Search

Abstract 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.

The fairness & bias of narrow coverage of AI becomes another challenge for AI researchers. If a commercial AI trains with a biased dataset, there will be severe gender or racial fairness and bias issues. Since the researchers use primary language datasets to train AI, the broad audience cannot be satisfied if a novel LLM (Large Language Model) AI shows a knowledge or creativity limitation on their specific spoken language. Narrow coverage of the LLMs can lead the audience to misinterpretation and confusion if the service involves STT (Speech-To-Text). In this paper, to overcome this issue of data diversity, we propose the idea that the embedded, extracted features have captured semantic proximity information that can be useful to mitigate diversity issues. This project focused on the Korean language food dataset for STT services, where a narrow-trained A.I. is prone to show its limitations, such as lifestyle-related elements. To present our proof of concept, we trained a baseline model, GPT2, with the Korean Wikipedia dataset in 2022. Then, we employed DistilBERT and KoBERT for comparison. The extracted hidden_state_output features from each model were utilized to build feature-extraction-based text search engines. We used the same idea of Local Sensitive Hashing (LSH) but effectively located a similar hash by applying transposed weights. We also present conventional classification benchmarks for performance comparison using top-k measurements, times for training and memory & disc consumptions. In the discussion, we proposed that our idea can mitigate the diversity problem without re-training the model and tokenizer.

Glassy carbon (GC) microelectrodes have been successfully used for the detection of electroactive neurotransmitters such as dopamine and serotonin through voltammetry. However, non-electroactive neurotransmitters such as glutamate, lactate, and gamma-aminobutyric acid (GABA) are inherently unsuitable for detection through voltammetry techniques without functionalizing the surface of the microelectrodes. To this end, we present here the immobilization of the L-glutamate oxidase (GluOx) enzyme on the surface of GC microelectrodes to enable the catalysis of a chemical reaction between L-glutamate, oxygen, and water to produce H2O2, an electroactive byproduct that is readily detectable through voltammetry. This immobilization of GluOx on the surface of bare GC microelectrodes and the subsequent catalytic reduction in H2O2 through fast-scan cyclic voltammetry (FSCV) helped demonstrate the indirect in vitro detection of glutamate, a non-electroactive molecule, at concentrations as low as 10 nM. The functionalized microelectrodes formed part of a four-channel array of microelectrodes (30 μm × 60 μm) on a 1.6 cm long neural probe that was supported on a flexible polymer, with potential for in vivo applications. The types and strengths of the bond between the GC microelectrode surface and its functional groups, on one hand, and glutamate and the immobilized functionalization matrix, on the other hand, were investigated through molecular dynamic (MD) modeling and Fourier transform infrared spectroscopy (FTIR). Both MD modeling and FTIR demonstrated the presence of several covalent bonds in the form of C-O (carbon–oxygen polar covalent bond), C=O (carbonyl), C-H (alkenyl), N-H (hydrogen bond), C-N (carbon–nitrogen single bond), and C≡N (triple carbon–nitrogen bond). Further, penetration tests on an agarose hydrogel model confirmed that the probes are mechanically robust, with their penetrating forces being much lower than the fracture force of the probe material.

With the increasing use of unmanned aerial vehicles (UAVs) in various fields, achieving the precise localization of UAV images is crucial for enhancing their utility. Photogrammetry-based techniques, particularly bundle adjustment, serve as foundational methods for accurately determining the spatial coordinates of UAV images. The effectiveness of bundle adjustment is significantly influenced by the selection of input data, particularly the composition of overlapping image sets. The selection process of overlapping images significantly impacts both the accuracy of spatial coordinate determination and the computational efficiency of UAV image localization. Therefore, a strategic approach to this selection is crucial for optimizing the performance of bundle adjustment in UAV image processing. In this context, we propose an efficient methodology for determining overlapping image sets. The proposed method selects overlapping images based on image similarity, leveraging the complementary strengths of the bag of visual words and number of matches techniques. Essentially, our method achieves both high accuracy and high speed by utilizing a Bag of Visual Words for candidate selection and the number of matches for additional similarity assessment for overlapping image-set determination. We compared the performance of our proposed methodology with the conventional number of matches and bag-of-visual word-based methods for overlapping image-set determination. In the comparative evaluation, the proposed method demonstrated an average precision of 96%, comparable to that of the number of matches-based approach, while surpassing the 62% precision achieved by both bag-of-visual-word methods. Moreover, the processing time decreased by approximately 0.11 times compared with the number of matches-based methods, demonstrating relatively high efficiency. Furthermore, in the bundle adjustment results using image sets, the proposed method, along with the number of matches-based methods, showed reprojection error values of less than 1, indicating relatively high accuracy and contributing to the improvement in accuracy in estimating image positions.

