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Objectives. Air pollution is an increasing global concern, and its effect on allergic inflammation has attracted the attention of many researchers. Particulate matter (PM) is a major component of ambient air pollution, and heavy metals are the primary toxic constituents of PM. As previous studies on the impact of air pollutants on allergic inflammation did not adequately mimic real-world atmospheric exposure, we developed an experimental model to investigate the effects of aerosolized air pollutants on nasal epithelial cells and fibroblasts. Methods. We collected particulate matter 2.5 (PM2.5) samples from ambient 24-hour air samples obtained in Seoul from August 2020 to August 2022, and then conducted component analysis for metallic constituents. Primary nasal epithelial cells and nasal fibroblasts, obtained and cultured from the turbinate tissues of human participants, were treated with PM2.5. The associations of heavy metals identified from the component analysis with cytokine expression were investigated. A three-dimensional (3D)-hybrid culture model, consisting of co-culture of an air-liquid interface and nasal fibroblast spheroids, was constructed to observe the impact of aerosolized air pollutants. Results. Among the heavy metals, Si was the predominant component of PM2.5, and Zn showed the highest correlation with the concentration of PM2.5 in Seoul. PM2.5, Zn, and Si increased the production of epithelial cell-derived cytokines, and PM2.5 and Zn exhibited similar trends with one another. Exposure of the 3D-hybrid model to aerosolized PM2.5 and Zn resulted in elevated periostin, alpha-smooth muscle actin, and fibronectin expression in fibroblast spheroids, and those without an epithelial barrier exhibited a similar increase in periostin expression. Conclusion. Ambient air pollutants in the form of aerosols increase the expression of allergic inflammatory cytokines in both nasal epithelial cells and fibroblasts. Regulations on air pollution will help reduce the global burden of allergic diseases in the future.

Abstract This study investigated intraocular pressure (IOP) in Dutch belted rabbits using two different tonometers, rebound tonometry (TonoVet Plus; TVP) and a Tonopen (Tono-Pen AVIA Vet; TPA). Post-pubescent male Dutch belted rabbits aged 36 weeks (n = 10 animals) were used in the study. IOP measurements were conducted every 2 weeks for 22 weeks using TVP and TPA on both eyes of each rabbit. The average IOP measurements were compared by the paired Student’s t-test. Pairwise Pearson’s correlation coefficients and Bland–Altman statistics were used. The overall mean IOP measured with TPA was significantly higher than that with TVP (23.5 ± 4.9 vs. 21.8 ± 2.4 mmHg for the right eyes; P = 0.045, and 23.0 ± 4.7 vs. 21.5 ± 2.4 mmHg for the left eyes; P = 0.047). Both tonometers tended to show increased IOP readings with age, and positive correlations between IOP and age were observed with both TPA (r = 0.95, P

Abstract Chronic inflammation is a major cause of cancer worldwide. Interleukin 33 (IL-33) is a critical initiator of cancer-prone chronic inflammation; however, its induction mechanism by environmental causes of chronic inflammation is unknown. Herein, we demonstrate that Toll-like receptor (TLR)3/4-TBK1-IRF3 pathway activation links environmental insults to IL-33 induction in the skin and pancreas inflammation. An FDA-approved drug library screen identifies pitavastatin to effectively suppress IL-33 expression by blocking TBK1 membrane recruitment/activation through the mevalonate pathway inhibition. Accordingly, pitavastatin prevents chronic pancreatitis and its cancer sequela in an IL-33-dependent manner. The IRF3-IL-33 axis is highly active in chronic pancreatitis and its associated pancreatic cancer in humans. Interestingly, pitavastatin use correlates with a significantly reduced risk of chronic pancreatitis and pancreatic cancer in patients. Our findings demonstrate that blocking the TBK1-IRF3-IL-33 signaling axis suppresses cancer-prone chronic inflammation. Statins present a safe and effective prophylactic strategy to prevent chronic inflammation and its cancer sequela.

Abstract As there is an increasing need for an efficient solver of combinatorial optimization problems, much interest is paid to the Ising machine, which is a novel physics-driven computing system composed of coupled oscillators mimicking the dynamics of the system of coupled electronic spins. In this work, we propose an energy-efficient nano-oscillator, called OTSNO, which is composed of an Ovonic Threshold Switch (OTS) and an electrical resistor. We demonstrate that the OTSNO shows the synchronization behavior, an essential property for the realization of an Ising machine. Furthermore, we have discovered that the capacitive coupling is advantageous over the resistive coupling for the hardware implementation of an Ising solver by providing a larger margin of the variations of components. Finally, we implement an Ising machine composed of capacitively-coupled OTSNOs to demonstrate that the solution to a 14-node MaxCut problem can be obtained in 40 µs while consuming no more than 2.3 µJ of energy. Compared to a previous hardware implementation of the phase-transition nano-oscillator (PTNO)-based Ising machine, the OTSNO-based Ising machine in this work shows the performance of the increased speed by more than one order while consuming less energy by about an order.

Abstract Previous studies have rarely investigated the role of non-vitamin K oral anticoagulants (NOAC) and warfarin in the secondary prevention of ischemic stroke patients with nonvalvular atrial fibrillation (NVAF). In this study, we compared the effectiveness and safety of NOAC and warfarin for secondary prevention in Korean ischemic stroke patients with NVAF. Based on the Korean National Health Insurance Service Database, this study included 21,064 oral anticoagulants-naïve acute ischemic stroke patients with NVAF between July 2015 and June 2019. The main study outcomes included ischemic stroke, systemic embolism, major bleeding, and death. During the observational periods, NOAC users had a significantly decreased risk of ischemic stroke + systemic embolism (adjusted hazard ratio [aHR] 0.86; 95% confidence interval [CI] 0.78–0.95), ischemic stroke (aHR 0.89; 95% CI 0.81–0.99), major bleeding (aHR 0.78; 95% CI 0.68–0.89), and all-cause death (aHR 0.87; 95% CI 0.81–0.93). Standard-dose NOAC users had a lower risk of ischemic stroke, systemic embolism, and major bleeding events than warfarin users. In contrast, low-dose NOAC users did not differ in risk from warfarin users for all outcomes. In conclusion, NOACs were associated with a lower risk of secondary thromboembolic events and bleeding complications in Korean ischemic stroke patients with NVAF than warfarin.

Abstract Establishing dependable, cost-effective electrical connections is vital for enhancing device performance and shrinking electronic circuits. MXenes, combining excellent electrical conductivity, high breakdown voltage, solution processability, and two-dimensional morphology, are promising candidates for contacts in microelectronics. However, their hydrophilic surfaces, which enable spontaneous environmental degradation and poor dispersion stability in organic solvents, have restricted certain electronic applications. Herein, electrohydrodynamic printing technique is used to fabricate fully solution-processed thin-film transistors with alkylated 3,4-dihydroxy-L-phenylalanine functionalized Ti3C2T x (AD-MXene) as source, drain, and gate electrodes. The AD-MXene has excellent dispersion stability in ethanol, which is required for electrohydrodynamic printing, and maintains high electrical conductivity. It outperformed conventional vacuum-deposited Au and Al electrodes, providing thin-film transistors with good environmental stability due to its hydrophobicity. Further, thin-film transistors are integrated into logic gates and one-transistor-one-memory cells. This work, unveiling the ligand-functionalized MXenes’ potential in printed electrical contacts, promotes environmentally robust MXene-based electronics (MXetronics).

