tbuckley/cabot-search huggingface dataset:
Diabetes-associated sleep fragmentation impairs liver and heart function via SIRT1-dependent epigenetic modulation of NADPH oxidase 4
Authors: Yuanfang Guo, Jie Wang, Dongmei Zhang, Yufeng Tang, Quanli Cheng, Jiahao Li, Ting Gao, Xiaohui Zhang, Guangping Lu, Mingrui Liu, Xun Guan, Xinyu Tang, Junlian Gu
Journal: Acta Pharmaceutica Sinica B (2025)

Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.
SiCLAT: simultaneous imaging of chromatin loops and active transcription in living cells
Authors: Xin Wan, Jie Kong, Xiaodi Hu, Lulu Liu, Yuanping Yang, Hu Li, Gaoao Liu, Xingchen Niu, Fengling Chen, Dan Zhang, Dahai Zhu, Yong Zhang
Journal: Genome biology (2025)

We present SiCLAT, which introduces a dCas9-dCas13d cassette into the mouse genome. This model enables the stable expression of both dCas9 and dCas13 proteins in diverse cell populations, facilitating concurrent labeling of DNA and RNA across various cell types. Using SiCLAT, we accurately labeled chromatin loop anchor interactions and associated gene transcription during myogenic differentiation. This imaging system offers a novel means of directly observing cis-element interactions and the corresponding gene transcription in living primary cells, thus providing real-time imaging for comprehensive mechanistic investigations of dynamic enhancer-promoter or enhancer-enhancer interactions in regulating transcription activation within living cells.
Clickable liposomes for on-demand reversal of antiplatelet drugs: Towards a safe management of bleeding risks associated with antithrombotic therapy
Authors: Xiaoyu Cheng, Chunling Wang, Junchao Xu, Yubiao Huang, Zhuo Chen, Liyue Zhong, Chong Du, Guangjun Nie, Yinlong Zhang
Journal: Journal of Controlled Release (2025)
Disrupted callosal connectivity underlies long-lasting sensory-motor deficits in an NMDA receptor antibody encephalitis mouse model
Authors: Jing Zhou, Ariele L Greenfield, Rita P Loudermilk, Christopher M Bartley, Chun Chen, Xiumin Chen, Morgane Ah Leroux, Yujun Lu, Deanna Necula, Thomas T Ngo, Baouyen T Tran, Patrick S Honma, Kelli Lauderdale, Chao Zhao, Xiaoyuan Zhou, Hong Wang, Roger A Nicoll, Cong Wang, Jeanne T Paz, Jorge J Palop, Michael R Wilson, Samuel J Pleasure
Journal: Journal of Clinical Investigation (2024)

NMDA receptor mediated autoimmune encephalitis (NMDAR-AE) frequently results in persistent sensory-motor deficits, especially in children, yet the underlying mechanisms remain unclear. This study investigated the long- term effects of exposure to a patient-derived GluN1-specific monoclonal antibody (mAb) during a critical developmental period (from postnatal day 3 to day 12) in mice. We observed long-lasting sensory-motor deficits characteristic of NMDAR-AE, along with permanent changes in callosal axons within the primary somatosensory cortex (S1) in adulthood, including increased terminal branch complexity. This complexity was associated with paroxysmal recruitment of neurons in S1 in response to callosal stimulation. Particularly during complex motor tasks, mAb3-treated mice exhibited significantly reduced inter-hemispheric functional connectivity between S1 regions, consistent with pronounced sensory-motor behavioral deficits. These findings suggest that transient exposure to anti-GluN1 mAb during a critical developmental window may lead to irreversible morphological and functional changes in callosal axons, which could significantly impair sensory-motor integration and contribute to long-lasting sensory-motor deficits. Our study establishes a new model of NMDAR-AE and identifies novel cellular and network-level mechanisms underlying persistent sensory-motor deficits in this context. These insights lay the foundation for future research into molecular mechanisms and the development of targeted therapeutic interventions.
Ascorbate-loaded Mg Fe layered double hydroxide for osteomyelitis treatment
Authors: Wei Li, Yuliang Huang, Dongqiang Gu, Sijun Peng, Bao Zhang, Feng Peng, Dongdong Zhang, Mingjun Li, Jin Xiao, Zhiwei Jia, Longhai Qiu
Journal: Journal of Controlled Release (2025)
FOXO1 pathway activation by VISTA immune checkpoint restrains pulmonary ILC2 functions
Authors: Mohammad Hossein Kazemi, Zahra Momeni-Varposhti, Xin Li, Benjamin P. Hurrell, Yoshihiro Sakano, Stephen Shen, Pedram Shafiei-Jahani, Kei Sakano, Omid Akbari
Journal: Journal of Clinical Investigation (2025)

