tbuckley/cabot-search huggingface dataset:
Differential peripheral immune signatures elicited by vegan versus ketogenic diets in humans
Authors: Verena M. Link, Poorani Subramanian, Foo Cheung, Kyu Lee Han, Apollo Stacy, Liang Chi, Brian A. Sellers, Galina Koroleva, Amber B. Courville, Shreni Mistry, Andrew Burns, Richard Apps, Kevin D. Hall, Yasmine Belkaid
Journal: Nature Medicine (2024)

Abstract Nutrition has broad impacts on all physiological processes. However, how nutrition affects human immunity remains largely unknown. Here we explored the impact of a dietary intervention on both immunity and the microbiota by performing a post hoc analysis of a clinical trial in which each of the 20 participants sequentially consumed vegan or ketogenic diets for 2 weeks ( NCT03878108 ). Using a multiomics approach including multidimensional flow cytometry, transcriptomic, proteomic, metabolomic and metagenomic datasets, we assessed the impact of each diet, and dietary switch, on host immunity and the microbiota. Our data revealed that overall, a ketogenic diet was associated with a significant upregulation of pathways and enrichment in cells associated with the adaptive immune system. In contrast, a vegan diet had a significant impact on the innate immune system, including upregulation of pathways associated with antiviral immunity. Both diets significantly and differentially impacted the microbiome and host-associated amino acid metabolism, with a strong downregulation of most microbial pathways following ketogenic diet compared with baseline and vegan diet. Despite the diversity of participants, we also observed a tightly connected network between datasets driven by compounds associated with amino acids, lipids and the immune system. Collectively, this work demonstrates that in diverse participants 2 weeks of controlled dietary intervention is sufficient to significantly and divergently impact host immunity, which could have implications for precision nutritional interventions. ClinicalTrials.gov registration: NCT03878108 .
Striatal dopamine signals reflect perceived cue–action–outcome associations in mice
Authors: Tobias W. Bernklau, Beatrice Righetti, Leonie S. Mehrke, Simon N. Jacob
Journal: Nature Neuroscience (2024)

Abstract Striatal dopamine drives associative learning by acting as a teaching signal. Much work has focused on simple learning paradigms, including Pavlovian and instrumental learning. However, higher cognition requires that animals generate internal concepts of their environment, where sensory stimuli, actions and outcomes become flexibly associated. Here, we performed fiber photometry dopamine measurements across the striatum of male mice as they learned cue–action–outcome associations based on implicit and changing task rules. Reinforcement learning models of the behavioral and dopamine data showed that rule changes lead to adjustments of learned cue–action–outcome associations. After rule changes, mice discarded learned associations and reset outcome expectations. Cue- and outcome-triggered dopamine signals became uncoupled and dependent on the adopted behavioral strategy. As mice learned the new association, coupling between cue- and outcome-triggered dopamine signals and task performance re-emerged. Our results suggest that dopaminergic reward prediction errors reflect an agent’s perceived locus of control.
Somatosensory cortex and central amygdala regulate neuropathic pain-mediated peripheral immune response via vagal projections to the spleen
Authors: Xia Zhu, Ji-Ye Huang, Wan-Ying Dong, Hao-Di Tang, Si Xu, Qielan Wu, Huimin Zhang, Ping-Kai Cheng, Yuxin Jin, Meng-Yu Zhu, Wan Zhao, Yu Mao, Haitao Wang, Yan Zhang, Hao Wang, Wenjuan Tao, Yanghua Tian, Li Bai, Zhi Zhang
Journal: Nature Neuroscience (2024)
Dynamic Antimicrobial Poly(disulfide) Coatings Exfoliate Biofilms On Demand Via Triggered Depolymerization
Authors: Yang Lou, Edmund F. Palermo
Journal: Advanced Healthcare Materials (2024)

