tbuckley/cabot-search huggingface dataset:
Avian Migration-Mediated Transmission and Recombination driving the Diversity of Gammacoronaviruses and Deltacoronaviruses
Authors: Yuting Xu, Yelin Han, Panpan Xu, Siyu Zhou, Peng Zhao, Yuyang Wang, Jie Hu, Min Ma, Zirong Li, Shunqi Bo, Chenyao Zhao, Lei Ji, Yue Yuan, Wenliang Zhao, Jianwei Wang, Qi Jin, Guimei He, Zhiqiang Wu
Journal: Molecular Biology and Evolution (2025)

Abstract In the wake of pandemics like COVID-19, which have zoonotic origins, the role of wildlife as reservoirs for emerging infectious diseases has garnered heightened attention. Migratory birds, traversing continents, represent a potent but under-researched vector for the spread of infectious diseases, including novel coronaviruses. This study delves into the genetic diversity and transmission dynamics of coronaviruses in migratory birds, presenting pivotal findings. From April 2019 to April 2023, we screened 5,263 migratory bird samples collected from Shanghai, China, identifying 372 coronavirus-positive samples belonging to five avian-related coronavirus subgenera and subsequently obtaining 120 complete genome sequences. To facilitate further research with a global perspective, the study curated all available 19,000 avian-associated CoVs and expanded the original 12 species to 16, including three novel coronavirus species identified in our study and one re-classified species from the public domain. The study illuminates the intricate genetic evolution and transmission dynamics of birds-related coronaviruses on a global scale. A notable aspect of our research is the identification of complex recombination patterns within the spike protein across different virus species and subgenera, highlighting migratory birds as a reservoir of coronavirus. Notably, the coronaviruses found in migratory birds, predominantly from the orders Anseriformes, Charadriiformes, and Pelecaniformes, with domestic ducks from Anseriformes playing a key role in bridging the transmission of coronaviruses between migratory and non-migratory birds. These findings reveal the genetic and recombination characteristics of coronaviruses in migratory birds, emphasizing the critical role of ecologically pivotal bird species in coronavirus transmission and genetic diversity shaping.
Outcomes of patients with relapsed or refractory primary mediastinal B‐cell lymphoma treated with anti‐CD19 CAR‐T cells: CARTHYM, a study from the French national DESCAR‐T registry
Authors: Jean Galtier, Charles Mesguich, Pierre Sesques, Vivien Dupont, Emmanuel Bachy, Roberta Di Blasi, Catherine Thieblemont, Thomas Gastinne, Guillaume Cartron, Gabriel Brisou, François‐Xavier Gros, Justine Decroocq, Franck Morschhauser, Marie‐Thérèse Rubio, Laurianne Drieu La Rochelle, Fabien Le Bras, Sylvain Carras, Adrien Chauchet, Jacques‐Olivier Bay, Magalie Joris, Mickael Loschi, Aline Tanguy‐Schmidt, Alexandra Marquet, Vincent Camus, Steven Le Gouill, Roch Houot, Krimo Bouabdallah
Journal: HemaSphere (2025)

