Pub Date : 2026-01-03DOI: 10.1016/j.isci.2025.114622
Julia Arias-Martorell , Georgina Raventós-Izard , Oriol Monclús-Gonzalo , Alessandro Urciuoli , Jesús Gamarra , Masato Nakatsukasa , Salvador Moyà-Solà , David M. Alba
The 11.6. Ma pliopithecoid Pliobates was initially misinterpreted as a stem hominoid owing to multiple apelike postcranial features. Using 3D geometric morphometrics, we compare its radial shape with that of extant and extinct catarrhines to make locomotor inferences. The round and beveled radial head of Pliobates resembles that of modern apes, which we interpret as functionally related to efficient forearm rotation. This contrasts with its more plesiomorphic distal radius and proximal ulna, suggesting that Pliobates was more adapted for climbing than forelimb-dominated suspension and unable to perform gibbon-like ricochetal brachiation. Our results illustrate the mosaic and stepwise evolution of the catarrhine elbow and support the view that an apelike proximal radial morphology evolved multiple times as a climbing rather than suspensory adaptation. This agrees with the possibility that several features of the hominoid elbow were originally selected for climbing and subsequently co-opted for suspensory locomotion.
{"title":"Ape-like locomotor adaptations in the radius of the stem catarrhine Pliobates shed light on hominoid evolution","authors":"Julia Arias-Martorell , Georgina Raventós-Izard , Oriol Monclús-Gonzalo , Alessandro Urciuoli , Jesús Gamarra , Masato Nakatsukasa , Salvador Moyà-Solà , David M. Alba","doi":"10.1016/j.isci.2025.114622","DOIUrl":"10.1016/j.isci.2025.114622","url":null,"abstract":"<div><div>The 11.6. Ma pliopithecoid <em>Pliobates</em> was initially misinterpreted as a stem hominoid owing to multiple apelike postcranial features. Using 3D geometric morphometrics, we compare its radial shape with that of extant and extinct catarrhines to make locomotor inferences. The round and beveled radial head of <em>Pliobates</em> resembles that of modern apes, which we interpret as functionally related to efficient forearm rotation. This contrasts with its more plesiomorphic distal radius and proximal ulna, suggesting that <em>Pliobates</em> was more adapted for climbing than forelimb-dominated suspension and unable to perform gibbon-like ricochetal brachiation. Our results illustrate the mosaic and stepwise evolution of the catarrhine elbow and support the view that an apelike proximal radial morphology evolved multiple times as a climbing rather than suspensory adaptation. This agrees with the possibility that several features of the hominoid elbow were originally selected for climbing and subsequently co-opted for suspensory locomotion.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114622"},"PeriodicalIF":4.1,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035873","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}
Pub Date : 2026-01-03DOI: 10.1016/j.isci.2026.114626
Alaa Kamal Yousif Dafhalla , Tahani Abdalla Attia Gasmalla , Ameni Filali , Nada Mohamed Osman Sid Ahmed , Tijjani Adam , Mohamed Elshaikh Elobaid , Subash Chandra Bose Gopinath
This review examines the emerging integration of nanosensor networks with modern information and communication technologies to address critical needs in healthcare, environmental monitoring, and smart infrastructure. It evaluates how machine learning and artificial intelligence techniques improve data processing, energy management, real-time communication, and scalable system coordination within nanosensor environments. The analysis compares major learning approaches, including supervised, unsupervised, reinforcement, and deep learning methods, and highlights their effectiveness in data routing, anomaly detection, security, and predictive maintenance. The review also assesses new system architectures based on edge computing, cloud federated models, and intelligent communication protocols, focusing on performance indicators such as latency, throughput, and energy efficiency. Key challenges involving computational load, data privacy, and system interoperability are identified, and potential solutions inspired by biological systems, interpretable models, and quantum-based learning are explored. Overall, this work provides a unified framework for advancing intelligent and resource-efficient nanosensor communication systems with broad societal impact.
