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1.
Neuropsychiatr Dis Treat ; 20: 1097-1106, 2024.
Article in English | MEDLINE | ID: mdl-38774254

ABSTRACT

Objective: The purpose of this study was to evaluate the positive impact of mobile neurofeedback (MNF) in neurotypical children compared to sham mobile neurofeedback. Methods: Neurotypical children aged 10-15 participated in the study. All subjects were assessed using the Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version Korean Version (K-SADS-PL-K) and confirmed to have no psychiatric symptoms. The participants were randomly assigned to the MNF active (N=31) or sham control (N=30) groups. The MNF program was administered using a mobile app for 30 min/day, 3 days/week, for 3 months. All participants and their parents completed self-report scales and participants complete neurocognitive function assessments including the continuous performance test, Stroop, children's color trails test-1 and 2, and intelligence test at baseline and after the 3-month MNF program. Results: This study involved 61 participants (mean [SD] age, 11.24 [1.84] years; 30 male participants [49.2%]). To verify the difference between the MNF group and the sham group, 2(MNF-Sham) X 2(Pre-Post) repeated measures ANOVA was performed. The main effect of the K-scale (Korea Internet addiction scale) between-group factor (MNF vs Sham) was not significant, but the main effect of the within-group factor (Pre vs Post) was significant (F=7.595, p=0.008). The interaction effect of between-group factors and within-group factors was also significant (F=5.979, p=0.017). In other self-reported scales of children and parents and neurocognitive function assessments, there was no significant difference between the two groups. Conclusion: Active mobile neurofeedback significantly improved children's K-scale score compared to the sham group. Therefore, mobile neurofeedback could be an easy-to-access therapeutic option for children at risk of Internet addiction. On the other hand, there was no significant difference in other scales and neurocognitive function. A 3-month intervention may not have been long enough to cause change, so longer interventions are needed for confirmation.

2.
Heart Rhythm ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38697272

ABSTRACT

BACKGROUND: The association between alcohol consumption and risk of sudden cardiac death and/or fatal ventricular arrhythmia remains controversial. OBJECTIVE: We analyzed the association between alcohol consumption, genetic traits for alcohol metabolism, and the risk of sudden cardiac death and/or fatal ventricular arrhythmia. METHODS: We identified 397,164 subjects enrolled between 2006 and 2010 from the UK Biobank database and followed them until 2021. Alcohol consumption was categorized as current nondrinkers (nondrinkers and ex-drinkers), mild drinkers, moderate drinkers, or heavy drinkers. Genetic traits of alcohol metabolism were stratified according to the polygenic risk score tertiles. The primary and secondary outcomes were a composite of sudden cardiac death and fatal ventricular arrhythmia, as well as their individual components. RESULTS: During the follow-up (median 12.5 years), 3,543 cases of clinical outcomes occurred. Although mild, moderate, and heavy drinkers showed deceased risks of outcomes compared with current non-drinkers, there was no prognostic difference among non-drinkers, mild drinkers, moderate drinkers, and heavy drinkers. Ex-drinkers showed increased risk in the univariate analysis, but the significance was attenuated after adjusting covariates (hazard ratio (HR) 1.19; 95% confidence interval [CI]: 0.94-1.50). As a continuous variable, alcohol consumption was not associated with clinical outcomes (HR 1.01; 95% CI 0.99-1.02). Consistent with these findings, there was no association between genetic traits for alcohol metabolism, and the risk of clinical outcomes. CONCLUSIONS: Alcohol consumption was neither a protective nor a risk factor for sudden cardiac death or fatal ventricular arrhythmia. Genetic traits of alcohol metabolism were not associated with the clinical prognosis.

3.
Sci Rep ; 14(1): 11419, 2024 May 19.
Article in English | MEDLINE | ID: mdl-38763924

ABSTRACT

A novel auxetic structure applicable to airless tire spokes is designed based on the primitive-type triply periodic minimal surface (P-TPMS) to have higher stiffness through deformation under compressive force. For becoming higher stiffness by deformation, an unit cell of auxetic structure is proposed and its characteristics according to design parameters are studied. Based on the parametric study, a rotated primitive-type auxetic structure (RPAS) is designed, and the deformative behaviors of an airless tire with the RPAS spokes are compared with a generally used honeycomb spoke. Simulation and experiment results show that the designed RPAS tire exhibits more stable behavior through higher rigidity depending on the deformation state when compressed on flat ground and obstacles. This variable stiffness characteristic of RPAS tires can be advantageous for shock absorption and prevention of large local deformations. Also, the manufacturability of the designed auxetic structure is evaluated using real rubber-based additive manufacturing processes for practical application in the tire manufacturing industry.

