tbuckley/cabot-search huggingface dataset:
Acid‐Responsive Bacteria‐Targeted Zinc‐Porphyrin Based Sonosensitizer with Enhancing Antibacterial Efficacy and Biofilm Eradication for Infected Wounds Healing
Authors: Xingjun Zhao, Jiaxin Li, Peng Zhang, Chunsheng Xiao, Li Chen
Journal: Advanced Healthcare Materials (2025)

Abstract Diseases caused by bacterial infections place a significant burden on global public health. Sonodynamic therapy (SDT), as an emerging antibacterial treatment, faces clinical challenges due to the non‐polar nature of most sonosensitizers. To address this, an acid‐responsive zinc‐porphyrin‐based sonosensitizer (Zn‐TCPP) is developed via a simple thermal reaction, which is then coated with phenylboronic acid‐modified hyaluronic acid (B‐HA), to fabricate B‐HA@Zn‐TCPP. While in the mildly acidic microenvironment mimicking an infected wound site, the released B‐HA@Zn‐TCPP achieves effective SDT activity. The disruption of the bacterial membrane and the levels of intracellular reactive oxygen species (ROS) verified that the inhibition rate can reach 99% within 5 min, without any development of resistance after 15 consecutive generations of culture. Additionally, under ultrasound (US) ‐mediated cavitation, B‐HA@Zn‐TCPP exhibits excellent penetration into biofilms, achieving a 90.04% bactericidal rate for bacteria within biofilms. In vivo studies further demonstrated that B‐HA@Zn‐TCPP can effectively accelerate the healing of bacterial infected wounds with a wound healing rate of 98.65% within 9 days. Therefore, B‐HA@Zn‐TCPP as a novel sonosensitizer offers a viable strategy to overcome the limitations of traditional sonosensitizers for the bacterial wound infections.
Therapeutic potential of nicotinamide and ABT263 in alcohol‐associated liver disease through targeting cellular senescence
Authors: Naheemat Modupeola Gold, Qinchao Ding, Yang Yang, Shaoyan Pu, Wenjing Cao, Xinxuan Ge, Pengyun Yang, Michael Ngozi Okeke, Ayesha Nisar, Yongzhang Pan, Qiuni Luo, Xiayan Wang, Han Xu, Rui Tian, Meiting Zi, Xingjie Zhang, Songtao Li, Yonghan He
Journal: MedComm (2025)

Abstract Alcohol‐associated liver disease (ALD) is a major cause of liver‐related morbidity and mortality, yet clinically effective therapies for ALD remain lacking. Here, we demonstrate that alcohol intake and its metabolite, acetaldehyde (ACH), induce senescence in the liver and liver cells, respectively. To assess the therapeutic potential of targeting liver senescence in ALD, we treated ALD‐affected mice with the senolytic compound ABT263 and the senomorphic NAD + precursor, nicotinamide (NAM). The results show that ABT263 effectively clears senescent hepatocytes and stellate cells, and reduces liver triglyceride (TG), but increases plasma alanine aminotransferase and TG levels. Conversely, NAM efficiently suppresses senescence and the senescence‐associated secretory phenotype (SASP), protecting the liver from alcohol‐induced injury in ALD mice. RNA‐sequencing analysis revealed that ABT263 treatment downregulated genes involved in adipogenesis while activating the complement pathway. In contrast, NAM upregulated metabolism‐related genes, such as Sirt1 , and downregulated DNA damage marker genes, including Rec8 and E2f1 , in the liver. These findings suggest that cellular senescence plays a critical role in alcohol‐induced liver injury. Compared with senescent cell clearance by ABT263, suppressing senescence and SASP by NAM may provide a safer and more effective therapeutic approach for ALD.
MIIST305 mitigates gastrointestinal acute radiation syndrome injury and ameliorates radiation-induced gut microbiome dysbiosis
Authors: Debmalya Mitra, Gabriel K. Armijo, Elizabeth H. Ober, Shenda M. Baker, Helen C. Turner, Constantinos G. Broustas
Journal: Gut Microbes (2025)

