tbuckley/cabot-search huggingface dataset:
Long-Term Response of Obstructive Hypertrophic Cardiomyopathy Patients to Mavacamten Based on Sex
Authors: Milind Y Desai, Sara Saberi, Jeffrey B Geske, Andrew Wang, Paul Cremer, David R Fermin, Mark A Zenker, Neal K Lakdawala, Albree Tower-Rader, Srihari S Naidu, Kathy Lampl, Anjali Owens
Journal: JACC Heart Failure (2025)
Cognitive Function and Patient-Reported Outcomes After Cardiogenic Shock
Authors: Eric J Hall, Jeff Schaffert, Sachin Agarwal, Colby R Ayers, Alexandra V Sykes, Laura H Lacritz, Amil M Shah, E Wesley Ely, C Munro Cullum, Maryjane A Farr, James A de Lemos
Journal: Journal of the American College of Cardiology (2025)
Widespread impact of transposable elements on the evolution of post-transcriptional regulation in the cotton genus Gossypium
Authors: Xuehan Tian, Ruipeng Wang, Zhenping Liu, Sifan Lu, Xinyuan Chen, Zeyu Zhang, Fang Liu, Hongbin Li, Xianlong Zhang, Maojun Wang
Journal: Genome biology (2025)

Transposable element (TE) expansion has long been known to mediate genome evolution and phenotypic diversity in organisms, but its impact on the evolution of post-transcriptional regulation following species divergence remains unclear. To address this issue, we perform long-read direct RNA sequencing, polysome profiling sequencing, and small RNA sequencing in the cotton genus Gossypium, the species of which range more than three folds in genome size. We find that TE expansion contributes to the turnover of transcription splicing sites and regulatory sequences, leading to changes in alternative splicing patterns and the expression levels of orthologous genes. We also find that TE-derived upstream open reading frames and microRNAs serve as regulatory elements mediating differences in the translation levels of orthologous genes. We further identify genes that exhibit lineage-specific divergence at the transcriptional, splicing, and translational levels, and showcase the high flexibility of gene expression regulation in the evolutionary process. Our work highlights the significant role of TE in driving post-transcriptional regulation divergence in the cotton genus. It offers insights for deciphering the evolutionary mechanisms of cotton species and the formation of biological diversity.
The haplotype-resolved genome assembly of an ancient citrus variety provides insights into the domestication history and fruit trait formation of loose-skin mandarins
Authors: Minqiang Yin, Xiaochan Song, Chao He, Xiyuan Li, Mengyuan Li, Jiangbo Li, Hao Wu, Chuanwu Chen, Li Zhang, Zhenmei Cai, Liqing Lu, Yanhui Xu, Xin Wang, Hualin Yi, Juxun Wu
Journal: Genome biology (2025)

Loose-skin mandarins (LSMs) are among the oldest domesticated horticultural crops, yet their domestication history and the genetic basis underlying the formation of key selected traits remain unclear. We provide a chromosome-scale and haplotype-resolved assembly for the ancient Chinese citrus variety Nanfengmiju tangerine. Through the integration of 77 resequenced and 114 published citrus germplasm genomes, we categorize LSMs into 12 distinct groups based on population genomic analyses. We infer that the ancestors of modern cultivated mandarins diverged from wild mandarins in Daoxian approximately 500,000 years ago, when they entered the Yangtze and Pearl River Basins. There, they were domesticated into four ancient cultivation groups, forming the cornerstone of modern Chinese LSM cultivation. We identify selective sweeps underlying quantitative trait loci and genes related to important fruit quality traits, including sweetness and size. We reveal that the co-selection of sugar transporter and metabolism genes are associated with increased fruit sweetness. Significant alterations in the auxin and gibberellin signaling networks may contribute to the enlargement of LSM fruits. We also provide a comprehensive, high-spatiotemporal-resolution atlas of allelic gene expression during citrus fruit development. We detect 5890 allele pairs showing specific expression patterns and a significant increase in variation levels. Our study provides valuable genomic resources and further revises the origin and domestication history of LSMs, offering insights for genetic improvement of citrus plants.
Dual Functionalized Absorbable Hairy Cellulose‐Based Fabric for Efficient Hemostasis and Antibacterial Property
Authors: Nastaran Alipour, Seyedhosein Jarolmasjed, Salar Salmanipour, Ali Rezaie, Maryam Ghahremani‐Nasab, Morteza Milani, Ahmad Mehdipour, Roya Salehi
Journal: Advanced Healthcare Materials (2025)

