iScience最新文献_第4页

Variational adaptive Gaussian approximation filter for nonlinear systems with generalized unknown disturbances 广义未知扰动非线性系统的变分自适应高斯逼近滤波器

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-12-04 DOI: 10.1016/j.isci.2025.114331

Yuemei Qin , Jincheng Lv , Shuying Li , Yinlong Hou

This article investigates the joint estimation and identification problem of discrete-time nonlinear systems with generalized unknown disturbances (GUDs) and unknown noise covariance (UNC) in the measurement model. A variational adaptive Gaussian approximation filter (VAGAF) is proposed, in which the Gaussian approximation filter performs recursive state estimation, while the variational Bayesian inference identifies the UNC. Since the existence of GUDs makes it difficult to accurately derive the innovation covariance, it is approximated through matrix eigenvalue decomposition. The measurement noise covariance is estimated online by applying statistical linear regression (SLR) to the nonlinear measurement model, enabling the implementation of variational Bayesian inference. Based on the identified measurement noise covariance and the constructed innovation covariance, the Gaussian approximation filter recursively achieves high-precision state estimation. Target-tracking simulations demonstrate that the proposed filter attains superior estimation accuracy compared with the minimum upper-bound filter and interacting multiple model method without requiring a finely designed model set.

研究了测量模型中具有广义未知干扰（GUDs）和未知噪声协方差（UNC）的离散非线性系统的联合估计和辨识问题。提出了一种变分自适应高斯逼近滤波器（VAGAF），其中高斯逼近滤波器进行递归状态估计，变分贝叶斯推理识别UNC。由于GUDs的存在使创新协方差难以准确推导，故采用矩阵特征值分解的方法逼近创新协方差。对非线性测量模型应用统计线性回归（SLR）在线估计测量噪声协方差，实现变分贝叶斯推理。基于已识别的测量噪声协方差和构造的创新协方差，高斯逼近滤波器递归实现高精度状态估计。目标跟踪仿真表明，与最小上界滤波器和交互多模型方法相比，该滤波器在不需要精细设计模型集的情况下具有更高的估计精度。

{"title":"Variational adaptive Gaussian approximation filter for nonlinear systems with generalized unknown disturbances","authors":"Yuemei Qin , Jincheng Lv , Shuying Li , Yinlong Hou","doi":"10.1016/j.isci.2025.114331","DOIUrl":"10.1016/j.isci.2025.114331","url":null,"abstract":"<div><div>This article investigates the joint estimation and identification problem of discrete-time nonlinear systems with generalized unknown disturbances (GUDs) and unknown noise covariance (UNC) in the measurement model. A variational adaptive Gaussian approximation filter (VAGAF) is proposed, in which the Gaussian approximation filter performs recursive state estimation, while the variational Bayesian inference identifies the UNC. Since the existence of GUDs makes it difficult to accurately derive the innovation covariance, it is approximated through matrix eigenvalue decomposition. The measurement noise covariance is estimated online by applying statistical linear regression (SLR) to the nonlinear measurement model, enabling the implementation of variational Bayesian inference. Based on the identified measurement noise covariance and the constructed innovation covariance, the Gaussian approximation filter recursively achieves high-precision state estimation. Target-tracking simulations demonstrate that the proposed filter attains superior estimation accuracy compared with the minimum upper-bound filter and interacting multiple model method without requiring a finely designed model set.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114331"},"PeriodicalIF":4.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788917","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}

引用次数: 0

Meteorological and socioeconomic impacts on ozone in China: Past and future analysis 中国臭氧的气象和社会经济影响：过去和未来分析

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-12-04 DOI: 10.1016/j.isci.2025.114335

Yinchen Chen , Zunli Dai , Xiaohong Wang , Qiujing Zhang , Haoming Chen , Shiyuan Zhong , Qingheng Lu , Lejiang Yu

This study examines seasonal ozone (O₃) dynamics across China using a random forest model with partial dependence plots. Daily monitoring and ERA5 reanalysis data for 2015–2020, combined with CMIP6 projections to 2100, quantify the marginal effects of meteorology, socioeconomic factors, and O₃ precursors on O₃ changes. Warm-season O₃ peaks mainly north of 30°N, especially in North China, with surface temperature, relative humidity, and 500–850 hPa winds as dominant drivers. Cold-season patterns differ, reflecting widespread stagnation and reduced solar radiation. Scenario analyses under SSP 1–2.6, SSP 2–4.5, SSP 3–7.0, and SSP 5–8.5 reveal regionally heterogeneous trajectories, with some factors consistently elevating O₃ and others mitigating it depending on season and location. These results underscore the need for region-specific controls that integrate evolving climate and socioeconomic pathways and provide an evidence base for adaptive air-quality management and policy.

