Early Earth's UV-rich environment, together with abundant transition metals, likely shaped the stability of biomolecules. We investigated how cations influence the UV (254 nm) stability of diphenylalanine (FF). Among nine geologically relevant cations examined, Cu(Ⅱ) and Fe(Ⅲ) exhibited significantly different photolytic effects, Fe(Ⅲ) accelerated FF degradation, and Cu(Ⅱ) stabilized FF. Other metal ions had a minimal impact on FF stability. Mechanistic investigations revealed that Cu(Ⅱ) preferentially binds to the amide nitrogen, whereas Fe(Ⅲ) coordinates, primarily through oxygen atoms, significantly perturb the electron distribution of the phenyl and amide groups, thereby enhancing their susceptibility to hydroxyl radical attack. EPR spectroscopy further confirmed that Fe(Ⅲ) produces substantially higher levels of ⋅OH than Cu(Ⅱ), implicating ROS as the key driver of degradation. By uncovering cation-specific mechanisms of photodegradation, this study provides a physicochemical framework for understanding how metal ions may have influenced the selection and accumulation of proto-biomolecules in early chemical evolution.
{"title":"Metal-ion mediated photolytic regulation of diphenylalanine stability: Implications for prebiotic chemical evolution.","authors":"Wei Tang, Xingyi Shi, Jianxun Shen, Haotian Mao, Erjun Wei, Biling Huang, Jianxi Ying, Huahuan Cai, Yufen Zhao","doi":"10.1016/j.isci.2025.114432","DOIUrl":"https://doi.org/10.1016/j.isci.2025.114432","url":null,"abstract":"<p><p>Early Earth's UV-rich environment, together with abundant transition metals, likely shaped the stability of biomolecules. We investigated how cations influence the UV (254 nm) stability of diphenylalanine (FF). Among nine geologically relevant cations examined, Cu(Ⅱ) and Fe(Ⅲ) exhibited significantly different photolytic effects, Fe(Ⅲ) accelerated FF degradation, and Cu(Ⅱ) stabilized FF. Other metal ions had a minimal impact on FF stability. Mechanistic investigations revealed that Cu(Ⅱ) preferentially binds to the amide nitrogen, whereas Fe(Ⅲ) coordinates, primarily through oxygen atoms, significantly perturb the electron distribution of the phenyl and amide groups, thereby enhancing their susceptibility to hydroxyl radical attack. EPR spectroscopy further confirmed that Fe(Ⅲ) produces substantially higher levels of ⋅OH than Cu(Ⅱ), implicating ROS as the key driver of degradation. By uncovering cation-specific mechanisms of photodegradation, this study provides a physicochemical framework for understanding how metal ions may have influenced the selection and accumulation of proto-biomolecules in early chemical evolution.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"114432"},"PeriodicalIF":4.1,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12796767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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}
Freeform surfaces are widely used in off-axis pupil optical systems with large apertures, wide fields of view, and long focal lengths. Polarization effects in such systems significantly influence imaging quality. We proposed a polarization aberration analysis method for off-axis pupil freeform optical systems. An analytical model of phase aberration, diattenuation, and retardation was established. Low-order Zernike coefficients were analyzed to evaluate the impact on polarization aberration. The analysis results show that off-axis pupil freeform surfaces break the rotational symmetry of polarization aberration. By optimizing the freeform surface in the designed off-axis pupil triple-inverse spatial optical system, diattenuation and retardation decrease by 8.70% and 6.94%, while PSF ellipticity under non-polarized, horizontal polarized light, and vertical polarized light decreases by 0.12%, 7.31% and 10.69%, respectively. This study provides a theoretical basis for the design and polarization aberration calibration of off-axis pupil freeform optical systems.