4.
Article in English | MEDLINE | ID: mdl-38615329

ABSTRACT

Cell membranes are structures essential to the cell function and adaptation. Recent studies have targeted cell membranes to identify their protective and interactive properties. Leveraging these attributes of cellular membranes and their application to vaccine delivery is gaining increasing prominence. This study aimed to fuse synthetic polymeric nanoparticles with cell membranes to develop cell membrane hybrid polymersomes (HyPSomes) for enhanced vaccine delivery. We designed a platform to hybridize cell membranes with methoxy-poly(ethylene glycol)-block-polylactic acid nanoparticles by using the properties of both components. The formed HyPSomes were optimized by using dynamic light scattering, transmission electron microscopy, and Förster resonance energy transfer, and their stability was confirmed. The synthesized HyPSomes replicated the antigenic surface of the source cells and possessed the stability and efficacy of synthetic nanoparticles. These HyPSomes demonstrated enhanced cellular uptake and translation efficiency and facilitated endosome escape. HyPSomes showed outstanding capabilities for the delivery of foreign mRNAs to antigen-presenting cells. HyPSomes may serve as vaccine delivery systems by bridging the gap between synthetic and natural systems. These systems could be used in other contexts, e.g., diagnostics and drug delivery.

5.
Nat Commun ; 15(1): 3368, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38643233

ABSTRACT

The immune escape of Omicron variants significantly subsides by the third dose of an mRNA vaccine. However, it is unclear how Omicron variant-neutralizing antibodies develop under repeated vaccination. We analyze blood samples from 41 BNT162b2 vaccinees following the course of three injections and analyze their B-cell receptor (BCR) repertoires at six time points in total. The concomitant reactivity to both ancestral and Omicron receptor-binding domain (RBD) is achieved by a limited number of BCR clonotypes depending on the accumulation of somatic hypermutation (SHM) after the third dose. Our findings suggest that SHM accumulation in the BCR space to broaden its specificity for unseen antigens is a counterprotective mechanism against virus variant immune escape.


Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , BNT162 Vaccine , COVID-19/prevention & control , SARS-CoV-2/genetics , Antibodies, Neutralizing , Antibodies, Viral
6.
Adv Healthc Mater ; : e2303782, 2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38430208

ABSTRACT

Exosomes are small extracellular vesicles that play a crucial role in intercellular communication and offer significant potential for a wide range of biomedical applications. However, conventional methods for exosome isolation have limitations in terms of purity, scalability, and preservation of exosome structural integrity. To address these challenges, an exosome isolation platform using chitosan oligosaccharide lactate conjugated 1-pyrenecarboxylic acid (COL-Py) based self-assembled magnetic nanoclusters (CMNCs), is presented. CMNCs are characterized to optimize their size, stability, and interaction dynamics with exosomes. The efficiency of CMNCs in isolating exosomes is systematically evaluated using various analytical methods to demonstrate their ability to capture exosomes based on amphiphilic lipid bilayers. CMNC-based exosome isolation consistently yields exosomes with structural integrity and purity similar to those obtained using traditional methods. The reusability of CMNCs over multiple exosome isolation cycles underscores their scalability and offers an efficient solution for biomedical applications. These results are supported by western blot analysis, which demonstrated the superiority of CMNC-based isolation in terms of purity compared to conventional methods. By providing a scalable and efficient exosome isolation process that preserves both structural integrity and purity, CMNCs can constitute a new platform that can contribute to the field of exosome studies.