本研究采用部分相关图的随机森林模型研究了中国臭氧（O3）的季节性动态。2015-2020年的每日监测和ERA5再分析数据，结合CMIP6到2100年的预估，量化了气象、社会经济因素和O3前体对O3变化的边际效应。暖季O3峰值主要在30°N以北，以华北地区为主，地表温度、相对湿度和500 ~ 850 hPa风是主要驱动因素。寒冷季节的模式不同，反映了广泛的停滞和太阳辐射的减少。在SSP 1-2.6、SSP 2-4.5、SSP 3-7.0和SSP 5-8.5下的情景分析揭示了区域异质性的轨迹，根据季节和地点的不同，一些因素持续提高O3，而另一些因素则持续降低O3。这些结果强调需要针对特定区域的控制措施，将不断变化的气候和社会经济途径结合起来，并为适应性空气质量管理和政策提供证据基础。

{"title":"Meteorological and socioeconomic impacts on ozone in China: Past and future analysis","authors":"Yinchen Chen , Zunli Dai , Xiaohong Wang , Qiujing Zhang , Haoming Chen , Shiyuan Zhong , Qingheng Lu , Lejiang Yu","doi":"10.1016/j.isci.2025.114335","DOIUrl":"10.1016/j.isci.2025.114335","url":null,"abstract":"<div><div>This study examines seasonal ozone (O<sub>3</sub>) dynamics across China using a random forest model with partial dependence plots. Daily monitoring and ERA5 reanalysis data for 2015–2020, combined with CMIP6 projections to 2100, quantify the marginal effects of meteorology, socioeconomic factors, and O<sub>3</sub> precursors on O<sub>3</sub> changes. Warm-season O<sub>3</sub> peaks mainly north of 30°N, especially in North China, with surface temperature, relative humidity, and 500–850 hPa winds as dominant drivers. Cold-season patterns differ, reflecting widespread stagnation and reduced solar radiation. Scenario analyses under SSP 1–2.6, SSP 2–4.5, SSP 3–7.0, and SSP 5–8.5 reveal regionally heterogeneous trajectories, with some factors consistently elevating O<sub>3</sub> and others mitigating it depending on season and location. These results underscore the need for region-specific controls that integrate evolving climate and socioeconomic pathways and provide an evidence base for adaptive air-quality management and policy.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114335"},"PeriodicalIF":4.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788920","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}

引用次数: 0

Multifunctional carboxymethyl cellulose-based hydrogels with zwitterionic and silver nanowire components for wound management 多功能羧甲基纤维素为基础的水凝胶与两性离子和银纳米线成分的伤口管理

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-12-04 DOI: 10.1016/j.isci.2025.114336

Kit-Leong Cheong , Te Pan , Suresh Veeraperumal , Franck Quero , Gowsika Jaikumar , Timo Kikas , Malairaj Sathuvan , Karsoon Tan , Saiyi Zhong , Udayakumar Veerabagu

Chronic wounds represent a major global health burden, while conventional dressings often fail to meet the complex requirements of chronic wound management, including infection control, moisture balance, and tissue regeneration. In this study, two multifunctional zwitterionic hydrogels—vinylpyridine carboxybetaine/sulfobetaine/silver nanowire/carboxymethyl cellulose (VCS/Ag/CMC) and acrylamide carboxybetaine/sulfobetaine/silver nanowire/carboxymethyl cellulose (ACS/Ag/CMC) – were synthesized. Structural analyses confirmed the successful incorporation of aromatic or aliphatic zwitterionic components and uniform distribution of silver nanowires within the CMC-based hydrogel networks. Both hydrogels exhibited favorable mechanical strength, high swelling capacity, controlled degradability, and sustained silver release, providing a balanced profile for chronic wound applications. In vitro studies demonstrated potent antibacterial and antioxidant activities, while in vivo experiments revealed accelerated wound closure, enhanced re-epithelialization, collagen deposition, and neovascularization. Moreover, the hydrogels promoted macrophage polarization toward the pro-healing M2 phenotype. Collectively, these findings highlight the promise of zwitterionic hydrogels as multifunctional platforms for chronic wound management and regenerative medicine.

慢性伤口是一个主要的全球卫生负担，而传统敷料往往不能满足慢性伤口管理的复杂要求，包括感染控制、水分平衡和组织再生。本研究合成了乙烯基吡啶羧甜菜碱/亚砜甜菜碱/银纳米线/羧甲基纤维素（VCS/Ag/CMC）和丙烯酰胺羧甜菜碱/亚砜甜菜碱/银纳米线/羧甲基纤维素（ACS/Ag/CMC）两种多功能两性离子水凝胶。结构分析证实了芳香族或脂肪族两性离子组分的成功结合以及银纳米线在cmc基水凝胶网络中的均匀分布。两种水凝胶均表现出良好的机械强度、高溶胀能力、可控降解性和持续的银释放，为慢性伤口应用提供了平衡的配置文件。体外研究表明其具有强大的抗菌和抗氧化活性，而体内实验显示其加速伤口愈合、增强再上皮化、胶原沉积和新生血管。此外，水凝胶促进巨噬细胞向促愈合的M2表型极化。总的来说，这些发现突出了两性离子水凝胶作为慢性伤口管理和再生医学的多功能平台的前景。