Abstract Thermal losses in photoelectric devices limit their energy conversion efficiency, and cyclic input of energy coupled with pyroelectricity can overcome this limit. Here, incorporating a pyroelectric absorber into a photovoltaic heterostructure device enables efficient electricity generation by leveraging spontaneous polarization based on pulsed light-induced thermal changes. The proposed pyroelectric-photovoltaic device outperforms traditional photovoltaic devices by 2.5 times due to the long-range electric field that occurs under pulse illumination. Optimization of parameters such as pulse frequency, scan speed, and illumination wavelength enhances power harvesting, as demonstrated by a power conversion efficiency of 11.9% and an incident-photon-to-current conversion efficiency of 200% under optimized conditions. This breakthrough enables reconfigurable electrostatic devices and presents an opportunity to accelerate technology that surpasses conventional limits in energy generation.

Abtract Clinical circulating cell-free DNA (cfDNA) testing is now routine, however test accuracy remains limited. By understanding the life-cycle of cfDNA, we might identify opportunities to increase test performance. Here, we profile cfDNA release across a 24-cell line panel and utilize a cell-free CRISPR screen (cfCRISPR) to identify mediators of cfDNA release. Our panel outlines two distinct groups of cell lines: one which releases cfDNA fragmented similarly to clinical samples and purported as characteristic of apoptosis, and another which releases larger fragments associated with vesicular or necrotic DNA. Our cfCRISPR screens reveal that genes mediating cfDNA release are primarily involved with apoptosis, but also identify other subsets of genes such as RNA binding proteins as potential regulators of cfDNA release. We observe that both groups of cells lines identified primarily produce cfDNA through apoptosis. These results establish the utility of cfCRISPR, genetically validate apoptosis as a major mediator of DNA release in vitro, and implicate ways to improve cfDNA assays.

Abstract Nonviral delivery of the CRISPR/Cas9 system provides great benefits for in vivo gene therapy due to the low risk of side effects. However, in vivo gene editing by delivering the Cas9 ribonucleoprotein (RNP) is challenging due to the poor delivery into target tissues and cells. Here, we introduce an effective delivery method for the CRISPR/Cas9 RNPs by finely tuning the formulation of ionizable lipid nanoparticles. The LNPs delivering CRISPR/Cas9 RNPs (CrLNPs) are demonstrated to induce gene editing with high efficiencies in various cancer cell lines in vitro. Furthermore, we show that CrLNPs can be delivered into tumor tissues with high efficiency, as well as induce significant gene editing in vivo. The current study presents an effective platform for nonviral delivery of the CRISPR/Cas9 system that can be applied as an in vivo gene editing therapeutic for treating various diseases such as cancer and genetic disorders.

In this study, Ag-impregnated silica aerogel composites were fabricated via wet impregnation. In this approach, silver salt was reduced with ethylene glycol in the presence of polyvinylpyrrolidone (PVP) at reaction temperature 80°C. PVP was used as a capping agent to protect the Ag nanoparticles (NPs) from agglomeration. Wet impregnation was used to synthesize the Ag/SiO2 composite by combining the reduction of AgNO3 with a silica aerogel slurry. Experimental results showed that the AgNO3 concentration and PVP: AgNO3 ratio had an active influence on the growth of Ag NPs on silica surfaces. The X-ray diffraction (XRD) patterns of the composite material showed no imprints of impurities or parasitic materials except for Ag and SiO2. Scanning electron microscopy (SEM) images revealed that the Ag NPs were well impregnated into the porous silica aerogel structure. It was found that SiO2 aerogel surfaces were homogeneously surrounded by the Ag NPs.

Objective The efficacy of previously developed respiratory barrier enclosures to limit healthcare workers’ exposure to aerosols from COVID-19 patients remains unclear; in addition, the design of these devices is unsuitable for transportation or other emergency procedures. Therefore, we developed a novel negative pressure respiratory isolator to improve protection from patient-generated aerosols and evaluated its protective effect in conversion to systemic isolator. Methods This in vitro study simulated droplets by nebulizing 1% glycerol + 99% ethanol solution. We performed cardiopulmonary resuscitation (CPR) and converted a respiratory barrier enclosure into a systemic isolator with a respiratory barrier as well as a respiratory barrier with negative pressure generator (NPG), which were compared with control and room air. During the procedure, particles were counted for 30 seconds and the count was repeated 10 times. Results During CPR, the total number of particles in the respiratory barrier with NPG (280,529; interquartile range [IQR], 205,263–359,195; P=0.970) was similar to that in the control (308,789; IQR, 175,056–473,276). Using NPG with a respiratory barrier reduced the number of particles to 27,524 (IQR, 26,703–28,905; P=0.001). Particle number during conversion of the respiratory barrier into a systemic isolator was also lower than in the control (25,845; IQR, 19,391–29,772; P=0.001). Conclusion The novel isolator was converted to a systemic isolator without air leakage. The aerosol-blocking effect of the isolator was quantified using a particle counter during CPR. Further studies comparing the barrier effect of isolators within various pressure differentials are warranted.

Abstract The aim of this preliminary study was to assess the impact of injecting recombinant human bone morphogenetic protein-2 (rhBMP-2) with β-tricalcium phosphate (β-TCP) carrier into the uppermost instrumented vertebra (UIV) during surgery to prevent the development of proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). The 25 patients from study group had received 0.5 mg rhBMP-2 mixed with 1.5 g β-TCP paste injection into the UIV during surgery. The control group consisted of 75 patients who underwent surgery immediately before the start of the study. The incidences of PJK and PJF were analyzed as primary outcomes. Spinopelvic parameters and patient-reported outcomes were analyzed as secondary outcomes. Hounsfield unit (HU) measurements were performed to confirm the effect of rhBMP-2 with β-TCP on bone formation at preoperative and postoperative at computed tomography. PJK and PJF was more occurred in control group than study group (p = 0.02, 0.29, respectively). The HU of the UIV significantly increased 6 months after surgery. And the increment at the UIV was also significantly greater than that at the UIV-1 6 months after surgery. Injection of rhBMP-2 with β-TCP into the UIV reduced PJK and PJF rates 6 months after surgery with new bone formation.

Abstract This study aimed to compare the outcomes of flanged intraocular lens (IOL) fixation with new IOL exchange after dislocated IOL removal and repositioned dislocated IOL in patients with IOL dislocation. Eighty-nine eyes that underwent flanged IOL fixation were retrospectively included, with 51 eyes in the exchanged IOL group and 38 eyes in the repositioned IOL group. In both groups, best-corrected visual acuity (BCVA) improved at 1, 3, 6, and 12 months postoperatively and did not differ between the two groups at any of these time points. However, at 1 week postoperatively, BCVA in the repositioned IOL group improved compared with baseline, whereas that in the exchanged IOL group did not. Moreover, there were lesser changes in the corneal endothelial cell density (ECD) and corneal astigmatism in the repositioned IOL group than in the exchanged IOL group. The IOL positions, including IOL tilt and IOL decentration, were not different between the groups. Flanged IOL fixation with new IOL exchange and with repositioned dislocated IOL for patients with IOL dislocation had similar visual outcomes and IOL position. However, the latter had a smaller corneal ECD decrease and astigmatic change. This technique was effective in treating IOL dislocation while minimizing corneal injury.