7.
Toxicol In Vitro ; 97: 105810, 2024 May.
Article in English | MEDLINE | ID: mdl-38513818

ABSTRACT

Grown evidence has shown that the liver and reproductive organs were the main target organs of perfluorooctanoic acid (PFOA). Herein, we studied a toxic mechanism of PFOA using HeLa Chang liver epithelial cells. When incubated with PFOA for 24 h or 48 h, cell proliferation was inhibited in a concentration- and time-dependent fashion, but interestingly, the feature of dead cells was not notable. Mitochondrial volume was increased with concentration and time, whereas the mitochondrial membrane potential and produced ATP amounts were significantly reduced. Autophagosome-like vacuoles and contraction of the mitochondrial inner membrane were observed in PFOA-treated cells. The expression of acetyl CoA carboxylase (ACC) and p-ACC proteins rapidly decreased, and that of mitochondrial dynamics-related proteins increased. The expression of solute carrier family 7 genes, ChaC glutathione-specific gamma-glutamylcyclotransferase 1, and 5S ribosomal RNA gene was up-regulated the most in cells exposed to PFOA for 24 h, and the KEGG pathway analysis revealed that PFOA the most affected metabolic pathways and olfactory transduction. More importantly, PPAR alpha, fatty acid binding protein 1, and CYP450 family 1 subfamily A member 1 were identified as the target proteins for binding between PFOA and cells. Taken together, we suggest that disruption of mitochondrial integrity and function may contribute closely to PFOA-induced cell proliferation inhibition.


Subject(s)
Caprylates , Fluorocarbons , Caprylates/metabolism , Liver/metabolism , Hepatocytes , Fluorocarbons/metabolism , Cell Proliferation
8.
RSC Adv ; 14(14): 9943-9966, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38528920

ABSTRACT

This review examines the escalating issue of plastic pollution, specifically highlighting the detrimental effects on the environment and human health caused by microplastics and nanoplastics. The extensive use of synthetic polymers such as polyethylene (PE), polyethylene terephthalate (PET), and polystyrene (PS) has raised significant environmental concerns because of their long-lasting and non-degradable characteristics. This review delves into the role of enzymatic and microbial strategies in breaking down these polymers, showcasing recent advancements in the field. The intricacies of enzymatic degradation are thoroughly examined, including the effectiveness of enzymes such as PETase and MHETase, as well as the contribution of microbial pathways in breaking down resilient polymers into more benign substances. The paper also discusses the impact of chemical composition on plastic degradation kinetics and emphasizes the need for an approach to managing the environmental impact of synthetic polymers. The review highlights the significance of comprehending the physical characteristics and long-term impacts of micro- and nanoplastics in different ecosystems. Furthermore, it points out the environmental and health consequences of these contaminants, such as their ability to cause cancer and interfere with the endocrine system. The paper emphasizes the need for advanced analytical methods and effective strategies for enzymatic degradation, as well as continued research and development in this area. This review highlights the crucial role of enzymatic and microbial strategies in addressing plastic pollution and proposes methods to create effective and environmentally friendly solutions.

9.
Redox Biol ; 71: 103101, 2024 May.
Article in English | MEDLINE | ID: mdl-38408409

ABSTRACT

Physical activity has been considered an important non-medication intervention in preserving mnemonic processes during aging. However, how aerobic exercise promotes such benefits for human health remains unclear. In this study, we aimed to explore the neuroprotective and anti-inflammatory effects of aerobic exercise against lipopolysaccharide (LPS)-induced amnesic C57BL/6J mice and BV-2 microglial cell models. In the in vivo experiment, the aerobic exercise training groups were allowed to run on a motorized treadmill 5 days/week for 4 weeks at a speed of 10 rpm/min, with LPS (0.1 mg/kg) intraperitoneally injected once a week for 4 weeks. We found that aerobic exercise ameliorated memory impairment and cognitive deficits among the amnesic mice. Correspondingly, aerobic exercise significantly increased the protein expressions of FNDC5, which activates target neuroprotective markers BDNF and CREB, and antioxidant markers Nrf2/HO-1, leading to inhibiting microglial-mediated neuroinflammation and reduced the expression of BACE-1 in the hippocampus and cerebral cortex of amnesic mice. We estimated that aerobic exercise inhibited neuroinflammation in part through the action of FNDC5/irisin on microglial cells. Therefore, we explored the anti-inflammatory effects of irisin on LPS-stimulated BV-2 microglial cells. In the in vitro experiment, irisin treatment blocked NF-κB/MAPK/IRF3 signaling activation concomitantly with the significantly lowered levels of the LPS-induced iNOS and COX-2 elevations and promotes the Nrf2/HO-1 expression in the LPS-stimulated BV-2 microglial cells. Together, our findings suggest that aerobic exercise can improve the spatial learning ability and cognitive functions of LPS-treated mice by inhibiting microglia-mediated neuroinflammation through its effect on the expression of BDNF/FNDC5/irisin.