{"title":"Multifunctional carboxymethyl cellulose-based hydrogels with zwitterionic and silver nanowire components for wound management","authors":"Kit-Leong Cheong , Te Pan , Suresh Veeraperumal , Franck Quero , Gowsika Jaikumar , Timo Kikas , Malairaj Sathuvan , Karsoon Tan , Saiyi Zhong , Udayakumar Veerabagu","doi":"10.1016/j.isci.2025.114336","DOIUrl":"10.1016/j.isci.2025.114336","url":null,"abstract":"<div><div>Chronic wounds represent a major global health burden, while conventional dressings often fail to meet the complex requirements of chronic wound management, including infection control, moisture balance, and tissue regeneration. In this study, two multifunctional zwitterionic hydrogels—vinylpyridine carboxybetaine/sulfobetaine/silver nanowire/carboxymethyl cellulose (VCS/Ag/CMC) and acrylamide carboxybetaine/sulfobetaine/silver nanowire/carboxymethyl cellulose (ACS/Ag/CMC) – were synthesized. Structural analyses confirmed the successful incorporation of aromatic or aliphatic zwitterionic components and uniform distribution of silver nanowires within the CMC-based hydrogel networks. Both hydrogels exhibited favorable mechanical strength, high swelling capacity, controlled degradability, and sustained silver release, providing a balanced profile for chronic wound applications. <em>In vitro</em> studies demonstrated potent antibacterial and antioxidant activities, while <em>in vivo</em> experiments revealed accelerated wound closure, enhanced re-epithelialization, collagen deposition, and neovascularization. Moreover, the hydrogels promoted macrophage polarization toward the pro-healing M2 phenotype. Collectively, these findings highlight the promise of zwitterionic hydrogels as multifunctional platforms for chronic wound management and regenerative medicine.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114336"},"PeriodicalIF":4.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788832","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}

引用次数: 0

Novel adenovirus vaccine vectors lacking thrombosis-associated interactions with platelet factor 4 缺乏血小板因子4与血栓形成相关相互作用的新型腺病毒疫苗载体

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-12-04 DOI: 10.1016/j.isci.2025.114329

Erwan Sallard , Daniel Pembaur , Matias Ciancaglini , Lucie Manov-Bouard , Denice Weklak , Firas Hamdan , Chun Kit Chan , Franziska Jönsson , Elise Chabot , Carmen Musielak , Elena Scurti , Sara Feola , Sebastian Schellhorn , Nissai Beaude , Katrin Schröer , Daipayan Sarkar , Georgia Koukou , Xiaoyan Wang , Natascha Schmidt , Wibke Bayer , Anja Ehrhardt

The adenoviral vector-based AstraZeneca and Janssen COVID-19 vaccines have been associated with rare cases of thrombosis, believed to be triggered, among other factors, by vector binding to the blood protein platelet factor 4 (PF4). To identify vectors with lower thrombosis risk, we screened 50 natural and hexon-modified adenoviruses (Ads). Unlike the applied COVID-19 vaccines and most tested vectors, Ad34 and Ad80, as well as Ad5 vectors with deleted or chemically shielded hexon hyper-variable region 1 (HVR1), did not bind to PF4. Furthermore, interactions with PF4 substantially modified Ad5 infectivity in various immortalized and primary cells, suggesting that PF4 may influence existing vector tropism. Finally, HVR1-deleted Ad5 and Ad34 vectors expressing SARS-CoV-2 spike S1 domain were tested as vaccine candidates in mice and induced robust cellular immune responses. Therefore, the identified PF4 non-binding vectors may represent safe and efficient candidates for clinical applications.

基于腺病毒载体的阿斯利康和杨森COVID-19疫苗与罕见的血栓形成病例有关，据信，除其他因素外，由载体与血液蛋白血小板因子4 （PF4）结合引发。为了确定血栓形成风险较低的载体，我们筛选了50种天然和六元修饰腺病毒（Ads）。与应用的COVID-19疫苗和大多数测试的载体不同，Ad34和Ad80以及删除或化学屏蔽六元高变区1 （HVR1）的Ad5载体不与PF4结合。此外，与PF4的相互作用大大改变了Ad5在各种永生化细胞和原代细胞中的感染性，表明PF4可能影响现有载体的向性。最后，hvr1缺失表达SARS-CoV-2刺突S1结构域的Ad5和Ad34载体作为候选疫苗在小鼠体内进行了测试，并诱导了强大的细胞免疫反应。因此，鉴定的PF4非结合载体可能是安全有效的临床应用候选载体。

