tbuckley/cabot-search huggingface dataset:
Reducing Granules Without Splicing Restoration Alleviates RBM20 Cardiomyopathy
Authors: Mei Methawasin, Yanghai Zhang, Zachery R. Gregorich, Yaqin He, Chunling Liu, Julia Muldoon, Zaynab Hourani, John E. Smith, Henk Granzier, Wei Guo
Journal: Circulation Research (2025)

BACKGROUND: RBM20 (RNA binding motif protein 20) cardiomyopathy is a severe form of dilated cardiomyopathy (DCM). Genetic variants in the nuclear localization signal of Rbm20 hinder its nuclear import and promote cytoplasmic pathogenic RNP (ribonucleoprotein) granules. We aimed to investigate whether reducing RNP granules by inhibiting Rbm20 expression could alleviate the DCM phenotype in Rbm20 S639G ( Rbm20 S639G ) knock-in mice. METHODS: We downregulated Rbm20 , utilizing antisense oligonucleotides (ASOs) that specifically inhibit Rbm20 expression. We administered Rbm20 -ASOs in Rbm20 S639G mice that carry a serine-to-glycine substitution in the nuclear localization signal of RBM20. The Rbm20 -ASOs were administered subcutaneously at 25 mg/kg once a week for 8 weeks in both young (14-day-old) mice before the onset of DCM and adult (3-month-old) mice with established DCM phenotype. In vivo cardiac function was assessed by echocardiography. RNP granules were identified through fluorescent immunohistochemical staining, and the number and size of RNP granules were quantified using Cell Profiler software. Alternative splicing of RBM20 target genes was determined by reverse transcription polymerase chain reaction, and titin isoform expression was analyzed by gel electrophoresis. Cardiomyocyte Ca 2+ release-reuptake kinetics and mouse electrocardiography were also studied. RESULTS: The results revealed that reducing the level of Rbm20 expression through treatment with ASOs significantly decreased the cytoplasmic RNP granules within the Rbm20 S639G cardiomyocytes. ASO treatment reduced the severity of DCM developed when treatment was initiated before the onset of the disease. Importantly, ASO treatment reversed cardiac dysfunction and remodeling when treatment was commenced in mice with established DCM as shown by a significant improvement in ejection fraction and a decrease in the severity of left ventricular chamber dilation. Treatment with ASOs also effectively mitigated left ventricular hypertrophic remodeling and improved ECG parameters observed as normalized P wave and QRS durations. These beneficial effects occur without the restoration of mis-splicing of RBM20 target genes, including the primary target gene Ttn , and other genes such as Camk2d , Ryr2 , and Ank3 . CONCLUSIONS: The findings of this study demonstrated that RNP granules serve as a critical driver for RBM20 cardiomyopathy, and reduction of RNP granules through treatment with ASOs is a possible therapeutic option for RBM20 cardiomyopathy in patients carrying RBM20 genetic variants in the nuclear localization signal region.
DNA methylation dynamics play crucial roles in shaping the distinct transcriptomic profiles for different root-type initiation in rice
Authors: Wei Jiang, Zhou Zhou, Xiaoying Li, Yu Zhao, Shaoli Zhou
Journal: Genome biology (2025)