Abstract Background Low muscle mass is associated with adverse health outcomes such as functional decline and all-cause mortality. This study investigated the relationship between the risk of low muscle mass and the training period and/or frequency of resistance training (RT). Methods We included 126,339 participants (81,263 women) from nationwide cohorts in Korea. Low muscle mass was defined based on the fat-free mass index. To investigate the presence of an inverse dose–response relationship between RT levels and the risk of low muscle mass, the training period (months) and frequency (per week) of RT were used. Multiple logistic regression models were used to assess the risk of low muscle mass according to the RT levels. Results Prevalence rates for low muscle mass in our study population were 21.27% and 6.92% in men and women, respectively. When compared with not performing RT, performing RT for 3–4 days/week and ≥5 days/week decreased the risk of low muscle mass by 22% and 27%, respectively, and performing RT for 12–23 months and ≥24 months decreased the risk by 19% and 41%, respectively. When simultaneously considering both training period and frequency, performing RT for either 3–4 days/week or ≥5 days/week was significantly related to risk reduction, provided that the training period was at least 1 year. Importantly, performing RT for more than 2 years resulted in an additional risk reduction. However, there was no additional effect of performing RT for ≥5 days/week compared to 3–4 days/week, regardless of whether the RT duration was 1–2 years or more than 2 years. Conclusions Since performing RT for 5 days/week or more did not yield any additional effects on the risk of low muscle mass, performing RT for 3–4 days/week was sufficient to prevent low muscle mass. The effectiveness of this preventive measure can be further enhanced by engaging in long-term RT, specifically for more than 2 years.

Abstract Background Perceiving oneself as obese has been associated with weight loss attempts. However, such a perception may not sufficiently drive significant weight reduction in many individuals. Hence, relying solely on the traditionally emphasized perceived risk of behavioral changes in obesity is challenging. This study used an extended parallel process model and a risk perception attitude framework to explore the influence of perceived risk and perceived efficacy on individual obesity knowledge and obesity prevention behaviors. Methods Data were obtained from 1,100 Korean adults aged 40–69 years through an online survey conducted in October 2022. Multinomial logistic regression and analysis of variance were employed to assess the relationships among perceived risk, perceived efficacy, obesity knowledge, and obesity prevention behaviors. Results Sex was associated with being underweight, overweight, and obese. Moreover, perceived severity was associated with obesity, whereas perceived susceptibility was associated with overweight and obese. Response efficacy was related to being overweight alone, whereas self-efficacy was associated with being underweight, overweight, and obese. The main effects of sex and perceived risk, and their interaction effect were statistically significant for obesity knowledge. Additionally, the main effects of sex, perceived risk, and perceived efficacy on obesity prevention behaviors were statistically significant. Conclusions The extended parallel process model and risk perception attitude framework proved effective in classifying obesity based on body mass index, obesity knowledge, and obesity prevention behaviors.

Abstract This prospective cross-sectional study investigated the visual function of preperimetric glaucoma (PPG) patients based on hemifield (HF) pattern electroretinogram (PERG) amplitudes. Thirty-two (32) normal subjects and 33 PPG patients were enrolled in control and PPG groups, respectively. All of the participants had undergone full ophthalmic examinations, including spectral-domain optical coherence tomography (SD-OCT), visual field (VF) examination and pattern electroretinography (PERG). The PERG parameters along with the HF ratios of SD-OCT and PERG were compared between the control and PPG groups. Pairwise Pearson's correlation coefficients and linear regression models were fitted to investigate the correlations. The PERG N95 amplitudes were significantly lower in the PPG group (P

IntroductionDespite evidence suggesting that metabolic intermediates like β-HB influence white adipose tissue (WAT) metabolism, the precise molecular mechanisms remain unclear. The aim of this study was to investigate the impact of beta-hydroxybutyrate (β-HB) on the fat browning program and to explore the underlying molecular mechanisms using both in vitro and in vivo models. We assessed the effects of β-HB on fat browning in adipocytes using 3T3-L1 cells and rat models.MethodsWe evaluated the effects of β-HB on fat browning, thermogenesis, lipid accumulation, adipokine expression, and mitochondrial biogenesis by treating mature 3T3-L1 adipocytes with sodium β-HB for 24 h or by continuously exposing preadipocytes to β-HB during the 8-day differentiation process. Male Sprague Dawley rats were divided into control, exercise only (EX), ketogenic diet only (KD), and combined exercise and ketogenic diet (KE) groups for an 8-week intervention involving diet and/or exercise. After intervention, we evaluated WAT histology, plasma lipids and adipokines, and the expression of markers related to fat browning, thermogenesis and mitochondrial biogenesis in WAT of rats.ResultsIn our adipocyte culture experiments, β-HB reduced intracellular lipid accumulation by enhancing lipolysis and stimulated the expression of thermogenic and fat browning genes like uncoupling protein 1 (UCP1), PR domain containing 16 (PRDM16), and adipokines such as fibroblast growth factor 21 (FGF21) and Fibronectin type III domain-containing protein 5 (FDNC5). Additionally, β-HB activated the AMPK-SIRT1-PGC-1α pathway, with UCP1 and PRDM16 upregulation mediated by β-HB intracellular action and SIRT1 activity. In animal experiments, KE group raised β-HB levels, decreasing body weight and blood lipids. KD with EX promoted WAT browning possibly via AMPK-SIRT1-PGC-1α, augmenting PRDM16, UCP1, FGF21, and FNDC5 expression.Conclusionβ-HB induction via KD and/or EX shows potential in promoting WAT browning by activating mitochondrial biogenesis, lipolysis, and thermogenesis, suggesting that dietary and physical intervention inducing β-HB may benefit metabolic health.

Poor clearances, misalignments, and carbon deposits in a turbocharger due to high running hours can decrease engine efficiency. This study analyzes the effects of turbocharger reconditioning on the performance and emissions formation of a marine diesel generator engine. The engine test experiments were performed on a university training ship's auxiliary diesel engine with 4309 running hours before and after the TC overhaul. As a result, cylinder peak pressure was increased by a maximum of 3.57 % while fuel saving of 5–8 g/kWh was realized. Lower exhaust gas temperatures and improved charge air pressure by up to 7.7 % were recorded. A significant CO emission reduction of 21.6 % was recorded at idle load whereas NOx and CO2 emissions were reduced to a maximum of 4.86 % and 7.30 % at 50 % engine load. The results indicate that scheduled TC overhaul and maintenance are very useful to improve the engine’s fuel economy, and performance and reduce exhaust emissions.

Alzheimer’s disease (AD) is characterized by cognitive impairment, loss of learning and memory, and abnormal behaviors. Scopolamine (SCOP) is a non-selective antagonist of muscarinic acetylcholine receptors that exhibits the behavioral and molecular hallmarks of AD. Vanillic acid (VA), a phenolic compound, is obtained from the roots of a traditional plant called Angelica sinensis, and has several pharmacologic effects, including antimicrobial, anti-inflammatory, anti-angiogenic, anti-metastatic, and antioxidant properties. Nevertheless, VA’s neuroprotective potential associated with the memory has not been thoroughly investigated. Therefore, this study investigated whether VA treatment has an ameliorative effect on the learning and memory impairment induced by SCOP in rats. Behavioral experiments were utilized to assess the learning and memory performance associated with the hippocampus. Using western blotting analysis and assay kits, the neuronal damage, oxidative stress, and acetylcholinesterase activity responses of hippocampus were evaluated. Additionally, the measurement of long-term potentiation was used to determine the function of synaptic plasticity in organotypic hippocampal slice cultures. In addition, the synaptic vesicles’ density and the length and width of the postsynaptic density were evaluated using electron microscopy. Consequently, the behavioral, biochemical, electrophysiological, and ultrastructural analyses revealed that VA treatment prevents learning and memory impairments caused by SCOP in rats. The study’s findings suggest that VA has a neuroprotective effect on SCOP-induced learning and memory impairment linked to the hippocampal cholinergic system, oxidative damage, and synaptic plasticity. Therefore, VA may be a prospective therapeutic agent for treating AD.