Subject(s)
Cognitive Dysfunction , Lipopolysaccharides , Mice , Humans , Animals , Lipopolysaccharides/adverse effects , Neuroinflammatory Diseases , Fibronectins/metabolism , NF-E2-Related Factor 2/metabolism , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Mice, Inbred C57BL , Cognitive Dysfunction/therapy , Cognitive Dysfunction/drug therapy , Oxidative Stress , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , NF-kappa B/metabolism , Inflammation/therapy , Inflammation/drug therapy
10.
Discov Nano ; 19(1): 23, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38315307

ABSTRACT

There is growing evidence that neonatal porcine islet-like cell clusters (NPCCs) isolated from piglets can be used to treat type 1 diabetes in humans. However, graft rejection is a common complication in humans owing to the prevalence of xenoantigens in porcine. Therefore, researchers have investigated various islet encapsulation techniques that could protect against these antigens. To this end, this study presents a robust nano-encapsulation method based on bifunctional polymersomes (PSomes), in which N-hydroxysuccinimide (NHS) and maleimide (Mal) groups conjugated to the PSomes terminal interact with the amine and thiol groups on the surface of NPCCs to induce dual targeting via two covalent bonds. The findings indicate that the ratio of NHS to Mal on PSomes is optimal for dual targeting. Moreover, triiodothyronine (T3) is known to promotes pancreatic islet maturation and differentiation of endocrine cells into beta cells. T3 encapsulated in PSomes is shown to increase the glucose sensitivity of NPCCs and enhance insulin secretion from NPCCs. Furthermore, improvements in the nano-encapsulation efficiency and insulin-secreting capability of NPCCs through dual targeting via dual-Psomes are demonstrated. In conclusion, the proposed nano-encapsulation technique could pave the way for significant advances in islet nano-encapsulation and the imprevement of NPCC immaturity via T3 release.

11.
Nat Mach Intell ; 6(2): 180-186, 2024.
Article in English | MEDLINE | ID: mdl-38404481

ABSTRACT

The removal or cancellation of noise has wide-spread applications in imaging and acoustics. In applications in everyday life, such as image restoration, denoising may even include generative aspects, which are unfaithful to the ground truth. For scientific use, however, denoising must reproduce the ground truth accurately. Denoising scientific data is further challenged by unknown noise profiles. In fact, such data will often include noise from multiple distinct sources, which substantially reduces the applicability of simulation-based approaches. Here we show how scientific data can be denoised by using a deep convolutional neural network such that weak signals appear with quantitative accuracy. In particular, we study X-ray diffraction and resonant X-ray scattering data recorded on crystalline materials. We demonstrate that weak signals stemming from charge ordering, insignificant in the noisy data, become visible and accurate in the denoised data. This success is enabled by supervised training of a deep neural network with pairs of measured low- and high-noise data. We additionally show that using artificial noise does not yield such quantitatively accurate results. Our approach thus illustrates a practical strategy for noise filtering that can be applied to challenging acquisition problems.

12.
Heliyon ; 10(4): e26663, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38420468

ABSTRACT

Myasthenia Gravis (MG) patients with anti-acetylcholine receptor (AChR) antibodies frequently show hyperplastic thymi with ectopic germinal centers, where autoreactive B cells proliferate with the aid of T cells. In this study, thymus and peripheral blood (PB) samples were collected from ten AChR antibody-positive MG patients. T cell receptor (TCR) repertoires were analyzed using next-generation sequencing (NGS), and compared with that of an age and sex matched control group generated from a public database. Certain V genes and VJ gene recombination pairs were significantly upregulated in the TCR chains of αß-T cells in the PB of MG patients compared to the control group. Furthermore, the TCR chains found in the thymi of MG patients had a weighted distribution to longer CDR3 lengths when compared to the PB of MG patients, and the TCR beta chains (TRB) in the MG group's PB showed increased clonality encoded by one upregulated V gene. When TRB sequences were sub-divided into groups based on their CDR3 lengths, certain groups showed decreased clonality in the MG group's PB compared to the control group's PB. Finally, we demonstrated that stereotypic MG patient-specific TCR clonotypes co-exist in both the PB and thymi at a much higher frequency than that of the clonotypes confined to the PB. These results strongly suggest the existence of a biased T cell-mediated immune response in MG patients, as observed in other autoimmune diseases.

