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Abstract Background We recently reported that the dopamine (DA) analogue CA140 modulates neuroinflammatory responses in lipopolysaccharide-injected wild-type (WT) mice and in 3-month-old 5xFAD mice, a model of Alzheimer’s disease (AD). However, the effects of CA140 on Aβ/tau pathology and synaptic/cognitive function and its molecular mechanisms of action are unknown. Methods To investigate the effects of CA140 on cognitive and synaptic function and AD pathology, 3-month-old WT mice or 8-month-old (aged) 5xFAD mice were injected with vehicle (10% DMSO) or CA140 (30 mg/kg, i.p.) daily for 10, 14, or 17 days. Behavioral tests, ELISA, electrophysiology, RNA sequencing, real-time PCR, Golgi staining, immunofluorescence staining, and western blotting were conducted. Results In aged 5xFAD mice, a model of AD pathology, CA140 treatment significantly reduced Aβ/tau fibrillation, Aβ plaque number, tau hyperphosphorylation, and neuroinflammation by inhibiting NLRP3 activation. In addition, CA140 treatment downregulated the expression of cxcl10, a marker of AD-associated reactive astrocytes (RAs), and c1qa, a marker of the interaction of RAs with disease-associated microglia (DAMs) in 5xFAD mice. CA140 treatment also suppressed the mRNA levels of s100β and cxcl10, markers of AD-associated RAs, in primary astrocytes from 5xFAD mice. In primary microglial cells from 5xFAD mice, CA140 treatment increased the mRNA levels of markers of homeostatic microglia (cx3cr1 and p2ry12) and decreased the mRNA levels of a marker of proliferative region-associated microglia (gpnmb) and a marker of lipid-droplet-accumulating microglia (cln3). Importantly, CA140 treatment rescued scopolamine (SCO)-mediated deficits in long-term memory, dendritic spine number, and LTP impairment. In aged 5xFAD mice, these effects of CA140 treatment on cognitive/synaptic function and AD pathology were regulated by dopamine D1 receptor (DRD1)/Elk1 signaling. In primary hippocampal neurons and WT mice, CA140 treatment promoted long-term memory and dendritic spine formation via effects on DRD1/CaMKIIα and/or ERK signaling. Conclusions Our results indicate that CA140 improves neuronal/synaptic/cognitive function and ameliorates Aβ/tau pathology and neuroinflammation by modulating DRD1 signaling in primary hippocampal neurons, primary astrocytes/microglia, WT mice, and aged 5xFAD mice.

Objectives Between July 2, 2021, and September 20, 2022, a Mycobacterium bovis outbreak occurred among exhibition animals at a zoo in the Republic of Korea. This study was conducted to assess the likelihood of M. bovis transmission to human contacts through a contact investigation and to implement preventive treatment for latent tuberculosis infection (LTBI). Methods In this descriptive study, the Korea Disease Control and Prevention Agency conducted a contact investigation, which included interviews, interferon-gamma release assay (IGRA) tests, and chest X-rays. Contacts underwent IGRA testing on 2 occasions: initial testing of 29 contacts (15 in the first cluster of infection and 14 in the second cluster) and follow-up testing of the 15 contacts in the first cluster. Results The study included 29 participants, 18 of whom were male (62.1%) and 11 female (37.9%). The mean participant age was 37.3 years (standard deviation, 9.6 years). In the initial IGRA tests, 6 of the 29 participants tested positive, indicating a prevalence of 20.7%. Following prolonged exposure, 1 additional positive case was detected in follow-up testing, raising the prevalence of LTBI to 24.1%. None of the contacts had active tuberculosis. Among the 7 individuals with positive results, 2 (28.6%) underwent treatment for LTBI. Conclusion This study faced challenges in confirming the transmission of M. bovis infection from infected animals to humans in the Republic of Korea. Nevertheless, adopting a One Health approach necessitates the implementation of surveillance systems and infection control protocols, particularly for occupational groups at high risk of exposure.

