Chitosan polyplexes for targeted gene delivery: From mechanisms to clinical applications.

As a diverse natural polymer called Chitosan, it created ground-breaking advancements in nucleic acid therapeutic delivery techniques for handling essential DNA and RNA delivery hurdles. The article investigates how nucleic acids form stable polyplexes with chitosan through electrostatic bonds, as well as explores their chemical and biological properties. The review explores how molecular weight, combined with the degree of deacetylation, combined with advanced functionalization strategies, help enhance delivery results.

Ethanol consumption aggravates amyloid pathology and neuroinflammation in Alzheimer's disease associated with inflammasome activation and ASC speck propagation.

Background: Alcohol use disorder (AUD) has been associated with Alzheimer's disease (AD) and dementia, yet the underlying mechanisms and specific role of ethanol in AD progression remain poorly understood. Neuroinflammation has emerged as a key contributor to both AD pathogenesis and ethanol-induced brain damage. Activation of innate immune cells and signaling pathways, in particular NLRP3 inflammasome, plays a pivotal role in both AD and ethanol-induced inflammation.

P-selectin and E-selectin: Key macromolecules in thrombus formation and resolution.

Globally, deep vein thrombosis (DVT) is one of the major preventable causes of mortality and morbidity. Due to the paucity of objective clinical examination findings and non-specific subjective complaints, optimal modalities for the diagnosis of DVT remain unclear. Two adhesion molecules that are engaged in thrombus formation and inflammation, P- and E-selectins, have shown a potential to serve as excellent biomarkers for the early detection of DVT.

Genomic crosstalk between carbachol, a muscarinic receptor agonist, and the long-acting β-adrenoceptor agonist, indacaterol, in human airway epithelial cells.

Many patients with chronic obstructive pulmonary disease are susceptible to recurrent exacerbations. In this study, we hypothesized that endogenous acetylcholine (ACh) may act as a proinflammatory mediator because long-acting muscarinic receptor antagonists protect against exacerbations, which have an inflammatory basis. This possibility was explored by determining if carbachol (CCh), a stable ACh analog, was a genomic stimulus in BEAS-2B bronchial epithelial cells.

Gasdermin D deletion prevents liver injury and exacerbates extrahepatic damage in a murine model of alcohol-induced ACLF.

Background: Gasdermin D (GSDM-D), a key executor of pyroptosis, is increased in various liver diseases and contributes to disease progression. Alcohol induces inflammasome activation and cell death, which are both linked to GSDM-D activation. However, its role in alcohol-induced acute-on-chronic liver failure (ACLF) remains unclear.

A Novel Multi-organ Male Model of Alcohol-induced Acute-on-chronic Liver Failure Reveals NET-mediated Hepatocellular Death, Which is Prevented by RIPK3 Inhibition.

Background & Aims: Alcohol abuse is the most frequent precipitating factor of acute-on-chronic liver failure (ACLF). We aimed at developing an alcohol-induced ACLF model and dissecting its underlying molecular mechanisms.

Methods: ACLF was triggered by a single alcohol binge (5 g/kg) in a bile duct ligation (BDL) liver fibrosis murine model.

IRF3 regulates neuroinflammatory responses and the expression of genes associated with Alzheimer's disease.

The pathological role of interferon signaling is emerging in neuroinflammatory disorders, yet, the specific role of Interferon Regulatory Factor 3 (IRF3) in neuroinflammation remains poorly understood. Here, we show that global IRF3 deficiency delays TLR4-mediated signaling in microglia and attenuates the hallmark features of LPS-induced inflammation such as cytokine release, microglial reactivity, astrocyte activation, myeloid cell infiltration, and inflammasome activation. Moreover, expression of a constitutively active IRF3 (S388D/S390D: IRF3-2D) in microglia induces a transcriptional program reminiscent of the Activated Response Microglia and the expression of genes associated with Alzheimer's disease, notably apolipoprotein-e.

Modeling and Performance Analysis of LBT-Based RF-Powered NR-U Network for IoT.

Energy harvesting combined with spectrum sharing offers a promising solution to the growing demand for spectrum while keeping energy costs low. New Radio Unlicensed (NR-U) technology enables telecom operators to utilize unlicensed spectrum in addition to the licensed spectrum already in use. Along with this, the energy demands for the Internet of Things (IoT) can be met through energy harvesting.

