Pub Date : 2026-03-26DOI: 10.1016/j.jare.2026.03.049
Lipeng Liao, Yuan Meng, Yuhang Shi, Ben Wang, Chunping Liu, Wei Qiao, Jie Shen
Background
Organoids are moving from self-organized three-dimensional (3D) cultures toward engineered living systems with translational intent. Yet most platforms still rely on static, poorly defined matrices and limited control over architecture, maturation, and batch reproducibility. Clinical translation exposes scale dependent constraints
Aim of review
This review reframes organoid translation as an engineering continuum that links controllable variables across three stages: in vitro microenvironment engineering, engineering enabled in vitro translational workflows, and in vivo clinical translation.
Key scientific concepts of review
We summarize how engineered microenvironments provide quantitative control over stiffness, geometry, and transport to improve reproducibility during organoid construction. We then discuss engineering enabled workflows that introduce dynamic conditioning and functional benchmarking to bridge in vitro performance with translational requirements. For in vivo application, we highlight vascularization and immune compatibility as a coupled bottleneck and define functional integration as measurable system level contribution rather than structural persistence alone. Together, these strategies outline a scale aware and clinically aligned engineering framework for organoid translation.
{"title":"Engineering strategies for the clinical translation of organoids","authors":"Lipeng Liao, Yuan Meng, Yuhang Shi, Ben Wang, Chunping Liu, Wei Qiao, Jie Shen","doi":"10.1016/j.jare.2026.03.049","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.049","url":null,"abstract":"<h3>Background</h3>Organoids are moving from self-organized three-dimensional (3D) cultures toward engineered living systems with translational intent. Yet most platforms still rely on static, poorly defined matrices and limited control over architecture, maturation, and batch reproducibility. Clinical translation exposes scale dependent constraints<h3>Aim of review</h3>This review reframes organoid translation as an engineering continuum that links controllable variables across three stages: in vitro microenvironment engineering, engineering enabled in vitro translational workflows, and in vivo clinical translation.<h3>Key scientific concepts of review</h3>We summarize how engineered microenvironments provide quantitative control over stiffness, geometry, and transport to improve reproducibility during organoid construction. We then discuss engineering enabled workflows that introduce dynamic conditioning and functional benchmarking to bridge in vitro performance with translational requirements. For in vivo application, we highlight vascularization and immune compatibility as a coupled bottleneck and define functional integration as measurable system level contribution rather than structural persistence alone. Together, these strategies outline a scale aware and clinically aligned engineering framework for organoid translation.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"229 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 : 2026-03-25DOI: 10.1016/j.jare.2026.03.053
Hanpeng Luo, Xiuping Cui, Yaqin Li, Pin Lv, Haiyan Zhang, Weihua Xin, Tao Zhou, Bing Liu, Qin Li, Hongyu Zhang, Wei V. Zheng, Yu Wang
Background
T cell development in the thymus proceeds through coordinated transcriptional and spatial transitions. While key stages have been described, the precise timing and regulatory logic of lineage bifurcation-such as the separation between αβ and γδ T cells, and the commitment to CD4 or CD8 fates-remain incompletely understood. A high-resolution, integrated view is needed to clarify how distinct T cell identities are established.
Objectives
The goal is to construct a comprehensive, multimodal map of thymocyte development that defines early lineage decisions, intermediate states, and spatial checkpoints underlying T cell maturation.
Methods
We generated an integrated single-cell atlas by combining single-cell transcriptomics, protein profiling (CITE-seq), chromatin accessibility (scATAC-seq), and spatial transcriptomics of murine thymus. Data integration was used to resolve developmental trajectories, identify transcription factor programs, and map the anatomical localization of thymocyte subpopulations.
Results
Our analysis revealed that αβ and γδ lineages diverge as early as the DN1 stage. Within the αβ lineage, we identified a continuum of double-positive thymocyte substages distinguished by shifts in cell surface markers, cell-cycle activity, and recombination gene expression. CD4 lineage commitment emerged as a transcriptional default program initiated by Gata3. It was maintained independently of class II MHC signaling, whereas CD8 specification required Runx3 activation and class I MHC signaling, consistent with a sequential reprogramming model. We also identified a stem-like CD8-positive population enriched for self-renewal and developmental potential genes. Spatial mapping showed medullary enrichment of CD4 cells and localization of thymocyte exit cues to the cortico-medullary junction.
