tbuckley/cabot-search huggingface dataset:
CD36 Promotes Iron Accumulation and Dysfunction in CD8+ T Cells via the p38-CEBPB-TfR1 Axis in Early-stage Hepatocellular Carcinoma
Authors: Yifei Qin, Fei Huo, Zhuan Feng, Jialu Hou, Yaxin Ding, Quancheng Wang, Yu Gui, Ziwei Yang, Jiali Yang, Gang Zhou, Ling Li, Jianli Jiang, Lingmin Kong, Shijie Wang, Gang Nan, Dingqiao Xu, Xiaohang Xie, Lijuan Wang, Qian He, Ruibin Yang, Peng Lin, Huijie Bian, Zhi-Nan Chen, Jiao Wu
Journal: Clinical and Molecular Hepatology (2025)

The identification of factors that lead to CD8⁺ T cell dysfunction within the tumor microenvironment (TME) holds great promise for the development of innovative immunotherapies. However, the precise mechanisms underlying the exhausted phenotype of CD8⁺ T cells infiltrating early-stage hepatocellular carcinoma (HCC) tumors remains unclear. Single-cell RNA sequencing was performed using a murine HCC model. Flow cytometry and additional experimental approaches were employed to investigate the underlying mechanisms of CD8⁺ T cell exhaustion. CD8+ T cells infiltrating early-stage HCC tumors exhibited a functionally exhausted phenotype, which escalated with HCC progression. At early stages of murine and human HCC tumors, the TME was characterized by significant iron accumulation. Moreover, tumor-infiltrating CD8+ T cells in early-stage murine HCC tumors exhibited higher levels of intracellular ferrous iron compared to splenic CD8+ T cells. This excessive iron led to increased lipid peroxide levels and impaired the effector function of CD8+ T cells. Mechanistically, CD36 upregulated the major iron uptake protein transferrin receptor 1 (TfR1) by mediating the activation of oxidized low-density lipoprotein (oxLDL)-p38-CEBPB axis. Depletion of CD36 in CD8+ T cells inhibited the upregulation of TfR1 expression and the increase of intracellular ferrous iron levels triggered by iron-enriched conditions. Furthermore, constitutively activated nuclear factor erythroid 2-related factor 2 (NRF2) effectively suppressed iron accumulation and lipid peroxidation, thereby preserving the effector functions of intratumoral CD8+ T cells and ultimately inhibiting tumor growth. Our findings reveal a previously unidentified mechanism mediated by CD36 that regulating the progressive dysfunction of CD8+ T cells in early HCC TME and provide a potential novel therapeutic approach to restore T cells function.
The epigenetic hallmarks of immune cells in cancer
Authors: Yu Ji, Chu Xiao, Tao Fan, Ziqin Deng, Di Wang, Wenpeng Cai, Jia Li, Tianle Liao, Chunxiang Li, Jie He
Journal: Molecular Cancer (2025)

Targeting the dysregulation of epigenetic mechanisms in cancer has emerged as a promising therapeutic strategy. Although the significant rationale progress of epigenetic therapies in blocking cancer cells, how epigenetic regulation shapes tumor microenvironment (TME) and establishes antitumor immunity remains less understood. Recent study focus has been put on the epigenetic-mediated changes in the fate of immune cells, including the differentiation, expansion, recruitment, functionalization, and exhaustion of T cells, natural killer (NK) cells, tumor-associated macrophages (TAMs), dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), and B cells within the TME. Here, we review the latest molecular and clinical insights into how DNA modifications, histone modification, and epitranscriptome-related regulations shape immune cells of various cancers. We also discuss opportunities for leveraging epigenetic therapies to improve cancer immunotherapies. This review provides the epigenetic foundations of cancer immunity and proposes the future direction of combination therapies.
Reprogrammed glycolysis-induced augmentation of NIR-II excited photodynamic/photothermal therapy
Authors: Chunbai Xiang, Qihang Ding, Ting Jiang, Yu Liu, Chao Li, Xing Yang, Jia Jia, Jingjing Xiang, Yue Wang, Hui Zhou, Zhiyun Lu, Ping Gong, Jong Seung Kim
Journal: Biomaterials (2025)
Myeloid-derived suppressor cell-targeted virus-like particles synergistically activate innate immune response for cancer immunotherapy
Authors: Zhixiong Zhu, Shuqin Cao, Hanwen Li, Zongliang Zhang, Qizhong Lu, Hexian Li, Luxuan Shen, Zeng Wang, Nian Yang, Jiayun Yu, Jianshu Li, Meijun Zheng, Chunlai Nie, Aiping Tong, Bin Shao
Journal: Journal of Controlled Release (2025)
Improving vulnerable Calbindin1− neurons in the ventral hippocampus rescues tau-induced impairment of episodic memory
Authors: Huiyang Lei, Jingru Lv, Fuqiang Zhang, Linyu Wei, Kun Shi, Jiale Liu, Ting He, Rui Xiong, Fei Sun, Tongkai Zhong, Jingqi Zhao, Dan Ke, Qun Wang, Peiran Jiang, Ai-Min Bao, Jian-Zhi Wang, Ying Yang
Journal: Translational Neurodegeneration (2025)

