tbuckley/cabot-search huggingface dataset:
Inhibition of CAV1 attenuates diabetic cardiomyopathy through reducing ferroptosis via activating NRF2/GCLC signaling pathway
Authors: Guangru Li, Ruiqing Liu, Zeyan Peng, Shengzheng Zhang, Runjia Sun, Ziwei Wang, Jing Li, Yang Gao, Yang Xu, Jianlin Cui, Jie Liu, Jie Yan, Lei Cao, Shan Ren, Yushun Chu, Lifeng Feng, Liang Yang, Yanna Shen, Zhi Qi
Journal: Theranostics (2025)

Background: Diabetic cardiomyopathy (DCM), a prevalent complication of diabetes, is a major cause of heart failure and death among patients with diabetes. However, the pathological mechanisms underlying the development of DCM remain unclear. This study aims to investigate the role and underlying mechanisms of caveolin-1 (CAV1) in DCM. Methods: DCM model was established in vivo through intraperitoneal injection of streptozotocin in mice and in vitro through high-glucose (HG) treatment in neonatal rat ventricular myocytes (NRVMs). CAV1-knockout (CAV1-KO) and overexpression (by injecting adeno-associated virus 9 (AAV9) encoding CAV1) mice were utilized to explore the role of CAV1 in DCM. Nuclear factor erythroid 2-related factor 2 (NRF2)-KO and AAV9-NRF2 mice and ML385 (an NRF2 inhibitor) were used to investigate the effect of NRF2 on DCM. Results: CAV1 expression was significantly increased in the cardiac tissues of diabetic mice and HG-treated NRVMs. CAV1 deficiency significantly alleviated diabetes-induced myocardial hypertrophy, fibrosis, abnormal mitochondria, excessive reactive oxygen species production, and ferroptosis. Conversely, cardiac-specific overexpression of CAV1 exacerbated cardiac dysfunction and myocardial histological abnormalities caused by diabetes. Mechanistically, CAV1 directly bound to NRF2 and inhibited its nuclear translocation, reducing the transcription of glutamate cysteine ligase catalytic subunit (GCLC), accumulating excess peroxide, and inducing ferroptosis and myocardial injury. Conclusion: CAV1 exacerbates the progression of DCM by suppressing the NRF2/GCLC pathway, suggesting that targeting CAV1 is a potential therapeutic approach for DCM.
Acupuncture alleviates CSDS-induced depressive-like behaviors by modulating synaptic plasticity in vCA1
Authors: Lin Cong, Shengkai Ding, Yu Guo, Jiamin Tian, Lu Liu, Mengqi Su, Ruilin Xie, Yinuo Wang, Tongrui Wu, Lianbin Zhao, Xiaogang Pang, Yuhong Jing, Hao Wu, Hui Shen, Yuanyuan Li
Journal: Theranostics (2025)

Acupuncture (Acu) has been clinically validated as an effective treatment for depression. However, the underlying mechanism of Acu treatment's antidepressant effect remains unclear. Methods: We investigate the antidepressant effects of Acu treatment at the LR3 point in mice subjected to chronic social defeat stress (CSDS). GCaMP6m-based fiber-optic photometry was employed in the ventral CA1 (vCA1) regions for the first time to monitor Ca2+ transients in vivo during behavioral testing. Electrophysiological recordings were used to detect the activity and synaptic function of pyramidal neurons. Golgi staining was performed to measure the density of dendritic spines in the vCA1. Western blot analysis was conducted to quantify the expression levels of phosphorylated CaMKIIα, AMPA receptor protein (GluA1, GluA2), and brain-derived neurotrophic factor (BDNF) in the hippocampus. Results: Our findings indicated that Acu treatment significantly alleviated emotional deficits and restored the activity of pyramidal neurons, which were suppressed by CSDS. Acu treatment also reversed the decrease in spontaneous excitatory postsynaptic currents (sEPSCs), thereby enhancing glutamatergic transmission. Moreover, Acu treatment improved synaptic plasticity, as evidenced by increased dendritic spine density and restored expression levels of phosphorylated CaMKIIα, GluA1, GluA2 and BDNF. Conclusion: Collectively, these findings suggest that Acu treatment alleviates depressive-like behaviors induced by CSDS and enhances synaptic function in the vCA1 region, potentially through mechanisms involving increased AMPAR trafficking and BDNF expression.