Comparison of the Genomic Activity of an EP-Receptor and β-Adrenoceptor Agonist in BEAS-2B Human Bronchial Epithelial Cells: In Search of Compartmentalized, cAMP-Dependent Gene Expression.

It has been proposed that inhaled E-prostanoid 4 (EP)-receptor agonists could represent a new class of bronchodilators for the treatment of asthma that are as effective as -adrenoceptor agonists. However, the genomic impact of such drugs is unknown despite being potentially deleterious to respiratory health. Herein, we used mRNA-seq to compare the transcriptomic responses produced by 2-[3-[(1R,2S,3R)-3-hydroxy-2-[(E,3S)-3-hydroxy-5-[2-(methoxymethyl)phenyl]pent-1-enyl]-5-oxo-cyclopentyl]sulphanylpropylsulphanyl] acetic acid (ONO-AE1-329; an EP-receptor agonist) and vilanterol (a -adrenoceptor agonist) in BEAS-2B human airway epithelial cells.

Neutrophil extracellular traps activate hepatic stellate cells and monocytes via NLRP3 sensing in alcohol-induced acceleration of MASH fibrosis.

Objective: Alcohol use in metabolic dysfunction-associated steatohepatitis (MASH) is associated with an increased risk of fibrosis and liver-related death. Here, we aimed to identify a mechanism through which repeated alcohol binges exacerbate liver injury in a high fat-cholesterol-sugar diet (MASH diet)-induced model of MASH.

Design: C57BL/6 mice received either chow or the MASH diet for 3 months with or without weekly alcohol binges.

IRF3 regulates neuroinflammatory responses and the expression of genes associated with Alzheimer's disease.

The pathological role of interferon signaling is emerging in neuroinflammatory disorders, yet, the specific role of Interferon Regulatory Factor 3 (IRF3) in neuroinflammation remains poorly understood. Here, we show that global IRF3 deficiency delays TLR4-mediated signaling in microglia and attenuates the hallmark features of LPS-induced inflammation such as cytokine release, microglial reactivity, astrocyte activation, myeloid cell infiltration, and inflammasome activation. Moreover, expression of a constitutively active IRF3 (S388D/S390D:IRF3-2D) in microglia induces a transcriptional program reminiscent of the Activated Response Microglia and the expression of genes associated with Alzheimer's Disease, notably Lastly, using bulk-RNAseq of IRF3-2D brain myeloid cells, we identified Z-DNA binding protein-1 as a target of IRF3 that is relevant across various neuroinflammatory disorders.

No-Show Rates in an Academic Otolaryngology Practice Before and During the COVID-19 Pandemic.

Objective: Our objectives were to determine the no-show and nonattendance rate for an outpatient academic otolaryngology practice, to identify patient and systemic factors associated with nonattendance, and to evaluate the impact that the COVID-19 pandemic had on the rate of nonattendance.

Methods: This is a retrospective review of the Epic practice management and billing reports from all scheduled outpatient visits at a multi-physician, academic, general, and sub-specialty otolaryngology practice from January 2019 to December 2021.

Results: Over three years, 121,347 clinic visits were scheduled in the otolaryngology practice.

G-CSF increases calprotectin expression, liver damage and neuroinflammation in a murine model of alcohol-induced ACLF.

Granulocyte colony-stimulating factor (G-CSF) has been proposed as a therapeutic option for patients with ACLF, however clinical outcomes are controversial. We aimed at dissecting the role of G-CSF in an alcohol-induced murine model of ACLF. : ACLF was triggered by a single alcohol binge (5 g/kg) in a bile duct ligation (BDL) liver fibrosis model.

Molecular Dynamics in Rydberg Tweezer Arrays: Spin-Phonon Entanglement and Jahn-Teller Effect.

Atoms confined in optical tweezer arrays constitute a platform for the implementation of quantum computers and simulators. State-dependent operations are realized by exploiting electrostatic dipolar interactions that emerge, when two atoms are simultaneously excited to high-lying electronic states, so-called Rydberg states. These interactions also lead to state-dependent mechanical forces, which couple the electronic dynamics of the atoms to their vibrational motion.

Changes of microbiome in response to supplements with silver nanoparticles in cotton rhizosphere.

The current study focuses on analyzing the effects of supplements containing silver nanoparticles (AgNPs) on plant growth and rhizospheric bacterial communities. Specifically, the impact of AgNP supplements was assessed on both plant growth promoting traits and bacterial communities in the soil. To do this, a screening process was conducted to select bacteria capable of synthesizing AgNPs through extracellular biosynthesis.

