tbuckley/cabot-search huggingface dataset:
Short IL-18 generated by caspase-3 cleavage mobilizes NK cells to suppress tumor growth
Authors: Junchen Shen, Yu Zhang, Wenbo Tang, Mingxia Yang, Tong Cheng, Yihui Chen, Shi Yu, Qiuhong Guo, Limin Cao, Xun Wang, Hui Xiao, Lanfeng Wang, Chengyuan Wang, Chen-Ying Liu, Guangxun Meng
Journal: Nature Immunology (2025)
A BCL-xL/BCL-2 PROTAC effectively clears senescent cells in the liver and reduces MASH-driven hepatocellular carcinoma in mice
Authors: Yang Yang, Natacha Jn-Simon, Yonghan He, Chunbao Sun, Peiyi Zhang, Wanyi Hu, Tian Tian, Huadong Zeng, Sreenivasulu Basha, Araceli S Huerta, Lu-Zhe Sun, Xian-Ming Yin, Robert Hromas, Guangrong Zheng, Liya Pi, Daohong Zhou
Journal: Nature Aging (2025)
When unpacking the black box of motivation invites three forms of reductionism
Authors: Agnes Moors
Journal: Behavioral and Brain Sciences (2025)

Abstract In their proposal for unpacking the black box of motivation, Murayama and Jach (M&amp;J) propose three types of reductions: From high-level to low-level motivational constructs, from motivation to cognition, and from contentful to contentless explanations. Although these reductions come with the promise of parsimony, they carry the risk of losing vital explanatory power.
PMA1-containing extracellular vesicles of <i>Candida albicans</i> triggers immune responses and colitis progression
Authors: Zhen Xu, Shuping Qiao, Zelin Wang, Chen Peng, Yayi Hou, Baorui Liu, Guochun Cao, Tingting Wang
Journal: Gut Microbes (2025)

Candida albicans (C. albicans) exhibits aberrant changes in patients with colitis, and it has been reported to dominate the colonic mucosal immune response. Here, we found that PMA1 expression was significantly increased in C. albicans from patients with IBD compared to that in healthy controls. A Crispr-Cas9-based fungal strain editing system was then used to knock out PMA1 expression in C. albicans. Compared to WT-C.a, ΔPMA1-C.a could not aggravate colitis. Proteomic analysis showed that PMA1 was transported by extracellular vesicles (EVs) of C. albicans. PMA1-containing EVs aggravated colitis, modulated the migration of cDC2 from the lamina propria to mesenteric lymph nodes, and induced TH17 cell differentiation. Moreover, the adaptor protein CARD9 was critical in PMA1-containing EV-induced colitis, and CARD9-deficient DCs did not induce TH17 cell differentiation or IL-17A production. Mechanically, CARD9 combines with the glycolytic protein GAPDH (aa2-146 domain) through its CARD region. CARD9 deficiency led to decreased enzyme activity of GAPDH and decreased glycolysis of DCs. These findings indicate that PMA1 is a potential virulence factor responsible for the pathogenesis of C. albicans colitis.
Progressively differentiated TFH13 cells are stabilized by JunB to mediate allergen germinal center responses
Authors: Pragya Chandrakar, Cody S Nelson, Manuel A Podestà, Cecilia B Cavazzoni, Maya Gempler, Jeong-Mi Lee, Sierra Richardson, Hengcheng Zhang, Snigdha Samarpita, Maria Ciofani, Talal Chatila, Vijay K Kuchroo, Peter T Sage
Journal: Nature Immunology (2025)
Expectancy value theory's contribution to unpacking the black box of motivation
Authors: Jacquelynne S Eccles, Allan Wigfield
Journal: Behavioral and Brain Sciences (2025)