Light/Ultrasound Dual Responsive Carbon Dots‐Based Nanovaccines for Multimodal Activation Tumor Immunotherapy of Melanoma
Authors: Aijia Yang, Li Chen, Shunxin Tang, Xiaolu Guo, Hongqin Su, Bang‐Ping Jiang, Xing‐Can Shen
Journal: Advanced Healthcare Materials (2025)

Abstract Melanoma is a highly aggressive and metastatic tumor, and immunotherapy has become the current solution. However, conventional nanovaccines do not strongly activate T cell immune responses. Therefore, development of effective therapeutic nanovaccines to activate systemic antitumor immunity is urgently required. Herein, light/ultrasound (US) dual‐responsive carbon dot‐based nanovaccines (Cu‐N‐CDs@OVA) are designed using copper‐nitrogen‐coordinated carbon dots composited with ovalbumin. Under 650‐nm laser irradiation, Cu‐N‐CDs@OVA exhibited superior photothermal ablation of primary tumors, induced immunogenic cell death and released antigens by phototherapy, facilitating the maturation of dendritic cells (DCs). More importantly, Cu‐N‐CDs@OVA stably penetrated and diffused upon US treatment, eradicating metastatic tumors and generating low‐dose reactive oxygen species to activate DCs. By integrating with the model antigen OVA, the combined multimodal treatment promotes DC maturation to activate systematic antitumor immunity. This is the first example of a light/US dual‐responsive therapeutic nanovaccine that provides a paradigm for the production of personalized nanovaccines against malignant tumors.
Heparin Doped Polyaniline for Anticoagulation Supercapacitors
Authors: Yuxia Zhang, Xiangya Wang, Meimei Yu, Mohammed Kamal Hadi, Suting Zhou, Yumeng Wang, Fen Ran
Journal: Advanced Healthcare Materials (2025)

Abstract With the rapid development of implantable electronic medical devices, supercapacitors have gained significant attention as implantable energy storage devices due to their inherent advantages. However, these devices inevitably direct contact with blood and trigger coagulation or thrombus formation when implanted in the body. In severe cases, these negative effects compromise the functionality of the implantable energy storage system and even jeopardize human health. Herein, a biocompatible electrode material with high anticoagulant activity is designed by doping polyaniline with anticoagulant macromolecule heparin under neutral conditions, which macromolecules as dopants under neutral conditions not only avoids the toxicity of acids to biological tissues and de‐doping caused by small molecules, but also imparts high anticoagulant properties to the material. Based on the electrode material and in situ polymerization approach, an all‐in‐one anticoagulation supercapacitor is employed to manufacture and exhibits good electrochemical performance (energy density of 18.89 µWh cm −2 and a power density of 197.8 µW cm −2 ), cycling stability (capacitance retention of 70.23% after 2, 000 cycles), anticoagulant performance (APTT is 15.47 s, PT is 16.57 s, TT is 49.47 s, and FIB is 1.12 g L −1 ), and tissue compatibility. The doping strategy provides a valuable reference for energy supply in implantable bioelectronics.