Abstract Background General anesthesia is often necessary for dental treatment of outpatients with mental disabilities. Rapid recovery and effective management of postoperative nausea and vomiting (PONV) are critical for outpatients. This study aimed to investigate the effect of transitioning from propofol to remimazolam with flumazenil reversal administered toward the end of surgery during propofol-based total intravenous anesthesia (TIVA) on recovery. Methods Adults with mental disabilities scheduled to undergo dental treatment were randomly assigned to receive either propofol-based TIVA (Group P) or propofol-remimazolam-based TIVA with flumazenil reversal (Group PR). Propofol was replaced with remimazolam 1 h before the end of surgery in Group PR; moreover, 0.5 mg of flumazenil was administered after the neuromuscular blockade reversal agent. The primary outcome was the duration of stay in the post-anesthesia care unit (PACU). The secondary outcomes included time to eye-opening, time to extubation, occurrence of PONV, and quality of recovery. Results Fifty-four patients were included in this study. The duration of stay in the PACU in Group PR was significantly shorter than that in Group P (mean difference, 8.7 min; confidence interval [95% CI], 3.3–14.2; P = 0.002). Group PR exhibited a shorter time to eye opening (mean difference, 5.4 min; 95% CI, 3.3–8.1; P

Objective: To evaluate the relationship between dietary polyamine intake and all-cause and cardiovascular disease (CVD)-related mortality in Korean population. Methods: A total of 37,715 participants were included in a population-based cohort study. Dietary polyamine intake (µmol/d) were calculated using the average spermidine and spermine content (µmol/g) and daily consumed food components (mg/d) from 12 food groups. Cox proportional hazards examined associations between dietary polyamine and all-cause and CVD-related mortality. Results: Among the participants, 2,080 all-cause and 483 CVD-related deaths occurred. The lowest risk of all-cause and CVD-related mortality was found in the highest tertile of fruit, vegetables, legume, nut and seafood-derived spermidine and spermine intake, after adjusting covariates. The relationship between dietary polyamine intake and all-cause and CVD-related mortality was more pronounced in men and older individuals than in their counterparts. Conclusions: Higher intake of mediterranean-like diet derived polyamine was associated with lower CVD-related and all-cause mortality in Korean adults.

Background: Protease-activated receptor 1 (PAR1) is expressed in human platelets and can be activated by low concentrations of thrombin. Vorapaxar, a selective antagonist of PAR1, inhibits thrombin-induced calcium mobilization in human platelet, which is associated with an increased risk of bleeding. Conversely, the administration of a positive allosteric modulator (PAM) of PAR1 may pose a substantial risk of thrombosis due to inducing excessive platelet activation. In this study, we discovered a novel PAM of PAR1 and investigated the effect of enhanced PAR1 activation by PAM of PAR1 on platelet activation.Methods: To find PAMs of PAR1, a cell-based screen was performed in HT29 cells, and finally, gestodene, an oral contraceptive drug (OC), was identified as a novel PAM of PAR1. The mechanism of action of gestodene and its effects on platelet activation were investigated in human megakaryocytic leukemia cell line MEG-01 cells and human platelet.Results: Gestodene enhanced both thrombin- and PAR1-activating peptide (AP)-induced intracellular calcium levels in a dose-dependent manner without altering PAR2 and PAR4 activity. Gestodene significantly increased PAR1-AP-induced internalization of PAR1 and phosphorylation of ERK1/2, and the enhancing effects were significantly blocked by vorapaxar. Furthermore, gestodene potently increased PAR1-AP induced morphological changes in MEG-01 cells. Remarkably, in human blood, gestodene exerted a robust augmentation of PAR1-AP-induced platelet aggregation, and vorapaxar effectively attenuated the gestodene-induced enhancement of platelet aggregation mediated by PAR1.Conclusion: Gestodene is a selective PAM of PAR1 and suggest one possible mechanism for the increased risk of venous thromboembolism associated with OCs containing gestodene.

