MASLD/MetALD and mortality in individuals with any cardio-metabolic risk factor: A population-based study with 26.7 years of follow-up.

BACKGROUND AND AIMS: A new term, metabolic dysfunction-associated steatotic liver disease (MASLD), has been proposed by a multi-society expert panel. However, it remains unclear whether hepatic steatosis per se in MASLD contributes to an increased risk of mortality in individuals with any cardio-metabolic risk factor (CMRF), which is also a significant risk factor for increased mortality. This study aimed to compare all-cause and cause-specific mortality between the "MASLD/MetALD" and "no steatotic liver disease (SLD)" groups in individuals with any CMRF. APPROACH AND RESULTS: A population-based cohort study was conducted using 10,750 participants of the Third National Health and Nutrition Examination Survey. All-cause and cause-specific (cardiovascular, cancer, diabetes, and liver) mortality risks were compared between the "MASLD," "MetALD," and "no SLD" groups using the Cox proportional hazards model with complex survey design weights, adjusted for confounders. Over 26 years, the "MASLD" group did not show significantly increased all-cause (adjusted HR 1.04[95% CI: 0.95-1.14], p = 0.413), cardiovascular (0.88 [0.75-1.04], p = 0.139), or cancer (1.06[0.84-1.33], p = 0.635) mortality risk compared to the "no SLD" group in individuals with any CMRF. The MetALD group was associated with increased all-cause (1.41 [1.05-1.89], p = 0.022), cancer (2.35 [1.33-4.16], p = 0.004), and liver (15.04 [2.96-76.35], p = 0.002) mortality risk compared with the no SLD group. This trend was more pronounced in the MetALD group with advanced fibrosis assessed by Fibrosis-4 (FIB-4). CONCLUSIONS: In individuals with CMRF, the presence of steatotic liver disease (MASLD) alone did not increase the risk of mortality, except in cases with more alcohol consumption (MetALD). Therefore controlling metabolic risk factors and reducing alcohol consumption in people with MASLD or MetALD will be crucial steps to improve long-term health outcomes.

Progress and challenges of graphene and its congeners for biomedical applications.

Nanomaterials by virtue of their small size and enhanced surface area, present unique physicochemical properties that enjoy widespread applications in bioengineering, biomedicine, biotechnology, disease diagnosis, and therapy. In recent years, graphene and its derivatives have attracted a great deal of attention in various applications, including photovoltaics, electronics, energy storage, catalysis, sensing, and biotechnology owing to their exceptional structural, optical, thermal, mechanical, and electrical. Graphene is a two-dimensional sheet of sp2 hybridized carbon atoms of atomic thickness, which are arranged in a honeycomb crystal lattice structure. Graphene derivatives are graphene oxide (GO) and reduced graphene oxide (rGO), which are highly oxidized and less oxidized forms of graphene, respectively. Another form of graphene is graphene quantum dots (GQDs), having a size of less than 20 nm. Contemporary graphene research focuses on using graphene nanomaterials for biomedical purposes as they have a large surface area for loading biomolecules and medicine and offer the potential for the conjugation of fluorescent dyes or quantum dots for bioimaging. The present review begins with the synthesis, purification, structure, and properties of graphene nanomaterials. Then, we focussed on the biomedical application of graphene nanomaterials with special emphasis on drug delivery, bioimaging, biosensing, tissue engineering, gene delivery, and chemotherapy. The implications of graphene nanomaterials on human health and the environment have also been summarized due to their exposure to their biomedical applications. This review is anticipated to offer useful existing understanding and inspire new concepts to advance secure and effective graphene nanomaterials-based biomedical devices.

Needle-Free Jet Injection of Poly-(Lactic Acid) for Atrophic Acne Scars: Literature Review and Report of Clinical Cases.

Acne scars, particularly atrophic ones, present a persistent challenge in cosmetic medicine and surgery, requiring extended and multifaceted treatment approaches. Poly-(lactic acid) injectable fillers show promise in managing atrophic acne scars by stimulating collagen synthesis. However, the utilization of needle-free injectors for delivering poly-(lactic acid) into scars remains an area requiring further exploration. In this article, a summary of the latest advancements in needle-free jet injectors is provided, specifically highlighting the variations in jet-producing mechanisms. This summary emphasizes the differences in how these mechanisms operate, offering insights into the evolving technology behind needle-free injection systems. The literature review revealed documented cases focusing on treating atrophic acne scars using intralesional poly-(lactic acid) injections. The results of these clinical studies could be supported by separate in vitro and animal studies, elucidating the feasible pathways through which this treatment operates. However, there is limited information on the use of needle-free jet injectors for the intradermal delivery of poly-(lactic acid). Clinical cases of atrophic acne scar treatment are presented to explore this novel treatment concept, the needle-free delivery of poly-(lactic acid) using a jet pressure-based injector. The treatment demonstrated efficacy with minimal adverse effects, suggesting its potential for scar treatment. The clinical efficacy was supported by histological evidence obtained from cadaver skin, demonstrating an even distribution of injected particles in all layers of the dermis. In conclusion, we suggest that novel needle-free injectors offer advantages in precision and reduce patient discomfort, contributing to scar improvement and skin rejuvenation. Further comprehensive studies are warranted to substantiate these findings and ascertain the efficacy of this approach in scar treatment on a larger scale.