BackgroundAlzheimer’s disease (AD) is a complex neurodegenerative disorder influenced by various factors, including liver function, which may impact the clearance of amyloid-β (Aβ) in the brain. This study aimed to explore how the apolipoprotein E (APOE) ε4 allele affects the relationship of liver function markers with AD pathology and cognition.MethodsWe analyzed data from two independent cohorts, including 732 participants from the Hallym University Medical Center and 483 from the Alzheimer’s Disease Neuroimaging Initiative, each group consisting of individuals with and without the APOE ε4 allele. Cross-sectional analyses evaluated the associations of liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, total bilirubin, and albumin) with AD diagnosis, amyloid positron emission tomography (PET) burden, and cerebrospinal fluid biomarkers for AD (Aβ42, total tau, and phosphorylated tau181) at baseline. Longitudinally, we investigated the associations between these liver enzymes and changes in cognitive performance over the course of a year. Logistic and linear regression models were used to analyze these associations and mediation analyses were conducted to assess whether age and amyloid PET burden mediated these associations.ResultsOnly in the APOE ε4 carrier group, a high AST to ALT ratio and low ALT levels were significantly associated with AD diagnosis, increased amyloid PET burden, and faster longitudinal decline in cognitive function in both cohorts. In particular, the AST to ALT ratio was associated with cerebrospinal fluid Aβ42 levels exclusively in the APOE ε4 carrier group in the Alzheimer’s Disease Neuroimaging Initiative cohort but not with phosphorylated tau181 or total tau levels. Moreover, mediation analyses from both cohorts revealed that in the APOE ε4 carriers group, age did not mediate the associations between liver enzymes and AD diagnosis or amyloid PET burden. However, amyloid PET burden partially mediated the association between liver enzymes and AD diagnosis exclusively in the APOE ε4 carriers group.ConclusionThis study provides valuable insights into the significant association of the APOE ε4 allele with liver enzymes and their potential role in Aβ-related pathogenesis and cognition in AD. Further research is required to elucidate the underlying mechanisms and potential therapeutic implications of these findings.

Abstract Although sodium‐ion batteries (SIBs) offer promising low‐cost alternatives to lithium‐ion batteries (LIBs), several challenges need to be overcome for their widespread adoption. A primary concern is the optimization of carbon anodes. Graphite, vital to the commercial viability of LIBs, has a limited capacity for sodium ions. Numerous alternatives to graphite are explored, particularly focusing on disordered carbons, including hard carbon. However, compared with graphite, most of these materials underperform in LIBs. Furthermore, the reaction mechanism between carbon and sodium ions remains ambiguous owing to the structural diversity of disordered carbon. A straightforward mechanical approach is introduced to enhance the sodium ion storage capacity of graphite, supported by comprehensive analytical techniques. Mechanically activated graphite delivers a notable reversible capacity of 290.5 mAh·g−1 at a current density of 10 mA·g−1. Moreover, it maintains a capacity of 157.7 mAh·g−1 even at a current density of 1 A·g−1, benefiting from the defect‐rich structure achieved by mechanical activation. Soft X‐ray analysis revealed that this defect‐rich carbon employs a sodium‐ion storage mechanism distinct from that of hard carbon. This leads to an unexpected reversible reaction on the solid electrolyte surface. These insights pave the way for innovative design approaches for carbon electrodes in SIB anodes.

BackgroundChronic rhinosinusitis (CRS) is an inflammatory disease affecting more than 10% of the global adult population. It is classified into Th1, Th2, and Th17 endotypes and eosinophilic and non-eosinophilic types. Th2-based inflammation and eosinophilic CRS (ECRS) are associated with tissue remodeling and fibrinolytic system impairment.ObjectiveTo elucidate the role of eosinophils in inducing fibrin deposition in CRS nasal polyp tissues and explore potential regulatory mechanisms.MethodsWe analyzed the expression of genes related to the serpin family and fibrinolytic system using Gene Expression Omnibus and Next-generation sequencing data. Differentially expression genes (DEGs) analysis was used to compare control and nasal polyp tissues, followed by KEGG and Gene ontology (GO) analysis. We measured the expression and correlation of plasminogen activator-1 (PAI-1), tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), and urokinase plasminogen activator surface receptor (u-PAR) in CRS tissues, and evaluated the effect of eosinophils on the fibrinolytic system using a cytokine array and co-culture.ResultsNasal polyp tissues showed upregulated PAI-1, u-PA, and u-PAR expression and downregulated t-PA expression. Fibrinolytic system-related genes positively correlated with Th2 cytokines, except for t-PA. Eosinophil-derived Chitinase-3-like protein 1 (CHI3L1) increased PAI-1 expression and decreased t-PA levels in fibroblasts and epithelial cells. The inhibition of CHI3L1 suppresses these alterations.ConclusionCHI3L1 contributes to fibrin deposition by impairing the fibrinolytic system during nasal polyp formation. The regulation of CHI3L1 expression may inhibit fibrin deposition and edema in ECRS, presenting a potential treatment for this condition.

IntroductionHypertension is a primary risk factor for cardiovascular disease and all-cause mortality. This study investigated sex-based differences in the association between the risk of hypertension and resistance training (RT) levels, including training frequency and period.MethodsWe enrolled 162,102 participants from nationwide Korean cohorts. The training period (months) and frequency (per week) of RT were used to investigate the presence of an inverse dose–response relationship between RT levels and the risk of hypertension. Multiple logistic regression models were used to evaluate the risk of hypertension in relation to RT levels.ResultsThe prevalence of hypertension in the study population was 36.28% in men and 26.94% in women. Performing RT was associated with an 8% reduction in the risk of hypertension in women but not in men. In women, performing RT for 3–4 days/week, compared with not performing RT, reduced the risk of hypertension by 11%, even after adjusting for covariates, including RT time per week and period. However, in men, no significant association was observed between training frequency and the risk of hypertension. We also evaluated the risk of hypertension by simultaneously considering both the RT frequency and period. Performing RT for 3–4 days/week and ≥5 days/week were markedly related to 14 and 11% hypertension risk reduction, respectively, in women who had been performing RT for at least 6 months.ConclusionGiven that no inverse dose–response association was observed between RT frequency and hypertension risk, engaging in RT for 3–4 days/week for at least 6 months is recommended for women. Further longitudinal studies are needed to verify sex-based differences in the antihypertensive effects of regular RT.

Background In adult patients with high myopia (HM), progressive axial elongation poses a significant risk for the development of subsequent ocular complications that may lead to visual impairment. Effective strategies to reduce or prevent further axial elongation in highly myopic adult patients have not been available so far. Recent studies suggested that medically lowering intraocular pressure (IOP) may reduce axial elongation.Objective This clinical randomised controlled trial (RCT) aims to evaluate the efficacy of medical IOP reduction in adult patients with progressive HM (PHM).Trial design Single-centre, open-label, prospective RCT.Methods This RCT will recruit 152 participants with PHM at the Zhongshan Ophthalmic Center (ZOC). Randomised in a ratio of 1:1, participants will receive IOP-lowering eyedrops (intervention group) or will be followed without treatment (control group) for 12 months. Follow-up visits will be conducted at 1, 6 and 12 months after baseline. Only one eye per eligible participant will be included for analysis. The primary outcome is the change in axial length (AL) within the study period of 12 months. Secondary outcomes include the incidence and progression of visual field (VF) defects, changes in optic disc morphology and incidence and progression of myopic maculopathy. Difference in AL changes between the two groups will be analysed using linear regression analysis. For the secondary outcomes, a multifactor Poisson regression within a generalised linear model will be used to estimate the relative risk of progression in VF defects and myopic maculopathy, and the rate of thinning in retinal nerve fibre layer and ganglion cell-inner plexiform will be assessed through Kaplan-Meier curves and log-rank tests.Ethics and dissemination Full ethics approval for this trial has been obtained from the Ethics Committee of ZOC, Sun Yat-sen University, China (ID: 2023KYPJ110). Results of this trial will be disseminated through peer-reviewed journals and conference presentations.Trial registration number NCT05850936.