Type-2 innate lymphoid cells (ILC2s) play a pivotal role in the development of airway hyperreactivity (AHR). However, the regulatory mechanisms governing ILC2 function remain inadequately explored. This study uncovers V-domain Ig suppressor of T cell activation (VISTA) as an inhibitory immune checkpoint crucial for modulating ILC2-driven lung inflammation. VISTA is upregulated in activated pulmonary ILC2s and plays a key role in regulating lung inflammation, as VISTA-deficient ILC2s demonstrate increased proliferation and function, resulting in elevated type-2 cytokine production and exacerbation of AHR. Mechanistically, VISTA stimulation activates Forkhead box O1 (FOXO1), leading to modulation of ILC2 proliferation and function. The suppressive effects of FOXO1 on ILC2 effector function were confirmed using FOXO1 inhibitors and activators. Moreover, VISTA-deficient ILC2s exhibit enhanced fatty acid oxidation and oxidative phosphorylation to meet their high energy demands. Therapeutically, VISTA agonist treatment reduces ILC2 function both ex vivo and in vivo, significantly alleviating ILC2-driven AHR. Our murine findings were validated in human ILC2s, where a VISTA agonist reduces their function ex vivo and in a humanized mouse model of ILC2-driven AHR. Our studies unravel VISTA as an immune checkpoint for ILC2 regulation via the FOXO1 pathway, presenting potential therapeutic strategies for allergic asthma by modulating ILC2 responses.
Functional germline variants in DNA damage repair pathways are associated with altered survival in adults with glioma treated with temozolomide
Authors: Geno Guerra, George Wendt, Lucie McCoy, Helen M Hansen, Linda Kachuri, Annette M Molinaro, Terri Rice, Victoria Guan, Lianne Capistrano, Allison Hsieh, Veruna Kalsi, Jaimie Sallee, Jennie W Taylor, Jennifer L Clarke, Eduardo Rodriguez Almaraz, John K Wiencke, Jeanette E Eckel-Passow, Robert B Jenkins, Margaret Wrensch, Stephen S Francis
Journal: Neuro-Oncology (2025)

Temozolomide (TMZ) treatment has demonstrated, but variable, impact on glioma prognosis. This study examines associations of survival with DNA repair gene germline polymorphisms among glioma patients who did and did not have TMZ treatment. Identifying genetic markers which sensitize tumor cells to TMZ could personalize therapy and improve outcomes.
Prevalence of Diagnosed Diabetes Among U.S. Adults Aged ≥18 Years With Disabilities, 2021–2022
Authors: Barbara H. Bardenheier, John D. Omura, Jinan B. Saaddine, Israel Hora, Kai McKeever Bullard
Journal: Diabetes Care (2025)

OBJECTIVE To compare the prevalence of diagnosed diabetes among U.S. adults with and without disabilities, overall and by subgroups. RESEARCH DESIGN AND METHODS We used data on adults aged ≥18 years from the cross-sectional 2021–2022 National Health Interview Survey to report the prevalence of diagnosed diabetes by functional disability status and for each disability type (hearing, seeing, mobility, cognition, self-care, and communication) separately. With use of the Washington Group Short Set on Functioning indicator, disability was defined according to the categories of milder (reporting some difficulty), moderate (reporting a lot of difficulty), and severe (cannot do at all) by disability type. Crude prevalence and age-standardized prevalence of diabetes were also calculated for adults with any difficulty with any disability by age, sex, race/ethnicity, education, insurance, and poverty-to-income ratio. RESULTS Diabetes prevalence increased with number of disability types, was lower among adults with no disability (5.8%) than among those with milder (9.5%) or moderate to more severe (18.3%) disability, and was 4.0–10.3 percentage points higher among those with moderate to more severe disability than among those with milder disability for vision, hearing, mobility, and cognitive disabilities. Diabetes prevalence was similar for adults with milder and moderate to more severe self-care and communication disabilities. CONCLUSIONS Prevalence of diabetes was higher among adults with any functional disability than without and increased with increasing number of disability types. Adults with multiple disability types, or those who have difficulty with self-care or communication or other moderate to more severe disabilities, may benefit from diabetes prevention programs.
circASAP1 induces renal clear cell carcinoma ferroptosis by binding to HNRNPC and thereby regulating GPX4
Authors: Yunfei Wang, Taowei Yang, Qihao Li, Zhousan Zheng, Lican Liao, Junjie Cen, Wei Chen, Junhang Luo, Yi Xu, Mi Zhou, Jiaxing Zhang
Journal: Molecular Cancer (2025)