{"title":"Analysis of polarization aberrations of the off-axis pupil freeform optical system.","authors":"Chenjie Gong, Yilan Zhang, Wancheng Liu, Jiayu Wang, Qiang Fu, Haodong Shi","doi":"10.1016/j.isci.2025.114435","DOIUrl":"https://doi.org/10.1016/j.isci.2025.114435","url":null,"abstract":"<p><p>Freeform surfaces are widely used in off-axis pupil optical systems with large apertures, wide fields of view, and long focal lengths. Polarization effects in such systems significantly influence imaging quality. We proposed a polarization aberration analysis method for off-axis pupil freeform optical systems. An analytical model of phase aberration, diattenuation, and retardation was established. Low-order Zernike coefficients were analyzed to evaluate the impact on polarization aberration. The analysis results show that off-axis pupil freeform surfaces break the rotational symmetry of polarization aberration. By optimizing the freeform surface in the designed off-axis pupil triple-inverse spatial optical system, diattenuation and retardation decrease by 8.70% and 6.94%, while PSF ellipticity under non-polarized, horizontal polarized light, and vertical polarized light decreases by 0.12%, 7.31% and 10.69%, respectively. This study provides a theoretical basis for the design and polarization aberration calibration of off-axis pupil freeform optical systems.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"114435"},"PeriodicalIF":4.1,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12796757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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}
Accurate prediction of intensive care unit (ICU) survival remains challenging due to heterogeneous clinical data. This study shows that contextualized biomedical language processing markedly enhances ICU survival prediction. Multimodal models integrating structured laboratory data with unstructured text (chief complaints and International Classification of Diseases [ICD] entries) were trained and validated using MIMIC-IV, MIMIC-III, and eICU datasets. The BioBERT-enhanced convolutional neural network achieved area under the receiver operating characteristic curves (AUROCs) of 0.889 (strict cohort, n = 5,795) and 0.974 (lenient cohort, n = 58,615) during external validation. Excluding text features or replacing free-text ICD entries with coded formats reduced performance (AUROC from 0.983 to 0.946-0.947), highlighting the importance of contextual embeddings. As a secondary task, cerebrospinal fluid culture prediction achieved AUROC = 0.853. Overall, integrating contextualized biomedical language representations significantly improves multimodal learning and ICU survival prediction.
{"title":"Contextualized biomedical language processing enhances ICU survival prediction.","authors":"Rui Chen, Yu Cai, Sitong Zhang, Zirong Huo, Mingming Song, Wenqing Li, Dongyan Yang, Seungyong Hwang, Ling Bai, Fuxin Han, Xi Zhang","doi":"10.1016/j.isci.2025.114442","DOIUrl":"https://doi.org/10.1016/j.isci.2025.114442","url":null,"abstract":"<p><p>Accurate prediction of intensive care unit (ICU) survival remains challenging due to heterogeneous clinical data. This study shows that contextualized biomedical language processing markedly enhances ICU survival prediction. Multimodal models integrating structured laboratory data with unstructured text (chief complaints and International Classification of Diseases [ICD] entries) were trained and validated using MIMIC-IV, MIMIC-III, and eICU datasets. The BioBERT-enhanced convolutional neural network achieved area under the receiver operating characteristic curves (AUROCs) of 0.889 (strict cohort, <i>n</i> = 5,795) and 0.974 (lenient cohort, <i>n</i> = 58,615) during external validation. Excluding text features or replacing free-text ICD entries with coded formats reduced performance (AUROC from 0.983 to 0.946-0.947), highlighting the importance of contextual embeddings. As a secondary task, cerebrospinal fluid culture prediction achieved AUROC = 0.853. Overall, integrating contextualized biomedical language representations significantly improves multimodal learning and ICU survival prediction.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"114442"},"PeriodicalIF":4.1,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12796750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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}
The zinc transporter SLC39A10 serves as a risk factor for malignant progression in gastric cancer (GC), characterized by the formation of an immunosuppressive tumor microenvironment (TME). As key cellular components within this microenvironment, both malignant cells and macrophages are influenced by SLC39A10, yet its regulatory mechanisms at the subpopulation level remain unclear. Using single-cell RNA sequencing and functional experiments, we investigated the cell-type-specific role of SLC39A10 in GC. Results demonstrated that oeSLC39A10 tumor cells exhibit activated MAPK14 signaling pathway, while tumor-associated macrophages (TAMs) display a biased M2 polarization state. These two cell populations establish intercellular communication through secretory factors IL-10 and TGF-β, synergistically promoting tumor proliferation and angiogenesis. This study identifies an SLC39A10-MAPK14-M2 macrophage regulatory axis that critically influences immune microenvironment remodeling and GC progression. Targeting this signaling axis may provide a viable therapeutic approach to alter the TME and suppress disease advancement.