Abstract Uncontrolled hemorrhage and subsequent infection at the injury sites are major causes of trauma‐related mortality. Herein, we present a novel approach to creating a multifunctional biodegradable textile fabric with hemostatic and antibacterial properties, synthesized through chemical modification, including etherification, oxidation (aldehyde), and amination via a Schiff‐based reaction between octadecyl ammonium and oxidized cellulose, followed by calcium ion cross‐linking. The fabric demonstrated significant antibacterial efficay against both gram‐positive ( Staphylococcus aureus ) and gram‐negative ( Escherichia coli ) bacteria, validated through assays such as colony counting, minimum inhibitory concentration (MIC), scanning electron microscopy, and fluorescent staining using Acridine Orange and Propidium Iodide. In vitro assessments demonstrated superior performance compared to commercial alternatives in red blood cell attachment (90%), blood clotting index (6%), platelet adhesion, and clotting time (20s) ( P ‐value &lt; 0.001). In vivo studies using a Wistar rat liver injury model confirmed the fabric's effectiveness, reducing bleeding time (3.1 and 6.2‐fold) and blood loss (1.2 and 5.48‐fold) compared to available commercial hemostatic agents. Pathological, hematological, and biochemical analyses demonstrated the biocompatibility and biodegradability of our developed material with no evidence of systemic toxicity, significant localized inflammatory reactions in the liver, renal, or skin tissues, or vascular thrombosis stimulation.
Lycium‐Barbarum Polysaccharide‐Loaded Dual‐Crosslinked Rigid Hydrogel Enhances Bone Healing in Diabetic Bone Defects by Scavenging Reactive Oxygen Species
Authors: Wenjie Zhong, Wenao Liao, Lingcong Xu, Niezhenghao He, Ke Xu, Caiyuan Liu, Fei Wang, Wei Zhang, Jiang Hu, Haowen Cui
Journal: Advanced Healthcare Materials (2025)

Abstract Diabetes‐induced oxidative stress can lead to poor bone defect healing, severely affecting the quality of life for patients. Studies show that improving the microenvironment and promoting bone formation can effectively accelerate the healing of bone defects. However, traditional local drug delivery methods face various challenges during the treatment process. Therefore, this study develops a novel hydrogel (HLBP) loaded with natural protein polysaccharides (LBP) extracted from goji berries, aiming to enhance the healing of diabetic bone defects. The hydrogel is composed of freeze‐dried polyvinyl alcohol (PVA) and photocrosslinked poly (ethylene glycol) diacrylate (PEGDA). This hydrogel exhibits excellent biocompatibility. Additionally, it demonstrates effective loading capacity for the LBP. LBP's bioactivity enables ROS scavenging and promotes bone regeneration at defect sites. In vitro, experimental results show that HLBP significantly reduces ROS levels and enhances osteogenic differentiation ability and cell viability of human bone marrow mesenchymal stem cells. In vivo studies using BKS‐db diabetic mice show that HLBP implantation at bone defects achieves over 80% healing, highlighting its strong healing potential. This method effectively avoids potential toxicity from systemic drug administration and significantly promotes regeneration at the bone defect site, providing a new strategy for treating diabetic bone defects.
Systematic interrogation of functional genes underlying cholesterol and lipid homeostasis
Authors: Haihuan Shan, Shuangshuang Fan, Quanrun Li, Ruipu Liang, Zhisong Chen, Shengnan Wang, Xiaofeng Wang, Yurong Li, Shuai Chen, Kun Yu, Teng Fei
Journal: Genome biology (2025)

Dyslipidemia or hypercholesterolemia are among the main risk factors for cardiovascular diseases. Unraveling the molecular basis of lipid or cholesterol homeostasis would help to identify novel drug targets and develop effective therapeutics. Here, we adopt a systematic approach to catalog the genes underlying lipid and cholesterol homeostasis by combinatorial use of high-throughput CRISPR screening, RNA sequencing, human genetic variant association analysis, and proteomic and metabolomic profiling. Such integrative multi-omics efforts identify gamma-glutamyltransferase GGT7 as an intriguing potential cholesterol and lipid regulator. As a SREBP2-dependent target, GGT7 positively regulates cellular cholesterol levels and affects the expression of several cholesterol metabolism genes. Furthermore, GGT7 interacts with actin-dependent motor protein MYH10 to control low-density lipoprotein cholesterol (LDL-C) uptake into the cells. Genetic ablation of Ggt7 in mice leads to reduced serum cholesterol levels, supporting an in vivo role of Ggt7 during cholesterol homeostasis. Our study not only provides a repertoire of lipid or cholesterol regulatory genes from multiple angles but also reveals a causal link between a gamma-glutamyltransferase and cholesterol metabolism.
Enhanced Immune Modulation and Bone Tissue Regeneration through an Intelligent Magnetic Scaffold Targeting Macrophage Mitochondria
Authors: Zuyun Yan, Tianshi Sun, Jin Zeng, Tao He, Yiwen He, Dongcheng Xu, Renfeng Liu, Wei Tan, Xiaofang Zang, Jinpeng Yan, Youwen Deng
Journal: Advanced Healthcare Materials (2025)

