ERK-USP9X-coupled regulation of thymidine kinase 1 promotes both its enzyme activity-dependent and its enzyme activity-independent functions for tumor growth.

Thymidine kinase 1 (TK1), a crucial enzyme in DNA synthesis, is highly expressed in various cancers. However, the mechanisms underlying its elevated expression and the implications for tumor metabolism remain unclear. Here we demonstrate that activation of growth factor receptors enhances TK1 expression.

Vericiguat improves cardiac remodelling and function in rats with doxorubicin-induced cardiomyopathy.

Purpose: Vericiguat, a soluble guanylate cyclase (sGC) stimulator, has been demonstrated effective in improving prognosis of patients with heart failure with reduced ejection fraction. However, there are limited data concerning the effect of vericiguat in patients with doxorubicin (DOX)-induced cardiomyopathy (DIC). In this study, we investigated the effects of vericiguat on cardiac structure and function in rats with DIC as well as their potential mechanisms of action.

Deubiquitinase MYSM1 promotes doxorubicin-induced cardiotoxicity by mediating TRIM21-ferroptosis axis in cardiomyocytes.

Anthracycline antitumor drug doxorubicin (DOX) induces severe cardiotoxicity. Deubiquitinating enzymes (DUBs) are crucial for protein stability and function and play a significant role in cardiac pathophysiology. By comparing RNA sequencing datasets and conducting functional screening, we determined that Myb-like, SWIRM, and MPN domains 1 (MYSM1) is a key regulator of DOX-induced cardiotoxicity.

H9 Consensus Hemagglutinin Subunit Vaccine with Adjuvants Induces Robust Mucosal and Systemic Immune Responses in Mice by Intranasal Administration.

The H9N2 subtype avian influenza viruses mainly cause respiratory symptoms, reduce the egg production and fertility of poultry, and result in secondary infections, posing a great threat to the poultry industry and human health. Currently, all H9N2 avian influenza commercial vaccines are inactivated vaccines, which provide protection for immunized animals but cannot inhibit the spread of the virus and make it difficult to distinguish between the infected animals and vaccinated animals. In this study, a trimeric consensus H9 hemagglutinin (HA) subunit vaccine for the H9N2 subtype avian influenza virus based on a baculovirus expression system was first generated, and then the effects of three molecular adjuvants on the H9 HA subunit vaccine, Cholera toxin subunit B (CTB), flagellin, and granulocyte-macrophage colony-stimulating factor (GM-CSF) fused with H9 HA, and one synthetic compound, a polyinosinic-polycytidylic acid (PolyI:C) adjuvant, were evaluated in mice by intranasal administration.

Cardiomyocyte-derived USP28 negatively regulates antioxidant response and promotes cardiac hypertrophy via deubiquitinating TRIM21.

Cardiac hypertrophy is an important pathological basis for heart failure. Most physiological activities of cardiomyocytes are regulated by proteins and their post-translational modification. Deubiquitinating enzymes (DUBs) are involved in protein stability maintenance and closely related to myocardial hypertrophy.

Lipidomic Profiling and Storage-Induced Changes in Cassava Flour Using LC-MS/MS.

Cassava serves as a primary staple food for over one billion people worldwide. The quality of cassava flour is markedly affected by the oxidation and deterioration of lipids during storage. Despite its significance, the lipid composition of cassava flour and its alterations throughout storage periods have not been extensively studied.

Achieving smooth motion in displacement amplification piezoelectric stick-slip actuator.

Traditional piezoelectric stick-slip actuators often suffer from significant backward motion phenomena, which greatly impact their output performance. To overcome this issue, a novel displacement amplification piezoelectric stick-slip actuator was meticulously designed. It integrates an L-shaped displacement amplification mechanism with a parallelogram-compliant mechanism.

Chinese visceral adipose index is more closely associated with risk of arterial stiffness than traditional obesity indicators: a cohort study.

Background: The Chinese visceral adiposity index (CVAI) is a new index to evaluate visceral adipose tissue in the Chinese population. Arterial stiffness (AS) is a kind of degeneration of the large arteries, and obesity is an essential contributing factor to AS. Our study aimed to explore the longitudinal association between CVAI and the risk of AS and to compare the predictive power of CVAI, body mass index (BMI), and waist circumference (WC) for AS.