Intraneuronal accumulation of hyperphosphorylated tau is a hallmark of Alzheimer's disease (AD). Given the significant correlation between tau pathology and memory loss in AD patients, identifying vulnerable brain regions, particularly susceptible neuron types in these regions, will advance our understanding of AD onset and shed light on therapeutic strategies to manage its progression. Immunofluorescent staining was employed to identify the brain regions and neuron types vulnerable to tau pathology in AD. A combination of chemogenetics, electrophysiological recording, in vivo Ca2+ recording, and a modified temporal-order discrimination behavior test was utilized to investigate the toxicity of tau accumulation to susceptible neurons in the dorsal part of the ventral hippocampus. Proteomics, phosphoproteomics, and molecular targeting were used to explore the underlying mechanisms of neuron susceptibility to tau accumulation in AD. The beneficial effects of microtubule affinity regulating kinase 4 (MARK4) knockdown and administration of DEPhosphorylation TArgeting Chimera (DEPTAC) were evaluated in AD mice with tau pathology. In postmortem brains of AD patients, we observed robust accumulation of hyperphosphorylated tau in the anterior hippocampal CA1 region, particularly in its Calbindin1- (Calb1-) neurons, as opposed to the posterior hippocampal CA1 region and Calb1+ neurons. The susceptibility of Calb1- neurons to phospho-tau accumulation was also observed in P301L mice, especially in the dorsal part of ventral (anterior in human) hippocampal CA1 (dvCA1). In P301L mice, dvCA1 displayed distinct protein and phosphorylated protein networks compared with dorsal CA1, accompanied by overactivation of MARK4. Overexpressing human tau in Calb1- neurons in the dvCA1 (dvCA1Calb1- neurons) specifically impairs the temporal-order discrimination of objects. Meanwhile, tau accumulation significantly inhibited the excitability and firing patterns of dvCA1Calb1- neurons associated with temporal-order discrimination. Knocking down MARK4 or reducing hyperphosporylated tau via DEPTAC in P301L mice significantly ameliorated AD-like tau pathology in dvCA1Calb1- neurons and improved temporal-order discrimination of objects. These findings highlight the crucial role of dvCA1Calb1- neurons in the early stage of tau pathology and demonstrate the potential of targeting phosphorylated tau through MARK4 knockdown or DEPTAC administration to counter the vulnerability of dvCA1Calb1- neurons and, consequently, ameliorate episodic memory deficits in AD.
A Formula for Love: Partner Merit and Appreciation Beget Actor Significance
Authors: Arie W Kruglanski, Molly Ellenberg, Huixian Yu, Edward P Lemay, Sophia Moskalenko, Ewa Szumowska, Erica Molinario, Antonio Pierro, Federico Contu
Journal: Behavioral and Brain Sciences (2025)

Abstract We offer a novel motivational account of romantic love, which portrays it as a means to the end of feeling significant and worthy. According to the model, falling in love with a partner depends on the actor's perceptions that (1) the partner possesses meritorious characteristics, and (2) that they appreciate the actor and view them as significant. We assume that these two factors multiplicatively combine with the magnitude of actor's quest for significance to determine the likelihood of actor becoming enamored with partner. The multiplicative model has two major implications: 1. If any one of the partner's merit , appreciation , or actor's significance quest factors falls below its respective threshold of acceptability (such that it is subjectively non-existent), the likelihood of falling in love will be negligible. 2. Above their acceptability thresholds, levels of (partner's) merit , appreciation and (actor's) significance quest factors compensate for one another. A partner's lower standing on merit or appreciation is compensated in its impact on falling in love by the partner's higher standing on the remaining dimension. Furthermore, lower levels of either or both of these factors are compensated for by the actor's higher level of significance quest. Our model affords a broad account of diverse love phenomena, allows the derivation of several specific hypotheses supported by prior close-relations research as well as new data, and it offers novel avenues for further research on classic issues in romantic love. The discussion considers our model's unique implications and examines its relation to other theories of love.
Engineering non-pathogenic bacteria for auto-transporter-driven secretion of functional interferon
Authors: May Tfilin Samuel, Irina Rostovsky, Alona Kuzmina, Ran Taube, Neta Sal-Man
Journal: Gut Microbes (2025)

