Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis.

In this study, we integrated transcriptomic and metabolomic analyses to achieve a comprehensive understanding of the underlying mechanisms of diabetic cardiomyopathy (DCM) in a diabetic rat model. Functional and molecular characterizations revealed significant cardiac injury, dysfunction, and ventricular remodeling in DCM. A thorough analysis of global changes in genes and metabolites showed that amino acid metabolism, especially the breakdown of branched-chain amino acids (BCAAs) such as valine, leucine, and isoleucine, is highly dysregulated.

Precise deletion, replacement and inversion of large DNA fragments in plants using dual prime editing.

Precise manipulation of genome structural variations holds great potential for plant trait improvement and biological research. Here we present a genome-editing approach, dual prime editing (DualPE), that efficiently facilitates precise deletion, replacement and inversion of large DNA fragments in plants. In our experiments, DualPE enabled the production of specific genomic deletions ranging from ~500 bp to 2 Mb in wheat protoplasts and plants.

TP53I11 Functions Downstream of Multiple MicroRNAs to Increase ER Calcium Levels and Inhibits Cancer Cell Proliferation.

Cells meticulously regulate free calcium ion (Ca) concentrations, with the endoplasmic reticulum (ER) being crucial for Ca homeostasis. Disruptions in ER Ca balance can contribute to various diseases, including cancer. Although considerable research has focused on the direct mechanisms of ER Ca regulation, the role of microRNAs (miRNAs) in this process remains underexplored.

SEAD reference panel with 22,134 haplotypes boosts rare variant imputation and genome-wide association analysis in Asian populations.

Limited whole genome sequencing (WGS) studies in Asian populations result in a lack of representative reference panels, thus hindering the discovery of ancestry-specific variants. Here, we present the South and East Asian reference Database (SEAD) panel ( https://imputationserver.westlake.

Determining the Optimal Age for Extracranial-Intracranial Bypass Surgery: A Post Hoc Analysis of the CMOSS Randomized Trial.

Background: Previous trials have failed to demonstrate the benefits of extracranial-intracranial (EC-IC) bypass surgery for patients with carotid or middle cerebral artery occlusion. However, little evidence has focused on the effect of age on prognosis. This study aimed to explore whether EC-IC bypass surgery can provide greater benefits than medical therapy alone in specific age groups.

Serum GFAP and UCH-L1 Levels for the Assessment of the Absence of Hemorrhagic Transformation: A Multicenter Prospective Cohort Study.

Background: Currently, validated biomarkers for assessing hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) are lacking. We aimed to validate a test combining GFAP (glial fibrillary acidic protein) and UCH-L1 (ubiquitin C-terminal hydrolase-L1) to indicate the absence of HT after IVT.

Methods: We prospectively enrolled consecutive patients with stroke treated with IVT from 16 hospitals.

Imetelstat, a novel, first-in-class telomerase inhibitor: Mechanism of action, clinical, and translational science.

Most cancers and neoplastic progenitor cells have elevated telomerase activity and preservation of telomeres that promote cellular immortality, making telomerase a rational target for the treatment of cancer. Imetelstat is a first-in-class, 13-mer oligonucleotide that binds with high affinity to the template region of the RNA component of human telomerase and acts as a competitive inhibitor of human telomerase enzymatic activity. Pharmacokinetics, pharmacodynamics, exposure-response analyses, efficacy, and safety of imetelstat have been evaluated in vitro, in vivo, and clinically in solid tumor and hematologic malignancies, including lower-risk myelodysplastic syndromes (LR-MDS) and myeloproliferative neoplasms.

Dual activation of soybean resistance against Phytophthora sojae by pectin lyase and degraded pectin oligosaccharides.

Phytophthora pathogens secrete numerous apoplastic effectors to manipulate host immunity. Herein, we identified a polysaccharide lyase 1 protein, PsPL1, which acts as an essential virulence factor of P. sojae infection in soybean.

Clinical Accuracy of the G.LAB MD41A0 Upper Arm Blood Pressure Monitor in Pregnancy and Pre-Eclampsia Using the AAMI/ESH/ISO as Reference Standard.