{"title":"AI-driven routing and layered architectures for intelligent ICT in nanosensor networked systems","authors":"Alaa Kamal Yousif Dafhalla , Tahani Abdalla Attia Gasmalla , Ameni Filali , Nada Mohamed Osman Sid Ahmed , Tijjani Adam , Mohamed Elshaikh Elobaid , Subash Chandra Bose Gopinath","doi":"10.1016/j.isci.2026.114626","DOIUrl":"10.1016/j.isci.2026.114626","url":null,"abstract":"<div><div>This review examines the emerging integration of nanosensor networks with modern information and communication technologies to address critical needs in healthcare, environmental monitoring, and smart infrastructure. It evaluates how machine learning and artificial intelligence techniques improve data processing, energy management, real-time communication, and scalable system coordination within nanosensor environments. The analysis compares major learning approaches, including supervised, unsupervised, reinforcement, and deep learning methods, and highlights their effectiveness in data routing, anomaly detection, security, and predictive maintenance. The review also assesses new system architectures based on edge computing, cloud federated models, and intelligent communication protocols, focusing on performance indicators such as latency, throughput, and energy efficiency. Key challenges involving computational load, data privacy, and system interoperability are identified, and potential solutions inspired by biological systems, interpretable models, and quantum-based learning are explored. Overall, this work provides a unified framework for advancing intelligent and resource-efficient nanosensor communication systems with broad societal impact.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114626"},"PeriodicalIF":4.1,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035683","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}
Pub Date : 2026-01-02DOI: 10.1016/j.isci.2025.114604
Taruna Likhariya , Pragnesh N. Dave
A LaMn0.4Fe0.6O3/rGO (6:1) perovskite composite was developed to enhance the thermal decomposition of ammonium perchlorate (AP). Optimization using DSC showed that the composite converts AP’s typical two-step decomposition into a single step and reduces the decomposition peak temperature from 351°C to 320°C at loadings of 1–5%. Structural analyses (IR, UV-Vis, XRD, and Raman) confirmed successful material formation, while FE-SEM showed uniformly distributed perovskite nanoparticles on reduced graphene oxide (rGO). BET measurements indicated a high surface area of 47.3 m2/g. An artificial neural network (ANN) model effectively predicted activation energy (MSE 0.0001–0.0017) and TG curves (MSE 0.01–0.37).
{"title":"Preparation of LaMn0.4Fe0.6O3/rGO composite catalyst for the thermolysis of ammonium perchlorate","authors":"Taruna Likhariya , Pragnesh N. Dave","doi":"10.1016/j.isci.2025.114604","DOIUrl":"10.1016/j.isci.2025.114604","url":null,"abstract":"<div><div>A LaMn<sub>0.4</sub>Fe<sub>0.6</sub>O<sub>3</sub>/rGO (6:1) perovskite composite was developed to enhance the thermal decomposition of ammonium perchlorate (AP). Optimization using DSC showed that the composite converts AP’s typical two-step decomposition into a single step and reduces the decomposition peak temperature from 351°C to 320°C at loadings of 1–5%. Structural analyses (IR, UV-Vis, XRD, and Raman) confirmed successful material formation, while FE-SEM showed uniformly distributed perovskite nanoparticles on reduced graphene oxide (rGO). BET measurements indicated a high surface area of 47.3 m<sup>2</sup>/g. An artificial neural network (ANN) model effectively predicted activation energy (MSE 0.0001–0.0017) and TG curves (MSE 0.01–0.37).</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114604"},"PeriodicalIF":4.1,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074773","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}
Pub Date : 2026-01-02DOI: 10.1016/j.isci.2025.114620
Yong Lyu , Yunhai Jia , Weihao Wan , Xiaofen Zhang , Liang Sheng , Haizhou Wang
To address the urgent need for inclusion analysis in clean steel production, this study develops an automated detection system for large metallic samples. Integrating a high-precision CNC stage, multi-unit microscopic imaging, laser spectroscopy, and a YOLOv11-based deep learning model, the system enables full-area rapid scanning of meter-scale samples. It automatically identifies and classifies inclusions (types A–D) with significantly improved efficiency—over 20 times faster than conventional methods. Experimental validation on automotive sheet samples successfully characterized 533,041 inclusions in size, distribution, and composition, while directly locating the largest inclusions, overcoming the limitations of small-area extrapolation.
