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Tuberculosis, a disease of poverty, continues to disproportionately affect socioeconomically disadvantaged populations worldwide. This is particularly concerning given the recent resurgence of TB following the COVID-19 pandemic. In South Korea, despite substantial socioeconomic development, TB remains a prominent problem, ranking as the leading infectious killer in the country. The severe stigma associated with TB, coupled with the significant vulnerability of TB patients, has resulted in the voices of these patients being completely underrepresented in both policy and research. This article addresses this research gap by conducting a qualitative assessment of Korea's national TB control efforts through the lens of the UN's AAAQ (Availability, Accessibility, Acceptability, Quality) right to health framework. Through field observations and 20 in-depth interviews with TB patients, healthcare providers, policymakers, and advocates, we explore the lived experiences of socioeconomically disadvantaged TB patients in accessing care and support in Korea. Findings reveal that the failure to integrate the right to health into TB care and support, including inadequate availability, accessibility, acceptability, and quality of services tailored to the needs of this population, contributes significantly to Korea's TB burden. The findings have important implications for TB policy and practice in countries with high TB burdens or those experiencing a resurgence of TB. Prioritizing the right to health in TB care and support is crucial to effectively combat this disease., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Walking is a fundamental aspect of daily life and exercise, with clinical benefits for cardiovascular health and muscle strength. However, accurately measuring energy efficiency during walking poses challenges due to equipment and spatial constraints. In this study, we proposed the cadence-based energy expenditure index (cEEI) and analyzed its correlation with the previously proposed index for measuring energy expenditure under various gait conditions. We enrolled 15 healthy participants and conducted an experimental protocol on a treadmill to measure the following energy expenditure-related indices: oxygen cost index (OCI), energy expenditure index (EEI), and cEEI. The participants underwent stages of walking at different speeds and inclinations that comply with the modified Bruce protocol, whereas their heart rate, oxygen uptake, and cadence were recorded. Participants showed significant increases in heart rate, oxygen uptake, and cadence with higher walking speeds and inclinations. Correlation analysis revealed strong associations between cEEI and OCI, especially during walking conditions. Bland-Altman plots and interclass correlation coefficient analysis demonstrated a favorable agreement between cEEI and OCI, outperforming EEI. In conclusion, this study proposes cEEI as a reliable metric for estimating energy expenditure during walking by proving a strong correlation and agreement with OCI across various gait conditions. This suggests the potential for cEEI to provide real-time, individualized feedback on energy expenditure during walking, facilitating more personalized exercise prescriptions. NEW & NOTEWORTHY We proposed cEEI as a reliable metric for estimating energy expenditure under various walking conditions. Its demonstrated accuracy and potential for real-time individualized feedback could revolutionize personalized exercise prescriptions for diverse sexes and age groups, as well as individuals with disabilities requiring real-time physical monitoring and home care.

Background: Immunotherapy is a powerful strategy for treating cancer and can be used to inhibit the post-surgical relapse of tumors., Methods: To achieve this, a Cell@hydrogel was developed as a template using a mixture of CT26 tumor cells and Pluronic® F-127/gelatin., Results: The proposed mixture has a solution-to-gelation functionality and vice versa. The morphology of the Cell@hydrogel was characterized by scanning electron microscopy and confocal microscopy. For photodynamic immunotherapy, the Cell@hydrogel was functionalized with Cy7 (Cy7-Cell@hydrogel) to quantify reactive oxygen species in CT26 tumor cells. Gel electrophoresis and membrane integrity tests were performed to determine the efficiency of the Cy7-Cell@hydrogel following photodynamic therapy., Conclusions: This protocol provides an alternative approach that mechanistically inhibits the post-surgical relapse of solid tumors based on immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Imaging-based spatial transcriptomics technologies such as Multiplexed error-robust fluorescence in situ hybridization (MERFISH) can capture cellular processes in unparalleled detail. However, rigorous and robust analytical tools are needed to unlock their full potential for discovering subcellular biological patterns. We present Intracellular Spatial Transcriptomic Analysis Toolkit (InSTAnT), a computational toolkit for extracting molecular relationships from spatial transcriptomics data at single molecule resolution. InSTAnT employs specialized statistical tests and algorithms to detect gene pairs and modules exhibiting intriguing patterns of co-localization, both within individual cells and across the cellular landscape. We showcase the toolkit on five different datasets representing two different cell lines, two brain structures, two species, and three different technologies. We perform rigorous statistical assessment of discovered co-localization patterns, find supporting evidence from databases and RNA interactions, and identify associated subcellular domains. We uncover several cell type and region-specific gene co-localizations within the brain. Intra-cellular spatial patterns discovered by InSTAnT mirror diverse molecular relationships, including RNA interactions and shared sub-cellular localization or function, providing a rich compendium of testable hypotheses regarding molecular functions., (© 2024. The Author(s).)

Edible plant-derived nanovesicles (ePDNs) have shown potential as a non-pharmacological option for inflammatory bowel disease (IBD) by maintaining gut health and showing anti-inflammatory effects. However, the effects of Allium tuberosum -derived nanovesicles (ADNs) on colitis have not been studied to date. Here, we extracted exosome-like nanovesicles from Allium tuberosum and investigated whether they have an anti-inflammatory effect in RAW 264.7 cells and colitis mice. The results showed that ADNs reduced the elevated levels of inflammatory factors such as IL-1β, IL-6, TNF-α, and NF-κB pathway-related proteins as a consequence of lipopolysaccharide (LPS) stimulation in RAW 264.7 cells. Furthermore, our mouse experiments demonstrated that ADNs could ameliorate dextran sulfate sodium (DSS)-induced colitis symptoms ( e.g. , increased disease activity index score, intestinal permeability, and histological appearance). Additionally, ADNs counteracted DSS-induced colitis by downregulating the expression of serum amyloid A (SAA), IL-1β, IL-6, and TNF-α and increasing the expression of tight junction proteins (ZO-1 and occludin) and the anti-inflammatory cytokine IL-10. 16S rRNA gene sequencing showed that ADN intervention restored the gut microbial composition, which was similar to that of the DSS non-treated group, by decreasing the ratio of Firmicutes to Bacteroidetes and the relative abundance of Proteobacteria . Furthermore, ADNs induced acetic acid production along with an increase in the abundance of Lactobacillus . Overall, our findings suggest that ADN supplementation has a crucial role in maintaining gut health and is a novel preventive therapy for IBD.

Therapeutic electrical stimulation, such as transcranial cortical stimulation and peripheral somatosensory stimulation, is used to improve motor function in patients with stroke. We hypothesized that these stimulations exert neuroprotective effects during the subacute phase of ischemic stroke by regulating novel common signaling pathways. Male C57BL/6J mouse models of ischemic stroke were treated with high-definition (HD)-transcranial alternating current stimulation (tACS; 20 Hz, 89.1 A/mm 2 ), HD-transcranial direct current stimulation (tDCS; intensity, 55 A/mm 2 ; charge density, 66,000 C/m 2 ), or electroacupuncture (EA, 2 Hz, 1 mA) in the early stages of stroke. The therapeutic effects were assessed using behavioral motor function tests. The underlying mechanisms were determined using transcriptomic and other biomedical analyses. All therapeutic electrical tools alleviated the motor dysfunction caused by ischemic stroke insults. We focused on electrically stimulating common genes involved in apoptosis and cell death using transcriptome analysis and chose 11 of the most potent targets (Trem2, S100a9, Lgals3, Tlr4, Myd88, NF-kB, STAT1, IL-6, IL-1β, TNF-α, and Iba1). Subsequent investigations revealed that electrical stimulation modulated inflammatory cytokines, including IL-1β and TNF-α, by regulating STAT1 and NF-kB activation, especially in amoeboid microglia; moreover, electrical stimulation enhanced neuronal survival by activating neurotrophic factors, including BDNF and FGF9. Therapeutic electrical stimulation applied to the transcranial cortical- or periphery-nerve level to promote functional recovery may improve neuroprotection by modulating a common neuronal death pathway and upregulating neurotrophic factors. Therefore, combining transcranial cortical and peripheral somatosensory stimulation may exert a synergistic neuroprotective effect, further enhancing the beneficial effects on motor deficits in patients with ischemic stroke.