ABSTRACT Primary mediastinal B‐cell lymphoma (PMBL) is often cured with dose‐dense anthracycline‐based regimens but the prognosis at relapse or progression remains poor. While anti‐CD19 CAR‐T cell therapy has dramatically improved outcomes in relapsed or refractory large B‐cell lymphoma, far less is known about their efficacy in PMBL. Using the systematic record of all patients treated with CAR‐T cells prospectively included in the DESCAR‐T registry in France, along with centrally reviewed positon‐emission tomography (PET) imaging, we describe the outcomes and key determinants of treatment success in PMBL patients treated over a 6‐year period. Among 82 patients infused in the registry we observed a best complete response (CR) rate, 2‐year progression‐free survival (PFS), and 2‐year overall survival (OS) of 68.1%, 57.4%, and 73.8%, respectively. Outcomes were even better for the 62 patients infused with axicabtagene ciloleucel, with best CR rate, 2‐year PFS, and 2‐year OS reaching 74.5%, 70.4%, and 86.9%, respectively. Achieving a Deauville score of 1–4 or a ΔSUVmax reduction of more than 24% at the 1‐month evaluation was associated with excellent outcomes, whereas increased total metabolic tumor volume baseline PET increased the risk of treatment failure. Surprisingly, neither the response to bridging therapy nor the type of bridging therapy (chemotherapy versus immune checkpoint inhibitors) were associated with long‐term outcomes. In conclusion, this study confirms that anti‐CD19 CAR‐T cells as a valid standard‐of‐care for relapsed and refractory PMBL and highlights key determinants of treatment success.
Predictors of Acitretin Efficacy in Keratinocyte Carcinoma Chemoprevention: A Retrospective Cohort Study
Authors: Elena Wei, Katherine Thompson, Raghav Tripathi, Anjana Srikumar, Daniela Barata Herrera, Tara McCaffrey, Kristin Bibee
Journal: Journal of the American Academy of Dermatology (2025)
SAE1 promotes tumor cell malignancy via SUMOylation and liquid–liquid phase separation facilitated nuclear export of p27
Authors: Ling Wang, Jie Min, Jinjun Qian, Xiaofang Huang, Xichao Yu, Yuhao Cao, Shanliang Sun, Mengying Ke, Xinyu Lv, Wenfeng Su, Mengjie Guo, Nianguang Li, Shiqian Qi, Hongming Huang, Chunyan Gu, Ye Yang
Journal: Acta Pharmaceutica Sinica B (2025)
Tailored Liposomal Nanomedicine Suppresses Incomplete Radiofrequency Ablation‐Induced Tumor Relapse by Reprogramming Antitumor Immunity
Authors: Duo Wang, Tianqi Nie, Yifei Fang, Linzhu Zhang, Chao Yu, Ming Yang, Ruijie Du, Junjie Liu, Lei Zhang, Liangzhu Feng, Haidong Zhu
Journal: Advanced Healthcare Materials (2025)

Radiofrequency ablation (RFA), a thermoablative treatment for small hepatocellular carcinoma (HCC), has limited therapeutic benefit for advanced HCC patients with large, multiple, and/or irregular tumors owing to incomplete RFA (iRFA) of the tumor mass. It is first identified that iRFA-treated tumors exhibited increased pyruvate kinase M2 (PKM2) expression, exacerbated tumor immunosuppression featured with increased tumor infiltration of suppressive immune cells and increased proliferation, and programmed cell death ligand 1 expression of cancer cell and ultimately a poor prognosis. Herein, a multifunctional nanomedicine is fabricated by encapsulating nanoassemblies of anti-PD-L1 and spermidine-grafted oxidized dextran with shikonin-containing lipid bilayers to reverse iRFA-induced treatment failure. Shikonin, a PKM2 inhibitor, is used to suppress glycolysis in cancer cells, while anti-PD-L1 and spermidine are introduced to collectively reprogram the proliferation and functions of infiltrated CD8+ T lymphocytes. Combined with iRFA, which promoted the exposure of tumor antigens, the intravenous injection of liposomal SPS-NPs effectively stimulated dendritic cell maturation and reversed tumor immunosuppression, thus eliciting potent antitumor immunity to synergistically suppress the growth of residual tumor masses and lung metastasis. The as-prepared liposomal nanomedicine is promising for potentiating the therapeutic benefits of RFA toward advanced HCC patients through reprogramming iRFA-induced tumor immunosuppression.
Multifunctional Carbon Quantum Dots for Monitoring and Therapy of Bacterial Infected Wounds
Authors: Wenxin Qi, Yihao Liu, Naijun Dong, Mengting Li, Jianxin Zhou, Yijun Xie, Qing Chang, Benxiang Luo, Christian Celia, Jiao Wang, Robert Chunhua Zhao, Xiaoyong Deng
Journal: Advanced Healthcare Materials (2025)

