Interactions between epithelial mesenchymal plasticity, barrier dysfunction and innate immune pathways shape the genesis of allergic airway disease.

Introduction: In genetically predisposed individuals, exposure to aeroallergens and infections from RNA viruses shape epithelial barrier function, leading to Allergic Asthma (AA). Here, activated pattern recognition receptors (PRRs) in lower airway sentinel cells signal epithelial injury-repair pathways leading to cell-state changes [epithelial mesenchymal plasticity (EMP)], barrier disruption and sensitization.

Areas Covered: 1.

Microbial hauberks: composition and function of surface layer proteins in gammaproteobacterial methanotrophs.

Unlabelled: Many species of proteobacterial methane-consuming bacteria (methanotrophs) form a hauberk-like envelope represented by a surface (S-) layer protein (SLP) matrix. While several proteins were predicted to be associated with the cell surface, the composition and function of the hauberk matrix remained elusive. Here, we report the identification of the genes encoding the hauberk-forming proteins in two gamma-proteobacterial (Type I) methanotrophs, 5GB1 (EQU24_15540) and 20Z (MEALZ_0971 and MEALZ_0972).

Biomarkers in the diagnosis of mast cell activation.

Purpose Of Review: Mast cell activation is defined by activation of mast cells by varying stimuli with release of chemical mediators either through degranulation or release of de novo synthesized proteins or lipid mediators. Currently, tryptase measurement increase during symptomatic episodes is the most accepted biomarker measurement for mast cell activation. However, newer diagnostic tools including clinically available urinary mast cell mediators are noninvasive and can be more readily obtained compared to serum tryptase levels.

Type 2 immunity to the rescue: enhancing antitumor immunity for skin cancer prevention.

Cutaneous squamous cell carcinoma (cSCC) incidence and deaths continue to rise, underscoring the need for improved cSCC prevention. Elimination of actinic keratosis (AK) precursor lesions is a major strategy to prevent cSCC. Topical calcipotriol and 5-fluorouracil (5-FU) have been shown to eliminate AKs and reduce the risk of cSCC development, but the mechanism was undefined.

T helper 2 cell-directed immunotherapy eliminates precancerous skin lesions.

The continuous rise in skin cancer incidence highlights an imperative for improved skin cancer prevention. Topical calcipotriol-plus-5-fluorouracil (calcipotriol-plus-5-FU) immunotherapy effectively eliminates precancerous skin lesions and prevents squamous cell carcinoma (SCC) in patients. However, its mechanism of action remains unclear.

Identification of Transdiagnostic Childhood Externalizing Pathology Within an Electronic Medical Records Database and Application to the Analysis of Rare Copy Number Variation.

Externalizing traits and behaviors are broadly defined by impairments in self-regulation and impulse control that typically begin in childhood and adolescence. Externalizing behaviors, traits, and symptoms span a range of traditional psychiatric diagnostic categories. In this study, we sought to generate an algorithm that could reliably identify transdiagnostic childhood-onset externalizing cases and controls within a university hospital electronic health record (EHR) database.

Inhibition of Bruton's tyrosine kinase restricts neuroinflammation following intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a devastating form of stroke with a lack of effective treatments. Following disease onset, ICH activates microglia and recruits peripheral leukocytes into the perihematomal region to amplify neural injury. Bruton's tyrosine kinase (BTK) controls the proliferation and survival of various myeloid cells and lymphocytes.

Whole genome methylation sequencing in blood from persons with mild cognitive impairment and dementia due to Alzheimer's disease identifies cognitive status.

Introduction: Whole genome methylation sequencing (WGMS) in blood identifies differential DNA methylation in persons with late-onset dementia due to Alzheimer's disease (AD) but has not been tested in persons with mild cognitive impairment (MCI).

Methods: We used WGMS to compare DNA methylation levels at 25,244,219 CpG loci in 382 blood samples from 99 persons with MCI, 109 with AD, and 174 who are cognitively unimpaired (CU).

Results: WGMS identified 9756 differentially methylated positions (DMPs) in persons with MCI, including 1743 differentially methylated genes encoding proteins in biological pathways related to synapse organization, dendrite development, and ion transport.

