tbuckley/cabot-search huggingface dataset:
Lateral inhibition in V1 controls neural and perceptual contrast sensitivity
Authors: Joseph Del Rosario, Stefano Coletta, Soon Ho Kim, Zach Mobille, Kayla Peelman, Brice Williams, Alan J. Otsuki, Alejandra Del Castillo Valerio, Kendell Worden, Lou T. Blanpain, Lyndah Lovell, Hannah Choi, Bilal Haider
Journal: Nature Neuroscience (2025)
Regulation of mammalian cellular metabolism by endogenous cyanide production
Authors: Karim Zuhra, Maria Petrosino, Lucia Janickova, Jovan Petric, Kelly Ascenção, Thibaut Vignane, Moustafa Khalaf, Thilo M. Philipp, Stella Ravani, Abhishek Anand, Vanessa Martins, Sidneia Santos, Serkan Erdemir, Sait Malkondu, Barbara Sitek, Taha Kelestemur, Anna Kieronska-Rudek, Tomas Majtan, Luis Filgueira, Darko Maric, Stefan Chlopicki, David Hoogewijs, György Haskó, Andreas Papapetropoulos, Brian A. Logue, Gerry R. Boss, Milos R. Filipovic, Csaba Szabo
Journal: Nature Metabolism (2025)

Abstract Small, gaseous molecules such as nitric oxide, carbon monoxide and hydrogen sulfide are produced as signalling molecules in mammalian cells. Here, we show that low concentrations of cyanide are generated endogenously in various mammalian tissues and cells. We detect cyanide in several cellular compartments of human cells and in various tissues and the blood of mice. Cyanide production is stimulated by glycine, occurs at the low pH of lysosomes and requires peroxidase activity. When generated at a specific rate, cyanide exerts stimulatory effects on mitochondrial bioenergetics, cell metabolism and cell proliferation, but impairs cellular bioenergetics at high concentrations. Cyanide can modify cysteine residues via protein S -cyanylation, which is detectable basally in cells and mice, and increases in response to glycine. Low-dose cyanide supplementation exhibits cytoprotective effects in hypoxia and reoxygenation models in vitro and in vivo. Conversely, pathologically elevated cyanide production in nonketotic hyperglycinaemia is detrimental to cells. Our findings indicate that cyanide should be considered part of the same group of endogenous mammalian regulatory gasotransmitters as nitric oxide, carbon monoxide and hydrogen sulfide.
GOLM1 Promotes Atherogenesis by Activating Macrophage EGFR-ERK Signaling Cascade
Authors: Xiaochen Gai, Fangming Liu, Yixin Chen, Baohui Zhang, Yinliang Zhang, Yuting Wu, Shuhui Yang, Linlin Chen, Weiwei Deng, Yuan Wang, Shuiyun Wang, Cuntao Yu, Jie Du, Zhengyi Zhang, Jing Wang, Hongbing Zhang
Journal: Circulation Research (2025)

BACKGROUND: Atherosclerosis is a chronic inflammatory disease. GOLM1 (Golgi membrane protein 1) is an inflammation-responsive protein and a mediator in some inflammation-associated pathological processes. Because we found a positive correlation between GOLM1 expression and atherosclerosis progression by checking the gene expression data set of human atherosclerotic lesions, we explored the potential significance of GOLM1 in atherosclerosis in this study. METHODS: GOLM1 levels in serums and lesions of patients with atherosclerosis and mice with atherosclerosis were examined by immunostaining and ELISA. Gain-of-function and loss-of-function approaches were used to study the impacts of GOLM1 in inflammation and atherogenesis of Apoe −/− mice on a Western diet. The effects of GOLM1 on macrophage behaviors were determined by OxLDL (oxidized low-density lipoprotein) uptake assay, single-cell sequencing analysis, global phosphoproteomics analysis, and molecular biological techniques. The therapeutic potential of GOLM1 neutralization for atherosclerosis was evaluated in Apoe −/− mice. RESULTS: GOLM1 was elevated in serums and lesions of patients with atherosclerosis and mice with atherosclerosis. Global deletion of GOLM1 ameliorated mouse inflammation and atherosclerosis, while knock-in of GOLM1 exacerbated these pathological manifestations. Furthermore, hepatic GOLM1 deletion reduced circulating GOLM1 and attenuated atherogenesis. Mechanistically, the expression and secretion of GOLM1 were induced in multiple mouse tissues by atherogenic stimulus, leading to the elevation of extracellular GOLM1. Extracellular GOLM1 then stimulated ERK (extracellular signal-regulated kinase) signaling cascade by binding to its putative receptor EGFR (epidermal growth factor receptor) to promote macrophage uptake of LDL (low-density lipoprotein) and enhance the corresponding macrophage immune response. Moreover, neutralizing GOLM1 by an antibody suppressed mouse inflammation and atherogenesis. CONCLUSIONS: GOLM1 is an atherogenic mediator and a promising therapeutic target for the intervention of atherosclerotic diseases.
Ireland: Europe's outlier in primary health care
Authors: None The Lancet Regional Health – Europe
Journal: The Lancet Regional Health - Europe (2025)

