Thiazole-Based IL-17 Inhibitors Discovered by Scaffold Morphing.

The pro-inflammatory cytokine interleukin-17A (IL-17) plays an important role in the body's defense against bacterial and fungal infections. However, overexpression of IL-17 has been associated with several diseases, including rheumatoid arthritis, asthma, psoriasis, and even cancer. The role of IL-17 in psoriasis has been confirmed by clinical use of IL-17 antibodies, e.

Genotype and Biological Age Impact Inter-Omic Associations Related to Bioenergetics.

Apolipoprotein E ( ) modifies human aging; specifically, the ε2 and ε4 alleles are among the strongest genetic predictors of longevity and Alzheimer's disease (AD) risk, respectively. However, detailed mechanisms for their influence on aging remain unclear. Herein, we analyzed inter-omic, context-dependent association patterns across genotypes, sex, and health axes in 2,229 community-dwelling individuals to test genotypes for variation in metabolites and metabolite-associations tied to a previously-validated metric of biological aging (BA) based on blood biomarkers.

Factors influencing postdeployment reintegration adjustment for U.S. service members and their spouses by spouse gender.

Research on spouses' adjustment after military deployment has focused primarily on female spouses of male service members; little is known about how adjustment differs by gender. We used Walsh's family resilience framework to examine communication, belief system, organizational factors, and other stressors, likely associated with postdeployment adjustment. Using Millennium Cohort Family Study data, logistic regressions assessed risk and protective factors on spouses' and service members' time to adjust, exploring whether spouse gender moderated their associations.

Magnesium and magnesium alloy dissolution by high intensity focused ultrasound: erosion/cavitation vs. Wave propagation.

The dissolution of metals, influenced by mechanical and chemical factors, plays a crucial role in various applications. Ultrasonic irradiation has been explored for its ability to enhance dissolution rates and modify surface characteristics. In this study, we investigate the dissolution of magnesium (Mg) and magnesium alloys under high-intensity focused ultrasound (HIFU) conditions with frequency sweeping (wobbling).

A framework towards digital twins for type 2 diabetes.

Introduction: A digital twin is a virtual representation of a patient's disease, facilitating real-time monitoring, analysis, and simulation. This enables the prediction of disease progression, optimization of care delivery, and improvement of outcomes.

Methods: Here, we introduce a digital twin framework for type 2 diabetes (T2D) that integrates machine learning with multiomic data, knowledge graphs, and mechanistic models.

Deep learning approach to predict optical attenuation in additively manufactured planar waveguides.

The booming demand for efficient, scalable optical networks has intensified the exploration of innovative strategies that seamlessly connect large-scale fiber networks with miniaturized photonic components. Within this context, our research introduces a neural network, specifically a convolutional neural network (CNN), as a trailblazing method for approximating the nonlinear attenuation function of centimeter-scale multimode waveguides. Informed by a ray tracing model that simulated many flexographically printed waveguide configurations, we cultivated a comprehensive dataset that laid the groundwork for rigorous CNN training.

Nano3'RACE: A Method to Analyze Poly(A) Tail Length and Nucleotide Additions at the 3' Extremity of Selected mRNAs Using Nanopore Sequencing.

Deadenylation is a major process that regulates gene expression by shaping the length of mRNA poly(A) tails. Deadenylation is controlled by factors in trans that recruit or impede deadenylases, by the incorporation of non-adenosines during poly(A) tail synthesis, and by the posttranscriptional addition of 3' nucleotides to poly(A) tails. Deciphering the regulation of poly(A) tail shortening requires both transcriptome-wide approaches and more targeted methodologies, allowing deep analyses of specific mRNAs.

Influence of the vestibular system on the neonatal motor behaviors in the gray short-tailed opossum ().

Marsupials are born very immature yet must be sufficiently autonomous to crawl on the mother's belly, find a teat and attach to it to pursue their development. Sensory inputs are necessary to guide the newborn to a teat and induce attachment. The vestibular system, which perceives gravity and head movements, is one of the senses proposed to guide newborns towards the teats but there are conflicting observations about its functionality at birth (postnatal day (P) 0).

DOT1L regulates chromatin reorganization and gene expression during sperm differentiation.

Spermatozoa have a unique genome organization. Their chromatin is almost completely devoid of histones and is formed instead of protamines, which confer a high level of compaction and preserve paternal genome integrity until fertilization. Histone-to-protamine transition takes place in spermatids and is indispensable for the production of functional sperm.

Partner Effects: Analyzing Service Member and Spouse Drinking Over Time.

Introduction: Excessive alcohol use is a significant problem in the military. Although there is a growing emphasis on family-centered alcohol prevention approaches, little is known about the interplay between partners' drinking behaviors. This study examines how service members and their spouses influence each other's drinking behavior over time and explores the complex individual, interpersonal, and organizational factors that may contribute to alcohol use.

Immune response to mRNA-based COVID-19 booster vaccination in people living with HIV.

Objectives: Our objective was to assess immune responses and their influencing factors in people living with HIV after messenger RNA (mRNA)-based COVID-19 booster vaccination (third dose).

Methods: This was a retrospective cohort study of people living with HIV who received booster vaccination with BNT-162b2 or mRNA-1273 between October 2021 and January 2022. We assessed anti-spike receptor-binding domain (RBD) immunoglobulin G (IgG), virus neutralizing activity (VNA) titres reported as 100% inhibitory dilution (ID ), and T-cell response (using interferon-gamma-release-assay [IGRA]) at baseline and quarterly follow-up visits.