High-dose radiation exposure results in gastrointestinal (GI) acute radiation syndrome identified by the destruction of mucosal layer, intestinal growth barrier dysfunction, and aberrant inflammatory responses. Further, radiation causes gut microbiome dysbiosis characterized by diminished microbial diversity, mostly commensal bacteria, and the spread of bacterial pathogens that trigger the recruitment of immune cells and the production of pro-inflammatory factors that lead to further GI tissue damage. Currently, there are no U.S. Food and Drug Administration (FDA) approved countermeasures that can treat radiation-induced GI injuries. To meet this critical need, Synedgen Inc. has developed a glycopolymer radiomitigator (MIIST305) that is specifically targeted to the GI tract, which acts by intercalating into the mucus layer and the glycocalyx of intestinal epithelial cells that could potentially ameliorate the deleterious effects of radiation. Male C57BL/6J adult mice were exposed to 13 Gy partial body X-irradiation with 5% bone marrow shielding and MIIST305 was administered on days 1, 3, and 5 post-irradiation. Approximately 85% of the animals survived the irradiation exposure and were apparently healthy until the end of the 30-day study period. In contrast, no control, Vehicle-treated animals survived past day 10 at this radiation dose. We show that MIIST305 improved intestinal epithelial barrier function and suppressed systemic inflammatory responses mediated by radiation-induced pro-inflammatory cytokines. Taxonomic profiling and community structure of the fecal and colonic mucosa microbiota demonstrated that MIIST305 treatment increased microbial diversity and restored abundance of beneficial commensal bacteria, including Lactobacillus and Bifidobacterium genera while suppressing potentially pathogenic bacteria Enterococcus and Staphylococcus compared with Vehicle-treated animals. In summary, MIIST305 is a novel GI-targeted therapeutic that greatly enhances survival in mice exposed to lethal radiation and protects the GI tract from injury by restoring a balanced gut microbiota and reducing pro-inflammatory responses. Further development of this drug as an FDA-approved medical countermeasure is of critical importance.
Corrigendum to ‘Layer-by-layer deposition of hyaluronic acid and poly-L-lysine for patterned cell co-cultures’ [Biomaterials 25 (2004) 3390]
Authors: Ali Khademhosseini, Kahp Y Suh, Jen M Yang, George Eng, Judy Yeh, Shulamit Levenberg, Robert Langer
Journal: Biomaterials (2025)
Sacituzumab govitecan in advanced urothelial carcinoma: TROPiCS-04, a phase III randomized trial
Authors: T Powles, S Tagawa, C Vulsteke, M Gross-Goupil, S H Park, A Necchi, M De Santis, I Duran, R Morales-Barrera, J Guo, C N Sternberg, J Bellmunt, P J Goebell, M Kovalenko, F Boateng, M Sierecki, L Wang, C S Sima, J Waldes, Y Loriot, P Grivas
Journal: Annals of Oncology (2025)
Lung Function Impairment and Risks of Incident Cardiovascular Diseases and Mortality Among People With Type 2 Diabetes: A Prospective Cohort Study
Authors: Chaolei Chen, Zehan Huang, Lin Liu, Bingbing Su, Yingqing Feng, Yuqing Huang
Journal: Diabetes Care (2025)

