Conformational dynamics in specialized CH zinc finger domains enable zinc-responsive gene repression in S. pombe.

Loz1 is a zinc-responsive transcription factor in fission yeast that maintains cellular zinc homeostasis by repressing the expression of genes required for zinc uptake in high zinc conditions. Previous deletion analysis of Loz1 found a region containing two tandem CH zinc-fingers and an upstream "accessory domain" rich in histidine, lysine, and arginine residues to be sufficient for zinc-dependent DNA binding and gene repression. Here we report unexpected biophysical properties of this pair of seemingly classical CH zinc fingers.

Maternal Western Diet Programmes Bile Acid Dysregulation and Hepatic Fibrosis in Fetal and Juvenile Macaques.

Background And Aims: Maternal obesity increases the risk of the paediatric form of metabolic dysfunction-associated steatotic liver disease (MASLD), affecting up to 30% of youth, but the developmental origins remain poorly understood.

Methods: Using a Japanese macaque model, we investigated the impact of maternal Western-style diet (mWSD) or chow diet followed by postweaning WSD (pwWSD) or chow diet focusing on bile acid (BA) homeostasis and hepatic fibrosis in livers from third-trimester fetuses and 3-year-old juvenile offspring.

Results: Juveniles exposed to mWSD had increased hepatic collagen I/III content and stellate cell activation in portal regions.

Cryo-EM SPR structures of Salmonella typhimurium ArnC; the key enzyme in lipid-A modification conferring polymyxin resistance.

Polymyxins are last-resort antimicrobial peptides administered clinically against multi-drug resistant bacteria, specifically in the case of Gram-negative species. However, an increasing number of these pathogens employ a defense strategy that involves a relay of enzymes encoded by the pmrE (ugd) loci and the arnBCDTEF operon. The pathway modifies the lipid-A component of the outer membrane (OM) lipopolysaccharide (LPS) by adding a 4-amino-4-deoxy-l-arabinose (L-Ara4N) headgroup, which renders polymyxins ineffective.

Cardio-renal effect of dapagliflozin and dapagliflozin- saxagliptin combination on CD34 + ve hematopoietic stem cells (HSCs) and podocyte specific markers in type 2 diabetes (T2DM) subjects: a randomized trial.

Introduction: Effects of Dapagliflozin (Dapa) and Dapagliflozin-Saxagliptin combination (Combo) was examined on peripheral blood derived CD34 + Hematopoetic Stem Cells (HSCs) as a cellular CVD biomarker. Both Dapa (a sodium-glucose co-transporter 2 or SGLT2, receptor inhibitor) and Saxagliptin (a Di-peptydl-peptidase-4 or DPP4 enzyme inhibitor) are commonly used type 2 diabetes mellitus or T2DM medications, however the benefit of using the combination has not been evaluated for cardio-renal risk assessment, in a real-life practice setting, compared to a placebo.

Hypothesis: We hypothesized that Dapa will improve the outcomes when compared to placebo and the Combo maybe even more beneficial.

Combination of Carbonic Anhydrase Isoform IX Inhibitors and Gefitinib Suppresses on the Invasive Potential of Non-Small Cell Lung Cancer Cells.

Human carbonic anhydrase IX (CAIX) plays a key role in maintaining pH homeostasis of malignant neoplasms, thus creating a favorable microenvironment for the growth, invasion, and metastasis of tumor cells. Recent studies have established that inhibition of CAIX expressed on the surface of tumor cells significantly increases the efficacy of classical chemotherapeutic agents and makes it possible to suppress the resistance of tumor cells to chemotherapy, as well as to increase their sensitivity to drugs (in particular, to reduce the required dose of cytostatic agents). In this work, we studied the ability of new CAIX inhibitors based on substituted 1,2,4-oxadiazole-containing primary aromatic sulfonamides, to potentiate the cytostatic effect of gefitinib (selective inhibitor of epidermal growth factor receptor tyrosine kinase domain) under hypoxic conditions.

Characterization of Carbohydrate Specificity of Monoclonal Antibodies to Fungal Antigenic Markers Using Biotinylated Oligosaccharides as Coating Antigens.

Mannan and β-(1→3)-glucan are two polysaccharide markers that are characteristic for a number of fungal pathogens, including , which is the most common cause of invasive mycoses in humans. In this study, we examined epitope specificity of two monoclonal antibodies, CM532 and FG70, which recognize certain oligosaccharide fragments of these fungal polysaccharides. Using a panel of biotinylated oligosaccharides as coating antigens, we found that the CM532 antibody obtained by immunization with the pentamannoside β-Man-(1→2)-β-Man-(1→2)-α-Man-(1→2)-α-Man-(1→2)-α-Man KLH conjugate, selectively recognizes the trisaccharide β-Man-(1→2)-α-Man-(1→2)-α-Man epitope.