Background: According to international pediatric urinary tract infection (UTI) guidelines, selecting ampicillin/sulbactam or amoxicillin/clavulanate is recommended as the first-line treatment for pediatric UTI. In Korea, elevated resistance to ampicillin and ampicillin/sulbactam has resulted in the widespread use of third-generation cephalosporins for treating pediatric UTIs. This study aims to compare the efficacy of piperacillin-tazobactam (TZP) and cefotaxime (CTX) as first-line treatments in hospitalized children with UTIs., Materials and Methods: The study, conducted at Jeju National University Hospital, retrospectively analyzed medical records of children hospitalized for febrile UTIs between 2014 and 2017. UTI diagnosis included unexplained fever, abnormal urinalysis, and the presence of significant uropathogens. Treatment responses, recurrence, and antimicrobial susceptibility were assessed., Results: Out of 323 patients, 220 met the inclusion criteria. Demographics and clinical characteristics were similar between TZP and CTX groups. For children aged ≥3 months, no significant differences were found in treatment responses and recurrence. Extended-spectrum beta-lactamase (ESBL)-positive strains were associated with recurrence in those <3 months., Conclusion: In Korea, escalating resistance to empirical antibiotics has led to the adoption of broad-spectrum empirical treatment. TZP emerged as a viable alternative to CTX for hospitalized children aged ≥3 months with UTIs. Consideration of ESBL-positive strains and individualized approaches for those <3 months are crucial., Competing Interests: No conflict of interest., (© 2024 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, The Korean Society for AIDS, and Korean Society of Pediatric Infectious Diseases.)

Social-emotional competence (SEC) has been demonstrated to be a crucial factor for student mental health and is malleable through the high-quality implementation of effective school-based social and emotional learning (SEL) programs. SEL is now widely practiced in the United States as a Tier 1 strategy for the entire student body, yet it remains unclear whether disparities exist in the development of SEC across socio-culturally classified subgroups of students. Also, despite the field's widespread concern about teacher bias in assessing SEC within diverse student bodies, little evidence is available on the measurement invariance of the SEC assessment tools used to explore and facilitate SEC development. Based on a sociocultural view of student SEC development, this study aimed to measure and examine the extent to which gender, racial-ethnic, and socioeconomic disparities exist in SEC developmental trajectories during elementary school years. Specifically, using 3 years of SEC assessment data collected from a districtwide SEL initiative (N = 5452; Grades K-2 at baseline; nine measurement occasions), this study (a) tested the measurement invariance of a widely-used, teacher-rated SEC assessment tool (DESSA-Mini) across student gender, race and ethnicity, and socioeconomic status (SES); and (b) examined the extent to which multiyear SEC growth trajectories differed across these subgroups under a routine SEL practice condition. The invariance testing results supported strict factorial invariance of the DESSA-Mini across all the examined subgroups, thereby providing a foundation for valid cross-group comparisons of student SEC growth. The piecewise latent growth modeling results indicated that boys (vs. girls), Black students (vs. White students), Hispanic students (vs. White students), and low-income students (vs. middle-to-high-income students) started with a lower level of SEC, with these gaps being sustained or slightly widened throughout 3 elementary school years. Based on these findings, this study calls for future research that can inform practice efforts to ensure equitable SEC assessments and produce more equitable SEL outcomes, thereby promoting equity in school mental health., Competing Interests: Declaration of competing interest The first author has no competing interests to declare. Although some of the other authors were involved in the development of the DESSA while employed at the Devereux Center for Resilient Children, no author of this paper receives any direct financial remuneration from the sale of the assessments or resources mentioned within this manuscript., (Copyright © 2023. Published by Elsevier Ltd.)

Probiotics can exert direct or indirect influences on various aspects of health claims by altering the composition of the gut microbiome and producing bioactive metabolites. The aim of this study was to examine the effect of Lacticaseibacillus rhamnosus IDCC3201 on skeletal muscle atrophy in dexamethasone-induced C2C12 cells and a mouse animal model. Dexamethasone treatment significantly reduced C2C12 muscle cell viability, myotube diameter, and levels of muscle atrophic markers (Atrogin-1 and MuRF-1). These effects were alleviated by conditioned media (CM) and cell extract (EX) derived from L. rhamnosus IDCC3201. In addition, we assessed the in vivo therapeutic effect of L. rhamnosus IDCC3201 in a mouse model of dexamethasone (DEX)-induced muscle atrophy. Supplementation with IDCC3201 resulted in significant enhancements in body composition, particularly in lean mass, muscle strength, and myofibril size, in DEX-induced muscle atrophy mice. In comparison to the DEX-treatment group, the normal and DEX + L. rhamnosus IDCC3201 groups showed a higher transcriptional level of myosin heavy chain family genes (MHC1, MHC1b, MHC2A, 2bB, and 2X) and a reduction in atrophic muscle makers. These analyses revealed that L. rhamnosus IDCC3201 supplementation led to increased production of branched-chain amino acids (BCAAs) and improved the Allobaculum genus within the gut microbiota of muscle atrophy-induced groups. Taken together, our findings suggest that L. rhamnosus IDCC3201 represents a promising dietary supplement with the potential to alleviate sarcopenia by modulating the gut microbiome and metabolites.

Single-molecule imaging at the tissue scale has revolutionized our understanding of biology by providing unprecedented insight into the molecular expression of individual cells and their spatial organization within tissues. However, achieving precise image stitching at the single-molecule level remains a challenge, primarily due to heterogeneous background signals and dim labeling signals in single-molecule images. This paper introduces Spot-Based Global Registration (SBGR), a novel strategy that shifts the focus from raw images to identified molecular spots for high-resolution image alignment. The use of spot-based data enables straightforward and robust evaluation of the credibility of estimated translations and stitching performance. The method outperforms existing image-based stitching methods, achieving subpixel accuracy (83 ± 36 nm) with exceptional consistency. Furthermore, SBGR incorporates a mechanism to surgically remove duplicate spots in overlapping regions, maximizing information recovery from duplicate measurements. In conclusion, SBGR emerges as a robust and accurate solution for stitching single-molecule resolution images in tissue-scale spatial transcriptomics, offering versatility and potential for high-resolution spatial analysis.

Quantum dots (QDs) hold immense promise for bioimaging, yet technical challenges in surface engineering limit their wider scientific use. We introduce poly(pentafluorophenyl acrylate) (PPFPA) as a user-friendly prepolymer platform for creating precisely controlled multidentate polymeric ligands for QD surface engineering, accessible to researchers without extensive synthetic expertise. PPFPA combines the benefits of both bottom-up and prepolymer approaches, offering minimal susceptibility to hydrolysis and side reactions for controlled chemical composition, along with simple synthetic procedures using commercially available reagents. Live cell imaging experiments highlighted a significant reduction in nonspecific binding when employing PPFPA, owing to its minimal hydrolysis, in contrast to ligands synthesized by using a conventional prepolymer prone to uncontrolled hydrolysis. This observation underscores the distinct advantage of our prepolymer system. Leveraging PPFPA, we synthesized biomolecule-conjugated QDs and performed QD-based immunofluorescence to detect a cytosolic protein. To effectively label cytosolic targets in such a dense and complex environment, probes must exhibit minimal nonspecific binding and be compact. As a result, QD-immunofluorescence has focused primarily on cell surface targets. By creating compact QD-F(ab')2, we sensitively detected alpha-tubulin with a ∼50-fold higher signal-to-noise ratio compared to organic dye-based labeling. PPFPA represents a versatile and accessible platform for tailoring QD surfaces, offering a pathway to realize the full potential of colloidal QDs in various scientific applications.

