cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.57770/k9hzhw
title: Ly6C+ Monocytes and Kupffer Cells Orchestrate Liver Immune Responses Against Hepatitis B Virus in Mice.

description: To understand the mechanism(s) of age-dependent outcomes of hepatitis B virus (HBV) infection in humans, we previously established an age-related HBV mouse model in which 6-week-old (N6W) C3H/HeN mice exhibited virus tolerance whereas 12-week-old (N12W) counterparts presented virus clearance. By investigating the hepatic myeloid cell dynamics in mice of these two ages, we aim to identify factors associated with HBV clearance. C3H/HeN mice were transfected with an HBV plasmid by hydrodynamic injection. Serum HBV markers were monitored weekly. Hepatic leucocyte populations and their cytokine/chemokine productions were examined at baseline, day 3 (D3), day 7 (D7), and day 14 after injection. C-C chemokine receptor type 2 (CCR2) antagonist and clodronate (CLD) were respectively administered to N12W and N6W mice to study the roles of lymphocyte antigen 6 complex, locus C (Ly6C)+ monocytes and Kupffer cells (KCs) in viral clearance. N12W mice had a significantly higher number of TNF-α-secreting Ly6C+ monocytes and fewer IL-10-secreting KCs at D3 in the liver than their younger N6W counterparts after HBV transfection. In addition, the elevated number of interferon-γ+ TNF-α+ CD8+ T cells at D7 was only seen in the older cohort. The enhanced Ly6C+ monocyte induction in N12W mice resulted from elevated C-C motif chemokine ligand 2 (CCL2) secretion by hepatocytes. CCR2 antagonist administration hampered Ly6C+ monocyte recruitment and degree of KC reduction and delayed HBV clearance in N12W animals. Depletion of KCs by CLD liposomes enhanced Ly6C+ monocyte recruitment and accelerated HBV clearance in N6W mice. Conclusions: Ly6C+ monocytes and KCs may, respectively, represent the resistance and tolerance arms of host defenses. These two cell types play an essential role in determining HBV clearance/tolerance. Manipulation of these cells is a promising avenue for immunotherapy of HBV-related liver diseases.
DOI: 10.57770/gi2psc
title: Long-Read Genome Sequencing of Abscondita cerata (Coleoptera: Lampyridae), the Endemic Firefly of Taiwan.

description: Abscondita cerata is the most abundant and widely distributed endemic firefly species in Taiwan and is considered a key environmental and ecological indicator organism. In this study, we report the first longread genome sequencing of Abs. cerata sequenced by Nanopore technology. The draft genome size, 967 Mb, was measured through a hybrid approach that consisted of assembling using 11.25-Gb Nanopore long reads and polishing using 9.47-Gb BGI PE100 short reads. The drafted genome was assembled into 4,855 contigs, with the N50 reaching 325.269 kb length. The assembled genome was predicted to possess 55,206 protein-coding genes, of which 20,862 (37.78%) were functionally annotated with public databases. 47.11% of the genome sequences consisted of repeat elements; among them DNA transposons accounted for the largest proportion (26.79%). A BUSCO (Benchmarking Universal Single Copy Orthologs) evaluation demonstrated that the genome and gene completeness were 84.8% and 79%, respectively. The phylogeny constructed using 1,792 single copy genes was consistent with previous studies. The comparative transcriptome between adult male head and lantern tissues revealed (1) the vision of Abs. cerata is primarily UV-sensitive to environmental twilight, which determines when it begins its nocturnal activity, (2) the major expressed OR56d receptor may be correlated to suitable humidity sensing, and (3) Luc1-type luciferase is responsible for Abs. cerata’s luminescent spectrum.
DOI: 10.15468/dl.fu6pm3
title: Occurrence Download

description: A dataset containing 16892 species occurrences available in GBIF matching the query:
{
 "and" : [
 "DatasetKey is one of (Invasive species - American bullfrog (Lithobates catesbeianus) in Flanders, Belgium, Invasive species - American bullfrog (Lithobates catesbeianus) in Flanders, Belgium (post 2018))",
 "TaxonKey is Lithobates catesbeianus (Shaw, 1802)"
 ]
}

 The dataset includes 16892 records from 2 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0006146-240626123714530/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.57770/q0rjdf
title: Isolation of murine hepatic myeloid cells with high yield and purity using immunomagnetic beads for subset analysis.