Objective: Validation of blood pressure (BP) monitors in pregnant women are needed to ensure the accurate measurement of BP in pregnancy. Therefore the study aimed to evaluate the measurement accuracy of the G.LAB MD41A0 oscillometric automatic upper-arm blood pressure monitor in pregnancy and pre-eclampsia women according to the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018).

Myocardial Fibrosis Assessment at 3-T versus 5-T Myocardial Late Gadolinium Enhancement MRI: Early Results.

Background Cardiac MRI at 5 T has recently become available and potentially improves tissue contrast enhancement at gadolinium chelate-enhanced T1-weighted imaging. Purpose To evaluate the feasibility of 5-T myocardial late gadolinium enhancement (LGE) MRI in assessing myocardial fibrosis by comparing image quality and LGE quantification with reference-standard 3-T myocardial LGE MRI. Materials and Methods Consecutive patients with confirmed myocardial fibrosis on previous 3-T MRI scans between January 2023 and July 2023 prospectively underwent follow-up imaging from August 2023 to November 2023.

The epithelial barrier theory and its associated diseases.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide.

The Influence of Identity Bubble Reinforcement on the Happiness Index among Chinese Medical Staff: The Mediating Role of General Self-Efficacy.

Objective: This study aimed to explore the mediating role of general self-efficacy in the influence of social media identity bubble reinforcement on the happiness index among Chinese medical staff.

Methods: This study utilized data (n = 877) from the 2022 Psychological and Behavioral Investigation of Chinese Residents (PBICR) related to medical staff. Correlation analysis was performed using SPSS 26.

A framework for human evaluation of large language models in healthcare derived from literature review.

With generative artificial intelligence (GenAI), particularly large language models (LLMs), continuing to make inroads in healthcare, assessing LLMs with human evaluations is essential to assuring safety and effectiveness. This study reviews existing literature on human evaluation methodologies for LLMs in healthcare across various medical specialties and addresses factors such as evaluation dimensions, sample types and sizes, selection, and recruitment of evaluators, frameworks and metrics, evaluation process, and statistical analysis type. Our literature review of 142 studies shows gaps in reliability, generalizability, and applicability of current human evaluation practices.

SIRT1 improves lactate homeostasis in the brain to alleviate parkinsonism via deacetylation and inhibition of PKM2.

Sirtuin 1 (SIRT1) is a histone deacetylase and plays diverse functions in various physiological events, from development to lifespan regulation. Here, in Parkinson's disease (PD) model mice, we demonstrated that SIRT1 ameliorates parkinsonism, while SIRT1 knockdown further aggravates PD phenotypes. Mechanistically, SIRT1 interacts with and deacetylates pyruvate kinase M2 (PKM2) at K135 and K206, thus leading to reduced PKM2 enzyme activity and lactate production, which eventually results in decreased glial activation in the brain.

Study on the Tribological Properties of Multilayer Concentric Hexagonal Laser Texturing on Rubber Surfaces of Screw Pumps.

Given the friction and drag reduction effects observed in various biological hexagonal structures in nature, a new design was implemented on the rubber surface of the stator of a submersible screw pump. This design featured a multilayer concentric hexagonal groove structure. Furthermore, a composite multilayer hexagonal structure integrating grooves and pits was also developed and applied.

The Protective Efficacy of a SARS-CoV-2 Vaccine Candidate B.1.351V against Several Variant Challenges in K18-hACE2 Mice.

The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.

Establishment of a normal control model of children's brain 18-fluorodeoxyglucose positron emission tomography and analysis of the changing pattern in patients aged 0-14 years.

Background: It is difficult to obtain 18-fluorodeoxyglucose positron emission tomography (FDG-PET) data from normal children, and changes in brain metabolism in children due to growth and development are poorly understood. For the first time, we established a normal control model of brain FDG-PET in children and evaluated its feasibility. The association of PET with age in children aged 0-14 years was analyzed.

Effects of the Thiol Methyltransferase Inhibitor (±)-2,3-Dichloro--Methylbenzylamine (DCMB) on the Pharmacokinetics and Metabolism of Vicagrel in Rats.

P2Y receptor inhibitors are commonly used in clinical antiplatelet therapy, typically alongside other medications. Vicagrel, a promising P2Y receptor inhibitor, has submitted a new drug marketing application to the United States Food and Drug Administration. Its primary metabolites and some metabolic pathways are identical to those of clopidogrel.