Background: Female infertility is a crucial problem with significant implications for individuals and society. In this study, we explore risk factors for infertility in Korean women., Methods: A total of 986 female patients who visited six major infertility clinics in Korea were recruited from April to December 2014. Fertile age-matched controls were selected from two nationwide survey study participants. Conditional logistic regression after age-matching was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of each risk factor for infertility., Results: Women with a body mass index (BMI) < 18.5 kg/m² had 1.35 times higher odds of infertility (OR, 1.35; 95% CI, 1.03-1.77), while those with a BMI ≥ 25.0 kg/m² had even higher odds (OR, 2.06; 95% CI, 1.61-2.64) compared to women with a normal BMI (18.5 kg/m² ≤ BMI < 25 kg/m²). Ever-smokers exhibited 4.94 times higher odds of infertility compared to never-smokers (95% CI, 3.45-8.85). Concerning alcohol consumption, women who consumed ≥ 7 glasses at a time showed 3.13 times significantly higher odds of infertility than those who consumed ≤ 4 glasses at a time (95% CI, 1.79-5.48). Lastly, women with thyroid disease demonstrated 1.44 times higher odds of infertility compared to women without thyroid disease (95% CI, 1.00-2.08)., Conclusion: Female infertility in Korea was associated with underweight, obesity, smoking, alcohol consumption, and thyroid disease., Competing Interests: Hoon Kim has received honoraria for participation on the advisory board of Bayer, consulting for Merck and LG Chemical, and lectures from Roche Diagnostics and Organon, which are unrelated to the subjects addressed in this paper., (© 2024 The Korean Academy of Medical Sciences.)

Alzheimer's disease (AD) is characterized by cognitive impairment. It is common in the elderly. Etiologically, dysfunction of cholinergic neurotransmitter system is prominent in AD. However, disease modifying drug for AD is still unavailable. We hypothesized that krill oil and modified krill oil containing 20 % lysophosphatidylcholine-docosahexaenoic acid (LPC-DHA, LPC20K) could play a crucial role in AD by improving cognitive functions measured by several behavioral tests. We found that LPC20K could ameliorate short-term, long-term, spatial, and object recognition memory under cholinergic hypofunction states. To find the underlying mechanism involved in the effect of LPC20K on cognitive function, we investigated changes of signaling molecules using Western blotting. Expression levels of protein kinase C zeta (PKCζ) and postsynaptic density protein 95 (PSD-95), and phosphorylation levels of extracellular signal-regulated kinase (ERK), Ca 2+ /calmodulin-dependent protein kinase Ⅱ (CaMKⅡ), and cAMP response element-binding protein (CREB) were significantly increased in LPC20K-administered group compared to those in the memory impairment group. Moreover, the expression levels of BDNF were temporally increased especially 6 or 9 h after administration of LPC20K compared with the control group. These results suggest that LPC20K could ameliorate memory impairment caused by hypocholinergic state by enhancing the expression levels of PKCζ and PSD-95, and phosphorylation levels of ERK, CaMKⅡ and CREB and increasing BDNF expression levels. Therefore, LPC20K could be used as a dietary supplement against cognitive impairment observed in diseases such as AD with a hypocholinergic state., Competing Interests: Author declarations The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pluronics are amphiphilic triblock copolymers composed of two hydrophilic poly (ethylene oxide) (PEO) chains linked via a central hydrophobic polypropylene oxide (PPO). Owing to their low molecular weight polymer and greater number of PEO segments, Pluronics induce micelle formation and gelation at critical micelle concentrations and temperatures. Pluronics F-68 and F-127 are the only United States (U.S.) FDA-approved classes of Pluronics and have been extensively used as materials for living bodies. Owing to the fascinating characteristics of Pluronics, many studies have suggested their role in biomedical applications, such as drug delivery systems, tissue regeneration scaffolders, and biosurfactants. As a result, various studies have been performed using Pluronics as a tool in nanomedicine and targeted delivery systems. This review sought to describe the delivery of therapeutic cargos using Pluronic F-68 and F-127-based cancer nanomedicines and their composites for combination therapy.

Cells constituting a multicellular organism die in a variety of ways throughout life, and most of them die via apoptosis under normal conditions. The occurrence of apoptosis is especially prevalent during development and in tissues with a high cellular turnover rate, such as the thymus and bone marrow. Interestingly, although the number of apoptotic cells produced daily is known to be innumerable in a healthy adult human body, apoptotic cells are rarely observed. This absence is due to the existence of a cellular process called efferocytosis that efficiently clears apoptotic cells. Studies over the past decades have focused on how phagocytes are able to remove apoptotic cells specifically, swiftly, and continuously, resulting in defined molecular and cellular events. In this review, we will discuss the current understanding of the clearance of apoptotic cells at the molecular level., (© 2023. The Author(s).)

Sarcopenia is defined as loss of muscle mass and strength due to aging. Recent studies show that sarcopenia may improve via the gut-muscle axis, suggesting that gut health may affect muscle phenotypes. In this study, we aimed to investigate the ability of Lactobacillus rhamnosus JY02 as a probiotic strain isolated from kimchi to alleviate sarcopenia. L. rhamnosus JY02-conditioned medium (CM) reduced dexamethasone (DEX)-induced myotube diameter atrophy and expression of muscle degradation markers (MuRF1 and atrogin-1) in C2C12 cells. The amelioration of sarcopenia was investigated by measuring body composition (lean mass), hand grip strength, myofibril size (using histological analysis), and mRNA and protein expression of muscle-related factors in a DEX-induced mouse model. The results of these analyses showed that L. rhamnosus JY02 supplementation promoted the production of muscle-enhancement markers (MHC Iβ, MHC IIα, and Myo-D) and reduced both the production of muscle degradation markers and the symptoms of muscle atrophy (loss of lean mass and muscle strength). We also found decreased levels of pro-inflammatory cytokines (IL-6, IFN- γ) and increased levels of anti-inflammatory cytokines (IL-10) in the serum of DEX+JY02-administered mice compared to those in DEX-treated mice. Overall, these results suggest that L. rhamnosus JY02 is a potent probiotic supplement that prevents sarcopenia by suppressing muscle atrophy.

School-based, universal social and emotional learning (SEL) has been widely practiced and promoted as a promising approach to prevent youth mental, emotional, and behavioral problems. Although prior research has accumulated robust evidence of the average effects of universal SEL, it remains unclear whether it works similarly or differentially across diverse sociocultural subgroups of students. Investigating subgroup effects has implications for understanding the impact of universal SEL on possible subgroup disparities in student social-emotional competence (SEC). This study examined whether the effects of a universal SEL program on student SEC development differed across diverse student subgroups classified by gender, race, ethnicity, socioeconomic status, disability status, and English learner status. Data came from student SEC progress monitoring collected during a 1-year quasi-experimental study of a universal SEL program (N = 1592; Grades K-2). The results of multigroup latent growth modeling suggest that (a) the intervention effects were slightly larger for Black students, compared to White or other racial-ethnic subgroups, and (b) the effects were not different across other examined subgroups. This study also found that in the comparison condition, the SEC disparities between Black and White students tended to widen throughout the year, whereas in the intervention condition, Black students showed a similar rate of growth as their White peers. Findings suggest that universal SEL may be similarly beneficial across many diverse student subgroups, while it may yield larger benefits among some racially marginalized subgroups, preventing racial disparities from further widening. Yet the benefits of SEL may not be sufficient to reduce existing subgroup disparities. These findings suggest a need for more studies to examine differential effects of universal preventive programs by diverse subgroups to better inform practices that enhance equity in youth outcomes., (© 2023. Society for Prevention Research.)

