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Abstract Background To compare and evaluate objective and subjective clinical parameters between 0.05% cyclosporine nanoemulsion (CsN) and 0.15% hyaluronic acid (HA) administration in patients with mild-to-moderate dry eyes. Methods In this prospective, randomized, double-masked, single-center, and placebo-controlled parallel study, patients with mild-to-moderate dry eyes were randomly allocated to be treated with 0.05% CsN or 0.15% HA twice daily. Patients were followed-up at 4, 8, and 12 weeks. Objective and subjective parameters were evaluated during each visit. Results A total of 35 patients were enrolled in this study. Compared with baseline, tear film break-up time and fluorescein staining scores at 4, 8, and 12 weeks significantly improved in the CsN group. However, the Schirmer I test showed no statistically significant change until week 12. Using the Symptom Assessment in Dry Eye (SANDE) score, both groups gradually showed significant improvement compared with baseline values. However, the Dry Eye-Related Quality-of-life Score Questionnaire (DEQS) showed no statistically significant change during the treatment period. Conclusions Both 0.05% CsN and 0.15% HA administration twice a day effectively improved the objective signs and subjective symptoms of patients with mild-to-moderate dry eyes. However, patients treated with 0.05% CsN experienced greater and faster improvement.

Abstract No study has analysed the temporal trends of the long-term results and clinical characteristics of patients with hepatocellular carcinoma (HCC) treated using radiofrequency ablation (RFA). Therefore, we examined temporal trends of characteristics of patients and treatment-naïve HCCs within the Milan criteria treated by RFA over 20 years. We retrospectively analysed 1099 patients with HCC within the Milan criteria treated with percutaneous RFA from January 2000 to December 2019. The overall survival (OS), recurrence-free survival (RFS), and factors affecting survival and local tumor progression were analysed using the Kaplan‒Meier method and Cox proportional hazards model. A trend test was performed to analyse the changing trends in participants and treatment outcomes. The overall and RFS of patients improved during the later period. In addition, viral hepatitis-related HCC incidence decreased, whereas that of alcohol- or non-alcoholic fatty liver disease-related HCC increased from the earlier to the later period (P for trend

Background Dipeptidyl peptidase-4 (DPP4) inhibitors are frequently prescribed for patients with type 2 diabetes; however, their cost can pose a significant barrier for those with impaired kidney function. This study aimed to estimate the economic benefits of substituting non-renal dose-adjusted (NRDA) DPP4 inhibitors with renal dose-adjusted (RDA) DPP4 inhibitors in patients with both impaired kidney function and type 2 diabetes. Methods This retrospective cohort study was conducted from January 1, 2012 to December 31, 2018, using data obtained from common data models of five medical centers in Korea. Model 1 applied the prescription pattern of participants with preserved kidney function to those with impaired kidney function. In contrast, model 2 replaced all NRDA DPP4 inhibitors with RDA DPP4 inhibitors, adjusting the doses of RDA DPP4 inhibitors based on individual kidney function. The primary outcome was the cost difference between the two models. Results In total, 67,964,996 prescription records were analyzed. NRDA DPP4 inhibitors were more frequently prescribed to patients with impaired kidney function than in those with preserved kidney function (25.7%, 51.3%, 64.3%, and 71.6% in patients with estimated glomerular filtration rates [eGFRs] of ≥60,

Abstract Background Despite the well-known health benefits of exercise, women’s participation in exercise is low worldwide. As women are at risk of developing various chronic diseases as they age, suggesting effective exercise methods that can maximize energy consumption is needed to prevent such conditions. Excess post-exercise oxygen consumption (EPOC) can maximize energy consumption. In this crossover, randomized controlled trial, we aimed to compare the EPOC for different exercise modalities including continuous exercise (CE), interval exercise (IE), and accumulated exercise (AE) that spent the homogenized energy expenditure during exercise in healthy women. Methods Forty-four participants (age, 36.09 ± 11.73 years) were recruited and randomly allocated to three groups. The intensity of each modality was set as follows: CE was performed for 30 min at 60% peak oxygen uptake (VO2peak). IE was performed once for 2 min at 80% VO2peak, followed by 3 min at 80% VO2peak, and 1 min at 40% VO2peak, for a total of six times over 26 min. AE was performed for 10 min with a 60% VO2peak and was measured thrice a day. Results During exercise, energy metabolism was higher for IE and CE than that for AE. However, this was reversed for AE during EPOC. Consequently, the greatest energy metabolism was shown for AE during total time (exercise and EPOC). Conclusions By encouraging regular exercises, AE can help maintain and improve body composition by increasing compliance with exercise participation, given its short exercise times, and by efficiently increasing energy consumption through the accumulation of EPOC. Trial registration Clinical number (KCT0007298), 18/05/2022, Institutional Review Board of Konkuk University (7001355-202201-E-160).

Abstract Background With the trend of digitalization, social activities among the older population are becoming more diverse as they increasingly adopt technology-based alternatives. To gain a comprehensive understanding of social activities, this study aimed to identify the patterns of digital and in-person social activities among community-dwelling older adults in South Korea, examine the associated factors, and explore the difference in depressive symptoms by the identified latent social activity patterns. Methods Data were extracted from a nationwide survey conducted with 1,016 community-dwelling older adults (mean age 68.0 ± 6.5 years, 47.8% male). The main variables assessed were digital social activities (eight items), in-person social activities (six items), and depressive symptoms (20 items). Data were analyzed using latent class analysis, multinomial logistic regression, and multiple linear regression. Results We identified four distinct social activity patterns: “minimal in both digital and in-person” (22.0%), “moderate in both digital and in-person” (46.7%), “moderate in digital & very high in in-person” (14.5%), and “high in both digital and in-person” (16.8%). Younger age, living in multi-generational households, and higher digital literacy were associated with a higher likelihood of being in the “moderate in both digital and in-person” than the “minimal in both digital and in-person” group. Younger age, male, living in multi-generational households, residing in metropolitan areas, no dependency on IADL items, doing daily physical exercise, and higher digital literacy were associated with a higher likelihood of being in the “moderate in digital & very high in in-person” than the “minimal in both digital and in-person” group. Younger age, living in multi-generational households, no dependency on IADL items, doing daily physical exercise, and higher digital literacy were associated with a higher likelihood of being in the “high in both digital and in-person” than the “minimal in both digital and in-person” group. Depressive symptoms were significantly higher in the group with minimal engagement in both digital and in-person activities, compared to other three groups. Conclusions This study highlights distinct patterns of social activities among Korean community-dwelling older adults. Since older adults with minimal social activity engagement can be more vulnerable to depressive symptoms, interventions that address modifiable attributes, such as supporting digital literacy and facilitating physical activity of older adults, could serve as potential strategies to enhance their social activity engagement and, consequently, their mental well-being.

Abstract A model of supergravity inflation we recently proposed can produce slow roll inflation and a realistic spectrum of particles even without F-term supersymmetry breaking. Supersymmetry is broken only by a D-term induced by a recently discovered new type of Fayet-Iliopoulos (FI) term. Almost all supersymmetric partners of the standard model fields can get masses as high as the inflationary Hubble scale. The exception is gauginos, for which the vanishing of F-terms implies an exact cancellation that keeps their masses exactly zero. To cure this problem without spoiling the simplicity of our model we introduce a new term that further enlarges the space of supergravity effective actions. It is an F-term that, similarly to the new FI term, becomes singular in the supersymmetric limit. We show that this term can produce large gaugino masses without altering the spectrum of other states and without lowering the cutoff of the effecive theory.