Abstract Although in basic agreement with Murayama and Jach's call for greater attention to the black boxes underlying motivated behavior, we provide examples of our published suggestions regarding how subjective task value (and ability self-concepts) “gets into people's knowledge structures.” We suggest additional mental computational processes to investigate and call for a developmental and situated individual differences approach to this work.
Endogenous reward is a bridge between social/cognitive and behavioral models of choice
Authors: George Ainslie
Journal: Behavioral and Brain Sciences (2025)

Abstract Endogenous reward (intrinsic reward at will) is a fiat currency that is occasioned by steps toward any goals which are challenging and/or uncommon enough to prevent its debasement by inflation. A “theory of mental computational processes” should propose what properties let goals grow from appetites for endogenous rewards. Endogenous reward may be the universal selective factor in all modifiable mental processes.
Don't throw motivation out with the black box: The value of a good theory revisited
Authors: Jutta Heckhausen, Falko Rheinberg
Journal: Behavioral and Brain Sciences (2025)

Abstract Murayama and Jach claim that current motivational constructs do not specify causal processes ( black-box problem ) and that mental computational processes solve this problem. We argue, process-focused research requires theoretical frameworks addressing situational variations, individual differences, and their interaction. Classic achievement motivation theory provides comprehensive models with empirically measurable process-related constructs and predictions. Recent developments build on this, addressing motivation, action, and their socio-cultural and lifespan context. Theory-free mental computational processes cannot do any of that.
Higher-order motivational constructs as personal-level fictions: A solution in search of a problem
Authors: Marko Jurjako
Journal: Behavioral and Brain Sciences (2025)

Abstract I argue that Murayama and Jach's claim that higher-order motivational constructs face the “black-box” problem is misconceived because it doesn't clearly distinguish between personal and subpersonal explanations. To solve it they propose interpreting motivations as causal effects of mental computational processes. I suggest that their solution might be more compellingly presented as providing a fictionalist perspective on some personal-level constructs.
One health investigation following a cluster of Crimean–Congo haemorrhagic fever, North Macedonia, July to November 2023
Authors: Dejan Jakimovski, Pavle Banović, Katerina Spasovska, Goran Rangelov, Marija Cvetanovska, Fadil Cana, Verica Simin, Ivana Bogdan, Dragana Mijatović, Aleksandar Cvetkovikj, Igor Djadjovski, Iva Christova, Eleftherios Meletis, Polychronis Kostoulas, Brigitta Zana, Zsófia Lanszki, Tamás Görföl, Zsófia Tauber, Gabor Kemenesi
Journal: Eurosurveillance (2025)

Background Crimean–Congo haemorrhagic fever (CCHF) is a severe illness characterised by fever, bleeding and high case-fatality rates. The disease is caused by CCHF virus (CCHFV), transmitted by ticks and infectious body fluids and tissues. Aim After CCHF was diagnosed in three persons in 2023, we aimed to investigate the presence of antibodies against CCHFV in healthcare workers (HCW), sheep and goats, and of CCHFV in ticks, in an area in North Macedonia and characterise virus strains. Methods In 2023, we collected blood samples from HCWs involved in treating CCHF patients and sera and ticks from sheep and goats in the village in North Macedonia where the index case resided. The blood samples were analysed by ELISA. Ticks were tested for presence of CCHFV, and the virus from a CCHF case was sequenced. Results Samples from four of 52 HCWs and 10 of 17 small ruminants had antibodies against CCHFV. The virus was not detected from any of the 24 Rhipicephalus bursa ticks. The virus strain from the index case clustered with regional strains within the Europe-1 lineage (genotype V) group and was closest to strains from Kosovo ‡ . Conclusion This report shows CCHFV is endemic in North Macedonia. Raising awareness of the risk factors and educating people about the measures they can take to reduce exposure to the virus is important. Healthcare workers need to be aware of the disease. Early detection, robust diagnostic methods, surveillance and collaborative efforts are necessary to prevent and control CCHF in the affected regions.
Resurrecting the “black-box” conundrum
Authors: Patricia A Alexander
Journal: Behavioral and Brain Sciences (2025)