Phagocytosis of apoptotic cells, called efferocytosis, requires calcium inside and outside of phagocytes. Due to its necessity, calcium flux is sophisticatedly modulated, and the level of intracellular calcium in phagocytes is ultimately elevated during efferocytosis. However, the role of elevated intracellular calcium in efferocytosis remains elusive. Here, we report that Mertk-mediated intracellular calcium elevation is necessary for internalization of apoptotic cells during efferocytosis. Drastic depletion of intracellular calcium abrogated the internalization step of efferocytosis by delaying phagocytic cup extension and closure. Especially, the defect of phagocytic cup closure for internalization of apoptotic cells was caused by impaired F-actin disassembly and the attenuated interaction of Calmodulin with myosin light chain kinase (MLCK), leading to diminished myosin light chain (MLC) phosphorylation. Genetic and pharmacological impairment of the Calmodulin-MLCK-MLC axis or Mertk-mediated calcium influx also resulted in inefficient efferocytosis due to a defect in internalization of the targets. Taken together, our observations imply that intracellular calcium elevation through Mertk-mediated calcium influx facilitates efferocytosis by inducing myosin II-mediated contraction and F-actin disassembly required for internalization of apoptotic cells., (© 2023. The Author(s).)

This study presents a DNA-compatible synthesis of diverse 5-arylimidazo[1,2- a ]pyridin-3-amine derivatives using the Suzuki-Miyaura reaction, followed by a Groebke-Blackburn-Bienaymé (GBB) reaction. The GBB reaction demonstrates a wide substrate scope, mild one-pot reaction conditions, and compatibility with subsequent enzymatic ligation, highlighting its potential in DNA-encoded library technology.

Cancer remains a major global health challenge. Traditional chemotherapy often results in side effects and drug resistance, necessitating the development of alternative treatment strategies such as gene therapy. Mesoporous silica nanoparticles (MSNs) offer many advantages as a gene delivery carrier, including high loading capacity, controlled drug release, and easy surface functionalization. MSNs are biodegradable and biocompatible, making them promising candidates for drug delivery applications. Recent studies demonstrating the use of MSNs for the delivery of therapeutic nucleic acids to cancer cells have been reviewed, along with their potential as a tool for cancer therapy. The major challenges and future interventions of MSNs as gene delivery carriers for cancer therapy are discussed.

Human sterile α motif and HD domain-containing protein 1 (SAMHD1) has deoxyribonucleoside triphosphohydrolase (dNTPase) activity that allows it to defend against human immunodeficiency virus type I (HIV-1) infections and regulate the cell cycle. Although SAMHD1 mutations have been identified in various cancer types, their role in cancer is unclear. Here, we aimed to investigate the oncogenic role of SAMHD1 in human clear cell renal cell carcinoma (ccRCC), particularly as a core molecule promoting cancer cell migration. We found that SAMHD1 participated in endocytosis and lamellipodia formation. Mechanistically, SAMHD1 contributed to the formation of the endosomal complex by binding to cortactin. Thereafter, SAMHD1-stimulated endosomal focal adhesion kinase (FAK) signaling activated Rac1, which promoted lamellipodia formation on the plasma membrane and enhanced the motility of ccRCC cells. Finally, we observed a strong correlation between SAMHD1 expression and the activation of FAK and cortactin in tumor tissues obtained from patients with ccRCC. In brief, these findings reveal that SAMHD1 is an oncogene that plays a pivotal role in ccRCC cell migration through the endosomal FAK-Rac1 signaling pathway., (© 2023. The Author(s).)

Backgrounds: Some observational studies have suggested a possible association between vitamin D deficiency and CKD. However, in most studies, the causality between low levels of vitamin D and risk of renal events could not be explained. We investigated the relationship between vitamin D deficiency and risk of severe CKD stage and renal event in a large-scale prospective cohort study., Methods: We used data from a prospective cohort of 2,144 patients with available information on serum 25-hydroxyvitamin D (25(OH)D) levels at baseline from KNOW-CKD, 2011-2015 were included. Vitamin D deficiency was defined as serum 25(OH)D levels < 15 ng/mL. We performed a cross-sectional analysis to elucidate the relationship between 25(OH)D and CKD stage using baseline CKD patient data. We further examined a cohort analysis to clarify the association between 25(OH)D and risk of renal event. Renal event was a composite of the first occurrence of a 50% decline in eGFR from the baseline value or the onset of CKD stage 5 (initiation of dialysis or kidney transplantation) across the follow-up period. We also investigated the associations of vitamin D deficiency with risk of renal event according to diabetes and overweight status., Results: Vitamin D deficiency were significantly associated with an increased risk of severe CKD stage - 1.30-fold (95% CI: 1.10-1.69) for 25(OH)D. Deficiency of 25(OH)D with 1.64-fold (95% CI: 1.32-2.65) was related to renal event compared with the reference. Furthermore, vitamin D deficiency patients with presence of DM and overweight status also displayed higher risk than non-deficient patients for risk of renal event., Conclusion: Vitamin D deficiency is associated with significantly increased risk of severe CKD stage and renal event., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Bae, Kim, Chung, Kim, Oh, Kim, Oh and Park.)

SGLT-2 inhibitor, traditionally used for glycemic control, has several beneficial effects that can help manage heart failure (HF). SGLT-2 inhibitors reduce the risk of cardiovascular mortality in patients with HF. As atrial fibrillation (AF) is closely associated with HF and diabetes mellitus (DM) is a risk factor for AF, we assume that SGLT-2 inhibitors will also show therapeutic benefits regarding AF, especially for rhythm control. This trial has a multicenter, prospective, open, blinded endpoint design. It is a 1:1 randomized and controlled study. A total of 716 patients who are newly diagnosed of AF and DM within 1 year will be enrolled from 7 tertiary medical centers. The trial is designed to compare the effects of SGLT-2 inhibitors and other oral hypoglycemic agents on atrial rhythm control in patients with AF and DM. The primary outcome is the recurrence of AF within a year (including post-antiarrhythmic drugs (AAD) or ablation). The secondary outcomes are the ablation rate within a year, change in AF burden, size of the left atrium, NT-proBNP, the AF symptom score, and the quality of life. This trial will prospectively evaluate the effect and safety of SGLT-2 inhibitors on AF rhythm control in patients with DM. It will provide an invaluable dataset on rhythm control in AF with DM for future studies and offer novel information to assist in clinical decisions. (BEYOND trial, ClinicalTrials.gov number: NCT05029115. https://clinicaltrials.gov/ct2/show/NCT05029115)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: This study examined changes in socioeconomic inequalities in mortality in Korea before and after the outbreak of coronavirus disease 2019 (COVID-19)., Methods: From 2017 to 2020, age-standardized mortality rates were calculated for all-cause deaths, avoidable deaths (preventable deaths, treatable deaths), and unavoidable deaths using National Health Insurance claims data and Statistics Korea's cause of death data. In addition, the slope index of inequality (SII) and the relative index of inequality (RII) by six income levels (Medical Aid beneficiary group and quintile of health insurance premiums) were computed to analyze the magnitude and change of mortality inequalities., Results: All-cause and avoidable mortality rates decreased steadily between 2017 and 2020, whereas unavoidable mortality remained relatively stable. In the case of mortality inequalities, the disparity in all-cause mortality between income classes was exacerbated in 2020 compared to 2019, with the SII increasing from 185.44 to 189.22 and the RII increasing from 3.99 to 4.29. In particular, the preventable and unavoidable mortality rates showed an apparent increase in inequality, as both the SII (preventable: 91.31 to 92.01, unavoidable: 69.99 to 75.38) and RII (preventable: 3.42 to 3.66, unavoidable: 5.02 to 5.89) increased., Conclusions: In the first year of the COVID-19 pandemic, mortality inequality continued to increase, although there was no sign of exacerbation. It is necessary to continuously evaluate mortality inequalities, particularly for preventable and unavoidable deaths.