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) infections are often difficult to treat because of their biofilm-forming ability and antimicrobial resistance. We investigated the effects of sub-minimal inhibitory concentrations (MICs) of antibiotics on MRSA biofilm formation. Clinical MRSA isolates were grown with sub-MICs (1/256–1/2 × MICs) of nafcillin, vancomycin, ciprofloxacin, and rifampin. The biofilm biomass was measured using crystal violet staining. Of the 107 MRSA isolates tested, 63 (58.9%) belonged to sequence type 5 (ST5), and 44 (41.1%) belonged to ST72. The MIC50/MIC90 values of nafcillin, vancomycin, ciprofloxacin, and rifampin were 256/512, 1/2, 64/512, and 0.008/0.03 mg/L, respectively. The sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin promoted biofilm formation in 75 (70.1%), 49 (45.8%), 89 (83.2%), and 89 (83.2%) isolates, respectively. At sub-MICs of nafcillin, the factors associated with strong biofilm induction were the ST5 strain (P = 0.001) and agr dysfunction (P = 0.005). For the sub-MICs of ciprofloxacin, the associated factors were the ST5 strain (P = 0.002), staphylococcal protein A type t002 strain (P < 0.001), and ciprofloxacin resistance (P < 0.001). Among the sub-MICs of rifampin, only ST5 was associated with strong biofilm induction (P = 0.006). Because the sub-MICs of rifampin were much lower than clinically relevant concentrations, we further tested the capability of biofilm induction in 0.03[Formula: see text]32 mg/L of rifampin. At these concentrations, rifampin-induced biofilm formation was rare in rifampin-susceptible MRSA [1.0% (1 of 100)] but common in rifampin-resistant MRSA [71.4% (5 of 7), P < 0.001]. Induction of biofilm biomass at sub-MICs of antibiotics is common in clinical MRSA isolates and is differentially affected by the MRSA strain and antibiotic class.IMPORTANCEBacteria can be exposed to sub-MICs of antibiotics at the beginning and end of a dosing regimen, between doses, or during low-dose therapies. Growing evidence suggests that sub-MICs of antimicrobials can stimulate MRSA biofilm formation and alter the composition of the biofilm matrix. Pevious studies have found that sub-MICs of oxacillin, methicillin, and amoxicillin promote biofilm formation in some community-acquired MRSA (CA-MRSA). We evaluated biofilm induction by sub-MICs of four different classes of antibiotics in 44 CA-MRSA and 63 healthcare-associated MRSA (HA-MRSA) strains. Our study indicated that sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin frequently promote biofilm induction in clinical MRSA isolates. Strong biofilm induction in sub-MICs of nafcillin, ciprofloxacin, and rifampin was more frequent in HA-MRSA than in CA-MRSA. Antibiotic-induced biofilm formation depends on the antibiotic class, MRSA strain, and antibiotic resistance. Our results emphasize the importance of maintaining effective bactericidal concentrations of antibiotics to treat biofilm-related infections.

Objectives The present study aimed to determine the effect of music-based auditory training on older adults with hearing loss and decreased cognitive ability, which are common conditions in the older population. Methods In total, 20 older adults diagnosed with both mild-to-moderately severe hearing loss and mild cognitive impairment (MCI) participated. Half of this group were randomly assigned to the auditory training group (ATG), and the other half were designated as the control group (CG). For the ATG, a 40-minute training session (10 minutes for singing a song, 15 minutes for playing instruments, and 15 minutes for playing games with music discrimination) was conducted twice a week for 8 weeks (for a total of 16 sessions). To confirm the training effects, all participants were given tests pre- and post-training, and then a follow-up test was administered 2 weeks after the training, using various auditory and cognitive tests and a self-reporting questionnaire. Results The ATG demonstrated significant improvement in all auditory test scores compared to the CG. Additionally, there was a notable enhancement in cognitive test scores post-training, except for the digit span tests. However, there was no statistically significant difference in the questionnaire scores between the two groups, although the ATG did score higher post-training. Conclusion The music-based auditory training resulted in a significant improvement in auditory function and a partial enhancement in cognitive ability among elderly patients with hearing loss and MCI. We anticipate that this music-based approach will be adopted for auditory training in clinical settings due to its engaging and easy-to-follow nature.

Abstract Blood urea nitrogen (BUN) to albumin ratio (BAR) is a comprehensive parameter that reflects renal, inflammatory, nutritional, and endothelial functions. BAR has been shown to be associated with various cancers, pneumonia, sepsis, and pulmonary and cardiovascular diseases; however, few studies have been conducted on its association with cerebrovascular diseases. In this study, we evaluated the association between BAR and cerebral small vessel disease (cSVD) in health check-up participants. We assessed consecutive health check-up participants between January 2006 and December 2013. For the cSVD subtype, we quantitatively measured the volume of white matter hyperintensity (WMH) and qualitatively measured the presence of lacune and cerebral microbleeds (CMBs). The BAR was calculated by dividing BUN by albumin as follows: BAR = BUN (mg/dl)/albumin (g/dl). A total of 3012 participants were evaluated. In multivariable linear regression analysis, BAR showed a statistically significant association with WMH volume after adjusting for confounders [β = 0.076, 95% confidence interval (CI): 0.027–0.125]. In multivariable logistic regression analyses, BAR was significantly associated with lacunes [adjusted odds ratio (aOR) = 1.20, 95% CI: 1.00–1.44] and CMBs (aOR = 1.28, 95% CI: 1.06–1.55). BAR was associated with all types of cSVD in the health check-up participants.

Abstract Inflammation is an essential defense mechanism in health; however, excessive inflammation contributes to the pathophysiology of several chronic diseases. Although anti-inflammatory drugs are essential for controlling inflammation, they have several side effects. Recent findings suggest that naturally derived compounds possess physiological activities, including anti-inflammatory, antifungal, antiviral, anticancer, and immunomodulatory activities. Therefore, this study aimed to investigate the anti-inflammatory effects and molecular mechanisms of 2,5,6-trimethoxy-p-terphenyl (TP1), extracted from the Antarctic lichen Stereocaulon alpinum, using in vitro models. TP1 treatment decreased the production of nitric oxide (NO) and reactive oxygen species (ROS) in LPS-stimulated Raw264.7 macrophages. Additionally, TP1 treatment significantly decreased the mRNA levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) and the mRNA and protein levels of the pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2). Moreover, TP1 suppressed lipopolysaccharide-induced phosphorylation of the NF-κB and MAPK signaling pathways in Raw264.7 macrophages. Conclusively, these results suggest that TP1 ameliorates inflammation by suppressing the expression of pro-inflammatory cytokines, making it a potential anti-inflammatory drug for the treatment of severe inflammatory diseases.

