tbuckley/cabot-search huggingface dataset:
A Smart MMP‐9‐responsive Hydrogel Releasing M2 Macrophage‐derived Exosomes for Diabetic Wound Healing
Authors: Hao Meng, Jianlong Su, Qi Shen, Wenzhi Hu, Pinxue Li, Kailu Guo, Xi Liu, Kui Ma, Weicheng Zhong, Shengqiu Chen, Liqian Ma, Yaying Hao, Junli Chen, Yufeng Jiang, Linlin Li, Xiaobing Fu, Cuiping Zhang
Journal: Advanced Healthcare Materials (2025)

Chronic diabetic wounds are characterized by prolonged inflammation and excessive accumulation of M1 macrophages, which impede the healing process. Therefore, resolving inflammation promptly and transitioning to the proliferative phase are critical steps for effective diabetic wound healing. Exosomes have emerged as a promising therapeutic strategy. In this study, a smart hydrogel capable of responding to pathological cues in the inflammatory microenvironment to promote the transition from inflammation to proliferation by delivering M2 macrophage-derived exosomes (M2-Exos) is developed. The smart hydrogel is synthesized through the cross-linking of oxidized dextran, a matrix metalloproteinase (MMP)-9-sensitive peptide, and carboxymethyl chitosan containing M2-Exos. In response to elevated MMP-9 concentrations in the inflammatory microenvironment, the hydrogel demonstrates diagnostic logic, adjusting the release kinetics of M2-Exos accordingly. The on-demand release of M2-Exos facilitated macrophage polarization from the M1 to the M2 phenotype, thereby promoting the transition from the inflammatory to the proliferative phase and accelerating diabetic wound healing. The transcriptomic analysis further reveals that the MMP-9-responsive hydrogel with M2-Exos delivery exerts anti-inflammatory and regenerative effects by downregulating inflammation-related pathways. This study introduces an innovative, microenvironment-responsive exosome delivery system that enables precise control of therapeutic agent release, offering a personalized approach for the treatment of chronic diabetic wounds.
Highly Extensible Physically Crosslinked Hydrogels for High‐Speed 3D Bioprinting
Authors: Ye Eun Song, Noah Eckman, Samya Sen, Carolyn K. Jons, Olivia M. Saouaf, Eric A. Appel
Journal: Advanced Healthcare Materials (2025)

Abstract Hydrogels have emerged as promising materials for bioprinting and many other biomedical applications due to their high degree of biocompatibility and ability to support and/or modulate cell viability and function. Yet, many hydrogel bioinks have suffered from low efficiency due to limitations on accessible printing speeds, often limiting cell viability and/or the constructs which can be generated. In this study, a highly extensible bioink system created by modulating the rheology of physically crosslinked hydrogels comprising hydrophobically‐modified cellulosics and either surfactants or cyclodextrins is reported. It is demonstrated that these hydrogels are highly shear‐thinning with broadly tunable viscoelasticity and stress‐relaxation through simple modulation of the composition. Rheological experiments demonstrate that increasing concentration of rheology‐modifying additives yields hydrogel materials exhibiting extensional strain‐to‐break values up to 2000%, which is amongst the most extensible examples of physically crosslinked hydrogels of this type. The potential of these hydrogels for use as bioinks is demonstrated by evaluating the relationship between extensibility and printability, demonstrating that greater hydrogel extensibility enables faster print speeds and smaller print features. The findings suggest that optimizing hydrogel extensibility can enhance high‐speed 3D bioprinting capabilities, reporting over 5000 fold enhancement in speed index compared to existing works reported for hydrogel‐based bioinks in extrusion‐based printing.
Injectable Microspheres With Cartilage‐Like Structure Facilitate Inflammation Inhibition and Tissue Regeneration
Authors: Qi Feng, Qingtao Li, Zequ Lin, Xinbin Xu, Yue Huang, Hua Dong, Xiaodong Cao
Journal: Advanced Healthcare Materials (2025)