The electrochemical production of H 2 O 2 via the two-electron oxygen reduction reaction (2e - ORR) has recently attracted attention as a promising alternative to the current anthraquinone process. Identification of active sites in O-doped carbon materials, which exhibit high activities and selectivities for the 2e - ORR, is important for understanding the selective electrocatalytic process and achieving the rational design of active electrocatalysts. However, this is impeded by the heterogeneous distribution of various active sites on these catalysts. In this study, we exploited the molecular functionalisation approach to implant anthraquinone, benzoic acid, and phenol groups on carbon nanotubes and systematically compared the electrocatalytic activities and selectivities of these functional groups. Among these oxygen functional groups, the anthraquinone group showed the highest surface-area-normalised and active-site-normalised activities.

The composition of commensal bacteria plays a critical role in controlling immune responses in the intestine. Studies have shown that specific bacterial strains may have the capacity to enhance host immune defense against gastrointestinal viral infections. While norovirus is known to be the most common cause of gastroenteritis, leading to an estimated 200,000 deaths every year, identification of bacterial strains with protective effects against norovirus infection remains elusive. Here, we discovered Lactobacillus salivarius HHuMin-U (HHuMin-U) as a potent antiviral strain against norovirus infection. HHuMin-U significantly suppressed murine norovirus replication and lowered viral RNA titers in macrophages. The transcriptome sequencing (RNA sequencing) analysis revealed that HHuMin-U markedly enhanced the expression level of antiviral interferon-stimulated genes compared to mock treatment. HHuMin-U treatment dose-dependently induced type I interferons (IFN-α and IFN-β) and tumor necrosis factor-α production in mouse and human macrophages, promoting antiviral innate responses against norovirus infection. Investigation on the molecular mechanism demonstrated that HHuMin-U can activate nuclear factor κB and TANK-binding kinase 1 (TBK1)-interferon regulatory factor 3 signaling pathways, leading to the phosphorylation of signal transducer and activator of transcription 1 and signal transducer and activator of transcription 2, the key mediators of interferon-stimulated genes. Finally, oral administration of HHuMin-U increased IFN-β levels in the ileum of mice and altered the gut microbiome profile. These results suggest the species/strain-specific importance of gut microbial composition for antiviral immune responses and the potential use of HHuMin-U as a probiotic agent., (Copyright © 2022 Da Hyun Kim et al.)

RNA interference (RNAi) therapies have significant potential for the treatment of inflammatory bowel diseases (IBD). Although administering small interfering RNA (siRNA) via an oral route is desirable, various hurdles including physicochemical, mucus, and cellular uptake barriers of the gastrointestinal tract (GIT) impede both the delivery of siRNA to the target site and the action of siRNA drugs at the target site. In this review, we first discuss various physicochemical and biological barriers in the GI tract. Furthermore, we present recent strategies and the progress of oral siRNA delivery strategies to treat IBD. Finally, we consider the challenges faced in the use of these strategies and future directions of oral siRNA delivery strategies., Competing Interests: The authors declare no conflict of interest.

Electroactive polymer (EAP) is a polymer that reacts to electrical stimuli, such as voltage, and can be divided into electronic and ionic EAP by an electrical energy transfer mechanism within the polymer. The mechanism of ionic EAP is the movement of the positive ions inducing voltage change in the polymer membrane. Among the ionic EAPs, an ionic polymer-metal composite (IPMC) is composed of a metal electrode on the surface of the polymer membrane. A common material for the polymer membrane of IPMC is Nafion containing hydrogen ions, and platinum, gold, and silver are commonly used for the electrode. As a result, IPMC has advantages, such as low voltage requirements, large bending displacement, and bidirectional actuation. Manufacturing of IPMC is composed of preparing the polymer membrane and plating electrode. Preparation methods for the membrane include solution casting, hot pressing, and 3D printing. Meanwhile, electrode formation methods include electroless plating, electroplating, direct assembly process, and sputtering deposition. The manufactured IPMC is widely demonstrated in applications such as grippers, micro-pumps, biomedical, biomimetics, bending sensors, flow sensors, energy harvesters, biosensors, and humidity sensors. This paper will review the overall field of IPMC by demonstrating the categorization, principle, materials, and manufacturing method of IPMC and its applications.

Introduction: This article reports on the results from a scoping review and a modified e-Delphi survey with experts which aimed to synthesize existing knowledge and identify research gaps on the health and health equity implications of informal employment in both low- and middle-income countries (LMICs) and high-income countries (HICs)., Methods: The scoping review included peer-reviewed articles published online between January 2015 and December 2019 in English. Additionally, a modified e-Delphi survey with experts was conducted to validate our findings from the scoping review and receive feedback on additional research and policy gaps. We drew on micro- and macro-level frameworks on employment relations and health inequities developed by the Employment Conditions Knowledge Network to synthesize and analyze existing literature., Results: A total of 540 articles were screened, and 57 met the eligibility criteria for this scoping review study, including 36 on micro-level research, 19 on macro-level research, and 13 on policy intervention research. Most of the included studies were conducted in LMICs while the research interest in informal work and health has increased globally. Findings from existing literature on the health and health equity implications of informal employment are mixed: informal employment does not necessarily lead to poorer health outcomes than formal employment. Although all informal workers share some fundamental vulnerabilities, including harmful working conditions and limited access to health and social protections, the related health implications vary according to the sub-groups of workers (e.g., gender) and the country context (e.g., types of welfare state or labour market). In the modified e-Delphi survey, participants showed a high level of agreement on a lack of consensus on the definition of informal employment, the usefulness of the concept of informal employment, the need for more comparative policy research, qualitative health research, and research on the intersection between gender and informal employment., Conclusions: Our results clearly identify the need for more research to further understand the various mechanisms through which informal employment affects health in different countries and for different groups of informal workers., (© 2022. The Author(s).)

As osteoporosis is a degenerative disease related to postmenopausal aging, early diagnosis is vital. This study used data from the Korea National Health and Nutrition Examination Surveys to predict a patient's risk of osteoporosis using machine learning algorithms. Data from 1431 postmenopausal women aged 40-69 years were used, including 20 features affecting osteoporosis, chosen by feature importance and recursive feature elimination. Random Forest (RF), AdaBoost, and Gradient Boosting (GBM) machine learning algorithms were each used to train three models: A, checkup features; B, survey features; and C, both checkup and survey features, respectively. Of the three models, Model C generated the best outcomes with an accuracy of 0.832 for RF, 0.849 for AdaBoost, and 0.829 for GBM. Its area under the receiver operating characteristic curve (AUROC) was 0.919 for RF, 0.921 for AdaBoost, and 0.908 for GBM. By utilizing multiple feature selection methods, the ensemble models of this study achieved excellent results with an AUROC score of 0.921 with AdaBoost, which is 0.1-0.2 higher than those of the best performing models from recent studies. Our model can be further improved as a practical medical tool for the early diagnosis of osteoporosis after menopause.

Guided by the contextual theory of elder mistreatment, this study examined the psychological mistreatment (PM) of aging parents and parents-in-law by their married children and compared the risk factors of PM. We used nationally representative data on the adverse experiences of Korean adults in 2017 (n=2,974). Results showed similarities and differences in the PM of aging parents and parents-in-law. Common risk factors included children's sex, greater victimization experiences, and co-residence. Daughters and daughters-in-law were more likely than their male counterparts to psychologically mistreat parents and parents-in-law. While parents' PM was more frequent when children had a temporary work status and when parents were younger, PM of parents-in-law occurred more often when children had a full-time job, poor self-rated health, and a negative perception of family relations. These findings provide insights into policy intervention against PM, suggesting the need for complex prevention strategies for PM of aging parents and parents-in-law.