Patient-derived response estimates from zero-passage organoids of luminal breast cancer.

Background: Primary luminal breast cancer cells lose their identity rapidly in standard tissue culture, which is problematic for testing hormone interventions and molecular pathways specific to the luminal subtype. Breast cancer organoids are thought to retain tumor characteristics better, but long-term viability of luminal-subtype cases is a persistent challenge. Our goal was to adapt short-term organoids of luminal breast cancer for parallel testing of genetic and pharmacologic perturbations.

Reassessing the roles of oxidative DNA base lesion 8-oxoGua and repair enzyme OGG1 in tumorigenesis.

ROS cause multiple forms of DNA damage, and among them, 8-oxoguanine (8-oxoGua), an oxidized product of guanine, is one of the most abundant. If left unrepaired, 8-oxoGua may pair with A instead of C, leading to a mutation of G: C to T: A during DNA replication. 8-Oxoguanine DNA glycosylase 1 (OGG1) is a tailored repair enzyme that recognizes 8-oxoGua in DNA duplex and initiates the base excision repair (BER) pathway to remove the lesion and ensure the fidelity of the genome.

An isothermal calorimetry assay for determining steady state kinetic and Ensitrelvir inhibition parameters for SARS-CoV-2 3CL-protease.

This manuscript details the application of Isothermal Titration Calorimetry (ITC) to characterize the kinetics of 3CL, the main protease from the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2), and its inhibition by Ensitrelvir, a known non-covalent inhibitor. 3CL is essential for producing the proteins necessary for viral infection, which led to the COVID-19 pandemic. The ITC-based assay provided rapid and reliable measurements of 3CL activity, allowing for the direct derivation of the kinetic enzymatic constants K and k by monitoring the thermal power required to maintain a constant temperature as the substrate is consumed.

Clinical predictors of 3-month isoniazid rifapentine (3HP)-related adverse drug reactions (ADR) during tuberculosis preventive therapy (PAnDoRA-3HP study): an observational study protocol.

Introduction: Tuberculosis (TB) is the leading infectious cause of death globally. Despite WHO recommendations for TB preventive therapy (TPT), challenges persist, including incompletion of treatment and adverse drug reactions (ADRs). There is limited data on the 3-month isoniazid and rifapentine (3HP) pharmacokinetics, pharmacogenomics and their relation with ADRs.

Comparison of Cell-death Kinetics of Recombinant Methioninase (rMETase)-treated Cancer and Normal Cells: Only Cancer Cells Undergo Methionine-depletion Catastrophe at Low rMETase Concentrations.

Background/aim: Methionine addiction, known as the Hoffman effect, makes cancer cells more sensitive to methionine restriction than normal cells. However, the long-term effects of methionine restriction on cancer and normal cells have not been thoroughly studied.

Materials And Methods: HCT-116 human colorectal-cancer cells and Hs27 normal skin fibroblasts were treated with 0-8 U/ml of recombinant methioninase (rMETase) for 12 days.

Phthalimides as anti-inflammatory agents.

Isoindoline-1,3-dione, also referred as phthalimide, has gained recognition as promising pharmacophore due to the documented biological activities of its derivatives. Phthalimides are a family of synthetic molecules that exhibit notable bioactivity across various fields, particularly as anticancer and anti-inflammatory agents. This review focuses on syntheses and anti-inflammatory studies of the reported phthalimide derivatives.

Rapid identification and phenotyping of nonalcoholic fatty liver disease patients using a machine-based approach in diverse healthcare systems.

Nonalcoholic fatty liver disease (NAFLD) is the most common global cause of chronic liver disease and remains under-recognized within healthcare systems. Therapeutic interventions are rapidly advancing for its inflammatory phenotype, nonalcoholic steatohepatitis (NASH) at all stages of disease. Diagnosis codes alone fail to recognize and stratify at-risk patients accurately.

US mortality trends from alcohol-associated hepatitis by sex, age, race, and ethnicity, 1999-2020.

Background: Alcohol-associated hepatitis (AH) is a subtype of alcohol-associated liver disease (ALD) resulting in severe acute liver inflammation. This study aims to examine longitudinal trends in mortality from AH in the United States (US) from 1999 to 2020, stratifying the data by sex, age, and racial/ethnic groups.

