Drug Development.

Background: Progranulin (PGRN), a glycoprotein secreted by microglia and neurons, regulates lysosomal function, neuroinflammation, and has neurotrophic effects. Variants in the granulin gene (GRN) that cause a reduction of PGRN in plasma and cerebrospinal fluid (CSF) are associated with an increased risk of Alzheimer's disease (AD). The sortilin receptor (SORT1) on neurons and microglia regulates PGRN degradation.

Effect of low birth weight and preterm delivery on the development of childhood celiac disease: a systematic review and meta-analysis on observational studies.

Purpose Of Review: Whether low birth weight (LBW) and preterm delivery (PD) are associated with the risk of developing celiac disease (CD) in children remains unclear. This systematic review and meta-analysis aimed to evaluate the association between LBW and PD with CD development in children.

Recent Findings: We searched PubMed, Embase, Scopus, Web of Science, and Google Scholar databases based on the Mesh terms to find observational studies that investigated the association of LBW and PD with CD development in children up to July 18, 2024.

Dementia Care Practice.

Dementia is a global public health challenge, impacting > 55 million individuals worldwide. However, widespread dissemination of efficacious non-pharmacologic interventions remains limited. A key implementation barrier is workforce preparation and support for healthcare professionals (HPs) and administrators when being trained in, implementing, and sustaining programs.

Prognostic factors in patients with localized and metastatic alveolar rhabdomyosarcoma. A report from two studies and two registries of the Cooperative Weichteilsarkom Studiengruppe CWS.

Background: The histologic classification of rhabdomyosarcoma (RMS) as alveolar (aRMS) or embryonal (eRMS) is of prognostic importance, with the aRMS being associated with a worse outcome. Specific gene fusions (PAX3/7::FOXO1) found in the majority of aRMS have been recognized as markers associated with poor prognosis and are included in current risk stratification instead of histologic subtypes in localized disease. In metastatic disease, the independent prognostic significance of fusion status has not been definitively established.

Small molecule probes for peroxynitrite detection.

Peroxynitrite (ONOO/ONOOH) is a short-lived but highly reactive species that is formed in the diffusion-controlled reaction between nitric oxide and the superoxide radical anion. It can oxidize certain biomolecules and has been considered as a key cellular oxidant formed under various pathophysiological conditions. It is crucial to selectively detect and quantify ONOO to determine its role in biological processes.

Antibiotic prescribing for care-home residents: a population-based, cross-classified multilevel analysis in Scotland, UK.

Background: There is wide variation in antibiotic prescribing across care-homes for older people, with implications for resident outcomes and antimicrobial resistance.

Objective: To quantify variation in antibiotic prescribing and associations with resident, care-home and general practice characteristics.

Design: Population-based analyses using administrative data.

The Impact of Silver Codoping on Tb Luminescence in Lithium Tetraborate Glasses.

Spectroscopic properties of Tb-doped and Tb-Ag codoped lithium tetraborate (LTB) glasses with LiBO (or LiO-2BO) composition are investigated and analysed using electron paramagnetic resonance (EPR), optical absorption, photoluminescence (PL) and photoluminescence excitation (PLE) spectra, PL decay kinetics and absolute quantum yield (QY) measurements. PL spectra of the investigated glasses show numerous narrow emission bands corresponding to the D → F (J = 6-0) and D → F (J = 5-3) transitions of Tb (4f) ions. The most intense PL band of Tb ions at 541 nm (D → F transition) is characterised by a lifetime slightly exceeding 2.

Defining an NK Cell-enriched Rejection-like Phenotype in Liver Transplant Biopsies From the INTERLIVER Study.

Background: Initial analysis of liver transplant biopsies in the INTERLIVER study (ClinicalTrials.gov; unique identifier NCT03193151) using rejection-associated transcripts failed to find an antibody-mediated rejection state (ie, rich in natural killer [NK] cells and with interferon-gamma effects). We recently developed an optimization strategy in lung transplants that isolated an NK cell-enriched rejection-like (NKRL) state that was molecularly distinct from T cell-mediated rejection (TCMR).

PRDX5 and PRDX6 translocation and oligomerization in bull sperm: a response to cryopreservation-induced oxidative stress.

Cryopreservation of bull sperm, crucial for breeding and assisted reproduction, often reduces sperm quality due to oxidative stress. This study examines how oxidative stress during cryopreservation affects peroxiredoxin 5 (PRDX5) and peroxiredoxin 6 (PRDX6) proteins, leading to their translocation and oligomerization in bull sperm. Increased reactive oxygen species (ROS) and nitric oxide (NO) levels were linked to reduced mitochondrial potential, higher DNA fragmentation, and increased membrane fluidity, prompting PRDX5 to move intracellularly and PRDX6 to the cell membrane.

Potentially actionable molecular alterations in particular related to poor oncologic outcomes in salivary gland carcinomas.

