Pub Date : 2025-02-11DOI: 10.1016/j.isci.2025.111994
Ketaki A. Katdare , Andrew Kjar , Natasha M. O’Brown , Emma H. Neal , Alexander G. Sorets , Alena Shostak , Wilber Romero-Fernandez , Alexander J. Kwiatkowski , Kate Mlouk , Hyosung Kim , Rebecca P. Cowell , Katrina R. Schwensen , Cristian O. Carvajal Tapia , Guste Venslovaite , Kensley B. Horner , John T. Wilson , Matthew S. Schrag , Sean G. Megason , Ethan S. Lippmann
Brain endothelial cells (BECs) play an important role in maintaining central nervous system (CNS) homeostasis through blood-brain barrier (BBB) functions. BECs express low baseline levels of adhesion receptors, which limits entry of leukocytes. However, the molecular mediators governing this phenotype remain mostly unclear. Here, we explored how infiltration of immune cells across the BBB is influenced by the scaffold protein IQ motif containing GTPase-activating protein 2 (IQGAP2). In mice and zebrafish, we demonstrate that loss of Iqgap2 increases infiltration of peripheral leukocytes into the CNS under homeostatic and inflammatory conditions. Using single-cell RNA sequencing and immunohistology, we further show that BECs from mice lacking Iqgap2 exhibit a profound inflammatory signature, including extensive upregulation of adhesion receptors and antigen-processing machinery. Human tissue analyses also reveal that Alzheimer's disease is associated with reduced hippocampal IQGAP2. Overall, our results implicate IQGAP2 as an essential regulator of BBB immune privilege and immune cell entry into the CNS.
{"title":"IQGAP2 regulates blood-brain barrier immune dynamics","authors":"Ketaki A. Katdare , Andrew Kjar , Natasha M. O’Brown , Emma H. Neal , Alexander G. Sorets , Alena Shostak , Wilber Romero-Fernandez , Alexander J. Kwiatkowski , Kate Mlouk , Hyosung Kim , Rebecca P. Cowell , Katrina R. Schwensen , Cristian O. Carvajal Tapia , Guste Venslovaite , Kensley B. Horner , John T. Wilson , Matthew S. Schrag , Sean G. Megason , Ethan S. Lippmann","doi":"10.1016/j.isci.2025.111994","DOIUrl":"10.1016/j.isci.2025.111994","url":null,"abstract":"<div><div>Brain endothelial cells (BECs) play an important role in maintaining central nervous system (CNS) homeostasis through blood-brain barrier (BBB) functions. BECs express low baseline levels of adhesion receptors, which limits entry of leukocytes. However, the molecular mediators governing this phenotype remain mostly unclear. Here, we explored how infiltration of immune cells across the BBB is influenced by the scaffold protein IQ motif containing GTPase-activating protein 2 (IQGAP2). In mice and zebrafish, we demonstrate that loss of Iqgap2 increases infiltration of peripheral leukocytes into the CNS under homeostatic and inflammatory conditions. Using single-cell RNA sequencing and immunohistology, we further show that BECs from mice lacking Iqgap2 exhibit a profound inflammatory signature, including extensive upregulation of adhesion receptors and antigen-processing machinery. Human tissue analyses also reveal that Alzheimer's disease is associated with reduced hippocampal IQGAP2. Overall, our results implicate IQGAP2 as an essential regulator of BBB immune privilege and immune cell entry into the CNS.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111994"},"PeriodicalIF":4.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465155","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 : 2025-02-11DOI: 10.1016/j.isci.2025.111998
César Trifone , Corentin Richard , Amélie Pagliuzza , Caroline Dufour , Audrée Lemieux , Natasha M. Clark , Sanath K. Janaka , Christine M. Fennessey , Brandon E. Keele , Rémi Fromentin , Jacob D. Estes , Daniel E. Kaufmann , Andrés Finzi , David T. Evans , Nicolas Chomont
Persistent SIV/HIV reservoirs are the primary obstacle to a cure and the source of viral rebound after ART interruption (ATI). However, the anatomical source of viral rebound remains elusive. Here, we characterized the proviral landscape in the blood, inguinal, and axillary lymph nodes and colon biopsies of five SHIV-infected rhesus macaques (RMs), under ART for 28 weeks. From the 144 near full-length (NFL) proviral sequences obtained pre-ATI, 35% were genetically intact and only 2.8% were found in multiple copies. Envelope sequences of plasma rebounding viruses after ATI, more frequently matched pre-ATI intact proviruses retrieved from lymph nodes compared to sequences isolated from the blood or the colon (4, 1, and 1 pair of matched sequences, respectively). Our results suggest that clonal expansion of infected cells rare in this model, and that intact proviruses persisting in the lymph nodes may be a preferential source of viral rebound upon ATI.