{"title":"Development and application of an instrument for microstructure matrix inclusion distribution analysis in oversized metallic materials","authors":"Yong Lyu , Yunhai Jia , Weihao Wan , Xiaofen Zhang , Liang Sheng , Haizhou Wang","doi":"10.1016/j.isci.2025.114620","DOIUrl":"10.1016/j.isci.2025.114620","url":null,"abstract":"<div><div>To address the urgent need for inclusion analysis in clean steel production, this study develops an automated detection system for large metallic samples. Integrating a high-precision CNC stage, multi-unit microscopic imaging, laser spectroscopy, and a YOLOv11-based deep learning model, the system enables full-area rapid scanning of meter-scale samples. It automatically identifies and classifies inclusions (types A–D) with significantly improved efficiency—over 20 times faster than conventional methods. Experimental validation on automotive sheet samples successfully characterized 533,041 inclusions in size, distribution, and composition, while directly locating the largest inclusions, overcoming the limitations of small-area extrapolation.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114620"},"PeriodicalIF":4.1,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035793","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}
The interrelationships among Acari groups, Acariformes (mites) and Parasitiformes (ticks and parasitic mites) have been debated for long. We interrogated 90 genomes of Arachnida through a customized Chelicerata-wide ultraconserved elements bait set to resolve higher-level relationships of these two orders, including the first genome of Opilioacaridae, the putative sister group to the remaining Parasitiformes. Datasets with variable locus occupancy thresholds and partitioning schemes supported the monophyly of Acariformes and Parasitiformes, including their major subgroups. Exploration for rare genomic changes as potential character systems was done using a custom 27 Acari-specific ancestral linkage group (AcarLGs). AcarLGs revealed distinct chromosomal fusion patterns within subsets of both orders, indicating robust signal at deeper nodes, supporting their respective monophyly. Syntenic signal is blurred in miniaturized parasitic taxa (e.g., Tetranychus, Eriophyidae). We discuss the strong potential of synteny as a phylogenetic character to overcome limitations posed by molecular phylogenies at deeper nodes across karyotypic diversity.
{"title":"Ancient gene linkages and ultraconserved elements disentangle Acari interrelationships","authors":"Jyoti Prakash Bhoi , Rushikesh Mule , Nishaad Savale , Prashant P. Sharma , Siddharth Kulkarni","doi":"10.1016/j.isci.2025.114616","DOIUrl":"10.1016/j.isci.2025.114616","url":null,"abstract":"<div><div>The interrelationships among Acari groups, Acariformes (mites) and Parasitiformes (ticks and parasitic mites) have been debated for long. We interrogated 90 genomes of Arachnida through a customized Chelicerata-wide ultraconserved elements bait set to resolve higher-level relationships of these two orders, including the first genome of Opilioacaridae, the putative sister group to the remaining Parasitiformes. Datasets with variable locus occupancy thresholds and partitioning schemes supported the monophyly of Acariformes and Parasitiformes, including their major subgroups. Exploration for rare genomic changes as potential character systems was done using a custom 27 Acari-specific ancestral linkage group (AcarLGs). AcarLGs revealed distinct chromosomal fusion patterns within subsets of both orders, indicating robust signal at deeper nodes, supporting their respective monophyly. Syntenic signal is blurred in miniaturized parasitic taxa (e.g., <em>Tetranychus</em>, Eriophyidae). We discuss the strong potential of synteny as a phylogenetic character to overcome limitations posed by molecular phylogenies at deeper nodes across karyotypic diversity.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114616"},"PeriodicalIF":4.1,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074692","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}
Pub Date : 2026-01-02DOI: 10.1016/j.isci.2025.114568
Mario Michiels , Vincent Man , David Luque , Ignacio Obeso
Replacing a habitual action with goal-directed control involves a cost whose neural mechanisms in humans are not well established. Our study quantifies this cost and uncovers its neural correlates using fMRI and neurostimulation. Training S-R links in overtrained stimuli (compared to less trained ones, termed standard-trained stimuli) increased RT switch costs, explained by drift diffusion modeling. Training engaged sensorimotor areas and the posterior putamen, whereas standard-trained behaviors recruited the posterior caudate, insula, and prefrontal regions. A cortical network orchestrated habit expression (right S1 with the left anterior insula/prefrontal areas) while also implicating the basal ganglia when overriding habits (left premotor with the putamen). Importantly, stimulation of the left premotor cortex played a causal role in habit control, enhancing performance across both the training and devaluation phases. Our findings reveal an interaction between habitual and goal-directed brain regions, highlighting shared neural dynamics when overriding habitual behaviors.