Development and validation of multimodal deep learning algorithms for detecting pulmonary hypertension
Authors: Wei Zhao, Zhihua Huang, Xiaolin Diao, Zhan Yang, Zhihui Zhao, Yun Xia, Qing Zhao, Zhaohong Sun, Qunying Xi, Yanni Huo, Ou Xu, Jiahui Geng, Xin Li, Anqi Duan, Sicheng Zhang, Luyang Gao, Yijia Wang, Sicong Li, Qin Luo, Zhihong Liu
Journal: npj Digital Medicine (2025)
Long-Read Genome Sequencing in Clinical Psychiatry: <i>RFX3</i> Haploinsufficiency in a Hospitalized Adolescent With Autism, Intellectual Disability, and Behavioral Decompensation
Authors: Milad Mortazavi, Sergey Batalov, Jerica Lenberg, Corrine Blucher, Aisha Omorodion, Daniel Helbling, Lucita Van Der Kraan, Zaira Bezares-Orin, Arivudainambi Ramalingam, Matthew N. Bainbridge, Jonathan Sebat, Aaron D. Besterman
Journal: American Journal of Psychiatry (2025)
Trends in Prescription Stimulant, Opioid, and Benzodiazepine Use and Diversion in U.S. Adolescents
Authors: Sean Esteban McCabe, Emily Pasman, Timothy E. Wilens, Ty S. Schepis, Vita V. McCabe, Jason A. Ford, John Jardine, Philip T. Veliz
Journal: American Journal of Psychiatry (2025)
Robustness of ancestral sequence reconstruction to among-site and among-lineage evolutionary heterogeneity
Authors: Ricardo Muñiz-Trejo, Yeonwoo Park, Joseph W Thornton
Journal: Molecular Biology and Evolution (2025)

Abstract Ancestral sequence reconstruction (ASR) is typically performed using homogeneous evolutionary models, which assume that the same substitution propensities affect all sites and lineages. These assumptions are routinely violated: heterogeneous structural and functional constraints favor different amino acids at different sites, and these constraints often change among lineages as epistatic substitutions accrue at other sites. To evaluate how violations of the homogeneity assumption affect ASR under realistic conditions, we developed site-specific substitution models and parameterized them using data from deep mutational scanning experiments on three protein families; we then used these models to perform ASR on the empirical alignments and on alignments simulated under heterogeneous conditions derived from the experiments. Extensive among-site and -lineage heterogeneity is present in these datasets, but the sequences reconstructed from empirical alignments are almost identical when heterogeneous or homogeneous models are used for ASR. Using models fit to DMS data from distantly related proteins in which mutational effects are very different also has a minimal impact on ASR. The rare differences occur primarily where phylogenetic signal is weak – at fast-evolving sites and nodes connected by long branches. When ASR is performed on simulated data, errors in the reconstructed sequences become more likely as branch lengths increase, but incorporating heterogeneity into the model does not improve accuracy. These data establish that ASR is robust to unincorporated realistic forms of evolutionary heterogeneity, because the primary determinant of ASR is phylogenetic signal, not the substitution model. The best way to improve accuracy is therefore not to develop more elaborate models but to apply ASR to densely sampled alignments that maximize phylogenetic signal at the nodes of interest.
MYO1F in neutrophils is required for the response to immune checkpoint blockade therapy
Authors: Yingying Qu, Wenhua Liang, Mingzhu Yu, Chenhui Wang, Min Luo, Lin Zhong, Zhigang Li, Feng Wang
Journal: The Journal of Experimental Medicine (2025)

Tumor-associated neutrophils (TANs) represent a significant barrier to the effectiveness of immune checkpoint blockade (ICB) therapy. A comprehensive understanding of TANs' regulatory mechanisms is therefore essential for predicting ICB efficacy and improving immunotherapy strategies. Our study reveals that MYO1F is selectively downregulated in neutrophils within both human cancers and murine tumor models, showing a negative correlation with ICB response. Mechanistically, MYO1F normally inhibits neutrophil immunosuppression and proliferation by restraining STAT3 activity. However, during tumorigenesis, tumor-derived TGF-β1 disrupts the binding of SPI1 to intron 8 of Myo1f via DNA methylation, thereby suppressing Myo1f transcription. The resultant decrease in MYO1F reprograms neutrophils into an immunosuppressive state through the STAT3-dependent signaling pathways. This immunosuppressive state further contributes to tumor microenvironment (TME) remodeling by inducing CTL exhaustion. These findings establish MYO1F as a critical regulator within TANs, highlighting its significant role in modulating ICB therapy efficacy.
