Soybean oil and probiotics improve meat quality, conjugated linoleic acid concentration, and nutritional quality indicators of goats.

This study aimed to investigate the impact of dietary soybean oil and probiotics on goat meat quality, total conjugated linoleic acids (TCLA) concentration, and nutritional quality indicators of goats. Thirty-six male crossbred goats (Anglo-Nubian♂× Thai native♀), weighing 18.3 ± 2.

Dietary carbohydrate to lipid ratio affects growth, reproductive performance and health of female yellow catfish (): A lipidomics analysis.

This study aimed to examine the impact of dietary carbohydrate to lipid (CHO/L) ratio on the growth, reproductive, and offspring performance of broodstock yellow catfish, and to elucidate the metabolic differences between mothers and offspring using lipidomics. Five isonitrogenous and isoenergetic diets with varying CHO/L ratios (0.65, 1.

Selective degradation of multimeric proteins by TRIM21-based molecular glue and PROTAC degraders.

Targeted protein degradation (TPD) utilizes molecular glues or proteolysis-targeting chimeras (PROTACs) to eliminate disease-causing proteins by promoting their interaction with E3 ubiquitin ligases. Current TPD approaches are limited by reliance on a small number of constitutively active E3 ubiquitin ligases. Here, we report that (S)-ACE-OH, a metabolite of the antipsychotic drug acepromazine, acts as a molecular glue to induce an interaction between the E3 ubiquitin ligase TRIM21 and the nucleoporin NUP98, leading to the degradation of nuclear pore proteins and disruption of nucleocytoplasmic trafficking.

Epilimnetic oligotrophication increases contribution of oxic methane production to atmospheric methane flux from stratified lakes.

Although considerable attention has been paid to the effects of eutrophication on aquatic methane (CH) emissions to the atmosphere, the ecosystem-level effects of oligotrophication/re-oligotrophication on aquatic CH production and subsequent ecological responses remain to be elucidated. It has been hypothesized that dissolved inorganic phosphorus (DIP)-deficient conditions drive the ecosystem to utilize poorly bioavailable organic phosphorus for biomass formation, thereby generating CH as a by-product. To test this hypothesis, a mass balance approach was used to estimate in situ oxic methane production (OMP) in an oligotrophic, deep Lake Fuxian.

Water transfer projects and microplastics: Analyzing changes in lake environments with a focus on Wabu Lake, China.

Microplastics are widespread in freshwaters, yet their interaction with navigational structures remains unclear. This study compared the distribution and characteristics of microplastics before and after navigation in Wabu Lake. Microplastic concentrations decreased significantly in both surface water and sediment due to navigation opened, from 13.

A mouse model of the protease-activated receptor 4 Pro310Leu variant has reduced platelet reactivity.

Background: Protease-activated receptor 4 (PAR4) mediates thrombin signaling on platelets and other cells. Our recent structural studies demonstrated that a single nucleotide polymorphism in extracellular loop 3 and PAR4-P310L (rs2227376) leads to a hyporeactive receptor.

Objectives: The goal of this study was to determine how the hyporeactive PAR4 variant in extracellular loop 3 impacts platelet function in vivo using a novel knock-in mouse model (PAR4-322L).

Multiparametric US for Identifying Metabolic Dysfunction-associated Steatohepatitis: A Prospective Multicenter Study.

Background Noninvasive evaluation of metabolic dysfunction-associated fatty liver disease (MAFLD) with multiparametric US is essential, but multicenter studies are lacking. Purpose To evaluate the ability of multiparametric US with attenuation imaging (ATI) and two-dimensional (2D) shear-wave elastography (SWE) for predicting metabolic dysfunction-associated steatohepatitis (MASH) in participants with MAFLD, regardless of hepatitis B virus infection status. Materials and Methods This prospective cross-sectional multicenter study of consecutive adults with MAFLD who underwent multiparametric US with ATI and 2D SWE, as well as liver biopsy, from September 2020 to June 2022 was conducted in 12 tertiary hospitals in China.

Glycolysis-Mediated Activation of v-ATPase by Nicotinamide Mononucleotide Ameliorates Lipid-Induced Cardiomyopathy by Repressing the CD36-TLR4 Axis.

Background: Chronic overconsumption of lipids followed by their excessive accumulation in the heart leads to cardiomyopathy. The cause of lipid-induced cardiomyopathy involves a pivotal role for the proton-pump vacuolar-type H-ATPase (v-ATPase), which acidifies endosomes, and for lipid-transporter CD36, which is stored in acidified endosomes. During lipid overexposure, an increased influx of lipids into cardiomyocytes is sensed by v-ATPase, which then disassembles, causing endosomal de-acidification and expulsion of stored CD36 from the endosomes toward the sarcolemma.

A Mouse Model of the Protease Activated Receptor 4 (PAR4) Pro310Leu Variant has Reduced Platelet Reactivity.