Abstract 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.

Abstract 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.

Abstract 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.

Reviews left by consumers on e-commerce platforms provide crucial marketing information as they are a publicly available source of information providing insight into consumers’ thoughts and opinions. However, it is physically impossible to read hundreds of reviews per product. Therefore, algorithmically extracting the necessary insights from a large volume of review data can provide more advanced information while reducing time and costs. This study aims to automate the process of extracting related products, pros and cons of products, and trend forecasting from review data using clustering algorithms. The review dataset for pros and cons of products and related products was constructed by selecting 17 products on the Naver Shopping platform and crawling them and the product keyword and search volume dataset for trend forecasting was constructed by crawling the data from Itemscout and Naver datalab platform. Various clustering-based algorithms such as Deep Clustering Network, BERTopic, and a Transformer-based forecasting model were used to conduct the research. It is expected that this will allow for a more accurate understanding of consumer thoughts, which can be utilized in marketing for various products and services.

Nephrogenic diabetes insipidus, decreased ability to concentrate urine, with production of large amounts of urine, is caused by the refractory response of renal tubules to the action of antidiuretic hormone. This rare disorder, known as X-linked nephrogenic diabetes insipidus, is caused by a mutation in the AVPR2 gene. Because it is hereditary, most patients are male. This report highlights a case of nephrogenic diabetes insipidus in a 3-year 5-month-old female; upon presentation to the hospital, her symptoms included frequent urination and consumption of a significant amount of water, which had begun 2 years ago. The results of blood tests showed increased levels of serum antidiuretic hormone, and sellar magnetic resonance imaging showed no abnormality. The results of the water restriction test and the desmopressin administration test confirmed the diagnosis of nephrogenic diabetes insipidus showing a partial response to desmopressin. The results of genetic testing indicated the presence of an AVPR2 mutation, a heterozygous missense mutation (p.Val88Met), suggesting inheritance of X-linked nephrogenic diabetes insipidus. This report describes a significant case of symptomatic X-linked nephrogenic diabetes insipidus in a female patient who showed a partial response to desmopressin.

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.

Abstract 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.

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.

BackgroundsSome 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.MethodsWe 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.ResultsVitamin 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.ConclusionVitamin D deficiency is associated with significantly increased risk of severe CKD stage and renal event.

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).

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.

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.

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.

Calcium flux must be carefully controlled during the phagocytosis of apoptotic cells (efferocytosis), although how this occurs is not fully understood. Here, the authors show that the Cereblon E3 ligase regulates Orai1 degradation and subsequently SOCE-mediated calcium influx.

Background:COVID-19 patients experience various stressors during the quarantine period and after release from quarantine. However, stressors experienced during each period remain unclear.MethodsA 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.ResultsDuring 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.ConclusionsCOVID-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.

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.

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.

Owing to the developments in imaging modalities, imaging has become an essential element in the early evaluation of and decision-making algorithm for patients with trauma. In particular, CT technology has developed over the past decades, resulting in faster image acquisition and higher image quality. Currently, CT is the key imaging modality for triaging surgical and non-surgical treatment in patients with abdominal trauma and plays an important role in increasing the frequency and success rate of non-surgical treatment. Because rapid and accurate diagnosis of injury in patients with trauma can improve the patients’ prognosis, radiologists should be familiar with the imaging findings, especially the CT findings, in patients with trauma. In this article, the authors reviewed the considerations when performing CT for evaluating abdominal trauma. In addition, they described the important imaging findings and pitfalls when diagnosing blunt trauma in various intra-abdominal organs.

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.

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.

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.

Redox reaction is a difficult concept to teach and learn in chemistry courses at the secondary level. Although the significance of connecting macroscopic, molecular, and symbolic levels of representation has been emphasized in the chemistry education literature, most redox instruction involves only macroscopic and symbolic representations. To address this challenge, we designed a blended-reality immersive environment (BRE) model, which blends a traditional experiment with immersive technologies to make the molecular representations of redox reactions visible. The effectiveness of this model in supporting students’ learning of redox reactions was first reported in a different article. In this paper, we further explore the features of BRE that drive learning gains. Results from six high school classes in the U.S. with 351 students indicate that integrating the molecular representation through adding the chemical bonds concept facilitates students in making connections between macroscopic and symbolic levels to promote learning. Dynamic demonstrations of electrons’ interaction with particles support students’ understanding of the nature of redox reactions. This study shows the promise of adopting immersive technologies to present all three representations of chemistry concepts in one learning model.