Reply to the Letter to the Editor by Perez et al. regarding “Survival among patients treated with total mesorectal excision or selective watch-and-wait after total neoadjuvant therapy: a pooled analysis of the CAO/ARO/AIO-12 and OPRA randomized phase II trials”
Authors: J Garcia-Aguilar, H Williams, E Fokas, C Rodel
Journal: Annals of Oncology (2025)
Re: Brian Shuch, Allan J. Pantuck, Jean-Christophe Bernhard, et al. [89Zr]Zr-girentuximab for PET-CT Imaging of Clear-cell Renal Cell Carcinoma: A Prospective, Open-label, Multicentre, Phase 3 Trial. Lancet Oncol 2024;25:1277–87
Authors: Zhuo Tony Su, Mohammad E Allaf, Nirmish Singla
Journal: European Urology (2025)
First-in-Human Implantable Inferior Vena Cava Sensor for Remote Care in Heart Failure
Authors: Paul R Kalra, Irakli Gogorishvili, George Khabeishvili, Filip Málek, Ondřej Toman, Chris Critoph, Andrew S Flett, Peter J Cowburn, Mandeep R Mehra, William S Sheridan, John R Britton, Teresa Buxo, Robyn M Kealy, Annette Kent, Barry R Greene, Kaushik Guha, Roy S Gardner, Ian Loke, Ali Vazir, Jasper J Brugts, Alastair Gray, Jeffrey M Testani, Kevin Damman
Journal: JACC Heart Failure (2025)

Variations of inferior vena cava (IVC) area and collapsibility serve as early markers of congestion and predict risk for heart failure (HF) events. The aim of this first-in-human study (FUTURE-HF [First in Human Clinical Investigation of the FIRE1 System in Heart Failure Patients]) was to evaluate the safety and feasibility of a novel implantable IVC sensor for remote management in patients with HF. This paper is the final report on primary (3-month) and exploratory (6-month) endpoints. Patients with HF hospitalizations within the previous year, with elevated natriuretic peptide levels, and on optimal HF treatment were included. The primary safety endpoints were procedural success without device- or procedure-related complications at 3 months. The primary technical endpoint was signal acquisition following implantation and at a clinic visit within 3 months. Sensor-derived IVC area was compared with computed tomography (CT)-based IVC dimensions. Patient adherence to daily readings and exploratory clinical findings at 6 months were assessed. Fifty patients underwent successful implantation (mean age 65 ± 9 years, 14% women, 72% in NYHA functional class III), with 49 contributing to the primary safety and technical endpoints at 3 months. Sensor-derived IVC area demonstrated excellent agreement with CT measurement (mean absolute error 13.53 mm2 [3.55%] R2 = 0.98). Median adherence was 96% at 6-month follow-up. Exploratory analyses of clinical outcomes suggested improvements in N-terminal pro-B-type natriuretic peptide, NYHA functional class, and quality of life and reduced HF events. This first-in-human experience demonstrated that the implantation of an IVC sensor was safe and feasible. Sensor-derived IVC area demonstrated excellent correlation with CT-derived IVC area, and exploratory clinical outcomes suggest that this may serve as a novel tool for ambulatory management of congestion to facilitate remote care in HF. (First in Human Clinical Investigation of the FIRE1 System in Heart Failure Patients [FUTURE-HF]; NCT04203576).
