tbuckley/cabot-search huggingface dataset:
Origin and de novo domestication of sweet orange
Authors: Shengjun Liu, Yuantao Xu, Kun Yang, Yue Huang, Zhihao Lu, Shulin Chen, Xiang Gao, Gongao Xiao, Peng Chen, Xiuli Zeng, Lun Wang, Weikang Zheng, Zishuang Liu, Guanglian Liao, Fa He, Junjie Liu, Pengfei Wan, Fang Ding, Junli Ye, Wenbiao Jiao, Lijun Chai, Zhiyong Pan, Fei Zhang, Zongcheng Lin, Yanjun Zan, Wenwu Guo, Robert M. Larkin, Zongzhou Xie, Xia Wang, Xiuxin Deng, Qiang Xu
Journal: Nature Genetics (2025)

Sweet orange is cultivated worldwide but suffers from various devastating diseases because of its monogenetic background. The elucidation of the origin of a crop facilitates the domestication of new crops that may better cope with new challenges. Here we collected and sequenced 226 citrus accessions and assembled telomere-to-telomere phased diploid genomes of sweet orange and sour orange. On the basis of a high-resolution haplotype-resolved genome analysis, we inferred that sweet orange originated from a sour orange × mandarin cross and confirmed this model using artificial hybridization experiments. We identified defense-related metabolites that potently inhibited the growth of multiple industrially important pathogenic bacteria. We introduced diversity to sweet orange, which showed wide segregation in fruit flavor and disease resistance and produced canker-resistant sweet orange by selecting defense-related metabolites. Our findings elucidate the origin of sweet orange and de novo domesticated disease-resistant sweet oranges, illuminating a strategy for the rapid domestication of perennial crops.
Identifying perturbations that boost T-cell infiltration into tumours via counterfactual learning of their spatial proteomic profiles
Authors: Zitong Jerry Wang, Abdullah S. Farooq, Yu-Jen Chen, Aman Bhargava, Alexander M. Xu, Matt W. Thomson
Journal: Nature Biomedical Engineering (2025)

Cancer progression can be slowed down or halted via the activation of either endogenous or engineered T cells and their infiltration of the tumour microenvironment. Here we describe a deep-learning model that uses large-scale spatial proteomic profiles of tumours to generate minimal tumour perturbations that boost T-cell infiltration. The model integrates a counterfactual optimization strategy for the generation of the perturbations with the prediction of T-cell infiltration as a self-supervised machine learning problem. We applied the model to 368 samples of metastatic melanoma and colorectal cancer assayed using 40-plex imaging mass cytometry, and discovered cohort-dependent combinatorial perturbations (CXCL9, CXCL10, CCL22 and CCL18 for melanoma, and CXCR4, PD-1, PD-L1 and CYR61 for colorectal cancer) that support T-cell infiltration across patient cohorts, as confirmed via in vitro experiments. Leveraging counterfactual-based predictions of spatial omics data may aid the design of cancer therapeutics.
Single-cell immune aging clocks reveal inter-individual heterogeneity during infection and vaccination
Authors: Wenchao Li, Zhenhua Zhang, Saumya Kumar, Javier Botey-Bataller, Martijn Zoodsma, Ali Ehsani, Qiuyao Zhan, Ahmed Alaswad, Liang Zhou, Inge Grondman, Valerie Koeken, Jian Yang, Gang Wang, Sonja Volland, Tania O. Crişan, Leo A. B. Joosten, Thomas Illig, Cheng-Jian Xu, Mihai G. Netea, Yang Li
Journal: Nature Aging (2025)

