tbuckley/cabot-search huggingface dataset:
Chromatin Landscape is Associated with Sex-biased Expression and Drosophila-like Dosage Compensation in <i>Artemia franciscana</i>
Authors: Vincent Kiplangat Bett, Minerva Susana Trejo Arellano, Beatriz Vicoso
Journal: Molecular Biology and Evolution (2025)

Abstract The males and females of the brine shrimp Artemia franciscana are highly dimorphic, and this dimorphism is associated with substantial sex-biased gene expression in heads and gonads. How these sex-specific patterns of expression are regulated at the molecular level is unknown. A. franciscana also has differentiated ZW sex chromosomes, with complete dosage compensation, but the molecular mechanism through which compensation is achieved is unknown. Here, we conducted CUT&amp;TAG assays targeting seven post-translational histone modifications (H3K27me3, H3K9me2, H3K9me3, H3K36me3, H3K27ac, H3K4me3 and H4K16ac) in heads and gonads of A. franciscana, allowing us to divide the genome into 12 chromatin states. We further defined functional chromatin signatures for all genes, which were correlated with transcript level abundances. Differences in the occupancy of the profiled epigenetic marks between sexes were associated with differential gene expression between males and females. Finally, we found a significant enrichment of the permissive H4K16ac histone mark in the Z-specific region in both tissues of females but not males, supporting a role of this histone mark in mediating dosage compensation of the Z chromosome.
Antitumor activity of vebreltinib and characterization of clinicogenomic features in solid tumors with MET rearrangements
Authors: Seshiru Nakazawa, Federica Pecci, Igor Odintsov, Dimitris Gazgalis, Felix H. Gottlieb, Biagio Ricciuti, Lodovica Zullo, Joao V. Alessi, Alessandro Di Federico, Mihaela Aldea, Edoardo Garbo, Malini M. Gandhi, Arushi Saini, William W. Feng, Jie Jiang, Simon Baldacci, Francesco Facchinetti, Maisam Makarem, Marie-Anais Locquet, Koji Haratani, Danielle Haradon, Benjamin Besse, Antoine Italiano, Jordi Remon, Pernelle Lavaud, Damien Vasseur, David Planchard, Yusuke Sato, Yukako Watanabe, Scott Owen, Alexis B. CORTOT, Hoda Mahran, Martin D. Forster, Jiaxin Niu, Pascale Tomasini, Leong Swan Swan, Kevin Tay, Emilio Esteban, Anna Minchom, Sani H. Kizilbash, Marcia Cruz-Correa, Kin-Hung Peony Yu, Xiaoling Zhang, Pan Chen, Mythili Sangem, Jianwei Che, Lynette M. Sholl, Pasi A. Janne, Mark M. Awad
Journal: Cancer Discovery (2025)

Abstract Oncogenic translocations involving the MET gene have been reported in several cancer types, but detailed clinicogenomic characterization of these cancers is not well defined. In addition, prospective clinical trials evaluating the antitumor activity of MET inhibitors in MET rearrangement-positive cancers are limited. Here, in a pan-cancer analysis of &amp;gt;46,000 solid tumors with comprehensive genomic profiling, we identified oncogenic MET rearrangements in ~0.04% of cancers. Preliminary analysis from a phase 2 clinical trial of the type I MET tyrosine kinase inhibitor (TKI) vebreltinib in MET fusion-positive solid tumors demonstrated an objective response rate of 50% and disease control rate of 79%, with antitumor activity seen in diverse cancer types including lung adenocarcinoma, intrahepatic cholangiocarcinoma, among others. Similar to MET exon 14-altered lung cancer, secondary mutations in the kinase domain can confer resistance to MET TKIs in MET fusion-positive cancers. Overall, these data categorize MET rearrangements as actionable targets in solid tumors.