In recent years, various strategies have been developed to enable the oral administration of protein-based drugs (biologics) with the aim of overcoming the degradation and inactivation of these drugs that can occur as they traverse the gastrointestinal tract (GIT). In this study, we investigated bacteria as a delivery vehicle for biologics, harnessing their ability to withstand the harsh gastric environment and deliver therapeutic drugs directly to the intestine. Specifically, we explored using the type 5 secretion system (T5SS) to secrete therapeutic cargoes under simulated gut conditions. Our research focused on EspC, a T5SS protein from enteropathogenic Escherichia coli, and its potential to secrete interferon-α (IFNα), a cytokine with immunomodulatory and antiviral properties widely used in the clinic. We demonstrated that EspC can facilitate the secretion of IFNα variant when expressed in nonpathogenic bacteria. Moreover, this EspC-secreted IFN was able to activate the JAK-STAT pathway, upregulate IFN-stimulated genes, and induce a robust antiviral response in cells. Collectively, these findings provide proof of concept supporting the utilization of the EspC protein as a novel delivery platform for protein-based therapeutics.
<i>Rhodococcus</i> spp. interacts with human norovirus in clinical samples and impairs its replication on human intestinal enteroids
Authors: Cristina Santiso-Bellón, Walter Randazzo, Noelia Carmona-Vicente, Nazaret Peña-Gil, Roberto Cárcamo-Calvo, Sergi Lopez-Navarro, Noemi Navarro-Lleó, Maria J. Yebra, Vicente Monedero, Javier Buesa, Roberto Gozalbo-Rovira, Jesús Rodríguez-Díaz
Journal: Gut Microbes (2025)

Viral infections, particularly human norovirus (NoV), are a leading cause of diarrheal diseases globally. To better understand NoV susceptibility, it is crucial to investigate both host glycobiology and the influence of the microbiota. Histo-blood group antigens (HBGA) displayed on surfaces of host cells act as NoV receptors, while certain bacteria express HBGA-like substances, facilitating virus-bacteria interactions. To identify bacterial species interacting with NoV during infection, stool samples from children infected with NoV GII.4 were analyzed. The samples were subjected to bacteria separation using anti-NoV GII.4 polyclonal antibodies coupled to magnetic beads, followed by microbiota profiling through 16S rDNA sequencing. This approach identified the genus Rhodococcus as enriched in samples captured with anti-NoV antibodies compared to controls. Electron microscopy confirmed the binding of NoV GII.4 Sydney 2012 viral-like particles (VLP) to five Rhodococcus strains from different species, which expressed HBGA-like substances on their surfaces, particularly from A and B blood groups. In human intestinal enteroids, Rhodococcus erythropolis reduced NoV GII.4 Sydney 2012 infection levels under displacement, exclusion and competitive exclusion settings. Extracellular polysaccharides (EPS) isolated from Rhodococcus strains bound VLP from both GII.4 and GII.6 genotypes. Blocking antibodies targeting A and B epitopes reduced the binding of the EPS from R. erythropolis to GII.6 VLP, while enhanced binding to GII.4 VLP was observed when A and B epitopes were blocked. These findings revealed the interaction of Rhodococcus to NoV in an in vitro setting and open new avenues for developing innovative antiviral strategies to prevent and treat NoV infections through the HBGA-like substances present in their EPS.
Interbacterial warfare in the human gut: insights from Bacteroidales’ perspective
Authors: Kun Jiang, Xinxin Pang, Weixun Li, Xiaoning Xu, Yan Yang, Chengbin Shang, Xiang Gao
Journal: Gut Microbes (2025)