Abstract The unique structure of cartilage tissue, characterized by a robust collagen fiber framework and a dynamic proteoglycan hydrogel filling, is crucial for maintaining biomechanical and biochemical homeostasis. Herein, a cartilage‐inspired microsphere with sponge framework and hydrogel filling (SponGel MS) is successfully prepared to restore cartilage homeostasis. Specifically, epigallocatechin gallate nanoparticles coated with MnO 2 (MnO 2 @EGCG) are first synthesized, which can scavenge H 2 O 2 and hydroxyl radicals. The formation of SponGel MS involves sequential fabrication of the sponge phase through cryogenic radical reaction and hydrogel phase via Schiff base reaction. The hydrogel phase can dynamically release MnO 2 @EGCG to inhibit inflammation and SDF‐1 to recruit stem cells. Porous sponge phase with favorable compressive performance and His‐Ala‐Val (HAV) peptide provides stable stem cell niches to regulate stem cell condensation, co‐assembly and chondrogenic differentiation. Animal experiments demonstrate that SponGel MS suppresses the expression of IL‐1β and collagen I, ultimately achieving cartilage regeneration. This study represents a novel strategy for constructing cartilage repair materials.
Application of 4D‐Printed Magnetoresponsive FOGS Hydrogel Scaffolds in Auricular Cartilage Regeneration
Authors: Hongyi Zhang, Shan Hua, Chenlong He, Ming Yin, Jingwen Qin, Huawei Liu, Han Zhou, Shengming Wu, Xingge Yu, Hua Jiang, Yilong Wang, Yuxin Qian
Journal: Advanced Healthcare Materials (2025)

3D-printed hydrogel scaffolds are widely utilized in auricular cartilage tissue engineering. However, issues such as graft-related inflammation, poor mechanical properties, and the lack of external modulation of 3D-printed scaffolds in vivo have raised significant concerns. To address these challenges, a "fried egg" structure is designed, consisting of chitosan-coated ferroferric oxide magnetic nanoparticles (Fe3O4@CS MNPs), which are uniformly incorporated into hydrogel. Through 4D printing technology, magnetoresponsive hydrogel scaffolds are constructed to overcome the aforementioned limitations. The results demonstrated that, compared to 3D printing, 4D-printed magnetic hydrogel scaffolds significantly enhanced cartilage tissue regeneration in both in vitro and in vivo environments when subjected to an external magnetic field (MF). Furthermore, the mechanical strength of regenerated cartilage approached to that of natural cartilage. The chitosan coating on the surface of MNPs exhibited anti-inflammatory and antibacterial properties, promoting M2 polarization of macrophages and suppressing graft-related inflammation and bacteria. Transcriptomic analysis confirmed that MNPs modulate macrophage immunity by activating JAK2/STAT3 signaling pathway. Taken together, a magnetoresponsive multifunctional scaffold is designed that can be externally controlled by magnetic fields to promote ear cartilage tissue regeneration. The regenerated cartilage exhibits excellent biocompatibility, anti-inflammatory, antibacterial properties, and mechanical performance, providing new insights for auricular cartilage tissue engineering.
Nonclassical action of Ku70 promotes Treg-suppressive function through a FOXP3-dependent mechanism in lung adenocarcinoma
Authors: Qianru Huang, Na Tian, Jianfeng Zhang, Shiyang Song, Hao Cheng, Xinnan Liu, Wenle Zhang, Youqiong Ye, Yanhua Du, Xueyu Dai, Rui Liang, Dan Li, Sheng-Ming Dai, Chuan Wang, Zhi Chen, Qianjun Zhou, Bin Li
Journal: Journal of Clinical Investigation (2025)
Regulation of TTN as a mechanism of and treatment for heart failure
Authors: Dominic E. Fullenkamp
Journal: Journal of Clinical Investigation (2025)

Truncation variants in the gene TTN encoding titin are the most common cause of familial dilated cardiomyopathy (DCM), with both haploinsufficiency and "poison peptide" implicated as contributory mechanisms of disease. In this issue of the JCI, Kim et al. identify a highly conserved enhancer element approximately 500 bp downstream of the transcriptional start site of TTN in intron 1, which they demonstrated to be critical in regulating TTN expression. This work helps to further clarify the relative role of haploinsufficiency in TTN-related DCM and provides a potential target for therapies aimed at treating TTN-related DCM.
Reinvigorating drug development around NGF signaling for pain
Authors: Andi Wangzhou, Theodore J. Price
Journal: Journal of Clinical Investigation (2025)

