Mouse models used to test the role of reactive oxygen species in aging and age-related chronic diseases.

With the development of the technology to generate transgenic and knockout mice in the 1990s, investigators had a powerful tool to directly test the impact of altering a specific gene on a biological process or disease. Over the past three decades, investigators have used transgenic and knockout mouse models, which have altered expression of antioxidant genes, to test the role of oxidative stress/damage in aging and age-related diseases. In this comprehensive review, we describe the studies using transgenic and knockout mouse models to test the role of oxidative stress/damage in aging (longevity) and three age-related diseases, e.

Characterizing age-related changes in intact mitochondrial proteoforms in murine hearts using quantitative top-down proteomics.

Background: Cardiovascular diseases (CVDs) are the leading cause of death worldwide, and the prevalence of CVDs increases markedly with age. Due to the high energetic demand, the heart is highly sensitive to mitochondrial dysfunction. The complexity of the cardiac mitochondrial proteome hinders the development of effective strategies that target mitochondrial dysfunction in CVDs.

Emerging interactions between mitochondria and NAD metabolism in cardiometabolic diseases.

Nicotinamide adenine dinucleotide (NAD) is an essential coenzyme for redox reactions and regulates cellular catabolic pathways. An intertwined relationship exists between NAD and mitochondria, with consequences for mitochondrial function. Dysregulation in NAD homeostasis can lead to impaired energetics and increased oxidative stress, contributing to the pathogenesis of cardiometabolic diseases.

One-Step Phase Separation and Mineralization Fabrication of Membranes for Oily Wastewater Treatment.

Oily wastewater threatens the environment and the human health. Membrane technology offers a simple and efficient alternative to separating oil and water. However, complex membrane modifications are usually employed to optimize the separation performance.

Hyperactive mTORC1/4EBP1 Signaling Dysregulates Proteostasis and Accelerates Cardiac Aging.

The mechanistic target of rapamycin complex 1 (mTORC1) has a major impact on aging by regulation of proteostasis. It is well established that mTORC1 signaling is hyperactivated with aging and age-related diseases. Previous studies have shown that partial inhibition of mTOR signaling by rapamycin reverses the age-related decline in cardiac function and structure in old mice.

Microwave-Assisted Synthesis of SnO@ZnInS Composites for Highly Efficient Photocatalytic Hydrogen Evolution.

This research successfully synthesized SnO@ZnInS composites for photocatalytic tap water splitting using a rapid two-step microwave-assisted synthesis method. This study investigated the impact of incorporating a fixed quantity of SnO nanoparticles and combining them with various materials to form composites, aiming to enhance photocatalytic hydrogen production. Additionally, different weights of SnO nanoparticles were added to the ZnInS reaction precursor to prepare SnO@ZnInS composites for photocatalytic hydrogen production.

Fabrication of polydopamine/rGO Membranes for Effective Radionuclide Removal.

In this work, a novel polydopamine/reduced graphene oxide (PDA/rGO) nanofiltration membrane was prepared to efficiently and stably remove radioactive strontium ions under an alkaline environment. Through the incorporation of PDA and thermal reduction treatment, not only has the interlayer spacing of graphene oxide (GO) nanosheets been appropriately regulated but also an improved antiswelling property has been achieved. The dosage of GO, reaction time with PDA, mass ratio of PDA to GO, and thermal treatment temperature have been optimized to achieve a high-performance PDA/rGO membrane.

Loss of Cardiac PFKFB2 Drives Metabolic, Functional, and Electrophysiological Remodeling in the Heart.

Background: Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2) is a critical glycolytic regulator responsible for upregulation of glycolysis in response to insulin and adrenergic signaling. PFKFB2, the cardiac isoform of PFK-2, is degraded in the heart in the absence of insulin signaling, contributing to diabetes-induced cardiac metabolic inflexibility. However, previous studies have not examined how the loss of PFKFB2 affects global cardiac metabolism and function.

Loss of cardiac PFKFB2 drives Metabolic, Functional, and Electrophysiological Remodeling in the Heart.

Background: Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2) is a critical glycolytic regulator responsible for upregulation of glycolysis in response to insulin and adrenergic signaling. PFKFB2, the cardiac isoform of PFK-2, is degraded in the heart in the absence of insulin signaling, contributing to diabetes-induced cardiac metabolic inflexibility. However, previous studies have not examined how the loss of PFKFB2 affects global cardiac metabolism and function.

Mitochondrial Targeted Interventions for Aging.

Changes in mitochondrial function play a critical role in the basic biology of aging and age-related disease. Mitochondria are typically thought of in the context of ATP production and oxidant production. However, it is clear that the mitochondria sit at a nexus of cell signaling where they affect metabolite, redox, and energy status, which influence many factors that contribute to the biology of aging, including stress responses, proteostasis, epigenetics, and inflammation.

Increased cardiac PFK-2 protects against high-fat diet-induced cardiomyopathy and mediates beneficial systemic metabolic effects.

A healthy heart adapts to changes in nutrient availability and energy demands. In metabolic diseases like type 2 diabetes (T2D), increased reliance on fatty acids for energy production contributes to mitochondrial dysfunction and cardiomyopathy. A principal regulator of cardiac metabolism is 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2), which is a central driver of glycolysis.

Rapid Microwave-Assisted Synthesis of ZnInS Nanosheets for Highly Efficient Photocatalytic Hydrogen Production.

In this study, a facile and rapid microwave-assisted synthesis method was used to synthesize InS nanosheets, ZnS nanosheets, and ZnInS nanosheets with sulfur vacancies. The two-dimensional semiconductor photocatalysts of ZnInS nanosheets were characterized by XRD, FESEM, BET, TEM, XPS, UV-vis diffuse reflectance, and PL spectroscopy. The ZnInS with sulfur vacancies exhibited an evident energy bandgap value of 2.