Bacterial infections in wounds and bacteremia present significant global health challenges, driving the urgent need for innovative alternatives to traditional antibiotics. Here, the development of PEI-EDTA-2Na carbon quantum dots (PECDs) synthesized via a hydrothermal method is reported. Synthesis conditions affect PECDs' antibacterial efficacy; those at 180 °C have optimal -NH2 functionalization for better adhesion and activity. PECDs are pH - responsive, eradicating bacteria in weakly acidic conditions by disrupting DNA and proteins. Following the resolution of infection, PECDs adapt to neutral and alkaline environments, where they scavenge reactive oxygen species (ROS), reduce inflammation, promote macrophage polarization, and accelerate wound healing. Furthermore, PECDs significantly improve survival in bacteremia models. Their intrinsic fluorescence enables real-time pH monitoring of wounds, offering a non-invasive diagnostic tool. Genomic and transcriptomic analyses reveal that PECDs disrupt bacterial metabolism and resistance pathways, while simultaneously supporting antibacterial and anti-inflammatory responses during tissue repair. This dual functionality-combining therapeutic efficacy in wound healing with antimicrobial and anti-inflammatory properties in bacteremia-positions PECDs as a versatile platform for smart wound management and an emerging candidate for advanced biomedical applications.
Immune‐Infiltrated Cancer Spheroid Model with Vascular Recirculation Reveals Temporally Dependent and Tissue‐Specific Macrophage Recruitment
Authors: Feng Zhang, Kimia Asadi Jozani, Anushree Chakravarty, Dawn Lin, Andrew Hollinger, Shravanthi Rajasekar, Boyang Zhang
Journal: Advanced Healthcare Materials (2025)

Abstract Immune cell infiltration in tumors has been reported to influence tumor progression and clinical outcomes. Considerable efforts have been made to understand interactions between tumors and the immune system. However, current models are either not comprehensive or limited to short‐term studies. Recognizing thedynamic and long‐term nature of tumor‐immune interactions, an immune‐infiltrated cancer spheroid model is developed by continuously perfusing and recirculating immune cells with gravity‐driven flow through a tubular blood vessel adjacent to a cancer spheroid. Fibroblasts and pericytes are embedded in the gel matrix to support endothelial cells and enhance the vascular barrier. With continuous monocyte recirculation, monocyte adhesion, transendothelium migration, differentiation, and macrophage recruitment into breast carcinoma and hepatoma spheroids is successfully demonstrated over a week. The macrophage recruitment process is temporally dependent and tissue‐specific, leading to the formation of cancer‐macrophage heterospheroids. Elevated secretion of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), which regulates monocyte recruitment and macrophage activation, is observed in the breast carcinoma model. Increased levels of Interleukin 6 (IL‐6) and Interleukin 8 (IL‐8) are detected, indicating a pro‐inflammatory environment associated with tumor progression and metastasis. This platform provides a valuable framework for investigating immune cell infiltration and differentiation within the tumor microenvironment, supporting the advancement of cancer immunotherapies.
YIGSR Functionalized Hybrid Exosomes Spatially Target Dasatinib to Laminin Receptors for Precision Therapy in Breast Cancer
Authors: Pratiksha Tiwari, Ravi Prakash Shukla, Krishna Yadav, Madhu Sharma, Avijit Kumar Bakshi, Dilip Panwar, Neha Singh, Neha Agarwal, Madhav Nilakanth Mugale, Prabhat Ranjan Mishra
Journal: Advanced Healthcare Materials (2025)