Clear cell renal cell carcinoma (ccRCC) represents the most prevalent subtype, accounting for nearly 80% of all RCC cases. Recent research has shown that high expression of circular non-coding RNA (circRNA) is associated with poor prognosis in patients with renal clear cell carcinoma (ccRCC), however, the underlying mechanism remains unclear. After analysing self-sequenced renal cancer and paracancer circRNA sequencing data and comparing it with the GEO public database, we discovered that circASAP1 expression was significantly up-regulated in renal cancers. We also tested circASAP1 levels in 102 renal cancer patients and found that high expression of circASAP1 was associated with poor prognosis and metastasis. The interaction between circASAP1, HNRNPC and their downstream target genes was confirmed through experiments such as RNA pull-down, RIP and fluorescence in situ hybridisation. A series of in vitro and in vivo functional experiments were performed to verify the effects of circASAP1 on RCC proliferation and metastasis. Circular RNA sequencing analysis revealed that circASAP1 expression was markedly elevated in ccRCC, with a significant association observed between elevated circASAP1 expression and poor prognosis and metastasis. Actinomycin D, RNase R, as well as fluorescence in situ hybridization (FISH) analyses revealed the ring structure and cytoplasmic localization of circASAP1. High circASAP1 expression was associated with ccRCC cell proliferative viability, invasion, and metastasis in CCK-8, transwell, plate cloning, and EdU experiments. Interaction of circASAP1 with HNRNPC and their downstream target genes was confirmed by RNA pull-down, RNA immunoprecipitation, FISH, silver staining, and mass spectrometry. Experiments using truncated isoforms demonstrated that amino acids 16–87 of HNRNPC bound circASAP1. Proteins altered by circASAP1 were enriched in the ferroptosis pathway on the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. The relationship between circRNA and the ASAP1/HNRNPC/GPX4 axis was demonstrated by experimental data, which was further confirmed by rescue experiments. circASAP1 influenced tumor growth and ferroptosis in animal experiments and predicted the prognosis of patients with ccRCC. The circASAP1/HNRNPC/GPX4 axis provides novel directions and potential targets for RCC treatment.
Rapid quantitative PCR on tongue swabs for pulmonary tuberculosis in adults: a prospective multicentre study
Authors: Yilin Wang, Junwei Cui, Yuanyuan Li, Miao Wang, Wenge Han, Aimei Liu, Furong Wang, Rongmei Liu, Shuhui Kang, Jianping Zhang, Sihong Zhu, Zhonghai Lai, Wenlong Guan, Shaomu Zou, Xiangyu Yin, JianZhi Qing, Guilan Mu, Liying Guan, Liang Li, Yu Pang
Journal: European Respiratory Journal (2025)