Competition and cooperation are fundamental to the stability and evolution of ecological communities. The human gut microbiota, a dense and complex microbial ecosystem, plays a critical role in the host's health and disease, with competitive interactions being particularly significant. As a dominant and extensively studied group in the human gut, Bacteroidales serves as a successful model system for understanding these intricate dynamic processes. This review summarizes recent advances in our understanding of the intricate antagonism mechanisms among gut Bacteroidales at the biochemical or molecular-genetic levels, focusing on interference and exploitation competition. We also discuss unresolved questions and suggest strategies for studying the competitive mechanisms of Bacteroidales. The review presented here offers valuable insights into the molecular basis of bacterial antagonism in the human gut and may inform strategies for manipulating the microbiome to benefit human health.
Re: Guillaume Ploussard, Patrick Coloby, Thierry Chevallier, et al. Whole-gland or Subtotal High-intensity Focused Ultrasound Versus Radical Prostatectomy: The Prospective, Noninferiority, Nonrandomized HIFI Trial. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2024.11.006
Authors: Mario Terlizzi, Youssef Ghannam, Pierre Blanchard
Journal: European Urology (2025)
Single-cell Atlas of Developing Mouse Palates Reveals Cellular and Molecular Transitions in Periderm Cell Fate
Authors: Wenbin Huang, Zhenwei Qian, Jieni Zhang, Yi Ding, Bin Wang, Jiuxiang Lin, Xiannian Zhang, Huaxiang Zhao, Feng Chen
Journal: Genomics Proteomics & Bioinformatics (2025)

Cleft palate is one of the most common congenital craniofacial disorders that affects children's appearance and oral functions. Investigating the transcriptomics during palatogenesis is crucial for comprehending the etiology of this disorder and facilitating prenatal molecular diagnosis. However, there is limited knowledge about the single-cell differentiation dynamics during mid-palatogenesis and late-palatogenesis, specifically regarding the subpopulations and developmental trajectories of periderm, a rare but critical cell population. Here we explored the single-cell landscape of mouse developing palates from embryonic day (E) 10.5 to E16.5. We systematically depicted the single-cell transcriptomics of mesenchymal and epithelial cells during palatogenesis, including subpopulations and differentiation dynamics. Additionally, we identified four subclusters of palatal periderm and constructed two distinct trajectories of cell fates for periderm cells. Our findings reveal that claudin-family coding genes and Arhgap29 play a role in the non-stick function of the periderm before the palatal shelves contact, and Pitx2 mediates the adhesion of periderm during the contact of opposing palatal shelves. Furthermore, we demonstrated that epithelial-mesenchymal transition (EMT), apoptosis, and migration collectively contribute to the degeneration of periderm cells in the medial epithelial seam. Taken together, our study suggests a novel model of periderm development during palatogenesis and delineates the cellular and molecular transitions in periderm cell determination.
Biological Data Resources and Machine Learning Frameworks for Hematology Research
Authors: Ying Yi, Yongfei Hu, Juanjuan Kang, Qifa Liu, Yan Huang, Dong Wang
Journal: Genomics Proteomics & Bioinformatics (2025)

Hematology research has greatly benefited from the integration of diverse biological data resources and advanced machine learning frameworks. This integration has not only deepened our understanding of blood diseases such as leukemia and lymphoma, but also enhanced diagnostic accuracy and personalized treatment strategies. By applying machine learning algorithms to analyze large-scale biological data, researchers are able to more effectively identify disease patterns, predict treatment responses, and provide new perspectives for the diagnosis and treatment of hematologic disorders. Here, we provide an overview of the current landscape of biological data resources and the application of machine learning frameworks pertinent to hematology research.
A Developmental Gene Expression Atlas Reveals Novel Biological Basis of Complex Phenotypes in Sheep
Authors: Bingru Zhao, Hanpeng Luo, Xuefeng Fu, Guoming Zhang, Emily L Clark, Feng Wang, Brian Paul Dalrymple, V Hutton Oddy, Philip E Vercoe, Cuiling Wu, George E Liu, Cong-jun Li, Ruidong Xiang, Kechuan Tian, Yanli Zhang, Lingzhao Fang
Journal: Genomics Proteomics & Bioinformatics (2025)

