Empagliflozin in nondiabetic individuals with calcium and uric acid kidney stones: a randomized phase 2 trial.

Efficacy of sodium-glucose cotransporter 2 inhibitors for kidney stone prevention in nondiabetic patients is unknown. In a double-blind, placebo-controlled, single-center, crossover phase 2 trial, 53 adults (≥18 and <75 years) with calcium (n = 28) or uric acid (UA; n = 25) kidney stones (at least one previous kidney stone event) without diabetes (HbA1c < 6.5%, no diabetes treatment) were randomized to once daily empagliflozin 25 mg followed by placebo or reverse (2 weeks per treatment).

Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.

G protein-coupled receptors (GPCRs) are the largest human membrane protein family that transduce extracellular signals into cellular responses. They are major pharmacological targets, with approximately 26% of marketed drugs targeting GPCRs, primarily at their orthosteric binding site. Despite their prominence, predicting the pharmacological effects of novel GPCR-targeting drugs remains challenging due to the complex functional dynamics of these receptors.

European consensus on endoscopic surgery for bilateral vocal fold immobility: classification and nomenclature.

Introduction: There are inconsistencies in how different endoscopic procedures to manage Bilateral Vocal Fold Immobility (BVFI) have been described in the literature. This limits our ability to compare functional outcomes. There is no unifying international terminology available that precisely describes the anatomical boundaries and extent of the different types of treatment.

RAGE is a key regulator of ductular reaction-mediated fibrosis during cholestasis.

Ductular reaction (DR) is the hallmark of cholestatic diseases manifested in the proliferation of bile ductules lined by biliary epithelial cells (BECs). It is commonly associated with an increased risk of fibrosis and liver failure. The receptor for advanced glycation end products (RAGE) was identified as a critical mediator of DR during chronic injury.

A phosphate-binding pocket in cyclin B3 is essential for XErp1/Emi2 degradation in meiosis I.

To ensure the correct euploid state of embryos, it is essential that vertebrate oocytes await fertilization arrested at metaphase of meiosis II. This MII arrest is mediated by XErp1/Emi2, which inhibits the ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome). Cyclin B3 in complex with Cdk1 (cyclin-dependent kinase 1) is essential to prevent an untimely arrest of vertebrate oocytes in meiosis I by targeting XErp1/Emi2 for degradation.

Viral oncogene EBNALP regulates YY1 DNA binding and alters host 3D genome organization.

The Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNALP) is essential for the immortalization of naive B lymphocytes (NBLs). However, the mechanisms remain elusive. To understand EBNALP's role in B-cell transformation, we compare NBLs infected with wild-type EBV and an EBNALP-null mutant EBV using multi-omics techniques.

Momentum tunnelling between nanoscale liquid flows.

The world of nanoscales in fluidics is the frontier where the continuum of fluid mechanics meets the atomic, and even quantum, nature of matter. While water dynamics remains largely classical under extreme confinement, several experiments have recently reported coupling between water transport and the electronic degrees of freedom of the confining materials. This avenue prompts us to reconsider nanoscale hydrodynamic flows under the perspective of interacting excitations, akin to condensed matter frameworks.

Coupling metabolomics and exome sequencing reveals graded effects of rare damaging heterozygous variants on gene function and human traits.

Genetic studies of the metabolome can uncover enzymatic and transport processes shaping human metabolism. Using rare variant aggregation testing based on whole-exome sequencing data to detect genes associated with levels of 1,294 plasma and 1,396 urine metabolites, we discovered 235 gene-metabolite associations, many previously unreported. Complementary approaches (genetic, computational (in silico gene knockouts in whole-body models of human metabolism) and one experimental proof of principle) provided orthogonal evidence that studies of rare, damaging variants in the heterozygous state permit inferences concordant with those from inborn errors of metabolism.

ESR Essentials: imaging of lymphoma-practice recommendations by the European Society of Oncologic Imaging.

Imaging is used for lymphoma detection, Ann Arbor/Lugano staging, and treatment response assessment. [F]FDG PET/CT should be used for most lymphomas, including Hodgkin lymphoma, aggressive/high-grade Non-Hodgkin lymphomas (NHL) such as diffuse large B-cell lymphoma, and many indolent/low-grade NHLs such as follicular lymphoma. Apart from these routinely FDG-avid lymphomas, some indolent NHLs, such as marginal zone lymphoma, are variably FDG-avid; here, [F]FDG PET/CT is an alternative to contrast-enhanced CT at baseline and may be used for treatment response assessment if the lymphoma was FDG-avid at baseline.

Efficiently accelerated bioimage analysis with NanoPyx, a Liquid Engine-powered Python framework.

The expanding scale and complexity of microscopy image datasets require accelerated analytical workflows. NanoPyx meets this need through an adaptive framework enhanced for high-speed analysis. At the core of NanoPyx, the Liquid Engine dynamically generates optimized central processing unit and graphics processing unit code variations, learning and predicting the fastest based on input data and hardware.

Long-term variability of extreme precipitation with WRF model at a complex terrain River Basin.

Global warming has profound effects on precipitation patterns, leading to more frequent and extreme precipitation events over the world. These changes pose significant challenges to the sustainable development of socio-economic and ecological environments. This study evaluated the performance of the new generation of the mesoscale Weather Research and Forecasting (WRF) model in simulating long-term extreme precipitation events over the Minjiang River Basin (MRB) of China from 1981 to 2020.

Digital PCR detection of microsporidia in household pipe water of patients with microsporidial keratitis.

This is a prospective non-comparative experimental study aimed to investigate the presence of microsporidia in household pipe water of microsporidial keratitis (MK) patients and to describe the patients' characteristics and behavioral risk factors. This study was conducted at Walailak University Hospital, Thailand, from July 2022 to February 2024. Patients diagnosed with MK were surveyed using a questionnaire to assess personal behaviors and source of household water.