Patients with inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), often have concomitant mental disorders such as depression and anxiety. Therefore, a bidirectional approach involving the gut and brain axes is necessary for the prevention and treatment thereof. In this study, we explored the potential of Poncirus trifoliata extract (PT), traditionally known for its neuroprotective effects against gastrointestinal diseases, as a natural treatment agent for IBD in a dextran sulfate sodium (DSS)-induced colitis model. Oral administration of PT ameliorated weight loss and inflammatory responses in mice with DSS-induced colitis. Furthermore, PT treatment effectively restored the colon length and ameliorated enterocyte death by inhibiting DSS-induced reactive oxygen species (ROS)-mediated necroptosis. The main bioactive components of PT, poncirin and naringin, confirmed using ultra-performance liquid chromatography-quadrupole time-of-flight (UPLC-qTOF), can be utilized to regulate necroptosis. The antidepressant-like effects of PT were confirmed using open field test (OFT) and tail suspension test (TST). PT treatment also restored vascular endothelial cell integrity in the hippocampus. In the Cornu Ammonis 1 (CA1) and dentate gyrus (DG) regions of the hippocampus, PT controlled the neuroinflammatory responses of proliferated microglia. In conclusion, PT, which contains high levels of poncirin and naringin, has potential as a bidirectional therapeutic agent that can simultaneously improve IBD-associated intestinal and mental disorders.

Chromium (III) oxide nanoparticles (NPs) have a wide range of industrial applications, particularly in the production of lithium-ion batteries; however, the toxicity of these NPs has not been studied extensively. The phytotoxicity and genotoxicity of chromium (III) oxide NPs have not been assessed, and only one study reported their cytotoxicity, underscoring the need to perform comprehensive toxicity studies on these NPs. Here, we showed that chromium (III) oxide NPs had no effect on germination rates, and only decreased root elongation in L. sativa as determined by root elongation and biomass studies. Chromium (III) oxide NPs had no phytotoxic effects under environmental realistic conditions, whereas they had cytotoxic effects against HK-2 and Raw 264.7 cells in vitro. However, the cytotoxicity of chromium (III) oxide NPs did not occur under environmentally realistic conditions. The genotoxicity of chromium (III) oxide NPs was not significant in HK-2 cells, suggesting that the potential environmental cytotoxicity of chromium (III) oxide NPs is limited. This study proposes comprehensive phytotoxicity, cytotoxicity, and genotoxicity testing tools that would be easy, safe, and effective for evaluating the toxicity of NPs. This integrated testing system could be an accurate and stable method for evaluating the toxicity of other nanomaterials.

Abstract This study aimed to address the diversity issue in fashion design education by developing two prototypes for Inclusive Fashion Design (IFD) education. The prototypes were constructed based on the 3C3R model of Project-Based Learning (PBL) and incorporated the Persona/Scenario (P/S) toolkit for IFD. Additionally, the study examined the effectiveness of the FEA (Function, Expressive, and Aesthetics) self-checklist and the P/S toolkit in the IFD process. The experiments involved two design instructors, two teaching assistants, and 12 senior-level students divided into four teams. Thematic analysis was conducted on the interview data collected from the participants. The results revealed that FEA factors were highly considered in both education prototypes, regardless of the presence of the P/S toolkit. Maintaining consistency of the IFD concept throughout each stage of the process was found to be crucial, and the use of the P/S toolkit played a significant role in achieving this consistency. Team communication emerged as an essential factor in IFD education, as team collaboration using the P/S toolkit triggered diverse perspectives on targets, facilitated design expansion, and extended individual competences. Overall, this study contributes to the understanding of the diversity issue in fashion design education and promotes the adoption of the IFD education methodology, emphasizing the significance of consistent concept development, effective toolkits, and team collaboration in achieving inclusive design practices.