description: There are numerous established techniques for isolating hepatic myeloid cells; however, preserving their phenotypic and functional characteristics can be challenging. We present a straightforward and efficient method to isolate hepatic myeloid cells, including Kupffer cells and lymphocyte antigen 6 complex, locus C+ (Ly6C+) monocytes/macrophages. The procedure involves perfusion of the liver with collagenase and purification with immunomagnetic particles. This protocol ensures the isolation of large quantities of purified, viable, and functional cells without influencing their physiological characteristics. For complete details on the use and execution of this protocol, please refer to Wu et al. (2019).
DOI: 10.57770/qzvksl
title: Direct effects of alcohol on gut-epithelial barrier: Unraveling the disruption of physical and chemical barrier of the gut-epithelial barrier that compromises the host-microbiota interface upon alcohol exposure.

description: The development of alcohol-associated diseases is multifactorial, mechanism of which involves metabolic alteration, dysregulated immune response, and a perturbed intestinal host-environment interface. Emerging evidence has pinpointed the critical role of the intestinal host–microbiota interaction in alcohol-induced injuries, suggesting its contribution to disease initiation and development. To maintain homeostasis in the gut, the intestinal mucosa serves as the first-line defense against exogenous factors in the gastrointestinal tract, including dietary contents and the commensal microbiota. The gut-epithelial barrier comprises a physical barrier lined with a single layer of intestinal epithelial cells and a chemical barrier with mucus trapping host regulatory factors and gut commensal bacteria. In this article, we review recent studies pertaining to the disrupted gut-epithelial barrier upon alcohol exposure and examine how alcohol and its metabolism can affect the regulatory ability of intestinal epithelium.
DOI: 10.57770/ysslpc
title: Exploring in vivo combinatorial chemo-immunotherapy: Addressing p97 suppression and immune reinvigoration in pancreatic cancer with tumor microenvironment-responsive nanoformulation.

description: Pancreatic ductal adenocarcinoma (PDAC) has an extremely devastating nature with poor prognosis and increasing incidence, making it a formidable challenge in the global fight against cancer-related mortality. In this innovative preclinical investigation, the VCP/p97 inhibitor CB-5083 (CB), miR-142, a PD-L1 inhibitor, and immunoadjuvant resiquimod (R848; R) were synergistically encapsulated in solid lipid nanoparticles (SLNs). These SLNs demonstrated features of peptides targeting PD-L1, EGFR, and the endoplasmic reticulum, enclosed in a pH-responsive polyglutamic (PGA)-polyethylene glycol (PEG) shell. The homogeneous size and zeta potential of the nanoparticles were stable for 28 days at 4°C. The study substantiated the concurrent modulation of key pathways by the CB, miR, and R-loaded nanoformulation, prominently affecting VCP/Bip/ATF6, PD-L1/TGF-β/IL-4, −8, −10, and TNF-α/IFN-γ/IL-1, −12/GM-CSF/CCL4 pathways. This adaptable nanoformulation induced durable antitumor immune responses and inhibited Panc-02 tumor growth by enhancing T cell infiltration, dendritic cell maturation, and suppressing Tregs and TAMs in mice bearing Panc-02 tumors. Furthermore, tissue distribution studies, biochemical assays, and histological examinations highlighted enhanced safety with PGA and peptide-modified nanoformulations for CB, miR, and/or R in Panc-02-bearing mice. This versatile nanoformulation allows tailored adjustment of the tumor microenvironment, thereby optimizing the localized delivery of combined therapy. These compelling findings advocate the potential development of a pH-sensitive, three-in-one PGA-PEG nanoformulation that combines a VCP inhibitor, a PD-L1 inhibitor, and an immunoadjuvant for cancer treatment via combinatorial chemo-immunotherapy.
DOI: 10.15468/dl.aqj7n8
title: Occurrence Download

description: A dataset containing 140500 species occurrences available in GBIF matching the query:
{
 "and" : [
 "TaxonKey is Ondatra zibethicus (Linnaeus, 1766)",
 "DatasetKey is one of (VMM - Rat control occurrences in Flanders, Belgium, Muskrat captures in Flanders, Belgium, MICA - Muskrat occurrences collected by RATO in East Flanders, Belgium, MICA - Muskrat occurrences collected by VMM in Flanders, Belgium, RATO - daily operations commissioned by the province East Flanders, Belgium)"
 ]
}

 The dataset includes 140500 records from 5 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0006140-240626123714530/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.57770/boku2r
title: Age-dependent effects of acute stress on the behavior, blood parameters, immunity, and enteric nerves of mice.