Abstract Background Monocots possess a fibrous root system comprising an embryonic root, crown roots, and lateral roots. The distinct cellular origins highlight the diversity of the initiation mechanism. To date, the distinct initiation mechanisms have been poorly studied. In this study, we conduct a comprehensive transcriptome and DNA methylome assay of these root types during their initiation. Results Our findings indicate significant divergence in transcriptome regulation trajectories with apparent transcriptional activation in post-embryonic root initials (crown root and lateral root) contrasted by suppression in embryonic root generation. Additionally, CHH methylation is dynamically and differentially regulated across the initiation stages of the various root types, and is significantly associated with the short transposon element within the promoter regions of functional genes, which plays crucial roles in determining the genes’ spatiotemporal transcription. Moreover, our work reveals that the activation of DNA glycosylase 702 (DNG702) and repression of Domains Rearranged Methyltransferase 2 (DRM2) play important roles in the erasure of CHH methylation and activation of functional genes during the processes, such as a novel identified key regulatory bZip65 , thus directly impacting the initiation of post-embryonic roots in rice. Conclusions Our extensive analysis delineates the landscapes of spatiotemporal transcriptomes and DNA methylomes during the initiation of the three root types in rice, shedding light on the pivotal role of CHH methylation in the spatiotemporal regulation of various key genes, ensuring the successful initiation of distinct root types in rice.
Author correction to “The upregulated intestinal folate transporters direct the uptake of ligand-modified nanoparticles for enhanced oral insulin delivery” [Acta Pharmaceutica Sinica B 12 (2022) 1460–1472]
Authors: Jingyi Li, Yaqi Zhang, Miaorong Yu, Aohua Wang, Yu Qiu, Weiwei Fan, Lars Hovgaard, Mingshi Yang, Yiming Li, Rui Wang, Xiuying Li, Yong Gan
Journal: Acta Pharmaceutica Sinica B (2025)
Publisher erratum to “Fenofibrate-promoted hepatomegaly and liver regeneration are PPARα-dependent and partially related to the YAP pathway” [Acta Pharmaceutica Sinica B 14 (2024) 2992-3008]
Authors: Shicheng Fan, Yue Gao, Pengfei Zhao, Guomin Xie, Yanying Zhou, Xiao Yang, Xuan Li, Shuaishuai Zhang, Frank J. Gonzalez, Aijuan Qu, Min Huang, Huichang Bi
Journal: Acta Pharmaceutica Sinica B (2025)
Light-Stimulated Smart Thermo-Responsive Constructs for Enhanced Wound Healing: A Streamlined Command Approach
Authors: Bingcheng Yi, Lei Yu, Yating Yang, Carlos F. Guimarães, Ruijie Xu, Thavasyappan Thambi, Boya Zhou, Qihui Zhou, Rui L. Reis
Journal: Asian Journal of Pharmaceutical Sciences (2025)
Single‐Cell Transcriptomics Revealed E‐Cigarettes‐Induced Vascular Remodeling by Enhancing <i>Tcf21</i> Expression
Authors: Ruiyang Ding, Xiaoke Ren, Qinglin Sun, Shiqian liu, Linyuan Huang, Zhiwei Sun, Junchao Duan
Journal: MedComm (2025)
Engineered platelet-derived exosomal spheres for enhanced tumor penetration and extended circulation in melanoma immunotherapy
Authors: Jian Zhao, Xinyan Lv, Qi Lu, Kaiyuan Wang, Lili Du, Xiaoyuan Fan, Fei Sun, Fengxiang Liu, Zhonggui He, Hao Ye, Jin Sun
Journal: Acta Pharmaceutica Sinica B (2025)
Inflammation-related collagen fibril destruction contributes to temporomandibular joint disc displacement via NF-κB activation
Authors: Shengjie Cui, Yanning Guo, Yu Fu, Ting Zhang, Jieni Zhang, Yehua Gan, Yanheng Zhou, Yan Gu, Eileen Gentleman, Yan Liu, Xuedong Wang
Journal: International Journal of Oral Science (2025)