Jasmonate signaling controls negative and positive effectors of salt stress tolerance in rice.

Plant responses to salt exposure involve large reconfigurations of hormonal pathways that orchestrate physiological changes towards tolerance. Jasmonate (JA) hormones are essential to withstand biotic and abiotic assaults, but their roles in salt tolerance remain unclear. Here we describe the dynamics of JA metabolism and signaling in root and leaf tissue of rice, a plant species that is highly exposed and sensitive to salt.

Short-Term Efficacy of Capacitive-Resistive Electrical Transfer Therapy in Short-Haired Sled Dogs in Middle-Distance Competition.

Achieving the successful recovery of sled dogs is one of the key tasks for veterinary teams involved in clinical care for middle-distance sled dog competitions. This study compares the efficacy of capacitive-resistive electrical transfer (CRet) with that of massage in the treatment of lower back pain in 40 short-haired sled dogs during a medium-distance snow sled race (Lekkarod-2021). The dogs were divided into two groups: a CRet group (20 dogs) and a massage group (20 dogs).

PlantRNA 2.0: an updated database dedicated to tRNAs of photosynthetic eukaryotes.

PlantRNA (http://plantrna.ibmp.cnrs.

Transient expression of NF200 by fibers in the nasal septum and rostral telencephalon of developing opossums (Monodelphis domestica).

Marsupials are born very immature and crawl on their mother's belly to attach to teats. Sensory information is required to guide the newborn and to induce attachment to the teat. Olfaction has been classically proposed to influence neonatal behaviors, but recent studies suggest that the central olfactory structures are too immature to account for them.

Analysis of the Arabidopsis coilin mutant reveals a positive role of AtCOILIN in plant immunity.

Biogenesis of ribonucleoproteins occurs in dynamic subnuclear compartments called Cajal bodies (CBs). COILIN is a critical scaffolding component essential for CB formation, composition, and activity. We recently showed that Arabidopsis (Arabidopsis thaliana) AtCOILIN is phosphorylated in response to bacterial elicitor treatment.

Pre- and Perinatal Risk Factors for Child Maltreatment in Military Families Across the First Two Years of Life.

Military families are exposed to a unique constellation of risk factors, which may impact maltreatment outcomes. The present study examined prospective relationships between demographic, health, birth-related, and military-specific risk factors identified prior to a child's birth on their risk for maltreatment in the first two years of life. Data from the Millennium Cohort Study, Department of Defense (DoD) operational records and Family Advocacy Program data on met-criteria maltreatment, and Birth and Infant Health Research program data on suspected maltreatment were linked for 9076 service member parents.

An integrative gene expression signature analysis identifies CMS4 KRAS-mutated colorectal cancers sensitive to combined MEK and SRC targeted therapy.

Background: Over half of colorectal cancers (CRCs) are hard-wired to RAS/RAF/MEK/ERK pathway oncogenic signaling. However, the promise of targeted therapeutic inhibitors, has been tempered by disappointing clinical activity, likely due to complex resistance mechanisms that are not well understood. This study aims to investigate MEK inhibitor-associated resistance signaling and identify subpopulation(s) of CRC patients who may be sensitive to biomarker-driven drug combination(s).

Patient-reported outcome measures of musculoskeletal symptoms and psychosocial factors in musicians: a systematic review of psychometric properties.

Purpose: To systematically review patient-reported outcome measures (PROMs) of musicians' musculoskeletal symptoms (MSS) and psychosocial factors and their psychometric properties.

Methods: Six databases were searched. Studies evaluating at least one psychometric property of a PROM developed for or adapted to adult musicians and measuring MSS or occupational psychosocial factors were included.

Genome-Wide Identification of Key Components of RNA Silencing in Two Genotypes of Contrasting Origin and Their Expression Analyses in Response to Fungal Infection.

RNA silencing serves key roles in a multitude of cellular processes, including development, stress responses, metabolism, and maintenance of genome integrity. Dicer, Argonaute (AGO), double-stranded RNA binding (DRB) proteins, RNA-dependent RNA polymerase (RDR), and DNA-dependent RNA polymerases known as Pol IV and Pol V form core components to trigger RNA silencing. Common bean () is an important staple crop worldwide.

Antiproliferation and Antiencystation Effect of Class II Histone Deacetylase Inhibitors on .

is a ubiquitous and free-living protozoan pathogen responsible for causing keratitis (AK), a severe corneal infection inflicting immense pain that can result in permanent blindness. A drug-based treatment of AK has remained arduous because trophozoites undergo encystment to become highly drug-resistant cysts upon exposure to harsh environmental conditions such as amoebicidal agents (e.g.

QSAR Classification Models for Prediction of Hydroxamate Histone Deacetylase Inhibitor Activity against Malaria Parasites.

Malaria, caused by parasites, results in >400,000 deaths annually. There is no effective vaccine, and new drugs with novel modes of action are needed because of increasing parasite resistance to current antimalarials. Histone deacetylases (HDACs) are epigenetic regulatory enzymes that catalyze post-translational protein deacetylation and are promising malaria drug targets.

Risk and protective factors predictive of marital instability in U.S. military couples.

The objective of this study was to predict marital instability from a range of risk and protective factors in a large, representative cohort of military couples participating in the Millennium Cohort Family Study. Online and paper surveys were administered to service members and their spouses in 2011-2013, which captured couples' demographic and background characteristics, family stressors, military experiences, and mental health risk factors as well as protective factors including family communication, and military support and satisfaction. Approximately 3 years later, change in marital status was examined among participants who completed a follow-up survey ( = 6,494 couples).