description: The impact of stress on mental and digestive health has been extensively studied, with chronic stress being associated with various disorders. However, age-related differences in the response to acute stress, both behaviorally and physiologically, remain poorly understood. Therefore, this study aimed to develop a model to detect transient stress in mice of different ages. The stressor employed in our experiments was a restraint stress procedure, where mice were subjected to brief periods of immobilization to induce an acute stress response. Male C3H/HeN mice aged 3, 6, 12, and 30 weeks were subjected to acute restrain stress (ARS) by being placed in a 50 ml conical centrifuge tube for 15 min. Subsequently, their behavior, organ tissues, hematological parameters, cortisol concentration, and immune responses were assessed. Following ARS, the increased in time and entries into the center by the 12-week-old mice following stress. In comparison to mice of other ages, those aged 6 weeks demonstrated notable elevations in erythrocytes, platelets, hemoglobin, and hematocrit, all of which were influenced by the time-dependent changes and the recovery process of ARS. Blood corticosterone levels were substantially elevated in all age groups after ARS. Furthermore, ARS induced a notable increase in leukocytes, basophils, residential macrophages, and CD4+ T cells in all age groups except for 3-week-old mice. However, the number of monocyte-derived macrophages and CD8+ T cells did not change significantly. Additionally, mice aged 3 and 6 weeks demonstrated an increase in GFAP+ cells following ARS, whereas NeuN+ cells decreased across all ages. These results suggest that ARS has varying effects on the behavior, cortisol concentration, and quantity of blood cells as well as hepatic immune cells in mice of different ages. These age-dependent responses shed light on the complex interplay between stress and physiological systems and contribute to the broader understanding of stress-related diseases.
DOI: 10.57770/21zg39
title: Antagonism Between Gut Ruminococcus gnavus and Akkermansia muciniphila Modulates the Progression of Chronic Hepatitis B.

description: Background & Aims A long immune-tolerant (IT) phase lasting for decades and delayed HBeAg seroconversion (HBe-SC) in patients with chronic hepatitis B (CHB) increase the risk of liver diseases. Early entry into the immune-active (IA) phase and HBe-SC confers a favorable clinical outcome with an unknown mechanism. We aimed to identify factor(s) triggering IA entry and HBe-SC in the natural history of CHB. Methods To study the relevance of gut microbiota evolution in the risk of CHB activity, fecal samples were collected from CHB patients (n = 102) in different disease phases. A hepatitis B virus (HBV)-hydrodynamic injection (HDI) mouse model was therefore established in several mouse strains and germ-free mice, and multiplatform metabolomic and bacteriologic assays were performed. Results Ruminococcus gnavus was the most abundant species in CHB patients in the IT phase, whereas Akkermansia muciniphila was predominantly enriched in IA patients and associated with alanine aminotransferase flares, HBeAg loss, and early HBe-SC. HBV-HDI mouse models recapitulated this human finding. Increased cholesterol-to-bile acids (BAs) metabolism was found in IT patients because R gnavus encodes bile salt hydrolase to deconjugate primary BAs and augment BAs total pool for facilitating HBV persistence and prolonging the IT course. A muciniphila counteracted this activity through the direct removal of cholesterol. The secretome metabolites of A muciniphila, which contained small molecules structurally similar to apigenin, lovastatin, ribavirin, etc., inhibited the growth and the function of R gnavus to allow HBV elimination. Conclusions R gnavus and A muciniphila play opposite roles in HBV infection. A muciniphila metabolites, which benefit the elimination of HBV, may contribute to future anti-HBV strategies.
DOI: 10.57770/2ar6nr
title: Macrophages and Myeloid-derived suppressor cells in the Tumor Microenvironment of Hepatocellular Carcinoma: Insights into Molecular Pathways, Immunometabolic Processes, and Implications for Immunotherapy.