{"title":"Contribution of intact viral genomes persisting in blood and tissues during ART to plasma viral rebound in SHIV-infected rhesus macaques","authors":"César Trifone , Corentin Richard , Amélie Pagliuzza , Caroline Dufour , Audrée Lemieux , Natasha M. Clark , Sanath K. Janaka , Christine M. Fennessey , Brandon E. Keele , Rémi Fromentin , Jacob D. Estes , Daniel E. Kaufmann , Andrés Finzi , David T. Evans , Nicolas Chomont","doi":"10.1016/j.isci.2025.111998","DOIUrl":"10.1016/j.isci.2025.111998","url":null,"abstract":"<div><div>Persistent SIV/HIV reservoirs are the primary obstacle to a cure and the source of viral rebound after ART interruption (ATI). However, the anatomical source of viral rebound remains elusive. Here, we characterized the proviral landscape in the blood, inguinal, and axillary lymph nodes and colon biopsies of five SHIV-infected rhesus macaques (RMs), under ART for 28 weeks. From the 144 near full-length (NFL) proviral sequences obtained pre-ATI, 35% were genetically intact and only 2.8% were found in multiple copies. Envelope sequences of plasma rebounding viruses after ATI, more frequently matched pre-ATI intact proviruses retrieved from lymph nodes compared to sequences isolated from the blood or the colon (4, 1, and 1 pair of matched sequences, respectively). Our results suggest that clonal expansion of infected cells rare in this model, and that intact proviruses persisting in the lymph nodes may be a preferential source of viral rebound upon ATI.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111998"},"PeriodicalIF":4.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512176","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 : 2025-02-11DOI: 10.1016/j.isci.2025.112002
Prateek Sharma , Tejeshwar Jain , Ali Sorgen , Srikanth Iyer , Mohammad Tarique , Pooja Roy , Saba Kurtom , Vrishketan Sethi , Ejas P. Bava , A.K. Gutierrez-Garcia , Utpreksha Vaish , Dhanisha Sulekha Suresh , Preeti Sahay , Dujon Edwards , Jumana Afghani , Satwikreddy Putluri , Karthik Reddy Kami Reddy , Chandra Sekhar Amara , Abu Hena Mustafa Kamal , Anthony Fodor , Vikas Dudeja
Cigarette smoke exposure (CSE) increases the risk for a plethora of cancers. Recent evidence indicates that the gut microbiome can influence cancer progression by immune system modulation. Since CSE alters the gut microbiome, we hypothesized that the gut microbiome serves as a causative link between smoking and cancer growth. Through a combination of syngeneic animal models and fecal microbiota transplantation studies, we established an essential role for smoke-induced dysbiosis in cancer growth. 16s rRNA sequencing and liquid chromatography-mass spectrometry indicated a unique CSE-associated microbial and metabolomic signature. Immunophenotyping of tumor specimens and experiments in Rag1-KO and CD8-KO demonstrated that smoke-induced tumor growth requires functional adaptive immunity. Finally, utilizing gut microbial ablation strategies with broad- and narrow-spectrum antibiotics, we demonstrated the reversal of phenotypic effects of CSE. Our study provides evidence for gut microbiome as an actionable target to mitigate CSE-induced tumor promotion.