Despite being one of the richest countries in Europe, Ireland is the only European country without universal coverage of primary health care. Although substantial investments have been made in health through the government budget—with public health spending increasing from €15.3 billion in 2018 to €22.8 billion in 2024—58% of residents do not have access to free primary health care. Ireland's primary health-care model stands in stark contrast to other European countries, where the costs of general practitioner (GP) visits are either fully or partially covered, for the whole population, through public health spending or compulsory health insurance.
Single-cell transcriptomic atlas of the human testis across the reproductive lifespan
Authors: Lina Cui, Xichen Nie, Yixuan Guo, Pengcheng Ren, Yifei Guo, Xiaoyan Wang, Ran Li, James M. Hotaling, Bradley R. Cairns, Jingtao Guo
Journal: Nature Aging (2025)

Testicular aging is associated with declining reproductive health, but the molecular mechanisms are unclear. Here we generate a dataset of 214,369 single-cell transcriptomes from testicular cells of 35 individuals aged 21–69, offering a resource for studying testicular aging and physiology. Machine learning analysis reveals a stronger aging response in somatic cells compared to germ cells. Two waves of aging-related changes are identified: the first in peritubular cells of donors in their 30s, marked by increased basement membrane thickness, indicating a priming state for aging. In their 50s, testicular cells exhibit functional changes, including altered steroid metabolism in Leydig cells and immune responses in macrophages. Further analyses reveal the impact of body mass index on spermatogenic capacity as age progresses, particularly after age 45. Altogether, our findings illuminate molecular alterations during testis aging and their relationship with body mass index, providing a foundation for future research and offering potential diagnostic markers and therapeutic targets. To enhance our understanding of aging in the human testis, the authors provide a single-cell map of testicular characteristics throughout the reproductive lifespan. Using samples from 35 donors, they identify two waves of molecular changes in somatic cells and examine interactions between aging and body mass index.
The neuroimmune nexus: unraveling the role of the mtDNA-cGAS-STING signal pathway in Alzheimer’s disease
Authors: Shuiyue Quan, Xiaofeng Fu, Huimin Cai, Ziye Ren, Yinghao Xu, Longfei Jia
Journal: Molecular Neurodegeneration (2025)

