Loss of pulmonary tissue protection and neutrophil microbicidal defects promote severe infection during influenza A virus infection.

Invasive pulmonary aspergillosis (IPA) is a severe fungal disease caused by () that may spread hematogenously to extrapulmonary organs. IPA is typically associated with a broad spectrum of immunocompromised conditions and constitutes a high mortality rate. While the association of influenza as a risk for secondary bacterial infections is well appreciated, emerging evidence indicates that influenza-hospitalized patients demonstrate increased susceptibility to severe aspergillosis infection.

Spatial profiling of chromatin accessibility reveals alteration of glial cells in Alzheimer's disease mouse brain.

Abnormal epigenetic modifications, including altered chromatin accessibility, have been implicated in the development and progression of Alzheimer's disease (AD). In this study, we applied spatially resolved chromatin accessibility profiling by performing spatial assay for transposase-accessible chromatin using sequencing (ATAC-seq) to analyze brain tissues from 5xFAD AD model and C57BL/6J control mice. Our analysis identified seven major cell types across 11 brain regions and further characterized glial subtypes microglia and astrocytes revealing subtype-specific chromatin accessibility changes in 5xFAD mice relative to controls.

Genetic modulation of protein expression in rat brain.

Genetic variations in protein expression are implicated in a broad spectrum of common diseases and complex traits but remain less explored compared to mRNA and classical phenotypes. This study systematically analyzed brain proteomes in a rat family using tandem mass tag (TMT)-based quantitative mass spectrometry. We quantified 8,119 proteins across two parental strains (SHR/Olalpcv and BN-Lx/Cub) and 29 HXB/BXH recombinant inbred (RI) strains, identifying 597 proteins with differential expression and 464 proteins linked to -acting quantitative trait loci (pQTLs).

Immunological Signatures for Early Detection of Human Head and Neck Squamous Cell Carcinoma through RNA Transcriptome Analysis of Blood Platelets.

Although there has been a reduction in head and neck squamous cell carcinoma occurrence, it continues to be a serious global health concern. The lack of precise early diagnostic biomarkers and postponed diagnosis in the later stages are notable constraints that contribute to poor survival rates and emphasize the need for innovative diagnostic methods. In this study, we employed machine learning alongside weighted gene co-expression network analysis (WGCNA) and network biology to investigate the gene expression patterns of blood platelets, identifying transcriptomic markers for HNSCC diagnosis.

Mitochondrial Oxidative Stress Regulates FOXP3+ T-Cell Activity and CD4-Mediated Inflammation in Older Adults with Frailty.

In healthy older adults, the immune system generally preserves its response and contributes to a long, healthy lifespan. However, rapid deterioration in immune regulation can lead to chronic inflammation, termed inflammaging, which accelerates pathological aging and diminishes the quality of life in older adults with frailty. A significant limitation in current aging research is the predominant focus on comparisons between young and older populations, often overlooking the differences between healthy older adults and those experiencing pathological aging.

Age-related dysregulation of intestinal epithelium fucosylation is linked to an increased risk of colon cancer.

Colon cancer affects people of all ages. However, its frequency, as well as the related morbidity and mortality, are high among older adults. The complex physiological changes in the aging gut substantially limit the development of cancer therapies.

The chemokine receptor CXCR3 promotes CD8 T cell-dependent lung pathology during influenza pathogenesis.

The dual role of CD8 T cells in influenza control and lung pathology is increasingly appreciated. To explore whether protective and pathological functions can be linked to specific subsets, we dissected CD8 T responses in influenza-infected murine lungs. Our single-cell RNA-sequencing (scRNA-seq) analysis revealed notable diversity in CD8 T subpopulations during peak viral load and infection-resolved state.

IL-17RA promotes pathologic epithelial inflammation in a mouse model of upper respiratory influenza infection.

The upper respiratory tract (nasopharynx or NP) is the first site of influenza replication, allowing the virus to disseminate to the lower respiratory tract or promoting community transmission. The host response in the NP regulates an intricate balance between viral control and tissue pathology. The hyper-inflammatory responses promote epithelial injury, allowing for increased viral dissemination and susceptibility to secondary bacterial infections.

Proteomics Profiling Reveals Regulation of Immune Response to Salmonella enterica Serovar Typhimurium Infection in Mice.

Regulation of the immune response to Salmonella enterica serovar Typhimurium ( Typhimurium) infection is a complex process, influenced by the interaction between genetic and environmental factors. Different inbred strains of mice exhibit distinct levels of resistance to Typhimurium infection, ranging from susceptible (e.g.

Cellular Heterogeneity and Molecular Reprogramming of the Host Response during Influenza Acute Lung Injury.

An exuberant host response contributes to influenza A virus (IAV) (or influenza)-mediated lung injury. However, despite significant information on the host response to IAV, the cellular framework and molecular interactions that dictate the development of acute injury in IAV-infected lungs remain incompletely understood. We performed an unbiased single-cell RNA sequencing (scRNAseq) analysis to examine the cellular heterogeneity and regulation of host responses in the IAV model of acute lung injury.

Promoting autophagy to mitigate coronavirus disease pathology in the elderly.