Conclusions
This multimodal atlas provides a detailed framework for T cell development’s molecular and spatial logic. The findings uncover early lineage bifurcation events, refine and mechanistically characterize intermediate developmental states, and highlight anatomical checkpoints critical for thymic output and immune competence.
{"title":"Spatiotemporal multiomics reveal a default CD4 fate and a stem-like CD8 T cell subset in the thymus","authors":"Hanpeng Luo, Xiuping Cui, Yaqin Li, Pin Lv, Haiyan Zhang, Weihua Xin, Tao Zhou, Bing Liu, Qin Li, Hongyu Zhang, Wei V. Zheng, Yu Wang","doi":"10.1016/j.jare.2026.03.053","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.053","url":null,"abstract":"<h3>Background</h3>T cell development in the thymus proceeds through coordinated transcriptional and spatial transitions. While key stages have been described, the precise timing and regulatory logic of lineage bifurcation-such as the separation between αβ and γδ T cells, and the commitment to CD4 or CD8 fates-remain incompletely understood. A high-resolution, integrated view is needed to clarify how distinct T cell identities are established.<h3>Objectives</h3>The goal is to construct a comprehensive, multimodal map of thymocyte development that defines early lineage decisions, intermediate states, and spatial checkpoints underlying T cell maturation.<h3>Methods</h3>We generated an integrated single-cell atlas by combining single-cell transcriptomics, protein profiling (CITE-seq), chromatin accessibility (scATAC-seq), and spatial transcriptomics of murine thymus. Data integration was used to resolve developmental trajectories, identify transcription factor programs, and map the anatomical localization of thymocyte subpopulations.<h3>Results</h3>Our analysis revealed that αβ and γδ lineages diverge as early as the DN1 stage. Within the αβ lineage, we identified a continuum of double-positive thymocyte substages distinguished by shifts in cell surface markers, cell-cycle activity, and recombination gene expression. CD4 lineage commitment emerged as a transcriptional default program initiated by Gata3. It was maintained independently of class II MHC signaling, whereas CD8 specification required Runx3 activation and class I MHC signaling, consistent with a sequential reprogramming model. We also identified a stem-like CD8-positive population enriched for self-renewal and developmental potential genes. Spatial mapping showed medullary enrichment of CD4 cells and localization of thymocyte exit cues to the cortico-medullary junction.<h3>Conclusions</h3>This multimodal atlas provides a detailed framework for T cell development’s molecular and spatial logic. The findings uncover early lineage bifurcation events, refine and mechanistically characterize intermediate developmental states, and highlight anatomical checkpoints critical for thymic output and immune competence.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"7 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 : 2026-03-23DOI: 10.1016/j.jare.2026.03.050
Liang Hong, Muyao Teng, Min He, Jing Zhao, Shaoping Li
{"title":"AI-driven multi-scale target analysis of traditional Chinese medicine: From the pharmacological effects of single compounds to the synergistic mechanisms of formulae","authors":"Liang Hong, Muyao Teng, Min He, Jing Zhao, Shaoping Li","doi":"10.1016/j.jare.2026.03.050","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.050","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"51 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147501919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 : 2026-03-22DOI: 10.1016/j.jare.2026.03.040
Chien-Wen Su, Tangyou Mao, Chih-Yu Chen, Qiaorong Ji, Lefei Jiao, Jinggang Lan, Shao Rong Long, Jing Yang, Qing Wang, Yuhang Zhao, Chongzhao Ran, W.Allan Walker, Xiqun Chen, Alessio Fasano, Bobby J. Cherayil, Junxiang Li, Hai Ning Shi
{"title":"Helminth infection induces malabsorption of dietary fat via STAT6-dependent intestinal MTTP suppression","authors":"Chien-Wen Su, Tangyou Mao, Chih-Yu Chen, Qiaorong Ji, Lefei Jiao, Jinggang Lan, Shao Rong Long, Jing Yang, Qing Wang, Yuhang Zhao, Chongzhao Ran, W.Allan Walker, Xiqun Chen, Alessio Fasano, Bobby J. Cherayil, Junxiang Li, Hai Ning Shi","doi":"10.1016/j.jare.2026.03.040","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.040","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"14 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147496210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 : 2026-03-22DOI: 10.1016/j.jare.2026.03.046
Olha Kholod, Hien M. Bui, H.Robert Frost, Brittany A. Goods
{"title":"A Composite interaction Score: Prioritizing cell–cell interactions from single-cell RNA-seq with application to pre-menopausal epithelial barriers","authors":"Olha Kholod, Hien M. Bui, H.Robert Frost, Brittany A. Goods","doi":"10.1016/j.jare.2026.03.046","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.046","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"20 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147496211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 : 2026-03-22DOI: 10.1016/j.jare.2026.03.044
Tian Zhao, Yansong Zhang, Zhangtie Wang, Junyi Yin, Shaoping Nie, Yuelu Jiang, Chongde Sun, Baiyi Lu
Introduction
Phytosterols (PS) are natural compounds with well-established cholesterol-lowering properties. However, their systemic bioavailability is remarkably low compared to cholesterol. While dietary Monounsaturated fatty acids (MUFA) are known to reduce cholesterol absorption and potentially positive role in PS absorption, their specific impact on the differential absorption and esterification of PS remains unclear.