Deciphering the Ligand-Binding Site in a DNA Aptamer Targeting Deoxynivalenol.

Food safety is one of the primary demands of modern society. Mycotoxins are toxic metabolites of food-contaminating fungi. Fungi enter the food chain by infecting crops and irreversibly contaminate them due to the structural stability of mycotoxins.

Metabolomic Profiles of Siberian Wood Frog in Hypoxia and Upon Reoxygenation.

Hypoxia poses a serious challenge for all animals; however, certain animals exhibit a remarkable resilience in the case of prolonged and severe hypoxia. The Siberian wood frog is a unique amphibian capable of surviving for up to several months at almost complete anoxia. We investigated changes in the metabolome of at the onset of hypoxia (day 1) and within 1 h of reoxygenation after a long-term hypoxia using H NMR.

Posttranslational modifications in cardiac metabolic remodeling mediated by metabolites: Implications for disease pathology and therapeutic potential.

The nonenergy-producing or biomass-accumulating functions of metabolism are attracting increasing attention, as metabolic changes are gaining importance as discrete signaling pathways in modulating enzyme activity and gene expression. Substantial evidence suggests that myocardial metabolic remodeling occurring during diabetic cardiomyopathy, heart failure, and cardiac pathological stress (e.g.

Using Laboratory Test Results for Surveillance During a New Outbreak of Acute Hepatitis in 3-Week- to 5-Year-Old Children in the United Kingdom, the Netherlands, Ireland, and Curaçao: Observational Cohort Study.

Background: In March 2022, a concerning rise in cases of unexplained pediatric hepatitis was reported in multiple countries. Cases were defined as acute hepatitis with serum transaminases >500 U/L (aspartate transaminase [AST] or alanine transaminase [ALT]) in children aged 16 years or younger. We explored a simple federated data analytics method to search for evidence of unreported cases using routinely held data.

Development of a versatile system for evaluating the target protein degradation activity of novel ubiquitin ligases utilizing existing PROTACs.

Proteolysis-Targeting Chimeras (PROTAC) are a bifunctional molecule that binds to a protein of interest (POI) and a ubiquitin ligase, thereby inducing the ubiquitination and degradation of POI. Many PROTACs currently utilize a limited number of ubiquitin ligases, such as von Hippel-Lindau (VHL) and Cereblon. Because these ubiquitin ligases are widely expressed in normal tissues, unexpected side effects can occur.

Association of Epstein-Barr Virus and its clinical relevance in Human Papillomavirus-negative oral squamous cell carcinoma: A cohort study from South India.

Objective: The study assessed the prevalence and clinical implications of Epstein Barr Virus (EBV)-positive but Human Papillomavirus (HPV)-negative oral squamous cell carcinoma (OSCC) in a tertiary care hospital setting. The overall goal was to elucidate the potential impact of EBV on OSCC disease progression and prognosis.

Design: A total of 134 surgically resected and histopathologically confirmed OSCC tumor biopsies were collected from a tertiary care hospital.

Pharmacological blocking of microfibrillar-associated protein 4 reduces retinal neoangiogenesis and vascular leakage.

Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision-loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin αβ ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell-types in close proximity to vascular endothelial cells including choroidal vascular mural cells and retinal astrocytes and Müller cells.

Unveiling the omics tapestry of B-acute lymphoblastic leukemia: bridging genomics, metabolomics, and immunomics.

Acute B-lymphoblastic leukemia (B-ALL) is a highly heterogeneous hematologic malignancy, characterized by significant molecular differences among patients as the disease progresses. While the PI3K-Akt signaling pathway and metabolic reprogramming are known to play crucial roles in B-ALL, the interactions between lipid metabolism, immune pathways, and drug resistance remain unclear. In this study, we performed multi-omics analysis on different patient cohorts (newly diagnosed, relapsed, standard-risk, and poor-risk) to investigate the molecular characteristics associated with metabolism, signaling pathways, and immune regulation in B-ALL.

Foliar application of nano biochar solution elevates tomato productivity by counteracting the effect of salt stress insights into morphological physiological and biochemical indices.

Nano-biochar considers a versatile and valuable sorbent to enhance plant productivity by improving soil environment and emerged as a novel solution for environmental remediation and sustainable agriculture in modern era. In this study, roles of foliar applied nanobiochar colloidal solution (NBS) on salt stressed tomato plants were investigated. For this purpose, NBS was applied (0%, 1% 3% and 5%) on two groups of plants (control 0 mM and salt stress 60 mM).

[NTRK gene fusion and molecular pathological characteristics of mismatch repair deficient colorectal cancer].

To investigate the expression pattern of pan-TRK protein in colorectal cancers with NTRK gene fusion and mismatch repair deficient (dMMR) and to analyze its molecular pathological characteristics. A total of 117 dMMR colorectal cancers diagnosed in the Department of Pathology of Henan Provincial People's Hospital, Zhengzhou, China from 2020 to 2023 were collected. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and DNA/RNA-based next-generation sequencing (NGS) were used to detect pan-TRK protein expression and fusion partner genes in tumors, and to further explore the correlation between pan-TRK staining patterns and partner genes.