{"title":"SLC39A10 drives M2 macrophage polarization and gastric cancer progression through the MAPK14(p38α) pathway.","authors":"Yinhua Liang, Mengting Li, Chihao Zhang, Chunpeng Pan, Shoulian Wang, Xin Xu, Jiwei Yu","doi":"10.1016/j.isci.2025.114400","DOIUrl":"https://doi.org/10.1016/j.isci.2025.114400","url":null,"abstract":"<p><p>The zinc transporter SLC39A10 serves as a risk factor for malignant progression in gastric cancer (GC), characterized by the formation of an immunosuppressive tumor microenvironment (TME). As key cellular components within this microenvironment, both malignant cells and macrophages are influenced by SLC39A10, yet its regulatory mechanisms at the subpopulation level remain unclear. Using single-cell RNA sequencing and functional experiments, we investigated the cell-type-specific role of SLC39A10 in GC. Results demonstrated that oeSLC39A10 tumor cells exhibit activated MAPK14 signaling pathway, while tumor-associated macrophages (TAMs) display a biased M2 polarization state. These two cell populations establish intercellular communication through secretory factors IL-10 and TGF-β, synergistically promoting tumor proliferation and angiogenesis. This study identifies an SLC39A10-MAPK14-M2 macrophage regulatory axis that critically influences immune microenvironment remodeling and GC progression. Targeting this signaling axis may provide a viable therapeutic approach to alter the TME and suppress disease advancement.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"114400"},"PeriodicalIF":4.1,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12796609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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}
Pub Date : 2025-12-12eCollection Date: 2026-01-16DOI: 10.1016/j.isci.2025.114421
Yangyang Sun, Zhuoqi Li, Baocong Yu, Chun Zhang, Lei Wang, Baorui Guo, Jiangwei Ding, Lifei Xiao, Peng Gao, Xinxiao Li, Tao Sun
Gabrg2fl/wtCre+ (CKO) mice are one of the models for studying "genetic epilepsy with febrile seizures plus (GEFS+)." A previous study revealed increased cortical excitability in CKO mice subjected to hyperthermia (CKO-heat mice), but the mechanism remains unclear. We investigated electrophysiological and morphological changes in layer 5 (L5) pyramidal neurons (PNs), and related molecules expression in CKO-heat mice. Hyperthermia increased the miniature excitatory postsynaptic current (mEPSC) increased, and decreased the miniature inhibitory postsynaptic current (mIPSC) in CKO mouse L5 PNs. The reduced complexity and dendritic spine density of in CKO mouse L5 PNs confirmed GEFS+-associated morphological changes. ITPR3 and GABRG2 (cytosolic protein) expression and the autophagosome number increased in the CKO mouse neocortex. These phenomena were attributed to PERK signaling pathway-mediated endoplasmic reticulum stress (ERS), which impaired vesicle transport. In summary, ERS reduces GABRG2 expression on the surface of L5 PNs in the CKO-heat mouse neocortex. This mechanism may underlie GEFS+ onset.
{"title":"Increased excitability of layer 5 neocortical pyramidal neurons and its contribution to seizure activity in Gabrg2 gene-deficient mice.","authors":"Yangyang Sun, Zhuoqi Li, Baocong Yu, Chun Zhang, Lei Wang, Baorui Guo, Jiangwei Ding, Lifei Xiao, Peng Gao, Xinxiao Li, Tao Sun","doi":"10.1016/j.isci.2025.114421","DOIUrl":"https://doi.org/10.1016/j.isci.2025.114421","url":null,"abstract":"<p><p><i>Gabrg2</i> <sup><i>fl/wt</i></sup> <i>Cre</i> <sup><i>+</i></sup> (CKO) mice are one of the models for studying \"genetic epilepsy with febrile seizures plus (GEFS+).\" A previous study revealed increased cortical excitability in CKO mice subjected to hyperthermia (CKO<sub>-heat</sub> mice), but the mechanism remains unclear. We investigated electrophysiological and morphological changes in layer 5 (L5) pyramidal neurons (PNs), and related molecules expression in CKO<sub>-heat</sub> mice. Hyperthermia increased the miniature excitatory postsynaptic current (mEPSC) increased, and decreased the miniature inhibitory postsynaptic current (mIPSC) in CKO mouse L5 PNs. The reduced complexity and dendritic spine density of in CKO mouse L5 PNs confirmed GEFS+-associated morphological changes. ITPR3 and GABRG2 (cytosolic protein) expression and the autophagosome number increased in the CKO mouse neocortex. These phenomena were attributed to PERK signaling pathway-mediated endoplasmic reticulum stress (ERS), which impaired vesicle transport. In summary, ERS reduces GABRG2 expression on the surface of L5 PNs in the CKO<sub>-heat</sub> mouse neocortex. This mechanism may underlie GEFS+ onset.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"114421"},"PeriodicalIF":4.1,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12796768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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}
Pub Date : 2025-12-12eCollection Date: 2026-01-16DOI: 10.1016/j.isci.2025.114430
Shyama Charan Mandal, Frank Abild-Pedersen
Surface energies of metal-based systems are important for determining the Wulff-constructed shapes of metal nanoparticles and understanding the stability. We have developed a physics informed method to predict the total energy of metal-based systems across a wide range of configurations. Our method has been tested against density functional theory (DFT) calculations for late transition metals. This method enables on-the-fly surface energy predictions based on the fundamental of materials property and allows for the Wulff construction of metal particles for a random number of elemental atoms and without the need for DFT calculations. By making a division between atoms in the different layers of the model system, we can improve the accuracy of the model, suggesting a dissimilarity between the electronic structure due to an alternating compression and expansion of atomic layers. We find that our model accurately and effectively provides valuable insights into the distribution and stability of nanoparticles.