13.
Psychiatry Investig ; 21(1): 9-17, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38281736

ABSTRACT

OBJECTIVE: The aim of this study was to explore the psychometric properties of the Insomnia Severity Index (ISI) based on modern test theory, such as item response theory (IRT) and Rasch analysis, with shortened versions of the ISI among the general population. METHODS: We conducted two studies to evaluate the reliability and validity of the shortened versions of the ISI in a Korean population. In Study I, conducted via online survey, we performed an exploratory factor analysis (n=400). In Study II, confirmatory factor analysis (CFA) was conducted (n=400). IRT and Rasch analysis were performed on all samples. Participants symptoms were rated using the ISI, Dysfunctional Beliefs and Attitudes about Sleep-16 items, Dysfunctional Beliefs about Sleep-2 items, Patient Health Questionnaire-9 items, and discrepancy between desired time in bed and desired total sleep time. RESULTS: CFA showed a good fit for the 2-factor model of the ISI (comparative fit index=0.994, Tucker-Lewis index=0.990, root-meansquare-error of approximation=0.039, and standardized root-mean-square residual=0.046). The 3-item versions also showed a good fit for the model. All scales showed good internal consistency reliability. The scale information curve of the 2-item scale was similar to that of the full-scale ISI. The Rasch analysis outputs suggested a good model fit. CONCLUSION: The shortened 2-factor ISI is a reliable and valid model for assessing the severity of insomnia in the Korean population. The results are needed to be explored further among the clinical sample of insomnia.

14.
Biomaterials ; 305: 122459, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38199216

ABSTRACT

Retinal detachment and other vision-threatening disorders often necessitate vitreous body removal and tamponade injection for retina stabilization. Current clinical tamponades such as silicone oil and expansile gases have drawbacks, including patient discomfort and the need for secondary surgery. We introduce a transparent alginate-phenylboronic acid/polyvinyl alcohol composite hydrogel (TALPPH) as a novel vitreous substitute with tamponading capabilities. In vitro physicochemical, rheological, and optical characterization of in situ self-healable TALPPH was performed, and long-term biocompatibility was assessed in a rabbit model of vitrectomy retinal detachment. In vivo evaluations confirmed TALPPH's ability to inhibit retinal detachment recurrence and preserve rabbit vision without adverse effects. TALPPH's close resemblance to the natural vitreous body suggests potential as a vitreous tamponade substitute for future ophthalmological applications.


Subject(s)
Hydrogels , Polyvinyl Alcohol , Retinal Detachment , Animals , Humans , Rabbits , Hydrogels/chemistry , Retinal Detachment/complications , Retinal Detachment/surgery , Alginates/pharmacology , Vitreous Body , Vitrectomy
15.
Adv Mater ; 36(3): e2307515, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37830432

ABSTRACT

The omnipresence of charge density waves (CDWs) across almost all cuprate families underpins a common organizing principle. However, a longstanding debate of whether its spatial symmetry is stripe or checkerboard remains unresolved. While CDWs in lanthanum- and yttrium-based cuprates possess a stripe symmetry, distinguishing these two scenarios is challenging for the short-range CDW in bismuth-based cuprates. Here, high-resolution resonant inelastic x-ray scattering is employed to uncover the spatial symmetry of the CDW in Bi2 Sr2 - x Lax CuO6 + δ . Across a wide range of doping and temperature, anisotropic CDW peaks with elliptical shapes are found in reciprocal space. Based on Fourier transform analysis of real-space models, the results are interpreted as evidence of unidirectional charge stripes, hosted by mutually 90°-rotated anisotropic domains. This work paves the way for a unified symmetry and microscopic description of CDW order in cuprates.