Nerve growth factor (NGF) signaling is a clinically validated target for the treatment of several prevalent types of chronic pain; however, addressing safety concerns remain a key challenge. In this issue of the JCI, Peach et al. take a major step forward in this area by deciphering complexities in the signaling of the NGF receptor TrkA, finding that neuropilin 1 (NRP1) acted as a coreceptor for NGF actions at TrkA and the receptor complex required scaffolding from GIPC1. Using a mix of techniques, including animal behavioral models, electrophysiology on mouse and human dorsal root ganglion (DRG) neurons, and elegant biochemical pharmacology, the authors demonstrated that this therapeutic target might more safely manipulate NGF signaling to achieve pain alleviation. While there are still important questions to answer, the innovative work paves the way for the development of nonopioid pain therapeutics.
The microbiome as a modulator of neurological health across the maternal-offspring interface
Authors: Stephanie B Orchanian, Elaine Y Hsiao
Journal: Journal of Clinical Investigation (2025)

The maternal microbiome is emerging as an important factor that influences the neurological health of mothers and their children. Recent studies highlight how microbial communities in the maternal gut can shape early-life development in ways that inform long-term health trajectories. Research on the neurodevelopmental effects of maternal microbiomes is expanding our understanding of the microbiome-gut-brain axis to include signaling across the maternal-offspring unit during the perinatal period. In this Review, we synthesize existing literature on how the maternal microbiome modulates brain function and behavior in both mothers and their developing offspring. We present evidence from human and animal studies showing that the maternal microbiome interacts with environmental factors to impact risk for neurodevelopmental abnormalities. We further discuss molecular and cellular mechanisms that facilitate maternal-offspring crosstalk for neuromodulation. Finally, we consider how advancing understanding of these complex interactions could lead to microbiome-based interventions for promoting maternal and offspring health.
Purifying and profiling lysosomes to expand understanding of lysosomal dysfunction–associated diseases
Authors: Ali Shilatifard, Issam Ben-Sahra
Journal: Journal of Clinical Investigation (2025)

Lysosome storage dysfunction plays a central role in numerous human diseases, but a lack of appropriate tools has hindered lysosomal content profiling in clinical settings. In this issue of the JCI, Saarela et al. introduce a method called tagless LysoIP that enabled rapid isolation of intact lysosomes from blood and brain cells via immunoprecipitation of the endogenous protein TMEM192. Applied to the neurodegenerative lysosomal storage disorder known as Batten disease (caused by mutations in the CLN3 gene), tagless LysoIP revealed substantial accumulation of glycerophosphodiesters (GPDs) in patient lysosomes. These findings highlight the role of CLN3 in GPD clearance and present an innovative method that will enable biomarker discovery and therapeutic advancement in lysosomal diseases.
Correction: p38γ MAPK Is Essential for Aerobic Glycolysis and Pancreatic Tumorigenesis
Authors: Fang Wang, Xiao-Mei Qi, Ryan Wertz, Matthew Mortensen, Catherine Hagen, John Evans, Yuri Sheinin, Michael James, Pengyuan Liu, Susan Tsai, James Thomas, Alexander Mackinnon, Michael Dwinell, Charles R. Myers, Ramon Bartrons Bach, Liwu Fu, Guan Chen
Journal: Cancer Research (2025)
Correction: Long Noncoding RNA MIR17HG Promotes Colorectal Cancer Progression via miR-17-5p
Authors: Jie Xu, Qingtao Meng, Xiaobo Li, Hongbao Yang, Jin Xu, Na Gao, Hao Sun, Shenshen Wu, Giuseppe Familiari, Michela Relucenti, Haitao Zhu, Jiong Wu, Rui Chen
Journal: Cancer Research (2025)
Bladder Preservation with Durvalumab plus Tremelimumab and Concurrent Radiotherapy in Patients with Localized Muscle-Invasive Bladder Cancer (IMMUNOPRESERVE): A Phase II Spanish Oncology GenitoUrinary Group Trial
Authors: Xavier Garcia-del-Muro, Begoña P. Valderrama, Ana Medina-Colmenero, Olatz Etxaniz, Regina Gironés Sarrió, María José Juan-Fita, Marcel Costa-García, Rafael Moreno, Isabel Miras Rodríguez, Irene Ortiz, Andrés Cuéllar, Ferran Ferrer, Francesc Vigués, Roberto de Haro Piedra, Arturo Candal Gomez, Salvador Villà, José Luis Pontones, Yasmina Murria, Guillermo Lendínez-Cano, Ramon Alemany
Journal: Clinical Cancer Research (2025)