Aging affects human immune system functionality, increasing susceptibility to immune-mediated diseases. While gene expression programs accurately reflect immune function, their relationship with biological immune aging and health status remains unclear. Here we developed robust, cell-type-specific aging clocks (sc-ImmuAging) for the myeloid and lymphoid immune cell populations in circulation within peripheral blood mononuclear cells, using single-cell RNA-sequencing data from 1,081 healthy individuals aged from 18 to 97 years. Application of sc-ImmuAging to transcriptome data of patients with COVID-19 revealed notable age acceleration in monocytes, which decreased during recovery. Furthermore, inter-individual variations in immune aging induced by vaccination were identified, with individuals exhibiting elevated baseline interferon response genes showing age rejuvenation in CD8+ T cells after BCG vaccination. sc-ImmuAging provides a powerful tool for decoding immune aging dynamics, offering insights into age-related immune alterations and potential interventions to promote healthy aging.
Asparagine deprivation enhances T cell antitumour response in patients via ROS-mediated metabolic and signal adaptations
Authors: Hsuan-Chia Chang, Chung-Ying Tsai, Cheng-Lung Hsu, Tzong-Shyuan Tai, Mei-Ling Cheng, Yu-Ming Chuang, Hsiang-Yu Tang, Kun-Ju Lin, Jia-Jin Chen, Szu-Han Chang, Yi-Ching Ko, Yu-Wen Chi, Hsuan Liu, Bertrand Chin-Ming Tan, Chia-Rui Shen, Chih-Wei Yang, Ping-Chih Ho, Huang-Yu Yang
Journal: Nature Metabolism (2025)

Preclinical studies have shown that asparagine deprivation enhances T cell antitumour responses. Here we apply compassionate use of L-asparaginase, usually employed to treat blood malignancies, on patients with recurrent metastatic nasopharyngeal carcinoma. The use of L-asparaginase notably enhances immune-checkpoint blockade therapy in patients by strengthening CD8+T cell fitness. Our study shows that this combination is a promising avenue for clinical application and provides further mechanistic insight into how asparagine restriction rewires T cell metabolism.
Noninvasive Quantification of Hepatic Steatosis Using Ultrasound‐Derived Fat Fraction (CHESS2303): A Prospective Multicenter Study
Authors: Yunlin Huang, Jia Li, Chuan Liu, Danlei Song, Chuanlong Zhu, Yongfeng Ren, Jiaojian Lv, Longfeng Jiang, Rong Shan, Hao Wang, Zhou Wang, Siqin Long, Fan Jiang, Xiang Xie, Liren Lu, Ruixiang Qi, Pengfei Rong, Chuxiao Shao, Wang Yao, Youfang Gao, Wenping Wang, Juan Cheng, Vincent Wai‐Sun Wong, Ying Wang, Wai‐Kay Seto, Yi Dong, Christoph F. Dietrich, Xiaolong Qi
Journal: MedComm (2025)

ABSTRACT Ultrasound‐derived fat fraction (UDFF) is designed to assess the hepatic fat content quantitatively. A multicenter study that verifies the diagnostic performance of UDFF for detecting hepatic steatosis has not yet been reported. This study aimed to evaluate the performance of UDFF for diagnosing and grading hepatic steatosis. Participants referred for assessment of hepatic steatosis were prospectively recruited from eight hospitals. All participants underwent UDFF and magnetic resonance imaging proton density fat fraction (MRI‐PDFF) examinations. MRI‐PDFF was used as the reference for diagnosing hepatic steatosis. From January 2023 to July 2023, a total of 300 participants were included. The median body mass index was 25.4 kg/m 2 (interquartile range: 22.7–28.1). UDFF values were positively correlated with MRI‐PDFF ( R = 0.80, p &lt; 0.001). Using MRI‐PDFF ≥ 5%, ≥ 15%, and ≥ 25% as the reference standard for detecting mild, moderate, and severe hepatic steatosis, the best cutoff values of UDFF were 7.6% (area under the receiver operating characteristic curves [AUC] = 0.90), 15.9% (AUC = 0.90), and 22.3% (AUC = 0.91), respectively. Thus, UDFF has excellent diagnostic performance in detecting and grading hepatic steatosis.
Peripheral Biomarker Signatures in Rheumatoid Arthritis‐Associated Interstitial Lung Disease
Authors: Austin M. Wheeler, Joshua F. Baker, Thomas R. Riley, Tate M. Johnson, Yangyuna Yang, Punyasha Roul, Katherine D. Wysham, Grant W. Cannon, Gary Kunkel, Gail Kerr, Dana P. Ascherman, Paul Monach, Andreas Reimold, Scott Matson, Jill A. Poole, Michael J. Duryee, Geoffrey M. Thiele, Ted R. Mikuls, Bryant R. England
Journal: Arthritis & Rheumatology (2025)