Methods: We performed a cross-sectional study using data from the US Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (WONDER) to determine annual AH-related mortality rates (MR) in adults ≥21 years between 1999 and 2020.

Synthesis And Photovoltaic Performance of Carbazole (Donor) Based Photosensitizers in Dye-Sensitized Solar Cells (DSSC): A Review.

Carbazoles are nitrogen-containing aromatic heterocycles, having widespread applications in the field of photovoltaics. Carbazole-based photosensitizers have tunable features for absorption on semi-conductor (tellurium dioxide or zinc oxide) layers to create sufficient push-pull force in the conversion of sunlight into electrical energy, thus presenting as promising heterocyclic donor candidates to be used in dye-sensitized solar cells. For the synthesis of these dyes, various structural designs are available, namely, D-A, D-π-A, D-D-π-A, D-A-π-A, A-π-D-π-A-π-A, and D2-π-A that all involve incorporating carbazole as a donor (D), along with spacer (π-extender) moieties, such as thiophene, phenol, ethynylene, nitromethane, azine, thiadiazole, or acetonitrile.

Severe aplastic anemia with acquired X chromosome clonality as a sole abnormality.

This case is a rare presentation of severe aplastic anemia in a 31-year-old male with acquired clonality of the X chromosome as the sole cytogenetic abnormality. This abnormality has not been reported to our knowledge, and the significance of this finding remains unclear. Comprehensive diagnostic workup included bone marrow biopsy, cytogenetic analysis, and Next-Generation sequencing, which revealed no tier I/II variants typically associated with clonal hematopoietic disorders.

Oxidized phospholipid and transcriptomic signatures of THC-related vaping associated lung injury.

E-cigarette/vaping-associated lung injury (EVALI) is strongly associated with vitamin E acetate and often occurs with concomitant tetrahydrocannabinol (THC) use. To uncover pathways associated with EVALI, we examined cytokines, transcriptomic signatures, and lipidomic profiles in bronchoalveolar lavage fluid (BALF) from THC-EVALI patients. At a single center, we prospectively enrolled mechanically ventilated patients with EVALI from THC-containing products (N = 4) and patients with non-vaping acute lung injury and airway controls (N = 5).

Design of an equilibrative nucleoside transporter subtype 1 inhibitor for pain relief.

The current opioid crisis urgently calls for developing non-addictive pain medications. Progress has been slow, highlighting the need to uncover targets with unique mechanisms of action. Extracellular adenosine alleviates pain by activating the adenosine A1 receptor (A1R).

Rapid nongenomic estrogen signaling controls alcohol drinking behavior in mice.

Ovarian-derived estrogen can signal non-canonically at membrane-associated receptors in the brain to rapidly regulate neuronal function. Early alcohol drinking confers greater risk for alcohol use disorder in women than men, and binge alcohol drinking is correlated with high estrogen levels, but a causal role for estrogen in driving alcohol drinking has not been established. We found that female mice displayed greater binge alcohol drinking and reduced avoidance when estrogen was high during the estrous cycle than when it was low.

Examining social attention as a predictor of problem drinking behavior: A longitudinal study using eye-tracking.

Background: Researchers have long been interested in identifying objective markers for problem drinking susceptibility informed by the environments in which individuals drink. However, little is known of objective cognitive-behavioral indices relevant to the social contexts in which alcohol is typically consumed. Combining group-based alcohol administration, eye-tracking technology, and longitudinal follow-up over a 2-year span, the current study examined the role of social attention in predicting patterns of problem drinking over time.

Microstructural mapping of neural pathways in Alzheimer's disease using macrostructure-informed normative tractometry.

Introduction: Diffusion-weighted magnetic resonance imaging (dMRI) is sensitive to the microstructural properties of brain tissues and shows great promise in detecting the effects of degenerative diseases. However, many approaches analyze single measures averaged over regions of interest without considering the underlying fiber geometry.

Methods: We propose a novel macrostructure-informed normative tractometry (MINT) framework to investigate how white matter (WM) microstructure and macrostructure are jointly altered in mild cognitive impairment (MCI) and dementia.