Abstract Purpose: The combination of radiation and immunotherapy potentiated antitumor activity in preclinical models. The purpose of this study is to explore the feasibility, safety, and efficacy of a bladder-preserving approach, including dual immune checkpoint blockade and radiotherapy, in patients with muscle-invasive bladder cancer (MIBC). Patients and Methods: Patients with localized MIBC underwent transurethral resection, followed by durvalumab (1,500 mg) plus tremelimumab (75 mg) every 4 weeks for three doses and concurrent radiotherapy (64–66 Gy to bladder). Patients with residual or relapsed MIBC underwent salvage cystectomy. The primary endpoint was complete response, defined as the absence of MIBC at posttreatment biopsy. Secondary endpoints were bladder-intact disease-free survival, distant metastasis–free survival, and overall survival. Results: Thirty-two patients were enrolled at six centers. Complete response was documented in 26 (81%) patients. Two patients had residual MIBC, and four patients were not evaluated. After a median follow-up of 27 months, 2 patients underwent salvage cystectomy. The 2-year rates for bladder-intact disease-free survival, distant metastasis–free survival, and overall survival were 65%, 83%, and 84%, respectively. The 2-year estimates of non–muscle-invasive bladder relapse, MIBC, and distant metastasis were 3%, 19%, and 16%, respectively. Grade 3 to 4 toxicities were reported in 31% of patients, with diarrhea (6%) and acute kidney failure (6%) being the most frequent. Conclusions: This multimodal approach including durvalumab plus tremelimumab with concurrent radiotherapy is feasible and safe, showing high efficacy in terms of response and eliciting bladder preservation in a large number of patients. Further research on this approach as an alternative to cystectomy is warranted.
Deterministic Role of FOXF2 in Organ-Specific Macrometastasis Transition
Authors: Igor L. Bado
Journal: Cancer Research (2025)

The mechanisms contributing to metastasis tropism in breast cancer are far from being understood. The ability of cancer cells to adapt to new microenvironments plays a crucial role in that process. In this issue of Cancer Research, Jiang and colleagues explored the tumor-intrinsic differences that affect seeding and tissue colonization by focusing on two major sites of breast cancer metastasis: the lung and bone. They used genetic approaches and metastasis modeling to assess the role of forkhead box F2 (FOXF2) in remodeling the tumor microenvironment and promoting metastasis outgrowth. Their findings suggest that FOXF2 promotes a micrometastasis-to-macrometastasis transition in bones through the direct activation of NF-κB and BMP4 signaling pathways, independently of tumor subtype. In contrast, FOXF2 was found to hinder the ability of basal models to colonize the lung microenvironment through inhibition of TGFβ signaling. Collectively, these findings underscore the subtype-specific and tissue-dependent roles of FOXF2 in organotropism. See related article by Jiang et al., p. 644
Parkinson's disease and glucose metabolism impairment
Authors: Liangjing Chen, Chunyu Wang, Lixia Qin, Hainan Zhang
Journal: Translational Neurodegeneration (2025)

Abstract Parkinson's disease (PD) is the second most common neurodegenerative disorder. PD patients exhibit varying degrees of abnormal glucose metabolism throughout disease stages. Abnormal glucose metabolism is closely linked to the PD pathogenesis and progression. Key glucose metabolism processes involved in PD include glucose transport, glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, the pentose phosphate pathway, and gluconeogenesis. Recent studies suggest that glucose metabolism is a potential therapeutic target for PD. In this review, we explore the connection between PD and abnormal glucose metabolism, focusing on the underlying pathophysiological mechanisms. We also summarize potential therapeutic drugs related to glucose metabolism based on results from current cellular and animal model studies.
Reply ‐ Hydroxychloroquine Dose After Hospitalization for <scp>SLE</scp>
Authors: Jacquelyn Nestor, Lingxiao Zhang, Karen H. Costenbader, Hyon Choi, April Jorge
Journal: Arthritis & Rheumatology (2025)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Tolerogenic nanovaccines for the treatment of type I allergic diseases
Authors: Yuxuan Ren, Daoke Yao, Fang Wu, Jing Xiao, Lixia Ma, Yong Zhang, Zhihui Zhang, Guangjie He, Wengjing Deng, Bo Qin, Ningjing Lei, Fazhan Wang
Journal: Journal of Controlled Release (2025)
Physician's global assessment of disease activity in juvenile idiopathic arthritis: consensus-based recommendations from an international task force
Authors: Veronika Rypdal, Hermine I Brunner, Brian M Feldman, Nicolino Ruperto, Amita Aggarwal, Sheila T Angeles-Han, Maria Backström, Erin Balay-Dustrude, Claudia Bracaglia, Fabrizio De Benedetti, Pavla Doležalová, Marco Garrone, Jaime Guzman, Daniel B Horton, Ronald M Laxer, Daniel J Lovell, Tonje Løvli, Silvia Magni-Manzoni, Francesca Minoia, Esi M Morgan, Jane Munro, Ellen B Nordal, Christophe Normand, Nancy Pan, Elisa Patrone, Angelo Ravelli, Claudia Saad Magalhães, Rashmi Sinha, Joost F Swart, Maarit Tarkiainen, Marinka Twilt, Paula Vähäsalo, Sebastiaan Vastert, Jelena Vojinovic, Pamela F Weiss, Beth Gottlieb, Alessandro Consolaro
Journal: Annals of the Rheumatic Diseases (2025)