The relationship between Alzheimer's disease (AD) and neuroimmunity has gradually begun to be unveiled. Emerging evidence indicates that cyclic GMP-AMP synthase (cGAS) acts as a cytosolic DNA sensor, recognizing cytosolic damage-associated molecular patterns (DAMPs), and inducing the innate immune response by activating stimulator of interferon genes (STING). Dysregulation of this pathway culminates in AD-related neuroinflammation and neurodegeneration. A substantial body of evidence indicates that mitochondria are involved in the critical pathogenic mechanisms of AD, whose damage leads to the release of mitochondrial DNA (mtDNA) into the extramitochondrial space. This leaked mtDNA serves as a DAMP, activating various pattern recognition receptors and immune defense networks in the brain, including the cGAS-STING pathway, ultimately leading to an imbalance in immune homeostasis. Therefore, modulation of the mtDNA-cGAS-STING pathway to restore neuroimmune homeostasis may offer promising prospects for improving AD treatment outcomes. In this review, we focus on the mechanisms of mtDNA release during stress and the activation of the cGAS-STING pathway. Additionally, we delve into the research progress on this pathway in AD, and further discuss the primary directions and potential hurdles in developing targeted therapeutic drugs, to gain a deeper understanding of the pathogenesis of AD and provide new approaches for its therapy.
Unexpected Extrarenal Uptake of 99mTc-DTPA in Renal Scintigraphy: Insights From Two Cases of Adrenal Tumors
Authors: Yanmei Han, Daijuan Huang, Zairong Gao, Xiaotian Xia
Journal: Clinical Nuclear Medicine (2025)

Renal dynamic scintigraphy is a crucial diagnostic tool for assessing renal function, yet unexpected findings can provide additional insights into extrarenal conditions. We report 2 rare cases of extrarenal 99m Tc-DTPA uptake associated with adrenal tumors: one adrenal cortical carcinoma and one pheochromocytoma. In both cases, significant tracer accumulation in the adrenal region was observed, highlighting an uncommon but noteworthy diagnostic consideration. These cases emphasize the importance of including adrenal tumors in the differential diagnosis when encountering abnormal 99m Tc-DTPA uptake patterns, offering valuable clinical insights for interpreting atypical imaging findings and broadening diagnostic perspectives.
Molecular Imaging Versus Adrenal Vein Sampling for the Detection of Surgically Curable Primary Aldosteronism
Authors: Emily Goodchild, Xilin Wu, Russell Senanayake, James MacFarlane, Giulia Argentesi, Kate Laycock, Waiel A. Bashari, Claudia P. Cabrera, Samuel M. O’Toole, Jackie Salsbury, Daniela Benu, Yun-Ni Lee, Aldons C.N. Chua, Matthew Matson, Brendan Koo, Laila Parvanta, Nicholas Hilliard, Vasilis Kosmoliaptsis, Alison Marker, Daniel M. Berney, Kiera Drew, Wilson Tan, Roger Foo, Charles A. Mein, Eva Wozniak, Jessica Kearney, Emanuel Savage, Anju Sahdev, Nicholas Bird, Graham Smith, Matthew Hird, Victoria Warnes, Daniel Gillett, Anne Dawnay, Elizabeth Adeyeye, Franklin Aigbirhio, Alasdair McIntosh, Alex McConnachie, J. Kennedy Cruickshank, Heok Cheow, Mark Gurnell, William M. Drake, Morris J. Brown
Journal: Annals of Internal Medicine (2025)