Regional and socioeconomic inequalities in access to pre-primary education in India: evidence from a recent household survey.

In India, the National Education Policy 2020 recommends ensuring universal access to high-quality early childhood care and education for children aged 3-6 years by 2030. Using the 75th round of National Statistical Office data (2017-2018), this paper analyses the regional and socioeconomic inequalities in access to pre-primary education. Also, we investigate the specific role of households' economic status and educational attainment in explaining these inequalities.

Innate immune activation: Parallels in alcohol use disorder and Alzheimer's disease.

Alcohol use disorder is associated with systemic inflammation and organ dysfunction especially in the liver and the brain. For more than a decade, studies have highlighted alcohol abuse-mediated impairment of brain function and acceleration of neurodegeneration through inflammatory mechanisms that directly involve innate immune cells. Furthermore, recent studies indicate overlapping genetic risk factors between alcohol use and neurodegenerative disorders, specifically regarding the role of innate immunity in the pathomechanisms of both areas.

Granulocyte colony-stimulating factor attenuates liver damage by M2 macrophage polarization and hepatocyte proliferation in alcoholic hepatitis in mice.

Massive inflammation and liver failure are main contributors to the high mortality in alcohol-associated hepatitis (AH). In recent clinical trials, granulocyte colony-stimulating factor (G-CSF) therapy improved liver function and survival in patients with AH. However, the mechanisms of G-CSF-mediated beneficial effects in AH remain elusive.

α and β catalytic subunits of cAMP-dependent protein kinase regulate formoterol-induced inflammatory gene expression changes in human bronchial epithelial cells.

Background And Purpose: It has been proposed that genomic mechanisms contribute to adverse effects often experienced by asthmatic subjects who take regular, inhaled β -adrenoceptor agonists as a monotherapy. Moreover, data from preclinical models of asthma suggest that these gene expression changes are mediated by β-arrestin-2 rather than PKA. Herein, we tested this hypothesis by comparing the genomic effects of formoterol, a β -adrenoceptor agonist, with forskolin in human primary bronchial epithelial cells (HBEC).

PERIOD Phosphoclusters Control Temperature Compensation of the Circadian Clock.

Ambient temperature varies constantly. However, the period of circadian pacemakers is remarkably stable over a wide-range of ecologically- and physiologically-relevant temperatures, even though the kinetics of most biochemical reactions accelerates as temperature rises. This thermal buffering phenomenon, called temperature compensation, is a critical feature of circadian rhythms, but how it is achieved remains elusive.

Secretory mouse quiescin sulfhydryl oxidase 1 aggregates defected human and mouse spermatozoa in vitro and in vivo.

A flavin-dependent enzyme quiescin Q6 sulfhydryl oxidase 1 (QSOX1) catalyzes the oxidation of thiol groups into disulfide bonds. QSOX1 is prominently expressed in the seminal plasma. However, its role in male reproduction is elusive.

-Adrenoceptor Agonists Promote Extracellular Signal-Regulated Kinase 1/2 Dephosphorylation in Human Airway Epithelial Cells by Canonical, cAMP-Driven Signaling Independently of -Arrestin 2.

Chronic use of -adrenoceptor agonists as a monotherapy in asthma is associated with a loss of disease control and an increased risk of mortality. Herein, we tested the hypothesis that -adrenoceptor agonists, including formoterol, biased, -arrestin (Arr) 2-dependent activation of the mitogen-activated protein kinases, ERK1/2, in human airway epithelial cells and, thereby, effect changes in gene expression that could contribute to their adverse clinical outcomes. Three airway epithelial cell models were used: the BEAS-2B cell line, human primary bronchial epithelial cells (HBEC) grown in submersion culture, and HBEC that were highly differentiated at an air-liquid interface.

Study to Assess Birth Preparedness and Complication Readiness to Promote Safe Motherhood among Women from a Rural Area of Western Maharashtra.

Background: Promotion of maternal health should be an integrated approach comprising adequate planning of pregnancy coupled with the awareness of the available maternal and child health services and its utilization.

Objectives: The aim of this study is to determine birth preparedness and complication readiness (BPACR) among antenatal and postnatal women and to assess the factors related to it.

Materials And Methods: This hospital-based cross-sectional study was conducted on 400 antenatal and postnatal women attending a tertiary care hospital of Karad.