[Application of PMS2 and MSH6 double-antibody detection in screening of mismatch repair deficient tumors].

To investigate whether the immunohistochemical results of two markers PMS2 and MSH6 (2-MMR) could replace the four markers MLH1, PMS2, MSH2 and MSH6 (4-MMR) to detect mismatch repair deficient (dMMR) cancers. A retrospective analysis was conducted with summary of immunohistochemical data from 7 867 cases of gastric cancer, colorectal cancer, endometrial cancer, and other diseases in the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China, from March 2018 to March 2023. The consistency of 2-MMR and 4-MMR results was examined.

P3 site-directed mutagenesis: An efficient method based on primer pairs with 3'-overhangs.

Site-directed mutagenesis is a fundamental tool indispensable for protein and plasmid engineering. An important technological question is how to achieve the efficiency at the ideal level of 100%. Based on complementary primer pairs, the QuickChange method has been widely used, but it requires significant improvements due to its low efficiency and frequent unwanted mutations.

Therapeutic outcomes and safety of radiofrequency ablation for primary papillary thyroid carcinoma: A game-changing meta-analysis.

Background: Radiofrequency ablation (RFA) is an emerging treatment option for small, low-risk papillary thyroid carcinoma (PTC). This systematic review and meta-analysis aimed to evaluate and compare the efficacy and safety profiles of RFA for primary T1a vs. T1b PTC.

Okra seed polysaccharides mitigate neuroinflammation and cognitive impairment via modulation of Nrf2/HO-1, HMGB1/RAGE/TLR4/NF-κB, NLRP3/Caspase-1, JAK-2/STAT-3, AMPK/SIRT1/m-TOR, PI3K/AKT/CREB/BDNF/TrkB and PERK/CHOP/Bcl-2 axes.

Global healthcare systems are under tremendous strain due to the increasing prevalence of neurodegenerative disorders. Growing data suggested that overconsumption of high-fat/high-carbohydrates diet (HFHCD) is associated with enhanced incidence of metabolic alterations, neurodegeneration, and cognitive dysfunction. Functional foods have gained prominence in curbing metabolic and neurological deficits.

Glucometer versus analyzer: comparable results with negligible clinical risk.

This study assessed the reliability of Roche Accu-Chek Inform II glucometers in a real-world setting. A retrospective analysis was conducted on 6,695 paired results. Capillary samples were tested using Roche Accu-Chek Inform II glucometers, while venous samples were analyzed using Roche Cobas c503/702 analyzers.

Biochemical osteomalacia in adults undergoing vitamin D testing in the North-East of Scotland.

Background: International guidelines give greatly varying definitions of 25-hydroxyvitamin D (25OHD) insufficiency and deficiency. Vitamin D testing is increasing despite 2016 UK guidance for adults advising routine vitamin D supplementation October-March and year-round for high risk groups. A service evaluation of vitamin D testing and biochemical osteomalacia in the North-East of Scotland (57-58°N) could inform definitions and testing guidance.

Monocyte and Macrophage in Follicular Liquid: Predictive Markers of Embryo Quality in Women with Obesity and Infertility.

Background: Over the past five years, the pregnancy rate in assisted reproductive technology (ART) programs in Russia has remained relatively stable. The aim of this study was to assess the distribution of monocyte and macrophage subsets in the blood and follicular fluid of infertile women undergoing assisted reproductive technology.

Methods: The study involved 45 women with a mean age of 35 ± 4.

The Impact of Optical Undersampling on the Ca Signal Resolution in Ca Imaging of Spontaneous Neuronal Activity.

Background: In neuroscience, Ca imaging is a prevalent technique used to infer neuronal electrical activity, often relying on optical signals recorded at low sampling rates (3 to 30 Hz) across multiple neurons simultaneously. This study investigated whether increasing the sampling rate preserves critical information that may be missed at slower acquisition speeds.

Methods: Primary neuronal cultures were prepared from the cortex of newborn pups.

Egyptian Novel Goose Parvovirus in Immune Organs of Naturally Infected Ducks: Next-Generation Sequencing, Immunohistochemical Signals, and Comparative Analysis of Pathological Changes Using Multiple Correspondence and Hierarchical Clustering Approach.

The present study aims to better understand the nature of currently circulating GPV strains and their pathological impact on the immune system during natural outbreaks among different duck breeds in Egypt. For this purpose, 99 ducks (25 flocks) of different breeds, aged 14-75 days, were clinically examined, and 75 tissue pools from the thymus, bursa of Fabricius, and spleen were submitted for virus detection and identification. Clinical and postmortem findings were suggestive of GPV infection.