Abstract In their article, Murayama and Jach contend that a mental computational model demonstrates that high-level motivations are emergent properties from underlying cognitive processes rather than instigators of behaviors. Despite points of agreement with the authors' critiques of the motivation literature, I argue that their claim of dismantling the black box of the human mind has been constructed on shaking grounds.
It's bigger on the inside: mapping the black box of motivation
Authors: Marco Del Giudice
Journal: Behavioral and Brain Sciences (2025)

Abstract Many motivational constructs are opaque “black boxes,” and should be replaced by an explicit account of the underlying psychological mechanisms. The theory of motivational systems has begun to provide such an account. I recently contributed to this tradition with a general architecture of motivation, which connects “energization” and “direction” through the goal-setting activity of emotions, and serves as an evolutionary grounded map of motivational processes.
Interim estimates of vaccine effectiveness against influenza A(H1N1)pdm09 and A(H3N2) during a delayed influenza season, Canada, 2024/25
Authors: Lea Separovic, Yuping Zhan, Samantha E Kaweski, Suzana Sabaiduc, Sara Carazo, Romy Olsha, Richard G Mather, James A Dickinson, Maan Hasso, Isabelle Meunier, Agatha N Jassem, Nathan Zelyas, Ruimin Gao, Nathalie Bastien, Danuta M Skowronski
Journal: Eurosurveillance (2025)

The Canadian Sentinel Practitioner Surveillance Network (SPSN) reports interim 2024/25 vaccine effectiveness (VE) against acute respiratory illness due to laboratory-confirmed influenza during a delayed season of predominant A(H1N1)pdm09 and lower A(H3N2) co-circulation. Through mid-January, the risk of outpatient illness due to influenza A is reduced by about half among vaccinated vs unvaccinated individuals. Adjusted VE is 53% (95% CI: 36-65) against A(H1N1)pdm09, comprised of clades 5a.2a and 5a.2a.1, and 54% (95% CI: 29-70) against A(H3N2), virtually all clade 2a.3a.1.
Familial confounding in the associations between maternal health and autism
Authors: Vahe Khachadourian, Elias Speleman Arildskov, Jakob Grove, Paul F. O’Reilly, Joseph D. Buxbaum, Abraham Reichenberg, Sven Sandin, Lisa A. Croen, Diana Schendel, Stefan Nygaard Hansen, Magdalena Janecka
Journal: Nature Medicine (2025)

Evidence suggests that maternal health in pregnancy is associated with autism in the offspring. However, most diagnoses in pregnant women have not been examined, and the role of familial confounding remains unknown. Our cohort included all children born in Denmark between 1998 and 2015 (n = 1,131,899) and their parents. We fitted Cox proportional hazard regression models to estimate the likelihood of autism associated with each maternal prenatal ICD-10 diagnosis, accounting for disease chronicity and comorbidity, familial correlations and sociodemographic factors. We examined the evidence for familial confounding using discordant sibling and paternal negative control designs. Among the 1,131,899 individuals in our sample, 18,374 (1.6%) were diagnosed with autism by the end of follow-up. Across 236 maternal diagnoses we tested (prevalence ≥0.1%), 30 were significantly associated with autism after accounting for sociodemographic factors, disorder chronicity and comorbidity, and correction for multiple testing. This included obstetric, cardiometabolic and psychiatric disorders (for example, diabetes in pregnancy (hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.08-1.31) and depression (HR 1.49, 95% CI 1.27-1.75)), previously shown to be associated with autism. Family-based analyses provided strong evidence for familial confounding in most of the observed associations. Our findings indicate pervasive associations between maternal health in pregnancy and offspring autism and underscore that these associations are largely attributable to familial confounding.
Ginkgolide B increases healthspan and lifespan of female mice
Authors: Chien-Wei Lee, Belle Yu-Hsuan Wang, Shing Hei Wong, Yi-Fan Chen, Qin Cao, Allen Wei-Ting Hsiao, Sin-Hang Fung, Yu-Fan Chen, Hao-Hsiang Wu, Po-Yu Cheng, Zong-Han Chou, Wayne Yuk-Wai Lee, Stephen Kwok Wing Tsui, Oscar Kuang-Sheng Lee
Journal: Nature Aging (2025)
Preservation of Vascular Endothelial Function in Late-Onset Postmenopausal Women
Authors: Sanna Darvish, Kevin O. Murray, Katelyn R. Ludwig, Krisha H. Avalani, Daniel H. Craighead, Kaitlin A. Freeberg, Shaun Bevers, Julie A. Reisz, Angelo D’Alessandro, Kerrie L. Moreau, Douglas R. Seals, Matthew J. Rossman
Journal: Circulation Research (2025)

