Identify novel therapeutic targets for type II diabetes and periodontitis: insights from single-cell analysis and Mendelian randomization analysis.

Background: Periodontitis is a common complication of type II diabetes (T2D). However, the existing research cannot fully elucidate the association between them, let alone identify therapeutic targets for precise treatment of diabetic periodontitis. Therefore, we employed integrated genetic approaches such as single-cell analysis, Mendelian randomization (MR) analysis and colocalization analysis to uncover novel therapeutic targets for T2D and periodontitis.

Effect of Microalloying Rare-Earth Nd on Microstructure Evolution and Mechanical Property of Cu Alloy.

Cu alloys have been widely used in the manufacture of liners because of their high density, good plasticity, and excellent thermal conductivity. In order to achieve excellent jet stability and penetration performance, it is necessary to further improve the mechanical properties of Cu-based liners. Nevertheless, the simultaneous enhancement of strength and ductility of the Cu alloys remains a huge challenge due to the strength-ductility trade-off phenomenon of metals/alloys.

A Single Interfacial Point Mutation Rescues Solution Structure Determination of the Complex of HMG-D with a DNA Bulge.

Broadening of signals from atoms at interfaces can often be a limiting factor in applying solution NMR to the structure determination of complexes. Common contributors to such problems include exchange between free and bound states and the increased molecular weight of complexes relative to the free components, but another cause that can be more difficult to deal with occurs when conformational dynamics within the interface takes place at an intermediate rate on the chemical shift timescale. In this work we show how a carefully chosen mutation in the protein HMG-D rescued such a situation, making possible high-resolution structure determination of its complex with a dA bulge DNA ligand designed to mimic a natural DNA bend, and thereby revealing a new spatial organization of the complex.

Ribosomal modification protein rimK-like family member A activates betaine-homocysteine S-methyltransferase 1 to ameliorate hepatic steatosis.

Nonalcoholic fatty liver disease (NAFLD) is a serious threat to public health, but its underlying mechanism remains poorly understood. In screening important genes using Gene Importance Calculator (GIC) we developed previously, ribosomal modification protein rimK-like family member A (RIMKLA) was predicted as one essential gene but its functions remained largely unknown. The current study determined the roles of RIMKLA in regulating glucose and lipid metabolism.

PANX1-mediated ATP release confers FAM3A's suppression effects on hepatic gluconeogenesis and lipogenesis.

Background: Extracellular adenosine triphosphate (ATP) is an important signal molecule. In previous studies, intensive research had revealed the crucial roles of family with sequence similarity 3 member A (FAM3A) in controlling hepatic glucolipid metabolism, islet β cell function, adipocyte differentiation, blood pressure, and other biological and pathophysiological processes. Although mitochondrial protein FAM3A plays crucial roles in the regulation of glucolipid metabolism via stimulating ATP release to activate P2 receptor pathways, its mechanism in promoting ATP release in hepatocytes remains unrevealed.

Novel Protein Biomarkers and Therapeutic Targets for Type 1 Diabetes and Its Complications: Insights from Summary-Data-Based Mendelian Randomization and Colocalization Analysis.

Millions of patients suffer from type 1 diabetes (T1D) and its associated complications. Nevertheless, the pursuit of a cure for T1D has encountered significant challenges, with a crucial impediment being the lack of biomarkers that can accurately predict the progression of T1D and reliable therapeutic targets for T1D. Hence, there is an urgent need to discover novel protein biomarkers and therapeutic targets, which holds promise for targeted therapy for T1D.

Precision detection of hepatocellular carcinoma-associated telomerase RNA with SA@Comb-HCR nanosystem.

Accurate intracellular visualization of human telomerase RNA (hTR) is imperative for early diagnosis and treatment monitoring of hepatocellular carcinoma (HCC). While isothermal amplification-based DNA cascade strategies are promising, challenges persist in achieving great intake efficiency of detection probes within tumor cells and enhancing intracellular reaction efficiency. This study introduces a SA@Comb-HCR nanosystem, a highly effective approach for in situ hTR detection in HCC cells.

The Influence of Rare Earth Ce on the Microstructure and Properties of Cast Pure Copper.

The effects of rare earth Ce on the microstructure and properties of cast pure copper were investigated through thermodynamic calculations, XRD analysis, mechanical testing, metallographic microscopy, and scanning electron microscopy (SEM). The experimental results demonstrate that the reaction between rare earth Ce and oxygen as well as sulfur in copper exhibits a significantly negative Gibbs free energy value, indicating a strong thermodynamic driving force for deoxidation and desulfurization reactions. Ce is capable of removing trace amounts of O and S from copper.

Study on Influence of Rare Earth Ce on Micro and Macro Properties of U75V Steel.

Non-metallic inclusions in steel have great influence on the continuity of the steel matrix and the mechanical properties of steel. The precipitation sequence of Ce inclusions in molten steel is predicted by thermodynamic calculations. The results show that Ce content will affect the precipitation sequence of rare earth inclusions in molten steel, and the formation of CeO, CeO and CeAlO will be inhibited with the increase in Ce content.