Abstract Free radical is a marker in various inflammatory diseases. The antioxidant effect protects us from this damage, which also plays an essential role in preventing inflammation. Inflammation protects the body from biological stimuli, and pro-inflammatory mediators are negatively affected in the immune system. Inflammation caused by LPS is an endotoxin found in the outer membrane of Gram-negative bacteria, which induces immune cells to produce inflammatory cytokines such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase. Based on this, the antioxidant and anti-inflammatory effects of plant extracts were investigated. First, the main phenolic compounds for the five peaks obtained from Stachys affinis extract (SAE) were identified. The antioxidant effect of each phenolic compound was confirmed through HPLC analysis before and after the competitive binding reaction between DPPH and the extract. Afterward, the anti-inflammatory effect of each phenolic compound was confirmed through competitive binding between COX2 and the extract in HPLC analysis. Lastly, the anti-inflammatory effect of SAE was confirmed through in vitro experiments and also confirmed in terms of structural binding through molecular docking. This study confirmed that phenolic compounds in SAE extract have potential antioxidant and anti-inflammatory effects, and may provide information for primary screening of medicinal plants.

Background/Aims Statins are common lipid-lowering agents used in dyslipidemia. However, they increase serum creatinine phosphokinase (CPK) levels. Currently, there are no studies on the effect of thyroid-stimulating hormone (TSH) levels on CPK levels after statin administration. Therefore, this study aimed to investigate CPK level alterations after statin administration according to TSH quartiles in participants with euthyroidism. Methods This retrospective analysis included 25,047 patients with euthyroidism. CPK levels were measured before and 6 months after statin administration. Normal TSH levels were divided into four quartiles, and the CPK levels and proportions of patients with normal CPK levels after statin administration for each TSH quartile were evaluated. Results The baseline CPK level was significantly higher in the lowest TSH quartile (Q1) compared to the other quartiles but decreased after statin administration. Thus, the difference between the CPK levels and the other quartile groups was not significant. The proportion of patients with normal CPK levels was also significantly lowest in Q1 before statin administration; however, no significant difference was noted in the ratio among each group after statin administration. These findings were consistent with the findings of the analysis according to statin intensity. Conclusions In patients in the lowest TSH quartile of the normal TSH range, the CPK level decreased, and the proportion of normal CPK levels increased significantly after statin administration. However, similar changes were not observed in other TSH quartiles. Therefore, further studies are required to mechanistically confirm these conclusions.

Highlights Vacancy in the transition metal layer of sodium cathode material induces the formation lone-pair electrons in the O 2p orbital. Material delivers more capacity from the oxygen redox validated by density functional calculation. Widened dominance of the OP4 phase without releasing O2 gas.

Rational urban design helps to build sustainable cities with high ventilation capacity and pollutant removal capacity, but the effect of building height on ventilation and pollutant dispersion inside asymmetric canyons has not been fully studied. In this paper, we studied the effect of increasing the degree of building height asymmetry (DBHA) on canyon ventilation and pollutant diffusion in shallow and deep asymmetric street canyons by considering six different building height ratios (BHR = 3/4, 1/2, 1/3, 4/3, 2/1 and 3/1). The results show that increasing the DBHA in asymmetric canyons can improve the ventilation and pollutant removal capacity. For step-up canyons, increasing the downwind building height is very useful to improve ventilation and pollutant removal. For shallow/deep step-up canyons with BHR = 1/3, the air exchange rate (ACH) increased to 211.2% and 380.1% of the flat canyons, respectively. The spatially-average pollutant concentration in the pedestrian zones (leeward Kavg* ang windward Kavg*) decreases significantly with the increase of DBHA, especially for the deep step-up canyon with BHR = 1/3, the leeward Kavg* and windward Kavg* decrease to 15.3% and 3%, respectively. Also, increasing the upwind building height can also improve the ventilation capacity in the step-down canyons. For the deep step-down canyon with BHR = 3/1, the leeward Kavg* and windward Kavg* decreased to 40.6% and 24.1% of the deep flat canyon, respectively. Notably, the ventilation capacity is very low for step-down canyons with BHR = 4/3, and for step-down canyons with BHR ≥ 2/1, the ventilation capacity and pollutant removal capacity increase significantly with the increase of DBHA. Therefore, in urban planning, step-down canyons with BHR = 4/3 should be avoided and designed to satisfy the condition of BHR ≥ 2/1. These findings will be a valuable reference for urban designers to build sustainable cities with high ventilation capacity.

Abstract This study aimed to evaluate the changes in intraocular pressure (IOP) before and after femtosecond laser capsulorhexis and lens fragmentation for cataract surgery. We measured the IOP before, immediately, 30 min, and 1 h after the laser procedure in 47 eyes of 47 patients who underwent the femtosecond laser procedure. The mean IOP was 17.51 ± 3.28 mmHg, 30.23 ± 6.70 mmHg, 17.96 ± 3.75 mmHg, and 21.77 ± 5.88 mmHg before, immediately after, 30 min after, and 1 h after the laser procedure, respectively. The mean IOP significantly increased immediately (adjusted P

Due to its significance in fostering 21st-century skills, Science, Technology, Engineering, and Mathematics (STEM) education has rapidly evolved across the country. However, designing effective and meaningful STEM-based lessons is still challenging, especially at the elementary school level. Thus, future elementary teachers should be trained to develop integrated STEM-based lesson plans. This research aims to explore the quality of STEM-based lessons designed by pre-service elementary teachers. This study analyzed six STEM-based lesson plans created by 32 preservice elementary teachers as a final group project in the STEM Learning in Elementary School course. Employing a descriptive analysis method, the study evaluated the lesson plans using STEM Integration Curriculum Assessment (STEM-ICA) indicators to shed light on the lesson design quality. Findings reveal varying scores across STEM-ICA indicators, emphasizing ideal science integration but indicating room for improvement in mathematics integration within the lesson. Assessment alignment and the need for stronger connections in engineering design activities are highlighted. This contributes to discussions on enhancing preparation programs for high-quality STEM educators in elementary schools.

Leaf blight caused by Stemphylium vesicarium is one of the most important fungal diseases of garlic (Allium sativum L.) worldwide, which results in a reduction of quality and yield. The breeding of resistant cultivars is an efficient approach to decrease the use of chemical fungicides and minimize crop losses. In this study, to find the resistant garlic resources against S. vesicarium, we evaluated the resistance degree of 20 garlic germplasms. To do this, garlic seedlings at four-leaf stage were rubbed with nonabsorbent cotton and then inoculated with spore suspension (3.0×105 spores/ml of potato dextrose broth) of S. vesicarium by spray method. Three to seven days after inoculation, the infected leaf area (%) of garlic seedling was measured. ‘Daeseo’ and ‘Namdo’ were included as susceptible and resistant control cultivars, respectively. After 3 to 7 days of incubation, the infected leaf area (%) of garlic seedling was measured. Our results showed that IT245512, IT245528, and IT244068 lines exhibited the highest resistance against S. vesicarium, whereas IT257134 and IT253043 lines were more susceptible than the susceptible cultivar ‘Daeseo’. Based on the results, the resistant genetic resources selected in this study can be used a basic material for resistant garlic breeding system against leaf blight.