Objective Rheumatoid arthritis‐associated interstitial lung disease (RA‐ILD) is a significant cause of morbidity and mortality among patients with RA, yet effective risk stratification for RA‐ILD is lacking. We sought to characterize unique peripheral blood biomarker signatures in RA that could improve RA‐ILD discrimination beyond clinical and genetic risk factors. Methods We performed a cross‐sectional study of participants in the Veterans Affairs Rheumatoid Arthritis (VARA) registry. ILD was validated through systematic record review. Autoantibodies (n=14), pro‐inflammatory cytokines/chemokines (n=36), adipokines (n=3), alarmins (n=3), and matrix metalloproteinases (n=9) were measured from banked serum or plasma. MUC5B rs35705950 genotyping was obtained via microarray. Principal component analysis (PCA) was performed to derive unique biomarker signatures. Logistic regression was used to compare models predicting RA‐ILD presence using combinations of clinical, peripheral biomarker, and genetic variables. Results Among 2,001 participants with RA (88.7% male, mean age 63.7 years), 121 (6.4%) had RA‐ILD. Fifteen principal components (PCs) were identified, with eight significantly associated with RA‐ILD after adjusting for clinical factors. These eight included biomarker themes of innate and allergic responses, autoantibodies (anti‐cyclic citrullinated peptide, rheumatoid factor, anti‐malondialdehyde‐acetaldehyde adduct), adipokines, alarmins, tissue remodeling, and neutrophil chemotaxis. Models with PCs (area under the curve [AUC] 0.739) and PCs + MUC5B (AUC 0.751) outperformed clinical risk factors alone (AUC 0.630; p&lt;0.001). Conclusion Peripheral biomarker signatures are associated with RA‐ILD and improve RA‐ILD identification beyond clinical risk factors. In addition to demonstrating the potential for peripheral biomarkers to aid RA‐ILD risk stratification, these findings suggest diverse pathways are involved in RA‐ILD pathogenesis. image
Microenvironment‐Regulated Hydrogels Prepared with a Brand‐New Small Molecule Cross‐Linker for Stepwise Treatment of Myocardial Infarction
Authors: Yu Wu, Wen Zhang, Linlin Huang, Xinping Xu, Shuyi He, Zhicun Wang, Wenqi Liu, Ya Yao, Li Yang, Cheng Hu, Yunbing Wang
Journal: Advanced Healthcare Materials (2025)

Abstract Despite the development of many injectable hydrogels intended for the repair of myocardial infarction (MI), their effectiveness is often compromised because they target merely one or two phases of MI's pathological progression. Here, a multifunctional hydrogel delivery platform is prepared with a brand‐new small molecule cross‐linker for stepwise treatment of MI. The synthesis and reporting of a novel small‐molecule phenylboronic acid cross‐linker ((N(BA) 3 )) with a precise molecular structure is conducted for the first time, and it is successfully utilized with polyvinyl alcohol (PVA) dopamine to prepare a hydrogel with infarct microenvironmental responsiveness and anti‐oxidant. Further, considering the multistage of MI repair, hydrogel contains both hyperoside bioactive nanoparticles (EGCG@Hyp&amp;Arg NPs) and PLGA microspheres loaded with galunisertib (PLGA@Gal Ms). The EGCG@Hyp&amp;Arg NPs are rapidly released and demonstrate anti‐inflammatory and pro‐angiogenesis effects, while in the long term, Gal is released from the PLGA@Gal Ms to inhibit myocardial fibrosis and improve cardiac function. Results from both in vitro and in vivo studies reveal that the hydrogel is engineered with programmed capabilities for anti‐oxidation, reducing inflammation, promoting new blood vessel formation, and inhibiting fibrosis, thereby significantly enhancing heart function post‐MI. Overall, this multifunctional hydrogel delivery platform has great potential for application as a therapeutic strategy for MI.
Energy Metabolism Supports Molecular and Functional Heterogeneity of Reactive Astrocytes in Central Nervous System Disorders
Authors: Jie Song, Jianning Kang, Ying Zhang, Yinghui Wang, Rui Yang, Bin Ning
Journal: Medicinal Research Reviews (2025)