First-in-human Study of a Dual-modality Prostate-specific Membrane Antigen–targeted Probe for Preoperative Positron Emission Tomography/Computed Tomography Imaging and Intraoperative Fluorescence Imaging in Prostate Cancer
Authors: Silu Chen, Hongchuang Xu, Xueqi Chen, Qi Shen, Xu Chen, Meng Zhang, Zhihua Li, Zhongyuan Zhang, Han Hao, Wei Yu, Yan Fan, Liqun Zhou, Ning Zhang, Jianhua Zhang, Xing Yang, Cheng Shen, Xuesong Li
Journal: European Urology (2025)
Effect of extending PrEP initiation to primary care settings: a nationwide cohort study in France
Authors: Sophie Bamouni, Sophie Billioti de Gage, David Desplas, Julie Valbousquet, Julie Lamant, Jean-Philippe Joseph, François Dabis, Agnès Viot, Mojgan Hessamfar, Salim Fakir, Rosemary Dray-Spira, Michel Carles
Journal: The Lancet Public Health (2025)

Pre-exposure prophylaxis (PrEP) medicines are key to reducing HIV infection. Improving access, increasing initiation, and expanding the populations covered is therefore important. In June, 2021, in France, PrEP initiation was extended to primary care. The aim of this study was to describe the deployment and characteristics of PrEP initiation in primary care. We did a nationwide cohort study using data obtained from the French National Health Data System (Système National des Données de Santé). We included all people aged 15 years or older, who initiated PrEP in primary care between June 1, 2021, and Dec 31, 2022. We estimated the number of PrEP initiations per month over the period, and the characteristics of people initiating PrEP and prescribers, and PrEP use. 13 500 individuals initiated PrEP in primary care during the study period. The mean number of PrEP initiations increased from 654 (SD 64) per month between July and December, 2021, to 783 (SD 86) per month between July and December, 2022. Individuals initiating PrEP were predominantly male (12 996 [96·3%] of 13 500 individuals) with a mean age of 36 years (SD 11·8), who lived in large urban areas (9581 [71·0%]). 1012 (7·5%) of 13 500 individuals were socioeconomically disadvantaged. Of the 5125 PrEP initiation prescribers, 4542 (88·6%) were general practitioners (GPs), and 4713 (44·7%) of 10 525 were the patient's family practitioner. In the 6 months after PrEP initiation, 6216 (70·8%) of 8783 PrEP initiators had at least one monthly renewal (mean 3·3 renewals [SD 1·7]). 11 961 (82·4%) of 14 507 renewals were made by the same practitioner who had initiated PrEP, and this proportion was higher when the prescriber who had initiated PrEP was the family practitioner (6225 [92·5%] of 7135 renewals). Although the number of PrEP initiations in primary care steadily increased over the study period, the profile of users was unchanged when compared with before extension. The high proportion of PrEP initiations not prescribed by family practitioners highlights potential barriers to sharing sexual health concerns with the family practitioner. Extending PrEP to women, individuals who are socioeconomically disadvantaged, and all those who might benefit from it will require increased awareness among target audiences and practitioners. French National Agency for Medicines and Health Products Safety.