Abstract Inflammation acts as a dual role in disease initiation and progression, while Cannabis sativa L. (hemp) seeds, known for their abundance of anti-inflammatory phytochemicals, present a promising food source. Additionally, fermentation may optimize the food matrix, thereby augmenting its developmental prospects. This study explores the anti-inflammatory potential of hemp seeds fermented with 10 different probiotic strains. Among these, Lactiplantibacillus plantarum fermented hemp seeds (FHS) demonstrated a significant anti-inflammatory ability, accompanied by a reduction in the expression of critical inflammatory markers such as TLR4, NF-κBp65, and iNOS. Moreover, there is a noteworthy dose-dependent inhibition of inflammatory cytokines TNF-α, IL-6, IL-1β, and NO within a concentration range of 50 to 500 µg/mL. Subsequently, metabolomics analysis using UHPLC-QTOF-MS highlighted significant metabolic alterations in FHS compared to raw hemp seeds (RHS). Through multivariate, univariate, and correlation analyses, indolelactic acid (IA) and homovanillic acid (HVA) emerged as the main anti-inflammatory metabolites in FHS. Validation via HPLC confirmed the concentration of IA and HVA in RHS and FHS and both organic acids demonstrated lower IC50 values for TNF-α, IL-1β, IL-6, IL-18, and NO inhibition, showcasing their potent anti-inflammatory abilities. Furthermore, in vitro gastro-intestinal digestion coupled with the Caco-2 cell monolayer model validates the uptake and bioaccessibility of FHS, further affirming IA and HVA as major anti-inflammatory compounds. Overall, this research sets the stage for the development of novel hemp seed-based products targeting inflammation-associated disorders.

Abstract Nowadays, the focus of diabetes treatment has switched from lowering the glucose level to preserving glycemic homeostasis and slowing the disease progression. The main pathophysiology of both type 1 diabetes and long‐standing type 2 diabetes is pancreatic β‐cell mass loss and dysfunction. According to recent research, human pancreatic β‐cells possess the ability to proliferate in response to elevated insulin demands. It has been demonstrated that in insulin‐resistant conditions in humans, such as obesity or pregnancy, the β‐cell mass increases. This ability could be helpful in developing novel treatment approaches to restore a functional β‐cell mass. Treatment strategies aimed at boosting β‐cell function and mass may be a useful tool for managing diabetes mellitus and stopping its progression. This review outlines the processes of β‐cell failure and detail the many β‐cell abnormalities that manifest in people with diabetes mellitus. We also go over standard techniques for determining the mass and function of β‐cells. Lastly, we provide the therapeutic implications of utilizing antidiabetic drugs in controlling the mass and function of pancreatic β‐cells.

Abstract More than half of tumor patients with high PD-L1 expression do not respond to anti-PD-1/PD-L1 therapy, and the underlying mechanisms are yet to be clarified. Here we show that developmentally regulated GTP-binding protein 2 (DRG2) is required for response of PD-L1-expressing tumors to anti-PD-1 therapy. DRG2 depletion enhanced IFN-γ signaling and increased the PD-L1 level in melanoma cells. However, it inhibited recycling of endosomal PD-L1 and reduced surface PD-L1 levels, which led to defects in interaction with PD-1. Anti-PD-1 did not expand effector-like T cells within DRG2-depleted tumors and failed to improve the survival of DRG2-depleted tumor-bearing mice. Cohort analysis revealed that patients bearing melanoma with low DRG2 protein levels were resistant to anti-PD-1 therapy. These findings identify DRG2 as a key regulator of recycling of endosomal PD-L1 and response to anti-PD-1 therapy and provide insights into how to increase the correlation between PD-L1 expression and response to anti-PD-1 therapy.

Abstract Background Psoriasis is an inflammatory skin disease characterized by the hyperproliferative epidermal keratinocytes and significant immune cells infiltration, leading to cytokines production such as IL-1β, TNF-α, IL-23, and IL-17. Recent study highlights the critical role of IL-1β in the induction and activation of pathogenic Th17 and IL-17-producing γδ T cells, contributing to psoriasis. However, the mechanism underlying IL-1β dysregulation in psoriasis pathogenesis is unclear. Autophagy regulates IL-1β production and has a pleiotropic effect on inflammatory disorders. Previous studies showed controversial role of autophagy in psoriasis pathogenesis, either pro-inflammatory in autophagy-deficient keratinocyte or anti-inflammatory in pharmacologically autophagy-promoting macrophages. Thus, the direct role of autophagy and its therapeutic potential in psoriasis remains unclear. Methods We used myeloid cell-specific autophagy-related gene 7 (Atg7)-deficient mice and determined the effect of autophagy deficiency in myeloid cells on neutrophilia and disease pathogenesis in an imiquimod-induced psoriasis mouse model. We then assessed the pathogenic mechanism focusing on immune cells producing IL-1β and IL-17 along with gene expression profiles associated with psoriasis in mouse model and public database on patients. Moreover, therapeutic potential of IL-1β blocking in such context was assessed. Results We found that autophagy deficiency in myeloid cells exacerbated neutrophilic inflammation and disease pathogenesis in mice with psoriasis. This autophagy-dependent effect was associated with a significant increase in IL-1β production from myeloid cells, particularly macrophages, Cxcl2 expression, and IL-17 A producing T cells including γδ T cells. Supporting this, treatment with systemic IL-1 receptor blocking antibody or topical saccharin, a disaccharide suppressing pro-IL-1β expression, led to the alleviation of neutrophilia and psoriatic skin inflammation linked to autophagy deficiency. The pathophysiological relevance of this finding was supported by dysregulation of autophagy-related genes and their correlation with Th17 cytokines in psoriatic skin lesion from patients with psoriasis. Conclusions Our results suggest that autophagy dysfunction in myeloid cells, especially macrophages, along with IL-1β dysregulation has a causal role in neutrophilic inflammation and psoriasis pathogenesis.

Purpose This study aimed to examine the health concerns of parents regarding their premature infants and to identify changes in these concerns during perinatal period and after discharge. Methods This was a retrospective study performed at a single tertiary center that enrolled 119 premature infants who were discharged from the neonatal intensive care unit (NICU) and visited the outpatient pediatrics department between December 2018 and October 2021. Data on the concerns of 176 parents regarding enrolled premature infants’ health from before birth to 1 week after NICU discharge were obtained from outpatient records. The t test and with the chi-squared test were used to analyze the data for this study. Results The consistently greatest focus of parents' health concerns was the respiratory system. The second focus of parents' health concerns before discharge was the central nervous system. However, during the first week after NICU discharge, the gastrointestinal system was the second-most frequent focus of parents’ health concerns among parents of infants without diseases related to prematurity and infants with older gestational ages. Conclusion The results of this study offer insights into the health concerns among parents of premature infants. Parental health concerns about premature infants vary over time, from before birth to post-discharge, necessitating supportive interventions to enhance parental understanding of their child's health status.

Bacterial soft rot caused by Pectobacterium carotovorum subsp. carotovorum (Pcc) is one of the most severe diseases in radish cultivation. To control this plant disease, the most effective method has been known to cultivate resistant cultivars. Previously, we developed an efficient bioassay method for investigating resistance levels with 21 resistant and moderately resistant cultivars of radish against a strain Pcc KACC 10421. In this study, our research expanded to investigate the resistance of radish cultivars against six Pcc strains, KACC 10225, KACC 10421, ATCC 12312, ATCC 15713, LY34, and ECC 301365. To this end, the virulence of the six Pcc strains was determined based on the development of bacterial soft rot in seedlings of four susceptible radish cultivars. The results showed that the Pcc strains exhibited different virulence in the susceptible cultivars. To explore the race differentiation of Pcc strains corresponding to the resistance in radish cultivars, we investigated the occurrence of bacterial soft rot caused by the six Pcc strains on the 21 resistant and moderate resistant cultivars. Our results showed that the average values of the area under the disease progress curve were positively correlated with the virulence of the strains and the number of resistant cultivars decreased as the virulence of Pcc strains increased. Taken together, our results suggest that the resistance to Pcc of the radish cultivars commercialized in Korea is more likely affected by the virulence of Pcc strains rather than by race differentiation of Pcc.