Abstract During the bone tissue repair process, the highly dynamic interactions between the host and materials hinder precise, stable, and sustained immune modulation. Regulating the immune response based on potential mechanisms of macrophage phenotypic changes may represent an effective strategy for promoting bone healing. This study successfully constructs a co‐dispersed pFe₃O₄‐MXene nanosystem by loading positively charged magnetite (pFe₃O₄) nanoparticles onto MXene nanosheets using electrostatic self‐assembly. Subsequently, this work fabricates a biomimetic porous bone scaffold (PFM) via selective laser sintering, which exhibit superior magnetic properties, mechanical performance, hydrophilicity, and biocompatibility. Further investigations demonstrate that the PFM scaffold could precisely and remotely modulate macrophage polarization toward the M2 phenotype under a static magnetic field, significantly enhancing osteogenesis and angiogenesis. Proteomic analysis reveal that the scaffold upregulates Arg2 expression, enhancing mitochondrial function and accelerating oxidative phosphorylation, thereby inducing the M2 transition. In vivo experiments validated the scaffold's immune regulatory capacity in subcutaneous and cranial defect repairs in rats, effectively promoting new bone formation. Overall, this strategy of immune modulation targeting macrophage metabolism and mitochondrial function offers novel insights for material design in tissue engineering and regenerative medicine.
Mitigation of atrial fibrillation‐related complications with antithrombotic and cytoreductive therapy in patients with Myeloproliferative Neoplasms: Implications from the GSG‐MPN bioregistry
Authors: Hyunyee Rosa Cho, Susanne Isfort, Kim Kricheldorf, Frank Stegelmann, Martine Klausmann, Florian H. Heidel, Martin Griesshammer, Holger Schulz, Andreas Hochhaus, Joachim Göthert, Rudolf Schlag, Wiebke Hollburg, Lino Teichmann, Katja Sockel, Stefan Wilop, Deniz Gezer, Martin Kirschner, Konstanze Döhner, Tim H. Brümmendorf, Steffen Koschmieder
Journal: HemaSphere (2025)
Loss of CYLD promotes splenic marginal zone lymphoma
Authors: Athanasios Pseftogas, Jessica Bordini, Silvia Heltai, Ferdinando Bonfiglio, Georgios Gavriilidis, Vasileios Vasileiou, Sofoklis Keisaris, Daniela Belloni, Caterina Taccetti, Pamela Ranghetti, Eleonora Perotta, Michela Frenquelli, Uday Aditya Sarkar, Elisa Albi, Francesca Martini, Emmanuela Sant'Antonio, Fabrizio Mavilia, Fotis Psomopoulos, Manasori Daibata, José Ángel Martínez Climent, George Mosialos, Davide Rossi, Alessandro Campanella, Lydia Scarfò, Kostas Stamatopoulos, Konstantinos Xanthopoulos, Paolo Ghia
Journal: HemaSphere (2025)

Abstract Splenic marginal zone lymphoma (SMZL) is a distinct clinical and pathological entity among marginal zone lymphomas. Genetic and microenvironmental factors leading to aberrant activation of the NF‐κB pathway have been implicated in SMZL pathogenesis. CYLD is a negative regulator of NF‐κB and other signaling pathways acting as a deubiquitinase of regulatory molecules and has been reported as a tumor suppressor in different types of cancer, including B‐cell malignancies. To assess whether CYLD is implicated in the natural history of SMZL, we profiled primary cells from patients with SMZL and SMZL cell lines for CYLD expression and functionality. We report that CYLD is downregulated in patients with SMZL and that CYLD ablation in vitro leads to NF‐κB pathway hyperactivation, promoting the proliferation of SMZL cells. In addition, we found that CYLD deficiency was associated with increased migration of SMZL cells in vitro, through CCR7 receptor signaling, and with increased dissemination in vivo. CYLD loss was sufficient to induce BcR signaling, conferring increased resistance to ibrutinib treatment in vitro. In summary, our work uncovers a novel role of CYLD as a key regulator in SMZL pathogenesis, dissemination, and resistance to targeted agents. On these grounds, CYLD could be proposed as a novel target for patient stratification and personalized interventions.
Metatranscriptomic profiling reveals pathogen and host response signatures of pediatric acute sinusitis and upper respiratory infection
Authors: Andrew C. Doxey, Nooran Abu Mazen, Max Homm, Vivian Chu, Manjot Hunjan, Briallen Lobb, Sojin Lee, Marcia Kurs-Lasky, John V. Williams, William MacDonald, Monika Johnson, Jeremy A. Hirota, Nader Shaikh
Journal: Genome Medicine (2025)

