high-content screening reveals miR-429 as a protective molecule in photoreceptor degeneration.

Inherited retinal diseases (IRDs) are clinically and genetically heterogeneous disorders characterized by progressive photoreceptor degeneration and irreversible vision loss. MicroRNAs (miRNAs), a class of endogenous non-coding RNAs with post-transcriptional regulatory properties, are known to play a major role in retinal function, both in physiological and pathological conditions. Given their ability to simultaneously modulate multiple molecular pathways, miRNAs represent promising therapeutic tools for disorders with high genetic heterogeneity, such as IRDs.

Spatiotemporal analysis of the effects of exercise on the hemodynamics of the aorta in hypertensive rats using fluid-structure interaction simulation.

Background And Objective: Hemodynamic changes that lead to increased blood pressure represent the main drivers of organ damage in hypertension. Prolonged increases to blood pressure can lead to vascular remodeling, which also affects vascular hemodynamics during the pathogenesis of hypertension. Exercise is beneficial for relieving hypertension, however the mechanistic link between exercise training and how it influences hemodynamics in the context of hypertension is not well understood.

Association between genetic variants in hsa-miR-27a and hsa-miR-146a genes and male infertility.

Background: miRNAs have enormous potential to be used as diagnostic and prognostic markers as well as therapeutic targets in male infertility and diseases of the reproductive system. This study aimed to investigate the association between the two functional genetic variants in the hsa-miR27a (rs2910164) and hsa-miR-146a gene (rs895819) and male infertility in North Macedonian population, as well as to test their association with the values of major seminal parameters.

Methods: The case group included in this study comprised 158 men initially diagnosed with idiopathic male infertility.

IDH-mutant gliomas in children and adolescents - from biology to clinical trials.

Gliomas account for nearly 30% of all primary central nervous system (CNS) tumors in children and adolescents and young adults (AYA), contributing to significant morbidity and mortality. The updated molecular classification of gliomas defines molecularly diverse subtypes with a spectrum of tumors associated with age-distinct incidence. In adults, gliomas are characterized by the presence or absence of mutations in isocitrate dehydrogenase (), with mutated (mIDH) gliomas providing favorable outcomes and avenues for targeted therapy with the emergence of mIDH inhibitors.

Chemotaxonomy and Bioactive Potential of High-Mountain Plantago atrata.

Plantago atrata Hoppe is a high-altitude mountain plant exposed to harsh environmental factors. This study aims to elucidate the ecological, phytochemical and pharmacological characteristics of this lesser-known plantain. Despite nutrient-poor peat soil, the leaves of P.

Context-specific eQTLs provide deeper insight into causal genes underlying shared genetic architecture of critically ill COVID-19 and idiopathic pulmonary fibrosis.

Most genetic variants identified through genome-wide association studies (GWAS) are suspected to be regulatory in nature, but only a small fraction colocalize with expression quantitative trait loci (eQTLs, variants associated with expression of a gene). Therefore, it is hypothesized but largely untested that integration of disease GWAS with context-specific eQTLs will reveal the underlying genes driving disease associations. We used colocalization and transcriptomic analyses to identify shared genetic variants and likely causal genes associated with critically ill COVID-19 and idiopathic pulmonary fibrosis.

A DOF transcriptional repressor-gibberellin feedback loop plays a crucial role in modulating light-independent seed germination.

Plants evolved several strategies to cope with the ever-changing environment. One example of this is given by seed germination, which must occur when environmental conditions are suitable for plant life. In the model system Arabidopsis thaliana seed germination is induced by light; however in nature, seeds of several plant species can germinate regardless of this stimulus.

Modeling Sporadic Progressive Supranuclear Palsy in 3D Midbrain Organoids: Recapitulating Disease Features for In Vitro Diagnosis and Drug Discovery.