Abstract Background Myocardial infarction (MI), a representative form of ischemic heart disease, remains a huge burden worldwide. This study aimed to explore whether extracellular vesicles (EVs) secreted from hyaluronic acid (HA)-primed induced mesenchymal stem cells (HA-iMSC-EVs) could enhance the cardiac repair after MI. Results HA-iMSC-EVs showed typical characteristics for EVs such as morphology, size, and marker proteins expression. Compared with iMSC-EVs, HA-iMSC-EVs showed enhanced tube formation and survival against oxidative stress in endothelial cells, while reduced reactive oxygen species (ROS) generation in cardiomyocytes. In THP-1 macrophages, both types of EVs markedly reduced the expression of pro-inflammatory signaling players, whereas HA-iMSC-EVs were more potent in augmenting anti-inflammatory markers. A significant decrease of inflammasome proteins was observed in HA-iMSC-EV-treated THP-1. Further, phospho-SMAD2 as well as fibrosis markers in TGF-β1-stimulated cardiomyocytes were reduced in HA-iMSC-EVs treatment. Proteomic data showed that HA-iMSC-EVs were enriched with multiple pathways including immunity, extracellular matrix organization, angiogenesis, and cell cycle. The localization of HA-iMSC-EVs in myocardium was confirmed after delivery by either intravenous or intramyocardial route, with the latter increased intensity. Echocardiography revealed that intramyocardial HA-iMSC-EVs injections improved cardiac function and reduced adverse cardiac remodeling and necrotic size in MI heart. Histologically, MI hearts receiving HA-iMSC-EVs had increased capillary density and viable myocardium, while showed reduced fibrosis. Conclusions Our results suggest that HA-iMSC-EVs improve cardiac function by augmenting vessel growth, while reducing ROS generation, inflammation, and fibrosis in MI heart. Graphical Abstract

Acetate ester compounds find widespread use in various applications such as surface coatings, ink formulations, pharmaceuticals, and adhesives. It is essential to investigate the phase transition behavior of amyl acetate, amyl acetoacetate, and isoamyl acetoacetate in high-pressure supercritical CO2 (SC-CO2). The vapor-liquid equilibria (VLE) of the SC-CO2 + amyl acetate, SC-CO2 + amyl acetoacetate, and SC-CO2 + isoamyl acetoacetate systems were examined at different temperatures (313.2 ≤ T ≤ 393.2 K) and pressures (1.67 ≤ P ≤ 20.76 MPa). The solubility curve of these systems shows Type-I phase behavior, and the critical points of these binary mixtures were observed between the critical properties of the pure components involved in the systems. The solubility of amyl acetate, amyl acetoacetate, and isoamyl acetoacetate in the SC-CO2 + amyl acetate, SC-CO2 + amyl acetoacetate, and SC-CO2 + isoamyl acetoacetate systems increases with increasing temperature at constant pressure. The two-parameter model of Peng-Robinson equation of state along with a mixing rule, accurately correlated the phase transition behavior and critical mixtures curves for all three systems. The binary interaction parameters (BIPs) were adjusted, and the minimum root mean square deviation percentage was identified for all three systems. The calculated error% was found to be within reasonable limits, with values of 4.95 %, 3.93 %, and 4.18 % for SC-CO2 + amyl acetate, SC-CO2 + amyl acetoacetate, and SC-CO2 + isoamyl acetoacetate systems, respectively. Furthermore, the interaction parameters for the SC-CO2 + amyl acetoacetate mixture was found to be temperature-dependent, and the tested linear regression correlation coefficient for the BIPs parameters of (kij) and (ηij) are 0.98533 and 0.99083, respectively. This is the first research study on the phase behavior of acetate ester compounds in SC-CO2 solvents, and the results have a significant impact on industries at different operating conditions.

Abstract Distant metastasis, the leading cause of cancer death, is efficiently kept in check by immune surveillance. Studies have uncovered peripheral natural killer (NK) cells as key antimetastatic effectors and their dysregulation during metastasis. However, the molecular mechanism governing NK cell dysfunction links to metastasis remains elusive. Herein, MAP4K1 encoding HPK1 is aberrantly overexpressed in dysfunctional NK cells in the periphery and the metastatic site. Conditional HPK1 overexpression in NK cells suffices to exacerbate melanoma lung metastasis but not primary tumor growth. Conversely, MAP4K1‐deficient mice are resistant to metastasis and further protected by combined immune‐checkpoint inhibitors. Mechanistically, HPK1 restrains NK cell cytotoxicity and expansion via activating receptors. Likewise, HPK1 limits human NK cell activation and associates with melanoma NK cell dysfunction couples to TGF‐β1 and patient response to immune checkpoint therapy. Thus, HPK1 is an intracellular checkpoint controlling NK‐target cell responses, which is dysregulated and hijacked by tumors during metastatic progression.

Abstract Batteries that utilize low‐cost elemental sulfur and light metallic lithium as electrodes have great potential in achieving high energy density. However, building a lithium–sulfur (Li–S) full battery by controlling the electrolyte volume generally produces low practical energy because of the limited electrochemical Li–S redox. Herein, the high energy/high performance of a Li–S full battery with practical sulfur loading and minimum electrolyte volume is reported. A unique hybrid architecture configured with Ni–Co metal alloy (NiCo) and metal oxide (NiCoO2) nanoparticles heterogeneously anchored in carbon nanotube‐embedded self‐standing carbon matrix is fabricated as a host for sulfur. This work demonstrates the considerable improvement that the hybrid structure's high conductivity and satisfactory porosity promote the transport of electrons and lithium ions in Li–S batteries. Through experimental and theoretical validations, the function of NiCo and NiCoO2 nanoparticles as an efficient polysulfide mediator is established. These particles afford polysulfide anchoring and catalytic sites for Li–S redox reaction, thus improving the redox conversion reversibility. Even at high sulfur loading, the nanostructured Ni–Co metal alloy and metal oxide enable to have stable cycling performance under lean electrolyte conditions both in half‐cell and full‐cell batteries using a graphite anode.

ABSTRACT Plant pathogenic fungi cause serious diseases, which result in the loss of crop yields and reduce the quality of crops worldwide. To counteract the escalating risks of chemical fungicides, interest in biological control agents to manage plant diseases has significantly increased. In this study, we comprehensively screened microbial culture filtrates using a yeast screening system to find microbes exhibiting respiratory inhibition activity. Consequently, we found a soil-borne microbe Brevibacillus brevis HK544 strain exhibiting a respiration inhibitory activity and identified edeine B1 (EB1) from the culture filtrate of HK544 as the active compound of the respiration inhibition activity. Furthermore, against a plant pathogenic fungus Fusarium graminearum, our results showed that EB1 has effects on multiple aspects of respiration with the downregulation of most of the mitochondrial-related genes based on transcriptome analysis, differential EB1-sensitivity from targeted mutagenesis, and the synergistic effects of EB1 with electron transport chain complex inhibitors. With the promising plant disease control efficacy of B. brevis HK544 producing EB1, our results suggest that B. brevis HK544 has potential as a biocontrol agent for Fusarium head blight.IMPORTANCEAs a necrotrophic fungus, Fusarium graminearum is a highly destructive pathogen causing severe diseases in cereal crops and mycotoxin contamination in grains. Although chemical control is considered the primary approach to control plant disease caused by F. graminearum, fungicide-resistant strains have been detected in the field after long-term continuous application of fungicides. Moreover, applying chemical fungicides that trigger mycotoxin biosynthesis is a great concern for many researchers. Biocontrol of Fusarium head blight (FHB) by biological control agents (BCAs) represents an alternative approach and could be used as part of the integrated management of FHB and mycotoxin production. The most extensive studies on bacterial BCAs-fungal communications in agroecosystems have focused on antibiosis. Although many BCAs in agricultural ecology have already been used for fungal disease control, the molecular mechanisms of antibiotics produced by BCAs remain to be elucidated. Here, we found a potential BCA (Brevibacillus brevis HK544) with a strong antifungal activity based on the respiration inhibition activity with its active compound edeine B1 (EB1). Furthermore, our results showed that EB1 secreted by HK544 suppresses the expression of the mitochondria-related genes of F. graminearum, subsequently suppressing fungal development and the virulence of F. graminearum. In addition, EB1 exhibited a synergism with complex I inhibitors such as rotenone and fenazaquin. Our work extends our understanding of how B. brevis HK544 exhibits antifungal activity and suggests that the B. brevis HK544 strain could be a valuable source for developing new crop protectants to control F. graminearum.