Genomic and functional analysis of rmp locus variants in Klebsiella pneumoniae
Authors: Margaret M C Lam, Stephen M Salisbury, Logan P Treat, Ryan R Wick, Louise M Judd, Kelly L Wyres, Sylvain Brisse, Kimberly A Walker, Virginia L Miller, Kathryn E Holt
Journal: Genome Medicine (2025)

Abstract Background Klebsiella pneumoniae is an opportunistic pathogen and a leading cause of healthcare-associated infections in hospitals, which are frequently antimicrobial resistant (AMR). Exacerbating the public health threat posed by K. pneumoniae , some strains also harbour additional hypervirulence determinants typically acquired via mobile genetic elements such as the well-characterised large virulence plasmid KpVP-1. The rmpADC locus is considered a key virulence feature of K. pneumoniae and is associated with upregulated capsule expression and the hypermucoid phenotype, which can enhance virulence by contributing to serum resistance. Typically such strains have been susceptible to all antimicrobials besides ampicillin; however, the recent emergence of AMR hypermucoid strains is concerning. Methods Here, we investigate the genetic diversity, evolution, mobilisation and prevalence of rmpADC , in a dataset of 14,000 genomes from isolates of the Klebsiella pneumoniae species complex, and describe the RmST virulence typing scheme for tracking rmpADC variants for the purposes of genomic surveillance. Additionally, we examine the functionality of representatives for variants of rmpADC introduced into a mutant strain lacking its native rmpADC locus. Results The rmpADC locus was detected in 7% of the dataset, mostly from genomes of K. pneumoniae and a very small number of K. variicola and K. quasipneumoniae . Sequence variants of rmpADC grouped into five distinct lineages ( rmp1 , rmp2 , rmp2A , rmp3 and rmp4 ) that corresponded to unique mobile elements, and were differentially distributed across different populations (i.e. clonal groups) of K. pneumoniae . All variants were demonstrated to produce enhanced capsule production and hypermucoviscosity. Conclusions These results provide an overview of the diversity and evolution of a prominent K. pneumoniae virulence factor and support the idea that screening for rmpADC in K. pneumoniae isolates and genomes is valuable to monitor the emergence and spread of hypermucoid K. pneumoniae , including AMR strains.
IL-34 promotes the inflammatory role of the IL-1β-producing myeloid cells in pemphigus lesions
Authors: Zixuan Huang, Wenzhe Zhao, Chuqiao Xu, Jie Zheng, Chuanxin Huang, Haiqin Zhu, Meng Pan
Journal: British Journal of Dermatology (2025)

Abstract Background Pemphigus is a life-threatening autoimmune disease mediated by anti-desmoglein(Dsg) autoantibodies. Ectopic lymphoid-like structures (ELSs) are frequently found in chronic skin lesions and are thought to contribute to local autoantibody production. However, the mechanisms driving ELS formation at lesion sites remain unclear. Objectives To investigate the role of myeloid cells in the formation of ELSs in pemphigus lesions and to identify potential therapeutic targets by better understanding the underlying mechanisms that contribute to this process. Methods We used single-cell RNA sequencing to identify the myeloid subpopulation in pemphigus lesions and study their functions. Immunohistochemistry(IHC), immunofluorescence, and flow cytometry were used to validate the presence of interleukin (IL)-1β-producing myeloid cells. Culture, bulk RNA sequencing and trans-well chemotaxis experiments were conducted to assess the effects of IL-34 and tumor Necrosis Factor (TNF)-α on monocytes. Additionally, the high expression of IL-34 in pemphigus keratinocytes was validated by IHC. Results We first confirmed the abundant presence of myeloid cells within ELSs in pemphigus skin lesions, including PV and PF. Single-cell RNA sequencing revealed that IL1B_Macro is the dominant myeloid subpopulation in pemphigus lesions, originating from classical monocytes. These cells have a strong inflammatory and chemotactic transcriptomic profile, expressing high levels of IL1B, IL6, and chemokines such as CCL20, CCL3, CCL5, and CXCL5, promoting leukocyte infiltration. Ex-vivo experiments showed that IL1B_Macro differentiation is enhanced by the synergistic action of IL-34 and TNF-α, and this can be attenuated by a CSF-1R inhibitor. IL-34 alone also promotes IL1B and CCL20 expression, and keratinocytes were found to be the major source of elevated IL-34 in pemphigus lesions. Bulk RNA sequencing data indicated that high IL-34 expression in pemphigus keratinocytes correlates with increased levels of CCL5, IL6, and IL23A. Conclusions IL-1β-producing myeloid cells play a crucial role in forming ELSs in pemphigus lesions through inflammatory and chemotactic pathways. Keratinocytes contribute to this process by producing IL-34, which fuels local inflammation. These findings offer new insights into pemphigus immunopathogenesis and suggest the IL-34/CSF-1R pathway as a potential therapeutic target.