OBJECTIVE Individuals with type 2 diabetes (T2D) frequently exhibit impaired lung function, potentially accelerating the onset of cardiovascular disease (CVD), although prospective studies remain limited. We aimed to explore the relationship between lung function impairment and risk of CVD and mortality within this high-risk population. RESEARCH DESIGN AND METHODS This prospective study included 16,242 participants with T2D and free of CVD from the UK Biobank. Obstructive physiology (OP), restrictive physiology (RP), and preserved ratio impaired spirometry (PRISm) were defined using spirometry, including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). Fine-Gray subdistribution hazards models and Cox proportional hazards models were used to estimate risks of CVD and all-cause mortality, respectively. RESULTS During a median follow-up of 13.9 years, 2,825 incident cases of CVD and 2,811 deaths were documented. Lower FEV1, FVC, FEV1/FVC ratio, FEV1 percent predicted, and FVC percent predicted were related to higher risks of CVD and all-cause mortality. Compared with preserved lung function, the adjusted subdistribution hazard ratios (HRs) for CVD were 1.19 (95% CI 1.05–1.35) for OP and 1.47 (95% CI 1.33–1.65) for RP. Compared with the control group, the subdistribution HRs for CVD were 1.20 (95% CI 1.06–1.36) for OP and 1.43 (95% CI 1.29–1.59) for PRISm. These associations were consistent across subgroups and sensitivity analyses. Adding lung function measurements significantly enhanced the performance of CVD prediction beyond the SCORE2-Diabetes model. CONCLUSIONS Lung function impairment was associated with increased risks of CVD and all-cause mortality among individuals with T2D.
Characterization of plasma cell-free DNA variants as of tumor- or clonal hematopoiesis-origin in 16,812 advanced cancer patients
Authors: Daniel Magee, Valeriy Domenyuk, Jim Abraham, Nieves Perdigones Borderias, Jeff Swensen, Praveena Solipuram, Adanma Ayanambakkam, Raja Mehdi, Jagathi Challagalla, Elisabeth Heath, Megan Landsverk, Magdalena Jurkiewicz, Brian Shimkus, Ian Pinto, Daniel Patterson, David Hsiehchen, Supriya Koya, Bradley Somer, Michel Velez, Anthony F. Shields, Jennifer Cultrera, Jennifer R. Ribeiro, Robert Hahn-Lowry, George W. Sledge, Matthew Oberley, Milan Radovich, David Spetzler
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Plasma-based liquid biopsy tests can detect tumor-specific genetic alterations and offer many advantages that complement tissue-based Comprehensive Genomic Profiling (CGP). However, age-related clonal hematopoiesis (CH) mutations can confound liquid biopsy results and potentially lead to incorrect therapy choice. Experimental Design: We assessed the landscape of 16,812 liquid profiles across 49 cancer types using the Caris Assure assay, a whole exome and whole transcriptome NGS workflow that independently sequences both plasma-derived cell-free total nucleic acids (cfTNA) as well as the white blood cell DNA and RNA from the buffy coat. The variant source was identified algorithmically by comparing plasma and buffy coat variant frequency and read quality metrics. Results: 42.3% of 16,812 patients presented at least one CH variant among reportable clinical genes. We found 39% of BRCA2 variants to be of CH origin, as well as 37.9% of CHEK2, 27.4% of BRCA1, 20.1% of ATM, 7.3% NRAS, 5.8% BRAF, 2.1% EGFR, 2.1% KRAS, and 18.5% TP53. For patients aged 65-69, the median proportion of CH variant classification was 20%, whereas it was 33% for patients aged 70-74, 33% for ages 75-79, and 50% for ages 80+. We found high rates of CH detected in what would be otherwise druggable targets in many cancer types typically treated with PARP inhibitors, including breast, female genital tract, ovarian, pancreatic, prostate, and endometrial cancers. Conclusion: This large study highlights the need for thorough CH classification during liquid biopsy to appropriately recommend therapies, especially PARP inhibitors.
Emerging role of Cellular communication network factor 2 (CCN2) as a guardian of smooth muscle cell phenotype and vascular integrity
Authors: J H Larsen, L B Steffensen
Journal: Cardiovascular Research (2025)

Journal Article Accepted manuscript Emerging role of Cellular communication network factor 2 (CCN2) as a guardian of smooth muscle cell phenotype and vascular integrity Get access J H Larsen, J H Larsen Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar L B Steffensen L B Steffensen Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark Corresponding author: Lasse Bach Steffensen, Department of Molecular Medicine, University of Southern Denmark +45-25531280 [email protected] https://orcid.org/0000-0001-6353-4227 Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, cvaf015, https://doi.org/10.1093/cvr/cvaf015 Published: 11 February 2025 Article history Received: 13 November 2024 Revision received: 12 December 2024 Accepted: 07 January 2025 Published: 11 February 2025
Glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist tirzepatide promotes branched chain amino acid catabolism to prevent myocardial infarction in non-diabetic mice
Authors: Mengya Chen, Nan Zhao, Wenke Shi, Yun Xing, Shiqiang Liu, Xianxian Meng, Lanlan Li, Heng Zhang, Yanyan Meng, Saiyang Xie, Wei Deng
Journal: Cardiovascular Research (2025)

A novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, tirzepatide (LY3298176, TZP), has been developed to treat Type 2 diabetes mellitus (T2DM). In ischaemic heart diseases, TZP is involved in cardiac metabolic processes. However, its efficacy and safety in treating heart failure (HF) following myocardial infarction (MI) remain uncertain. Herein, 12 week C57BL/6J mice were subjected to MI surgery, followed by administration of TZP. The effects of TZP on cardiac function and metabolism were thoroughly assessed by physiological, histological, and cellular analyses. Downstream effectors of TZP were screened through untargeted metabolomics analysis and molecular docking. Construct a lower branched chain amino acid (BCAA) diet model to determine whether TZP's cardioprotective effect is associated with reducing BCAA levels. Our results demonstrated that TZP reduced mortality following MI, decreased the infarct area, and attenuated cardiomyocyte necrosis. Pathological evaluation of cardiac tissues demonstrated increased fibrosis repair and decreased inflammatory infiltration. Mechanistically, untargeted metabolomics analysis uncovered a positive correlation between TZP and the BCAA catabolism pathway. The molecular docking verified that TZP could bind with branched-chain keto acid dehydrogenase E1 subunit α (BCKDHA). TZP reduced BCKDHA phosphorylation at S293, enhanced BCAA catabolism, and inhibited the activation of metabolism by activating rapamycin (mTOR) signalling pathway. Furthermore, mice fed a low-BCAA diet post-MI demonstrated reduced cardiomyocyte necrosis, increased fibrosis repair, and decreased inflammatory infiltration. These cardioprotective effects were further enhanced when used synergistically with TZP. Taken together, our findings provide new perspectives on the unrecognized role of TZP in cardiac protection. TZP enhanced BCAA catabolism and attenuated BCAA/mTOR signalling pathway in MI mice. Consequently, this study may present novel therapeutic options for patients with HF.
Global study of 17,009 women reveal significant skin condition changes associated with irregular menstrual cycles
Authors: Christos C Zouboulis, Claire Deloche, Charbel Skayem, Stéphanie Leclerc-Mercier, Philippe Martel, Beatriz Sant’Anna, Charles Taieb, Thierry Passeron
Journal: British Journal of Dermatology (2024)

