Pharmacokinetics, tolerability, and safety of TBI-223, a novel oxazolidinone, in healthy participants.

TBI-223 is an oxazolidinone antibiotic under clinical development for the treatment of tuberculosis. Preclinical data indicate potent antituberculosis activity and a potentially improved safety profile over linezolid. In a single-ascending dose study and a multiple-ascending dose study in 114 healthy adults, TBI-223 was generally safe and well tolerated at single doses up to 2,600 mg and multiple doses up to 2,400 mg daily over 14 days.

BET degraders reveal BRD4 disruption of 7SK and P-TEFb is critical for effective reactivation of latent HIV in CD4+ T-cells.

Unlabelled: HIV cure strategies that aim to induce viral reactivation for immune clearance leverage latency reversal agents to modulate host pathways which directly or indirectly facilitate viral reactivation. Inhibition of bromo and extra-terminal domain (BET) family member BRD4 reverses HIV latency, but enthusiasm for the use of BET inhibitors in HIV cure studies is tempered by concerns over inhibition of other BET family members and dose-limiting toxicities in oncology trials. Here, we evaluated the potential for bivalent chemical degraders targeted to the BET family as alternative latency reversal agents.

Integrated Analysis of WES and scRNA-Seq Data Reveals the Genetic Basis of Immune Dysregulation in Unexplained Recurrent Pregnancy Loss.

Objective: This study aimed to identify genetic variants and their functional consequences underlying Unexplained Recurrent Pregnancy Loss (uRPL) through comprehensive genomic and transcriptomic analyses.

Methods: We recruited 13 Chinese uRPL patients and performed Whole Exome Sequencing (WES) on chorionic villi samples from miscarriage tissues. Additionally, we conducted an integrative analysis using single-cell RNA sequencing data from decidual immune cells to examine expression patterns.

Illuminating the dark space of bioactive peptides with mass spectrometry.

Natural product peptides embody a suite of inherent bioactivities and serve as a template to inspire new chemistries and molecular scaffolds in drug discovery and agrotechnology. Mapping the vast and diverse bioactive peptidome, however, is largely obfuscated by unpredictable molecular transformations in both non-ribosomal sequences and highly post-translationally modified ribosomal protein products. Mass spectrometry is a powerful analytical technique with modern instrumentation achieving unprecedented resolving power, rapid and sensitive gas-phase separations, and versatile multistage fragmentation techniques.

Constitutive overexpression of gene simultaneously improves starch and protein content in bioengineered cassava ( Crantz).

Cassava is a crucial source of daily calorie intake for millions of people in sub-Saharan Africa (SSA) but has an inferior protein content. Despite numerous attempts utilizing both traditional and biotechnological methods, efforts to address protein deficiency in cassava have yet to meet with much success. We aim to leverage modern biotechnologies to enhance cassava's nutritional value by creating bioengineered cassava cultivars with increased protein and starch content.

Equine neutrophils selectively release neutrophil extracellular traps in response to chemical and bacterial agonists.

Introduction: Neutrophil extracellular traps (NETs) play a significant role in response to a variety of infectious and inflammatory stimuli in human and veterinary medicine. Although entrapment of bacteria can be an important function of NETs, the exuberant release of DNA and other intracellular molecules has also been negatively implicated in the pathogenesis of different diseases. Thus, NET formation must be tightly controlled and represents an opportunity for therapeutic interventions.

Surgical treatment of acute high-grade acromioclavicular joint dislocations.

Treatment options for acute acromioclavicular joint (ACJ) instability include several surgical and non-surgical approaches. Recent trends indicate a shift towards nonoperative treatment, even for severe Rockwood type V injuries, which traditionally required surgery. Despite this shift, some patients may still benefit from surgical stabilisation, particularly if significant pain and disability persist.

Multiple Pathways of Visual Adaptations for Water Column Usage in an Antarctic Adaptive Radiation.

Evolutionary transitions in water column usage have played a major role in shaping ray-finned fish diversity. However, the extent to which vision-associated trait complexity and water column usage is coupled remains unclear. Here we investigated the relationship between depth niche, eye size, and the molecular basis of light detection across the Antarctic notothenioid adaptive radiation.

Improving Health-Related Quality of Life in Hepatocellular Carcinoma Patients: Key Methodologies for Assessing Patient Reported Outcomes and Intervention Targets.

Hepatocellular carcinoma (HCC) is a complex cancer that generally arises in the context of cirrhosis. Patients with HCC have symptom burden and impact on health-related quality of life (HRQOL) resulting from underlying liver disease, HCC, and cancer treatments. Patient-reported outcome (PRO) measures may improve the management of patients with HCC by accurately capturing the patient perspective, informing prognosis, guiding treatment decisions, and supporting symptom based and palliative care.

Deficiency of H3K27 histone demethylase UTX in T cells blunts allergic sensitization and anaphylaxis to peanut.

Whether epigenetic factor UTX, a histone H3 lysine 27 (H3K27) demethylase, is critical for type 2 immunity, including allergic sensitization and antigen-driven anaphylaxis, is unclear. We used UTXfl/fl x Lck-Cre mice with UTX-deficient T cells (UTX-TCD) to determine whether T cell-specific UTX expression regulates antigen-specific IgE production after airway sensitization to peanut and anaphylaxis following intraperitoneal (i.p.

The impact of lifestyle-based weight loss in older adults with obesity on muscle and bone health: a balancing act.