Abstract Bacterial biofilms are notoriously problematic in applications ranging from biomedical implants to ship hulls. Cationic, amphiphilic antibacterial surface coatings delay the onset of biofilm formation by killing microbes on contact, but they lose effectiveness over time due to non‐specific binding of biomass and biofilm formation. Harsh treatment methods are required to forcibly expel the biomass and regenerate a clean surface. Here, a simple, dynamically reversible method of polymer surface coating that enables both chemical killing on contact, and on‐demand mechanical delamination of surface‐bound biofilms, by triggered depolymerization of the underlying antimicrobial coating layer, is developed. Antimicrobial polymer derivatives based on α‐lipoic acid (LA) undergo dynamic and reversible polymerization into polydisulfides functionalized with biocidal quaternary ammonium salt groups. These coatings kill &gt;99.9% of Staphylococcus aureus cells, repeatedly for 15 cycles without loss of activity, for moderate microbial challenges (≈10 5 colony‐forming units (CFU) mL −1 , 1 h), but they ultimately foul under intense challenges (≈10 7 CFU mL −1 , 5 days). The attached biofilms are then exfoliated from the polymer surface by UV‐triggered degradation in an aqueous solution at neutral pH. This work provides a simple strategy for antimicrobial coatings that can kill bacteria on contact for extended timescales, followed by triggered biofilm removal under mild conditions.
Ancestral genome reconstruction enhances transposable element annotation by identifying degenerate integrants
Authors: Wayo Matsushima, Evarist Planet, Didier Trono
Journal: Cell Genomics (2024)

Growing evidence indicates that transposable elements (TEs) play important roles in evolution by providing genomes with coding and non-coding sequences. Identification of TE-derived functional elements, however, has relied on TE annotations in individual species, which limits its scope to relatively intact TE sequences. Here, we report a novel approach to uncover previously unannotated degenerate TEs (degTEs) by probing multiple ancestral genomes reconstructed from hundreds of species. We applied this method to the human genome and achieved a 10.8% increase in coverage over the most recent annotation. Further, we discovered that degTEs contribute to various cis-regulatory elements and transcription factor binding sites, including those of a known TE-controlling family, the KRAB zinc-finger proteins. We also report unannotated chimeric transcripts between degTEs and human genes expressed in embryos. This study provides a novel methodology and a freely available resource that will facilitate the investigation of TE co-option events on a full scale.
Tailoring Biomaterials Ameliorate Inflammatory Bone Loss
Authors: Shi Cheng, Kong‐Huai Wang, Lu Zhou, Zhi‐Jun Sun, Lu Zhang
Journal: Advanced Healthcare Materials (2024)

Abstract Inflammatory diseases, such as rheumatoid arthritis, periodontitis, chronic obstructive pulmonary disease, and celiac disease, disrupt the delicate balance between bone resorption and formation, leading to inflammatory bone loss. Conventional approaches to tackle this issue encompass pharmaceutical interventions and surgical procedures. Nevertheless, pharmaceutical interventions exhibit limited efficacy, while surgical treatments impose trauma and significant financial burden upon patients. Biomaterials show outstanding spatiotemporal controllability, possess a remarkable specific surface area, and demonstrate exceptional reactivity. In the present era, the advancement of emerging biomaterials has bestowed upon more efficacious solutions for combatting the detrimental consequences of inflammatory bone loss. In this review, the advances of biomaterials for ameliorating inflammatory bone loss are listed. Additionally, the advantages and disadvantages of various biomaterials‐mediated strategies are summarized. Finally, the challenges and perspectives of biomaterials are analyzed. This review aims to provide new possibilities for developing more advanced biomaterials toward inflammatory bone loss.
Age- and Race-Specific Changes in ESKD Incidence over Four Decades
Authors: Chyng-Wen Fwu, Paul W. Eggers, Jenna M. Norton, Debbie S. Gipson, Paul L. Kimmel, Ivonne H. Schulman, Kevin E. Chan, Kara Bennett, Susan R. Mendley
Journal: Journal of the American Society of Nephrology (2024)