Objective
This study aimed to identify the key step limiting PS absorption and to reveal the mechanism by which dietary MUFA regulates PS absorption and sterol homeostasis.
Methods
In vitro digestion models received PS and cholesterol, while high-MUFA diet-fed mice were administered PS. Enterocytes were treated with oleic acid (OA) and PS. PS absorption, Acyl-Coenzyme A: cholesterol acyltransferase 2 (ACAT2) activity, and blood lipid were evaluated. Dynamic molecular simulation assessed enzyme-substrate binding, and the FXR/CDX2/ACAT2 pathway governing sterol esterification was explored.
Results
MUFA reprogrammed intestinal sterol metabolism through dual regulation of ACAT2, shifting control from enzyme abundance to catalytic efficiency. While FXR/CDX2-mediated repression reduced cholesterol esterification, MUFA-derived oleoyl-CoA allosterically stabilized the ACAT2 active site, selectively enhancing PS turnover. This asymmetric compensatory mechanism redirected ACAT2 substrate preference, promoting phytosterol ester (PE) accumulation while limiting cholesterol ester (CE) production.
Conclusion
Evidence demonstrate that dietary MUFA enhances the catalytic preference of ACAT2 for PS while transcriptionally fine-tuning the overall enzyme activity through the FXR/CDX2/ACAT2 pathway. These finding of ACAT2 as a key mediator for nutritional strategies aimed at improving sterol homeostasis and combating metabolic diseases.
{"title":"Phytosterol alleviates cholesterol accumulation by influencing intestinal esterification rather than competitive solubilization under dietary MUFA","authors":"Tian Zhao, Yansong Zhang, Zhangtie Wang, Junyi Yin, Shaoping Nie, Yuelu Jiang, Chongde Sun, Baiyi Lu","doi":"10.1016/j.jare.2026.03.044","DOIUrl":"https://doi.org/10.1016/j.jare.2026.03.044","url":null,"abstract":"<h3>Introduction</h3>Phytosterols (PS) are natural compounds with well-established cholesterol-lowering properties. However, their systemic bioavailability is remarkably low compared to cholesterol. While dietary Monounsaturated fatty acids (MUFA) are known to reduce cholesterol absorption and potentially positive role in PS absorption, their specific impact on the differential absorption and esterification of PS remains unclear.<h3>Objective</h3>This study aimed to identify the key step limiting PS absorption and to reveal the mechanism by which dietary MUFA regulates PS absorption and sterol homeostasis.<h3>Methods</h3>In vitro digestion models received PS and cholesterol, while high-MUFA diet-fed mice were administered PS. Enterocytes were treated with oleic acid (OA) and PS. PS absorption, Acyl-Coenzyme A: cholesterol acyltransferase 2 (ACAT2) activity, and blood lipid were evaluated. Dynamic molecular simulation assessed enzyme-substrate binding, and the FXR/CDX2/ACAT2 pathway governing sterol esterification was explored.<h3>Results</h3>MUFA reprogrammed intestinal sterol metabolism through dual regulation of ACAT2, shifting control from enzyme abundance to catalytic efficiency. While FXR/CDX2-mediated repression reduced cholesterol esterification, MUFA-derived oleoyl-CoA allosterically stabilized the ACAT2 active site, selectively enhancing PS turnover. This asymmetric compensatory mechanism redirected ACAT2 substrate preference, promoting phytosterol ester (PE) accumulation while limiting cholesterol ester (CE) production.<h3>Conclusion</h3>Evidence demonstrate that dietary MUFA enhances the catalytic preference of ACAT2 for PS while transcriptionally fine-tuning the overall enzyme activity through the FXR/CDX2/ACAT2 pathway. These finding of ACAT2 as a key mediator for nutritional strategies aimed at improving sterol homeostasis and combating metabolic diseases.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"15 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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