description: Hepatocellular carcinoma (HCC) is a major global health concern, and understanding the complex interplay of immune cells within the tumor microenvironment is crucial. This review explores the roles of myeloid-derived suppressor cells (MDSCs) and macrophages in HCC, focusing on their molecular pathways, immunometabolic processes, and implications for immunotherapy. We begin by elucidating the origin, expansion, and immunosuppressive mechanisms of MDSCs, emphasizing the importance of molecular pathways and immunometabolism in regulating their functions. In parallel, we delve into the dual nature of tumor-associated macrophages (TAMs) and discuss the molecular and metabolic cues governing their plasticity. Tumor metabolism is a central theme, with a comprehensive overview of altered metabolic processes in cancer cells and their impact on immune cells in the tumor microenvironment. We examine the metabolic crosstalk between tumor cells, MDSCs, and macrophages, shedding light on how tumor metabolism contributes to immune evasion. Furthermore, we discuss the challenges and limitations faced in the clinical application of immunotherapy in HCC. In conclusion, this review highlights the intricate web of molecular pathways and immunometabolic processes shaping the functions of MDSCs and macrophages in HCC. Understanding these dynamics is essential for the innovative immunotherapeutic interventions in HCC, improving outcomes of this devastating disease.
DOI: 10.57770/ajc52a
title: Gut microbiota in the innate immunity against hepatitis B virus-implication in age-dependent HBV clearance.

description: Hepatitis B virus (HBV) chronically infects 257 million people and is one of the most important liver diseases worldwide. A unique feature of HBV infection in humans is that viral clearance heavily depends on the age at exposure. Recent studies demonstrated that the virus takes advantage of immature innate immunity, especially hepatic macrophages, and not-yet-stabilized gut microbiota in early life to establish a chronic infection. The liver contains resident and infiltrating myeloid cells involved in immune responses to pathogens. They influence both innate and adaptive sectors of the immune system and their interplay with HBV has only been noticed recently. Here, we discuss how interactions between gut microbiota and hepatic macrophages influence the outcomes of HBV infection. Understanding the underlying mechanism would pave the way for the treatment of chronic HBV infection.
DOI: 10.57770/p7zwbm
title: Robust induction of TRMs by combinatorial nanoshells confers cross-strain sterilizing immunity against lethal influenza viruses.

description: Antigen-specific lung-resident memory T cells (TRMs) constitute the first line of defense that mediates rapid protection against respiratory pathogens and inspires novel vaccine designs against infectious pandemic threats, yet effective means of inducing TRMs, particularly via non-viral vectors, remain challenging. Here, we demonstrate safe and potent induction of lung-resident TRMs using a biodegradable polymeric nanoshell that co-encapsulates antigenic peptides and TLR9 agonist CpG-oligodeoxynucleotide (CpG-ODN) in a virus-mimicking structure. Through subcutaneous priming and intranasal boosting, the combinatorial nanoshell vaccine elicits prominent lung-resident CD4+ and CD8+ T cells that surprisingly show better durability than live viral infections. In particular, nanoshells containing CpG-ODN and a pair of conserved class I and II major histocompatibility complex-restricted influenza nucleoprotein-derived antigenic peptides are demonstrated to induce near-sterilizing immunity against lethal infections with influenza A viruses of different strains and subtypes in mice, resulting in rapid elimination of replicating viruses. We further examine the pulmonary transport dynamic and optimal composition of the nanoshell vaccine conducive for robust TRM induction as well as the benefit of subcutaneous priming on TRM replenishment. The study presents a practical vaccination strategy for inducing protective TRM-mediated immunity, offering a compelling platform and critical insights in the ongoing quest toward a broadly protective vaccine against universal influenza as well as other respiratory pathogens.
DOI: 10.57770/okqtjk
title: HBV X protein-based therapeutic vaccine accelerates viral antigen clearance by mobilizing monocyte infiltration into the liver in HBV carrier mice.