{"title":"The neural basis of habit formation measured in goal-directed response switching","authors":"Mario Michiels , Vincent Man , David Luque , Ignacio Obeso","doi":"10.1016/j.isci.2025.114568","DOIUrl":"10.1016/j.isci.2025.114568","url":null,"abstract":"<div><div>Replacing a habitual action with goal-directed control involves a cost whose neural mechanisms in humans are not well established. Our study quantifies this cost and uncovers its neural correlates using fMRI and neurostimulation. Training S-R links in overtrained stimuli (compared to less trained ones, termed standard-trained stimuli) increased RT switch costs, explained by drift diffusion modeling. Training engaged sensorimotor areas and the posterior putamen, whereas standard-trained behaviors recruited the posterior caudate, insula, and prefrontal regions. A cortical network orchestrated habit expression (right S1 with the left anterior insula/prefrontal areas) while also implicating the basal ganglia when overriding habits (left premotor with the putamen). Importantly, stimulation of the left premotor cortex played a causal role in habit control, enhancing performance across both the training and devaluation phases. Our findings reveal an interaction between habitual and goal-directed brain regions, highlighting shared neural dynamics when overriding habitual behaviors.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114568"},"PeriodicalIF":4.1,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975107","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}
Pub Date : 2026-01-02DOI: 10.1016/j.isci.2025.114623
Shuangping Li , Shenshen Huang , Wei Wang , Jing Zhang , Bo Chen , Kelei Guo , Chenglong Ma , Shuaihui Hou , Pengfei Gao , Yimin Mao
Risk stratification guides management in acute pulmonary embolism (APE), yet current models have limitations. We investigated the Prognostic Nutritional Index (PNI) as a potential biomarker to refine risk assessment. Analyzing 1,163 discovery, 208 internal-validation, and 212 external-validation APE patients, we found that a higher PNI was independently associated with lower 30-day and in-hospital mortality after multivariable adjustment. Incorporating PNI into the European Society of Cardiology (ESC) risk model improved its predictive performance for 30-day mortality. Crucially, a PNI ≤42.5 effectively stratified intermediate-risk patients, identifying subgroups with 4.7- and 6-fold higher 30-day mortality in the intermediate-low- and intermediate-high-risk categories, respectively. These findings position PNI as a simple, valuable tool for enhancing precision in APE risk stratification.
{"title":"The prognostic nutritional index improves risk stratification for acute pulmonary embolism","authors":"Shuangping Li , Shenshen Huang , Wei Wang , Jing Zhang , Bo Chen , Kelei Guo , Chenglong Ma , Shuaihui Hou , Pengfei Gao , Yimin Mao","doi":"10.1016/j.isci.2025.114623","DOIUrl":"10.1016/j.isci.2025.114623","url":null,"abstract":"<div><div>Risk stratification guides management in acute pulmonary embolism (APE), yet current models have limitations. We investigated the Prognostic Nutritional Index (PNI) as a potential biomarker to refine risk assessment. Analyzing 1,163 discovery, 208 internal-validation, and 212 external-validation APE patients, we found that a higher PNI was independently associated with lower 30-day and in-hospital mortality after multivariable adjustment. Incorporating PNI into the European Society of Cardiology (ESC) risk model improved its predictive performance for 30-day mortality. Crucially, a PNI ≤42.5 effectively stratified intermediate-risk patients, identifying subgroups with 4.7- and 6-fold higher 30-day mortality in the intermediate-low- and intermediate-high-risk categories, respectively. These findings position PNI as a simple, valuable tool for enhancing precision in APE risk stratification.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114623"},"PeriodicalIF":4.1,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975166","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}
Pub Date : 2026-01-02DOI: 10.1016/j.isci.2025.114615
Moeko Minakuchi , Haoran Zhang , Joel Cassel , Yusuke Shiromoto , Jessie Villanueva , Emmanuel Skordalakes , Joseph M. Salvino , Qin Li , Kazuko Nishikura