To develop consensus-based recommendations for physician's global assessment of disease activity (PhGA) scoring and to standardise definitions of disease activity. An international task force of 34 members was assembled, and recommendations were developed in 3 phases: (1) 2 preliminary surveys of paediatric rheumatologists and a literature review; (2) 14 videoconference meetings, informed by multicriteria decision analysis and formal anonymous voting; and (3) a 2-day in-person consensus conference using structured nominal group technique discussions and formal voting. The threshold for achieving consensus was ≥78% of voting task force members. Agreement with the final statements was rated using a numerical rating scale from 0, strongly disagree, to 10, strongly agree. Eighteen points to consider were agreed upon. All statements achieved consensus (≥78%), with a level of agreement ≥9.2. Points included the definition of disease activity in juvenile idiopathic arthritis (JIA), factors to assess in nonsystemic JIA and systemic JIA, consideration of available imaging and laboratory tests, the role of extra-articular manifestations, the evaluation of treatment, and the timing of PhGA scoring. The task force developed consensus-based recommendations when scoring the PhGA in nonsystemic and systemic JIA. These recommendations will lead to more reliable scoring of disease activity in patients with JIA.
Revealing new biomarker to predict MASLD progression
Authors: Gowthami Kanagalingam, Juan Pablo Arab
Journal: Hepatology (2025)

1Department of Internal Medicine, Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA 2Department of Gastroenterology, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile Abbreviation: MASLD, metabolic dysfunction–associated steatotic liver disease.
Trapped in fibrosis: How neutrophil extracellular traps drive HSC activation
Authors: Sofia Jerez
Journal: Hepatology (2025)

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA Abbreviations: COX-2, cyclooxygenase 2; MASH, metabolic dysfunction–associated steatohepatitis; NET, neutrophil extracellular trap. Correspondence Sofia Jerez, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA. Email: [email protected]
More than a lark? LRRK2 inhibitors to treat alpha-1 antitrypsin deficiency
Authors: George Marek
Journal: Hepatology (2025)

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA Abbreviations: A1ATD, alpha-1 antitrypsin deficiency; LRRK2, leucine-rich repeat kinase 2. Correspondence George Marek, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st St SW, Rochester, MN 55901, USA. Email: [email protected]
Erratum: Refitting the model for end‐stage liver disease for the eurotransplant region
Authors: Ben F. J. Goudsmit, Hein Putter, Maarten E. Tushuizen, Serge Vogelaar, Jacques Pirenne, Alwayn Ian P. J., Bart van Hoek, Andries E. Braat
Journal: Hepatology (2025)
Erratum: CCL15 recruits suppressive monocytes to facilitate immune escape and disease progression in hepatocellular carcinoma
Authors: Long-Zi Liu, Zhao Zhang, Bo-Hao Zheng, Yang Shi, Men Duan, Li-Jie Ma, Zhi-Chao Wang, Liang-Qing Dong, Ping-Ping Dong, Jie-Yi Shi, Shu Zhang, Zhen-Bin Ding, Ai-Wu Ke, Ya Cao, Xiao-Ming Zhang, Ruibin Xi, Jian Zhou, Jia Fan, Xiao-Ying Wang, Qiang Gao
Journal: Hepatology (2025)
Deep learning: Cracking the metabolic code
Authors: Mian B. Khalid
Journal: Hepatology (2025)

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA Abbreviations: AI, artificial intelligence; DL, deep learning; SLD, steatotic liver disease. Correspondence Mian B. Khalid, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA. Email: [email protected]