ABSTRACT Astrocytes undergo a reactive transformation in central nervous system (CNS) disorders, manifesting significant heterogeneity in morphology, molecules, function, and spatial distribution. Just like all cells, astrocytes necessitate energy for their basic functions. Energy production proves critical for the survival and development of astrocytes, as well as their fate determination and functional diversity. The activation process of astrocytes involves a metabolic shift in energy, yet our understanding of how this change impacts the heterogeneity of reactive astrocytes remains limited. In this comprehensive review, we begin by outlining the advancements in research on reactive astrocytes in CNS disorders, establishing a crucial association between the energy metabolism of reactive astrocytes and their molecular and functional aspects. Following this, we delve into a thorough analysis of the energy metabolic transitions of reactive astrocytes within the context of CNS diseases. Starting from the essential pathways of energy metabolism, we present a novel perspective, shedding light on the molecular and functional heterogeneity of reactive astrocytes by considering the heterogeneity in energy metabolism. In conclusion, we propose that the modulation of energy metabolism in reactive astrocytes, coupled with the promotion of their functionality toward disease recovery, represents a cutting‐edge and promising strategy for the treatment of CNS diseases.
Inflamed Tissue‐Targeting Polyphenol‐Condensed Antioxidant Nanoparticles with Therapeutic Potential
Authors: Dohyub Jang, Honghwan Choi, Juhyang Lee, Yousun Chun, Yoon‐Ho Heo, Luke P. Lee, Dong June Ahn, Ik‐Soo Shin, Dong Ha Kim, Young Hun Seo, Sehoon Kim
Journal: Advanced Healthcare Materials (2025)

Abstract Inflammation is essential for pathogen eradication and tissue repair; However, chronic inflammation can bring on multi‐organ dysfunction due to an overproduction of reactive oxygen species (ROS). Among various anti‐inflammatory agents, polyphenol‐based nanotherapeutics offer potential advantages, including enhanced stability, targeted delivery, multiple therapeutic functions, and personalized therapy tailored to the severity. Despite these advantages, the development of biocompatible nanomedicines capable of selective accumulation in inflamed tissues and efficient inhibition of ROS‐induced inflammatory signaling pathways remains a considerable challenge. In this study, a novel anti‐inflammatory nanotherapeutic is engineered through the temperature‐dependent condensation of polyphenolic catechin facilitated by hydrothermal reactions. The resulting catechin‐condensed nanotherapeutic (CCN150), synthesized at a relatively low temperature, retains physicochemical and functional properties akin to its precursor, catechin, but with a marked enhancement in water solubility. CCN150 protects cells from oxidative stress by eliminating intracellular ROS and augmenting antioxidant enzymes. In vivo studies reveal that intravenously administered CCN150 predominantly accumulates in inflamed tissues, with minimal distribution to healthy regions. Furthermore, CCN150 effectively reduces systemic inflammation in mouse models by disrupting the cycles of ROS instigated by a pro‐inflammatory oxidative milieu. Exhibiting negligible toxicity, CCN150 holds substantial promise for extensive therapeutic applications in the treatment of various ROS‐mediated inflammatory diseases.
Advanced Toolboxes for Cryobioprinting Human Tissue Analogs
Authors: Francisca P. Correia, Maria V. Monteiro, Mafalda Borralho, Yu Shrike Zhang, João F. Mano, Vítor M. Gaspar
Journal: Advanced Healthcare Materials (2025)