Optical and UV Shielding Properties of Inorganic Nanoparticles Embedded in Polymethyl Methacrylate Nanocomposite Freestanding Films.

Polymethyl methacrylate (PMMA) is an interesting polymer employed in various applications due to its outstanding properties. However, its electrical and mechanical properties can be further improved by incorporating nanoparticles, and in particular, PMMA nanocomposite with nanoparticles provides various multifunctional properties. This work reports PMMA nanocomposite preparation and structural and optical characterizations incorporating carbon nanotubes (CNTs), TiO2 nanoparticles, and carbon quantum dots (CQDs). CNT/PMMA, TiO2/PMMA, and CQD/PMMA nanocomposite freestanding films were prepared using a simple solution method. Various properties of the prepared composite films were analyzed using scanning electron microscopy, X-ray diffraction, photoluminescence, Fourier transform infrared, and UV-Vis and Raman spectroscopy. Optical parameters and photocatalytic dye degradation for the films are reported, focusing on the properties of the materials. The CNT/PMMA, TiO2/PMMA, and CQD/PMMA films achieved, respectively, good electrical conductivity, photodegradation, and fluorescence compared with other composite films.

CRISPR/Cas9 targeting of passenger single nucleotide variants in haploinsufficient or essential genes expands cancer therapy prospects.

CRISPR/Cas9 technology has effectively targeted cancer-specific oncogenic hotspot mutations or insertion-deletions. However, their limited prevalence in tumors restricts their application. We propose a novel approach targeting passenger single nucleotide variants (SNVs) in haploinsufficient or essential genes to broaden therapeutic options. By disrupting haploinsufficient or essential genes through the cleavage of DNA in the SNV region using CRISPR/Cas9, we achieved the selective elimination of cancer cells without affecting normal cells. We found that, on average, 44.8% of solid cancer patients are eligible for our approach, a substantial increase compared to the 14.4% of patients with CRISPR/Cas9-applicable oncogenic hotspot mutations. Through in vitro and in vivo experiments, we validated our strategy by targeting a passenger mutation in the essential ribosomal gene RRP9 and haploinsufficient gene SMG6. This demonstrates the potential of our strategy to selectively eliminate cancer cells and expand therapeutic opportunities.

Experimental analysis of PM2.5 reduction characteristics between Korean red pine (Pinus densiflora) and sawtooth oak (Quercus acutissima) saplings under different densities and arrangement structures.

As global air pollution, particularly fine particulate matter (PM2.5), has become a major environmental problem, various PM2.5 mitigation technologies including green infrastructure have received significant attention. However, owing to spatial constraints on urban greening, there is a lack of management plans for urban forests to efficiently mitigate PM2.5. In this study, we assessed the PM2.5 reduction capabilities of Pinus densiflora (Korean red pine) and Quercus acutissima (sawtooth oak) by measuring the changes of PM2.5 concentrations using an experimental chamber system. In addition, the PM2.5 reduction efficiency in 90 min (PMRE90) and the amount of PM2.5 reduction per leaf area (PMRLA) were compared based on arrangement structures and density levels. The results showed that the PM2.5 reduction by plants was significantly greater than that of the control experiment without any plants, and an additional reduction effect of approximately 1.38 times was induced by a 1.5 m s-1 air flow. The PMRE90 of Korean red pine was the highest at medium density. In contrast, the PMRE90 of sawtooth oak was the highest at high density. The PMRLA of both species was highest at low densities. The different responses of the species to total reduction were well explained by total leaf area (TLA). The PMRE90 of both species was positively correlated with TLA. The PMRLA of sawtooth oak was approximately 2.3 times greater than that of Korean red pine. However, there were no significant differences in both PMRE90 and PMRLA between the arrangement structures. Our findings reveal the potential mechanisms of vegetation in reducing PM2.5 according to arrangement structure and density. This highlights the importance of efficiently using urban green spaces with spatial constraints on PM2.5 mitigation in the future.