Cross-species comparison reveals that Hmga1 reduces H3K27me3 levels to promote cardiomyocyte proliferation and cardiac regeneration.

In contrast to adult mammalian hearts, the adult zebrafish heart efficiently replaces cardiomyocytes lost after injury. Here we reveal shared and species-specific injury response pathways and a correlation between Hmga1, an architectural non-histone protein, and regenerative capacity, as Hmga1 is required and sufficient to induce cardiomyocyte proliferation and required for heart regeneration. In addition, Hmga1 was shown to reactivate developmentally silenced genes, likely through modulation of H3K27me3 levels, poising them for a pro-regenerative gene program.

Direct specification of lymphatic endothelium from mesenchymal progenitors.

During embryogenesis, endothelial cells (ECs) are generally described to arise from a common pool of progenitors termed angioblasts, which diversify through iterative steps of differentiation to form functionally distinct subtypes of ECs. A key example is the formation of lymphatic ECs (LECs), which are thought to arise largely through transdifferentiation from venous endothelium. Opposing this model, here we show that the initial expansion of mammalian LECs is primarily driven by the in situ differentiation of mesenchymal progenitors and does not require transition through an intermediate venous state.

Mechanisms of concentration control alkali activated fly ash stabilized saline soil in seasonally frozen regions.

In the framework of sustainable development and environmental preservation, this research aims to improve the stability and frost resistance of sulfate saline soil by utilizing industrial solid waste. Geopolymer materials containing fly ash (FA) activated by different NaOH concentrations were studied for study on stabilized soil with saline soil, with NaOH concentrations used ranged from 0.1 to 0.

All-electrical recursive generation and time-domain mode division multiplexing of Hermite-Gaussian pulses for optical, THz and RF links.

Space division multiplexing (SDM) with Hermite Gaussian (HG) modes, for instance, can significantly boost the transmission link capacity. However, SDM is not suitable in existing single mode fiber networks, and in long-distance wireless, microwave, THz or optical links, the far-field beam distribution may present a problem. Recently it has been demonstrated, that time domain HG modes can be employed to enhance the link capacity.

Choice of props for courtship dancing in estrildid finches.

Among the diverse sexual signals used by birds, the possible signaling functions of non-bodily objects during mating/courting displays remain unexplained. It is unclear whether such object-holding gestures are purely ritualistic or serve as an advertisement of an extended phenotype to potential mates. Estrildid finches (family Estrildidae) are characterized by mutual courtship, during which either a male or female will hold nesting material (usually grass stems or straw) in the beak while singing and dancing toward the opposite sex.

Structural insights into distinct mechanisms of RNA polymerase II and III recruitment to snRNA promoters.

RNA polymerase III (Pol III) transcribes short, essential RNAs, including the U6 small nuclear RNA (snRNA). At U6 snRNA genes, Pol III is recruited by the snRNA Activating Protein Complex (SNAPc) and a Brf2-containing TFIIIB complex, forming a pre-initiation complex (PIC). Uniquely, SNAPc also recruits Pol II at the remaining splicesosomal snRNA genes (U1, 2, 4 and 5).

Ironing out differences in attenuation and blooming artifact in acute stroke thrombi.

This study aims to improve our understanding of acute ischemic stroke clot imaging by integrating CT attenuation information with MRI susceptibility signal of thrombi. For this proof-of-principle experimental study, fifty-seven clot analogs were produced using ovine venous blood with a broad histological spectrum. Each clot analog was analyzed to determine its RBC content and chemical composition, including water, Fe III, sodium, pH, and pO2.

Exploring the catalytic hydrothermal liquefaction of Namibian encroacher bush.

An urgent ecological issue is the threat posed by invasive species, which are becoming more widespread especially in Africa. These encroachments damage ecosystems, pose a threat to biodiversity, and outcompete local plants and animals. This article focuses on converting Acacia Mellifera from Namibia, commonly known as encroacher bush (EB) into high-quality drop-in intermediates for the chemical and transport industry via hydrothermal liquefaction (HTL).

Development of colorimetric and fluorescent closed tube LAMP assay using simplified extraction for diagnosis of Meloidogyne enterolobii in root tissues.

Meloidogyne enterolobii, a guava root-knot nematode, is a highly virulent pest in tropical and subtropical regions causing galls or knots in roots of diverse plant species posing a serious threat to agriculture. Managing this nematode is challenging due to limitations in conventional identification based on isolation and microscopic classification requiring expertise and time. A colorimetric and fluorescent LAMP assay using simplified extraction method targeting rDNA-ITS region was developed to detect M.

Targeting pleuro-alveolar junctions reverses lung fibrosis in mice.

Lung fibrosis development utilizes alveolar macrophages, with mechanisms that are incompletely understood. Here, we fate map connective tissue during mouse lung fibrosis and observe disassembly and transfer of connective tissue macromolecules from pleuro-alveolar junctions (PAJs) into deep lung tissue, to activate fibroblasts and fibrosis. Disassembly and transfer of PAJ macromolecules into deep lung tissue occurs by alveolar macrophages, activating cysteine-type proteolysis on pleural mesothelium.

Long non-coding RNAs direct the SWI/SNF complex to cell type-specific enhancers.

The coordination of chromatin remodeling is essential for DNA accessibility and gene expression control. The highly conserved and ubiquitously expressed SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex plays a central role in cell type- and context-dependent gene expression. Despite the absence of a defined DNA recognition motif, SWI/SNF binds lineage specific enhancers genome-wide where it actively maintains open chromatin state.