Podocyte OTUD5 alleviates diabetic kidney disease through deubiquitinating TAK1 and reducing podocyte inflammation and injury.

Recent studies have shown the crucial role of podocyte injury in the development of diabetic kidney disease (DKD). Deubiquitinating modification of proteins is widely involved in the occurrence and development of diseases. Here, we explore the role and regulating mechanism of a deubiquitinating enzyme, OTUD5, in podocyte injury and DKD.

Glycolytic enzyme PFKL governs lipolysis by promoting lipid droplet-mitochondria tethering to enhance β-oxidation and tumor cell proliferation.

Lipid droplet tethering with mitochondria for fatty acid oxidation is critical for tumor cells to counteract energy stress. However, the underlying mechanism remains unclear. Here, we demonstrate that glucose deprivation induces phosphorylation of the glycolytic enzyme phosphofructokinase, liver type (PFKL), reducing its activity and favoring its interaction with perilipin 2 (PLIN2).

Coconstruction of Supramolecular Lithium-Conducting Cross-Linked Networks Based on PVDF and Triblock Polymer Nanomicrosphere Solid-State Polymer Electrolytes for Lithium-Metal Batteries.

Uneven lithium plating and low ionic conductivity currently impede the realization of high-capacity rechargeable lithium metal batteries. And the conventional poly(ethylene oxide) (PEO) solid-state electrolytes are unsuitable for high-energy-density Li anode applications due to their low lithium-ion transference number and high reactivity with Li metal, leading to detrimental dendrite formation and potentially hazardous exothermic reactions with the electrolyte. In this study, we employ a supramolecular approach to develop a novel polymer solid-state electrolyte based on poly(vinylidene fluoride) (PVDF) and a novel triblock polymer nanomicrosphere, (poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone), (PCL-PEG-PCL).

Carnosol attenuates angiotensin II-induced cardiac remodeling and inflammation via directly binding to p38 and inhibiting p38 activation.

Chronic inflammation is a significant contributor to hypertensive heart failure. Carnosol (Car), primarily derived from the sage plant (Salvia carnosa), exhibits anti-inflammatory properties in a range of systems. Nevertheless, the influence of angiotensin II (Ang II) on cardiac remodeling remains uncharted.

Epsilon-poly-l-lysine microneedle patch loaded with amorphous doxycycline nanoparticles for synergistic treatment of skin infection.

The development of antibiotic-loaded microneedles has been hindered for years by limited excipient options, restricted drug-loading space, poor microneedle formability, and short-term drug retention. Therefore, this study proposes a dissolving microneedle fabricated from the host-defense peptide ε-poly-l-lysine (EPL) as an antibacterial adjuvant system for delivering antibiotics. EPL serves not only as a major matrix material for the microneedle tips, but also as a broad-spectrum antibacterial agent that facilitates the intracellular accumulation of the antibiotic doxycycline (DOX) by increasing bacterial cell membrane permeability.

Deubiquitinase OTUD6a drives cardiac inflammation and hypertrophy by deubiquitination of STING.

Background: Cardiac hypertrophy is a crucial pathological characteristic of hypertensive heart disease and subsequent heart failure. Deubiquitinating enzymes (DUBs) have been found to be involved in the regulation of myocardial hypertrophy. OTU Domain-Containing Protein 6a (OTUD6a) is a recently identified DUB.

Metagenomic insights into protein degradation mechanisms in natural fermentation of cassava leaves.

Cassava (Manihot esculenta Crantz) leaves, the primary by-product of cassava processing, constitute a significant protein source, accounting for 18 to 38 percent on a dry weight basis. Despite their nutritional value, a substantial portion of these leaves is often discarded post-harvest, resulting in notable resource waste. This study employs metagenomic technology to investigate the protein degradation mechanism in cassava leaves, aiming to provide a technical reference for value-added of this by-product.

Cardiovascular health and life expectancy with and without cardiovascular disease in the middle-aged and elderly Chinese population.