ESKD incidence has changed substantially in the past four decades, but differences by age and race have been unexplored. Using data from the United States Renal Data System, we found that ESKD incidence rose for Black and White teenagers, adults, and older adults for two decades beginning in 1980. Growth in incidence slowed for most groups by 1993, and by 2006, the annual percent change (APC) in ESKD incidence had declined for all groups, except White adults, for whom rates continued to rise. By 2019, ESKD incidence among Black and White adolescents nearly returned to 1980 levels, but no other group achieved that degree of improvement. Nonetheless, the ESKD incidence rate among Black American patients exceeds that of White patients in every age group. Distinct patterns in ESKD incidence among patients of different age, sex, and racial groups are shown. These findings could reflect changes in dialysis acceptance rates, access to preventive health care, incidence of diabetes mellitus, implementation of evidence-based guidelines for treatment of CKD, or other unrecognized factors. There may be population-specific opportunities to change the growth of the US ESKD population and address current racial disparities.
Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma
Authors: Zheqi Liu, Zhen Zhang, Yu Zhang, Wenkai Zhou, Xu Zhang, Canbang Peng, Tong Ji, Xin Zou, Zhiyuan Zhang, Zhenhu Ren
Journal: International Journal of Oral Science (2024)

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.
Mapping cancer biology in space: applications and perspectives on spatial omics for oncology
Authors: Sumin Lee, Gyeongjun Kim, JinYoung Lee, Amos C. Lee, Sunghoon Kwon
Journal: Molecular Cancer (2024)

Technologies to decipher cellular biology, such as bulk sequencing technologies and single-cell sequencing technologies, have greatly assisted novel findings in tumor biology. Recent findings in tumor biology suggest that tumors construct architectures that influence the underlying cancerous mechanisms. Increasing research has reported novel techniques to map the tissue in a spatial context or targeted sampling-based characterization and has introduced such technologies to solve oncology regarding tumor heterogeneity, tumor microenvironment, and spatially located biomarkers. In this study, we address spatial technologies that can delineate the omics profile in a spatial context, novel findings discovered via spatial technologies in oncology, and suggest perspectives regarding therapeutic approaches and further technological developments.
Nanomedicine Targeting Myeloid‐Derived Suppressor Cells Enhances Anti‐Tumor Immunity
Authors: En‐Li Yang, Zhi‐Jun Sun
Journal: Advanced Healthcare Materials (2024)

Abstract Cancer immunotherapy, a field within immunology that aims to enhance the host's anti‐cancer immune response, frequently encounters challenges associated with suboptimal response rates. The presence of myeloid‐derived suppressor cells (MDSCs), crucial constituents of the tumor microenvironment (TME), exacerbates this issue by fostering immunosuppression and impeding T cell differentiation and maturation. Consequently, targeting MDSCs has emerged as crucial for immunotherapy aimed at enhancing anti‐tumor responses. The development of nanomedicines specifically designed to target MDSCs aims to improve the effectiveness of immunotherapy by transforming immunosuppressive tumors into ones more responsive to immune intervention. This review provides a detailed overview of MDSCs in the TME and current strategies targeting these cells. Also the benefits of nanoparticle‐assisted drug delivery systems, including design flexibility, efficient drug loading, and protection against enzymatic degradation, are highlighted. It summarizes advances in nanomedicine targeting MDSCs, covering enhanced treatment efficacy, safety, and modulation of the TME, laying the groundwork for more potent cancer immunotherapy.
Radiotherapy Resistance of 3D Bioprinted Glioma via ITGA2/p‐AKT Signaling Pathway
Authors: Dongdong Liu, Haotian Tian, Huaixu Li, Jianyu Nie, Zhenyu Han, Guozhang Tang, Peng Gao, Hongwei Cheng, Xingliang Dai
Journal: Advanced Healthcare Materials (2024)

Due to the inherent radiation tolerance, patients who suffered from glioma frequently encounter tumor recurrence and malignant progression within the radiation target area, ultimately succumbing to treatment ineffectiveness. The precise mechanism underlying radiation tolerance remains elusive due to the dearth of in vitro models and the limitations associated with animal models. Therefore, a bioprinted glioma model is engineered, characterized the phenotypic traits in vitro, and the radiation tolerance compared to 2D ones when subjected to X-ray radiation is assessed. By comparing the differential gene expression profiles between the 2D and 3D glioma model, identify functional genes, and analyze distinctions in gene expression patterns. Results showed that 3D glioma models exhibited substantial alterations in the expression of genes associated with the stromal microenvironment, notably a significant increase in the radiation tolerance gene ITGA2 (integrin subunit A2). In 3D glioma models, the knockdown of ITGA2 via shRNA resulted in reduced radiation tolerance in glioma cells and concomitant inhibition of the p-AKT pathway. Overall, 3D bioprinted glioma model faithfully recapitulates the in vivo tumor microenvironment (TME) and exhibits enhanced resistance to radiation, mediated through the ITGA2/p-AKT pathway. This model represents a superior in vitro platform for investigating glioma radiotherapy tolerance.
Cancer‐Thylakoid Hybrid Membrane Camouflaged Thulium Oxide Nanoparticles with Oxygen Self‐Supply Capability for Tumor‐Homing Phototherapy
Authors: Yu‐Cheng Zuo, Cong‐Min Huo, Yu Chen, Peng‐Li Ding, Si‐Ye Tong, Wei Xue, Jing‐Yi Zhu
Journal: Advanced Healthcare Materials (2024)