Bisphenol S exposure and MASLD: a mechanistic study in mice
Authors: Shiqi Li, Yun Fan, Min Tang, Xiaorong Wu, Shengjun Bai, Xiancheng Yang, Xueer Zhang, Chuncheng Lu, Chenbo Ji, Paul A Wade, Xu Wang, Wei Gu, Guizhen Du, Yufeng Qin
Journal: Environmental Health Perspectives (2025)

Bisphenol S (BPS) is a substitute for bisphenol A in various commercial products and is increasingly used globally due to restrictions on bisphenol A usage. Consequently, there are increasing public health concerns that substantial effects mediated by synthetic chemicals may impact human health. Recently, epidemiology studies reported associations between bisphenol exposure and non-alcoholic fatty liver disease (MASLD). However, the causal relationship and the molecular mechanisms affecting hepatocellular functions are still unknown. Our study aimed to understand the molecular mechanism by which BPS exposure caused hepatic lipid deposition. C57BL/6J mice were exposed to BPS for three months and its effects were assessed by histology. RNA sequencing (RNA-seq), Assay for Transposase Accessible Chromatin with high throughout sequencing (ATAC-seq) and Cleavage Under Targets and Tagmentation (CUT&Tag) were used to investigate mechanistic details. ATF3 liver-specific knock out mice and cells were used to validate its functions in BPS induced hepatotoxicity. Here, mice that were chronically exposed to BPS showed significant lipid deposition in liver and dyslipidemia, and were predisposed to MASLD, accompanied with reprogrammed liver transcriptional network and chromatin accessibility that were enriched for Atf3 binding motif. Comparing to the control group, we identified numerous differential Atf3 binding sites associated with signaling pathways integral to lipid catabolism and synthesis in BPS exposure group, resulting in a drastic surge in lipid accumulation. Moreover, knocking out Atf3 in vitro and in vivo significantly attenuates BPS-induced hepatic lipid accumulation via the regulation of chromatin accessibility and gene expression. Besides, inhibiting the JunB also eliminates the BPS-induced Atf3 upregulation and lipid accumulation. Our study reveals a novel mechanism, through which BPS upregulates JunB and Atf3 to impair hepatic lipid metabolism and provides new insights into the hepatotoxicity of BPS.. https://doi.org/10.1289/EHP17057.
Concomitant Surgical Procedures and Aspirin Avoidance With Left Ventricular Assist Device Therapy
Authors: Francis D Pagani, Ivan Netuka, Ulrich P Jorde, Jason N Katz, Finn Gustafsson, Jean M Connors, Nir Uriel, Edward G Soltesz, Peter Ivak, Aditya Bansal, Abbas Bitar, J David Vega, Daniel Goldstein, Matthew Danter, Yuriy Pya, Ashwin Ravichandran, Jennifer Conway, Eric D Adler, Eugene S Chung, Jonathan Grinstein, Nick Dirckx, Behzad Iravani, Mandeep R Mehra
Journal: JACC Heart Failure (2025)
The 2023 American College of Cardiology Advanced Heart Failure Staffing Survey
Authors: Maya Guglin, Amrut V Ambardekar, Anju Bhardwaj, Lauren Beth Cooper, Ersilia M DeFilippis, Nadia Fida, Shelley Hall, Dustin Hillerson, Onyedika J Ilonze, Anuradha Lala, Nikhil Narang, Megan N Pelter, Navin Rajagopalan, Bhavadharini Ramu, Anne K Rzeszut
Journal: JACC Heart Failure (2025)
Racial and Ethnic Differences in Long-Term Cardiovascular Mortality Among Women and Men From the CAC Consortium
Authors: Shmuel Rosenblatt, Michael J Blaha, Ron Blankstein, Khurram Nasir, Fay Lin, Yvette Yeboah-Kordieh, Daniel S Berman, Michael D Miedema, Seamus P Whelton, John Rumberger, Matthew J Budoff, Jonathon Leipsic, Leslee J Shaw
Journal: JACC. Cardiovascular imaging (2025)