，通过控制代谢、炎症和细胞分化，在维持代谢稳态和调节疾病进展中发挥重要作用。由于它们在这些通路中的中心位置，NRs已成为一系列代谢和心血管疾病的关键治疗靶点，包括糖尿病、代谢功能障碍相关的脂肪性肝病（[MASLD]；以前称为非酒精性脂肪性肝病[NAFLD]）和动脉粥样硬化。本文综述了目前对NRs调节代谢功能的分子机制的理解，特别强调了它们在疾病发病机制中的作用。我们进一步概述了临床前和临床研究的最新进展，这些研究探索了nr靶向治疗策略。更深入地了解NR生物学在代谢和心血管方面的作用，有助于开发更有效和有选择性的干预措施。

引用次数: 0

Advancements and challenges in autonomous endovascular interventional robotics: A comprehensive review 自主血管内介入机器人的进展与挑战：综述

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-11-14 DOI: 10.1016/j.isci.2025.114024

Jingqian Sun , Ruichao Tang , Quan Zhang , Jiacheng Liu , Liming Gao , Weidong Yang , Xu Chen , Yichao Tang

Cardiovascular and cerebrovascular diseases remain major global health challenges. Minimally invasive endovascular interventions have become preferred treatments due to reduced trauma, pain, and recovery time. However, the advancement of endovascular interventional robotic systems (EIRSs) is constrained by limited imaging depth, heavy dependence on physician experience, and restricted device maneuverability. This review provides a comprehensive overview of the sensing, control, and execution modules that form the core of these EIRSs. It analyzes the fundamental challenges within each component and explores potential strategies to enhance system intelligence and autonomy. By integrating current progress with forward-looking insights, the review highlights pathways toward safer, more efficient, and greater autonomous robotic interventions. The ultimate aim is to advance the development of next-generation robotic platforms that can improve procedural precision and broaden patient access to high-quality vascular care.

心脑血管疾病仍然是全球卫生的主要挑战。由于减少创伤、疼痛和恢复时间，微创血管内介入治疗已成为首选的治疗方法。然而，血管内介入机器人系统（EIRSs）的发展受到成像深度有限、严重依赖医生经验和设备可操作性受限的限制。这篇综述提供了构成这些eirs核心的传感、控制和执行模块的全面概述。它分析了每个组件中的基本挑战，并探讨了增强系统智能和自主性的潜在策略。通过整合当前进展和前瞻性见解，该综述强调了更安全、更高效、更自主的机器人干预途径。最终目标是推进下一代机器人平台的发展，以提高手术精度，扩大患者获得高质量血管护理的机会。

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引用次数: 0

Review on manganese carbon interactions in manganese oxide-modified biochar for environmental remediation 氧化锰改性生物炭中锰碳相互作用的研究进展

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-11-13 DOI: 10.1016/j.isci.2025.113991

Anyu Li , Song Lei , Shujia Chen , Xiaotong Zhou , Zhihua Wu , Feng Jiang , Peng Zheng , Lening Hu , Hua Deng

Manganese oxide-modified biochar (MBC) has attracted much attention as a multifunctional environmental remediation material. This work systematically examines the remediation mechanisms of MBC and its applications in environmental pollution control, with a focus on its potential for adsorbing and immobilizing soil and water pollutants. We provide a detailed analysis of the relevant interfacial reaction processes, including charge interactions, surface coordination, redox reactions, and ion exchange, emphasizing their roles in pollutant remediation and degradation. In terms of environmental applications, this review summarizes the research progress on the utilization of MBC in the treatment of wastewater and contaminated soils, with a particular focus on its effectiveness in removing these pollutants. This work establishes a theoretical basis for the utilization of MBC as a highly efficient and sustainable adsorption material for environmental pollution control and provides a scientific reference for further research on its interfacial mechanisms and practical application.