{"title":"Novel adenovirus vaccine vectors lacking thrombosis-associated interactions with platelet factor 4","authors":"Erwan Sallard , Daniel Pembaur , Matias Ciancaglini , Lucie Manov-Bouard , Denice Weklak , Firas Hamdan , Chun Kit Chan , Franziska Jönsson , Elise Chabot , Carmen Musielak , Elena Scurti , Sara Feola , Sebastian Schellhorn , Nissai Beaude , Katrin Schröer , Daipayan Sarkar , Georgia Koukou , Xiaoyan Wang , Natascha Schmidt , Wibke Bayer , Anja Ehrhardt","doi":"10.1016/j.isci.2025.114329","DOIUrl":"10.1016/j.isci.2025.114329","url":null,"abstract":"<div><div>The adenoviral vector-based AstraZeneca and Janssen COVID-19 vaccines have been associated with rare cases of thrombosis, believed to be triggered, among other factors, by vector binding to the blood protein platelet factor 4 (PF4). To identify vectors with lower thrombosis risk, we screened 50 natural and hexon-modified adenoviruses (Ads). Unlike the applied COVID-19 vaccines and most tested vectors, Ad34 and Ad80, as well as Ad5 vectors with deleted or chemically shielded hexon hyper-variable region 1 (HVR1), did not bind to PF4. Furthermore, interactions with PF4 substantially modified Ad5 infectivity in various immortalized and primary cells, suggesting that PF4 may influence existing vector tropism. Finally, HVR1-deleted Ad5 and Ad34 vectors expressing SARS-CoV-2 spike S1 domain were tested as vaccine candidates in mice and induced robust cellular immune responses. Therefore, the identified PF4 non-binding vectors may represent safe and efficient candidates for clinical applications.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114329"},"PeriodicalIF":4.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788922","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}

引用次数: 0

Decoding IFN-mediated immunity and cell dynamics in viral encephalitis: Insights from coxsackievirus B3 infection 解码干扰素介导的免疫和细胞动力学在病毒性脑炎：从柯萨奇病毒B3感染的见解

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-12-03 DOI: 10.1016/j.isci.2025.114324

Lisa Marie Stach , Lisa Gerarda Maria Huis in ‘t Veld , Theres Schaub , Marina Jendrach , Marta Ornaghi , Marius Schwabenland , Antje Beling , Sandra Pinkert

This study presents an in vivo model of coxsackievirus B3 infection in the brain to examine interferon (IFN) responses and effects on tissue-resident immune cells. Primary cell culture studies revealed that neurons exhibited substantial viral replication with a limited IFN response, whereas microglia, which showed no viral replication, displayed strong immune activation. In vivo analysis captured IFN responses and immune cell dynamics across both acute and chronic inflammation phases. During the acute stage, IFN responses intensified in a dose-dependent manner, with upregulated IFN-stimulated genes (ISGs), increased ISGylation, and microglial activation. Chemokine release coincided with the infiltration of monocytes and T cells in the injured brain. In the chronic phase, viral RNA was undetectable, yet flow cytometry showed persistent T cell presence and low-level microglial activation, indicating ongoing inflammation. This model provides a valuable platform for investigating IFN responses and immune cell interactions in central nervous system (CNS) viral infections and neuroinflammatory conditions.

本研究提出了柯萨奇B3病毒在脑内感染的体内模型，以检查干扰素（IFN）的反应和对组织驻留免疫细胞的影响。原代细胞培养研究表明，神经元表现出大量的病毒复制和有限的IFN反应，而小胶质细胞没有病毒复制，却表现出强烈的免疫激活。体内分析捕获了急性和慢性炎症阶段的IFN反应和免疫细胞动力学。在急性期，IFN反应以剂量依赖的方式增强，IFN刺激基因（ISGs）上调，isg酰化增加，小胶质细胞活化。趋化因子的释放与损伤脑中单核细胞和T细胞的浸润一致。在慢性期，无法检测到病毒RNA，但流式细胞术显示持续的T细胞存在和低水平的小胶质细胞激活，表明持续的炎症。该模型为研究中枢神经系统（CNS）病毒感染和神经炎症条件下IFN反应和免疫细胞相互作用提供了一个有价值的平台。

{"title":"Decoding IFN-mediated immunity and cell dynamics in viral encephalitis: Insights from coxsackievirus B3 infection","authors":"Lisa Marie Stach , Lisa Gerarda Maria Huis in ‘t Veld , Theres Schaub , Marina Jendrach , Marta Ornaghi , Marius Schwabenland , Antje Beling , Sandra Pinkert","doi":"10.1016/j.isci.2025.114324","DOIUrl":"10.1016/j.isci.2025.114324","url":null,"abstract":"<div><div>This study presents an <em>in vivo</em> model of coxsackievirus B3 infection in the brain to examine interferon (IFN) responses and effects on tissue-resident immune cells. Primary cell culture studies revealed that neurons exhibited substantial viral replication with a limited IFN response, whereas microglia, which showed no viral replication, displayed strong immune activation. <em>In vivo</em> analysis captured IFN responses and immune cell dynamics across both acute and chronic inflammation phases. During the acute stage, IFN responses intensified in a dose-dependent manner, with upregulated IFN-stimulated genes (ISGs), increased ISGylation, and microglial activation. Chemokine release coincided with the infiltration of monocytes and T cells in the injured brain. In the chronic phase, viral RNA was undetectable, yet flow cytometry showed persistent T cell presence and low-level microglial activation, indicating ongoing inflammation. This model provides a valuable platform for investigating IFN responses and immune cell interactions in central nervous system (CNS) viral infections and neuroinflammatory conditions.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114324"},"PeriodicalIF":4.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788758","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}