BACKGROUND: Postmenopausal women (PMW) who complete menopause at a late age (55+ years) have lower cardiovascular disease risk than PMW who complete menopause at a normal age (45–54 years). However, the influence of late-onset menopause on vascular endothelial dysfunction is unknown. Moreover, the mechanisms by which a later age at menopause may modulate endothelial function remain to be determined. METHODS: We measured endothelial function (brachial artery flow-mediated dilation [FMD BA ]) in age-matched late- and normal-onset PMW and a young premenopausal reference group. We determined mitochondrial reactive oxygen species (mitoROS)–related suppression of endothelial function (change in FMD BA with an acute dose of the mitochondria-targeted antioxidant MitoQ; ΔFMD BA, MTQ ) in PMW. The effects of serum from late- and normal-onset PMW and premenopausal women on mitoROS bioactivity in human aortic endothelial cells in culture were assessed. Metabolomics analyses in combination with serum metabolite level normalization and human aortic endothelial cell serum exposure experiments were performed to identify the circulating factors contributing to the serum effects on endothelial cell mitoROS bioactivity. RESULTS: FMD BA in PMW was lower than in premenopausal women. However, FMD BA was &gt;50% higher in late- versus normal-onset PMW and positively related to age at menopause. ΔFMD BA, MTQ was &gt;50% lower in late- versus normal-onset PMW. Serum from normal-onset PMW but not late-onset PMW induced higher mitoROS bioactivity in human aortic endothelial cells compared with serum from premenopausal women. mitoROS bioactivity was negatively related to FMD BA and age at menopause. Seventeen metabolites significantly differed between late- and normal-onset PMW; 15 were lipid specific; 8 were triglyceride derived. TG(16:0) was most strongly correlated with mitoROS bioactivity. Normalization of TG(16:0) concentrations in serum from premenopausal women and late-onset PMW to match serum levels in normal-onset PMW abrogated differences in mitoROS bioactivity in serum-treated human aortic endothelial cells. CONCLUSIONS: Late-onset menopause is associated with preservation of endothelial function, which is mediated by lower mitoROS-associated oxidative stress. A more favorable profile of circulating lipid metabolites, specifically triglyceride-derived metabolites, contributes to lower endothelial cell mitoROS in late-onset PMW. These findings provide new insight into the possible mechanisms of reduced cardiovascular disease risk in late-onset menopause.
Maternal exercise prevents metabolic disorders in offspring mice through SERPINA3C
Authors: Yang Li, Ruo-Ying Li, Jie-Ying Zhu, Min Chen, Wang-Jing Mu, Hong-Yang Luo, Shan Li, Lin-Jing Yan, Meng-Ting Yin, Xin Li, Hu-Min Chen, Liang Guo
Journal: Nature Metabolism (2025)
Multiple phenotypes and epigenetic profiles in a three-generation family history with GATA2 deficiency
Authors: Damia Romero-Moya, Joan Pera, Oskar Marin-Bejar, Eric Torralba-Sales, Laura Murillo-Sanjuán, Cristina Diaz-de-Heredia, Julia Montoro, Javier Rodríguez-Ubreva, Alessandro Liquori, José Cervera, Marcin W. Wlodarski, Albert Català, Alessandra Giorgetti
Journal: Leukemia (2025)
Outer membrane vesicle contributes to the <i>Pseudomonas aeruginosa</i> resistance to antimicrobial peptides in the acidic airway of bronchiectasis patients
Authors: Yingzhou Xie, Yi‐Han Shi, Le‐Le Wang, Cheng‐Wei Li, Min Wu, Jin‐Fu Xu
Journal: MedComm (2025)