Disease intervention at the DNA level generally has been avoided because of off-target effects. Recent advances in genome editing technologies using CRISPR-Cas9 have opened a new era in DNA-targeted therapeutic approaches. However, delivery of such systems remains a major challenge. Here, we report a selective DNA-modifying small molecule that targets a disease-specific structure and mismatches involved in myotonic dystrophy type 1 (DM1). This ligand alkylates T-T mismatch-containing hairpins formed in the expanded CTG repeats (d(CTG) exp ) in DM1. Ligand alkylation of d(CTG) exp inhibits the transcription of d(CAG·CTG) exp , thereby reducing the level of the toxic r(CUG) exp transcript. The bioactivity of the ligand also included a reduction in DM1 pathological features such as disease foci formation and misregulation of pre-mRNA splicing in DM1 model cells. Furthermore, the CTG-alkylating ligand may change the d(CAG·CTG) exp repeat length dynamics in DM1 patient cells. Our strategy of linking an alkylating moiety to a DNA mismatch-selective small molecule may be generally applicable to other repeat expansion diseases such as Huntington's disease and amyotrophic lateral sclerosis.

Background: Comparison of the prevalence of cardiometabolic disorders (CMDs) and comorbidities in Korea and the United States (US) can be an important indicator for forecasting future risk of cardiovascular events in Korea. This study aimed to estimate and compare the prevalence of hypertension, diabetes mellitus (DM), dyslipidemia, obesity, and metabolic syndrome (MetS) in Korea and the US., Methods: A total of 15,872 individuals from the US National Health and Nutrition Examination Survey (NHANES) 2003-2014 and 26,492 from the Korea NHANES (KNHANES) 2007-2014 were included. Additionally, 164,339 (139,345 from the Health Examinees-Gem Study and 24,994 from the Cardiovascular Disease Association Study) participants enrolled in the Korea Genome and Epidemiology Study were included to investigate the differences of CMDs between urban and rural regions. To estimate the age-standardized prevalence of CMDs in individuals aged 40-69 years, direct standardization using the World Health Organization standard population was performed., Results: The prevalence of CMDs was lower in Korea than the US (hypertension 49.9% vs. 56.8%; DM 13.4% vs. 14.3%; hypercholesterolemia 16.8% vs. 17.8%; obesity 36.2% vs. 38.6%; and MetS 29.4% vs. 36.5%). According to the median survey years, dyslipidemia has become more prevalent in Korea than in the US since 2010. The prevalence of CMDs was greater in rural than that in urban areas in Korea., Conclusion: The prevalence of dyslipidemia in Korea exceeded that of the US after 2010, which was associated with increasing burden of cardiovascular events. The present study suggests that further preventive strategies are needed to mitigate the prevalence of CMDs in Korea., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Background: COVID-19 patients experience various stressors during the quarantine period and after release from quarantine. However, stressors experienced during each period remain unclear., Methods: A total of 15 mental health experts from the integrated psychological support group for COVID-19participated in this study. Psychological support was provided for the total 932 confirmed COVID-19 patients and their families. Qualitative data were collected using Focus Group Interview (FGI). The participants were divided into two groups and semi-structured questions were used to allow participants to speak their minds., Results: During the quarantine period, difficulties of being diagnosed with COVID-19, concerns about recovery from COVID-19, stress related to quarantine, issues related to the treatment environment, and limited information about COVID-19 and communication were frequently reported. After release from quarantine, the reported main stressors include reinfection or reactivation, concerns about complications, and financial difficulties. Confusion as vectors and victims, stigma and discrimination, and conflicts within a family were observed during both periods., Conclusions: COVID-19 patients suffered various stressors during the quarantine period and after release from quarantine. Moreover, returning to their daily life required timely psychosocial support, intervention, and treatment for COVID-19 infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Park, Lee, Lee, Lee, Kim, Kim, Oh, Ha, Hyun, Lee, Kim, Jeon, Kim and Sim.)

In this study, we investigated the relation of probiotic activity of Lacticaseibacillus rhamnosus strain GG (LGG) and expression of microRNA to immune response and longevity in Caenorhabditis elegans host model. First, we evaluated the survival rate of C. elegans due to LGG exposure and bacterial colonization in the intestine. Next, the expression of mRNA and miRNA was analyzed in C. elegans exposure to LGG for 24 h using microarray. After exposure to LGG to C. elegans , colonized LGG was observed in the intestines of C. elegans and induced to extend lifespan. Moreover, persistent LGG in the intestine significantly enhanced the resistance of C. elegans exposed to both pathogenic bacteria and prolonged the lifespan of C. elegans . Transcriptome analysis indicated that LGG affected the expression levels of genes related to the innate immune response and upregulated the abundance of genes in multiple pathways of C. elegans , including Wnt signaling, TGF-beta signaling and mitogen-activated protein kinase (MAPK) pathways. In addition, qRT-PCR analysis confirmed that the expression of antibacterial genes was increased by LGG. Moreover, as the expression of microRNA miR-34 and immune-related pathways increased by exposure to LGG, the lifespan of C. elegans increased. However, in the miR-34 mutant C. elegans , the lifespan by LGG did not increase, so it was determined that miR-34 indirectly affects immune-related pathways. There was no significant difference in the expression of PMK-1 for LGG exposure in miR-34 mutants, suggesting that miR-34 may regulate PMK-1. In conclusion, we suggest that exposure of LGG to C. elegans enhances lifespan and resistance to food-borne pathogen infection by stimulating miR-34 and indirectly promoting PMK-1 activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yun, Ryu, Kang, Lee, Yoo, Kim and Oh.)

Deer antler velvet is widely used in traditional medicine for its anti-aging, antioxidant, and immunity-enhancing effects. However, few studies have reported on the discovery of probiotic strains for deer antler fermentation to increase functional ingredient absorption. This study evaluated the ability of probiotic lactic acid bacteria to enhance the concentrations of bioactive molecules (e.g., sialic acid and gamma-aminobutyric acid [GABA]) in extracts of deer antler velvet. Seventeen strains of Lactobacillus spp. that were isolated from kimchi and infant feces, including L. sakei , L. rhamnosus , L. brevis , and L. plantarum , and those that improved the life span of Caenorhabditis elegans were selected for evaluation. Of the 17 strains, 2 ( L. rhamnosus LFR20-004 and L. sakei LFR20-007) were selected based on data showing that these strains increased both the sialic acid and GABA contents of deer antler extract after fermentation for 2 d and significantly improved the life span of C. elegans . Co-fermentation with both strains further increased the concentrations of sialic acid, GABA, and metabolites such as short-chain fatty acids and amino acids. We evaluated the biological effects of the fermented antler velvet (FAV) on the antibacterial immune response in C. elegans by assessing worm survival after pathogen infection. The survival of the C. elegans conditioned with FAV for 24 h was significantly higher compared with that of the control worm group fed only normal feed (non-pathogenic E. coli OP50) exposed to E. coli O157:H7, Salmonella typhi , and Listeria monocytogenes . To evaluate the protective effects of FAV on immune response, cyclophosphamide (Cy), an immune-suppressing agent was treated to in vitro and in vivo . We found that FAV significantly restored viability of mice splenocytes and immune promoting-related cytokines (interleukin [IL]-6, IL-10, inducible nitric oxide synthase [iNOS], interferon [IFN]-γ, and tumor necrosis factor [TNF]-α) were activated compared to non-fermented deer antlers. This finding indicated the protective effect of FAV against Cy-induced cell death and immunosuppressed mice. Taken together, our study suggests that immune-promoting antler velvet can be produced through fermentation using L. rhamnosus LFR20-004 and L. sakei LFR20-007., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2022 Korean Society of Animal Science and Technology.)