The purpose of our study to determine the effects of interval hypoxic training (IHT) and repeated sprint training in hypoxia (RSH) on metabolic and cardiac function during submaximal exercise, aerobic and anaerobic performance, and time trial performance in elite Korean national male mountain bike (MTB) cyclists. The participants included elite Korean national male MTB cyclists (n = 4) preparing for the 19th Asian Games in Hangzhou 2022. The hypoxic training frequency was 90 min (3 days per week for 4 weeks). Before and after hypoxic training, metabolic and cardiac functions during submaximal exercise, aerobic performance, anaerobic performance and time trial performance were measured. Oxygen uptake, carbon dioxide excretion, and heart rate tended to decrease, and stroke volume, end-diastolic volume and cardiac output tended to increase. In aerobic, anaerobic and time trial performances, the peak torque in aerobic performance significantly increased (p = 0.046). Maximal oxygen uptake and exercise time in aerobic performance, relative peak power, relative mean power, post-exercise blood lactate level, fatigue index in anaerobic performance, and time trial performance showed an improved tendency (all p = 0.068). Our pilot study confirmed that although the sample size was small, IHT and RSH can potentially improve athletic performance in elite Korean national male MTB cyclists.

Portal vein tumor thrombosis (PVTT) is an uncommon condition in which tumor cells expand into the vessels, causing blood clot formation in the portal vein. PVTT is mainly associated with hepatocellular carcinoma, leading to an unfavorable prognosis; however, it can also develop in patients with other cancer types. Herein, we report a case of metastatic renal cell carcinoma diagnosed by a blind liver biopsy in a patient with dynamic computed tomography-confirmed portal vein thrombosis and cholangiopathy. This case illustrates the importance of systematic surveillance with routine laboratory tests and contrast-enhanced imaging studies on patients with cancer to detect potential liver infiltration of metastatic cancer.

Abstract Potential synergism between Bruton’s tyrosine kinase (BTK) inhibitor and lenalidomide in treating aggressive B-cell lymphoma has been suggested. Here, the authors report a single-arm phase II clinical trial of combination of acalabrutinib, lenalidomide and rituximab (R2A) in patients with aggressive relapsed/refractory aggressive (R/R) B-cell non-Hodgkin lymphoma (NHL). The primary endpoint of this study is objective response rate (ORR), and the secondary endpoints are complete remission (CR) rate, duration of response (DoR), progression-free survival (PFS) and overall survival (OS). A total of 66 patients are enrolled mostly with diffuse large B-cell lymphoma. The ORR is 54.5% and CR rate is 31.8% meeting the primary end point. The median DoR is 12.9 months, and 1-year PFS and OS rate is 33.1% and 67.5% respectively. Adverse events (AE) are manageable with the most frequent AE being neutropenia (31.8%). Patients with MYD88 mutations, subtypes known for NF-κB activation, and high BTK expression by immunohistochemistry respond well. Overall, these results show a significant efficacy of the R2A regimen in patients with aggressive R/R B-cell NHL, with exploratory biomarkers suggesting potential associations with response. (ClinicalTrials.gov 51 identifier: NCT04094142)

Abstract Engineered human cardiac tissues have been utilized for various biomedical applications, including drug testing, disease modeling, and regenerative medicine. However, the applications of cardiac tissues derived from human pluripotent stem cells are often limited due to their immaturity and lack of functionality. Therefore, in this study, we establish a perfusable culture system based on in vivo-like heart microenvironments to improve human cardiac tissue fabrication. The integrated culture platform of a microfluidic chip and a three-dimensional heart extracellular matrix enhances human cardiac tissue development and their structural and functional maturation. These tissues are comprised of cardiovascular lineage cells, including cardiomyocytes and cardiac fibroblasts derived from human induced pluripotent stem cells, as well as vascular endothelial cells. The resultant macroscale human cardiac tissues exhibit improved efficacy in drug testing (small molecules with various levels of arrhythmia risk), disease modeling (Long QT Syndrome and cardiac fibrosis), and regenerative therapy (myocardial infarction treatment). Therefore, our culture system can serve as a highly effective tissue-engineering platform to provide human cardiac tissues for versatile biomedical applications.

As the older population increases worldwide, frailty is the area of research that deserve further investigation and is considered a major social and public health concern. Frailty appears physically and mentally, and recently, the term cognitive frailty has been used to combine physical frailty and mild cognitive impairment syndrome. Frailty in older adults is characterized by low physical activity levels and a sedentary lifestyle. Physical activity is essential in managing mental health issues such as depression and can improve the executive function and memory of older adults with mild cognitive impairment. Therefore, this study aimed to examine the prevalence of cardiometabolic diseases, self-reported memory loss, and depression among older adults in Korea according to frailty and physical activity status. Using data from the 2019 Korea National Health and Nutrition Survey, this study analyzed 613 community-dwelling older males aged ≥65 years. Physical activity was measured using a Global Physical Activity Questionnaire. A health-related quality of life instrument with eight items (HINT-8) was used to assess self-reported memory loss and depressed mood. Relationships between physical activity levels, self-reported memory loss and depressed mood were analyzed using logistic regression. The incidence of HINT-8 memory (0.52 (95% confidence interval (CI): 0.32–0.85)) was significantly lower in the Physical Activity Level (PAL)-high/pre-frail; the incidence of HINT-8 depression (0.35 (95% CI: 0.21–0.59); 0.29 (95% CI: 0.17–0.52)) was significantly lower in the and PAL-high/pre-frail. We verified that the group with PAL-low/frail had the highest self-reported memory loss and depressed mood, suggesting that more physical activity may reduce self-reported memory loss and depressed mood among frail older males in Korea. However further research is needed to analyze the level of physical activity separately between work and leisure.

Background Cardiovascular disease is life-threatening yet preventable for patients with type 2 diabetes mellitus (T2DM). Because each patient with T2DM has a different risk of developing cardiovascular complications, the accurate stratification of cardiovascular risk is critical. In this study, we proposed cardiovascular risk engines based on machine-learning algorithms for newly diagnosed T2DM patients in Korea. Methods To develop the machine-learning-based cardiovascular disease engines, we retrospectively analyzed 26,166 newly diagnosed T2DM patients who visited Seoul St. Mary’s Hospital between July 2009 and April 2019. To accurately measure diabetes-related cardiovascular events, we designed a buffer (1 year), an observation (1 year), and an outcome period (5 years). The entire dataset was split into training and testing sets in an 8:2 ratio, and this procedure was repeated 100 times. The area under the receiver operating characteristic curve (AUROC) was calculated by 10-fold cross-validation on the training dataset. Results The machine-learning-based risk engines (AUROC XGBoost=0.781±0.014 and AUROC gated recurrent unit [GRU]-ordinary differential equation [ODE]-Bayes=0.812±0.016) outperformed the conventional regression-based model (AUROC=0.723± 0.036). Conclusion GRU-ODE-Bayes-based cardiovascular risk engine is highly accurate, easily applicable, and can provide valuable information for the individualized treatment of Korean patients with newly diagnosed T2DM.