Re: Ventral Versus Dorsal Onlay Buccal Mucosal Graft Urethroplasty for Non-traumatic Proximal Bulbar Urethral Strictures in Sexually Active Men: Erectile and Urinary Functions
Authors: Navid Roessler, Jakob Klemm, Wesley Verla, Malte W Vetterlein
Journal: European Urology (2025)
Biologic switch timing and risk of infection in patients with ulcerative colitis/Crohn’s disease: a retrospective study
Authors: Annie J Kruger, Flavio Dormont, Nicolas Capit, Samantha Schilsky, Andrew Roberts, Yong Lin, Salvatore Badalamenti, Maria Wiekowski, Meenakshi Bewtra, Jean-Frederic Colombel
Journal: Clinical Gastroenterology and Hepatology (2025)
Seeds-and-Soil Inspired Hydrogel Microspheres: A Dual-Action Antioxidant and Cellular Therapy for Reversing Intervertebral Disc Degeneration
Authors: Yilin Yang, Jiangbo Guo, Haifei Cao, Xin Tian, Hao Shen, Junjie Niu, Huilin Yang, Qin Shi, Yong Xu
Journal: Biomaterials (2025)
Thermal-responsive ultrasound activatable <i>in situ</i> production of therapeutics for real-time imaging and targeted tumor therapy
Authors: Meng Du, Fengyi Zeng, Ting Wang, Jinghui Fang, Yuhao Chen, Likang Hou, Bin Li, Qingrong Xia, Zhen Yuan, Fei Yan, Zhiyi Chen
Journal: Theranostics (2025)

Rationale: Engineered bacteria with tumor-targeting capabilities and genetic modification potential have emerged as promising vectors for targeted tumor therapy through the effective production and release of therapeutic molecules. Controlled gene expression and real-time monitoring of therapeutic protein expression in tumors are of great significance for optimizing the therapeutic effective of engineered bacteria production as well as anti-tumor effects. Methods: We constructed engineered E. coli MG1655 cells using recombinant thermal plasmid pBV220 carrying the optical imaging reporter gene miRFP720 and the therapeutic gene Cytolysin A, which could be controlled expressed synchronously by thermal effect produced by focused ultrasound. The concentrations of miRFP720 and Cytolysin A expressed by engineered bacteria after focused ultrasound irradiation were detected in vitro and in vivo with western blot analysis and enzyme-linked immunosorbent assay (ELISA) analysis. The immune cell infiltration rate and inflammation factors after treatment were detected by flow cytometry and ELISA analysis. The anti-tumor efficacy of engineered bacteria alone or combined with anti-Programmed cell death 1 ligand 1 (aPD-L1) immunotherapy were evaluated on subcutaneous tumor models and orthotopic glioblastoma models. Results: Upon ultrasound-controlled activation, the expression level of therapeutic molecule Cytolysin A as well as the optical imaging probe miRFP720 were enhanced. Importantly, the expression level of Cytolysin A could be monitored in vivo non-invasively by the signal intensity produced by miRFP720, which provided guidance for optimized ultrasound-mediated therapeutic production in situ. Furthermore, with optimized ultrasound activation, Cytolysin A not only exerted potent anti-tumor effects but also induced immunogenic cell death, enhancing the therapeutic efficiency of aPD-L1 immunotherapy for deep site tumor treatment. Conclusion: In this study, a real-time imaging guided ultrasound activatable tumor targeted therapy mode was established. Utilizing the thermal effect of focused ultrasound, Cytolysin A-miRFP720 engineered bacteria can concurrently express the therapeutic molecule Cytolysin A and the imaging probe miRFP720, which optimized the expression level of therapeutic production by engineered bacteria through imaging guided ultrasound irradiation mode, and realized enhanced the therapeutic efficiency of local tumor anti-tumor efficiency as well as aPD-L1 immunotherapy.