Despite adverse metabolic and functional consequences of obesity (BMI ≥30 kg/m), clinical recommendations for weight loss (WL) in older adults (65+ years) with obesity remain controversial. Reluctance stems partly from epidemiologic data demonstrating musculoskeletal tissue loss with WL and increased risk of disability and osteoporotic fracture. Randomized controlled trials in older adults complement and extend knowledge in this area showing: (1) lifestyle-based WL interventions often yield clinically meaningful (~8%-10%) WL in older adults; (2) lean mass loss is significant, although fat mass loss is preferential and physical performance is often improved, particularly when combined with aerobic and resistance training (RT); (3) bone loss is also significant, with some evidence that RT can attenuate WL-associated bone loss; and (4) fat mass regain after intervention cessation is common, yet physical performance gains appear to be maintained.

Photodynamic priming overcomes platinum resistance from short-term exposure to select perfluoroalkyl substances in endometrial cancer cell lines.

First-line treatment for advanced-stage or recurrent endometrial cancer consists of platinum- and taxane-based chemotherapy, to which many patients will develop resistance. Determining the factors that contribute to platinum resistance and developing alternate treatment options for patients with advanced-stage gynecologic malignancies is critical to improving survival outcomes. Recently, we published the first study evaluating the contribution of perfluoroalkyl substances (PFAS) exposure to platinum resistance in endometrial cancer cell lines and found that select PFAS induce carboplatin resistance, potentially by dysregulating mitochondrial function.

Exploring stress and morphology in two songbird species across urban, agricultural, and natural habitats on San Cristobal Island, Galapagos.

Land use changes can have morphological and physiological impacts on wildlife. This study aimed to explore the influence of anthropogenic land use on the morphology and corticosterone concentrations in two songbirds endemic to the Galapagos archipelago: the granivorous Small Ground Finch Geospiza fuliginosa and the insectivorous Galapagos Yellow Warbler Setophaga petechia aureola in San Cristobal Island. Birds were caught and measured between June and August 2018 and June and July 2019 across four areas with different human land uses: urban green areas in the coastal town of Puerto Baquerizo Moreno, natural deciduous forest in the lowlands, agricultural areas in the highlands, and seasonal evergreen forest in the highlands.

Global scientific research landscape on binge drinking: a comprehensive bibliometric and visualization analysis of trends, collaborations, and future directions.

Background: Binge drinking constitutes a significant public health concern. Defined as the consumption of five or more alcoholic beverages on a single occasion, binge drinking leads to acute cognitive and motor impairments and is associated with a multitude of detrimental health consequences. Therefore, the aim of this study was to analyse globally published peer-reviewed literature on binge drinking.

A genome-wide association study of methamphetamine use among people with HIV.

Background: Amphetamine-like stimulants are the most used psychostimulants in the world; methamphetamine use is the most prevalent in people with HIV. Prolonged methamphetamine use can cause lasting damage to the heart, gut, and brain, as well as auditory hallucinations and paranoid thinking. However, relatively little is known about methamphetamine use and its genetic contributors.

LILRB3 genetic variation is associated with kidney transplant failure in African American recipients.

African American (AA) kidney transplant recipients exhibit a higher rate of graft loss compared with other racial and ethnic populations, highlighting the need to identify causative factors. Here, in the Genomics of Chronic Allograft Rejection cohort, pretransplant blood RNA sequencing revealed a cluster of four consecutive missense single-nucelotide polymorphisms (SNPs), within the leukocyte immunoglobulin-like receptor B3 (LILRB3) gene, strongly associated with death-censored graft loss. This SNP cluster (named LILRB3-4SNPs) encodes missense mutations at amino acids 617-618 proximal to a SHP1/2 phosphatase-binding immunoreceptor tyrosine-based inhibitory motif.

Variation in wood density across South American tropical forests.

Wood density is a critical control on tree biomass, so poor understanding of its spatial variation can lead to large and systematic errors in forest biomass estimates and carbon maps. The need to understand how and why wood density varies is especially critical in tropical America where forests have exceptional species diversity and spatial turnover in composition. As tree identity and forest composition are challenging to estimate remotely, ground surveys are essential to know the wood density of trees, whether measured directly or inferred from their identity.

Discrete and conserved inflammatory signatures drive thrombosis in different organs after Salmonella infection.

Inflammation-induced thrombosis is a common consequence of bacterial infections, such as those caused by Salmonella Typhimurium (STm). The presentation of multi-organ thrombosis post-infection that develops and resolves with organ-specific kinetics raises significant challenges for its therapeutic control. Here, we identify specific inflammatory events driving thrombosis in the spleens and livers of STm-infected mice.

Investing in U.S. forests to mitigate climate change.

In recent years several U.S. federal policies have been adopted to support forest-based climate mitigation actions.

Replicating and extending the reliability, criterion validity, and treatment sensitivity of the shortened PANSS for pediatric trials.

Do the shortened Positive and Negative Syndrome Scale (PANSS) (Kay et al., J Clin Psychiatry 58:538-546, 1987) versions recently developed from a National Institute of Mental Health (NIMH) pediatric dataset continue to perform well in a third independent randomized double-blind clinical trial of adolescents with schizophrenia? Secondary analysis of the double-blind, placebo-controlled aripiprazole pivotal trial data (N = 302) found that the 10-item (and 20-item) PANSS versions on which we have previously reported (Findling et al., J Am Acad Child Adolesc Psychiatry, https://doi.