Background Tuberculosis (TB) remains a major cause of infectious disease mortality globally, with significant underdiagnosis perpetuating transmission. Tongue swab analysis has emerged as a promising non-invasive method for pulmonary TB diagnosis. This study evaluates the diagnostic accuracy of the TB-EASY quantitative PCR (qPCR) assay using tongue swab specimens. Methods In this prospective multicentre study, conducted across seven designated TB hospitals in China, 729 participants were included in the analysis. Tongue swabs were tested using the new TB-EASY assay from Hugobiotech, while sputum samples were analysed by Xpert MTB/RIF (Xpert), smear and culture tests. Diagnostic performance was compared to a composite microbiological reference standard (MRS). Results The TB-EASY assay demonstrated high diagnostic accuracy, with sensitivity and specificity of 89.6% and 96.2% compared to sputum Xpert, and 87.4% and 98.0% compared to the MRS. Sensitivity varied by bacterial load, ranging from 100% in high-load cases to 70.4% in very-low-load cases. The assay demonstrated robust performance in diverse epidemiological settings. Conclusions The TB-EASY qPCR assay using tongue swabs offers a reliable, non-invasive diagnostic alternative for pulmonary TB, especially where sputum collection is challenging. Its potential for wider use in high TB burden settings warrants further validation in community-based studies. Limitations include potential overestimation of sensitivity due to the selection of symptomatic patients and the use of sputum Xpert rather than Xpert Ultra. Additionally, the performance in non-sputum-producing patients remains untested, and the cost-effectiveness should be further evaluated to assess the feasibility of its implementation.
Buddy, bystander or betrayer: B cells in lymphoid aggregates in AATD emphysema
Authors: P. Padmini S.J. Khedoe, Emily F.A. van ’t Wout
Journal: European Respiratory Journal (2025)

<title>Extract</title> Alpha-1 antitrypsin (AAT) is a major serine protease inhibitor, protecting lung tissue against the destructive effects of (chronic) release of neutrophil elastase by degranulating neutrophils during inflammation. Over the past decade, other anti-inflammatory properties of AAT have become more apparent, including regulation of human neutrophil chemotaxis [1], suppression of interferon-γ-induced M1 macrophage activation/polarisation [2], and attenuation of nuclear factor-κB activation in lung epithelial cells [3]. Alpha-1 antitrypsin deficiency (AATD) is the most widely recognised genetic disorder causing early-onset emphysema. The Z-mutation of AAT (Z-AAT) comprises more than 85% of the mutations leading to severe AATD due to accumulation of Z-AAT polymers inside hepatocytes, leading to lowered circulating AAT levels. In the past decades, the main research focus in the pathophysiology of AATD has been on protease/anti-protease imbalance and epithelial cell damage; however, it has become clear that AAT has pleiotropic functions, including the above-mentioned anti-inflammatory actions, but also modification of B cell responses [4]. This is relevant, since the mechanism of AATD-induced emphysema is suggested to be more complex, involving the adaptive immune system [5].
Body mass index trajectories may represent modifiable targets in the promotion of respiratory health
Authors: Nicole Prince, Rachel S. Kelly
Journal: European Respiratory Journal (2025)

<title>Extract</title> Lung function and development are critical to long-term respiratory health [1, 2]. Identifying modifiable factors, particularly within the early life period, that can be targeted to optimise lung function is therefore a critical priority. Body mass index (BMI) is a well-established risk factor for poor lung function [3], and given the inherently variable nature of BMI, could offer such a target. However, conflicting reports [4–6] from the literature have limited our understanding of the impact of BMI on lung health, specifically with regards to changes in an individual's BMI trajectory over time, which does not necessarily follow a linear or predictable course [7]. Furthermore, the biochemical underpinnings of the purported relationship between BMI and lung health have not been well explored. In this issue of the <italic>European Respiratory Journal</italic>, W<sc>ang</sc> <italic>et al</italic>.
Respiratory oscillometry in neonates and small infants: has the time come?
Authors: Sotirios Fouzas, Gabriel Dimitriou
Journal: European Respiratory Journal (2025)

<title>Extract</title> Pulmonary function testing in early life offers objective evidence of lung disease, supports clinical decision-making, and provides insights into lung growth and development [1]. However, lung function testing in newborns and small infants presents distinct technical and methodological challenges, which have hindered the development of a gold standard method suitable for routine use in the neonatal intensive care unit (NICU) and beyond [1].
Treat-and-repair: a simple but powerful term for a complex multimodal approach in patients with pulmonary arterial hypertension associated with congenital heart disease
Authors: Konstantinos Dimopoulos, Andrew Constantine
Journal: European Respiratory Journal (2025)