Pseudomonas aeruginosa is the predominant pathogen causing chronic infection in the airway of patients with bronchiectasis (BE), a chronic respiratory disease with high prevalence worldwide. Environmental factors are vital for bacterial successful colonization. Here, with sputa and bronchoalveolar lavage fluids, we determined that the concentration of airway antimicrobial peptide LL-37 and lactate was elevated in BE patients, especially in those infected with P. aeruginosa. The in vitro antibacterial assay revealed the bactericidal activity of LL-37 against the clinical P. aeruginosa isolates, which were dampened in the acidic condition. P. aeruginosa production of outer membrane vesicles (OMVs) enhanced in the lactate-adjusted acidic condition. Transcriptomic analysis suggested that OMVs induce the hyperproduction of the chemical compound 2-heptyl-4-quinolone (HHQ) in the bacterial population, which was verified by high-performance liquid chromatography. The positively charged HHQ interfered with the binding of LL-37 to bacterial cell membrane, potentiating the P. aeruginosa resistance to LL-37. To our knowledge, this is a new resistance mechanism of P. aeruginosa against antimicrobial peptides and may provide theoretical support for the development of new antibacterial therapies.
Antimicrobial peptide DP7 alleviates dextran sulfate sodium (DSS)‐induced colitis via modifying gut microbiota and regulating intestinal barrier function
Authors: Binyan Zhao, Hongyou Zhou, Ke Lin, Jie Xu, Bailing Zhou, Daoyuan Xie, Jing Ma, Lei Yang, Chunyan Su, Li Yang
Journal: MedComm (2025)

Inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), represent a growing global health concern. Restoring the balance of the gut microbiota, a crucial factor in intestinal health, offers potential for treating IBD. DP7, a novel antimicrobial peptide with potent antibacterial activity, was investigated for its anti-inflammatory effects in a dextran sulfate sodium (DSS)-induced UC mouse model. DP7 significantly ameliorated key disease parameters, including disease activity index, weight loss, and shortened colon length, while preserving colonic epithelial integrity and reducing inflammatory infiltration. Further analysis revealed potential targets of DP7, highlighting the significant role of Muribaculaceae bacteria during inflammatory states. To further explore the role of the gut microbiota in DP7's efficacy, fecal microbiota transplantation (FMT) was performed using feces from DP7-treated mice. FMT successfully ameliorated colitis in recipient mice, providing further evidence for the crucial role of the gut microbiome in IBD treatment and DP7's ability to modulate the gut microbiota for therapeutic benefit. Moreover, our findings suggest that DP7's modulation of the immune system is intricately linked to the complex microbial environment. Our findings demonstrate that DP7 effectively mitigates inflammation, attenuates barrier dysfunction, and shapes the gut microbiota, suggesting its potential as a therapeutic agent for UC.
CircRNF13 enhances IGF2BP1 phase separation-mediated ITGB1 mRNA stabilization in an m6A-dependent manner to promote oral cancer cisplatin chemoresistance
Authors: Xuemeng Xu, Qiu Peng, Zongyao Ren, Yaqian Han, Xianjie Jiang, Zhu Wu, Shiming Tan, Wenjuan Yang, Linda Oyang, Xia Luo, Jinguan Lin, Longzheng Xia, Mingjing Peng, Nayiyuan Wu, Yanyan Tang, Hao Tian, Yujuan Zhou, Qianjin Liao
Journal: Molecular Cancer (2025)