Abstract Temporomandibular joint (TMJ) disc displacement is one of the most significant subtypes of temporomandibular joint disorders, but its etiology and mechanism are poorly understood. In this study, we elucidated the mechanisms by which destruction of inflamed collagen fibrils induces alterations in the mechanical properties and positioning of the TMJ disc. By constructing a rat model of TMJ arthritis, we observed anteriorly dislocated TMJ discs with aggravated deformity in vivo from five weeks to six months after a local injection of Freund’s complete adjuvant. By mimicking inflammatory conditions with interleukin-1 beta in vitro, we observed enhanced expression of collagen-synthesis markers in primary TMJ disc cells cultured in a conventional two-dimensional environment. In contrast, three-dimensional (3D)-cultivated disc cell sheets demonstrated the disordered assembly of inflamed collagen fibrils, inappropriate arrangement, and decreased Young’s modulus. Mechanistically, inflammation-related activation of the nuclear factor kappa-B (NF-κB) pathway occurs during the progression of TMJ arthritis. NF-κB inhibition reduced the collagen fibril destruction in the inflamed disc cell sheets in vitro, and early NF-κB blockade alleviated collagen degeneration and dislocation of the TMJ discs in vivo. Therefore, the NF-κB pathway participates in the collagen remodeling in inflamed TMJ discs, offering a potential therapeutic target for disc displacement.
The Prospective Registry of MyositIS (PROMIS): I. Next-generation sequencing identifies HLA-DQA1 as a novel genetic risk of anti-MDA5 antibody-positive dermatomyositis
Authors: Xinzhuang Yang, Chen Yu, Xiuling Zhang, Chanyuan Wu, Zhao Peng, Yixuan Gai, Jinmin Peng, Shuang Zhou, Lan Song, Hui Huang, Dong Xu, Jiuliang Zhao, Xinping Tian, Xinwang Duan, Xiaofeng Zeng, Mengtao Li, Qian Wang
Journal: Annals of the Rheumatic Diseases (2025)

Antimelanoma differentiation-associated gene 5-positive dermatomyositis (anti-MDA5+ DM) is a rare subtype of myositis with a poor prognosis and insufficient genetic understanding. Our study aimed to identify risk variants associated with anti-MDA5+ DM and to assess their correlation with clinical outcomes. We enrolled 231 anti-MDA5+ DM patients, 127 anti-MDA5⁻ DM patients, 1468 patients with non-DM rheumatic disease, and 1027 healthy controls, with an additional 51 anti-MDA5+ DM patients for validation. Whole-exome sequencing was used to identify human leukocyte antigen (HLA) alleles, amino acids, and single nucleotide polymorphisms (SNPs) in major histocompatibility complex (MHC) and non-MHC regions. Association studies were performed to identify genetic variants associated with anti-MDA5+ DM by comparing different sets of control groups. A clinical association study was conducted to further explore the influence of genetic factors on clinical manifestations. Two novel genetic risks, HLA-DQA1*06:01 and HLA-DQB1*06:09, were significantly associated with anti-MDA5+ DM in both the discovery and validation cohorts. HLA-DQA1*06:01 was particularly prevalent in anti-MDA5+ DM (20.4%) compared with anti-MDA5⁻ DM (6.69%) and non-DM rheumatic disease (5.93%). Besides, the strongest associated amino acid was HLA-DQα1:69 (P = 3.27 × 10-11), and 1 SNP in the ARHGAP22 gene (rs76208937) showed suggestive significance (P = 7.99 × 10-6). In addition, HLA-DQA1*06:01 was linked to acute rapidly progressive interstitial lung disease (P < .001), elevated levels of lactate dehydrogenase (P = .026), and death (P = .049) in patients with anti-MDA5+ DM. HLA-DQA1*06:01 is a new genetic and prognostic factor for anti-MDA5+ DM, potentially serving as a biomarker for early diagnosis and intervention.
TREM2 and sTREM2 in Alzheimer’s disease: from mechanisms to therapies
Authors: Lianshuai Zhang, Xianyuan Xiang, Yahui Li, Guojun Bu, Xiao-Fen Chen
Journal: Molecular Neurodegeneration (2025)

Abstract Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor predominantly expressed by microglia in the brain. Recent studies have established TREM2 as a central immune signaling hub in neurodegeneration, where it triggers immune responses upon sensing pathological development and tissue damages. TREM2 binds diverse ligands and activates downstream pathways that regulate microglial phagocytosis, inflammatory responses, and metabolic reprogramming. Interestingly, TREM2 exists both in its membrane-bound form and as a soluble variant (sTREM2), that latter is generated through proteolytic shedding or alternative splicing and can be detected in cerebrospinal fluid and plasma. Emerging clinical and preclinical evidence underscores the potential of TREM2 and sTREM2 as diagnostic biomarkers and therapeutic targets in Alzheimer’s disease (AD). This review provides a comprehensive overview of the molecular functions, regulatory mechanisms, and pathological implications of TREM2 and sTREM2 in AD. Furthermore, we explore their potential roles in diagnostics and therapeutics while suggesting key research directions for advancing TREM2/sTREM2-based strategies in combating AD.
Therapeutic effects of adipose-derived mesenchymal stem cells combined with glymphatic system activation in prion disease
Authors: Mohammed Zayed, Yong-Chan Kim, Byung-Hoon Jeong
Journal: Molecular Neurodegeneration (2025)