This international study assesses the impact of menstrual irregularity on skin disorders in women aged between 18 and 55 across 20 countries. It reveals that menstrual irregularities are significantly associated with an increase in the prevalence of acne, rosacea, seborrhoeic dermatitis and melasma. The results underline the importance of an integrated, personalised approach to dermatology for women with irregular menstrual cycles.
VITT-like Monoclonal Gammopathy of Thrombotic Significance
Authors: Jing Jing Wang, Theodore E Warkentin, Linda Schönborn, Matthew B Wheeler, William H Geerts, Nathalie Costedoat-Chalumeau, Nicolas Gendron, Gabriela Ene, Miquel Lozano, Florian Langer, Edelgard Lindhoff-Last, Kathrin Budde, Tim Chataway, Alexander Troelnikov, Jo-Ann I Sheppard, Yi Zhang, Donald M Arnold, Tom P Gordon, Thomas Thiele, Andreas Greinacher, Ishac Nazy
Journal: New England Journal of Medicine (2025)

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is associated with antibodies that target platelet factor 4 (PF4) and are heparin-independent. VITT antibodies are implicated in acute, transient prothrombotic disorders that are triggered by adenoviral vector vaccines against coronavirus disease 2019 or by adenovirus infection. We describe chronic prothrombotic disorders featuring anticoagulant-refractory thromboses and intermittent thrombocytopenia that were associated with VITT-like antibodies in five patients (four patients with newly reported cases and the index patient). The patients had low levels of M proteins (median level, 0.14 g per deciliter); in each patient, we found that the M protein was the VITT-like antibody. The antibody clonotype profiles and binding epitopes on PF4 were different from those observed with the acute disorders occurring after vaccination or viral infection, features that reflect distinct immunopathogenesis. Treatment strategies besides anticoagulation alone are needed for the chronic disorders, referred to as VITT-like monoclonal gammopathy of thrombotic significance. (Funded by the Canadian Institutes of Health Research and others.).
The Consequences of Silencing the “Voice of CDC”
Authors: Sonja A Rasmussen, Mary Lou Lindegren, Lawrence K Altman, Michael F Iademarco
Journal: New England Journal of Medicine (2025)

For more than 60 years, the MMWR has published life-saving information on U.S. public health crises. The Trump administration's pause on health communications has disrupted that essential mission.
MYSTERY-HF - Myeloperoxidase Inhibition in Patients With Heart Failure and Reduced Ejection Fraction – a Phase II Randomized Controlled Trial
Authors: Simon Braumann, Sascha Macherey-Meyer, Amin Polzin, Angelika Costard-Jäckle, Caroline Morbach, Bernhard Haring, Harald Lapp, Vincent ten Cate, Alexander Gieswinkel, Jithmi Weliwitage, Martin Hellmich, Erik Michaëlsson, Karin Nelander, Nelli Ens-Jäger, Stephan Rosenkranz, Simon Gei&#c00DF;en, Norbert Frey, P Christian Schulze, Malin Aurell, Michael Böhm, Stefan Frantz, Malte Kelm, Volker Rudolph, Sanjiv J. Shah, Philipp Wild, Stephan Baldus
Journal: Circulation (2025)
Gatekeeping gender-affirming care is detrimental to detrans people
Authors: Florence Ashley, Neeki Parsa, Til Kus, Lee Leveille, Ky Schevers, G. Nic Rider
Journal: International Journal of Transgender Health (2025)