H 2 O 2 electrosynthesis is an emerging clean chemical technology, whose efficiency critically depends on the activity and selectivity of electrocatalysts for two-electron oxygen reduction reaction (2e - ORR). Here, we demonstrate that 2e - ORR activity of oxygen-doped carbons, which have been one of the most promising catalysts for this reaction, can be substantially influenced by the types and concentrations of cations in electrolytes. Heat-treated carbon comprising active oxygen functional groups exhibits cation-dependent 2e - ORR activity trends in alkaline media, following the order Cs + > K + > Li + . Importantly, an electrolyte with a high cation concentration (0.1 M KOH + 0.5 M KCl) afforded the highest 2e - ORR mass activity (250 ± 30 A g cat -1 at 0.70 V vs reversible hydrogen electrode) ever reported. We have established that the cation promotion effect correlates with cation-dependent electron-transfer kinetics, which regulates the rate-determining first electron transfer to O 2 .

In order to examine the association between plasma phytoestrogen concentration (genistein, daidzein, equol and enterolactone) and hypertension, we conducted a nested case-control study for 229 hypertension cases including 112 prehypertension and 159 healthy controls derived from the Korean Multi-center Cancer Cohort (KMCC). The concentration of plasma phytoestrogens was measured using time-resolved fluoroimmunoassay. We assessed the association between plasma phytoestrogens and hypertension using logistic regression models using odds ratio (OR) and 95% confidence interval (95%CI). The highest tertile of plasma equol and enterolactone concentration exhibited a significantly decreased risk of hypertension (equol, OR = 0.34, 95%CI 0.20-0.57; enterolactone, OR = 0.32, 95%CI 0.18-0.57), compared with the lowest tertile. Equol and enterolactone showed reduced ORs for prehypertension (the highest tertile relative to the lowest tertile, OR = 0.50, 95%CI 0.26-0.96; OR = 0.38, 95%CI 0.19-0.75, respectively) and hypertension (OR = 0.42, 95%CI 0.22-0.81; OR = 0.28, 95%CI 0.14-0.54, respectively). There was a stronger association in hypertension (the highest tertile relative to the lowest tertile in obesity vs. non-obesity; equol, OR = 0.06 vs. 0.63; enterolactone, OR = 0.07 vs. 0.46; both p -heterogeneity < 0.01). This study suggests that equol and enterolactone may contribute to prevent primarily prehypertension and hypertension, and control cardiovascular disease (CVD) based on the continuum of hypertension and CVD. Further study to assess hypertension risk based on useful biomarkers, including phytoestrogens, may contribute to primary prevention of hypertension.

Apoptotic cells generated during development and for tissue homeostasis are swiftly and continuously removed by phagocytes via a process called efferocytosis. Efficient efferocytosis can be achieved via transcriptional modulation in phagocytes that have engulfed apoptotic cells. However, such modulation and its effect on efferocytosis are not completely understood. Here, we report that phagocytes are recruited to apoptotic cells being cleared through the Mcp-1-Ccr2 axis, which facilitates clearance of apoptotic cells. We identified Mcp-1 as a modulated transcript using a microarray and found that Mcp-1 secretion was augmented in phagocytes engulfing apoptotic cells. This augmented Mcp-1 secretion was impaired by blocking phagolysosomal degradation of apoptotic cells. Conditioned medium from wild type (WT) phagocytes promoted cell migration, but that from Mcp-1 -/- phagocytes did not. In addition, blockade of Ccr2, the receptor for Mcp-1, abrogated cell migration to conditioned medium from phagocytes incubated with apoptotic cells. The intrinsic efferocytosis activity of Mcp-1 - / - and Ccr2 - / - phagocytes was unaltered, but clearance of apoptotic cells was less efficient in the peritoneum of Mcp-1 - / - and Ccr2 - / - mice than in that of WT mice because fewer Ccr2-positive phagocytes were recruited. Taken together, our findings demonstrate a mechanism by which not only apoptotic cells but also phagocytes induce chemoattraction to recruit phagocytes to sites where apoptotic cells are cleared for efficient efferocytosis.

Swift and continuous phagocytosis of apoptotic cells can be achieved by modulation of calcium flux in phagocytes. However, the molecular mechanism by which apoptotic cells modulate calcium flux in phagocytes is incompletely understood. Here, using biophysical, biochemical, pharmaceutical, and genetic approaches, we show that apoptotic cells induced the Orai1-STIM1 interaction, leading to store-operated calcium entry (SOCE) in phagocytes through the Mertk-phospholipase C (PLC) γ1-inositol 1,4,5-triphosphate receptor (IP 3 R) axis. Apoptotic cells induced calcium release from the endoplasmic reticulum, which led to the Orai1-STIM1 association and, consequently, SOCE in phagocytes. This association was attenuated by masking phosphatidylserine. In addition, the depletion of Mertk, which indirectly senses phosphatidylserine on apoptotic cells, reduced the phosphorylation levels of PLCγ1 and IP 3 R, resulting in attenuation of the Orai1-STIM1 interaction and inefficient SOCE upon apoptotic cell stimulation. Taken together, our observations uncover the mechanism of how phagocytes engulfing apoptotic cells elevate the calcium level.

Probiotics, as living microorganisms, exert health benefits to the host by alleviating excess inflammation through modulating the immune system and establishing intestinal homeostasis. In this study, we evaluated the probiotic characteristics and inflammation alleviatory effects of Bacillus amyloliquefaciens isolated from traditional Korean fermented foods. The strains withstood the acidic environment of the digestive process, extended the lifespan of Caenorhabditis elegans , and enhanced pmk-1 expression. However, only B . amyloliquefaciens SCGB1 could attach to C. elegans in the intestines, which enhanced their survival upon exposure to Escherichia coli O157:H7. We also investigated the anti-inflammatory effect of SCGB1 using the RAW264.7 macrophage stimulated with lipopolysaccharide. The strain treatment enhanced anti-inflammatory cytokine interleukin (IL)-10 secretion and downregulated proinflammatory cytokine IL-6 expression in vitro . Next, we used a dextran sulfate sodium (DSS)-induced colitis mouse model to investigate whether SCGB1 can ameliorate gut inflammation in vivo . Compared to those in the DSS-induced mice, histological damage and IL-6 cytokine levels were significantly reduced in SCGB1-fed mice. These results suggest that B. amyloliquefaciens SCGB1 as potential probiotics may have health-promoting effects by reduction of inflammatory responses.

Tim-4 promotes the engulfment of apoptotic cells or exogenous particles by securing them on phagocytes. It is unable to transduce signals by itself but helps other engulfment receptors sense and internalize them. However, the identity of the engulfment receptors collaborating with Tim-4 is still incompletely understood. In this study, we searched for a candidate transmembrane protein with a FN3 domain, important for interaction with Tim-4, in silico and investigated whether it indeed interacts with Tim-4 and is involved in Tim-4-mediated phagocytosis. We found that EphA2 containing a FN3 domain in the extracellular region interacted with Tim-4, which was mediated by the IgV domain of Tim-4 and the FN3 domain of EphA2. Nevertheless, we found that EphA2 expression failed to alter Tim-4-mediated phagocytosis of apoptotic cells or polystyrene beads. Taken together, our findings suggest that EphA2, a new Tim-4 interacting protein, may intervene in a Tim-4-mediated cellular event even if it is not phagocytosis of endogenous or exogenous particles and vice versa.