{"title":"Smoking-induced gut microbial dysbiosis mediates cancer progression through modulation of anti-tumor immune response","authors":"Prateek Sharma , Tejeshwar Jain , Ali Sorgen , Srikanth Iyer , Mohammad Tarique , Pooja Roy , Saba Kurtom , Vrishketan Sethi , Ejas P. Bava , A.K. Gutierrez-Garcia , Utpreksha Vaish , Dhanisha Sulekha Suresh , Preeti Sahay , Dujon Edwards , Jumana Afghani , Satwikreddy Putluri , Karthik Reddy Kami Reddy , Chandra Sekhar Amara , Abu Hena Mustafa Kamal , Anthony Fodor , Vikas Dudeja","doi":"10.1016/j.isci.2025.112002","DOIUrl":"10.1016/j.isci.2025.112002","url":null,"abstract":"<div><div>Cigarette smoke exposure (CSE) increases the risk for a plethora of cancers. Recent evidence indicates that the gut microbiome can influence cancer progression by immune system modulation. Since CSE alters the gut microbiome, we hypothesized that the gut microbiome serves as a causative link between smoking and cancer growth. Through a combination of syngeneic animal models and fecal microbiota transplantation studies, we established an essential role for smoke-induced dysbiosis in cancer growth. 16s rRNA sequencing and liquid chromatography-mass spectrometry indicated a unique CSE-associated microbial and metabolomic signature. Immunophenotyping of tumor specimens and experiments in Rag1-KO and CD8-KO demonstrated that smoke-induced tumor growth requires functional adaptive immunity. Finally, utilizing gut microbial ablation strategies with broad- and narrow-spectrum antibiotics, we demonstrated the reversal of phenotypic effects of CSE. Our study provides evidence for gut microbiome as an actionable target to mitigate CSE-induced tumor promotion.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 112002"},"PeriodicalIF":4.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509072","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 intravenous immunoglobulin (IVIG) resistance is crucial for the effective treatment of Kawasaki disease(KD). This study aimed to develop a predictive model for IVIG resistance in patients with Kawasaki disease and to identify the key predictors. The training set underwent cross-validation, and models were constructed using six machine learning algorithms. Model performance was validated through cross-validation, test set evaluation, and two external validation sets evaluation. The model constructed using the random forest algorithm demonstrated the best overall performance among six models. The areas under the receiver operating characteristic curve (AUCs) for 5-fold cross-validation, internal validation, and external validations from Shaoxing and Quzhou were 0.711, 0.751, 0.827, and 0.735, respectively. According to the Shapley additive explanation (SHAP) method, C-reactive protein-to-albumin ratio, prognostic nutritional index, and sex were identified as the most important predictors. Our model demonstrates strong predictive capability for assessing IVIG resistance in Kawasaki disease patients.
{"title":"A machine learning-based model to predict intravenous immunoglobulin resistance in Kawasaki disease","authors":"Yuhan Xia , Yuezhong Huang , Min Gong , Weirong Liu , Yuanhui Meng , Huiyang Wu , Hui Zhang , Hao Zhang , Luyi Weng , Xiao-Li Chen , Huixian Qiu , Xing Rong , Rongzhou Wu , Maoping Chu , Xiu-Feng Huang","doi":"10.1016/j.isci.2025.112004","DOIUrl":"10.1016/j.isci.2025.112004","url":null,"abstract":"<div><div>Accurate prediction of intravenous immunoglobulin (IVIG) resistance is crucial for the effective treatment of Kawasaki disease(KD). This study aimed to develop a predictive model for IVIG resistance in patients with Kawasaki disease and to identify the key predictors. The training set underwent cross-validation, and models were constructed using six machine learning algorithms. Model performance was validated through cross-validation, test set evaluation, and two external validation sets evaluation. The model constructed using the random forest algorithm demonstrated the best overall performance among six models. The areas under the receiver operating characteristic curve (AUCs) for 5-fold cross-validation, internal validation, and external validations from Shaoxing and Quzhou were 0.711, 0.751, 0.827, and 0.735, respectively. According to the Shapley additive explanation (SHAP) method, C-reactive protein-to-albumin ratio, prognostic nutritional index, and sex were identified as the most important predictors. Our model demonstrates strong predictive capability for assessing IVIG resistance in Kawasaki disease patients.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 112004"},"PeriodicalIF":4.6,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512175","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 : 2025-02-10DOI: 10.1016/j.isci.2025.111993
Baptiste Caziot , Sadra Fathkhani , Frank Bremmer
The encoding of three-dimensional visual information is of important in everyday life. Eye-movements challenge this spatial encoding: they shift the image of the outside world across the retina. In the macaque ventral intraparietal area (VIP), many neurons encode visual information irrespective of horizontal and vertical eye position. Does this gaze invariance of spatial encoding extend to egocentric distances? Such invariance would correspond to a shift of disparity-tuning curves by vergence angle. Here, monkeys fixated one of three distances (vergence), while a visual stimulus was shown at one of seven distances (disparity). Most neurons’ activity was modulated independently by both disparity and eye vergence, and we did not observe shifts of disparity-tuning curves as expected from encoding egocentric distances at a single-cell level. By using population activity, however, we were able to decode egocentric distance. Our results provide further strong evidence for a role of area VIP in 3D space encoding.