Gender assessments are often required to access gender-affirming medical interventions. These assessments are typically defended as a way of preventing regret, offering a compromise between the interests of trans and detrans people. Whether they do is integral to ongoing debates about models of care in transgender health. Building on previous work demonstrating the inefficacy of gender assessments, this article explores the impact of gender assessments and argues that they are detrimental to detrans people. Assessments appear to be detrimental to detrans people because they disincentivize honesty and authenticity, inhibit gender exploration, increase shame and anger associated with detransition, foster transnormativity, hinder the development of a strong therapeutic alliance, and diminish the quality of informational disclosure. Given the detrimental consequences of gender assessments, clinicians should reconsider gatekeeping practices in favor of supporting patient decision-making and offering better care to people who detransition.
Concurrent Inhibition of the RAS-MAPK Pathway and PIKfyve is a Therapeutic Strategy for Pancreatic Cancer
Authors: Jonathan M. DeLiberty, Mallory K. Roach, Clint A. Stalnecker, Ryan Robb, Elyse G. Schechter, Noah L. Pieper, Khalilah E. Taylor, Lily M. Pita, Runying Yang, Scott Bang, Kristina Drizyte-Miller, Sarah E. Ackermann, Sheila R. Nicewarner Peña, Elisa Baldelli, Sophia M. Min, David H. Drewry, Emanuel F. Petricoin, John P. Morris, Channing J. Der, Adrienne D. Cox, Kirsten L. Bryant
Journal: Cancer Research (2025)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by KRAS- and autophagy-dependent growth. Inhibition of the KRAS-RAF-MEK-ERK pathway enhances autophagic flux and dependency, and concurrent treatment with the nonspecific autophagy inhibitor chloroquine (CQ) and ERK-MAPK pathway inhibitors can synergistically block PDAC growth. However, CQ is limited in terms of specificity and potency. To find alternative anti-autophagy strategies, here we performed a CRISPR-Cas9 loss-of-function screen in PDAC cell lines that identified the lipid kinase PIKfyve as a growth-promoting gene. PIKfyve inhibition by the small molecule apilimod resulted in durable growth suppression, with much greater potency than CQ treatment. PIKfyve inhibition caused lysosomal dysfunction, reduced autophagic flux, and led to the accumulation of autophagy-related proteins. Furthermore, PIKfyve inhibition blocked the compensatory increases in autophagic flux associated both with MEK inhibition and with direct RAS inhibition. Accordingly, combined inhibition of PIKfyve and the RAS-MAPK pathway showed robust growth suppression across a panel of KRAS-mutant PDAC models. Growth suppression was due, in part, to potentiated cell cycle arrest and induction of apoptosis following loss of IAP proteins. These findings indicate that concurrent inhibition of RAS and PIKfyve is a synergistic, cytotoxic combination that may represent a therapeutic strategy for PDAC.
An Enhanced Osseointegration of Titanium Implants by H<sub>2</sub>S Sustained‐Release Coating via Promoting Osteogenesis and Inhibiting Osteoclastogenesis
Authors: Zuyan Xia, Xinyu Sun, Caiyun Mu, Kai Wang, Wenyu Ma, Wei Yang, Kui Xu
Journal: Advanced Healthcare Materials (2025)

Abstract The surfaces of titanium implants lack the ability of promoting osteogenesis and inhibiting osteoclastogenesis, which primarily contributes to their inadequate integration with surrounding bone tissue in osteoporotic environments. Developing a bioactive coating for the materials is regarded as a promising approach to address the challenge. In this study, a hydrogen sulfide (H 2 S) sustained‐release coating is fabricated on the surfaces of titanium implants. The coating consists of bovine serum albumin nanoparticles encapsulating the H 2 S donor morpholin‐4‐ium(4‐methoxyphenyl)‐morpholin‐4‐ylsulfanylidenesulfido‐λ 5 ‐phosphane (GYY4137), which is prepared with the participation of dopamine self‐polymerization. The release rate of H 2 S could be precisely controlled by adjusting the crosslinking degree of the nanoparticles. The coating proves to have excellent biocompatibility and satisfactory hemocompatibility. In vitro, the coating could significantly promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and inhibit the osteoclastic differentiation of mouse monocytic macrophage leukemia cells (RAW264.7 cells). In vivo, this work successfully verifies the conclusion obtained in vitro experiments. The coating restores the bone homeostasis imbalance surrounding the functionalized titanium implants in the femurs of osteoporotic rats, thereby accelerating new bone formation and enhancing the osseointegration capability of the implants. This work provides a practical strategy for the development of titanium implants suitable for osteoporosis patients.