{"title":"A physics informed model for the prediction of surface energies and the shape of metal particles.","authors":"Shyama Charan Mandal, Frank Abild-Pedersen","doi":"10.1016/j.isci.2025.114430","DOIUrl":"https://doi.org/10.1016/j.isci.2025.114430","url":null,"abstract":"<p><p>Surface energies of metal-based systems are important for determining the Wulff-constructed shapes of metal nanoparticles and understanding the stability. We have developed a physics informed method to predict the total energy of metal-based systems across a wide range of configurations. Our method has been tested against density functional theory (DFT) calculations for late transition metals. This method enables on-the-fly surface energy predictions based on the fundamental of materials property and allows for the Wulff construction of metal particles for a random number of elemental atoms and without the need for DFT calculations. By making a division between atoms in the different layers of the model system, we can improve the accuracy of the model, suggesting a dissimilarity between the electronic structure due to an alternating compression and expansion of atomic layers. We find that our model accurately and effectively provides valuable insights into the distribution and stability of nanoparticles.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"114430"},"PeriodicalIF":4.1,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12796764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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}
Pub Date : 2025-12-12eCollection Date: 2026-01-16DOI: 10.1016/j.isci.2025.114419
Yi-Yin Zhang, Xin-Yu Shen, Dian-Shu Zhao, Ary Hoffmann, Xiao-Yue Hong
Wolbachia is a ubiquitous endosymbiont in arthropods that produces small non-coding RNAs, which function as regulators in both the bacterium and its host. Although recent studies have shown cross-kingdom communication between Wolbachia and its host through Wolbachia-derived small non-coding RNAs (WsnRNAs), the functions of WsnRNAs have not been systematically examined. Here, we identify WsnRNAs in Wolbachia-infected Tetranychus truncatus Ehara via RNA-seq and investigate their impacts on host reproductive fitness. A total of 12 WsnRNAs were identified, along with their predicted precursors and hairpin structures. The predicted target genes of five highly expressed WsnRNAs are involved in reproductive development, as revealed by enrichment analysis. Inhibition of WsnRNA-744 and WsnRNA-3640 reduced fecundity, whereas inhibition of WsnRNA-6108 promoted it, indicating that different WsnRNAs exert opposing effects on host fecundity. These findings suggest that WsnRNAs mediate host-endosymbiont communication across species and could represent promising targets for Wolbachia-based pest control strategies.