16.
ACS Appl Mater Interfaces ; 15(50): 58451-58461, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38051908

ABSTRACT

The demand for lithium-ion batteries (LIBs) has increased rapidly. However, commercial inorganic-based cathode materials have a low theoretical capacity and inherent disadvantages, such as high cost and toxicity. Redox-active organic cathodes with a high theoretical capacity, eco-friendly properties, and sustainability have been developed to overcome these limitations. Herein, perylene diimide derivatives N-substituted with 1,2,4-triazol-3-yl rings (PDI-3AT) were developed to apply as a cathode material for LIBs. The PDI-3AT cathode exhibited discharge capacities of 85.2 mAh g-1 (50 mA g-1 over 100 cycles) and 64.5 mAh g-1 (500 mA g-1 over 1000 cycles) with ratios to the theoretical capacities of 84 and 64%, respectively. Electrochemical kinetics analysis showed capacitive behaviors of the PDI-3AT cathode with efficient pathways for lithium-ion transport. Also, the activation step of the PDI-3AT cathode was demonstrated by improving the charge transfer resistance and lithium-ion diffusion coefficient during the initial few charge-discharge cycles. Furthermore, DFT calculations at the B3LYP/6-311+G** level and ex situ analysis of various charge states of the PDI-3AT electrode using attenuated total reflection Fourier transform infrared (ATR FT-IR) analysis, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) were conducted for the further study of the lithium-ion storage mechanism. The results showed that the lithiation process formed the lithium enolate (═C-O-Li) coordinated with the N atoms of the 1,2,4-triazole ring. It is expected that our study results will encourage the production and use of redox-active perylene diimide derivatives as next-generation cathode materials.

17.
Pharmaceutics ; 15(12)2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38140121

ABSTRACT

Messenger RNA (mRNA) therapies have emerged as potent and personalized alternatives to conventional DNA-based therapies. However, their therapeutic potential is frequently constrained by their molecular instability, susceptibility to degradation, and inefficient cellular delivery. This study presents the nanoparticle "ChargeSome" as a novel solution. ChargeSomes are designed to protect mRNAs from degradation by ribonucleases (RNases) and enable cell uptake, allowing mRNAs to reach the cytoplasm for protein expression via endosome escape. We evaluated the physicochemical properties of ChargeSomes using 1H nuclear magnetic resonance, Fourier-transform infrared, and dynamic light scattering. ChargeSomes formulated with a 9:1 ratio of mPEG-b-PLL to mPEG-b-PLL-SA demonstrated superior cell uptake and mRNA delivery efficiency. These ChargeSomes demonstrated minimal cytotoxicity in various in vitro structures, suggesting their potential safety for therapeutic applications. Inherent pH sensitivity enables precise mRNA release in acidic environments and structurally protects the encapsulated mRNA from external threats. Their design led to endosome rupture and efficient mRNA release into the cytoplasm by the proton sponge effect in acidic endosome environments. In conclusion, ChargeSomes have the potential to serve as effective secure mRNA delivery systems. Their combination of stability, protection, and delivery efficiency makes them promising tools for the advancement of mRNA-based therapeutics and vaccines.

18.
BMC Med ; 21(1): 509, 2023 12 21.
Article in English | MEDLINE | ID: mdl-38129845

ABSTRACT

BACKGROUND: The predictive relationship between mild-to-moderate alcohol consumption and the risk of incident atrial fibrillation (AF) remains controversial. OBJECTIVE: We investigated whether the relationship between alcohol consumption and the risk of incident AF could be associated with the genetic predisposition to alcohol metabolism. METHODS: A total of 399,329 subjects with genetic data from the UK Biobank database, enrolled between 2006 and 2010, were identified and followed for incident AF until 2021. Genetic predisposition to alcohol metabolism was stratified according to the polygenic risk score (PRS) tertiles. Alcohol consumption was categorized as non-drinkers, mild-to-moderate drinkers (< 30 g/day), and heavy drinkers (≥ 30 g/day). RESULTS: During the follow-up (median 12.2 years), 19,237 cases of AF occurred. When stratified by PRS tertiles, there was a significant relationship between genetic predisposition to alcohol metabolism and actual alcohol consumption habits (P < 0.001). Mild-to-moderate drinkers showed a decreased risk of AF (HR 0.96, 95% CI 0.92-0.99), and heavy drinkers showed an increased risk of AF (HR 1.06, 95% CI 1.02-1.10) compared to non-drinkers. When stratified according to PRS tertiles for genetic predisposition to alcohol metabolism, mild-to-moderate drinkers had equivalent AF risks, and heavy drinkers showed increased AF risk in the low PRS tertile group. However, mild-to-moderate drinkers had decreased AF risks and heavy drinkers showed similar risks of AF in the middle/high PRS tertile groups. CONCLUSIONS: Differential associations between alcohol consumption habits and incident AF across genetic predisposition to alcohol metabolism were observed; individuals with genetic predisposition to low alcohol metabolism were more susceptible to AF.