Abstract Various plasma biomarkers for amyloid-β (Aβ) have shown high predictability of amyloid PET positivity. However, the characteristics of discordance between amyloid PET and plasma Aβ42/40 positivity are poorly understood. Thorough interpretation of discordant cases is vital as Aβ plasma biomarker is imminent to integrate into clinical guidelines. We aimed to determine the characteristics of discordant groups between amyloid PET and plasma Aβ42/40 positivity, and inter-assays variability depending on plasma assays. We compared tau burden measured by PET, brain volume assessed by MRI, cross-sectional cognitive function, longitudinal cognitive decline and polygenic risk score (PRS) between PET/plasma groups (PET−/plasma−, PET−/plasma+, PET+/plasma−, PET+/plasma+) using Alzheimer’s Disease Neuroimaging Initiative database. Additionally, we investigated inter-assays variability between immunoprecipitation followed by mass spectrometry method developed at Washington University (IP-MS-WashU) and Elecsys immunoassay from Roche (IA-Elc). PET+/plasma+ was significantly associated with higher tau burden assessed by PET in entorhinal, Braak III/IV, and Braak V/VI regions, and with decreased volume of hippocampal and precuneus regions compared to PET−/plasma-. PET+/plasma+ showed poor performances in global cognition, memory, executive and daily-life function, and rapid cognitive decline. PET+/plasma+ was related to high PRS. The PET−/plasma+ showed intermediate changes between PET−/plasma− and PET+/plasma+ in terms of tau burden, hippocampal and precuneus volume, cross-sectional and longitudinal cognition, and PRS. PET+/plasma− represented heterogeneous characteristics with most prominent variability depending on plasma assays. Moreover, IP-MS-WashU showed more linear association between amyloid PET standardized uptake value ratio and plasma Aβ42/40 than IA-Elc. IA-Elc showed more plasma Aβ42/40 positivity in the amyloid PET-negative stage than IP-MS-WashU. Characteristics of PET−/plasma+ support plasma biomarkers as early biomarker of amyloidopathy prior to amyloid PET. Various plasma biomarker assays might be applied distinctively to detect different target subjects or disease stages.

Abstract Numerous studies have explored the cultivation of muscle cells using non-animal materials for cultivated meat production. Achieving muscle cell proliferation and alignment using 3D scaffolds made from plant-based materials remains challenging. This study introduces a technique to culture and align muscle cells using only plant-based materials, avoiding toxic chemical modifications. Zein-alginate fibers (ZA fibers) were fabricated by coating zein protein onto alginate fibers (A fibers). Zein’s excellent cell compatibility and biodegradability enable high cell adhesion and proliferation rates, and the good ductility of the ZA fibers enable a high strain rate (>75%). We demonstrate mature and aligned myotube formation in ZA fibers, providing a simple way to align muscle cells using plant-based materials. Additionally, cultivated meat was constructed by assembling muscle, fat, and vessel fibers. This method holds promise for the future mass production of cultivated meat.

Background Many studies have shown that Hashimoto’s thyroiditis (HT) acts as a protective factor in differentiated thyroid cancer (DTC), but little is known about its effects on mortality. Therefore, this study was performed to reveal the prognosis of HT on mortality in patients with DTC. Methods This study included two types of research results: retrospective cohort study using the National Epidemiologic Survey of Thyroid cancer (NEST) in Korea and meta-analysis study with the NEST data and eight selected studies. Results Of the 4,398 patients with DTC in NEST, 341 patients (7.8%) died during the median follow-up period of 15 years (interquartile range, 12.3 to 15.6). Of these, 91 deaths (2.1%) were related to DTC. HT was associated with a smaller tumor size and less aggressive DTC. In Cox regression analysis after adjusting for age and sex, patients with HT showed a significantly lower risk of all-cause death (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52 to 0.96) and DTC-related death (HR, 0.33; 95% CI, 0.14 to 0.77). The analysis with inverse probability of treatment weight data adjusted for age, sex, and year of thyroid cancer registration showed similar association. The meta-analysis showed that patients with HT showed a lower risk of all-cause mortality (risk ratio [RR], 0.24; 95% CI, 0.13 to 0.47) and thyroid cancer-related mortality (RR, 0.23; 95% CI, 0.13 to 0.40) in comparison with patients without HT. Conclusion This study showed that DTC co-presenting with HT is associated with a low risk of advanced DTC and presents a low risk for all-cause and DTC-related death.

The objective of this study was to develop a sound recognition-based cardiopulmonary resuscitation (CPR) training system that is accessible, cost-effective, easy-to-maintain and provides accurate CPR feedback. Beep-CPR, a novel device with accordion squeakers that emit high-pitched sounds during compression, was developed. The sounds emitted by Beep-CPR were recorded using a smartphone, segmented into 2-second audio fragments, and then transformed into spectrograms. A total of 6,065 spectrograms were generated from approximately 40 minutes of audio data, which were then randomly split into training, validation, and test datasets. Each spectrogram was matched with the depth, rate, and release velocity of the compression measured at the same time interval by the ZOLL X Series monitor/defibrillator. Deep learning models utilizing spectrograms as input were trained using transfer learning based on EfficientNet to predict the depth (Depth model), rate (Rate model), and release velocity (Recoil model) of compressions. Results: The mean absolute error (MAE) for the Depth model was 0.30 cm (95% confidence interval [CI]: 0.27–0.33). The MAE of the Rate model was 3.6/min (95% CI: 3.2–3.9). For the Recoil model, the MAE was 2.3 cm/s (95% CI: 2.1–2.5). External validation of the models demonstrated acceptable performance across multiple conditions, including the utilization of a newly-manufactured device, a fatigued device, and evaluation in an environment with altered spatial dimensions. We have developed a novel sound recognition-based CPR training system, that accurately measures compression quality during training. Significance: Beep-CPR is a cost-effective and easy-to-maintain solution that can improve the efficacy of CPR training by facilitating decentralized at-home training with performance feedback.

Abstract This study focused on patients with advanced open-angle glaucoma (OAG) and aimed to identify key factors for monitoring them. We included 127 such patients who were followed for seven years or more, undergoing annual ophthalmic examinations. Glaucoma progression was defined as a deterioration in either structure or function. The progression rates and risk factors were evaluated. The patients were divided into upper- and lower-half subgroups based on the reduction in intraocular pressure (IOP) from the baseline. Over an 11-year period, glaucoma progression was detected in 59 eyes (46.5%). The rate of change in mean deviation (MD) was − 0.43 dB/year for the entire population; − 0.67 dB/year for progressors; and − 0.20 dB/year for non-progressors. Hypertension and disc hemorrhage (DH) were more common in progressors compared to non-progressors (45.8 vs. 23.5%, 11.9 vs. 1.5%; P = 0.008 and P = 0.016). Multivariate Cox’s proportional hazard model revealed that the presence of DH and a better baseline MD were associated with glaucoma progression. Additionally, patients with a higher percentage reduction in IOP (> 20.94%) had a lower risk of progression compared to those with less reduction. Inadequate IOP reduction, better baseline MD, presence of DH, and lower central corneal thickness were identified as risk factors for progression in advanced OAG patients.