Abstract Nanomaterials that generate reactive oxygen species (ROS) upon light irradiation have significant applications in various fields, including photodynamic therapy (PDT) that is widely recognized as a highly momentous strategy for the eradication of cancer cells. However, the ROS production rate of photosensitizers, as well as the tumor hypoxia environment, are two major challenges that restrict the widespread application of PDT. In this study, a cancer‐thylakoid hybrid membrane‐camouflaged thulium oxide nanoparticles (Tm 2 O 3 ) for tumor‐homing phototherapy through dual‐stage‐light‐guided ROS generation and oxygen self‐supply is developed. Tm 2 O 3 as a type II photosensitizer are viable for NIR‐stimulated ROS generation due to the unique energy levels, large absorption cross section, and long lifetime of the 3H4 state of Tm ions. The thylakoid membrane (TK) plays a catalase‐like role in converting hydrogen peroxide into oxygen and also acts as a natural photosensitizer that can generate lethal ROS through electron transfer when exposed to light. In addition, fluorescence dye DiR is embedded in the hybrid membrane for in vivo tracing as well as photothermal therapy. Results show that tumors in Tm 2 O 3 @TK‐M/DiR group are effectively ablated following dual‐stage‐light irradiation, highlighting the promising potential of rare‐earth element‐based type II photosensitizers in various applications.
Persistent Targeting DNA Nanocarrier Made of 3D Structural Unit Assembled from Only One Basic Multi‐Palindromic Oligonucleotide for Precise Gene Cancer Therapy
Authors: Jingting Wu, Xiaoqi Zheng, Wenqing Lin, Linhuan Chen, Zai‐Sheng Wu
Journal: Advanced Healthcare Materials (2024)

Abstract Construction of a simple, reconfigurable, and stimuli‐responsive DNA nanocarrier remains a technical challenge. In this contribution, by designing three palindromic fragments, a simplest four‐sticky end‐contained 3D structural unit (PS‐unit) made of two same DNA components is proposed. Via regulating the rotation angle of central longitudinal axis of PS‐unit, the oriented assembly of one‐component spherical architecture is accomplished with high efficiency. Introduction of an aptamer and sticky tail warehouse into one component creates a size‐change‐reversible targeted siRNA delivery nanovehicle. Volume swelling of 20 nm allows one carrier to load 1987 siPLK1s. Once entering cancer cells and responding to glutathione (GSH) stimuli, siPLK1s are almost 100% released and original size of nanovehicle is restored, inhibiting the expression of PLK1 protein and substantially suppressing tumor growth (superior to commercial transfection agents) in tumor‐bearing mice without systemic toxicity.
deMULTIplex2: robust sample demultiplexing for scRNA-seq
Authors: Qin Zhu, Daniel N. Conrad, Zev J. Gartner
Journal: Genome biology (2024)