Abstract Efficient pathogen enrichment and nucleic acid isolation are critical for accurate and sensitive diagnosis of infectious diseases, especially those with low pathogen levels. Our study introduces a biporous silica nanofilms-embedded sample preparation chip for pathogen and nucleic acid enrichment/isolation. This chip features unique biporous nanostructures comprising large and small pore layers. Computational simulations confirm that these nanostructures enhance the surface area and promote the formation of nanovortex, resulting in improved capture efficiency. Notably, the chip demonstrates a 100-fold lower limit of detection compared to conventional methods used for nucleic acid detection. Clinical validations using patient samples corroborate the superior sensitivity of the chip when combined with the luminescence resonance energy transfer assay. The enhanced sample preparation efficiency of the chip, along with the facile and straightforward synthesis of the biporous nanostructures, offers a promising solution for polymer chain reaction-free detection of nucleic acids.

Objective: EuCorVac-19 (ECV-19), an adjuvanted liposome-displayed receptor binding domain (RBD) COVID-19 vaccine, previously reported interim Phase 2 trial results showing induction of neutralizing antibodies 3 weeks after prime-boost immunization. The objective of this study was to determine the longer-term antibody response of the vaccine. Methods: To assess immunogenicity 6 and 12 months after vaccination, participants in the Phase 2 trial (NCT04783311) were excluded if they: 1) withdrew, 2) reported COVID-19 infection or additional vaccination, or 3) exhibited increasing Spike (S) antibodies (representing possible non-reported infection). Following exclusions, of the 197 initial subjects, anti-S IgG antibodies and neutralizing antibodies were further assessed in 124 subjects at the 6-month timepoint, and 36 subjects at the 12-month timepoint. Results: Median anti-S antibody half-life was 52 days (interquartile range [IQR]:42-70), in the “early” period from 3 weeks to 6 months, and 130 days (IQR:97-169) in the “late” period from 6 to 12 months. There was a negative correlation between initial antibody titer and half-life. Anti-S and neutralizing antibody responses were correlated. Neutralizing antibody responses showed longer half-lives; the early period had a median half-life of 120 days (IQR:81-207), and the late period had a median half-life of 214 days (IQR:140-550). Conclusion: These data establish antibody durability of ECV-19, using a framework to analyze COVID-19 vaccine-induced antibodies during periods of high infection.

Summary: Empathy, crucial for social interaction, is impaired across various neuropsychiatric conditions. However, the genetic and neural underpinnings of empathy variability remain elusive. By combining forward genetic mapping with transcriptome analysis, we discover that aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) is a key driver modulating observational fear, a basic form of affective empathy. Disrupted ARNT2 expression in the anterior cingulate cortex (ACC) reduces affect sharing in mice. Specifically, selective ARNT2 ablation in somatostatin (SST)-expressing interneurons leads to decreased pyramidal cell excitability, increased spontaneous firing, aberrant Ca2+ dynamics, and disrupted theta oscillations in the ACC, resulting in reduced vicarious freezing. We further demonstrate that ARNT2-expressing SST interneurons govern affective state discrimination, uncovering a potential mechanism by which ARNT2 polymorphisms associate with emotion recognition in humans. Our findings advance our understanding of the molecular mechanism controlling empathic capacity and highlight the neural substrates underlying social affective dysfunctions in psychiatric disorders.