Abstract There is currently no effective therapy for prion diseases. The glymphatic system is an organized system of perivascular spaces that facilitates the removal of metabolic waste from the brain. This study demonstrates the therapeutic potential of a combination therapy of adipose-derived mesenchymal stem cells (AdMSCs) and a glymphatic system-activated drug, clonidine, against prion disease. The therapy has the potential to clear PrP Sc accumulation, ameliorate astrocytosis, and prolong the survival time of ME7-infected mice.
Nanomaterials-driven in situ vaccination: a novel frontier in tumor immunotherapy
Authors: Naimeng Liu, Xiangyu Wang, Zhongzhao Wang, Yonemori Kan, Yi Fang, Jidong Gao, Xiangyi Kong, Jing Wang
Journal: Journal of Hematology & Oncology (2025)

In situ vaccination (ISV) has emerged as a promising strategy in cancer immunotherapy, offering a targeted approach that uses the tumor microenvironment (TME) to stimulate an immune response directly at the tumor site. This method minimizes systemic exposure while maintaining therapeutic efficacy and enhancing safety. Recent advances in nanotechnology have enabled new approaches to ISV by utilizing nanomaterials with unique properties, including enhanced permeability, retention, and controlled drug release. ISV employing nanomaterials can induce immunogenic cell death and reverse the immunosuppressive and hypoxic TME, thereby converting a "cold" tumor into a "hot" tumor and facilitating a more robust immune response. This review examines the mechanisms through which nanomaterials-based ISV enhances anti-tumor immunity, summarizes clinical applications of these strategies, and evaluates its capacity to serve as a neoadjuvant therapy for eliminating micrometastases in early-stage cancer patients. Challenges associated with the clinical translation of nanomaterials-based ISV, including nanomaterial metabolism, optimization of treatment protocols, and integration with other therapies such as radiotherapy, chemotherapy, and photothermal therapy, are also discussed. Advances in nanotechnology and immunotherapy continue to expand the possible applications of ISV, potentially leading to improved outcomes across a broad range of cancer types.
KRAS mutation detection by liquid biopsy for pancreatic ductal adenocarcinoma
Authors: Mahmoud Yousef, Abdelrahman Yousef, Mark W Hurd, Ashwathy Pillai, Saikat Chowdhury, Rebecca Snyder, Mark Knafl, Ryan L Lewis, Paul M Roy, Mohammad Fanaeian, Sali Albarouki, Luca F Castelnovo, Jennifer Peterson, Brandon G Smaglo, Robert A Wolff, Shubham Pant, Jason Willis, Ryan Huey, Michael Overman, Ching-Wei Tzeng, Michael P Kim, Naruhiko Ikoma, Jess E Maxwell, Matthew H G Katz, Huamin Wang, Anirban Maitra, Eugene Koay, Ethan B Ludmir, Anthony Chen, Camila Lopez, Haoqiang Ying, John Paul Shen, Dan Zhao
Journal: Journal of Hematology & Oncology (2025)