Abstract In this study, YIGSR‐functionalized exosomes (Exo) are engineered and hybridized with lipid polymeric nanoparticles (LPNPs) followed by loading of chemotherapy Dasatinib (DST) to spatially target laminin receptors on tumors. Exo derived from differentiated macrophages are engineered with YIGSR targeting peptides.These YIGSR‐Exo are subsequently fused with LPNPs membranes using the freeze‐thaw method, resulting in fused hybrid YIGSR‐Exo, which are then loaded with DST, creating DST‐FuNP@YIGSR‐Exo and targeted breast cancer (BC), leading to enhanced mitochondrial membrane potential (54.50 ±5.0%), increased reactive oxygen species (59.50 ± 6.0%), and apoptosis (63 ± 6.5%), ultimately inducing cell death. Further, cellular uptake and receptor blocking studies confirm the binding affinity and interaction of DST‐FuNP@YIGSR‐Exo with laminin receptors, Intravenous pharmacokinetic analysis of DST‐FuNP@YIGSR‐Exo reveals a significant improvement in AUC0‐∞, with a 20.84‐fold increase compared to free DST and a 1.61‐fold enhancement over DST‐FuNP@Exo. This is further supported by in vivo imaging and demonstrated improved tumor localization. A tumor regression study shows a 6.8‐fold reduction in tumors. Tumor tissue‐specific IHC for the Ki67 proliferative marker is significantly reduced in the targeted formulation. The potential of DST‐FuNP@YIGSR‐Exo as an effective carrier for delivering chemotherapeutic drugs, paving the path for the advancement of biologically obtained nanocarriers for targeted breast cancer.
Mimicking the Dystrophic Cardiac Extracellular Environment through DystroGel
Authors: Maila Chirivì, Fabio Maiullari, Marika Milan, Maria Grazia Ceraolo, Nicole Fratini, Alessandra Fasciani, Salma Bousselmi, Michael Stirm, Francesca Scalera, Francesca Gervaso, Michela Villa, Raffaello Viganò, Francesca Brambilla, Pierluigi Mauri, Elena De Falco, Dario Di Silvestre, Marco Costantini, Eckhard Wolf, Claudia Bearzi, Roberto Rizzi
Journal: Advanced Healthcare Materials (2025)

Abstract Advances in understanding the mechanisms behind genetic diseases like Duchenne muscular dystrophy (DMD) underscore the critical role of the extracellular matrix (ECM) composition in disease progression. Effective in vitro models must replicate the intercellular relationships and physicochemical properties of native ECM to fully capture disease‐specific characteristics. Although recent biomaterials support the in vitro biofabrication of pathophysiological environments, they often lack disease‐specific ECM features. In this study, DystroGel, a hydrogel derived from the cardiac ECM of a porcine DMD model, replicates the distinct molecular composition of dystrophic cardiac tissue for the first time. The findings indicate that the dystrophic ECM matrix exhibits a unique protein profile, impacting cellular processes critical to DMD pathology. This work demonstrates the importance of using a 3D substrate that recreates intercellular dynamics within a defined pathological environment, enhancing the ability to model genetic disorders and providing a valuable tool for advancing personalized therapeutic strategies.
Addition of anti‐PD‐1 immunotherapy to BRAF inhibitor‐based targeted therapy improves real‐world survival and delays brain metastases in patients with BRAF<sup>V600</sup>‐mutant advanced melanoma: a multicenter cohort study
Authors: Junwan Wu, Qiuyue Ding, Qiong Zhang, Qianqi Chen, Xizhi Wen, Ya Ding, Jingjing Li, Ziluan Chen, Tao Zhang, Jiuhong Wang, Fuxue Huang, Hang Jiang, Linbin Chen, Qiming Zhou, Ke Li, Xiaoshi Zhang, Dandan Li
Journal: MedComm (2025)

Abstract Anti‐PD‐1 immunotherapy and targeted therapy (TT) represent two major therapeutic modalities for BRAF V600 ‐mutant advanced melanoma, but the efficacy of combination therapy in Asian populations remains unknown. Asian melanoma patients differ significantly from Caucasians in tissue subtypes, pathogenesis and response to treatment. We retrospectively analyzed data of BRAF V600 ‐mutant advanced melanoma patients treated with first‐line vemurafenib (V) ± anti‐PD‐1 or dabrafenib+trametinib (D+T) ± anti‐PD‐1 between 2014 and 2023 from three centers in China. 178 patients were included, with V ( n = 45), D+T ( n = 51), V+anti‐PD‐1 ( n = 39) and D+T+anti‐PD‐1 ( n = 43). The median PFS (21.9 vs. 11.1 months, p &lt; 0.001), OS (NR vs. 32.6 months, p = 0.027), and DoR (20.0 vs. 8.4 months, p = 0.002) were significantly prolonged with D+T+anti‐PD‐1 versus D+T. Addition of anti‐PD‐1 to V also significantly prolonged PFS, OS, and DoR ( p &lt; 0.001). V+anti‐PD‐1 was superior to D+T in terms of PFS (15.0 vs. 11.1 months, p = 0.007) and DoR (18.0 vs. 8.4 months, p = 0.013), and was comparable to D+T+anti‐PD‐1. Addition of anti‐PD‐1 to BRAF inhibitor‐based TT was associated with lower incidence of brain metastases ( p = 0.032). Addition of anti‐PD‐1 to BRAF inhibitor‐based TT appears to be a safe and effective treatment option, conferring a survival benefit and delaying the onset brain metastases in patients with BRAF V600 ‐mutant advanced melanoma.
Early‐life antibiotic exposure aggravates hepatic steatosis through enhanced endotoxemia and lipotoxic effects driven by gut <i>Parabacteroides</i>
Authors: Xi Zhang, Darren Chak Lun Chan, Jie Zhu, Daniel Zhen Ye Sin, Ye Peng, Matthew Kwok Leong Wong, Wenyi Zhu, Yee Tsui, Andrea M. Haqq, Joseph Y. Ting, Anita Kozyrskyj, Francis Ka Leung Chan, Siew Chien Ng, Hein Min Tun
Journal: MedComm (2025)