引用次数: 0

Tropism, replication competence, and cellular responses of HAdV-14p1 in human airway organoids HAdV-14p1在人气道类器官中的趋向性、复制能力和细胞反应

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-12-03 DOI: 10.1016/j.isci.2025.114323

Wenyu Guo , Yihao Yang , Ying Liang , Fei Cui , Lianzhong Li , Xuechun Peng , Jing Zhou , Ya Li , Yuezhi Deng , Yixuan Wang , Rong Chen , Tao Wen , Cheng Lin , Weihong Lin , Lidong Liu , Yongping Lin , Qigao Chen

Human adenovirus type 14p1 (HAdV-14p1) is associated with severe respiratory illness. Using human airway organoids, we characterized the cellular tropism, infection dynamics, and cellular response to HAdV-14p1, and evaluated the antiviral efficacy of cidofovir. HAdV-14p1 robustly infected and replicated in human airway organoids, particularly targeting ciliated, basal, and goblet cells. CCL5, CXCL10, CXCL11, and TNFSF13B were significantly upregulated upon HAdV-14p1 infection, indicating inflammatory activation. Pathway enrichment analysis revealed that upregulated genes were enriched in p53 signaling, cytokine-cytokine receptor interaction, and NOD-like receptor signaling pathways, whereas downregulated genes were linked to focal adhesion, tight junction, metabolic pathways, and oxidative phosphorylation pathways. Furthermore, treatment with cidofovir effectively inhibited viral replication with low cytotoxicity. Our findings highlight the robust replication and proinflammatory response that shape HAdV-14p1 pathogenesis and underscore the value of organoid systems in probing virus-host interactions and evaluating candidate antiviral strategies.

人类腺病毒14p1型（HAdV-14p1）与严重呼吸道疾病相关。利用人气道类器官，研究了HAdV-14p1的细胞趋向性、感染动力学和细胞反应，并评估了西多福韦的抗病毒效果。HAdV-14p1在人气道类器官中强烈感染和复制，特别是针对纤毛细胞、基底细胞和杯状细胞。CCL5、CXCL10、CXCL11和TNFSF13B在HAdV-14p1感染后显著上调，表明炎症激活。通路富集分析显示，上调基因富集于p53信号通路、细胞因子-细胞因子受体相互作用通路和nod样受体信号通路，而下调基因则与局灶黏附、紧密连接、代谢通路和氧化磷酸化通路相关。此外，西多福韦治疗有效地抑制病毒复制，具有低细胞毒性。我们的研究结果强调了HAdV-14p1致病机制的强大复制和促炎反应，并强调了类器官系统在探测病毒-宿主相互作用和评估候选抗病毒策略方面的价值。

{"title":"Tropism, replication competence, and cellular responses of HAdV-14p1 in human airway organoids","authors":"Wenyu Guo , Yihao Yang , Ying Liang , Fei Cui , Lianzhong Li , Xuechun Peng , Jing Zhou , Ya Li , Yuezhi Deng , Yixuan Wang , Rong Chen , Tao Wen , Cheng Lin , Weihong Lin , Lidong Liu , Yongping Lin , Qigao Chen","doi":"10.1016/j.isci.2025.114323","DOIUrl":"10.1016/j.isci.2025.114323","url":null,"abstract":"<div><div>Human adenovirus type 14p1 (HAdV-14p1) is associated with severe respiratory illness. Using human airway organoids, we characterized the cellular tropism, infection dynamics, and cellular response to HAdV-14p1, and evaluated the antiviral efficacy of cidofovir. HAdV-14p1 robustly infected and replicated in human airway organoids, particularly targeting ciliated, basal, and goblet cells. CCL5, CXCL10, CXCL11, and TNFSF13B were significantly upregulated upon HAdV-14p1 infection, indicating inflammatory activation. Pathway enrichment analysis revealed that upregulated genes were enriched in p53 signaling, cytokine-cytokine receptor interaction, and NOD-like receptor signaling pathways, whereas downregulated genes were linked to focal adhesion, tight junction, metabolic pathways, and oxidative phosphorylation pathways. Furthermore, treatment with cidofovir effectively inhibited viral replication with low cytotoxicity. Our findings highlight the robust replication and proinflammatory response that shape HAdV-14p1 pathogenesis and underscore the value of organoid systems in probing virus-host interactions and evaluating candidate antiviral strategies.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114323"},"PeriodicalIF":4.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788916","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}