Abstract Background Acute sinusitis (AS) is a frequent cause of antibiotic prescriptions in children. Distinguishing bacterial AS from common viral upper respiratory infections (URIs) is crucial to prevent unnecessary antibiotic use but is challenging with current diagnostic methods. Despite its speed and cost, untargeted RNA sequencing of clinical samples from children with suspected AS has the potential to overcome several limitations of other methods. In addition, RNA-seq may reveal novel host-response biomarkers for development of future diagnostic assays that distinguish bacterial from viral infections. There are however no available RNA-seq datasets of pediatric AS that provide a comprehensive view of both pathogen etiology and host immune response. Methods Here, we performed untargeted RNA-seq (metatranscriptomics) of nasopharyngeal samples from 221 children with AS and performed a comprehensive analysis of pathogen etiology and the impact of bacterial and viral infections on host immune responses. Accuracy of RNA-seq-based pathogen detection was evaluated by comparison with culture tests for three common bacterial pathogens and qRT-PCR tests for 12 respiratory viruses. Host gene expression patterns were explored to identify potential host responses that distinguish bacterial from viral infections. Results RNA-seq-based pathogen detection showed high concordance with culture or qRT-PCR, showing 87%/81% sensitivity (sens) / specificity (spec) for detecting three AS-associated bacterial pathogens, and 86%/92% (sens/spec) for detecting 12 URI-associated viruses, respectively. RNA-seq also detected an additional 22 pathogens not tested for clinically and identified plausible pathogens in 11/19 (58%) of cases where no organism was detected by culture or qRT-PCR. We reconstructed genomes of 196 viruses across the samples including novel strains of coronaviruses, respiratory syncytial virus, and enterovirus D68, which provide useful genomic data for ongoing pathogen surveillance programs. By analyzing host gene expression, we identified host-response signatures that differentiate bacterial and viral infections, revealing hundreds of candidate gene biomarkers for future diagnostic assays. Conclusions Our study provides a one-of-kind dataset that profiles the interplay between pathogen infection and host responses in pediatric AS and URI. It reveals bacterial and viral-specific host responses that could enable new diagnostic approaches and demonstrates the potential of untargeted RNA-seq in diagnostic analysis of AS and URI.
Exos‐Loaded Gox‐Modified Smart‐Response Self‐Healing Hydrogel Improves the Microenvironment and Promotes Wound Healing in Diabetic Wounds (Adv. Healthcare Mater. 7/2025)
Authors: Pu Yang, Yikun Ju, Naisi Shen, Shuai Zhu, Jiaqian He, Lingxiu Yang, Jiajie Lei, Xiaoli He, Wenjia Shao, Lanjie Lei, Bairong Fang
Journal: Advanced Healthcare Materials (2025)
o8G-modified circPLCE1 inhibits lung cancer progression via chaperone-mediated autophagy
Authors: Qingyun Zhao, Dunyu Cai, Haotian Xu, Yihong Gao, Ruirui Zhang, Xiaodong Zhou, Xingcai Chen, Sixian Chen, Jiaxi Wu, Wenyi Peng, Shengyi Yuan, Deqing Li, Gang Li, Aruo Nan
Journal: Molecular Cancer (2025)