Abstract The clinical utility of liquid biopsy (LB) for pancreatic ductal adenocarcinoma (PDAC) remain understudied. Our single-institution cohort of 311 PDAC patients with non-tumor tissues informed LB found 81.2% positivity ( N = 186) in metastatic cases and in 52.4% ( N = 43) of localized disease. KRAS mutations were detected in 64.6% ( N = 148) of metastatic cases and 16% ( N = 13) for localized disease. Positive LB, especially KRAS mutation detection, is associated with worse overall survival (OS) in metastatic PDAC (median 14.5 vs. 31.3 months, HR = 2.7, 95%CI = 1.7–4.3, P &lt; 0.0001). The positive concordance rates of KRAS and TP53 mutations were 63% and 68% in metastatic disease but only 7% ( KRAS ) and 33% ( TP53 ) in localized disease, respectively. Among the 41 patients who underwent serial liquid biopsy testing, 25% tested positive after an initial negative result. LB detects therapeutically targetable mutations in 58.5% of PDAC patients and is associated with OS.
Concurrent Norovirus Outbreaks Associated with Consumption of Oysters Harvested in Mexico — California, December 2023–January 2024
Authors: Sophie Zhu, Christina Grant, Chao-Yang Pan, Brandon Adcock, Annie Kao, Sarah Stous, Lisa Yee, Olivia Springfield, Madeline Poranski, Audrey Kennar, Mark Beatty, Seema Shah, Heather Watson, Heather Buonomo, Anna Liza M. Manlutac, Heriberto Lima, Devon Mendez, Bianca Clark, Marifi Pulido, Melina Bakshi, Charlene Contreras, Nicole Green, Taylor Burleson, Jenafer Forester, Stephen W. Klish, Matthew Feaster, Elizabeth V. Taylor, Nora Balanji, Vanna Kho, April Hatada, Chelsea Wright, Christina Morales, Melissa Abbott, Floyd Raymond Burditt, Elisa Elliot, Jessica L. Jones, Marshall Kinsey, Michael Lombardi, Kristina Phelps, Jaquelina W. Woods, Akiko Kimura, Katherine Lamba
Journal: MMWR Morbidity and Mortality Weekly Report (2025)

Norovirus is the most common cause of foodborne illness outbreaks in the United States. In January 2024, local health jurisdictions and the California Department of Public Health (CDPH) identified two concurrent norovirus outbreaks across eight Southern California local health jurisdictions. CDPH was notified in late December 2023 and early January 2024 of gastrointestinal illnesses in persons who consumed raw oysters from food service facilities in San Diego County (outbreak 1). Additional illness reports came from multiple jurisdictions that included Los Angeles County and other areas in Southern California (outbreak 2). In total, approximately 400 persons across eight local health jurisdictions reported gastrointestinal illness after raw oyster consumption. A multiagency investigation confirmed that outbreaks 1 and 2 were unrelated, and implicated oysters were traced to two separate, nonoverlapping harvest regions in Mexico. A total of 179 outbreak-associated cases, including 24 laboratory-confirmed norovirus cases, were identified. Patient samples from both outbreaks identified norovirus genogroups I and II; other enteric viruses (sapovirus, astrovirus, rotavirus, and adenovirus) were also identified from one or both outbreaks. Noroviruses were genetically related by genotype within each outbreak but dissimilar between outbreaks. In outbreak 2, oysters might have been contaminated at a location separate from the original growing area, also known as wet storage. Concurrent outbreaks with similar modes of transmission can be unrelated, and the source for each should be confirmed through traceback. Proper storage and handling of shellfish is essential to maintaining safety of food products to consumers. Cooking oysters to 145°F (62.8°C) is recommended before consumption.
Hmgb2 improves astrocyte to neuron conversion by increasing the chromatin accessibility of genes associated with neuronal maturation in a proneuronal factor-dependent manner
Authors: Priya Maddhesiya, Tjasa Lepko, Andrea Steiner-Mezzardi, Julia Schneider, Veronika Schwarz, Juliane Merl-Pham, Finja Berger, Stefanie M Hauck, Lorenza Ronfani, Marco Bianchi, Tatiana Simon, Anthodesmi Krontira, Giacomo Masserdotti, Magdalena Götz, Jovica Ninkovic
Journal: Genome biology (2025)
Abstract P3036: Predicting Risk of Obesity-Related Outcomes in People with Obesity or Overweight: the Role of Social Risk Factors
Authors: Bonny Rockettewagner, Kelsey Leonard, Steven Belle, Zichong Liu, Hong Kan, Nadia Ahmad, Lisa Neff, Kathleen McTigue, Hannah Daugherty
Journal: Circulation (2025)