description: Background: Hepatitis B virus (HBV) persistently infected about 250 million people worldwide, and a curative treatment remains an unmet medical need. Among many approaches to treat chronic hepatitis B (CHB), therapeutic vaccines have been developed for two decades, but none have yielded promising results in clinical trials. Therefore, dissection of HBV clearance mechanisms during therapeutic vaccination in appropriate models, which could give rise to new curative therapies, is urgently needed. Growing evidence indicates that prolonged and intensive exposure of antigen-specific T cells to viral antigens is a major cause of T cell exhaustion, and decreases anti-HBV immunity efficacy of therapeutic vaccination. HBV X protein (HBx) is expressed at low levels, and the understanding of its immunogenicity and potential in therapeutic CHB vaccines is limited. Methods: HBV genome sequences from CHB patients were cloned into a pAAV plasmid backbone and transfected into immunocompetent mouse hepatocytes through hydrodynamic injection. Mice carrying &gt; 500 IU/mL serum HBV surface antigen (HBs) for more than 4 weeks were considered HBV carriers mimicking human CHB and received 3 doses of weekly HBx vaccine by subcutaneous immunization. Serum HBV clearance was evaluated by monitoring serum HBs and HBV-DNA titers. Residual HBV in the liver was evaluated by western blotting for HBV core antigen. The splenic antigen-specific T cell response was quantified by a 15-mer overlapping peptide-stimulated interferon-γ enzyme-linked immunospot assay. Blood and hepatic immune cells were quantified by flow cytometric analysis. Results: Our HBx-based vaccine induced systemic HBx-specific CD4+ and CD8+ T cell responses in HBV carrier mice and demonstrated significant HBs and HBV-DNA elimination. The protective effect persisted for at least 30 days without additional booster immunization. Different infiltrating myeloid cell subsets, each with distinctive roles during immune-mediated HBV clearance, were found in the liver of vaccinated mice. During vaccine therapy, inflammatory monocyte depletion resulted in sustained HBV clearance inhibition, whereas phagocytic monocyte-derived macrophage and Kupffer cell elimination resulted in only transient inhibition of vaccine-induced HBV clearance. Conclusions: We report the potential role of HBx as a major immunogen in an HBV therapeutic vaccine and the significance of a liver-infiltrating monocyte subset during hepatic viral clearance.
DOI: 10.57770/5coim6
title: Gut microbial transcytosis induced by tumor necrosis factor-like 1A-dependent activation of a myosin light chain kinase splice variant contributes to IBD.

description: nflammatory bowel disease [IBD] is characterised by abnormal host-microbe interactions. Proinflammatory cytokine IFNγ and a novel tumour necrosis factor [TNF] superfamily member, TL1A, have been implicated in epithelial barrier dysfunction. The divergent regulatory mechanisms of transcellular versus paracellular hyperpermeability remain poorly understood. Intestinal epithelia express two splice variants of long myosin light chain kinase [MLCK], of which the full-length MLCK1 differ from the shorter isoform MLCK2 by an Src kinase phosphorylation site. The aim of this study was to investigate the roles of MLCK splice variants in gut barrier defects under proinflammatory stress. Methods and Results Upregulated expression of TL1A, IFNγ, and two MLCK variants was observed in human IBD biopsy specimens. The presence of intraepithelial bacteria preceded tight junction [TJ] damage in dextran sodium sulphate-treated and TL1A-transgenic mouse models. Lack of barrier defects was observed in long MLCK[-/-] mice. TL1A induced MLCK-dependent terminal web [TW] contraction, brush border fanning, and transepithelial bacterial internalisation. The bacterial taxa identified in the inflamed colonocytes included Escherichia, Enterococcus, Staphylococcus, and Lactobacillus. Recombinant TL1A and IFNγ at low doses induced PI3K/Akt/MLCK2-dependent bacterial endocytosis, whereas high-dose IFNγ caused TJ opening via the iNOS/Src/MLCK1 axis. Bacterial internalisation was recapitulated in MLCK-knockout cells individually expressing MLCK2 but not MLCK1. Immunostaining showed different subcellular sites of phosphorylated MLC localised to the TJ and TW in the MLCK1- and MLCK2-expressing cells, respectively. Conclusions Proinflammatory cytokines induced bacterial influx through transcellular and paracellular routes via divergent pathways orchestrated by distinct MLCK isoforms. Bacterial transcytosis induced by TL1A may be an alternative route causing symptom flares in IBD.
DOI: 10.57770/bb6bdu
title: Hydrodynamic HBV transfection in mouse models.

description: The method of hydrodynamic delivery was used to establish a mouse model of hepatitis B virus persistence by transfecting hepatocytes in vivo with HBV genome expressing viral antigens and replicative intermediates, producing viral particles. Using the hydrodynamic transfection method, we demonstrated that host genetics, age, and their interaction are crucial in generating robust, diverse immune responses against HBV. We took advantage of an established HBV-persistence mouse model, by injecting cloned HBV DNA through the tail vein in appropriate, immune-competent mouse strains, to investigate the detailed immune responses against HBV. Germ-free animals with hydrodynamic HBV plasmid DNA injection provide an invaluable experimental tool for immunologic role of the gut microbiota in chronic HBV infection, and a direct role for the microbiota in disease development was demonstrated by the use of germ-free mice with HDI. This protocol has been previously shown in Hepatitis B Virus: Methods and Protocols-Methods in Molecular Biology.