<title>Extract</title> We would like to extend our congratulations to the paediatric task force members of the 7th World Symposium on Pulmonary Hypertension for their insightful report and recommendations in this area of critical importance [1]. We are particularly relieved to see the reintroduction of complex congenital heart disease (CHD), including segmental pulmonary hypertension (PH) [2], in the proposed PH classification. We are, however, left wondering why complex conditions with unprotected pulmonary circulation (<italic>e.g.</italic> a functional single ventricle without pulmonary stenosis) are not considered within the spectrum of Eisenmenger syndrome, as originally described by W<sc>ood</sc> [3]. It is also disappointing that adult CHD was not included as a topic in this or other reports from the World Symposium, though I<sc>vy</sc> <italic>et al</italic>. [1] do discuss the merits of indexing pulmonary vascular resistance (PVR) in children <italic>versus</italic> adolescents and adults.
Disarming the cavalry: targeting neutrophils to limit collateral damage in non-CF bronchiectasis
Authors: Omri A. Arbiv, Bradley S. Quon
Journal: European Respiratory Journal (2025)

<title>Extract</title> Bronchiectasis is a heterogeneous disease characterised by mucous stasis, chronic bacterial infection and neutrophilic inflammation, resulting in airway destruction and irreversible bronchial dilatation [1]. Non-cystic fibrosis bronchiectasis (NCFB) is recognised as a growing source of morbidity but with a paucity of innovative treatment options [2, 3]. Treatments to date have largely focused on inhaled antibiotics and oral macrolides to reduce bacterial infection and inflammation, as well as inhaled mucoactive therapies to reduce mucous stasis [4].
Casting a wider net for tuberculosis cases
Authors: Gerard A. Cangelosi, Max Salfinger
Journal: European Respiratory Journal (2025)

<title>Extract</title> In 1882, Robert Koch was the first to stain tubercle bacilli, the causative micro-organisms for tuberculosis (TB). His culture method using inspissated blood-serum was later improved by Loewenstein and Jensen using eggs to enrich the culture medium, followed by Middlebrook introducing a medium containing agar. It took several weeks, and sometimes months, to yield a positive TB result. To hasten the laboratory diagnosis, Middlebrook developed a <sup>14</sup>C-labelled medium and with Johnston Laboratories constructed the BACTEC 460TB instrument [1]. The radiometric broth medium was succeeded by non-radiometric stand-alone culture and detection systems offered by several companies. More recently, molecular testing platforms such as the Cepheid GeneXpert MTB/RIF Ultra, which rapidly detects <italic>Mycobacterium tuberculosis</italic> DNA in patient samples by nucleic acid amplification testing (NAAT), have enabled same-day microbiological diagnosis of TB.
Comment on: Inflammatory plasma protein levels are elevated years before sarcoidosis diagnosis: a nested case–control study in Sweden
Authors: Marie Robert, Etienne Villain, Nader Yatim, Arthur Mageau, Nicolas Charles, Slobodan Culina, Nathan Peiffer-Smadja, Raphaël Borie, Darragh Duffy, Karim Sacré
Journal: European Respiratory Journal (2025)

<title>Extract</title> We read with great interest the paper by A<sc>rkema</sc> <italic>et al.</italic> [1] that was recently published in the <italic>European Respiratory Journal</italic>. Through a large nested case–control study in Sweden, the authors demonstrated that several inflammatory plasma proteins were significantly elevated in patients with sarcoidosis at least 2 years prior to diagnosis.
Blood-based diagnosis of pediatric tuberculosis: a prospective cohort study in South Africa and Dominican Republic
Authors: Lin Li, Liyan Mao, Marieke M van der Zalm, Juan Olivo, Shan Liu, Carlos Vergara, Megan Palmer, Qingbo Shu, Anne-Marie Demers, Christopher J Lyon, Pierre Goussard, H Simon Schaaf, Anneke C Hesseling, Sharon Nachman, Eddy Pérez-Then, Charles D Mitchell, Elisabetta Ghimenton, Tony Y Hu
Journal: Journal of Infection (2025)
Dasabuvir: An FDA-approved drug inhibiting poxvirus transmission by targeting both migrasome formation and extracellular enveloped virus production
Authors: Ting Xu, Daoqun Li, Junwen Luan, Leiliang Zhang
Journal: Journal of Infection (2025)

Highlights•An FDA-approved drug dasabuvir inhibits vaccinia virus-induced migrasome formation•Dasabuvir reduces the plaque size of vaccinia virus•Dasabuvir inhibits extracellular enveloped virus production of vaccinia virus•Dasabuvir tends to associate with the palmitoylated F13