Abstract Compelling evidence supports a link between early‐life gut microbiota and the metabolic outcomes in later life. Using an early‐life antibiotic exposure model in BALB/c mice, we investigated the life‐course impact of prenatal and/or postnatal antibiotic exposures on the gut microbiome of offspring and the development of metabolic dysfunction‐associated steatotic liver disease (MASLD). Compared to prenatal antibiotic exposure alone, postnatal antibiotic exposure more profoundly affected gut microbiota development and succession, which led to aggravated endotoxemia and metabolic dysfunctions. This was primarily resulted from the overblooming of gut Parabacteroides and hepatic accumulation of cytotoxic lysophosphatidyl cholines (LPCs), which acted in conjunction with LPS derived from Parabacteroides distasonis (LPS_PA) to induce cholesterol metabolic dysregulations, endoplasmic reticulum (ER) stress and apoptosis. Integrated serum metabolomics, hepatic lipidomics and transcriptomics revealed enhanced glycerophospholipid hydrolysis and LPC production in association with the upregulation of PLA2G10, the gene controlling the expression of the group X secretory Phospholipase A2s (sPLA2‐X). Taken together, our results show microbial modulations on the systemic MASLD pathogenesis and hepatocellular lipotoxicity pathways following early‐life antibiotic exposure, hence help inform refined clinical practices to avoid any prolonged maternal antibiotic administration in early life and potential gut microbiota‐targeted intervention strategies.
Changes in L‐phenylalanine concentration reflect and predict response to anti‐PD‐1 treatment combined with chemotherapy in patients with non‐small cell lung cancer
Authors: Yaqing Liu, Yu Ping, Liubo Zhang, Qitai Zhao, Yachang Huo, Congcong Li, Jiqi Shan, Yanwen Qi, Liping Wang, Yi Zhang
Journal: MedComm (2025)

Abstract Chemotherapy combined with checkpoint blockade antibodies targeting programmed cell death protein (PD‐1) has achieved remarkable success in non‐small cell lung cancer. However, few patients benefit from long‐term treatment. Therefore, biomarkers capable of guiding the optimal therapeutic selection and reducing unnecessary toxicity are of pressing importance. In our research, we gathered serial blood samples from two groups of non‐small cell lung cancer patients: 49 patients received a combination of therapies, and 34 patients went under chemotherapy alone. Utilizing non‐targeted metabolomic analysis, we examined different metabolites’ disparity. Among the lot, L‐phenylalanine emerged as a significant prognostic marker in the combination treatment of non‐small cell lung cancer patients, interestingly absent in patients under sole chemotherapy. The reduced ratio of L‐phenylalanine concentration (two‐cycle treatment vs. pre‐treatment) was associated with improved progression‐free survival (hazard ratio = 1.8000, 95% confidence interval: 0.8566‒3.7820, p &lt; 0.0001) and overall survival (hazard ratio = 1.583, 95% confidence interval: 0.7416‒3.3800, p &lt; 0.005). We further recruited two validation cohorts (cohort 1: 40 patients and cohort 2: 30 patients) to validate the sensitivity and specificity of L‐phenylalanine prediction. Our results demonstrate that a model based on L‐phenylalanine variations could serve as an early risk‐assessment tool for non‐small cell lung cancer patients undergoing treatment, potentially facilitating strategic clinical decision‐making.
Contrast‐enhanced ultrasound enables precision diagnosis of preoperative muscle invasion in bladder cancer: a prospective study
Authors: Qiyun Ou, Weibin Xie, Yunfang Yu, Bing Ou, Man Luo, Yongjian Chen, Weiwei Pan, Yiming Lai, Zhuohang Li, Jianqiu Kong, Zhuo Wu, Jingliang Ruan, Jingjing Han, Tianxin Lin, Baoming Luo
Journal: MedComm (2025)