氧化锰改性生物炭作为一种多功能的环境修复材料受到了广泛的关注。本工作系统地研究了MBC的修复机制及其在环境污染控制中的应用，重点是其吸附和固定土壤和水污染物的潜力。我们详细分析了相关的界面反应过程，包括电荷相互作用、表面配位、氧化还原反应和离子交换，强调了它们在污染物修复和降解中的作用。在环境应用方面，综述了MBC在废水和污染土壤处理中的研究进展，重点介绍了其去除污染物的效果。本研究为将MBC作为一种高效、可持续的吸附材料用于环境污染治理奠定了理论基础，并为进一步研究其界面机理和实际应用提供了科学参考。

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引用次数: 0

A review of organ-on-chip fabrication methods: From early developments to overcoming inert barriers 芯片上器官制造方法综述：从早期发展到克服惰性障碍

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-11-12 DOI: 10.1016/j.isci.2025.113992

Claudia Olaizola-Rodrigo , Clara Bayona , Sara Oliván , Rosa Monge

Organ-on-chip (OOC) systems represent a significant advance in the effort to replicate human physiology in vitro, providing versatile models that extend beyond the limitations of static culture and animal experimentation. The fabrication methods and materials underlying these platforms play a decisive role in determining their structural accuracy, biological relevance, and potential for large-scale adoption. This review surveys the historical progression of OOC manufacturing, beginning with established microfabrication techniques such as photolithography, soft lithography, hot embossing, microinjection molding, and xurography and extending to recent innovations in additive manufacturing. Particular attention is given to emerging barrier-free strategies, including laminar flow patterning, hydrogel photopatterning, phaseguide design, and surface treatment patterning that permit direct tissue-tissue communication. These methods aim to enhance biomimicry by reducing artificial interfaces, thereby improving the simulation of intercellular gradients, multicellular crosstalk, and pathophysiological dynamics. Alongside their benefits, the review discusses the practical challenges these approaches introduce in terms of reproducibility, throughput, and scalability. By integrating advances in materials science, fabrication techniques, and microphysiological design, this review highlights the potential of next-generation OOC devices to provide predictive, translationally relevant platforms that narrow the divide between preclinical experimentation and clinical application.

器官芯片（OOC）系统在体外复制人体生理方面取得了重大进展，提供了超越静态培养和动物实验限制的多功能模型。这些平台的制造方法和材料在决定其结构精度、生物学相关性和大规模采用的潜力方面起着决定性作用。本文回顾了OOC制造的历史进展，从已建立的微加工技术开始，如光刻、软光刻、热压印、微注射成型和光刻，并扩展到最近的增材制造创新。特别关注新兴的无障碍策略，包括层流图型，水凝胶光图型，相位引导设计和表面处理图型，允许直接组织-组织通信。这些方法旨在通过减少人工界面来增强仿生学，从而改善细胞间梯度、多细胞串扰和病理生理动力学的模拟。除了它们的优点之外，本文还讨论了这些方法在再现性、吞吐量和可伸缩性方面带来的实际挑战。通过整合材料科学、制造技术和微生理设计方面的进步，本综述强调了下一代OOC设备提供预测、翻译相关平台的潜力，从而缩小了临床前实验和临床应用之间的差距。

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引用次数: 0

Integration of efficient photothermal and flexible solid-solid PCM for personal thermoregulation in cold environments 集成高效光热和灵活的固体-固体PCM，用于寒冷环境中的个人体温调节

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-11-12 DOI: 10.1016/j.isci.2025.114032

Peijia Bai , Qiaoying Yang , Shixiong Yu

Personal thermal management (PTM) technology demonstrates extensive development prospects in the domains of energy, environment, and medicine. Nevertheless, it still suffers from drawbacks such as high costs and restricted environmental adaptability. The integration of phase change materials (PCMs) and photothermal conversion technologies holds the potential to address these issues. In this study, an efficient photothermal and flexible solid-solid phase change composite was successfully fabricated. This composite exhibits excellent processing and molding performance, and it remains free of liquid leakage at elevated temperatures. It exhibits high thermal conductivity (2.9 W m⁻¹ K⁻¹) and a high phase transition enthalpy (184 kJ/kg), and the absorptivity exceeds 90%. The phase change composite is capable of performing efficient photothermal phase change heat storage in extreme cold environments (such as at Zhongshan Station in Antarctica) and maintaining a temperature above 16°C for 8 h, thereby demonstrating significant application potential in wearable thermal management garments for personal thermoregulation.