Introduction: Social risk factors have been shown to be related to overweight/obesity and developing related poor health outcomes. Prediction models for obesity-related outcomes in people with obesity or overweight developed within clinical care settings can be used in decision making to identify individual patient risk for poor outcomes. There have been calls to link person-level or census tract level social risk factors to Electronic Health Record (EHR) data for use in clinical decision-making. However, such methods have not been fully developed and more information is needed regarding which social risk factors are relevant for predicting risk. Objective: To examine whether adding primary payer type and publicly available zip code level composite (Area Deprivation Index; National Walk Index; Rural-urban Commuting Area) or non-composite (poverty rate, low-income tract, median family income, population density) risk factors improve risk prediction model fit and accuracy. Methods: EHR data for 837,373 eligible patients (18-80 years, BMI 25-80 kg/m 2 , with 5-digit zip code to link to census data) were utilized to determine the value of adding social risk factors to validated prediction models developed for use in clinical care settings. Outcomes were times to event for type 2 diabetes (T2DM), atherosclerotic cardiovascular disease, heart failure, sleep apnea, and obesity-related cancer. Models were fit using a multi-level Cox regression with a competing risk of death. Adaptive LASSO was applied to add social risk factors to existing models. Full models with all significant social risk variables and reduced models in which highly correlated social risk variables were removed, were examined. Assessments of model fit were done utilizing the AIC/BIC and Harrel’s C-index was calculated to assess predictive ability. Results: Several models retained some social risk factors. The model for T2DM was the only one in which social risk factors did not improve the EHR-only models, though increases in Harrel’s C-index values were small (&lt;0.01) for the other models with social risk factors added. Conclusions: Individual and composite zip code level social risk factors were statistically significantly associated with all outcomes and improved the models, except for T2DM, but did not meaningfully improve predictive ability. Additional studies are warranted examining effects of social risk closer to, or at, the individual level, such as census block or neighborhood.
Abstract P2071: Effects of Dietary Patterns and Sodium Intake on Blood Pressure Variability: Results from the DASH and DASH-Sodium Trials
Authors: Siyu Zou, Sunan Gao, Stephen Juraschek, Edgar Miller, Kunihiro Matsushita, Lawrence Appel
Journal: Circulation (2025)

Background: Increased blood pressure (BP) variability is associated with adverse cardiovascular disease outcomes. The Dietary Approaches to Stop Hypertension (DASH) diet and sodium reduction lower BP and cardiovascular risk, but their effects on office and ambulatory BP variability are uncertain. Methods: This study analyzed data from the DASH and DASH-Sodium trials, including those participants who were randomized to the DASH or Control diet and had both office and 24-hour ambulatory BP measurements. Office BP was measured at baseline and end of feeding periods using a random-zero sphygmomanometer. Ambulatory BP was measured at the end of intervention periods in both trials and at baseline in DASH trial. BP variability was quantified using the variation independent of the mean (VIM) and compared across groups using t-tests. We used bias-corrected and accelerated bootstrap methods to calculate 95% CIs for the difference in VIM. Results: The DASH trial analyses included 214 participants (mean age, 45 years; 48% Female; 59% Black) while the DASH-Sodium trial analyses included 337 participants (mean age, 49 years; 58% Female; 60% Black). After intervention, neither the DASH diet nor sodium reduction significantly affected BP variability in office or ambulatory measurements. In DASH trial, the difference in VIM for office systolic BP between DASH and Control diets was -0.17 (95% CI -0.82 to 0.47), and for ambulatory systolic BP was 0.59 (95% CI -0.23 to 1.41). In the DASH-Sodium trial, compared to high sodium levels, low sodium levels showed similar BP variability (e.g., ΔVIM for office systolic BP: 0.29, 95% CI -0.08 to 0.69; ΔVIM for ambulatory systolic BP: 0.05, 95% CI -0.27 to 0.37). No significant combined or interactive effects of diet and sodium level on BP variability were observed. Conclusion: While the DASH diet and reduced sodium intake effectively lower absolute BP levels, these dietary interventions do not significantly affect BP variability. These findings suggest that the BP-related benefits of the DASH diet and sodium reduction primarily result from reducing absolute BP rather than reducing BP variability.