We tackle a multi-layer knowledge distillation problem between deep models with heterogeneous architectures. The main challenges of that are the mismatches of the feature maps in terms of the resolution or semantic levels. To resolve this, we propose a novel transformer-based multi-layer correlation knowledge distillation (TMC-KD) method in order to bridge the knowledge gap between a pair of networks. Our method aims to narrow the relational knowledge gaps between teacher and student models by minimizing the local and global feature correlations. Based on extensive comparisons with the recent KD methods on classification and detection tasks, we prove the effectiveness and usefulness of our TMC-KD method.

Abstract Epithelial–mesenchymal transition (EMT) is the process by which epithelial cells acquire mesenchymal characteristics. This process induces cell migration and invasion, which are closely related to cancer metastasis and malignancy. EMT consists of various intermediate states that express both epithelial and mesenchymal traits, called partial EMT. Recently, several studies have focused on the roles of voltage-gated potassium (Kv) channels associated with EMT in cancer cell migration and invasion. In this study, we demonstrate the relationship between Kv3.4 and EMT and confirm the effects of cell migration and invasion. With TGF-β treatment, EMT was induced and Kv3.4 was also increased in A549 cells, human lung carcinoma cells. The knockdown of Kv3.4 blocked the EMT progression reducing cell migration and invasion. However, the Kv3.4 overexpressed cells acquired mesenchymal characteristics and increased cell migration and invasion. The overexpression of Kv3.4 also has a synergistic effect with TGF-β in promoting cell migration. Therefore, we conclude that Kv3.4 regulates cancer migration and invasion through TGF-β-induced EMT and these results provide insights into the understanding of cancer metastasis.

Abstract Background We aimed to explore the associations between thigh muscle fat density and vascular events. Methods A total of 3,595 adults (mean age, 57.2 years; women, 1,715 [47.7%]) without baseline cardiovascular events from the Korean Atherosclerosis Study-2 were included. Muscle and fat area at the mid-thigh level were measured by computed tomography (CT) using the following Hounsfield Unit range: 0–30 for low density muscle (LDM); 31–100 for normal density muscle (NDM); and − 250 to − 50 for fat. Results During a median follow-up period of 11.8 (4.3–13.9) years, vascular events occurred in 11.6% of men and 5.9% of women. Individuals with vascular events had a larger LDM area (men: 48.8 ± 15.5 cm2 vs. 44.6 ± 14.5 cm2; women: 39.4 ± 13.2 cm2 vs. 35.0 ± 11.8 cm2, both P < 0.001) compared with those who did not have vascular events during the follow-up of at least 5 years. The LDM/NDM ratio was also independently associated with vascular events after adjusting for cardiometabolic risk factors. Moreover, the LDM/NDM ratio improved the prognostic value for vascular events when added to conventional risk factors. Conclusions The current study suggests that a higher thigh muscle fat infiltration is associated with an increased risk of developing vascular events among Korean adults.

AbstractTranscription factor 3 (TCF3) is a DNA transcription factor that modulates megakaryocyte development. Although abnormal TCF3 expression has been identified in a range of hematological malignancies, to date, it has not been investigated in myelofibrosis (MF). MF is a Philadelphia-negative myeloproliferative neoplasm (MPN) that can arise de novo or progress from essential thrombocythemia [ET] and polycythemia vera [PV] and where dysfunctional megakaryocytes have a role in driving the fibrotic progression. We aimed to examine whether TCF3 is dysregulated in megakaryocytes in MPN, and specifically in MF. We first assessed TCF3 protein expression in megakaryocytes using an immunohistochemical approach analyses and showed that TCF3 was reduced in MF compared with ET and PV. Further, the TCF3-negative megakaryocytes were primarily located near trabecular bone and had the typical “MF-like” morphology as described by the WHO. Genomic analysis of isolated megakaryocytes showed three mutations, all predicted to result in a loss of function, in patients with MF; none were seen in megakaryocytes isolated from ET or PV marrow samples. We then progressed to transcriptomic sequencing of platelets which showed loss of TCF3 in MF. These proteomic, genomic and transcriptomic analyses appear to indicate that TCF3 is downregulated in megakaryocytes in MF. This infers aberrations in megakaryopoiesis occur in this progressive phase of MPN. Further exploration of this pathway could provide insights into TCF3 and the evolution of fibrosis and potentially lead to new preventative therapeutic targets.

Many studies have explored indigenous religious believers struggle against world religions domination. However, studies on the employment of virtual space to heighten indigenous believers' tactical solidarity from the Global South remain understudy. This paper explores indigenous religious followers' struggles through access to virtual space as a tactic of everyday solidarity against world religions spatial domination and the state politics of religion in North Sulawesi, Indonesia. It focuses on the efforts of Minahasa indigenous religious believers to advocate for their existence through virtual media collectively. Indigenous religious believers have experienced various forms of spatial domination, such as destroying ancestral sites and ritual places that they consider sacred to realize their beliefs. The single truth perspective has produced the domination of the world religions monotheistic paradigm and the state politics of religion. The single truth has resulted in hate speech, stigmatization, and physical destruction of indigenous religious sacred sites. Through click activism, indigenous religious believers employ virtual media to advocate Minahasa indigenous religions/beliefs. The concept of tactical media is used in this study to analyze how the tactics of indigenous religious believers collectively produce a discourse of resistance critique and discourse on the importance of their places of belief to the public. This study uses qualitative research: observation, in-depth interviews, and literature review to argue that indigenous religious believers have tactically used virtual media as a critical discourse of resistance to the spatial domination constructed by world religious relations and state religious policies.

In bacterial-based cancer therapy, while attenuated Salmonella treatment effectively inhibits tumor progression, single bacterial therapy struggles to completely suppress tumor growth and metastasis. Metformin, a natural compound derived from Galega officinalis L. and known for its antidiabetic properties, also demonstrates significant anti-tumor activity. However, the combined effect of metformin and attenuated Salmonella on tumor treatment has not been thoroughly investigated. In this study, we observed that metformin enhances attenuated Salmonella-mediated recruitment of tumor-infiltrating immune cells, such as NK cells, neutrophils, M1 macrophages, CD4+, and CD8+T lymphocytes in CT26 tumor-bearing mice. Furthermore, the combined treatment of metformin and attenuated Salmonella increases the protein expression of PEN2, PD1, and PD-L1. This finding is likely associated with the enhanced anti-tumor effects of S.t ΔppGpp by metformin, indicating that the combination of S.t ΔppGpp and metformin holds promise as a synergistic strategy for attenuated Salmonella-based immunotherapy.