Abstract The increasing demand for biofabricating human tissue analogs for therapeutic applications has encouraged the pursuit of innovative techniques that shift from conventional bioprint‐to‐use approaches toward instantaneous bioprint‐cryopreserve strategies. Such enabling concepts and next‐generation technologies open new possibilities for fabricating shelf‐ready living constructs for applications in regenerative medicine, preclinical disease modeling, and beyond. The generation of living constructs either for short‐ or long‐term cryostorage requires, however, a careful design of cryoprotective bioinks to maximize biofunctionality and limit cell damage during processing. Gathering on this, herein the most recent updates in cryo(bio)printing technologies are showcased and discussed, along with demonstrative applications of these approaches. The technical toolboxes for designing cryoprotective inks and optimizing freezing/thawing processes are also critically addressed, considering their underlying bioengineering challenges. Realizing the full potential of cryobioprinting is envisioned to unlock the fabrication of increasingly biomimetic tissue constructs and personalized medicine solutions that are readily available, precisely when needed.
Phase 2‐3 Trial: Prevention of the Progression to Moderate and Severe <scp>COVID</scp>‐19 in <scp>SARS</scp>‐<scp>CoV</scp>‐2‐Infected Non‐Hospitalized Adults With Inhaled <scp>siRNA</scp>‐Based <scp>MIR</scp> 19
Authors: M. Khaitov, A. Nikonova, V. Smirnov, I. Shilovsky, I. Kofiadi, E. Ruzanova, V. Teplykh, D. Makarov, A. Vertichikh, S. Teplykh, D. Alpenidze, E. Muldagalieva, E. Simakina, T. Ivanushkina, K. Zakharov, L. Melnikova, D. Medvedev, O. Zuev, D. Kudlay, D. Kruchko, I. Berzin, R. Valenta, V. Skvortsova
Journal: Allergy (2025)

ABSTRACT Background COVID‐19 continues to be a major global health challenge. Inhaled siRNA‐based MIR 19 has been shown to reduce the time to clinical improvement in patients hospitalized with moderate COVID‐19. Methods We conducted an open‐label, randomized, controlled multicenter phase 2b‐3 trial (NCT05783206) evaluating the safety and efficacy of inhaled siR‐7‐EM/KK‐46 (MIR 19) (5.55 mg/day) in comparison with standard care (control group) in outpatients with mild COVID‐19 ( N = 492 for each group). The primary endpoint was the proportion of patients who developed moderate or severe COVID‐19 by the 28th day of randomization. Results Moderate or severe course of the disease was detected in 14 (2.85%) and 34 (6.91%) patients in the siR‐7‐EM/KK‐46 (5.55 mg) and standard therapy groups, respectively (the difference in proportions was −4.107% [95% CI: −7.28% to −1.03%] ( p = 0.002)). Adverse events (AE) were reported in 77 (15.65%) patients from the siR‐7‐EM/KK‐46 (5.55 mg) group, while in the standard therapy group AEs were registered in 100 (20.33%) patients. No severe, treatment‐related AEs were observed in the siR‐7‐EM/KK‐46 group. Conclusions siR‐7‐EM/KK‐46, a SARS‐CoV‐2‐specific RNAi‐based drug, was well‐tolerated and significantly decreased the progression to moderate/severe disease in outpatients with mild COVID‐19.
Minimal Tofacitinib dose for Maintenance in Axial Spondyloarthritis: Real world data from a Resource‐limited setting
Authors: Anu Sreekanth, Justin George, Sakir Ahmed, Pankti Mehta, Sanjo Saijan, Aparna R Menon, Bhowmik Meghnathi, Padmanabha Shenoy D
Journal: Arthritis & Rheumatology (2025)
CircAars‐Engineered ADSCs Facilitate Maxillofacial Bone Defects Repair Via Synergistic Capability of Osteogenic Differentiation, Macrophage Polarization and Angiogenesis
Authors: Yi He, Yunyang Lu, Runze Li, Yuquan Tang, Weidong Du, Lejia Zhang, Jie Wu, Kechen Li, Weijie Zhuang, Shiyu Lv, Yaoling Han, Bailong Tao, Feilong Deng, Wei Zhao, Dongsheng Yu
Journal: Advanced Healthcare Materials (2025)