Aim: The study was designed to evaluate molecular alterations, relevant to the prognosis and personalized therapy of salivary gland cancers (SGCs).

Materials And Methods: DNA was extracted from archival tissue of 40 patients with various SGCs subtypes. A targeted next-generation sequencing (NGS) panel was used for the identification of small-scale mutations, focal and chromosomal arm-level copy number changes.

The different response of PM stimulated nasal epithelial spheroids in control, asthma and COPD groups.

Background: Pathobiology of asthma and chronic obstructive pulmonary disease (COPD) is associated with changes among respiratory epithelium structure and function. Increased levels of PM from urban particulate matter (UPM) are correlated with enlarged rate of asthma and COPD morbidity as well as acute disease exacerbation. It has been suggested that pre-existing pulmonary obstructive diseases predispose epithelium for different biological response than in healthy airways.

Insights into Treponema pallidum genomics from modern and ancient genomes using a novel mapping strategy.

Background: Treponemal diseases are a significant global health risk, presenting challenges to public health and severe consequences to individuals if left untreated. Despite numerous genomic studies on Treponema pallidum and the known possible biases introduced by the choice of the reference genome used for mapping, few investigations have addressed how these biases affect phylogenetic and evolutionary analysis of these bacteria. In this study, we ascertain the importance of selecting an appropriate genomic reference on phylogenetic and evolutionary analyses of T.

Reinventing type 2 immunity in cancer.

Our understanding of type 2 immunity has undergone a substantial transformation in recent years, revealing previously unknown functions. Beyond its canonical role in defence against parasitic helminth infections, type 2 immunity safeguards the host through additional mechanisms, including the suppression of excessive type 1 immune responses, regulation of tissue repair and maintenance of adipose tissue homeostasis. However, unlike type 1 immune responses, type 2 immunity is perceived as a potential promoter of tumorigenesis.

Pancreatic organogenesis mapped through space and time.

The spatial organization of cells within a tissue is dictated throughout dynamic developmental processes. We sought to understand whether cells geometrically coordinate with one another throughout development to achieve their organization. The pancreas is a complex cellular organ with a particular spatial organization.

High resolution Brillouin spectroscopy of the surface acoustic waves in SbTe van der Waals single crystals.

High-resolution Brillouin spectroscopy was employed to investigate the anisotropy in surface wave velocities within a bulk single crystal of SbTe, a well-known layered van der Waals material. By leveraging the bulk elastic constants derived from various simulation methods, we were able to theoretically calculate the distribution of surface acoustic phonon velocities on the cleavage plane of the material. Upon analyzing multiple simulation results, it became evident that the most significant discrepancies arose in the calculations of the elastic constant c, with values ranging from 48 to 98 GPa.

Stabilization of soil organic matter in Luvisols under the influence of various tree species in temperate forests.

Tree species through aboveground biomass and roots are a key factors influencing the quality and quantity of soil organic matter. Our study aimed to determine the stability of soil organic matter in Luvisols under the influence of five different tree species. The study areas were located 25 km north of Krakow, in southern Poland.

The non-nutritive sweetener rebaudioside a enhances phage infectivity.

Non-nutritive sweeteners (NNS) are widely employed in foodstuffs. However, it has become increasingly evident that their consumption is associated with bacterial dysbiosis, which, in turn, is linked to several health conditions, including a higher risk of type 2 diabetes and cancer. Among the NNS, stevia, whose main component is rebaudioside A (rebA), is gaining popularity in the organic food market segment.

Optimizing concrete sustainability with bagasse ash and stone dust and its impact on mechanical properties and durability.

Addressing environmental challenges such as pollution and resource depletion requires innovative industrial and municipal waste management approaches. Cement production, a significant contributor to greenhouse gas emissions, highlights the need for eco-friendly building materials to combat global warming and promote sustainability. This study evaluates the simultaneous use of Sugarcane Bagasse Ash (SCBA) and Stone Dust (SD) as partial replacements by volume for cement and sand, respectively, at varying ratios in eco-strength concrete mixes designed for 28 MPa (ES-28) and 34 MPa (ES-34), emphasizing their economic and environmental benefits.

Harnessing light-activated gallium porphyrins to combat intracellular Staphylococcus aureus using an in vitro keratinocyte infection model.

Staphylococcus aureus (S. aureus) can survive inside nonprofessional phagocytes such as keratinocytes, enabling it to evade antibiotics and cause recurrent infections once treatment stops. New antibacterial strategies to eliminate intracellular, multidrug-resistant bacteria are needed.

Influence of selected dosages of plastic microparticles on the porcine fecal microbiome.

Studies conducted so far have shown that nano- and microplastic may disturb the intestinal microenvironment by interacting with the intestinal epithelium and the gut microbiota. Depending on the research model used, the effect on the microbiome is different-an increase or decrease in selected taxa resulting in the development of dysbiosis. Dysbiosis may be associated with intestinal inflammation, development of mental disorders or diabetes.