Abstract An important cause of stunting is limited consumption of complementary foods, in terms of both quantities and nutrients. Although existing studies show a positive association between fathers' engagement and children's diet, programmes designed to improve complementary feeding practices often only target mothers. In response to this, maternal behaviour change communication (BCC), paternal BCC and food voucher programmes were designed and implemented in Ethiopia using a clustered randomized controlled trial design. The paternal BCC programme included gender‐equal messages to increase fathers' participation in childcare, household labour and decision making. The research reported in this paper is an examination of the BCC programmes, characterizing the behavioural, normative and control beliefs of both mothers and fathers in BCC households compared to those in control households. In this study, a total of 40 participants were included, with 13 mother–father pairs in the BCC + food voucher group, and seven pairs in the control group. Each participant was interviewed separately. We found that BCC mothers showed more gender‐equal tendencies than the control mothers despite being more rural in location. By contrast, the beliefs of BCC and control fathers were similar overall, suggesting men are more resistant to gender‐equal BCC. More work is needed to develop and test effective methods for changing fathers' beliefs and practices.

BackgroundThe in vitro and in vivo anti-inflammatory and anti-oxidative effects of an amino acid (AA) blend (tryptophan, threonine, and methionine) in pigs.ObjectiveThis study aimed to evaluate the in vitro anti-inflammatory and anti-oxidative effects of an AA blend on intestinal porcine epithelial cells (IPEC-J2) and the in vivo anti-inflammatory and anti-oxidative effects in pigs experimentally challenged with Salmonella Typhimurium.MethodsIPEC-J2 were pretreated with an AA blend for 25 h and then treated with lipopolysaccharide (LPS), deoxynivalenol (DON), or H2O2 for in vitro evaluation. A controlled standard diet supplemented with 0.3% of the AA blend was orally fed to the treated group pigs for 14 days, beginning at 21 days of age. At the end of the feeding period, pigs were orally inoculated with Salmonella Typhimurium.ResultsPre-treatment with the AA blend reduced LPS/DON-induced interleukin (IL)-8 mRNA as a measurement of the anti-inflammatory effect and H2O2-induced reactive oxygen species (ROS) as a measurement of the anti-oxidative effect on IPEC-J2. Feeding with an AA blend resulted in a reduction of proinflammatory (tumor necrosis factor-α, IL-6, and IL-8) cytokine levels, while treated pigs experienced an increase in anti-inflammatory IL-10 cytokine in their sera. The addition of an AA blend-supplemented pig feed resulted in significantly lower Salmonella-induced cecal lesion scores compared to untreated pigs.DiscussionSupplementation of feed with an AA blend reduced intestinal inflammation and pathology in pigs and may be applied for the control of Salmonella Typhimurium infection, as demonstrated in this study.

Abstract To assess the prevalence and abundance of antibiotic resistance genes in human and livestock gut microbiomes, 87 humans (healthy individuals and patients with Clostridioides difficile infection (CDI)) and 108 livestock (swine, cattle, and chickens) were enrolled. Gut microbiomes and fluoroquinolone-resistant Escherichia coli isolates were sequenced, and mobile genetic elements adjacent to the β-lactamase (bla) and transferable quinolone resistance (qnr) genes were compared using metagenomic contigs. Each group of humans and livestock exhibited distinctive microbiota and resistome compositions in the gut. Concerning the resistome of bla and qnr, the prevalence rates between chickens and patients with CDI were the most similar (R2 = 0.46); bla TEM, bla OXA, bla CTX-M, and qnrS were highly prevalent in both groups. According to genomic and phylogenetic analyses, bla CTX-M and bla OXA expressed lineage specificity to either humans or livestock, while qnrS and bla TEM displayed a shared lineage between humans and livestock. A qnrS1 mobilome comprising five genes, including two recombinases, a transposase, and a plasmid gene, is commonly found in human and chicken gut microbiomes. Humans and chickens showed the most similar gut resistomes to β-lactams and quinolones. QnrS and bla TEM displayed especially strong co-occurrence between the guts of humans and livestock.