引用次数: 0

Non-invasive detection of bone marrow fibrosis in myeloproliferative neoplasms using cell-free RNA 无细胞RNA无创检测骨髓增生性肿瘤骨髓纤维化

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-12-03 DOI: 10.1016/j.isci.2025.114325

Mohamed Saad , Stijn N.R. Fuchs , Carmen Schalla , Katrin Götz , Jessica E. Pritchard , Niclas Flosdorf , Adam Benabid , Hélène F.E. Gleitz , Nils Leimkühler , Aurélien Dugourd , Rebekka K. Schneider

Myeloproliferative neoplasms (MPNs), particularly with myelofibrosis (MF), involve a disrupted perivascular hematopoietic niche, ultimately leading to bone marrow fibrosis. We asked if the transcriptome in cell-free RNA (cf-RNA) from the peripheral blood of patients with MPN (with JAK2V617F mutation) can detect bone marrow fibrosis. Transcriptomic profiling revealed significant gene expression changes correlating with reticulin fibrosis grades. Advanced reticulin fibrosis grades (2–3) showed upregulation of TGF-β pathways and extracellular matrix (ECM) remodeling markers, with decreased hematopoietic support. Grade 3 fibrosis was associated with increased proliferation signals and elevated inflammatory markers (S100A8/9). RUNX1 was identified as a key transcription factor in fibrosis, with its overexpression driving myofibroblast differentiation in mesenchymal stromal cells. IL-18 emerged as a critical inflammatory mediator, with elevated plasma levels correlating with the transformation to high-grade fibrosis (reticulin grades 2–3). Functional assays confirmed that the IL-18 stimulation of mesenchymal stromal cells induced fibrotic transformation, emphasizing its role as a biomarker and target.

骨髓增生性肿瘤（mpn），特别是骨髓纤维化（MF），涉及血管周围造血生态位的破坏，最终导致骨髓纤维化。我们询问来自MPN （JAK2V617F突变）患者外周血的无细胞RNA （cf-RNA）中的转录组是否可以检测骨髓纤维化。转录组学分析显示与网状蛋白纤维化等级相关的显著基因表达变化。晚期网状蛋白纤维化等级（2-3）显示TGF-β通路和细胞外基质（ECM）重塑标志物上调，造血支持减少。3级纤维化与增殖信号增加和炎症标志物升高相关（S100A8/9）。RUNX1被确定为纤维化的关键转录因子，其过表达驱动间充质基质细胞的肌成纤维细胞分化。IL-18是一种关键的炎症介质，血浆中IL-18水平升高与向高级别纤维化（网状蛋白2-3级）的转变相关。功能分析证实IL-18刺激间充质间质细胞诱导纤维化转化，强调其作为生物标志物和靶点的作用。

{"title":"Non-invasive detection of bone marrow fibrosis in myeloproliferative neoplasms using cell-free RNA","authors":"Mohamed Saad , Stijn N.R. Fuchs , Carmen Schalla , Katrin Götz , Jessica E. Pritchard , Niclas Flosdorf , Adam Benabid , Hélène F.E. Gleitz , Nils Leimkühler , Aurélien Dugourd , Rebekka K. Schneider","doi":"10.1016/j.isci.2025.114325","DOIUrl":"10.1016/j.isci.2025.114325","url":null,"abstract":"<div><div>Myeloproliferative neoplasms (MPNs), particularly with myelofibrosis (MF), involve a disrupted perivascular hematopoietic niche, ultimately leading to bone marrow fibrosis. We asked if the transcriptome in cell-free RNA (cf-RNA) from the peripheral blood of patients with MPN (with JAK2V617F mutation) can detect bone marrow fibrosis. Transcriptomic profiling revealed significant gene expression changes correlating with reticulin fibrosis grades. Advanced reticulin fibrosis grades (2–3) showed upregulation of TGF-β pathways and extracellular matrix (ECM) remodeling markers, with decreased hematopoietic support. Grade 3 fibrosis was associated with increased proliferation signals and elevated inflammatory markers (S100A8/9). RUNX1 was identified as a key transcription factor in fibrosis, with its overexpression driving myofibroblast differentiation in mesenchymal stromal cells. IL-18 emerged as a critical inflammatory mediator, with elevated plasma levels correlating with the transformation to high-grade fibrosis (reticulin grades 2–3). Functional assays confirmed that the IL-18 stimulation of mesenchymal stromal cells induced fibrotic transformation, emphasizing its role as a biomarker and target.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114325"},"PeriodicalIF":4.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788913","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}

引用次数: 0

ABCA1 acts as a protective modulator in amyotrophic lateral sclerosis ABCA1在肌萎缩性侧索硬化症中起保护性调节作用

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-12-03 DOI: 10.1016/j.isci.2025.114320

Qiang Li , Ge Zhang , Honglin Zheng , Taiqi Zhao , Hang Zhang , Yaochong Zhang , Haiyang Luo , Yuming Xu