ABSTRACT The mycelium of the plant pathogenic fungus Fusarium graminearum exhibits distinct structures for vegetative growth, asexual sporulation, sexual development, virulence, and chlamydospore formation. These structures are vital for the survival and pathogenicity of the fungus, necessitating precise regulation based on environmental cues. Initially identified in Magnaporthe oryzae, the transcription factor Con7p regulates conidiation and infection-related morphogenesis, but not vegetative growth. We characterized the Con7p ortholog FgCon7, and deletion of FgCON7 resulted in severe defects in conidium production, virulence, sexual development, and vegetative growth. The mycelia of the deletion mutant transformed into chlamydospore-like structures with high chitin level accumulation. Notably, boosting FgABAA expression partially alleviated developmental issues in the FgCON7 deletion mutant. Chromatin immunoprecipitation (ChIP)–quantitative PCR (qPCR) analysis confirmed a direct genetic link between FgABAA and FgCON7. Furthermore, the chitin synthase gene Fg6550 (FGSG_06550) showed significant upregulation in the FgCON7 deletion mutant, and altering FgCON7 expression affected cell wall integrity. Further research will focus on understanding the behavior of the chitin synthase gene and its regulation by FgCon7 in F. graminearum. This study contributes significantly to our understanding of the genetic pathways that regulate hyphal differentiation and conidiation in this plant pathogenic fungus.IMPORTANCEThe ascomycete fungus Fusarium graminearum is the primary cause of head blight disease in wheat and barley, as well as ear and stalk rot in maize. Given the importance of conidia and ascospores in the disease cycle of F. graminearum, precise spatiotemporal regulation of these biological processes is crucial. In this study, we characterized the Magnaporthe oryzae Con7p ortholog and discovered that FgCon7 significantly influences various crucial aspects of fungal development and pathogenicity. Notably, overexpression of FgABAA partially restored developmental defects in the FgCON7 deletion mutant. ChIP-qPCR analysis confirmed a direct genetic link between FgABAA and FgCON7. Furthermore, our research revealed a clear correlation between FgCon7 and chitin accumulation and the expression of chitin synthase genes. These findings offer valuable insights into the genetic mechanisms regulating conidiation and the significance of mycelial differentiation in this plant pathogenic fungus.

BackgroundHepatocellular carcinoma (HCC) is the most common malignant liver tumor in dogs. Although surgical resection is a major treatment option for canine HCC, there are no distinct strategies for unresectable tumor subtypes or adjuvant chemotherapy for tumors with positive margins. We aimed to establish and characterize novel HCC cell lines from canine patients.MethodsThe cellular morphology, general growth features and tumorigenicity of the established cell lines were evaluated. We also examined the sensitivity of the cell lines to multi-target tyrosine kinase inhibitors (TKIs).ResultsWe established novel canine HCC cell lines from hepatic tumors and an additional kidney tumor of six canine patients. All cell lines showed colony forming and migratory ability. KU-cHCC-001 and KU-cHCC-001-Kidney, two cell lines exhibiting high epithelial–mesenchymal transition characteristics, showed tumorigenicity in xenografted mice. Toceranib, a veterinary TKI that targets vascular endothelial growth factor (VEGFR)/platelet-derived growth factor receptor (PDGFR)/c-kit, effectively inhibited the mitogen-activated protein kinase pathway and induced apoptosis. The established canine HCC cell lines showed greater sensitivity to toceranib than to sorafenib, a first-line treatment for human HCC targeting RAF/VEGFR/PDGFR. Sorafenib showed improved anti-tumor effects when co-treated with SCH772984, an extracellular signal-regulated kinase inhibitor.ConclusionOur study suggests new therapeutic strategies for canine HCC, and these cell lines are valuable research materials for understanding HCC tumor biology in both humans and dogs.

The coexistence of carbon neutrality and capitalism can be realized if environmentally friendly management is proven to enhance profitability. The focus of green logistics practices (GLPs) is on maximizing energy efficiency in logistics services, potentially leading to cost reductions for companies. Such practices can be supported through public reports, such as Environmental, Social, and Governance (ESG) reports, and government policies, including government certification. The primary objective of this study is to investigate whether the financial efficiency of logistics companies can be improved through the implementation of GLPs and a relevant government policy. To achieve this objective, a two-stage analysis was conducted using Data Envelopment Analysis - Slack-Based Measure (DEA-SBM) and Tobit regression analysis. The DEA-SBM was employed to assess whether the financial efficiency of logistics companies adopting GLPs and a relevant government policy was superior to that of companies not adopting such practices. Additionally, Tobit regression analysis was employed to analyze the effects of GLPs, ESG reports, and a government policy on the financial efficiency of logistics companies. The findings of the study indicate the necessity for collaboration between the private and public sectors to implement GLPs in a financially positive manner. In conclusion, the research demonstrated that the implementation of GLPs, coupled with public disclosure through ESG reports or equivalents and a government policy, had a positive impact on the financial efficiency of logistics companies.

To address the common issues of wrinkling, tearing, and uneven wall thickness in the actual sheet metal stamping process of the outer ring of needle roller bearings, this study analyzes critical technical indicators such as forming limits, thickness distribution, and principal strains in the forming process in detail. Three-dimensional models of the concave and convex dies were constructed. The effects of different process parameters, including stamping speed, edge pressure, sheet metal thickness, and friction coefficient, on the quality of the forming parts were investigated by varying these parameters. Subsequently, the orthogonal experimental method was used to determine an optimal experimental group from multiple sets of experiments. It was found that under the process parameters of a stamping speed of 3000 mm/s, edge pressure of 2000 N, sheet metal thickness of 0.9 mm, and friction coefficient of 0.125, the forming quality of the outer ring of the bearing is ideal.

Objective: To evaluate and compare the magnitude of intraocular lens (IOL) decentration and tilt following conventional and femtosecond laser-assisted cataract surgery (FLACS) using swept-source anterior optical coherence tomography (SS-OCT). Methods: In this retrospective observational study, we enrolled patients who underwent conventional cataract surgery or FLACS with the implantation of hydrophobic 1-piece monofocal IOL. The magnitude of IOL decentration and tilt were measured using SS-OCT. Visual acuity, intraocular pressure, spherical equivalent, axial length, contrast sensitivity, and satisfaction questionnaire were evaluated before and one-month post-surgery. Additionally, postoperative internal cylinder measurements were obtained using a wavefront aberrometer. Correlation factors between each parameter and IOL decentration or tilt were analyzed. Results: This study included 100 eyes from 100 patients. Mean IOL decentration and tilt were 0.21 ± 0.13 mm and 5.01 ± 1.49°, respectively. Conventional cataract surgery (versus FLACS, P = 0.001) and male sex (versus female, P = 0.047) were significantly correlated with higher postoperative decentration. Preoperative lens diameter (P

Hepatocellular carcinoma (HCC) stands as a leading cause of mortality, and despite recent advancements in the overall survival rates, the prognosis remains dismal. Prunetin 4-O-glucoside (Prunetrin or PUR), an active compound derived from Prunus sp., was explored for its impact on HepG2 and Huh7 cells. The cytotoxicity assessment revealed a notable reduction in cell viability in both cell lines, while exhibiting non-toxicity towards HaCaT cells. Colony formation studies underscored PUR's inhibitory effect on cell proliferation, dose-dependently. Mechanistically, PUR downregulated cell cycle proteins (CDC25c, Cdk1/CDC2, and Cyclin B1), inducing G2/M phase arrest, corroborated by flow cytometry. Western blot analyses exhibited dose-dependent cleavages of PARP and caspase 3, indicative of apoptosis. Treatment with the apoptotic inhibitor z-vmd-fmk provided evidence of PUR-induced apoptosis. Annexin V and PI flow cytometry further affirmed apoptotic induction. Enhanced expression of cleaved-caspase 9 and the pro-apoptotic protein Bak, coupled with reduced anti-apoptotic Bcl-xL, and affirmed PUR's induction of intrinsic apoptosis. Additionally, PUR activated the MAPK pathway, evidenced by elevated phospho p38 and phospho ERK expressions in both cell lines. Notably, a concentration-dependent decrease in mTOR and Akt expressions indicated PUR's inhibition of the Akt/mTOR pathway in HepG2 and Huh7 cells. These findings illuminate PUR's multifaceted impact, revealing its potential as a promising therapeutic agent against HepG2 and Huh7 cells through modulation of cell cycle, apoptosis, and key signaling pathways.