Energy deprivation affects nitrogen assimilation and fatty acid biosynthesis leading to leaf chlorosis under waterlogging stress in the endangered Abies koreana.

Energy deprivation triggers various physiological, biochemical and molecular changes in plants under abiotic stress. We investigated the oxidative damages in the high altitude grown conifer Korean fir (Abies koreana) exposed to waterlogging stress. Our experimental results showed that waterlogging stress led to leaf chlorosis, 35 days after treatment. A significant decrease in leaf fresh weight, chlorophyll and sugar content supported this phenotypic change. Biochemical analysis showed a significant increase in leaf proline, lipid peroxidase and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical content of waterlogged plants. To elucidate the molecular mechanisms, we conducted RNA-sequencing (RNA-seq) and de novo assembly. Using RNA-seq analysis approach and filtering (P < 0.05 and false discovery rate <0.001), we obtained 134 unigenes upregulated and 574 unigenes downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis placed the obtained differentially expressed unigenes in α-linoleic pathway, fatty acid degradation, glycosis, glycolipid metabolism and oligosaccharide biosynthesis process. Mapping of unigenes with Arabidopsis using basic local alignment search tool for nucleotides showed several critical genes in photosynthesis and carbon metabolism downregulated. Following this, we found the repression of multiple nitrogen (N) assimilation and nucleotide biosynthesis genes including purine metabolism. In addition, waterlogging stress reduced the levels of polyunsaturated fatty acids with a concomitant increase only in myristic acid. Together, our results indicate that the prolonged snowmelt may cause inability of A. koreana seedlings to lead the photosynthesis normally due to the lack of root intercellular oxygen and emphasizes a detrimental effect on the N metabolic pathway, compromising this endangered tree's ability to be fully functional under waterlogging stress.

Chitosan-Integrated Curcumin-Graphene Oxide/Copper Oxide Hybrid Nanocomposites for Antibacterial and Cytotoxicity Applications.

This study deals with the facile synthesis of a single-pot chemical technique for chitosan-curcumin (CUR)-based hybrid nanocomposites with nanostructured graphene oxide (GO) and copper oxide (CuO) as the antibacterial and cytotoxic drugs. The physicochemical properties of synthesized hybrid nanocomposites such as CS-GO, CS-CuO, CS-CUR-GO, and CS-CUR-GO/CuO were confirmed with various advanced tools. Moreover, the in vitro drug release profile of the CS-CUR-GO/CuO nanocomposite exhibited sustained and controlled release during different time intervals. Also, the antibacterial activity of the CS-CUR-GO/CuO hybrid nanocomposite presented the maximum bactericidal effect against Staphylococcus aureus and Escherichia coli pathogens. The hybrid nanocomposites revealed improved cytotoxicity behaviour against cultured mouse fibroblast cells (L929) via cell adhesion, DNA damage, and proliferation. Thus, the chitosan-based hybrid nanocomposites offer rich surface area, biocompatibility, high oxidative stress, and bacterial cell disruption functionalities as a potential candidate for antibacterial and cytotoxicity applications.

Energy Storage Application of CaO/Graphite Nanocomposite Powder Obtained from Waste Eggshells and Used Lithium-Ion Batteries as a Sustainable Development Approach.

The reuse of waste materials has recently become appealing due to pollution and cost reduction factors. Using waste materials can reduce environmental pollution and product costs, thus promoting sustainability. Approximately 95% of calcium carbonate-containing waste eggshells end up in landfills, unused. These eggshells, a form of bio-waste, can be repurposed as catalytic electrode material for various applications, including supercapacitors, after being converted into CaO. Similarly, used waste battery electrode materials pose environmental hazards if not properly recycled. Various types of batteries, particularly lithium-ion batteries, are extensively used worldwide. The recycling of used lithium-ion batteries has become less important considering its low economic benefits. This necessitates finding alternative methods to recover and reuse the graphite rods of spent batteries. Therefore, this study reports the conversion of waste eggshell into calcium oxide by high-temperature calcination and extraction of nanographite from spent batteries for application in energy storage fields. Both CaO and CaO/graphite were characterized for their structural, morphological, and chemical compositions using XRD, SEM, TEM, and XPS techniques. The prepared CaO/graphite nanocomposite material was evaluated for its efficiency in electrochemical supercapacitor applications. CaO and its composite with graphite powder obtained from used lithium-ion batteries demonstrated improved performance compared to CaO alone for energy storage applications. Using these waste materials for electrochemical energy storage and conversion devices results in cheaper, greener, and sustainable processes. This approach not only aids in energy storage but also promotes sustainability through waste management by reducing landfills.