Background: Protease activated receptor 4 (PAR4) mediates thrombin signaling on platelets and other cells. Our recent structural studies demonstrated a single nucleotide polymorphism in extracellular loop 3 (ECL3), PAR4-P310L (rs2227376) leads to a hypo-reactive receptor.

Objectives: The goal of this study was to determine how the hypo-reactive PAR4 variant in ECL3 impacts platelet function in vivo using a novel knock-in mouse model (PAR4-322L).

Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial.

KRAS G12C mutation is prevalent in ~4% of colorectal cancer (CRC) and is associated with poor prognosis. Divarasib, a KRAS G12C inhibitor, has shown modest activity as a single agent in KRAS G12C-positive CRC at 400 mg. Epidermal growth factor receptor has been recognized as a major upstream activator of RAS-MAPK signaling, a proposed key mechanism of resistance to KRAS G12C inhibition in CRC.

Cascaded metasurfaces for high-purity vortex generation.

We introduce a new paradigm for generating high-purity vortex beams with metasurfaces. By applying optical neural networks to a system of cascaded phase-only metasurfaces, we demonstrate the efficient generation of high-quality Laguerre-Gaussian (LG) vortex modes. Our approach is based on two metasurfaces where one metasurface redistributes the intensity profile of light in accord with Rayleigh-Sommerfeld diffraction rules, and then the second metasurface matches the required phases for the vortex beams.

Toward Integrating EBPR and the Short-Cut Nitrogen Removal Process in a One-Stage System for Treating High-Strength Wastewater.

Enhanced biological phosphorus removal (EBPR) is an economical and sustainable process for phosphorus removal from wastewater. Despite the widespread application of EBPR for low-strength domestic wastewater treatment, limited investigations have been conducted to apply EBPR to the high-strength wastewaters, particularly, the integration of EBPR and the short-cut nitrogen removal process in the one-stage system remains challenging. Herein, we reported a novel proof-of-concept demonstration of integrating EBPR and nitritation (oxidation of ammonium to nitrite) in a one-stage sequencing batch reactor to achieve simultaneous high-strength phosphorus and short-cut nitrogen removal.

Single-Agent Divarasib (GDC-6036) in Solid Tumors with a G12C Mutation.

Background: Divarasib (GDC-6036) is a covalent KRAS G12C inhibitor that was designed to have high potency and selectivity.

Methods: In a phase 1 study, we evaluated divarasib administered orally once daily (at doses ranging from 50 to 400 mg) in patients who had advanced or metastatic solid tumors that harbor a G12C mutation. The primary objective was an assessment of safety; pharmacokinetics, investigator-evaluated antitumor activity, and biomarkers of response and resistance were also assessed.

Multimodality US versus Thyroid Imaging Reporting and Data System Criteria in Recommending Fine-Needle Aspiration of Thyroid Nodules.

Background Current guidelines recommend the use of conventional US for risk stratification and management of thyroid nodules. However, fine-needle aspiration (FNA) is often recommended in benign nodules. Purpose To compare the diagnostic performance of multimodality US (including conventional US, strain elastography, and contrast-enhanced US [CEUS]) with the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) in the recommendation of FNA for thyroid nodules to reduce unnecessary biopsies.

Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke.

Background And Objectives: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance.

Microwave Ablation for Papillary Thyroid Microcarcinoma with and without US-detected Capsule Invasion: A Multicenter Prospective Cohort Study.

Background Microwave ablation (MWA) has achieved favorable results in the treatment of papillary thyroid microcarcinoma (PTMC) confined in glandular parenchyma. However, studies on the outcome of MWA for PTMC with US-detected capsular invasion remain unclarified in the literature. Purpose To compare the feasibility, effectiveness, and safety of MWA in the treatment of PTMC with and without US-detected capsular invasion.

Deficiency Promotes Pulmonary Arterial Hypertension via HGF/c-Met Signaling.

Background: In large-scale genomic studies, , an endothelial-specific transcription factor, has been suggested as a putative causal gene of pulmonary arterial hypertension (PAH); however, its role and molecular mechanisms remain to be elucidated. We investigated the functional impacts and acting mechanisms of impaired Sox17 (SRY-related HMG-box17) pathway in PAH and explored its potential as a therapeutic target.

Methods: In adult mice, deletion in pulmonary endothelial cells (ECs) induced PAH under hypoxia with high penetrance and severity, but not under normoxia.

Cell-specific regulation of gene expression using splicing-dependent frameshifting.

Precise and reliable cell-specific gene delivery remains technically challenging. Here we report a splicing-based approach for controlling gene expression whereby separate translational reading frames are coupled to the inclusion or exclusion of mutated, frameshifting cell-specific alternative exons. Candidate exons are identified by analyzing thousands of publicly available RNA sequencing datasets and filtering by cell specificity, conservation, and local intron length.