Primary aldosteronism (PA) causes hypertension and is potentially surgically curable when it is caused by a unilateral aldosterone-producing adrenal adenoma (APA). Adrenal vein sampling (AVS) is required to guide surgery, but it is invasive, is technically difficult, and has limited availability. To determine whether the accuracy of post-dexamethasone [11C]metomidate ([11C]MTO) positron emission tomography-computed tomography, a diagnostic test for APAs, is superior or noninferior to the accuracy of AVS in predicting outcomes from unilateral adrenalectomy, and whether [11C]MTO is interchangeable with its longer-half-life analogue, para-chloro-2-[18F]fluoroethyletomidate ([18F]CETO). Prospective within-patient comparison of diagnostic interventions. (ClinicalTrials.gov: NCT02945904). Three referral centers. 174 patients with PA desiring surgery if a unilateral source of PA was diagnosed. [11C]MTO and AVS in 169 patients, plus [18F]CETO in the final 31. International consensus criteria for biochemical and clinical success at 6 and 24 months after surgery; κ statistic and Bland-Altman analyses comparing predictions of surgical outcomes by [11C]MTO and [18F]CETO. Eighty-nine of 169 (52.7%), 78 of 169 (46.2%), and 43 of 169 (25.4%) patients were predicted to have unilateral PA by [11C]MTO, AVS, or both, respectively. One hundred of 169 (59.1%) were assigned to adrenalectomy by the multidisciplinary team; primary outcome data were available for 156 of 169. Predictions were most accurate for complete or partial biochemical success ([11C]MTO, 71.3% [95% CI, 61.0% to 80.1%]; AVS, 62.8% [CI, 52.2% to 72.6%]) and least accurate for complete clinical success (home blood pressure <135/85 mm Hg off treatment). The 95% CIs around differences between accuracies crossed zero, excluding superiority for [11C]MTO, but not the prespecified lower bound of -17%, allowing [11C]MTO to be declared noninferior to AVS. [18F]CETO and [11C]MTO agreed in 29 of 31 patients (κ = 0.85 [CI, 0.68 to 1.00]). The accuracy of [11C]MTO could be assessed only in the surgical group. Molecular imaging is an accurate, noninvasive alternative to AVS. National Institute for Health and Care Research.
Circadian Control of Hepatic Ischemia/Reperfusion Injury via HSD17B13-Mediated Autophagy in Hepatocytes
Authors: Hui Wang, Meina Guo, Baoyin Ren, Haibo Zhang, Jiayang Zhang, Rongfang Qiao, Lei Qian, Jingwen Zhu, Shuying Zhang, Xiaoyan Zhang, Guangrui Yang, Youfei Guan, Lihong Chen
Journal: Journal of Hepatology (2025)
Dual Functional Radioactive Gel‐Microspheres for Combinatorial Radioembolization and Photothermal Therapy of Hepatocellular Carcinoma
Authors: Jing Sun, Xingwei Sun, Liang Yin, Shuo Jin, Qian Huang, Yi Dong, Xiaolei Gu, Yujuan Zhang, Yong Jin, Ran Zhu, Guanglin Wang
Journal: Advanced Healthcare Materials (2025)

Abstract Transarterial radioembolization (TARE) is an established clinical therapy for treating patients with intermediate to advanced hepatocellular carcinoma (HCC) or those who cannot undergo radical treatment. However, the delivery of a high radiation dose is associated with several adverse effects, such as radiation pneumonitis. Additionally, the available radioactive microspheres (MSs) are dense and unsuitable for interventional delivery. This study proposes the use of commercial CalliSpheres polyvinyl alcohol (PVA) gel MSs coated with polydopamine (PDA) as a carrier for radioactive iodine ( 131 I) labeled using the iodogen method, denoted as 131 I‐PDA@PVA MSs, which can be for radioembolization combined photothermal therapy (PTT) of HCC. In vitro experiments have demonstrated that 131 I‐PDA@PVA MSs have high radiolabeling stability and photothermal properties. Single photon emission computed tomography (SPECT)/computed tomography (CT) imaging and biodistribution experiments have shown that 131 I‐PDA@PVA MSs remain stable in vivo without any radioactive leakage. The results of the antitumor study suggest that 131 I‐PDA@PVA MSs are an effective treatment for inhibiting tumor growth through a combination of radioembolization and PTT while avoiding significant side effects. These multifunctional MSs have great potential for clinical application in the treatment of HCC.
Porous PtCu Alloys Decode Plasma Metabolic Fingerprints for the Recognition of Severe Community‐Acquired Pneumonia
Authors: Kexin Meng, Yao Shen, Dongni Hou, Hanbing Hu, Shouzhi Yang, Ziyue Zhang, Ayizekeranmu Yiming, Dingyitai Liang, Weibin Tian, Ludan He, Shuoyan Wei, Ying Wang, Jie Shen, Yuanlin Song, Sai Gu, Haiyang Su, Jian Zhou, Kun Qian
Journal: Advanced Healthcare Materials (2025)