{"title":"Coding of egocentric distance in the macaque ventral intraparietal area","authors":"Baptiste Caziot , Sadra Fathkhani , Frank Bremmer","doi":"10.1016/j.isci.2025.111993","DOIUrl":"10.1016/j.isci.2025.111993","url":null,"abstract":"<div><div>The encoding of three-dimensional visual information is of important in everyday life. Eye-movements challenge this spatial encoding: they shift the image of the outside world across the retina. In the macaque ventral intraparietal area (VIP), many neurons encode visual information irrespective of horizontal and vertical eye position. Does this gaze invariance of spatial encoding extend to egocentric distances? Such invariance would correspond to a shift of disparity-tuning curves by vergence angle. Here, monkeys fixated one of three distances (vergence), while a visual stimulus was shown at one of seven distances (disparity). Most neurons’ activity was modulated independently by both disparity and eye vergence, and we did not observe shifts of disparity-tuning curves as expected from encoding egocentric distances at a single-cell level. By using population activity, however, we were able to decode egocentric distance. Our results provide further strong evidence for a role of area VIP in 3D space encoding.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111993"},"PeriodicalIF":4.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454917","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 : 2025-02-10DOI: 10.1016/j.isci.2025.111987
Bansidhar Patel , Antonio Sorrentino , Tanja Vidakovic-Koch
Optimizing electrochemical devices requires an understanding of the complex interplay between mass transport and electrokinetics at the electrode-electrolyte interface. Electrochemical impedance spectroscopy (EIS) is a powerful tool for probing these processes, with analysis typically performed using equivalent circuit models (ECMs). However, selecting the appropriate ECM is challenging, as different models can yield deceptively similar spectra, complicating the accurate representation of the underlying physics. This work presents a data-driven approach for extracting the distribution of relaxation times (DRTs) through the Loewner framework (LF), facilitating the identification of the most suitable ECM for a given EIS dataset. The method is validated on different variants of Randles ECMs, which are commonly used to describe electrochemical interfaces. Its robustness to noisy datasets, as well as its advantages over similar methods that employ inversion algorithms, are also discussed.
{"title":"Data-driven analysis of electrochemical impedance spectroscopy using the Loewner framework","authors":"Bansidhar Patel , Antonio Sorrentino , Tanja Vidakovic-Koch","doi":"10.1016/j.isci.2025.111987","DOIUrl":"10.1016/j.isci.2025.111987","url":null,"abstract":"<div><div>Optimizing electrochemical devices requires an understanding of the complex interplay between mass transport and electrokinetics at the electrode-electrolyte interface. Electrochemical impedance spectroscopy (EIS) is a powerful tool for probing these processes, with analysis typically performed using equivalent circuit models (ECMs). However, selecting the appropriate ECM is challenging, as different models can yield deceptively similar spectra, complicating the accurate representation of the underlying physics. This work presents a data-driven approach for extracting the distribution of relaxation times (DRTs) through the Loewner framework (LF), facilitating the identification of the most suitable ECM for a given EIS dataset. The method is validated on different variants of Randles ECMs, which are commonly used to describe electrochemical interfaces. Its robustness to noisy datasets, as well as its advantages over similar methods that employ inversion algorithms, are also discussed.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111987"},"PeriodicalIF":4.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474151","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 : 2025-02-10DOI: 10.1016/j.isci.2025.111976
Yaqi Qiao , Xiaoqing Fan , Chengcheng Yuan , Zheng Fang , Chengkou Liu
1,n-Dual Π systems including 1,4-diene derivatives have been widely used as the elegant radical receptors to promote cascade radical additions to give the highly functionalized polycyclic scaffolds. However, the tedious and complicated preparation of the former deters broad utilization and compromises the practical value. Herein, a straightforward preparation of 1,4-diene derivatives was developed from the easily accessible alkynes and γ,δ-unsaturated carboxylic acids via electrochemical oxidation cyclization and Hofmann elimination. This transformation features with good to excellent yields, functional group compatibility, and selectivity without any Zaitsev elimination product detected.