Sheep (Ovis aries) represents one of the most important livestock species for animal protein and wool production worldwide. However, little is known about the genetic and biological basis of ovine phenotypes, particularly for those of high economic value and environmental impact. Here, by integrating 1413 RNA-seq samples from 51 distinct tissues across 14 developmental time points, representing early prenatal, late prenatal, neonate, lamb, juvenile, adult, and elderly stages, we built a high-resolution developmental Gene Expression Atlas (dGEA) in sheep. We observed dynamic patterns of gene expression and regulatory networks across tissues and developmental stages. When harnessing this resource for interpreting genetic associations of 48 monogenetic and 12 complex traits in sheep, we found that genes upregulated at prenatal developmental stages played more important roles in shaping these phenotypes than those upregulated at postnatal stages. For instance, genetic associations of crimp number, mean staple length (MSL), and individual birth weight were significantly enriched in the prenatal rather than postnatal skin and immune tissues. By comprehensively integrating GWAS fine-mapping results and the sheep dGEA, we proposed several candidate genes for complex traits in sheep, such as SOX9 for MSL, GNRHR for litter size at birth, and PRKDC for live weight. These results provide novel insights into the developmental and molecular architecture underlying ovine phenotypes. The dGEA (https://sheepdgea.njau.edu.cn/) will serve as an invaluable resource for sheep developmental biology, genetics, genomics, and selective breeding.
PhaSeDis: A Manually Curated Database of Phase Separation–Disease Associations and Corresponding Small Molecules
Authors: Taoyu Chen, Guoguo Tang, Tianhao Li, Zhining Yanghong, Chao Hou, Zezhou Du, Kaiqiang You, Liwei Ma, Tingting Li
Journal: Genomics Proteomics & Bioinformatics (2025)

Biomacromolecules form membraneless organelles through liquid-liquid phase separation in order to regulate the efficiency of particular biochemical reactions. Dysregulation of phase separation might result in pathological condensation or sequestration of biomolecules, leading to diseases. Thus, phase separation and phase separating factors may serve as drug targets for disease treatment. Nevertheless, such associations have not yet been integrated into phase separation related databases. Therefore, based on MloDisDB, a database for membraneless organelle factor-disease association previously developed by our lab, we constructed PhaSeDis, the phase separation-disease association database. We increased the number of phase separation entries from 52 to 185, and supplemented the evidence provided by the original article verifying the phase separation nature of the factors. Moreover, we included the information of interacting small molecules with low-throughput or high-throughput evidence that might serve as potential drugs for phase separation entries. PhaSeDis strives to offer comprehensive descriptions of each entry, elucidating how phase separating factors induce pathological conditions via phase separation and the mechanisms by which small molecules intervene. We believe that PhaSeDis would be very important in the application of phase separation regulation in treating related diseases. PhaSeDis is available at http://mlodis.phasep.pro.
Molecular insights into sperm head shaping and its role in human male fertility
Authors: Jiaxin He, Xinle Lin, Chen Tan, Yong Li, Lilan Su, Ge Lin, Yue-Qiu Tan, Chaofeng Tu
Journal: Human Reproduction Update (2025)

Sperm head shaping, controlled by the acrosome-acroplaxome-manchette complex, represents a significant morphological change during spermiogenesis and involves numerous proteins expressed in a spatially and temporally specific manner. Defects in sperm head shaping frequently lead to teratozoospermia concomitant with oligozoospermia and asthenozoospermia, but the pathogenic mechanism underlying sperm head shaping, and its role in male infertility, remain poorly understood. This review aims to summarize the mechanism underlying sperm head shaping, reveal the relationship between gene defects associated with sperm head shaping and male infertility in humans and mice, and explore potential clinical improvements in ICSI treatment. We searched the PubMed database for articles published in English using the keyword 'sperm head shaping' in combination with the following terms: 'acrosome formation', 'proacrosomal vesicles (PAVs)', 'manchette', 'perinuclear theca (PT)', 'chromatin condensation', 'linker of nucleoskeleton and cytoskeleton (LINC) complex', 'histone-to-protamine (HTP) transition', 'male infertility', 'ICSI', and 'artificial oocyte activation (AOA)'. The selected publications until 1 August 2024 were critically summarized, integrated, and thoroughly discussed, and the irrelevant literature were excluded. A total of 6823 records were retrieved. After careful screening, integrating relevant literature, and excluding articles unrelated to the topic of this review, 240 articles were ultimately included in the analysis. Firstly, we reviewed the important molecular events and structures integral to sperm head shaping, including PAV formation to fusion, acrosome attachment to the nucleus, structure and function of the manchette, PT, chromatin condensation, and HTP transition. Then, we set forth human male infertility associated with sperm head shaping and identified genes related to sperm head shaping resulting in teratozoospermia concomitant with oligozoospermia and asthenozoospermia. Finally, we summarized the outcomes of ICSI in cases of male infertility resulting from mutations in the genes associated with sperm head shaping, as well as the ICSI outcomes through AOA for infertile men with impaired sperm head. Understanding the molecular mechanisms of sperm head shaping and its relationship with human male infertility holds profound clinical implications, which may contribute to risk prediction, genetic diagnosis, and the potential treatment of human male infertility.