Abstract Rapid and accurate recognition of severe community‐acquired pneumonia (CAP) would facilitate the optimal intervention. Currently, the diagnosis of severe CAP is commonly based on the criteria established by Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS), which include 2 primary and 9 secondary criteria, making the process cumbersome and time‐consuming. Here, a porous PtCu alloy‐assisted laser desorption/ionization mass spectrometry (LDI MS) is designed for the extraction of plasma metabolic fingerprints (PMFs), coupling with machine learning for the diagnosis of severe CAP. The PtCu alloys with optimal particle size exhibit excellent sensitivity, reproducibility, and universality for metabolite detection, due to the porous structure, promising photoelectric effect, and improved melting surface structure. Further, the nanoplatform successfully records the PMFs within seconds, using only 0.5 µL native plasma. Machine learning of PMFs on 69 individuals produces a diagnostic model with an area under curve (AUC) of 0.832. Particularly, a three metabolic biomarker panel demonstrates enhanced diagnostic efficiency (AUC of 0.846), outperforming reported biomarkers (AUC of 0.560–0.770). Notably, the diagnosis can be completed in ≈35 min. The work affords a rapid and precise method for CAP management through metabolite analysis.
Advancing Chronic Wound Healing through Electrical Stimulation and Adipose‐Derived Stem Cells
Authors: Qiuyue Peng, Yu Qian, Xinxin Xiao, Fengdi Gao, Guoqiang Ren, Cristian Pablo Pennisi
Journal: Advanced Healthcare Materials (2025)

Abstract Chronic cutaneous wounds are a major clinical challenge worldwide due to delayed healing, recurrent infections, and resistance to conventional therapies. Adipose‐derived stem cells (ASCs) have shown promise as a cell‐based therapy, but their therapeutic efficacy is often compromised by the harsh microenvironment of chronic wounds. Recent advances in bioengineering, particularly the application of electrical stimulation (ES), offer an innovative approach to enhancing the regenerative properties of ASCs. By restoring the natural electrical current in the wound, ES provides a strong stimulus to the cells involved in healing, thereby accelerating the overall wound‐healing process. Recent studies show that ASCs can be significantly activated by ES, which increases their viability, proliferation, migration, and secretory capacity, all of which are crucial for the proper healing of chronic wounds. This review examines the synergistic effects of ES and ASCs on wound healing, focusing on the biological mechanisms involved. The review also highlights novel self‐powered systems and other emerging technologies such as advanced conductive materials and devices that promise to improve the clinical translation of ES‐based treatments. By summarizing the current state of knowledge, this review aims to provide a framework for future research and clinical application of ES and ASCs in wound care.
Identification of pathogenic <scp>PD</scp>‐1<sup>+</sup><scp>CD8</scp><sup>+</sup> T cells for effective chimeric antigen receptor therapy in a murine model of Sjögren's disease
Authors: Jin‐Fen Ma, Ting Xu, Hao‐Xian Zhu, Xiao‐Min Chen, Liang Li, Zhi‐Bin Zhao, Liwei Lu, Yang Li, Zhe‐Xiong Lian, Cai‐Yue Gao
Journal: Arthritis & Rheumatology (2025)

Objective Activated T cells play a pivotal pathogenic role in the progression of Sjögren's disease (SjD); however, there are currently no targeted therapies specifically designed to address them. This study aims to identify pathogenic CD8 + T cells in SjD and develop targeted therapeutic strategies. Methods Il12b ‐/‐ Il2ra ‐/‐ mice, a murine model for overlapping primary biliary cholangitis (PBC) and SjD, were employed in this study. Pathogenic CD8 + T cells were identified through single‐cell RNA sequencing (scRNA‐seq) and flow cytometry analyses of samples from both SjD patients and relevant murine models. Shared T cell receptor (TCR) analysis was conducted to trace the potential precursors of pathogenic CD8 + T cells. The efficacy of PD‐1‐targeted CAR‐T cell therapy was evaluated through the assessment of salivary gland secretory function, immunological profiles, and histopathological changes in the murine model. Results We identified programmed cell death protein 1 (PD‐1) as a comprehensive marker of clonally expanded and activated pathogenic CD8 + T cells in the salivary glands and peripheral tissues. Flow cytometry further confirmed the activation phenotype and cytotoxicity of PD‐1 + CD8 + T cells in the salivary glands of patients with SjD. Notably, the number of PD‐1 + CD8 + T cells in the labial glands positively correlated with disease activity in SjD patients. These findings highlight the therapeutic potential of depleting PD‐1 + CD8 + T cells in SjD. Furthermore, PD‐1‐targeted CAR‐T cell therapy significantly alleviated SjD symptoms in a murine model. Conclusion We identified the pathogenic role of PD‐1 + CD8 + T cells in both SjD patients and a murine model and demonstrated the efficacy of PD‐1‐targeted CAR‐T cell therapy in SjD model mice. Our findings suggest a promising avenue for developing clinical therapeutic strategies for SjD patients.
Kidney status and events preceding death in heart failure: A real‐world nationwide study
Authors: Deewa Zahir Anjum, Caroline Hartwell Garred, Nicholas Carlson, Emil Fosbol, Mariam Elmegaard, Pardeep S. Jhund, John J.V. McMurray, Mark C. Petrie, Lars Kober, Morten Schou
Journal: European Journal of Heart Failure (2025)