Sample multiplexing enables pooled analysis during single-cell RNA sequencing workflows, thereby increasing throughput and reducing batch effects. A challenge for all multiplexing techniques is to link sample-specific barcodes with cell-specific barcodes, then demultiplex sample identity post-sequencing. However, existing demultiplexing tools fail under many real-world conditions where barcode cross-contamination is an issue. We therefore developed deMULTIplex2, an algorithm inspired by a mechanistic model of barcode cross-contamination. deMULTIplex2 employs generalized linear models and expectation-maximization to probabilistically determine the sample identity of each cell. Benchmarking reveals superior performance across various experimental conditions, particularly on large or noisy datasets with unbalanced sample compositions.
Author Correction: Health effects associated with exposure to secondhand smoke: a Burden of Proof study
Authors: Luisa S. Flor, Jason A. Anderson, Noah Ahmad, Aleksandr Aravkin, Sinclair Carr, Xiaochen Dai, Gabriela F. Gil, Simon I. Hay, Matthew J. Malloy, Susan A. McLaughlin, Erin C. Mullany, Christopher J. L. Murray, Erin M. O’Connell, Chukwuma Okereke, Reed J. D. Sorensen, Joanna Whisnant, Peng Zheng, Emmanuela Gakidou
Journal: Nature Medicine (2024)
Idiopathic Pulmonary Fibrosis: From Common Microscopy to Single-Cell Biology and Precision Medicine
Authors: Moisés Selman, Annie Pardo
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Idiopathic pulmonary fibrosis is a chronic, progressive, and usually fatal lung disease of unknown etiology and is included in the large, complex, and heterogeneous group of interstitial lung diseases (ILD). IPF is characterized by an aberrant activation of epithelial cells and fibroblasts and excessive accumulation of extracellular matrix, resulting in the progressive destruction of the lung architecture. Here we approach the fascinating historical evolution of our knowledge about this disorder from the past century, when most efforts were focused on ILD classification and terminology, until the current century, when the explosive progress in molecular genetics, epigenetics, and multiomics, as well as the development of complex computational tools, resulted in a huge advance in unveiling the pathogenic mechanisms of the disease. Recent advances in artificial intelligence, machine and deep learning, and artificial neural networks show promising results in identifying lung fibrotic patterns in high-resolution computed tomography or helping to create a tissue genomic classifier for specific diagnosis. Finally, incipient approaches to precision medicine are ongoing in the area of pharmacogenetics.
IL15 and IL21: Better When Membrane-Tethered Together on Antitumor T Cells
Authors: Ayana T. Ruffin, Megen C. Wittling, Anna C. Cole, Chrystal M. Paulos
Journal: Clinical Cancer Research (2024)

Summary Systemic administration of homeostatic γ-chain cytokines mediates antitumor responses in some patients treated with adoptive immunotherapy. Yet many patients experience toxic side effects. New work presented herein suggests these limitations can be overcome by membrane-tethering IL15 and IL21 to T-cell products. This finding has major implications in advancing medicine. See related article by Nguyen et al., p. 1555
Anti-S-layer monoclonal antibodies impact <i>Clostridioides difficile</i> physiology
Authors: Lise Hunault, Emile Auria, Patrick England, Julien Deschamps, Romain Briandet, Vanessa Kremer, Bruno Iannascoli, Léo Vidal-Maison, Chunguang Guo, Lynn Macdonald, Séverine Péchiné, Cécile Denève-Larrazet, Bruno Dupuy, Guy Gorochov, Pierre Bruhns, Delphine Sterlin
Journal: Gut Microbes (2024)

Clostridioides difficile (C. difficile), a gram-positive anaerobic and spore-forming bacterium, is the leading cause of nosocomial antibiotic-associated diarrhea in adults which is characterized by high levels of recurrence and mortality. Surface (S)-layer Protein A (SlpA), the most abundantly expressed protein on the bacterial surface, plays a crucial role in the early stages of infection although the nature of its involvement in C. difficile physiology is yet to be fully understood. Anti-S-layer antibodies have been identified in the sera of convalescent patients and have been correlated with improved outcomes of C. difficile infection (CDI). However, the precise mechanisms by which anti-S-layer antibodies confer protection to the host remain unknown. In this study, we report the first monoclonal antibodies (mAbs) targeting the S-layer of reference strain 630. Characterization of these mAbs unraveled important roles for the S-layer protein in growth, toxin secretion, and biofilm formation by C. difficile, with differential and even opposite effects of various anti-SlpA mAbs on these functions. Moreover, one anti-SlpA mAb impaired C. difficile growth and conferred sensitivity to lysozyme-induced lysis. The results of this study show that anti-S-layer antibody responses can be beneficial or harmful for the course of CDI and provide important insights for the development of adequate S-layer-targeting therapeutics.