{"title":"Electrosynthesis of 1,4-diene derivatives bearing cyclopentene skeleton","authors":"Yaqi Qiao , Xiaoqing Fan , Chengcheng Yuan , Zheng Fang , Chengkou Liu","doi":"10.1016/j.isci.2025.111976","DOIUrl":"10.1016/j.isci.2025.111976","url":null,"abstract":"<div><div>1,n-Dual Π systems including 1,4-diene derivatives have been widely used as the elegant radical receptors to promote cascade radical additions to give the highly functionalized polycyclic scaffolds. However, the tedious and complicated preparation of the former deters broad utilization and compromises the practical value. Herein, a straightforward preparation of 1,4-diene derivatives was developed from the easily accessible alkynes and γ,δ-unsaturated carboxylic acids via electrochemical oxidation cyclization and Hofmann elimination. This transformation features with good to excellent yields, functional group compatibility, and selectivity without any Zaitsev elimination product detected.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111976"},"PeriodicalIF":4.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444281","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 : 2025-02-10DOI: 10.1016/j.isci.2025.111990
Tao Li , Zhaoxuan Zhu
Self-accelerating beams, characterized by their low diffraction and self-bending properties, have found extensive applications in industrial and medical fields. However, microwave self-accelerating beams typically exhibit extremely limited transmission distances, failing to meet long-distance transmission requirements. By solving the Helmholtz equation, the initial amplitude and phase distribution for self-accelerating beam generation are obtained. Secondly, combined with the flexible amplitude-phase control characteristics of metasurfaces, a method of generating long-distance self-accelerating beams is proposed. Thirdly, a three-layer double-split-ring resonator metasurface unit is designed to achieve control of phase and amplitude. An amplitude-phase dual-controlled array for long-distance self-accelerating beam generation is constructed. The primary factors affecting the beam’s self-bending displacement are analyzed by simulation. Finally, a 30 × 30 cm amplitude-phase dual-controlled metasurface is fabricated and tested. The results demonstrate that the self-accelerating beam can achieve a transmission distance exceeding 700 mm, thereby verifying the feasibility of the proposed long-distance self-accelerating beam generation method.
{"title":"Generation of long-distance self-accelerating beam based on amplitude-phase dual-controlled metasurfaces","authors":"Tao Li , Zhaoxuan Zhu","doi":"10.1016/j.isci.2025.111990","DOIUrl":"10.1016/j.isci.2025.111990","url":null,"abstract":"<div><div>Self-accelerating beams, characterized by their low diffraction and self-bending properties, have found extensive applications in industrial and medical fields. However, microwave self-accelerating beams typically exhibit extremely limited transmission distances, failing to meet long-distance transmission requirements. By solving the Helmholtz equation, the initial amplitude and phase distribution for self-accelerating beam generation are obtained. Secondly, combined with the flexible amplitude-phase control characteristics of metasurfaces, a method of generating long-distance self-accelerating beams is proposed. Thirdly, a three-layer double-split-ring resonator metasurface unit is designed to achieve control of phase and amplitude. An amplitude-phase dual-controlled array for long-distance self-accelerating beam generation is constructed. The primary factors affecting the beam’s self-bending displacement are analyzed by simulation. Finally, a 30 × 30 cm amplitude-phase dual-controlled metasurface is fabricated and tested. The results demonstrate that the self-accelerating beam can achieve a transmission distance exceeding 700 mm, thereby verifying the feasibility of the proposed long-distance self-accelerating beam generation method.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111990"},"PeriodicalIF":4.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534394","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 : 2025-02-10DOI: 10.1016/j.isci.2025.111986
Meige Sun , Fei Lin , Jing Shi , Xiang-Guang Wu , Yunyi Liang , Jialing Chen , Qinglei Gao , Shuzhong Yao , Jiangtao Fan , Youguo Chen , Danbo Wang , Yi Huang , Liang-Sheng Fan , Jun Yang , Wei Wang
This study investigated the prognostic impact of lymph node dissection (LND) in patients with stage I ovarian endometrioid carcinoma (OEC) and aimed to identify the optimal LND range for improved survival. By analyzing data from the Surveillance, Epidemiology, and End Results (SEER) database conducted in USA and NUWA database in China, we found that patients who underwent LND in the SEER cohort exhibited significantly improved long-term survival rates compared to those who did not undergo LND, while the difference was not statistically significant in the NUWA cohort. Cox regression and restricted cubic spline analyses indicated an inverted U-shaped association between the number of LNDs and hazard ratios, identifying 29–34 lymph nodes as the optimal range. This finding suggests that performing LND within this specified range may enhance survival outcomes for patients with stage I OEC.