Background: High cardiovascular health (CVH) was associated with lower risk of cardiovascular disease (CVD) and longer life expectancy. However, whether life years lived without CVD could increase faster than or at least at the same pace as total lifespan remains unknown. We aimed to explore the associations of CVH status with total life expectancy and life years lived with and without CVD among middle-aged and elderly men and women.

Advances in device-based treatment of heart failure with preserved ejection fraction: evidence from clinical trials.

Heart failure with preserved ejection fraction (HFpEF) is a group of clinical syndromes that exhibit a remarkably heterogeneous phenotype, characterized by symptoms and signs of heart failure, left ventricular diastolic dysfunction, elevated levels of natriuretic peptides, and an ejection fraction greater than or equal to 50%. With the aging of the population and the escalating prevalence of hypertension, obesity, and diabetes, the incidence of HFpEF is progressively rising. Drug therapy options for HFpEF are currently limited, and the associated high risk of cardiovascular mortality and heart failure rehospitalization significantly impact patients' quality of life and longevity while imposing a substantial economic burden on society.

Intelligent Optimization Design of a Phononic Crystal Air-Coupled Ultrasound Transducer.

To further improve the operational performance of a phononic crystal air-coupled ultrasonic transducer while reducing the number of simulations, an intelligent optimization design strategy is proposed by combining finite element simulation analysis and artificial intelligence (AI) methods. In the proposed strategy, the structural design parameters of 1-3 piezoelectric composites and acoustic impedance gradient matching layer are sampled using the optimal Latin hypercube sampling (OLHS) method. Moreover, the COMSOL software is utilized to calculate the performance parameters of the transducer.

Advance in the pharmacological and comorbidities management of heart failure with preserved ejection fraction: evidence from clinical trials.

The prevalence of heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of the total heart failure population, and with the aging of the population and the increasing prevalence of hypertension, obesity, and type 2 diabetes (T2DM), the incidence of HFpEF continues to rise and has become the most common subtype of heart failure. Compared with heart failure with reduced ejection fraction, HFpEF has a more complex pathophysiology and is more often associated with hypertension, T2DM, obesity, atrial fibrillation, renal insufficiency, pulmonary hypertension, obstructive sleep apnea, and other comorbidities. HFpEF has generally been considered a syndrome with high phenotypic heterogeneity, and no effective treatments have been shown to reduce mortality to date.

Association of the time course of Chinese visceral adiposity index accumulation with cardiovascular events in patients with hypertension.

Background: The Chinese visceral adiposity index (CVAI), a simple surrogate measure of visceral fat, is significantly associated with cardiovascular disease (CVD) risk in the general population. This study aimed to evaluate the association of cumulative CVAI (cumCVAI) exposure and its accumulation time course with CVD risk among patients with hypertension.

Methods: This prospective study involved 15,350 patients with hypertension from the Kailuan Study who were evaluated at least three times in the observation period of 2006 to 2014 (2006-2007, 2010-2011, and 2014-2015) and who were free of myocardial infarction and stroke before 2014.

Liraglutide ameliorates oxidized LDL-induced endothelial dysfunction by GLP-1R-dependent downregulation of LOX-1-mediated oxidative stress and inflammation.

Objective: To investigate the effects of glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide on endothelial dysfunction in LDL receptor-deficient (LDLR-KO) mice and ox-LDL-challenged human umbilical vein endothelial cells (HUVECs) and its possible mechanism.

Methods: LDLR-KO mice were randomly treated with normal saline, liraglutide, or liraglutide plus a GLP-1R antagonist exendin-9 for four weeks. In parallel, HUVECs were cultured with ox-LDL alone or combined with liraglutide, in the presence or absence of lectin-like ox-LDL receptor-1(LOX-1) overexpression or GLP-1R knockdown.

Association of Cardiovascular Health Assessed by the New Life's Essential 8 Metrics With Years Lived Without Cardiovascular Disease.

Background The American Heart Association recently proposed an updated definition of cardiovascular health (CVH) named as Life's Essential 8. We aimed to explore the association between this latest published CVH measurement and years lived without cardiovascular disease (CVD) among the Chinese population. Methods and Results We included 89 755 adults free of CVD at baseline from the Kailuan study.