Abstract Background Using reliable measurement tools is becoming increasingly important as the prevalence of obesity among children increases in Korea. The Dutch Eating Behavior Questionnaire for Children (DEBQ-C) measures three eating behaviors associated with overeating. This study aims to validate the DEBQ-C for use among Korean children and adolescents with high body weight. It examines the psychometric features of the Korean translation of the DEBQ-C and investigates the relationship between the subscale scores of the DEBQ-C and the weight status of participants (categorized into overweight, obese, and morbidly obese). Methods A total of 233 children and adolescents (mean age: 11.4 ± 1.6 years) completed the questionnaire. The study verified the factor structure of the DEBQ-C using confirmatory factor analysis (CFA) and estimated its internal consistency with Cronbach’s alpha. For convergent validity, it employed Pearson’s correlation coefficient to assess relationships between the three eating behaviors of the DEBQ-C and the number of food addiction symptoms of the Yale Food Addiction Scale for Children (YFAS-C). Lastly, it examined the relationship between DEBQ-C scores and weight status via multinomial logistic regression analysis. Results The three-factor model demonstrated goodness-of-fit (χ2 = 253, df = 167, χ2/df = 1.515, p

The human respiratory and circulatory systems collaborate intricately to ensure oxygen delivery to all cells, which is vital for ATP production and maintaining physiological functions and structures. During limited oxygen availability, hypoxia-inducible factors (HIFs) are stabilized and play a fundamental role in maintaining cellular processes for hypoxia adaptation. First discovered during investigations of erythropoietin production regulation, HIFs influence physiological and pathological processes, including development, inflammation, wound healing, and cancer. HIFs promote extracellular adenosine signaling by enhancing adenosine generation and receptor signaling, representing an endogenous feedback mechanism that curbs excessive inflammation, supports injury resolution, and enhances hypoxia tolerance. This is especially important for conditions that involve tissue hypoxia, such as acute respiratory distress syndrome (ARDS), which globally poses significant health challenges without specific treatment options. Consequently, pharmacological strategies to amplify HIF-mediated adenosine production and receptor signaling are of great importance.

In the human brain, attention plays a crucial role in encoding information into memory. Therefore, focused attention during encoding enhances the likelihood of information being effectively encoded and stored in memory. This phenomenon is creatively replicated in our proposed synaptic devices, which regulate the forgetting curves by manipulating the gate voltage. Thus, the proposed transistor devices separate long-term memory from long-lasting memory. TiO2-based synaptic transistors are used to replicate brain functions, from vision processing to memory retention. The photosensitive nature of TiO2 enables the utilization of both photo- and electric stimuli. The electrical properties of the synaptic devices induced by photostimulation replicate the human-vision process, while those elicited by electric stimulation simulate memory-retention capabilities. By applying a shallow trap with a short lifetime, light stimulation can be utilized to mimic the effects of short-term memory. A deep trap with a long lifetime is employed in electrical memory to replicate the phenomena associated with persisting memory. A simulation of the MNIST recognition of an artificial neural network constructed with the measured synaptic characteristics exhibit an accuracy rate of 92.96%, which indicates that the proposed device can be successfully incorporated into neuromorphic devices.

Abstract Red blood cell (RBC) generation from human pluripotent stem cells (PSCs) offers potential for innovative cell therapy in regenerative medicine as well as developmental studies. Ex vivo erythropoiesis from PSCs is currently limited by the low efficiency of functional RBCs with β-globin expression in culture systems. During induction of β-globin expression, the absence of a physiological microenvironment, such as a bone marrow niche, may impair cell maturation and lineage specification. Here, we describe a simple and reproducible culture system that can be used to generate erythroblasts with β-globin expression. We prepared a two-dimensional defined culture with ferric citrate treatment based on definitive hemogenic endothelium (HE). Floating erythroblasts derived from HE cells were primarily CD45+CD71+CD235a+ cells, and their number increased remarkably upon Fe treatment. Upon maturation, the erythroblasts cultured in the presence of ferric citrate showed high transcriptional levels of β-globin and enrichment of genes associated with heme synthesis and cell cycle regulation, indicating functionality. The rapid maturation of these erythroblasts into RBCs was observed when injected in vivo, suggesting the development of RBCs that were ready to grow. Hence, induction of β-globin expression may be explained by the effects of ferric citrate that promote cell maturation by binding with soluble transferrin and entering the cells. Taken together, upon treatment with Fe, erythroblasts showed advanced maturity with a high transcription of β-globin. These findings can help devise a stable protocol for the generation of clinically applicable RBCs.