Objective: Progressive Supranuclear Palsy (PSP) is a severe neurodegenerative disease characterized by tangles of hyperphosphorylated tau protein and tufted astrocytes. Developing treatments for PSP is challenging due to the lack of disease models reproducing its key pathological features. This study aimed to model sporadic PSP-Richardson's syndrome (PSP-RS) using multi-donor midbrain organoids (MOs).

Cryptic genetic diversity and molecular detection of Trypanosoma theileri complex in the deer fly Chrysops dispar Fabricius from Thailand.

The deer fly (Diptera, Tabanidae), Chrysops dispar Fabricius is a common and widespread pest and vector species transmitting pathogens to animals including economically significant livestock. However, there is only limited information on genetic diversity, which crucial for understanding disease epidemiology. In this study, we examined genetic diversity of C.

Accelerated amyloid fibril formation at the interface of liquid-liquid phase-separated droplets by depletion interactions.

Amyloid fibril formation of α-synuclein (αSN) is a hallmark of synucleinopathies. Although the previous studies have provided numerous insights into the molecular basis of αSN amyloid formation, it remains unclear how αSN self-assembles into amyloid fibrils in vivo. Here, we show that αSN amyloid formation is accelerated in the presence of two macromolecular crowders, polyethylene glycol (PEG) (MW: ~10,000) and dextran (DEX) (MW: ~500,000), with a maximum at approximately 7% (w/v) PEG and 7% (w/v) DEX.

Cysteine S-conjugate sulfoxide β-lyase activity for human ACCS.

1-Aminocyclopropane-1-carboxylate synthase (ACCS) catalyzes the conversion of S-adenosyl-methionine to 1-aminocyclopropane-1-carboxylate (ACC), a rate-limiting step in ethylene biosynthesis. A gene encoding a putative ACCS protein was identified in the human genome two decades ago. It has been shown to not exhibit any canonical ACC synthase activity and its true function remains obscure.

PSSKB: A Web Application to Study Protein Structures.

The proteins expressed during the cell cycle determine cell function and ensure signaling pathway activation in response to environmental influences. Developments in structural biology, biophysics, and bioinformatics provide information on the structure and function of particular proteins including that on the structural changes in proteins due to post-translational modification (PTM) and amino acid substitutions (AAS), which is essential for understanding protein function and life cycle. These are PTMs and AASs that often modulate the function and alter the stability and localization of a protein in a cell.

Molecular and functional profiling unravels targetable vulnerabilities in colorectal cancer.

Colorectal cancer (CRC) patients with microsatellite-stable (MSS) tumors are mostly treated with chemotherapy. Clinical benefits of targeted therapies depend on mutational states and tumor location. Many tumors carry mutations in KRAS proto-oncogene, GTPase (KRAS) or B-Raf proto-oncogene, serine/threonine kinase (BRAF), rendering them more resistant to therapies.

Allogeneic DNT cell therapy synergizes with T cells to promote anti-leukemic activities while suppressing GvHD.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a second-line treatment with curative potential for leukemia patients. However, the prognosis of allo-HSCT patients with disease relapse or graft-versus-host disease (GvHD) is poor. CD4 or CD8 conventional T (Tconv) cells are critically involved in mediating anti-leukemic immune responses to prevent relapse and detrimental GvHD.

Cell-specific transcriptional signatures of vascular cells in Alzheimer's disease: perspectives, pathways, and therapeutic directions.

Alzheimer's disease (AD) is a debilitating neurodegenerative disease that is marked by profound neurovascular dysfunction and significant cell-specific alterations in the brain vasculature. Recent advances in high throughput single-cell transcriptomics technology have enabled the study of the human brain vasculature at an unprecedented depth. Additionally, the understudied niche of cerebrovascular cells, such as endothelial and mural cells, and their subtypes have been scrutinized for understanding cellular and transcriptional heterogeneity in AD.

Effects of intra-class peer mentorship intervention programme on the academic performances of academically underperforming medical students in Nigeria.