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease lacking reliable biomarkers and effective therapeutic targets. We performed an integrative multiscale analysis combining global epidemiology, whole-blood transcriptomics, machine learning, and Mendelian randomization (MR). We developed a nine-gene diagnostic signature (AUC = 0.75 in external validation) and identified ATP-binding cassette transporter A1 (ABCA1) as a central feature. MR analyses supported a protective causal relationship between increased ABCA1 expression and reduced ALS risk (OR = 0.93, p = 0.02). We validated this at the protein level, finding serum ABCA1 significantly elevated in an in-house ALS cohort (p = 0.006) and correlated with metabolic parameters (BMI and LDL). Spatiotemporal profiling confirmed ABCA1 upregulation in ALS patient blood and spinal cords, and progressive upregulation in ALS model mice. Collectively, we validated a diagnostic signature and identified ABCA1 as a protective, compensatory biomarker in ALS, emphasizing the link between metabolic adaptation and neurodegeneration.

肌萎缩侧索硬化症（ALS）是一种进行性运动神经元疾病，缺乏可靠的生物标志物和有效的治疗靶点。我们结合全球流行病学、全血转录组学、机器学习和孟德尔随机化（MR）进行了综合多尺度分析。我们开发了一个9个基因的诊断特征（外部验证的AUC = 0.75），并确定了atp结合盒转运蛋白A1 （ABCA1）为中心特征。MR分析支持ABCA1表达增加与ALS风险降低之间的保护性因果关系（OR = 0.93, p = 0.02）。我们在蛋白质水平上验证了这一点，发现血清ABCA1在内部ALS队列中显著升高（p = 0.006），并与代谢参数（BMI和LDL）相关。时空分析证实ABCA1在ALS患者血液和脊髓中上调，并在ALS模型小鼠中进行性上调。总的来说，我们验证了一个诊断特征，并确定ABCA1在ALS中是一个保护性的代偿性生物标志物，强调了代谢适应和神经变性之间的联系。

{"title":"ABCA1 acts as a protective modulator in amyotrophic lateral sclerosis","authors":"Qiang Li , Ge Zhang , Honglin Zheng , Taiqi Zhao , Hang Zhang , Yaochong Zhang , Haiyang Luo , Yuming Xu","doi":"10.1016/j.isci.2025.114320","DOIUrl":"10.1016/j.isci.2025.114320","url":null,"abstract":"<div><div>Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease lacking reliable biomarkers and effective therapeutic targets. We performed an integrative multiscale analysis combining global epidemiology, whole-blood transcriptomics, machine learning, and Mendelian randomization (MR). We developed a nine-gene diagnostic signature (AUC = 0.75 in external validation) and identified ATP-binding cassette transporter A1 (<em>ABCA1</em>) as a central feature. MR analyses supported a protective causal relationship between increased ABCA1 expression and reduced ALS risk (OR = 0.93, <em>p</em> = 0.02). We validated this at the protein level, finding serum ABCA1 significantly elevated in an in-house ALS cohort (<em>p</em> = 0.006) and correlated with metabolic parameters (BMI and LDL). Spatiotemporal profiling confirmed ABCA1 upregulation in ALS patient blood and spinal cords, and progressive upregulation in ALS model mice. Collectively, we validated a diagnostic signature and identified ABCA1 as a protective, compensatory biomarker in ALS, emphasizing the link between metabolic adaptation and neurodegeneration.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114320"},"PeriodicalIF":4.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788764","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}

引用次数: 0

Prognostic value of BTG1 for predicting decitabine sensitivity in de novo acute myeloid leukemia BTG1对新发急性髓性白血病地西他滨敏感性的预测价值

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-12-03 DOI: 10.1016/j.isci.2025.114327

Shiyuan Zhang , Mengyuan Li , Bin Xu , Xiaojian Zhu , Xia Mao , Hao Zhou , Xiwen Tong , Shuai Su , Yi Zhu , Donghua Zhang

Decitabine has demonstrated efficacy in the treatment of acute myeloid leukemia (AML), though therapeutic responses vary widely due to the disease’s inherent heterogeneity. To address this clinical challenge, we aimed to identify reliable biomarkers for predicting decitabine responsiveness in patients with AML. In our previous studies, integrated epigenetic and transcriptomic profiling identified BTG1 as a methylation-associated tumor suppressor gene correlated with decitabine sensitivity. We found that decitabine upregulates BTG1 expression through demethylation, and this upregulation enhances the sensitivity of AML cells to decitabine. BTG1 may exert its effect through the Wnt/β-catenin signaling pathway. Notably, BTG1 expression levels were significantly associated with treatment outcomes, including complete remission (CR) rates and measurable residual disease (MRD) negativity in patients receiving decitabine-containing regimens (either “7 + 3” or alternative combinations). Importantly, peripheral blood BTG1 mRNA expression levels reliably predicted therapeutic response to decitabine, establishing BTG1 as a robust biomarker of decitabine efficacy in AML management.