Design and assembly of Ag-decorated BiO @ 3D MXene Schottky heterojunction for the highly permeable and multiple-antifouling of fibrous membrane in the purification of complex emulsified oil pollutants.

Membrane separation technology has potential for purifying emulsified oily wastewater. However, the oils, soluble organic substances, and microorganisms can cause complex membrane fouling problems, thereby reducing the separation efficiency and service life. Herein, a highly permeable and multiple-antifouling composite membrane was prepared using porous PAN fibrous mat as support backbone for the assembly of Ag-decorated BiO @ 3D MXene Schottky heterojunction and hydrophilic TA as the adhesive.

Late-life Rapamycin Treatment Enhances Cardiomyocyte Relaxation Kinetics and Reduces Myocardial Stiffness.

Diastolic dysfunction is a key feature of the aging heart. We have shown that late-life treatment with mTOR inhibitor, rapamycin, reverses age-related diastolic dysfunction in mice but the molecular mechanisms of the reversal remain unclear. To dissect the mechanisms by which rapamycin improves diastolic function in old mice, we examined the effects of rapamycin treatment at the levels of single cardiomyocyte, myofibril and multicellular cardiac muscle.

Side-Chain-Dependent Functional Intercalations in Graphene Oxide Membranes for Selective Water and Ion Transport.

Subnanometer interlayer space in graphene oxide (GO) laminates is desirable for use as permselective membrane nanochannels. Although the facile modification of the local structure of GO enables various nanochannel functionalizations, precisely controlling nanochannel space is still a challenge, and the roles of confined nanochannel chemistry in selective water/ion separation have not been clearly defined. In this study, macrocyclic molecules with consistent basal plane but varying side groups were used to conjunct with GO for modified nanochannels in laminates.

Intermittent treatment with elamipretide preserves exercise tolerance in aged female mice.

The pathology of aging impacts multiple organ systems, including the kidney and skeletal and cardiac muscles. Long-term treatment with the mitochondrial-targeted peptide elamipretide has previously been shown to improve in vivo mitochondrial function in aged mice, which is associated with increased fatigue resistance and treadmill performance, improved cardiovascular diastolic function, and glomerular architecture of the kidney. However, elamipretide is a short tetrameric peptide that is not orally bioavailable, limiting its routes of administration.

Effects of Co-Solvent-Induced Self-Assembled Graphene-PVDF Composite Film on Piezoelectric Application.

A persistent purpose for self-powered and wearable electronic devices is the fabrication of graphene-PVDF piezoelectric nanogenerators with various co-solvents that could provide enhanced levels of durability and stability while generating a higher output. This study resulted in a piezoelectric nanogenerator based on a composite film composed of graphene, and poly (vinylidene fluoride) (PVDF) as a flexible polymer matrix that delivers high performance, flexibility, and cost-effectiveness. By adjusting the co-solvent in the solution, a graphene-PVDF piezoelectric nanogenerator can be created (acetone, THF, water, and EtOH).

Sexually dimorphic effects of SARM1 deletion on cardiac NAD metabolism and function.

Nicotinamide adenine dinucleotide (NAD) decline is repeatedly observed in heart disease and its risk factors. Although strategies promoting NAD synthesis to elevate NAD levels improve cardiac function, whether inhibition of NAD consumption can be therapeutic is less investigated. In this study, we examined the role of sterile-α and TIR motif containing 1 (SARM1) NAD hydrolase in mouse hearts, using global SARM1-knockout mice (KO).

Age and Sex Differences in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a multi-organ disorder that represents about 50% of total heart failure (HF) cases and is the most common form of HF in the elderly. Because of its increasing prevalence caused by the aging population, high mortality and morbidity, and very limited therapeutic options, HFpEF is considered as one of the greatest unmet medical needs in cardiovascular medicine. Despite its complex pathophysiology, numerous preclinical models have been established in rodents and in large animals to study HFpEF pathophysiology.

Harnessing NAD Metabolism as Therapy for Cardiometabolic Diseases.

Purpose Of The Review: This review summarizes current understanding on the roles of nicotinamide adenine dinucleotide (NAD) metabolism in the pathogeneses and treatment development of metabolic and cardiac diseases.

Recent Findings: NAD was identified as a redox cofactor in metabolism and a co-substrate for a wide range of NAD-dependent enzymes. NAD redox imbalance and depletion are associated with many pathologies where metabolism plays a key role, for example cardiometabolic diseases.

Nanofiltration Membranes Formed through Interfacial Polymerization Involving Cycloalkane Amine Monomer and Trimesoyl Chloride Showing Some Tolerance to Chlorine during Dye Desalination.

Wastewater effluents containing high concentrations of dyes are highly toxic to the environment and aquatic organisms. Recycle and reuse of both water and dye in textile industries can save energy and costs. Thus, new materials are being explored to fabricate highly efficient nanofiltration membranes for fulfilling industrial needs.

Bi-functional super-hydrophilic/underwater super-oleophobic 2D lamellar TiCT MXene/poly (arylene ether nitrile) fibrous composite membrane for the fast purification of emulsified oil and photodegradation of hazardous organics.

Developing the multi-functional membranes including oil/water emulsion separation and removal of hazardous organic pollutants is essential to the purification of the complicated wastewater. However, it remains a daunting challenge to combine these intended functions while maintaining high separation efficiency. Herein, we developed a new 2D lamellar MXene/poly (arylene ether nitrile) (PEN) fibrous composite membrane through the self-assembly of TiO nanoparticles intercalated MXene nanosheets onto the porous PEN nanofibrous mats and bioinspired polydopamine triggered chemical-crosslinking with polyethyleneimine (PEI).