Correlations between heart sound components and hemodynamic variables.

Although the esophageal stethoscope is used for continuous auscultation during general anesthesia, few studies have investigated phonocardiographic data as a continuous hemodynamic index. In this study, we aimed to induce hemodynamic variations and clarify the relationship between the heart sounds and hemodynamic variables through an experimental animal study. Changes in the cardiac contractility and vascular resistance were induced in anesthetized pigs by administering dobutamine, esmolol, phenylephrine, and nicardipine. In addition, a decrease in cardiac output was induced by restricting the venous return by clamping the inferior vena cava (IVC). The relationship between the hemodynamic changes and changes in the heart sound indices was analyzed. Experimental data from eight pigs were analyzed. The mean values of the correlation coefficients of changes in S1 amplitude (ΔS1amp) with systolic blood pressure (ΔSBP), pulse pressure (ΔPP), and ΔdP/dt during dobutamine administration were 0.94, 0.96, and 0.96, respectively. The mean values of the correlation coefficients of ΔS1amp with ΔSBP, ΔPP, and ΔdP/dt during esmolol administration were 0.80, 0.82, and 0.86, respectively. The hemodynamic changes caused by the administration of phenylephrine and nicardipine did not correlate significantly with changes in the heart rate. The S1 amplitude of the heart sound was significantly correlated with the hemodynamic changes caused by the changes in cardiac contractility but not with the variations in the vascular resistance. Heart sounds can potentially provide a non-invasive monitoring method to differentiate the cause of hemodynamic variations.

Exposure to an enriched environment modulates the synaptic vesicle cycle in a mouse spinal cord injury model.

Spinal cord injury (SCI) leads to motor and sensory impairment below the site of injury, thereby necessitating rehabilitation. An enriched environment (EE) increases social interaction and locomotor activity in a mouse model, similar to human rehabilitation. However, the impact of EE on presynaptic plasticity in gene expression levels remains unclear. Hence, this study aimed to investigate the therapeutic potential of EE in an SCI mouse model. Mice with spinal cord contusion were divided into two groups: those housed in standard cages (control) and those in EE conditions (EE). Each group was housed separately for either 2- or 8-weeks post-injury, after which RNA sequencing was performed and compared to a sham group (receiving only a dorsal laminectomy). The synaptic vesicle cycle (SVC) pathway and related genes showed significant downregulation after SCI at both time points. Subsequently, we investigated whether exposure to EE for 2- and 8-weeks post-SCI could modulate the SVC pathway and its related genes. Notably, exposure to EE for 8 weeks resulted in a marked reversal effect of SVC-related gene expression, along with stimulation of axon regeneration and mitigation of locomotor activity loss. Thus, prolonged exposure to EE increased presynaptic activity, fostering axon regeneration and functional improvement by modulating the SVC in the SCI mouse model. These findings suggest that EE exposure proves effective in inducing activity-dependent plasticity, offering a promising therapeutic approach akin to rehabilitation training in patients with SCI.

Optimization of Gate-Head-Top/Bottom Lengths of AlGaN/GaN High-Electron-Mobility Transistors with a Gate-Recessed Structure for High-Power Operations: A Simulation Study.

In this study, we propose an optimized AlGaN/GaN high-electron-mobility transistor (HEMT) with a considerably improved breakdown voltage. First, we matched the simulated data obtained from a basic T-gate HEMT with the measured data obtained from the fabricated device to ensure the reliability of the simulation. Thereafter, to improve the breakdown voltage, we suggested applying a gate-head extended structure. The gate-head-top and gate-head-bottom lengths of the basic T-gate HEMT were symmetrically extended by 0.2 µm steps up to 1.0 µm. The breakdown voltage of the 1.0 µm extended structure was 52% higher than that of the basic T-gate HEMT. However, the cutoff frequency (fT) and maximum frequency (fmax) degraded. To minimize the degradation of fT and fmax, we additionally introduced a gate-recessed structure to the 1.0 µm gate-head extended HEMT. The thickness of the 25 nm AlGaN barrier layer was thinned down to 13 nm in 3 nm steps, and the highest fT and fmax were obtained at a 6 nm recessed structure. The fT and fmax of the gate-recessed structure improved by 9% and 28%, respectively, with respect to those of the non-gate-recessed structure, and further improvement of the breakdown voltage by 35% was observed. Consequently, considering the trade-off relationship between the DC and RF characteristics, the 1.0 µm gate-head extended HEMT with the 6 nm gate-recessed structure was found to be the optimized AlGaN/GaN HEMT for high-power operations.