Clinical trial registration: ChiCTR2000037928.

地西他滨在治疗急性髓性白血病（AML）中已被证明有效，尽管由于该疾病固有的异质性，治疗反应差异很大。为了应对这一临床挑战，我们旨在确定可靠的生物标志物来预测AML患者地西他滨的反应性。在我们之前的研究中，综合表观遗传学和转录组学分析发现BTG1是与地西他滨敏感性相关的甲基化相关肿瘤抑制基因。我们发现地西他滨通过去甲基化上调BTG1的表达，这种上调增强了AML细胞对地西他滨的敏感性。BTG1可能通过Wnt/β-catenin信号通路发挥作用。值得注意的是，BTG1表达水平与治疗结果显著相关，包括接受含地西他滨方案（“7 + 3”或替代组合）的患者的完全缓解（CR）率和可测量的残留疾病（MRD）阴性。重要的是，外周血BTG1 mRNA表达水平可靠地预测了地西他滨的治疗反应，确立了BTG1作为地西他滨治疗AML疗效的强有力的生物标志物。临床试验注册：ChiCTR2000037928。

{"title":"Prognostic value of BTG1 for predicting decitabine sensitivity in de novo acute myeloid leukemia","authors":"Shiyuan Zhang , Mengyuan Li , Bin Xu , Xiaojian Zhu , Xia Mao , Hao Zhou , Xiwen Tong , Shuai Su , Yi Zhu , Donghua Zhang","doi":"10.1016/j.isci.2025.114327","DOIUrl":"10.1016/j.isci.2025.114327","url":null,"abstract":"<div><div>Decitabine has demonstrated efficacy in the treatment of acute myeloid leukemia (AML), though therapeutic responses vary widely due to the disease’s inherent heterogeneity. To address this clinical challenge, we aimed to identify reliable biomarkers for predicting decitabine responsiveness in patients with AML. In our previous studies, integrated epigenetic and transcriptomic profiling identified BTG1 as a methylation-associated tumor suppressor gene correlated with decitabine sensitivity. We found that decitabine upregulates BTG1 expression through demethylation, and this upregulation enhances the sensitivity of AML cells to decitabine. BTG1 may exert its effect through the Wnt/β-catenin signaling pathway. Notably, BTG1 expression levels were significantly associated with treatment outcomes, including complete remission (CR) rates and measurable residual disease (MRD) negativity in patients receiving decitabine-containing regimens (either “7 + 3” or alternative combinations). Importantly, peripheral blood BTG1 mRNA expression levels reliably predicted therapeutic response to decitabine, establishing BTG1 as a robust biomarker of decitabine efficacy in AML management.</div><div>Clinical trial registration: ChiCTR2000037928.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114327"},"PeriodicalIF":4.1,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788754","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}

引用次数: 0

Chronic hepatitis b coinfection and survival in pediatric T-ALL: A propensity-matched analysis 慢性乙型肝炎合并感染和儿童T-ALL的生存：倾向匹配分析

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience

Pub Date : 2025-12-03 DOI: 10.1016/j.isci.2025.114319

Yutong Zhang , Ruihong Wu , Yuan Zhang , Yufei Zhao , Xiaodan Zhong , Xianmei Jin , Chao Zhang , Jian Chang

In this retrospective study of 251 pediatric patients with T cell acute lymphoblastic leukemia (T-ALL), chronic hepatitis B virus (HBV) infection with acute exacerbation (CHB-AE) was associated with significantly poorer outcomes. Compared to patients with HBV-negative, the CHB-AE cohort had markedly inferior 5-year event-free survival (13.24% vs. 80.58%) and overall survival. After using propensity score matching to balance baseline characteristics, the difference in event-free survival remained significant. Subgroup analyses consistently showed worse outcomes for patients with CHB-AE, particularly those with high-risk features such as elevated leukocyte counts or central nervous system involvement. The study identifies HBV coinfection as an independent adverse prognostic factor in pediatric T-ALL. These findings highlight the urgent need for prospective studies to investigate the underlying mechanisms and to develop novel therapeutic strategies for this high-risk patient subgroup.

在这项对251名儿童T细胞急性淋巴细胞白血病（T- all）患者的回顾性研究中，慢性乙型肝炎病毒（HBV）感染急性加重（CHB-AE）与预后明显较差相关。与hbv阴性患者相比，CHB-AE队列的5年无事件生存率（13.24%比80.58%）和总生存率明显低于hbv阴性患者。在使用倾向评分匹配来平衡基线特征后，无事件生存率的差异仍然显著。亚组分析一致显示CHB-AE患者的预后较差，特别是那些具有白细胞计数升高或中枢神经系统受累等高危特征的患者。该研究确定HBV合并感染是儿童T-ALL的独立不良预后因素。这些发现强调了迫切需要前瞻性研究来调查潜在的机制，并为这一高危患者亚群开发新的治疗策略。

引用次数: 0