Background: A significant gap exists in understanding the effectiveness of intra-class (same-class) level peer mentorship programmes designed to enhance academic performance, well-being, and student involvement among underperforming medical students. This study assessed the effectiveness of intra-class (same-class) peer mentorship programme on the academic performances, subjective well-being and school engagement of academically underperforming medical students in Nigeria.

Methods: This was a quasi-experimental research consisting of the pretest-posttest control design at Nnamdi Azikiwe University, Awka, Nigeria.

Deciphering the therapeutic effects of Xiyanping injection: insights into pulmonary and gut microbiome modulation, SerpinB2/PAI-2 targeting, and alleviation of influenza a virus-induced lung injury.

Infection with Influenza A virus (IAV) induces severe inflammatory responses and lung injury, contributing significantly to mortality and morbidity rates. Alterations in the microbial composition of the lungs and intestinal tract resulting from infection could influence disease progression and treatment outcomes. Xiyanping (XYP) injection has demonstrated efficacy in clinical treatment across various viral infections.

Ibuprofen reduces inflammation, necroptosis and protects photoreceptors from light-induced retinal degeneration.

Background: The retinal degenerative diseases retinitis pigmentosa (RP) and atrophic age- related macular degeneration (AMD) are characterized by vision loss from photoreceptor (PR) degeneration. Unfortunately, current treatments for these diseases are limited at best. Genetic and other preclinical evidence suggest a relationship between retinal degeneration and inflammation.

Genotype-driven sensitivity of mice to tick-borne encephalitis virus correlates with differential host responses in peripheral macrophages and brain.

Background: Tick-borne encephalitis (TBE) is the most common tick-borne viral infection in Eurasia. Outcomes range from asymptomatic infection to fatal encephalitis, with host genetics likely playing a role. BALB/c mice have intermediate susceptibility to TBE virus (TBEV) and STS mice are highly resistant, whereas the recombinant congenic strain CcS-11, which carries 12.

Marigold: a machine learning-based web app for zebrafish pose tracking.

Background: High-throughput behavioral analysis is important for drug discovery, toxicological studies, and the modeling of neurological disorders such as autism and epilepsy. Zebrafish embryos and larvae are ideal for such applications because they are spawned in large clutches, develop rapidly, feature a relatively simple nervous system, and have orthologs to many human disease genes. However, existing software for video-based behavioral analysis can be incompatible with recordings that contain dynamic backgrounds or foreign objects, lack support for multiwell formats, require expensive hardware, and/or demand considerable programming expertise.

NPT100-18A rescues mitochondrial oxidative stress and neuronal degeneration in human iPSC-based Parkinson's model.

Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by protein aggregates mostly consisting of misfolded alpha-synuclein (αSyn). Progressive degeneration of midbrain dopaminergic neurons (mDANs) and nigrostriatal projections results in severe motor symptoms. While the preferential loss of mDANs has not been fully understood yet, the cell type-specific vulnerability has been linked to a unique intracellular milieu, influenced by dopamine metabolism, high demand for mitochondrial activity, and increased level of oxidative stress (OS).

Metabolic profiles and potential antioxidant mechanisms of hawk tea.

Hawk tea has received increasing attention for its unique flavor and potential health benefits, with antioxidant function being one of its significant bioactivities. However, the metabolic profiles, potential antioxidant components, and action mechanisms of different types of hawk tea are still unclear. In this study, the chemical components of five hawk teas were determined using untargeted metabolomics.

Structural basis for human NKCC1 inhibition by loop diuretic drugs.

Na-K-Cl cotransporters functions as an anion importers, regulating trans-epithelial chloride secretion, cell volume, and renal salt reabsorption. Loop diuretics, including furosemide, bumetanide, and torsemide, antagonize both NKCC1 and NKCC2, and are first-line medicines for the treatment of edema and hypertension. NKCC1 activation by the molecular crowding sensing WNK kinases is critical if cells are to combat shrinkage during hypertonic stress; however, how phosphorylation accelerates NKCC1 ion transport remains unclear.