Oral cancer ranks among the most common malignancies within the head and neck region; however, its etiology remains inadequately understood despite substantial research advances in recent years. Many studies highlight the regulatory role of circular RNAs (circRNAs) in human cancers, suggesting their potential as cancer biomarkers. However, their specific mechanisms in oral cancer are not well understood. This study analyzed circRNAs expression in oral cancer, identifying circRNF13 (circbaseID: has_circ_0006801) as having elevated expression in oral cancer cells and tissues. Our study demonstrated that circRNF13 is correlated with increased tumor grade and stage in oral cancer. Results from both in vitro and in vivo experiments indicated that circRNF13 enhances cancer cell proliferation and tumor growth, while concurrently diminishing tumor sensitivity to cisplatin. Mechanistically, circRNF13 interacts with the m6A "reader" protein IGF2BP1, inhibiting its ubiquitin-mediated degradation and promoting its phase separation formation. Subsequently, circRNF13 augments the stability of ITGB1 mRNA via IGF2BP1 in a manner dependent on m6A modification. The m6A modification of ITGB1 mRNA is modulated by the phase separation of IGF2BP1, thereby promoting the malignant progression of oral cancer cells. This evidence positions circRNF13 as a crucial regulatory molecule in the pathogenesis of oral cancer and suggests its potential as a therapeutic target. This discovery enriches our understanding of the mechanistic role of circRNAs.
Remote Ischemic Conditioning Attenuates Transneuronal Degeneration and Promotes Stroke Recovery via CD36-Mediated Efferocytosis
Authors: Hyunwoo Ju, Il-Doo Kim, Ina Pavlova, Shang Mu, Keun Woo Park, Joseph Minkler, Ahmed Madkoor, Wei Wang, Xiaoman Wang, Zhuhao Wu, Jiwon Yang, Maria Febbraio, John W. Cave, Sunghee Cho
Journal: Circulation Research (2025)

BACKGROUND: Remote ischemic conditioning (RIC) has been implicated in cross-organ protection in cerebrovascular disease, including stroke. However, the lack of a consensus protocol and controversy over the clinical therapeutic outcomes of RIC suggest an inadequate mechanistic understanding of RIC. The current study identifies RIC-induced molecular and cellular events in the blood, which enhance long-term functional recovery in experimental cerebral ischemia. METHODS: Naive mice or mice subjected to transient ischemic stroke were randomly selected to receive sham conditioning or RIC in the hindlimb at 2 hours post-stroke. At 3 days post-stroke, monocyte composition in the blood was analyzed, and brain tissue was examined for monocyte-derived macrophage (Mφ), levels of efferocytosis, and CD36 expression. Mouse with a specific deletion of CD36 in monocytes/Mφs was used to establish the role of CD36 in RIC-mediated modulation of efferocytosis, transneuronal degeneration, and recovery following stroke. RESULTS: RIC applied 2 hours after stroke increased the entry of monocytes into the injured brain. In the postischemic brain, Mφ had increased levels of CD36 expression and efferocytosis. These changes in brain Mφ were derived from RIC-induced changes in circulating monocytes. In the blood, RIC increased CD36 expression in circulating monocytes and shifted monocytes to a proinflammatory LY6C High state. Conditional deletion of CD36 in Mφ abrogated the RIC-induced monocyte shift in the blood and efferocytosis in the brain. During the recovery phase of stroke, RIC rescued the loss of the volume and of tyrosine hydroxylase+ neurons in substantia nigra and behavioral deficits in wild-type mice but not in mice with a specific deletion of CD36 in monocytes/Mφs. CONCLUSIONS: RIC induces a shift in monocytes to a proinflammatory state with elevated CD36 levels, and this is associated with CD36-dependent efferocytosis in Mφs that rescues delayed transneuronal degeneration in the postischemic brain and promotes stroke recovery. Together, these findings provide novel insight into our mechanistic understanding of how RIC improves poststroke recovery.