个人热管理（PTM）技术在能源、环境、医学等领域具有广阔的发展前景。然而，它仍然存在成本高、环境适应性有限等缺点。相变材料（PCMs）和光热转换技术的集成具有解决这些问题的潜力。本研究成功制备了一种高效的光热柔性固-固相变复合材料。这种复合材料具有优异的加工和成型性能，并且在高温下保持无液体泄漏。它具有高导热系数（2.9 W m−1 K−1）和高相变焓（184 kJ/kg），吸收率超过90%。相变复合材料能够在极寒环境下（如南极中山站）进行高效光热相变储热，并保持温度在16°C以上8小时，从而在可穿戴热管理服装中显示出巨大的应用潜力，用于个人体温调节。

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引用次数: 0

Ruminal microbial dysbiosis induces mastitis in dairy goats by activating oxidative stress and ferritinophagy-ferroptosis 瘤胃微生物生态失调通过激活氧化应激和铁蛋白吞噬-铁下垂诱导奶山羊乳腺炎

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-11-12 DOI: 10.1016/j.isci.2025.114012

Yuhong He , Wei Zhang , Can Zhang , Nier Su , Zeming Zhou , Chong Peng , Chongshan Yuan , Yunhe Fu , Xiaoyu Hu , Yue Zhang

Recent studies indicate that ruminal microbiota dysbiosis plays a significant role in the development of mastitis in ruminants, though the exact mechanisms remain incompletely understood. In this study, a high-concentration (HC) diet led to subacute ruminal acidosis (SARA) in dairy goats, as evidenced by prolonged daily periods of ruminal pH below 5.8. The HC group exhibited disrupted ruminal microbiota, elevated serum levels of LPS, TNF-α, and IL-1β, and a markedly increased milk somatic cell count (SCC) exceeding 500,000/mL, indicating mastitis. Ruminal microbiota transplantation (RMT) from HC goats induced mastitis in mice, which is associated with oxidative stress and ferritinophagy-ferroptosis. The administration of ferrostatin-1 (Fer-1) alleviated mastitis in mice. Further in vitro experiments showed that LPS dose-dependently triggered oxidative stress and ferritinophagy-ferroptosis in mouse mammary epithelial cells (MMECs). Collectively, HC diet-induced ruminal dysbiosis elevates systemic and mammary LPS levels, reduces antioxidant capacity, and activates oxidative stress and ferritinophagy-ferroptosis, ultimately leading to mastitis.

最近的研究表明，瘤胃微生物群失调在反刍动物乳腺炎的发展中起着重要作用，尽管其确切机制尚不完全清楚。在本研究中，高浓度（HC）饲粮导致奶山羊亚急性瘤胃酸中毒（SARA），瘤胃pH值低于5.8的日持续时间延长。HC组瘤胃微生物群被破坏，血清LPS、TNF-α和IL-1β水平升高，乳体细胞计数（SCC）明显增加，超过50万/mL，提示乳腺炎。HC山羊瘤胃微生物群移植（RMT）诱导小鼠乳腺炎，其与氧化应激和铁蛋白吞噬-铁下垂有关。给药铁抑素-1 （fer1）可减轻小鼠乳腺炎。进一步的体外实验表明，LPS剂量依赖性地触发小鼠乳腺上皮细胞（mmec）的氧化应激和铁蛋白吞噬-铁凋亡。总之，HC饮食诱导的瘤胃生态失调会升高全身和乳腺LPS水平，降低抗氧化能力，激活氧化应激和铁蛋白吞噬-铁下垂，最终导致乳腺炎。

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