Two ADAR1 isoforms, p150 and p110, are involved in adenosine-to-inosine RNA editing. ADAR1p150-mediated hyper-editing of endogenous dsRNAs prevents their activation of type I interferon signaling-mediated via Melanoma Differentiation-Associated Protein 5 (MDA5), which enables cancer resistance to immune checkpoint blockade. ADAR1p150 also inhibits Z-RNA-mediated activation of Z-DNA Binding Protein 1 (ZBP1) and induction of necroptosis. ADAR1p110 suppresses the formation of telomeric repeat R-loops, which would otherwise induce apoptosis in telomerase-reactivated cancer cells. Together, ADAR1 inhibitors could serve as novel cancer therapeutics. Here, we identified, ADAR1i-124, which inhibits the catalytic activities of both ADAR1p150 and ADAR1p110. ADAR1i-124 activated MDA5 and ZBP1 pathways and dose-dependently inhibited viability across different types of cancer cell lines. Some cancer cell lines, unresponsive to ADAR1i-124 alone, became responsive when co-treated with 5-Aza-CdR. The DNA methylase inhibitor reactivated endogenous retroviruses, leading to the formation of retrovirus dsRNAs and the emergence of a new ADAR1 dependency. Our study establishes the potential of ADAR1i-124 as a future cancer therapeutic.
{"title":"Identification of ADAR1i-124: The first effective A-to-I RNA editing inhibitor with promising cancer therapeutic potential","authors":"Moeko Minakuchi , Haoran Zhang , Joel Cassel , Yusuke Shiromoto , Jessie Villanueva , Emmanuel Skordalakes , Joseph M. Salvino , Qin Li , Kazuko Nishikura","doi":"10.1016/j.isci.2025.114615","DOIUrl":"10.1016/j.isci.2025.114615","url":null,"abstract":"<div><div>Two ADAR1 isoforms, p150 and p110, are involved in adenosine-to-inosine RNA editing. ADAR1p150-mediated hyper-editing of endogenous dsRNAs prevents their activation of type I interferon signaling-mediated via Melanoma Differentiation-Associated Protein 5 (MDA5), which enables cancer resistance to immune checkpoint blockade. ADAR1p150 also inhibits Z-RNA-mediated activation of Z-DNA Binding Protein 1 (ZBP1) and induction of necroptosis. ADAR1p110 suppresses the formation of telomeric repeat R-loops, which would otherwise induce apoptosis in telomerase-reactivated cancer cells. Together, ADAR1 inhibitors could serve as novel cancer therapeutics. Here, we identified, ADAR1i-124, which inhibits the catalytic activities of both ADAR1p150 and ADAR1p110. ADAR1i-124 activated MDA5 and ZBP1 pathways and dose-dependently inhibited viability across different types of cancer cell lines. Some cancer cell lines, unresponsive to ADAR1i-124 alone, became responsive when co-treated with 5-Aza-CdR. The DNA methylase inhibitor reactivated endogenous retroviruses, leading to the formation of retrovirus dsRNAs and the emergence of a new ADAR1 dependency. Our study establishes the potential of ADAR1i-124 as a future cancer therapeutic.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114615"},"PeriodicalIF":4.1,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975165","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}
Pub Date : 2026-01-02DOI: 10.1016/j.isci.2025.114613
Xingxian Luo (罗兴献) , Xin Du (杜鑫) , Qi Chen (陈琪) , Cen Wang (王岑) , Lizong Li (李理总) , Xu He (何旭) , Yiru Gong (龚怡如) , Jiali Chen (陈佳丽) , Xue Zhong (钟雪) , Yi Liu (刘一) , Xiaohong Zhang (张晓红) , Lin Huang (黄琳)
Hepatotoxicity is a known side effect of ALK inhibitors in non-small cell lung cancer. This meta-analysis assessed the hepatotoxicity risk, measured by elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), for new-generation ALK inhibitors versus crizotinib through eight randomized controlled trials with 2,114 patients. The results suggested that new-generation ALK inhibitors were associated with a significantly reduced risk of all-grade ALT elevation (RR = 0.73, 95% confidence interval [CI] [0.58, 0.92]) and a trend toward reduced risk of grades 3–5 ALT elevation (RR = 0.55, 95% CI [0.29, 1.06]). Alectinib, lorlatinib, and brigatinib are associated with lower risks of hepatotoxicity when compared with crizotinib. New-generation ALK inhibitors improved progression-free survival but not in discontinuation rates. Lorlatinib conferred a greater reduction in any grades AST than second-generation inhibitors compared to crizotinib. Our findings suggest that the selection of the ALK inhibitor should be individualized based on the specific profile of hepatotoxicity and their efficacy.