OBJECTIVES We aimed to identify occupational groups at high-risk of coronavirus disease 2019 (COVID-19) infection in Korea, to estimate the number of such workers, and to examine the prevalence of protective resources by employment status. METHODS Based on the sixth Standard Occupational Classification codes, 2015 census data were linked with data from the fifth Korean Working Conditions Survey, which measured how frequently workers directly come into contact with people other than fellow employees in the workplace. RESULTS A total of 30 occupational groups, including 7 occupations from the healthcare and welfare sectors and 23 from other sectors, were classified as high-risk occupational groups involving frequent contact with people other than fellow employees in the workplace (more than half of the working hours). Approximately 1.4 million (women, 79.1%) and 10.7 million workers (46.3%) are employed in high-risk occupations. Occupations with a larger proportion of women are more likely to be at a high-risk of infection and are paid less. For wage-earners in high-risk occupations, protective resources to deal with COVID-19 (e.g., trade unions and health and safety committees) are less prevalent among temporary or daily workers than among those with permanent employment. CONCLUSIONS Given the large number of Koreans employed in high-risk occupations and inequalities within the working population, the workplace needs to be the key locus for governmental actions to control COVID-19, and special consideration for vulnerable workers is warranted.

Item response theory modeling articles from 83 years of Psychometrika are sorted based on the taxonomy by Thissen and Steinberg (1986). Results from 377 research and review articles indicate that the usual unidimensional parametric item response theory models for dichotomous items were employed in 51 per cent of the articles. The usual unidimensional parametric item response theory models for polytomous items were employed in 21 per cent of the articles. The multidimensional item response theory models were employed in 11 per cent of the articles. Item response theory models from the selected psychometric textbooks are also reviewed and contrasted with those from Psychometrika to explore the instructional use of various item response models. A new classification based on data types is proposed and discussed.

Abstract Background Previous studies have reported an association between dietary sodium intake and overweight/central obesity. However, dietary survey methods were prone to underestimate sodium intake. Therefore, this study investigated the associations of calculated 24-h urinary sodium excretion, an index of dietary sodium intake, with various obesity parameters including body mass index (BMI) and waist circumference (WC) in a population with a relatively high sodium intake. Methods A total of 16,250 adults (aged ≥19 years) and 1476 adolescents (aged 10-18 years), with available information on spot urine sodium levels and anthropometric measurements from the Korea National Health and Nutrition Examination Survey (KNHANES) were included in this study. We calculated 24-h urine sodium excretion levels from spot urine sodium levels using the Tanaka formula. Results In adults, those with high sodium excretion levels (≥ 3200 mg) showed increased odds of overweight and central obesity compared to those with low urinary sodium excretion level (

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 (IP3R) 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 IP3R, 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.

Abstract Ephexin4, a guanine nucleotide-exchange factor for RhoG, promotes engulfment of apoptotic cells and cancer cell migration in a RhoG-dependent manner, which is synergistically augmented by Elmo1, an Ephexin4-interacting protein. However, the underlying molecular mechanism remains elusive. Here, we report a mechanism by which Elmo1 cooperates with Ephexin4 to activate RhoG. We found that Ephexin4 activity was increased by elimination of its SH3 domain which intermolecularly interacts with the N20 region of Ephexin4. This interaction prevented RhoG from binding to Ephexin4 and thus inhibited RhoG activation. Moreover, we also found that Elmo1 associated with the SH3 domain as well as the N20 region and competed with the SH3 domain for binding to the N20 region, interrupting the interaction of the SH3 domain with the N20 region and thereby promoting RhoG binding to Ephexin4. In addition, the activity of Ephexin4 lacking the SH3 domain was comparable to that of Ephexin4 with Elmo1. Taken together, the data suggest that Elmo1 relieves the steric hindrance of Ephexin4 generated by the intermolecular interaction of the SH3 domain and makes Ephexin4 more accessible to RhoG.

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.