Ultra-efficient radio-immunotherapy for reprogramming the hypoxic and immunosuppressive tumor microenvironment with durable innate immune memory.

Radiosensitization efficacy of conventional tumor radiosensitizers has been frequently limited by insufficient competence for tumor microenvironment (TME) regulation and unfavorable cellular uptake at biological barriers. Here, we reported an ultra-efficient radiotherapy (RT) strategy by synthesizing an extracellular vesicles (EVs)-encapsulated hollow MnO to load metformin (Met@HMnER). It demonstrated significant RT enhancement by morphological control of catalyst and cellular respiratory depression against conventional solid MnO.

Trajectories of antepartum depressive symptoms and birthweight: a multicenter and prospective cohort study.

Background: Antepartum depression is a prevalent unhealthy mental health problem worldwide, particularly in low-income countries. It is a major contributor to adverse birth outcomes. Previous studies linking antepartum depression to birthweight have yielded conflicting results, which may be the reason that the depressive symptoms were only measured once during pregnancy.

A smart TESTER for reliable discrimination of cancer-derived small extracellular vesicles.

Cancer-derived small extracellular vesicles (csEVs) are crucial liquid biopsy indicators that reflect the presence and progression of many malignancies. However, reliable discrimination of csEVs remains a great challenge owing to the interference from normal sEVs (nsEVs) and low abundance in the early stages of cancer. In this work, we developed a Two-Elements Selectively Triggered csEVs Recognization (TESTER) strategy for selective identification of csEVs from the complex clinical body fluid samples.

Hepatocyte-secreted FAM3D ameliorates hepatic steatosis by activating FPR1-hnRNP U-GR-SCAD pathway to enhance lipid oxidation.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide; however, the underlying mechanisms remain poorly understood. FAM3D is a member of the FAM3 family; however, its role in hepatic glycolipid metabolism remains unknown. Serum FAM3D levels are positively correlated with fasting blood glucose levels in patients with diabetes.

Trajectories of depressive symptoms during pregnancy and risk of premature birth: A multicenter and prospective cohort study.

Previous studies only assessed the association between depressive symptoms and risk of preterm birth (PTB) at a time-point during pregnancy, resulting in inconsistent or contradictory results. Therefore, we aimed to explore the associations between the trajectories of depressive symptoms during pregnancy and risk of PTB. In total, 7732 pregnant women were included in 24 hospitals from 15 provinces of China.

Trim-Away ubiquitinates and degrades lysine-less and N-terminally acetylated substrates.

TRIM proteins are the largest family of E3 ligases in mammals. They include the intracellular antibody receptor TRIM21, which is responsible for mediating targeted protein degradation during Trim-Away. Despite their importance, the ubiquitination mechanism of TRIM ligases has remained elusive.

FAM3A Deficiency - Induced Mitochondrial Dysfunction Underlies Post-Infarct Mortality and Heart Failure.

Mitochondrial protein sequence similarity 3 gene family member A (FAM3A) plays important roles in the electron transfer chain, while its functions in the heart are still unknown. This study aims to explore the roles and mechanisms of FAM3A after myocardial infarction (MI). FAM3A-deficient (Fam3a) mice were implemented with MI injury and showed lower survival rates at 4 weeks as well as decreased cardiac systolic function.

Comparative effectiveness of different hepatocellular carcinoma screening intervals or modalities: a systematic review and meta-analysis.

Background: Current guidelines recommend hepatocellular carcinoma (HCC) screening in high-risk populations. However, the ideal HCC screening interval and screening modality have not been determined. This study aimed to compare the screening efficacy among different modalities with various intervals.

High-fidelity imaging of intracellular microRNA a bioorthogonal nanoprobe.

The spatiotemporal visualization of intracellular microRNA (miRNA) plays a critical role in the diagnosis and treatment of malignant disease. Although DNAzyme-based biosensing has been regarded as the most promising candidate, inefficient analytical resolution is frequently encountered. Here, we propose a bioorthogonal approach toward high-fidelity imaging of intracellular miRNA by designing a multifunctional nanoprobe that integrates MnO nanosheet-mediated intracellular delivery and activation by a fat mass and obesity-associated protein (FTO)-switched positive feedback.

Pre-pregnancy body mass index and risk of maternal or infant complications with gestational diabetes mellitus as a mediator: A multicenter, longitudinal cohort study in China.

Aims: We explored the complex relationships between pre-pregnancy body mass index (pBMI) and maternal or infant complications and the mediating role of gestational diabetes mellitus (GDM) in these relationships.

Methods: Pregnant women from 24 hospitals in 15 different provinces of China were enrolled in 2017 and followed through 2018. Propensity score-based inverse probability of treatment weighting, logistic regression, restricted cubic spline models, and causal mediation analysis were utilized.

KAT8 acetylation-controlled lipolysis affects the invasive and migratory potential of colorectal cancer cells.

Epigenetic mechanisms involved in gene expression play an essential role in various cellular processes, including lipid metabolism. Lysine acetyltransferase 8 (KAT8), a histone acetyltransferase, has been reported to mediate de novo lipogenesis by acetylating fatty acid synthase. However, the effect of KAT8 on lipolysis is unclear.