{"title":"The impact of lymph node dissection on stage I ovarian endometrioid carcinoma: A US-China Comparative Analysis","authors":"Meige Sun , Fei Lin , Jing Shi , Xiang-Guang Wu , Yunyi Liang , Jialing Chen , Qinglei Gao , Shuzhong Yao , Jiangtao Fan , Youguo Chen , Danbo Wang , Yi Huang , Liang-Sheng Fan , Jun Yang , Wei Wang","doi":"10.1016/j.isci.2025.111986","DOIUrl":"10.1016/j.isci.2025.111986","url":null,"abstract":"<div><div>This study investigated the prognostic impact of lymph node dissection (LND) in patients with stage I ovarian endometrioid carcinoma (OEC) and aimed to identify the optimal LND range for improved survival. By analyzing data from the Surveillance, Epidemiology, and End Results (SEER) database conducted in USA and NUWA database in China, we found that patients who underwent LND in the SEER cohort exhibited significantly improved long-term survival rates compared to those who did not undergo LND, while the difference was not statistically significant in the NUWA cohort. Cox regression and restricted cubic spline analyses indicated an inverted U-shaped association between the number of LNDs and hazard ratios, identifying 29–34 lymph nodes as the optimal range. This finding suggests that performing LND within this specified range may enhance survival outcomes for patients with stage I OEC.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111986"},"PeriodicalIF":4.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454919","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 : 2025-02-10DOI: 10.1016/j.isci.2025.111989
Wanjun Zhang , Jun Wang , Hanning Li , Xue Zhang , Dunjie Yao , Huimin Zhang , Xinhong Zhou , Jiaqi Nie , Tongxing Lai , Haichuan Zhu , Yiping Gong , Yoshimasa Tanaka , Xingrui Li , Xinghua Liao , Li Su
Identification of metastasis drivers of triple-negative breast cancer (TNBC) is a multifaceted challenge. Here, we identified TATA-box binding protein associated factor 7 (TAF7) as a candidate to modulate TNBC metastasis. TAF7 exhibited high expression in metastatic TNBC patients, and its elevated expression showed a negative correlation with overall survival in TNBC patients. The knockdown of TAF7 suppressed the migration and invasion of TNBC, suggesting TAF7 plays a role in the metastatic processes. Further, TAF7 was enhancing serum amyloid A1 (SAA1) transcription by binding to a specific motif in the SAA1 gene promoter. The elevated SAA1 in TNBC cells directly increased E-cadherin and N-cadherin phosphorylation thereby regulating cell adhesion. Mechanistically, TAF7 modulated cell invasion, migration, and lung metastasis through an SAA1-dependent manner in vitro and in vivo experiments. Taken together, it is likely that TAF7 could directly act on the SAA1 gene promoter, upregulating SAA1 and consequently promoting TNBC metastasis.
{"title":"TAF7 directly targets SAA1 to enhance triple-negative breast cancer metastasis via phosphorylating E-cadherin and N-cadherin","authors":"Wanjun Zhang , Jun Wang , Hanning Li , Xue Zhang , Dunjie Yao , Huimin Zhang , Xinhong Zhou , Jiaqi Nie , Tongxing Lai , Haichuan Zhu , Yiping Gong , Yoshimasa Tanaka , Xingrui Li , Xinghua Liao , Li Su","doi":"10.1016/j.isci.2025.111989","DOIUrl":"10.1016/j.isci.2025.111989","url":null,"abstract":"<div><div>Identification of metastasis drivers of triple-negative breast cancer (TNBC) is a multifaceted challenge. Here, we identified TATA-box binding protein associated factor 7 (TAF7) as a candidate to modulate TNBC metastasis. TAF7 exhibited high expression in metastatic TNBC patients, and its elevated expression showed a negative correlation with overall survival in TNBC patients. The knockdown of TAF7 suppressed the migration and invasion of TNBC, suggesting TAF7 plays a role in the metastatic processes. Further, TAF7 was enhancing serum amyloid A1 (SAA1) transcription by binding to a specific motif in the SAA1 gene promoter. The elevated SAA1 in TNBC cells directly increased E-cadherin and N-cadherin phosphorylation thereby regulating cell adhesion. Mechanistically, TAF7 modulated cell invasion, migration, and lung metastasis through an SAA1-dependent manner <em>in vitro</em> and <em>in vivo</em> experiments. Taken together, it is likely that TAF7 could directly act on the SAA1 gene promoter, upregulating SAA1 and consequently promoting TNBC metastasis.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 3","pages":"Article 111989"},"PeriodicalIF":4.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474149","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}
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