Apoptotic cells expressing phosphatidylserine (PS) on their cell surface are directly or indirectly recognized by phagocytes through PS-binding proteins. The PS-binding protein Tim-4 secures apoptotic cells to phagocytes to facilitate the engulfment of apoptotic cells. However, the molecular mechanism by which Tim-4 transduces signals to phagocytes during Tim-4-mediated efferocytosis is incompletely understood. Here, we report that Tim-4 collaborates with Mertk during efferocytosis through a biochemical interaction with Mertk. Proximal localization between the two proteins in phagocytes was observed by immunofluorescence and proximal ligation assays. Physical association between Tim-4 and Mertk, which was mediated by an interaction between the IgV domain of Tim-4 and the fibronectin type-III domain of Mertk, was also detected with immunoprecipitation. Furthermore, the effect of Mertk on Tim-4-mediated efferocytosis was abolished by GST-MertkFnIII, a soluble form of the fibronectin type-III domain of Mertk that disrupts the interaction between Tim-4 and Mertk. Taken together, the results from our study suggest that a physical interaction between Tim-4 and Mertk is necessary for Mertk to enhance efferocytosis mediated by Tim-4.

Retinal pigment epithelium (RPE) plays an essential role in maintaining retinal function, and its defect is thought to be critically implicated in various ocular disorders. This study demonstrated that the matricellular protein CCN5 was down-regulated in ARPE-19 cells treated with the pro-fibrotic agent transforming growth factor (TGF)-β. A recombinant adenovirus expressing CCN5 (AdCCN5) was used to restore the level of CCN5 in these cells. AdCCN5 prevented TGF-β-induced fibrotic changes, including disruption of tight junctions, up-regulation of mesenchymal marker proteins, and down-regulation of epithelial marker proteins. In addition, AdCCN5 prevented TGF-β-induced functional defects, including increased migratory activity and reduced phagocytic activity. Notably, AdCCN5 reversed morphological and functional defects pre-established by TGF-β prior to viral infection. The CCN5 level was down-regulated in RPE of 18-month-old Ccl2-/- mice, which exhibited retinal defects. Restoration of the CCN5 level via intravitreal injection of a recombinant adeno-associated virus expressing CCN5 (AAV9-CCN5) normalized the altered expression of mesenchymal, epithelial, and functional marker proteins, as assessed by western blotting and immunohistochemistry. Taken together, these data suggest that down-regulation of CCN5 is associated with fibrotic deformation of RPE under pathological conditions and that restoration of the CCN5 level effectively promotes recovery of deformed RPE.

Ephexin4 is a guanine nucleotide-exchange factor (GEF) for RhoG and is involved in various RhoG-related cellular processes such as phagocytosis of apoptotic cells and migration of cancer cells. Ephexin4 forms an oligomer via an intermolecular interaction, and its GEF activity is increased in the presence of Elmo, an Ephexin4-interacting protein. However, it is uncertain if and how Ephexin4 is autoinhibited. Here, using an Ephexin4 mutant that abrogated the intermolecular interaction, we report that this interaction impeded binding of RhoG to Ephexin4 and thus inhibited RhoG activation. Mutation of the glutamate residue at position 295, which is a highly conserved residue located in the region of Ephexin4 required for the intermolecular interaction, to alanine (Ephexin4E295A) disrupted the intermolecular interaction and increased binding of RhoG, resulting in augmented RhoG activation. In addition, phagocytosis of apoptotic cells and formation of membrane ruffles were increased more by expression of Ephexin4E295A than by expression of wild-type Ephexin4. Taken together, our data suggest that Ephexin4 is autoinhibited through its intermolecular interaction, which impedes binding of RhoG.

This study aimed to develop a specialized rule-based AI chatbot tailored for a sixth-grade optics unit and to evaluate the impact of the implementation of the chatbot on students' cognitive and affective outcomes related to science within the classroom setting. Specifically, this study explored how factors such as gender and achievement levels have an impact on student attitudes. The development of the rule-based chatbot adhered to the network-based instructional systems design framework, which involves the application of the analyze, design, develop, implement, and evaluate model to the e-learning design and development process. The participants were 192 sixth-grade students, with 81 in the experimental group and 111 in the control group. The results revealed a positive effect on students' science achievement and interest, with a particularly significant impact on those with lower achievement levels. Notably, the chatbot played a crucial role in elevating the interest of female students in science. These findings highlight the need for continued research into the integration of rule-based AI chatbots in science education.

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. [ABSTRACT FROM AUTHOR]