Natural killer (NK) cells are key effectors in cancer immunosurveillance, eliminating a broad spectrum of cancer cells without major histocompatibility complex (MHC) specificity and graft-versus-host diseases (GvHD) risk. The use of allogeneic NK cell therapies from healthy donors has demonstrated favorable clinical efficacies in treating diverse cancers, particularly hematologic malignancies, but it requires cytokines such as IL-2 to primarily support NK cell persistence and expansion. However, the role of IL-2 in the regulation of activating receptors and the function of NK cells expanded for clinical trials is poorly understood and needs clarification for the full engagement of NK cells in cancer immunotherapy. Here, we demonstrated that IL-2 deprivation significantly impaired the cytotoxicity of primary expanded NK cells by preferentially downregulating NKp30 but not NKp46 despite their common adaptor requirement for expression and function. Using NK92 and IL-2-producing NK92MI cells, we observed that NKp30-mediated cytotoxicity against myeloid leukemia cells such as K562 and THP-1 cells expressing B7-H6, a ligand for NKp30, was severely impaired by IL-2 deprivation. Furthermore, IL-2 deficiency-mediated NK cell dysfunction was overcome by the ectopic overexpression of an immunostimulatory NKp30 isoform such as NKp30a or NKp30b. In particular, NKp30a overexpression in NK92 cells improved the clearance of THP-1 cells in vivo without IL-2 supplementation. Collectively, our results highlight the distinct role of IL-2 in the regulation of NKp30 compared to that of NKp46 and suggest NKp30 upregulation, as shown here by ectopic overexpression, as a viable modality to harness NK cells in cancer immunotherapy, possibly in combination with IL-2 immunocytokines.

The Sengkang General Hospital Orthopaedic Spine Outpatient Service is facing a growing challenge of increasing number of referrals and waiting times, placing a significant burden on the system. Primary care referrals have an average wait time of 61.1 days, with 34.5%f patients waiting longer than 60 days from referral to appointment, to see a spine physician.Back pain is a very common presentation, with the vast majority resolving after conservative management which commonly includes analgesia, physiotherapy and reassurance. Unfortunately, many referrals from primary care involve patients who have yet to explore the avenues of conservative management with 90% of our referrals being managed without surgery. Globally, triage services in Western countries conducted by allied health professionals have shown to be an effective method at addressing the escalating wait times with high satisfaction rates. We have endeavoured to emulate this within our department through the implementation of the Spine Triage and Rehabilitation (STAR) Clinic. The STAR clinic aims to empower physiotherapists with the ability to triage patients into surgical and non-surgical categories with their primary physiotherapy expertise to reduce waiting times and increase outpatient capacity.More than 300 patients were recruited, and their progress was tracked over 13 months under the four Ss of: waiting timeS, cost Savings, Safety and patient Satisfaction. This pilot study has been overwhelmingly positive, with significantly reduced waiting times and high cost savings, without any compromise on patient safety and satisfaction.

Abstract Our study evaluated the clinical outcomes after implantation of a monofocal intraocular lens (IOL) with enhanced intermediate function in eyes with epiretinal membrane (ERM). Patients with preexisting ERM who underwent cataract surgery with implantation of monofocal IOL with enhanced intermediate function were included retrospectively. According to the ERM grade and central subfield thickness (CST) obtained from preoperative optical coherence tomography, patients were divided into non-fovea-involving and fovea-involving ERM groups. At 1 month after surgery, uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), contrast sensitivity, defocus curve, and satisfaction questionnaire were evaluated. Postoperative clinical findings were compared with age-matched controls without ERM. A total of 50 patients’ eyes (28 and 22 in the non-fovea-involving and fovea-involving ERM groups, respectively) were compared with 42 control eyes. One month post-surgery, significant differences in UDVA, CDVA, and CST (corrected P was

Few studies have compared the differences between protein (whey protein hydrolysate (WPH) or whey protein concentrate (WPC)) intake conditions (at rest or post-resistance exercise). Therefore, the purpose of this study was to investigate the plasma amino acid levels after intake of WPH compared with WPC intake in young men at rest and post-resistance exercise. We also aimed to compare the differences in plasma amino acid levels after WPH intake with or without resistance exercise. Fifteen young men were recruited for this crossover study, where each participant took three supplements (placebo, WPH and WPC) once each at rest and post-resistance exercise over 9 weeks. Blood samples were collected at nine (0, 15, 30, 45, 60, 90, 120, 180, 240 min) and ten (pre, 0, 15, 30, 45, 60, 90, 120, 180, 240 min) time points, at rest and post-resistance exercise, respectively. Plasma amino acids (total amino acids, essential amino acids, branched amino acids and leucine) were measured. WPH intake resulted in faster bioavailability (approximately 15 min) and higher plasma amino acid concentrations in all plasma amino acids, regardless of the condition. In addition, WPH bioavailability tended to have similar peaks concentrations at rest and post-resistance exercise, whereas post-resistance exercise of WPC decreased sharply after 30 min and maintained a lower concentration than normal after 60 min. In conclusion, the results that WPH intake initially increased the concentration of plasma amino acids than WPC suggests that WPH is absorbed into the blood faster and may be more effective in increasing the rate of muscle protein synthesis. Moreover, although the intake of WPH after resistance exercise does not upregulate the peak concentrations of plasma amino acids, the synthesis of skeletal muscle can be increased through a rapid supply to tissues that require amino acids.

Abstract Aims The long‐term effect of angiotensin receptor–neprilysin inhibitor (ARNI) remains uncertain in patients who have experienced improvements in left ventricular (LV) systolic function or significant LV reverse remodelling following a certain period of treatment. It is also unclear how ARNI performs in patients who have not shown these improvements. This study aimed to assess the impact of prolonged ARNI use compared with angiotensin‐converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) in patients with and without significant treatment response after 1 year of heart failure (HF) treatment. Methods and results The present study enrolled patients with HF with reduced ejection fraction (HFrEF) who were treated with either ARNI or ACEIs/ARBs within 1 year of undergoing index echocardiography. After 1 year of treatment, patients were reclassified into the following groups: (i) patients with HF with improved ejection fraction and persistent HFrEF and (ii) patients with and without LV reverse remodelling based on the follow‐up echocardiography. The effect of ARNI versus that of ACEIs/ARBs in each group was assessed from the time of categorizing into new groups using the composite event of all‐cause mortality and HF hospitalization. A total of 671 patients with HFrEF (age, 66.4 ± 14.1 years; males, 66.8%) were included, and 133 (19.8%) composite events of death and rehospitalization for HF were observed during the follow‐up (median follow‐up, 44 [interquartile range, 34–51] months). ARNI had a significantly lower event rate than ACEIs/ARBs in patients with HF with improved ejection fraction (7.0% vs. 30.4%, P = 0.020) and those with persistent HFrEF (17.6% vs. 49.7%, P

Standard approach to predict the decrease in physical fitness that will occur following a transition to a higher altitude is unavailable. Therefore, the study aimed to design simple mathematical models to predict submaximal exercise performance in various altitude environments, using a simple physical work capacity test conducted at sea level involving >200 subjects. After splitting the subjects’ data in a ratio of 7:3, we used 70% of the data for regression model development and employed 30% for cross-validation testing. All subjects performed submaximal exercise tests using a cycle ergometer at artificial altitudes of 2000 m, 3000 m, 4000 m, 5000 m, and at sea level. We applied simple regression analysis to create a predictive model with the statistical significance set at the level of