In this commentary, we highlight autophagy's important function, while identifying potential therapeutic targets for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the elderly. Autophagy's decline in the elderly causes increased cell senescence and a dysregulated immune system. As this demographic often faces decreased vaccine-provided immunity, coronavirus disease 2019 treatments must be developed.

Interferon-γ promotes monocyte-mediated lung injury during influenza infection.

Influenza A virus (IAV) infection triggers an exuberant host response that promotes acute lung injury. However, the host response factors that promote the development of a pathologic inflammatory response to IAV remain incompletely understood. In this study, we identify an interferon-γ (IFN-γ)-regulated subset of monocytes, CCR2 monocytes, as a driver of lung damage during IAV infection.

Performance enhancement of solar photovoltaic (PV) module using a novel flat plate (NFP) glass cover by reducing the effect of bird dropping (BD) settlement.

A massive bird dropping (BD) deposition on the common rectangular flat plate (RFP) of photovoltaic (PV) module is a matter of great concern in Western Rajasthan (WR) that diminish the overall energy production capacity of the system remarkably. In this research article, a prototype novel flat plate (NFP) design of a front glass cover of PV module is proposed to prevent the impact of BD settlement by the restriction of bird's sitting/movement on the front glass cover. In this regard, the performance analysis of PV module with common RFP and newly designed NFP glass covers has been assessed at the different inclination β° (0-90).

An Account of Immune Senescence in the Clinical Pathophysiology of COVID-19 Infection in Aging.

Worldwide COVID-19 infection poses an enormous risk to public health and an alarming global socioeconomic burden. The impact of the COVID-19 pandemic on individuals with underlying health conditions as well as on the elderly population is extensive and effective strategies are needed to understand the mechanism behind it. Cellular senescence defines as an irreversible cell cycle arrest due to DNA damage leading to accumulation of senescent cells in the elderly population and may result in worsening of COVID-19 mediated increased mortality.

Deficiency of Microglial Autophagy Increases the Density of Oligodendrocytes and Susceptibility to Severe Forms of Seizures.

Excessive activation of mTOR in microglia impairs CNS homeostasis and causes severe epilepsy. Autophagy constitutes an important part of mTOR signaling. The contribution of microglial autophagy to CNS homeostasis and epilepsy remains to be determined.

Microglial mTOR is Neuronal Protective and Antiepileptogenic in the Pilocarpine Model of Temporal Lobe Epilepsy.

Excessive activation of mammalian target of rapamycin (mTOR) signaling is epileptogenic in genetic epilepsy. However, the exact role of microglial mTOR in acquired epilepsy remains to be clarified. In the present study, we found that mTOR is strongly activated in microglia following excitatory injury elicited by status epilepticus.

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin.

Significant studies have been carried out to understand effective management of intestinal fibrosis. However, the lack of better knowledge of fibrosis has hindered the development of a preventative drug. Primarily, finding a suitable animal model is challenging in understanding the mechanism of Crohn's-associated intestinal fibrosis pathology.

Targeting Microglia Using Cx3cr1-Cre Lines: Revisiting the Specificity.

Microglia play a pivotal role in maintaining homeostasis of the CNS. There is growing interest in understanding how microglia influence normal brain function and disease progression. Several microglia-specific Cx3cr1-Cre lines have been developed and have become indispensable tools in many investigations of microglial function.

Induction of autophagy in Cx3cr1 mononuclear cells limits IL-23/IL-22 axis-mediated intestinal fibrosis.

Intestinal fibrosis is an excessive proliferation of myofibroblasts and deposition of collagen, a condition frequently seen in Crohn's disease (CD). The mechanism underlying myofibroblast hyper-proliferation in CD needs to be better understood. In this report, we found that mTOR inhibitor rapamycin or mTOR deletion in CX3Cr1 mononuclear phagocytes inhibits expression of interleukin (IL)-23, accompanied by reduced intestinal production of IL-22 and ameliorated fibrosis in the TNBS-induced fibrosis mouse model.

Noninflammatory Changes of Microglia Are Sufficient to Cause Epilepsy.

Microglia are well known to play a critical role in maintaining brain homeostasis. However, their role in epileptogenesis has yet to be determined. Here, we demonstrate that elevated mTOR signaling in mouse microglia leads to phenotypic changes, including an amoeboid-like morphology, increased proliferation, and robust phagocytosis activity, but without a significant induction of pro-inflammatory cytokines.

Attenuation of in vitro host-pathogen interactions in quinolone-resistant Salmonella Typhi mutants.

Objectives: The relationship between quinolone resistance acquisition and invasion impairment has been studied in some Salmonella enterica serovars. However, little information has been reported regarding the invasive human-restricted pathogen Salmonella Typhi. The aim of this study was to investigate the molecular mechanisms of quinolone resistance acquisition and its impact on virulence in this serovar.

Recognition of profilin by Toll-like receptor 12 is critical for host resistance to Toxoplasma gondii.

Toll-like receptor 11 (TLR11) recognizes T. gondii profilin (TgPRF) and is required for interleukin-12 production and induction of immune responses that limit cyst burden in Toxoplasma gondii-infected mice. However, TLR11 only modestly affects survival of T.