{"title":"<i>Wolbachia</i>-derived small non-coding RNAs exhibit cross-kingdom regulatory effects on host reproduction of a polyphagous mite.","authors":"Yi-Yin Zhang, Xin-Yu Shen, Dian-Shu Zhao, Ary Hoffmann, Xiao-Yue Hong","doi":"10.1016/j.isci.2025.114419","DOIUrl":"https://doi.org/10.1016/j.isci.2025.114419","url":null,"abstract":"<p><p><i>Wolbachia</i> is a ubiquitous endosymbiont in arthropods that produces small non-coding RNAs, which function as regulators in both the bacterium and its host. Although recent studies have shown cross-kingdom communication between <i>Wolbachia</i> and its host through <i>Wolbachia</i>-derived small non-coding RNAs (<i>W</i>snRNAs), the functions of <i>W</i>snRNAs have not been systematically examined. Here, we identify <i>W</i>snRNAs in <i>Wolbachia</i>-infected <i>Tetranychus truncatus</i> Ehara via RNA-seq and investigate their impacts on host reproductive fitness. A total of 12 <i>W</i>snRNAs were identified, along with their predicted precursors and hairpin structures. The predicted target genes of five highly expressed <i>W</i>snRNAs are involved in reproductive development, as revealed by enrichment analysis. Inhibition of <i>W</i>snRNA-744 and <i>W</i>snRNA-3640 reduced fecundity, whereas inhibition of <i>W</i>snRNA-6108 promoted it, indicating that different <i>W</i>snRNAs exert opposing effects on host fecundity. These findings suggest that <i>W</i>snRNAs mediate host-endosymbiont communication across species and could represent promising targets for <i>Wolbachia</i>-based pest control strategies.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"114419"},"PeriodicalIF":4.1,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12796755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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}
Pub Date : 2025-12-12DOI: 10.1016/j.isci.2025.114429
Linsha Zhu , Xiangbo Jia , Lei Xu , Li Chen , Xiangning Fu , Hua Yan , Bo Ai , Shu Peng
KRAS G12C inhibitors (G12Cis) have revolutionized the treatment of cancers driven by this historically undruggable mutation, offering unprecedented clinical responses in non-small cell lung cancer (NSCLC) and other malignancies. However, both primary and acquired resistance rapidly curtail their efficacy. Emerging clinical and preclinical evidence underscores the heterogeneity of resistance mechanisms. Strikingly, in KRAS-driven NSCLC, a common phenomenon is co-mutations in tumor suppressor genes (TSGs), which orchestrate resistance through multifaceted pathways such as sustained proliferation, metabolic reprogramming, phenotypic plasticity, and immune microenvironment remodeling. Accordingly, this review summarizes relevant reasons underlying diverse resistant mechanisms in KRAS G12C-mutated NSCLC, with an emphasis on deciphering the mechanism of tumor suppressor gene (TSG) alterations serving as key mediators linking oncogenic KRAS dependency to therapeutic resistance. Our research continued to discuss relevant preclinical models to facilitate the advancement of the study of these resistance mechanisms.
{"title":"Tumor suppressor genes and KRAS G12C inhibitor resistance in non-small cell lung cancer","authors":"Linsha Zhu , Xiangbo Jia , Lei Xu , Li Chen , Xiangning Fu , Hua Yan , Bo Ai , Shu Peng","doi":"10.1016/j.isci.2025.114429","DOIUrl":"10.1016/j.isci.2025.114429","url":null,"abstract":"<div><div>KRAS G12C inhibitors (G12Cis) have revolutionized the treatment of cancers driven by this historically undruggable mutation, offering unprecedented clinical responses in non-small cell lung cancer (NSCLC) and other malignancies. However, both primary and acquired resistance rapidly curtail their efficacy. Emerging clinical and preclinical evidence underscores the heterogeneity of resistance mechanisms. Strikingly, in KRAS-driven NSCLC, a common phenomenon is co-mutations in tumor suppressor genes (TSGs), which orchestrate resistance through multifaceted pathways such as sustained proliferation, metabolic reprogramming, phenotypic plasticity, and immune microenvironment remodeling. Accordingly, this review summarizes relevant reasons underlying diverse resistant mechanisms in KRAS G12C-mutated NSCLC, with an emphasis on deciphering the mechanism of tumor suppressor gene (TSG) alterations serving as key mediators linking oncogenic KRAS dependency to therapeutic resistance. Our research continued to discuss relevant preclinical models to facilitate the advancement of the study of these resistance mechanisms.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114429"},"PeriodicalIF":4.1,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881000","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 : 2025-12-12eCollection Date: 2026-01-16DOI: 10.1016/j.isci.2025.114427
Josephine Ansorge, Denise Manahan-Vaughan
The medial posterior (POm) and ventral posterior medial (VPM) thalamic nuclei sort and filter somatosensory information that is sent to the primary somatosensory cortex (S1). Corticothalamic feedback from distinct cell populations of S1 layer 6 (S1L6) targets both POm and VPM. To differentiate their roles, electrophysiological recordings were conducted in awake mice during the photoinactivation of S1L6B-Drd1-expressing neurons (that project to POm), or S1L6-Ntsr1-expressing neurons (that project to POm and VPM). Photoinactivation of either pathway suppressed POm activity when whiskers were deflected, regardless of whisking state, but S1L6-Ntsr1-POm inputs were most affected when whisker deflection occurred during non-whisking. Conversely, S1L6-Ntsr1-VPM inputs responded to whisker deflections during whisking. We identified a novel projection from S1L6-Drd1-expressing neurons to the zona incerta, indicating a role for this GABAergic structure in a corticothalamic circuit that modulates POm. These results indicate corticothalamic control of somatosensory thalamus is regulated, in a context-dependent manner, by two distinct S1L6 feedback systems supporting precision and fine-tuning of somatosensory perception.