Increase in travel time, beyond a critical point, to emergency care may lead to a residential disparity in the outcome of patients with acute conditions. However, few studies have evaluated the evidence of travel time benchmarks in view of the association between travel time and outcome. Thus, this study aimed to establish the optimal hospital access time (OHAT) for emergency care in South Korea. We used nationwide healthcare claims data collected by the National Health Insurance System database of South Korea. Claims data of 445,548 patients who had visited emergency centers between January 1, 2006 and December 31, 2014 were analyzed. Travel time, by vehicle from the residence of the patient, to the emergency center was calculated. Thirteen emergency care-sensitive conditions (ECSCs) were selected by a multidisciplinary expert panel. The 30-day mortality after discharge was set as the outcome measure of emergency care. A change-point analysis was performed to identify the threshold where the mortality of ECSCs changed significantly. The differences in risk-adjusted mortality between patients living outside of OHAT and those living inside OHAT were evaluated. Five ECSCs showed a significant threshold where the mortality changed according to their OHAT. These were intracranial injury, acute myocardial infarction, other acute ischemic heart disease, fracture of the femur, and sepsis. The calculated OHAT were 71-80 min, 31-40 min, 70-80 min, 41-50 min, and 61-70 min, respectively. Those who lived outside the OHAT had higher risks of death, even after adjustment (adjusted OR: 1.04-7.21; 95% CI: 1.03-26.34). In conclusion, the OHAT for emergency care with no significant increase in mortality is in the 31-80 min range. Optimal travel time to hospital should be established by optimal time for outcomes, and not by geographic time, to resolve the disparities in geographical accessibility to emergency care., Competing Interests: The authors have declared that no competing interests exist.

We investigated the association between dietary micronutrient intakes and the risk of chronic kidney disease (CKD) in the Ansan-Ansung study of the Korean Genome and Epidemiologic Study (KoGES), a population-based prospective cohort study. Of 9079 cohort participants with a baseline estimate glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m 2 and a urine albumin to creatinine ratio (UACR) <300 mg/g and who were not diagnosed with CKD, we ascertained 1392 new CKD cases over 12 year follow-up periods. The risk of CKD according to dietary micronutrient intakes was presented using hazard ratios (HRs) and 95% confidence intervals (95% CIs) in a full multivariable Cox proportional hazard models, adjusted for multiple micronutrients and important clinico-epidemiological risk factors. Low dietary intakes of phosphorus (<400 mg/day), vitamin B2 (<0.7 mg/day) and high dietary intake of vitamin B6 (≥1.6 mg/day) and C (≥100 mg/day) were associated with an increased risk of CKD stage 3B and over, compared with the intake at recommended levels (HR = 6.78 [95%CI = 2.18-21.11]; HR = 2.90 [95%CI = 1.01-8.33]; HR = 2.71 [95%CI = 1.26-5.81]; HR = 1.83 [95%CI = 1.00-3.33], respectively). In the restricted population, excluding new CKD cases defined within 2 years, an additional association with low folate levels (<100 µg/day) in higher risk of CKD stage 3B and over was observed (HR = 6.72 [95%CI = 1.40-32.16]). None of the micronutrients showed a significant association with the risk of developing CKD stage 3A. Adequate intake of micronutrients may lower the risk of CKD stage 3B and over, suggesting that dietary guidelines are needed in the general population to prevent CKD.

Phosphatidylserine (PS), a negatively charged phospholipid exclusively located in the inner leaflet of the plasma membrane, is involved in various cellular processes such as blood coagulation, myoblast fusion, mammalian fertilization, and clearance of apoptotic cells. Proteins that specifically interact with PS must be identified to comprehensively understand the cellular processes involving PS. However, only a limited number of proteins are known to associate with PS. To identify PS-associating proteins, we performed a pulldown assay using streptavidin-coated magnetic beads on which biotin-linked PS was immobilized. Using this approach, we identified Hsd17b4, a peroxisomal protein, as a PS-associating protein. Hsd17b4 strongly associated with PS, but not with phosphatidylcholine or sphingomyelin, and the Scp-2-like domain of Hsd17b4 was responsible for this association. The association was disrupted by PS in liposomes, but not by free PS or the components of PS. In addition, translocation of PS to the outer leaflet of the plasma membrane enriched Hsd17b4 in peroxisomes. Collectively, this study suggests an unexpected role of PS as a regulator of the subcellular localization of Hsd17b4.

Hydroponic cultivation is revolutionizing agricultural crop production techniques all over the world owing to its minimal environmental footprint, enhanced pest control, and high crop yield. However, waste nutrient solutions (WNS) generated from hydroponic systems contain high concentrations of N and P; moreover, they are discharged into surface and subsurface environments, leading to eutrophication and subsequent ecosystem degradation. In this study, the nutrient concentrations in WNS from 10 hydroponic indoor tomato, capsicum, and strawberry farms (greenhouses) were monitored for up to six months. The concentrations of N and P in WNS discharged from these farms were 48.0-494.0 mg L -1 and 12.7-96.9 mg L -1 , respectively, which exceeded the Korean water quality guidelines (40.0 mg L -1 N and 4.0 mg L -1 P) for effluents. These concentrations were varied and dependent on the supplied nutrient concentrations, crop types, and growth stages. In general, the concentrations of N and P were in the following order: tomato > capsicum > strawberry. High N as NO 3 - and P as PO 4 3- but low organic C in WNS warrant subsequent treatment before discharge. Therefore, this study tested a pilot-scale sequencing batch reactor (SBR) system as a potential technology for WNS treatment. The SBR system had BOD, COD, nitrate, and phosphate removal efficiency of 100, 100, 89.5, and 99.8%, respectively. In addition, the SBR system removed other cations such as Ca 2+ , dissolved Fe, K + , Mg 2+ , and Na + and the removal efficiencies of those ions were 48, 67, 18, 14 and 15%, respectively. Lower methanol addition (0.63 mg L -1 ) and extended aeration (~30 min) improved SBR performance efficiency of C, N, and P removal. Thus, SBR showed significant promise as a treatment alternative to WNS pollutants originating from hydroponic systems., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to determine whether nasal septal deviation and concha bullosa affect the maxillary sinus volume, and whether this effect is associated with the prevalence of chronic sinusitis., Materials and Methods: This study retrospectively reviewed 209 paranasal sinus CT (PNS CT) images of patients with sinonasal symptoms from January 2017 to December 2018. The maxillary sinus volume was measured twice by a radiologist, and statistical analysis was performed using SAS 9.4., Results: Intersex comparison of the maxillary sinus volume (on left and right sides) revealed that the volume was significantly larger on both the sides ( p < 0.0001) in men compared with that in women. Concha bullosa was found to occur mainly in the concave cavity of the septal deviation ( p < 0.0001). No significant association was found between nasal septal deviation and maxillary sinusitis ( p = 0.8756) as well as between concha bullosa and maxillary sinusitis prevalence ( p = 0.3401) or maxillary sinus volume (both: p = 0.6289, Rt.: p = 0.9522, Lt.: p = 0.9201)., Conclusion: Although nasal septal deviation and the location of concha bullosa may affect each other, maxillary sinus volume and maxillary sinusitis were neither associated with nasal septal deviation nor concha bullosa., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2020 The Korean Society of Radiology.)

Calcium flux regulating intracellular calcium levels is essential and modulated for efficient efferocytosis. However, the molecular mechanism by which calcium flux is modulated during efferocytosis remains elusive. Here, we report that Orai1, a Crbn substrate, is upregulated via its attenuated interaction with Crbn during efferocytosis, which increases calcium influx into phagocytes and thereby promotes efferocytosis. We found that Crbn deficiency promoted phagocytosis of apoptotic cells, which resulted from facilitated phagocytic cup closure and was nullified by a CRAC channel inhibitor. In addition, Orai1 associated with Crbn, resulting in ubiquitination and proteasomal degradation of Orai1 and alteration of SOCE-mediated calcium influx. The association of Orai1 with Crbn was attenuated during efferocytosis, leading to reduced ubiquitination of Orai1 and consequently upregulation of Orai1 and calcium influx. Collectively, our study reveals a regulatory mechanism by which calcium influx is modulated by a Crbn-Orai1 axis to facilitate efferocytosis.