Abstract Aims Chronic kidney disease is a frequent comorbidity in heart failure (HF) patients, affecting prognosis and mortality. This study investigates the relationship between kidney function and adverse kidney events preceding death in HF patients. Methods and results We analysed registry data of HF patients who died between 2014 and 2021, with at least 1 year of HF diagnosis. Adverse kidney events, including acute kidney injury (AKI) and end‐stage kidney disease (ESKD), were assessed. Patients were grouped by estimated glomerular filtration rate (eGFR) 1 year before death: eGFR ≥60, eGFR 30–59, and eGFR&lt;30 ml/min/1.73 m 2 . Among 36 435 HF patients who died, 37% had eGFR ≥60 ml/min/1.73 m 2 , 46% had eGFR 30–59 ml/min/1.73 m 2 , and 17% had eGFR &lt;30 ml/min/1.73 m 2 1 year before death. Median age was 81 years, and 61.2% were men. Adverse kidney events occurred in 13.1% of patients. AKI was inversely related to kidney function, affecting 6.5% (95% confidence interval 6.1–6.9) of those with eGFR ≥60 ml/min/1.73 m 2 , 7.0% (6.6–7.4) with eGFR 30–59 ml/min/1.73 m 2 , and 21.9% (20.9–22.9) with eGFR &lt;30 ml/min/1.73 m 2 . ESKD occurred in 0.7% (0.6–0.9), 2.6% (2.4–2.8), and 35.5% (34.3–36.7) of patients in the respective eGFR categories. In the last 3 months before death, kidney function notably declined, with increased chronic kidney replacement therapy. Factors associated with higher adverse kidney events included younger age, male sex, in‐hospital death, and greater frailty. Conclusions In HF patients, AKI and ESKD are common in the last year of life, particularly in those with lower baseline eGFR, with kidney decline accelerating in the final months.
Two Faces of NOTCH1 in Liver Cancer and Immunotherapy
Authors: Jiani Zhu, Ekaterina K. Koltsova
Journal: Cancer Discovery (2025)

High NOTCH1 expression inversely correlates with hepatocellular carcinoma tumorigenicity and contributes to better immune checkpoint inhibitor responses in male patients, whereas high NOTCH1 in females coincides with heightened hepatocellular carcinoma incidence and poor immunotherapy responses. Activated NOTCH1 generates enhanced antitumor CD8+ T-cell responses in a sex chromosome-dependent manner and facilitates responsiveness to immunotherapy treatment in males, whereas it drives immune escape in females. See related article by Lindblad et al., p. 495.
Illuminating a Dark Kinase in the Mesenchymal Cancer Cell State
Authors: Shensi Shen, Zhen Tan
Journal: Cancer Discovery (2025)

Killarney and colleagues identify PKN2 as a critical driver of mesenchymal cancer cell survival and drug resistance through YAP/TAZ activation. Targeting PKN2 in combination with first-line targeted therapies offers a potential strategy to eliminate mesenchymal-like drug-tolerant persister cells. See related article by Killarney et al., p. 595.