Sex bias in tumor immunity: insights from immune cells
Authors: Xuerui Tao, Yiling Wang, Binghua Xiang, Dongmei Hu, Wei Xiong, Wenjun Liao, Shichuan Zhang, Chi Liu, Xiaoxiao Wang, Yue Zhao
Journal: Theranostics (2025)

Significant sex disparities have been observed in cancer incidence, treatment response to immunotherapy, and susceptibility to adverse effects, affecting both reproductive and non-reproductive organ cancers. While lifestyle factors, carcinogenic exposure, and healthcare access contribute to these disparities, they do not fully explain the observed male-female variation in anti-tumor immunity. Despite the preferential expression of sex hormone receptors in immune cells, X chromosome also contains numerous genes involved in immune function, and its incomplete inactivation may enhance anti-tumor immune responses in females. In contrast, loss or downregulation of Y-linked genes in males has been associated with an increased cancer risk. Additionally, estrogen, progesterone and androgen signaling pathways influence both innate and adaptive immune responses, contributing to sex-specific outcomes in cancer progression and therapy. Sex-biased differences are also evident in the epigenetic regulation of gene expression, cellular senescence, microbiota composition, metabolism, and DNA damage response, all of which impact anti-tumor immunity and immunotherapy treatment efficacy. In general, the combination of sex chromosomes, sex hormones, and hormone receptors orchestrates the phenotype and function of various immune cells involved in tumor immunity. However, sex disparity in each specific immune cell are context and environment dependent, considering the preferential expression of hormone receptor in immune cell and sex hormone levels fluctuate significantly across different life stages. This review aims to outline the molecular, cellular, and epigenetic changes in T cells, B cells, NK cells, DCs, neutrophils, and macrophages driven by sex chromosomes and sex hormone signaling. These insights may inform the design of sex-specific targeted therapies and leading to more individualized cancer treatment strategies.
Decoding the role of microtubules: a trafficking road for vesicle
Authors: Jiaorong Qu, Jianan Li, Hong Wang, Jianhang Lan, Zixuan Huo, Xiaojiaoyang Li
Journal: Theranostics (2025)

Background: In eukaryotic cells, intracellular and extracellular vesicle transport systems are ubiquitous and tightly linked. This process involves well-defined initiation and termination points, as well as mechanisms for vesicle recycling. During transport, cytoskeletal components serve as "roads" to prevent disordered vesicular movement and to ensure efficient transport, particularly through microtubules. Microtubules primarily facilitate the long-distance transport of vesicles. The dynamic nature of microtubule structure makes its stability sensitive to proteins, drugs, and post-translational modifications such as acetylation, which in turn regulate microtubule-dependent vesicular transport. Furthermore, motor proteins interact with microtubules and bind to cargoes via their tail domains, driving vesicle transport along microtubules and determining the directionality of movement. Aim of review: To elucidate the detailed processes and mechanisms of microtubules-regulated long-distance vesicle transport, providing a comprehensive overview of current research in this area. Key scientific concepts of review: This review provides an in-depth analysis of microtubule-mediated vesicle transport, emphasizing the molecular mechanisms involved. It examines vesicle transport between organelles, the impact of microtubule characteristics on this process, and the role of motor proteins in vesicle dynamics. Additionally, it summarizes diseases associated with abnormal microtubule-mediated vesicle transport, aiming to offer insights for the treatment of related conditions.
LRG1 inhibition promotes acute pancreatitis recovery by inducing cholecystokinin Type 1 receptor expression via Akt
Authors: Seok Ting Lim, Xinmei Zhao, Shuqing Liu, Wenjuan Zhang, Yuanyang Tan, Nidula Mullappilly, Sandip M Swain, Mei Ling Leong, Ravisankar Rajarethinam, Kah Fei Wan, Christiane Ruedl, Rodger A Liddle, Liang Li, Xiaomeng Wang
Journal: Theranostics (2025)