{"title":"Hepatotoxicity of new-generation ALK inhibitors versus crizotinib in patients with non-small cell lung cancer: A systematic review and meta-analysis","authors":"Xingxian Luo (罗兴献) , Xin Du (杜鑫) , Qi Chen (陈琪) , Cen Wang (王岑) , Lizong Li (李理总) , Xu He (何旭) , Yiru Gong (龚怡如) , Jiali Chen (陈佳丽) , Xue Zhong (钟雪) , Yi Liu (刘一) , Xiaohong Zhang (张晓红) , Lin Huang (黄琳)","doi":"10.1016/j.isci.2025.114613","DOIUrl":"10.1016/j.isci.2025.114613","url":null,"abstract":"<div><div>Hepatotoxicity is a known side effect of ALK inhibitors in non-small cell lung cancer. This meta-analysis assessed the hepatotoxicity risk, measured by elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), for new-generation ALK inhibitors versus crizotinib through eight randomized controlled trials with 2,114 patients. The results suggested that new-generation ALK inhibitors were associated with a significantly reduced risk of all-grade ALT elevation (RR = 0.73, 95% confidence interval [CI] [0.58, 0.92]) and a trend toward reduced risk of grades 3–5 ALT elevation (RR = 0.55, 95% CI [0.29, 1.06]). Alectinib, lorlatinib, and brigatinib are associated with lower risks of hepatotoxicity when compared with crizotinib. New-generation ALK inhibitors improved progression-free survival but not in discontinuation rates. Lorlatinib conferred a greater reduction in any grades AST than second-generation inhibitors compared to crizotinib. Our findings suggest that the selection of the ALK inhibitor should be individualized based on the specific profile of hepatotoxicity and their efficacy.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 2","pages":"Article 114613"},"PeriodicalIF":4.1,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145975167","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}
Pub Date : 2026-01-02DOI: 10.1016/j.isci.2025.114612
Franka Klatte-Schulz , Sven Geißler , Nicole Bormann , Susann Minkwitz , Serafim Tsitsilonis , Sebastian Manegold , Tobias Gehlen , Josephine A. Melzer , Alper Kurtoglu , Aysha Bonell , Katharina Schmidt-Bleek , Georg N. Duda , Birgit Sawitzki , Britt Wildemann
Insufficient healing of the Achilles tendon remains a frequent clinical challenge, creating a need for early markers that identify patients at risk of impaired healing. To examine whether adaptive immunity contributes to these outcomes, we analyzed T cell subsets in blood and hematoma collected during surgery. Patients with a higher CD4+/CD8+ T cell ratio at surgery reported more pain, showed reduced functional recovery, and greater tendon strain after 12 months. Conversely, elevated CD8+ T cell levels, and the CD28-/CD57+ memory subset, coincided with more favorable outcomes. We then investigated how these cells affect tendon healing by co-culturing human tenocytes with CD4+ or CD8+ T cells. Exposure to CD4+ T cells increased collagen type 3, IL-17 receptors and matrix metalloproteinases expression, indicating a shift toward impaired extracellular matrix organization. These results suggest that the CD4+/CD8+ T cell balance may serve as a prognostic marker and that modulating CD4+ T cell activity or IL-17 signaling could improve tendon repair.
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