Abstract Adipose‐derived stem cells (ADSCs) hold significant promise in bone tissue engineering due to their self‐renewal capacity and easy accessibility. However, their limited osteogenic potential remains a critical challenge for clinical application in bone repair. Emerging evidence suggests that circular RNAs (circRNAs) play a key role in regulating stem cell fate and osteogenesis. Despite this, the specific mechanisms by which circRNAs influence ADSCs in the context of bone tissue engineering are largely unexplored. This study introduces a novel strategy utilizing circAars, a specific circRNA, to modify ADSCs, which are then incorporated into gelatin methacryloyl (GelMA) hydrogels for the repair of critical‐sized maxillofacial bone defects. The findings reveal that circAars predominantly localizes in the cytoplasm of ADSCs, where it acts as a competitive sponge for miR‐128‐3p, enhancing the osteogenic differentiation and migration capabilities of ADSCs. Furthermore, circAars‐engineered ADSCs facilitate macrophage polarization from the M1 to M2 phenotype and enhance endothelial cell (EC) angiogenic potential through a paracrine mechanism. Additionally, GelMA scaffolds loaded with circAars‐engineered ADSCs accelerate the repair of critical‐sized maxillofacial bone defects by synergistically promoting osteogenesis, macrophage M2 polarization, and angiogenesis. This approach offers a promising therapeutic strategy for the treatment of critical‐sized maxillofacial defects.
“Therapies Through Gut:” Targeted Drug Delivery for Non‐Gastrointestinal Diseases by Oral Administration
Authors: Subarna Ray, Shehzahdi S. Moonshi, Hang Thu Ta
Journal: Advanced Healthcare Materials (2025)

Abstract Oral drug delivery is a promising approach for the treatment of various gastrointestinal (GI) diseases but poses significant challenges to target non‐GI diseases. The intestinal barrier forms a significant anatomical challenge to reach the target diseased site, along with various physiological challenges such as stability in the GI tract. These challenges lead to development of various targeted nanoparticles and strategies to cross intestinal barrier and protect them from harsh conditions in the GI tract, improving absorption into the circulatory system, improving bioavailability, and ensuring a regulated release. Targeting ligands such as chitosan, Butyrate (BU), and yeast capsule (YC) shows effective permeability across the intestinal epithelium. After crossing the intestinal epithelium, these targeted strategies can effectively treat various non‐GI diseases such as atherosclerosis, cancers, neurodegenerative diseases, fibrosis, and post‐traumatic osteoarthritis. However, various challenges including stability and low bioavailability still persist, which can reduce the efficacy of these therapeutics and should be considered in designing potential therapies for non‐GI diseases in the near future.
A Consensus Statement on establishing causality, therapeutic applications and the use of preclinical models in microbiome research
Authors: Amira Metwaly, Aicha Kriaa, Zahra Hassani, Federica Carraturo, Celine Druart, Kaline Arnauts, Paul Wilmes, Jens Walter, Stephan Rosshart, Mahesh S Desai, Joel Dore, Hervé M Blottiere, Emmanuelle Maguin, Dirk Haller
Journal: Nature Reviews Gastroenterology & Hepatology (2025)
Liver Metastasis in Cancer: Molecular Mechanisms and Management
Authors: Wenchao Xu, Jia Xu, Jianzhou Liu, Nanzhou Wang, Li Zhou, Junchao Guo
Journal: MedComm (2025)

Abstract Liver metastasis is a leading cause of mortality from malignant tumors and significantly impairs the efficacy of therapeutic interventions. In recent years, both preclinical and clinical research have made significant progress in understanding the molecular mechanisms and therapeutic strategies of liver metastasis. Metastatic tumor cells from different primary sites undergo highly similar biological processes, ultimately achieving ectopic colonization and growth in the liver. In this review, we begin by introducing the inherent metastatic‐friendly features of the liver. We then explore the panorama of liver metastasis and conclude the three continuous, yet distinct phases based on the liver's response to metastasis. This includes metastatic sensing stage, metastatic stress stage, and metastasis support stage. We discuss the intricate interactions between metastatic tumor cells and various resident and recruited cells. In addition, we emphasize the critical role of spatial remodeling of immune cells in liver metastasis. Finally, we review the recent advancements and the challenges faced in the clinical management of liver metastasis. Future precise antimetastatic treatments should fully consider individual heterogeneity and implement different targeted interventions based on stages of liver metastasis.