Rationale: Acute pancreatitis (AP) is a common gastrointestinal disease affecting nearly 3 million people annually worldwide. Although AP is typically self-limiting, up to 20% of patients may develop life-threatening complications. Individuals who suffer from AP also have an increased likelihood of developing other exocrine and endocrine pancreatic disorders. However, to date, there are no specific, targeted treatment modalities that can effectively improve the clinical outcomes of AP. Leucine-rich alpha-2 glycoprotein 1 (LRG1) is a multifunctional protein with established roles in inflammation and cell mitosis. This study aims to investigate the functional role of LRG1 in AP progression and develop LRG1-targeted AP therapeutics. Methods: Levels of circulating and tissue LRG1 were determined in human patient samples and mouse models of caerulein-induced AP and pancreatic duct ligation-induced AP. Histopathological grading, amylase assay, real-time polymerase chain reaction analysis and Western blotting were used to evaluate the extent of pancreatic damage and recovery following caerulein-induced AP in both wild-type and Lrg1-/- mice. Primary acinar cells were also isolated from mice for in-vitro mechanistic studies. LRG1 neutralizing antibody was administered post-AP induction to evaluate its therapeutic potential in improving AP outcomes. Results: LRG1 is markedly increased in serum and acinar cells of AP patients and C57BL/6 mice subjected to caerulein-induced AP or pancreatic duct ligation-induced AP. Despite demonstrating no obvious pancreatic dysfunction, Lrg1-/- mice exhibited more severe pancreatic damage and inflammation during the early stages of caerulein-induced AP. However, the resolution of AP was accelerated in the absence of Lrg1, which is at least partially due to LRG1's role in regulating the expression of trophic cholecystokinin (CCK) Type 1 receptor (CCK1R) via the TGFβ/ALK5/AKT pathway in acinar cells. Importantly, the administration of an LRG1-blocking antibody promoted AP recovery, evidenced by reduced overall inflammation and increased acinar cell proliferation. Conclusions: Our data provide compelling evidence for targeting LRG1 as a potential innovative therapy for promoting AP recovery.
Noninvasive DWI tracking of hiPSCs differentiation into RTECs in AKI recovery via the KSP promoter-mediated AQP1 strategy
Authors: Yue Zhao, Mingfu Gong, Xu Liu, Qian Xie, Tao Sun, Chunyu Zhou, Tongsheng Shu, Shuang Wang, Liang Zhang, Dong Zhang
Journal: Theranostics (2025)

Rationale: Human-induced pluripotent stem cells (hiPSCs) exhibit great potential in the treatment of acute kidney injury (AKI), and their targeted differentiation into renal tubular epithelial cells (RTECs) is directly involved in the repair of the injured tissue. However, their differentiation during treatment is difficult to evaluate noninvasively. Methods: Aquaporin 1 (AQP1) can alter the dispersion of water molecules at the cellular level and thus can be detected with high sensitivity by diffusion-weighted imaging (DWI). In this study, a kidney-specific promoter (KSP-cadherin)-driven AQP1 overexpression lentivirus (KSP-AQP1) was constructed and used for tracking the differentiation of hiPSCs in vivo. Then, two AKI animal models were used to identify the feasibility of KSP-AQP1 for in vivo tracking of the differentiation of hiPSCs into RTECs. Results: We utilized KSP-positive and KSP-negative cells to examine the in vitro specificity of KSP-AQP1. It was found that only the KSP-positive cells showed a substantial expression of AQP1, accompanied by a significant variation in both the diffusion-weighted imaging (DWI) signal intensity (SI) and the apparent diffusion coefficient (ADC) values. whereas KSP-AQP1-transduced KSP-negative cells had no apparent SI and ADC changes. DWI results suggested that after the hiPSCs transplantation in vivo, the KSP-AQP1-pretransduced hiPSCs group exhibited a significantly decreased SI and increased ADC value when compared with the hiPSCs-treated and untreated AKI kidneys. In addition, the AQP1-mediated differences in DWI SI and ADC value between the KSP-AQP1-pretransduced hiPSCs group and hiPSCs group were confirmed by analysis of the KSP transcriptional activity using co-expressed exogenous flag gene mCherry. Conclusions: This study successfully developed a method for tracking the differentiation of hiPSCs into RTECs in vivo during the treatment of AKI using a KSP-regulated AQP1 overexpression strategy.