Subject(s)
Atrial Fibrillation , Humans , Atrial Fibrillation/epidemiology , Atrial Fibrillation/genetics , Cohort Studies , Risk Factors , UK Biobank , Biological Specimen Banks , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Alcohol Drinking/genetics , Genetic Predisposition to Disease
19.
ACS Appl Mater Interfaces ; 15(48): 55692-55702, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-37981729

ABSTRACT

Aqueous zinc-vanadium hybrid redox flow battery systems are an efficient strategy to address the problems of low voltage and high cost of conventional all-vanadium redox flow batteries. However, the low electrochemical activity of carbon-based electrodes toward a vanadium redox reaction limits the performance of redox flow batteries. In this study, polyhedral binary cerium titanium oxide (Ce2/3TiO3, CTO) is synthesized using molten salt synthesis. CTO is fabricated by adjusting the temperature and composition. Notably, the prepared CTO obtained at 1000 °C shows the highest catalytic activity for a VO2+/VO2+ redox reaction. Further, CTO is prepared as a composite electrocatalyst and applied to a high-voltage aqueous zinc-vanadium redox flow battery. The cell adopts an alkali zinc electrolyte containing a Zn/[Zn(OH)4]2- redox pair and exhibits a high operating voltage of 2.26 V. Remarkably, a zinc-vanadium redox flow battery using the composite electrocatalyst exhibits a high energy density of 42.68 Wh L-1 at 20 mA cm-2 and an initial voltage efficiency of 90.3%. The excellent cell performance is attributed to structural defects caused by A-site deficiency in the perovskite oxide structure as well as oxygen vacancies resulting from the low valence state of the metal ion, which enhance the catalytic activity of the vanadium ions.

20.
Nature ; 624(7990): 130-137, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37993711

ABSTRACT

The termination of a meal is controlled by dedicated neural circuits in the caudal brainstem. A key challenge is to understand how these circuits transform the sensory signals generated during feeding into dynamic control of behaviour. The caudal nucleus of the solitary tract (cNTS) is the first site in the brain where many meal-related signals are sensed and integrated1-4, but how the cNTS processes ingestive feedback during behaviour is unknown. Here we describe how prolactin-releasing hormone (PRLH) and GCG neurons, two principal cNTS cell types that promote non-aversive satiety, are regulated during ingestion. PRLH neurons showed sustained activation by visceral feedback when nutrients were infused into the stomach, but these sustained responses were substantially reduced during oral consumption. Instead, PRLH neurons shifted to a phasic activity pattern that was time-locked to ingestion and linked to the taste of food. Optogenetic manipulations revealed that PRLH neurons control the duration of seconds-timescale feeding bursts, revealing a mechanism by which orosensory signals feed back to restrain the pace of ingestion. By contrast, GCG neurons were activated by mechanical feedback from the gut, tracked the amount of food consumed and promoted satiety that lasted for tens of minutes. These findings reveal that sequential negative feedback signals from the mouth and gut engage distinct circuits in the caudal brainstem, which in turn control elements of feeding behaviour operating on short and long timescales.


Subject(s)
Appetite Regulation , Brain Stem , Eating , Feedback, Physiological , Food , Satiation , Stomach , Appetite Regulation/physiology , Brain Stem/cytology , Brain Stem/physiology , Eating/physiology , Neural Pathways/cytology , Neural Pathways/physiology , Neurons/metabolism , Prolactin-Releasing Hormone/metabolism , Satiation/physiology , Solitary Nucleus/cytology , Solitary Nucleus/physiology , Stomach/physiology , Taste/physiology , Time Factors , Animals , Mice
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