Lung cancer poses a serious threat to human health, but its molecular mechanisms remain unclear. Circular RNAs (circRNAs) are closely associated with tumour progression, and the important role of 8-oxoguanine (o8G) modification in regulating the fate of RNA has been gradually revealed. However, o8G modification of circRNAs has not been reported. We identified circPLCE1, which is significantly downregulated in lung cancer, and further investigated the o8G modification of circPLCE1 and the related mechanism in lung cancer progression. We identified differentially expressed circRNAs by RNA high-throughput sequencing and then conducted methylated RNA immunoprecipitation (MeRIP), immunofluorescence (IF) analysis, crosslinking immunoprecipitation (CLIP) and actinomycin D (ActD) assays to explore circPLCE1 o8G modification. The biological functions of circPLCE1 in vivo and in vitro were clarified via establishing a circPLCE1 silencing/overexpression system. Tagged RNA affinity purification (TRAP), RNA Immunoprecipitation (RIP) and coimmunoprecipitation (Co-IP) assays, and pSIN-PAmCherry-KFERQ-NE reporter gene were used to elucidate the molecular mechanism by which circPLCE1 inhibits lung cancer progression. This study revealed that reactive oxygen species (ROS) can induce circPLCE1 o8G modification and that AUF1 can mediate a decrease in circPLCE1 stability. We found that circPLCE1 significantly inhibited lung cancer progression in vitro and in vivo and that its expression was associated with tumour stage and prognosis. The molecular mechanism was elucidated: circPLCE1 targets the HSC70 protein, increases its ubiquitination level, regulates ATG5-dependent macroautophagy via the chaperone-mediated autophagy (CMA) pathway, and ultimately inhibits lung cancer progression. o8G-modified circPLCE1 inhibits lung cancer progression through CMA to inhibit macroautophagy and alter cell fate. This study provides not only a new theoretical basis for elucidating the molecular mechanism of lung cancer progression but also potential targets for lung cancer treatment. ROS induce circPLCE1 o8G modification, and AUF1 specifically recognizes o8G modification, thereby decreases circPLCE1 stability. circPLCE1 targets the HSC70 protein, increases its ubiquitination level, inhibits CMA activity, and promotes ATG5-dependent macroautophagy via the CMA pathway, altering the fate of tumour cells and ultimately inhibiting lung cancer progression.
An Energy Metabolism Nanoblocker for Cutting Tumor Cell Respiration and Inhibiting Mitochondrial Hijacking from Cytotoxic T Lymphocyte
Authors: Xiaojing Leng, Yang Yang, Tao Jiang, Jun Zheng, Liang Zhang, Ju Huang, Han Xu, Mingxiao Fang, Xingsheng Li, Zhigang Wang, Min Ge, Han Lin
Journal: Advanced Healthcare Materials (2025)

Abstract Energy metabolism modulation emerges as a highly regarded strategy for tumor therapy. However, the efficacy of targeting energy metabolism in tumor cells remains unsatisfactory due to the alternate energy production pathways by switching between mitochondrial respiration and glycolysis. In addition, tumor cells can hijack mitochondria from peripheral immune cells to maintain their energy metabolism as an extra respiratory pathway. In this study, a CD44 receptor‐targeted hyaluronic acid energy metabolism nanoblocker is developed to achieve bidirectional blockade of basal respiration in tumor cells with the loaded mitochondrial oxidative phosphorylation (OXPHOS) inhibitor nebivolol hydrochloride, and the glycolysis inhibitor 3‐bromopyruvate. Furthermore, combined intraperitoneal injection of L‐778123 hydrochloride inhibits mitochondrial transfer, thus blocking the extra respiratory pathway of tumor cells and the depletion of cytotoxic T lymphocytes. This emerging strategy, which involves depleting tumor cell energy through inhibition of basal respiration (OXPHOS/glycolysis) and extra respiration, while synergistically enhancing effector immune cells to maintain systemic anti‐tumor immune effects, demonstrates high efficacy and safety in both in vitro and in vivo experiments. It provides a conceptual paradigm shift in nanomedicine‐mediated energy metabolism‐based tumor therapy.
Title Actuated Hydrogel Platforms To Study Brain Cell Behavior
Authors: Kirill E. Zhurenkov, Darren Svirskis, Bronwen Connor, Jenny Malmström
Journal: Advanced Healthcare Materials (2025)

Abstract The human brain is a highly complex organ characterized by intricate neural networks, biochemical signaling, and unique mechanical properties. The soft and dynamic viscoelastic extracellular matrix (ECM) plays a crucial role in supporting different types of brain cells and influencing their behavior. Understanding how brain cells respond to mechanical stimuli within this complex environment is essential for unraveling fundamental mechanisms of healthy, unhealthy, and regenerative functions within the central nervous system. This requires the development of advanced materials and techniques to study the interplay between mechanical cues and cell responses. Hydrogels have become essential in this research, mimicking the brain's ECM in both chemical composition and mechanical behavior. Conventional hydrogels, while helpful, are static and lack dynamic stimulation. On the other hand, dynamic hydrogels provide reversible, dynamic stimulation, closely replicating the brain's ECM properties. This review discusses current hydrogel platforms used to investigate brain function in health and disease, focusing on traumatic brain injury (TBI)‐like conditions and brain tumors. These dynamic materials offer sophisticated tools for understanding brain cell mechanobiology and developing new therapeutic approaches.