Toward the clinical translation of safe intravenous long circulating ILNEs contrast agent for CT imaging
Authors: Mohamed F Attia, Ryan N Marasco, Samuel Kwain, Charity Foxx, Daniel C Whitehead, Alexander Kabanov, Yueh Z Lee
Journal: Theranostics (2025)

Rationale: X-ray computed tomography (CT) is crucial in precision medicine for diagnostic and therapeutic guidance. However, current small molecule CT contrast agents pose risks such as nephrotoxicity, short blood circulation time, limited scan durations, potential thyroid impact, and immune responses. These challenges necessitate the development of kidney-safe nanoparticle (NP)-based contrast agents (CAs). Methods: We developed safe intravenous blood pool NP-based CT CAs at a clinical-equivalent dose of 300 mgI/kg, suitable for vascular and hepatic imaging. Our iodinated lipid nanoemulsions (ILNEs) were optimized for shelf-life stability, osmolarity, and viscosity for excellent injectability. The ILNEs were designed to offer high contrast and were tested for minimal protein interaction, prolonged blood circulation, and hepatic clearance. In vitro studies, along with tests in mice and porcine models, were conducted to confirm safety, cytocompatibility, and absence of tissue damage. Results: The ILNEs demonstrated high x-ray attenuation, improved contrast enhancement, extended stability, and batch-to-batch consistency. They exhibited minimal protein interaction, prolonged blood residency of about 4 h, and hepatic clearance within three days, avoiding nephrotoxicity. Blood and thyroid-stimulating hormone (TSH) analyses, along with kidney and liver function tests, confirmed the safety of ILNEs. Conclusion: Our ILNEs offer a promising alternative to current CT contrast agents, with improved safety and efficacy profiles. The results support further toxicity evaluations for clinical translation, highlighting the potential of ILNEs in vascular and hepatic imaging without the associated risks of nephrotoxicity.
Mitochondria-targeting natural product rhein conjugated with dichloroacetate as the dual inhibitor of glycolysis and oxidative phosphorylation to off energize cancer cells and induce ROS storm
Authors: Zhili Zhang, Shiming Tang, Minghui Qi, Hongyang Zhao, Meng Wu, Shi-Wen Huang
Journal: Theranostics (2025)

Rationale: Metabolic reprogramming emerges as a remarkable hallmark of cancer cells and exhibits potential in the development of metabolic modulators. Numerous small-molecule inhibitors mainly target reversing the dominant-glycolysis pathway. However, energy metabolic adaptation that facilitates the alternation of metabolic phenotypes from glycolysis to oxidative phosphorylation (OXPHOS) undermines treatment efficacy. Thus, small molecular therapeutic agents, concurrently cutting off the cellular energy metabolism of glycolysis and OXPHOS and trigger oxidative stress damage, hold promise for cancer therapy. Methods: Herein, natural product rhein with the capacity of mitochondria-targeting was conjugated with pyruvate dehydrogenase kinase (PDK) inhibitor dichloroacetate (DCA) to form a multifunction small molecule drug Rhein-DCA conjugate. The ATP production inhibition, oxidative stress damage and antitumor efficacy of Rhein-DCA conjugate were evaluated both in vitro and in vivo. Results: Rhein unit not only led to the effective accumulation of Rhein-DCA conjugate in mitochondria, but also promoted the binding of DCA and PDK1, enhancing typical inhibition of glycolysis by DCA via PDK-PDH axis. Unlike classical PDK inhibitors, which restrained glycolysis and restored OXPHOS, rhein within the conjugate further suppressed mitochondrial respiratory chain complex and induced sustained opening of mitochondrial permeability transition pore, destroying intractable OXPHOS. Importantly, rhein component in the conjugate elevated the reactive oxygen species (ROS) level to further disrupt OXPHOS, and thus ROS triggered the release of damage associated molecular patterns. Simultaneously, the conjugate weakened lactate-mediated immunosuppression by reducing lactate levels in the tumor microenvironment. Eventually, the polarization state of tumor-associated macrophages could be effectively reversed following oral administration. Conclusion: This study designed a small-molecule dual-inhibitor of glycolysis and OXPHOS to circumvent metabolic adaptations and simultaneously induce immunogenic cell death for macrophages repolarization, thereby synergistically promoting antitumor efficacy.