Abstract Background Inflammation is a major pathological mechanism underlying cerebrovascular disease. Recently, a new inflammatory marker based on the ratio between monocyte count and high-density lipoprotein (HDL) cholesterol has been proposed. In this study, we evaluated the relationship between monocyte-to-HDL cholesterol ratio (MHR) and cerebral small vessel disease (cSVD) lesions in health check-up participants. Methods This study was a retrospective cross-sectional study based on a registry that prospectively collected health check-up participants between 2006 and 2013. Three cSVD subtypes were measured on brain magnetic resonance imaging. White matter hyperintensity (WMH) volume, and lacunes and cerebral microbleeds (CMBs) were quantitatively and qualitatively measured, respectively. The MHR was calculated according to the following formula: MHR = monocyte counts (× 103/μL) / HDL cholesterol (mmol/L). Results In total, 3,144 participants were evaluated (mean age: 56 years, male sex: 53.9%). In multivariable analyzes adjusting for confounders, MHR was significantly associated with WMH volume [β = 0.099, 95% confidence interval (CI) = 0.025 to 0.174], lacune [adjusted odds ratio (aOR) = 1.43, 95% CI = 1.07–1.91], and CMB (aOR = 1.51, 95% CI = 1.03–2.19). In addition, MHR showed a positive quantitative relationship with cSVD burden across all three subtypes: WMH (P

Abstract Background Petersen’s hernia, which occurs after Billroth-II (B-II) or Roux-en-Y (REY) anastomosis, can be reduced by defect closure. This study aims to compare the incidence of bowel obstruction above Clavien–Dindo classification grade III due to Petersen’s hernia between the mesenteric fixation method and the conventional methods after laparoscopic or robotic gastrectomy. Methods This study was designed as prospective, single-blind, non-inferiority randomized controlled multicenter trial in Korea. Patients with histologically diagnosed gastric cancer of clinical stages I, II, or III who underwent B-II or REY anastomosis after laparoscopic or robotic gastrectomy are enrolled in this study. Participants who meet the inclusion criteria are randomly assigned to two groups: a CLOSURE group that underwent conventional Petersen’s defect closure method and a MEFIX group that underwent the mesenteric fixation method. The primary endpoint is the number of patients who underwent surgery for bowel obstruction caused by Petersen’s hernia within 3 years after laparoscopic or robotic gastrectomy. Discussion This trial is expected to provide high-level evidence showing that the MEFIX method can quickly and easily close Petersen’s defect without increased postoperative complications compared to the conventional method. Trial registration ClinicalTrials.gov NCT05105360. Registered on November 3, 2021.

Abstract O-GlcNAcylation is a posttranslational modification where N-acetylglucosamine (O-GlcNAc) is attached and detached from a serine/threonine position by two enzymes: O-GlcNAc transferase and O-GlcNAcase. In addition to roles in diabetes and cancer, recent pharmacological and genetic studies have revealed that O-GlcNAcylation is involved in neuronal function, specifically synaptic transmission. Global alteration of the O-GlcNAc level does not affect basal synaptic transmission while the effect on synaptic plasticity is unclear. Although synaptic proteins that are O-GlcNAcylated are gradually being discovered, the mechanism of how O-GlcNAcylated synaptic protein modulate synaptic transmission has only been reported on CREB, synapsin, and GluA2 subunit of AMPAR. Future research enabling the manipulation of O-GlcNAcylation in individual synaptic proteins should reveal hidden aspects of O-GlcNAcylated synaptic proteins as modulators of synaptic transmission.

Background Fluid overload is an independent risk factor of mortality in patients with acute kidney injury (AKI) receiving continuous kidney replacement therapy (CKRT). However, the association between fluid status, as assessed by bioelectrical impedance analysis (BIA) or lung ultrasound, and survival in patients with AKI requiring CKRT has not been established. Methods We analyzed 36 participants with sepsis-associated AKI who received CKRT at a tertiary hospital. The main exposures were volume surrogates: 1) overhydration normalized by extracellular water (OH/ECW, L/L) assessed by BIA, 2) the number of B-lines measured by lung ultrasound, and 3) weight change ([body weight at CKRT initiation – body weight at admission] × 100/body weight at admission). The primary outcome was the 28-day mortality. Results Seventeen participants (47.2%) died within 28 days. There were no significant correlations between OH/ECW and weight change (R2 = 0.040, p = 0.24), number of B-lines and OH/ECW (R2 = 0.056, p = 0.16), or weight change and number of B-lines (R2 = 0.014, p = 0.49). Kaplan-Meier analyses revealed that patients in the highest tertile of OH/ECW showed a significantly lower cumulative 28-day survival probability than the others (the lowest + middle tertiles). The survival probability of participants in the highest tertile of the number of B-lines or weight change did not differ from that of their counterparts. In a multivariate Cox proportional hazard model, the hazard ratio for the highest tertile of OH/ECW was 3.83 (95% confidence interval, 1.04–14.03). Conclusion Volume overload assessed using BIA (OH/ECW) was associated with the 28-day survival rate in patients with sepsis-associated AKI who received CKRT.

This paper proposes a novel packaging and large-scale antenna-assembled structure for a printed circuit board (PCB) that reinforces productivity, facilitates cost reduction, and maintains reliability. This was achieved by splitting the antenna from the main board and packaging it into a radio-frequency integrated circuit. In addition, two innovative solutions—an externally attachable flexible PCB antenna and a PCB-embedded coaxial line—are introduced to overcome the degradation in antenna performance and vertical RF transition loss in the proposed low-cost hybrid PCB. First, the proposed externally attachable flexible PCB antenna and a parasitic air-coupled antenna, which were easily assembled on the PCB, achieved an antenna efficiency of 95% and an impedance bandwidth of 7 GHz. Second, the fabricated coaxial line exhibited enhanced impedance matching over a wide frequency range of 30–40 GHz and improved insertion loss of approximately 1.4 dB. Furthermore, the packaged antenna, composed of 256 dual-polarized antenna elements per stream, incorporated a 39 GHz CMOS-based 16-channel phased-array transceiver IC. The set-level beam-forming measurements were verified considering an effective isotropic radiated power of 55 dBm at boresight and a steering range >±60°. In addition to being suitable for mass production in terms of cost and reliability, the proposed structures and solutions met the required antenna and beam-forming performance for commercial 39 GHz base stations without sacrificing performance.

Abstract Background Alzheimer’s dementia (AD) pathogenesis involves complex mechanisms, including microRNA (miRNA) dysregulation. Integrative network and machine learning analysis of miRNA can provide insights into AD pathology and prognostic/diagnostic biomarkers. Methods We performed co-expression network analysis to identify network modules associated with AD, its neuropathology markers, and cognition using brain tissue miRNA profiles from the Religious Orders Study and Rush Memory and Aging Project (ROS/MAP) (N = 702) as a discovery dataset. We performed association analysis of hub miRNAs with AD, its neuropathology markers, and cognition. After selecting target genes of the hub miRNAs, we performed association analysis of the hub miRNAs with their target genes and then performed pathway-based enrichment analysis. For replication, we performed a consensus miRNA co-expression network analysis using the ROS/MAP dataset and an independent dataset (N = 16) from the Gene Expression Omnibus (GEO). Furthermore, we performed a machine learning approach to assess the performance of hub miRNAs for AD classification. Results Network analysis identified a glucose metabolism pathway-enriched module (M3) as significantly associated with AD and cognition. Five hub miRNAs (miR-129-5p, miR-433, miR-1260, miR-200a, and miR-221) of M3 had significant associations with AD clinical and/or pathologic traits, with miR129-5p by far the strongest across all phenotypes. Gene-set enrichment analysis of target genes associated with their corresponding hub miRNAs identified significantly enriched biological pathways including ErbB, AMPK, MAPK, and mTOR signaling pathways. Consensus network analysis identified two AD-associated consensus network modules and two hub miRNAs (miR-129-5p and miR-221). Machine learning analysis showed that the AD classification performance (area under the curve (AUC) = 0.807) of age, sex, and APOE ε4 carrier status was significantly improved by 6.3% with inclusion of five AD-associated hub miRNAs. Conclusions Integrative network and machine learning analysis identified miRNA signatures, especially miR-129-5p, as associated with AD, its neuropathology markers, and cognition, enhancing our understanding of AD pathogenesis and leading to better performance of AD classification as potential diagnostic/prognostic biomarkers.