Abstract Bladder cancer's high mortality underscores the need for precise staging, especially to differentiate between nonmuscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) types. This prospective study evaluated the efficacy of contrast‐enhanced ultrasound (CEUS) for preoperative staging, focusing on its ability to distinguish NMIBC from MIBC. Conducted from April 2020 to September 2021, the study involved 163 patients (median age: 64.0 years; 137 males, 26 females), with 133 NMIBC (81.6%) and 30 MIBC (18.4%). Each patient underwent CEUS followed by transurethral resection of bladder tumor or radical cystectomy. CEUS demonstrated high diagnostic accuracy in determining muscle invasion status (sensitivity 83.3%, specificity 92.5%, accuracy 90.8%, area under the receiver operating characteristic curve [AUC] 0.88). Comparative analyses against MRI (AUC 0.77) showed CEUS outperforming in muscle invasion detection. Combining CEUS with MRI improved diagnostic accuracy, particularly when MRI vesical imaging reporting and data system score was 3 points. The combined approach achieved an AUC of 0.73, with sensitivity, specificity, and accuracy of 76.2, 70.2, and 71.6%, respectively. Thus, CEUS emerges as a valuable diagnostic tool for preoperative staging of bladder cancer, particularly in its role in assessing muscle invasion status and thereby aiding in clinical decision‐making and intervention outcomes.
Targeting CDK4/6 suppresses colorectal cancer by destabilizing YAP1
Authors: Yalei Wen, Xiao Yang, Shengrong Li, Lei Huang, Jiayi Chen, Lirong Tan, Xiuqing Ma, Yingjie Zhu, Zhengqiu Li, Changliang Shan, Chunze Zhang, Qiushi Zhang, Mingchao Liang, Haoxing Zhang, Tongzheng Liu
Journal: MedComm (2025)

Abstract Colorectal cancer (CRC) is among the most prevalent and deadly cancers worldwide. The Yes‐associated protein 1 (YAP1) is frequently dysregulated in cancers, contributing to cancer stemness, chemoresistance, and cancer‐related death. However, strategies directly targeting YAP1 have not yet been successful because of the lack of active binding pockets and unregulated toxicity. In this study, our Food and Drug Administration (FDA)‐approved drug screening reveals that abemaciclib, a cyclin‐dependent kinase 4/6 (CDK4/6) inhibitor, dramatically promotes the proteasome‐dependent degradation of YAP1, thereby inhibiting tumor progression in CRC cells and patient‐derived xenograft models. We further identify deubiquitinating enzyme 3 (DUB3) as the bona fide deubiquitinase of YAP1 in CRC. Mechanistically, CDK4/6 directly phosphorylates DUB3 at Ser41, activating DUB3 to deubiquitinate and stabilize YAP1. Conversely, loss of Ser41 phosphorylation by CDK4/6 inhibition or Ser41A mutation, promotes YAP1 degradation and suppresses YAP1‐driven tumor progression. Histological analysis shows a positive correlation between DUB3 and YAP1 expression in CRC specimens. Collectively, our study uncovers a novel oncogenic role of the CDK4/6‐DUB3 pathway, which promotes YAP1 stabilization and tumor‐promoting function, highlighting that targeting CDK4/6 offers a potential therapeutic strategy for CRC with aberrantly upregulated DUB3 and YAP1.