{"title":"Somatosensory control of thalamic relay neurons is regulated by two distinct layer 6 feedback systems.","authors":"Josephine Ansorge, Denise Manahan-Vaughan","doi":"10.1016/j.isci.2025.114427","DOIUrl":"https://doi.org/10.1016/j.isci.2025.114427","url":null,"abstract":"<p><p>The medial posterior (POm) and ventral posterior medial (VPM) thalamic nuclei sort and filter somatosensory information that is sent to the primary somatosensory cortex (S1). Corticothalamic feedback from distinct cell populations of S1 layer 6 (S1L6) targets both POm and VPM. To differentiate their roles, electrophysiological recordings were conducted in awake mice during the photoinactivation of S1L6B-Drd1-expressing neurons (that project to POm), or S1L6-Ntsr1-expressing neurons (that project to POm and VPM). Photoinactivation of either pathway suppressed POm activity when whiskers were deflected, regardless of whisking state, but S1L6-Ntsr1-POm inputs were most affected when whisker deflection occurred during non-whisking. Conversely, S1L6-Ntsr1-VPM inputs responded to whisker deflections during whisking. We identified a novel projection from S1L6-Drd1-expressing neurons to the zona incerta, indicating a role for this GABAergic structure in a corticothalamic circuit that modulates POm. These results indicate corticothalamic control of somatosensory thalamus is regulated, in a context-dependent manner, by two distinct S1L6 feedback systems supporting precision and fine-tuning of somatosensory perception.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"114427"},"PeriodicalIF":4.1,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12796580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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}
Pub Date : 2025-12-12eCollection Date: 2026-01-16DOI: 10.1016/j.isci.2025.114420
Yinghai Lyu, Juan Li, Haoming Li, Xiao Li, Xiaoke Yang, Yuan Yuan, Xitong Song, Guijiang Li
This study explores the interactions between montmorillonite (MMT) and selected amino acids (lysine, arginine, serine, and aspartate), as well as their complexes with heavy metal ions. Multi-technique characterization (e.g., XRD, FT-IR, XPS, SEM, TEM, and ICP-MS) revealed that MMT exhibits high affinity for basic amino acids, with the adsorption capacity following the order: amino > carboxyl > hydroxyl. The adsorption kinetics of lysine were well described by pseudo-second-order, Elovich, and Weber-Morris models, indicating a chemically controlled, two-stage process involving initial surface diffusion and subsequent internal diffusion. In contrast to the adsorption of amino acids, that of Cu2+ exhibited a higher initial rate and greater adsorption energy. Furthermore, amino acid-MMT composites effectively immobilized metal ions via coordination and electrostatic interactions. These findings enhance the understanding of mineral-organic interactions and suggest potential applications in biocatalysis, biopharmaceuticals, and environmental remediation.
{"title":"Montmorillonite and amino acid composites for heavy metal ion adsorption.","authors":"Yinghai Lyu, Juan Li, Haoming Li, Xiao Li, Xiaoke Yang, Yuan Yuan, Xitong Song, Guijiang Li","doi":"10.1016/j.isci.2025.114420","DOIUrl":"https://doi.org/10.1016/j.isci.2025.114420","url":null,"abstract":"<p><p>This study explores the interactions between montmorillonite (MMT) and selected amino acids (lysine, arginine, serine, and aspartate), as well as their complexes with heavy metal ions. Multi-technique characterization (e.g., XRD, FT-IR, XPS, SEM, TEM, and ICP-MS) revealed that MMT exhibits high affinity for basic amino acids, with the adsorption capacity following the order: amino > carboxyl > hydroxyl. The adsorption kinetics of lysine were well described by pseudo-second-order, Elovich, and Weber-Morris models, indicating a chemically controlled, two-stage process involving initial surface diffusion and subsequent internal diffusion. In contrast to the adsorption of amino acids, that of Cu<sup>2+</sup> exhibited a higher initial rate and greater adsorption energy. Furthermore, amino acid-MMT composites effectively immobilized metal ions via coordination and electrostatic interactions. These findings enhance the understanding of mineral-organic interactions and suggest potential applications in biocatalysis, biopharmaceuticals, and environmental remediation.</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"114420"},"PeriodicalIF":4.1,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12796756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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}