Abstract Unbalanced carbohydrate diets are linked to metabolic disorders; however, there is limited information on the role of gut microbiota. We explored differences in mice gut microbiota and metabolic phenotypes resulting from diets with different carbohydrate sources. To investigate the metabolic dysfunction and mechanism of the wheat flour and starch on metabolic disorders, we analyzed the changes of phenotype and biomarkers in rice and wheat flour diet in C57BL/6 mice (specific pathogen‐free) and fecal transplantation from antibiotic‐treated or germ‐free (GF) mice model. Rice‐fed mice presented normal metabolic reactions, whereas wheat‐fed mice exhibited increased body weight, insulin resistance, serum triglycerides, and fasting glucose levels. Wheat starch‐fed mice displayed lower fecal microbiota alpha diversity, with a reduced abundance of Bacteroidetes, than high‐fat diet (HFD)‐fed and chow‐fed mice. Fecal transplantation from antibiotic‐treated or GF mice revealed that metabolic disruption induced by wheat diet feeding was mediated through gut microbiota and stearoyl‐CoA desaturase 1 (SCD1) signaling in the colon. Taken together, wheat‐based diets induce gut microbiota alterations, causing obesity and metabolic diseases through molecular activity linked to colonic SCD1. Therefore, colonic SCD1 could be a therapeutic target for patients with metabolic diseases who consume high‐carbohydrate diets.

Purpose Several studies demonstrated that obesity and underweight were negatively associated with outcomes of breast cancer. However, the results are still controversial, and the impact of body mass index (BMI) on distant metastasis-free survival (MFS), which might directly affect mortality, was less well evaluated. Our study aimed to verify the prognostic effect of BMI in breast cancer. Methods A retrospective analysis of 504 patients with stage I–III breast cancer who underwent surgery from January 2005 to December 2013 was performed. The patients were divided into three groups according to preoperative BMI: underweight

Autosomal recessive spastic ataxia in Charlevoix-Saguenay (ARSACS) is a neurodegenerative disorder caused by mutations in the sacsin molecular chaperone protein (SACS) gene. Since the first report from Quebec in 1978, many pathogenic ARSACS variants with significantly reduced chaperone activities have been reported worldwide in adolescents, with presumably altered protein folding. In this study, a novel SACS mutation (p.Val1335IIe, Heterozygous) was identified in a Korean patient in their 50s with late-onset ARSACS characterized by cerebellar ataxia and spasticity without peripheral neuropathy. The mutation was confirmed via whole exome sequencing and Sanger sequencing and was predicted to likely cause disease using prediction software. RT-PCR and ELISA showed decreased SACS mRNA expression and sacsin protein concentrations in the proband, supporting its implications in diseases with pathogenicity and reduced chaperone function from haploinsufficiency. Our results revealed the pathogenicity of the SACS Val1335IIe mutation in the proband patient’s disease manifestation, even though the symptoms had a limited correlation with the typical ARSACS clinical triad, which could be due to the reduced chaperon function from haploinsufficiency. Furthermore, our study suggests that variants of SACS heterozygosity may have diverse symptoms, with a wide range of disease onsets for late-onset sacsinopathy.

Abstract Background The prevalence of anxiety among patients undergoing arthroscopic surgery and its association with postoperative function has been well documented; however, the level of anxiety and anxiety-related characteristics remain unclear. As such, the present study investigated the characteristics of state anxiety in patients undergoing arthroscopic meniscectomy. Methods Data from 75 patients, who underwent arthroscopic partial meniscectomy under general anesthesia and completed an anxiety status questionnaire between April 2021 and March 2022, were retrospectively collected and reviewed. The State-Trait Anxiety Inventory (STAI)-X was used to measure state anxiety; a total score ≥ 52 was defined as clinically meaningful state anxiety. STAI score, main cause of preoperative anxiety, most anxious period, and most helpful factors for reducing perioperative anxiety were investigated. Patients were divided into 2 groups according to the main cause of preoperative anxiety; surgery or anesthesia (group I [n = 47]); and postoperative pain or rehabilitation (group II [n = 28]) Characteristics of state-anxiety between the two groups were compared using independent t-tests. Results The mean STAI score of the total population was 39.1 points (range, 20–60 points). The mean STAI score was significantly higher in group I than in group II (41.9 vs. 34.4 points, respectively; P

Abstract Owing to the intrinsic signal noise in the characterization of chemical structures through Fourier transform infrared (FT-IR) spectroscopy, the determination of the signal-to-noise ratio (SNR) depends on the level of the concentration of the chemical structures. In situations characterized by limited concentrations of chemical structures, the traditional approach involves mitigating the resulting low SNR by superimposing repetitive measurements. In this study, we achieved comparable high-quality results to data scanned 64 times and superimposed by employing machine learning algorithms such as the principal component analysis and non-negative matrix factorization, which perform the dimensionality reduction, on FT-IR spectral image data that was only scanned once. Furthermore, the spatial resolution of the mapping images correlated to each chemical structure was enhanced by applying both the machine learning algorithms and the Gaussian fitting simultaneously. Significantly, our investigation demonstrated that the spatial resolution of the mapping images acquired through relative intensity is further improved by employing dimensionality reduction techniques. Collectively, our findings imply that by optimizing research data through noise reduction enhancing spatial resolution using the machine learning algorithms, research processes can be more efficient, for instance by reducing redundant physical measurements.

Abstract Background Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE). Methods We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups. Results By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups. Conclusions The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD. Trial registration NCT04080726 ( https://classic.clinicaltrials.gov/ct2/show/NCT04080726 ), registration date: 25/10/2018.

Adefovir dipivoxil (ADV) is used for the treatment of hepatitis and acquired immunodeficiency syndrome, but long-term use can cause osteoporosis. In this study, the effect of ADV on the osteocyte maturation process was evaluated at the level of undifferentiated cells using mesenchymal stem cells (MSCs) and osteoblasts (MG63). First, MSCs and MG63 cells were treated with ADV at different concentrations, and then a Cell Counting Kit-8 analysis was performed to determine the effect on the proliferation of each cell. Additionally, crystal violet and Hoechst staining were performed for the morphological analysis of each cell and nucleus. To determine the cause of cell hypertrophy, the transforming growth factor-beta (TGF-β) expression was investigated, and alkaline phosphatase (ALP) staining and activity were measured to determine the degree of differentiation of the MSCs and MG63 cells into mature osteocytes. The results confirmed that the ADV increases the expression of TGF-β in MSCs and MG63 cells, causing cellular and nuclear hypertrophy, and can cause osteoporosis by inhibiting cell proliferation and affecting the differentiation of mature osteocytes. Therefore, it is believed that these results can be used as a basis for understanding the adverse effects of ADV at a cytological level in basic medicine and clinical research.

Abstract Background Agar is used as a gelling agent that possesses a variety of biological properties; it consists of the polysaccharides agarose and porphyrin. In addition, the monomeric sugars generated after agar hydrolysis can be functionalized for use in biorefineries and biofuel production. The main objective of this study was to develop a sustainable agar hydrolysis process for bioethanol production using nanotechnology. Peroxidase-mimicking Fe3O4-MNPs were applied for agar degradation to generate agar hydrolysate-soluble fractions amenable to Saccharomyces cerevisiae and Escherichia coli during fermentation. Results Fe3O4-MNP-treated (Fe3O4-MNPs, 1 g/L) agar exhibited 0.903 g/L of reducing sugar, which was 21-fold higher than that of the control (without Fe3O4-MNP-treated). Approximately 0.0181% and 0.0042% of ethanol from 1% of agar was achieved using Saccharomyces cerevisiae and Escherichia coli, respectively, after process optimization. Furthermore, different analytical techniques (FTIR, SEM, TEM, EDS, XRD, and TGA) were applied to validate the efficiency of Fe3O4-MNPs in agar degradation. Conclusions To the best of our knowledge, Fe3O4-MNP-treated agar degradation for bioethanol production through process optimization is a simpler, easier, and novel method for commercialization.