Anoctamin1 (ANO1), a calcium-activated chloride channel, is overexpressed in a variety of cancer cells, including prostate cancer, and is involved in cancer cell proliferation, migration, and invasion. Inhibition of ANO1 in these cancer cells exhibits anticancer effects. In this study, we conducted a screening to identify novel ANO1 inhibitors with anticancer effects using PC-3 human prostate carcinoma cells. Screening of 2978 approved and investigational drugs revealed that hemin is a novel ANO1 inhibitor with an IC50 value of 0.45 μM. Notably, hemin had no significant effect on intracellular calcium signaling and cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic AMP (cAMP)-regulated chloride channel, and it showed a weak inhibitory effect on ANO2 at 3 μM, a concentration that completely inhibits ANO1. Interestingly, hemin also significantly decreased ANO1 protein levels and strongly inhibited the cell proliferation and migration of PC-3 cells in an ANO1-dependent manner. Furthermore, it strongly induced caspase-3 activation, PARP degradation, and apoptosis in PC-3 cells. These findings suggest that hemin possesses anticancer properties via ANO1 inhibition and could be considered for development as a novel treatment for prostate cancer.

The impact of microplastics (MPs) on the metabolic functions of the liver is currently unclear and not completely understood. To investigate the effects of the administration of MPs on the hepatic metabolism of normal and obese mice, alterations in the lipid, glucose (Glu), and amino acid regulation pathways were analyzed in the liver and adipose tissues of C57BL/6Korl (wild type, WT) or C57BL/6-Lepem1hwl/Korl mice (leptin knockout, Lep KO) orally administered polystyrene (PS) MPs for 9 weeks. Significant alterations in the lipid accumulation, adipogenesis, lipogenesis, and lipolysis pathways were detected in the liver tissue of MP-treated WT and Lep KO mice compared to the vehicle-treated group. These alterations in their liver tissues were accompanied by an upregulation of the serum lipid profile, as well as alterations in the adipogenesis, lipogenesis, and lipolysis pathways in the adipose tissues of MP-treated WT and Lep KO mice. Specifically, the level of leptin was increased in the adipose tissues of MP-treated WT mice without any change in their food intake. Also, MP-induced disruptions in the glycogenolysis, Glu transporter type 4 (GLUT4)-5′ AMP-activated protein kinase (AMPK) signaling pathway, levels of lipid intermediates, and the insulin resistance of the liver tissues of WT and Lep KO mice were observed. Furthermore, the levels of seven endogenous metabolites were remarkably changed in the serum of WT and Lep KO mice after MP administrations. Finally, the impact of the MP administration observed in both types of mice was further verified in differentiated 3T3-L1 adipocytes and HepG2 cells. Thus, these results suggest that the oral administration of MPs for 9 weeks may be associated with the disruption of lipid, Glu, and amino acid metabolism in the liver tissue of obese WT and Lep KO mice.

The role of senior citizen centers is becoming more important, with a greater emphasis placed on ensuring that these establishments facilitate leisure and communication for older adults. These developments are taking place as population aging has now become an irreversible global trend. However, there is still a lack of systematic research on predicting the distribution density of senior citizen centers based on physical factors in urban planning. Therefore, this study set each administrative district in Busan as a unit and investigated physical factors affecting the distribution density of senior citizen centers around small apartment complexes to validate their effectiveness. First, the spatial hierarchy of each administrative district in Busan was examined. The city was divided into administrative districts while focusing on the distribution density of senior citizen centers (the dependent variable) around small apartment complexes where older adults live (within a 500 m radius). The spatial accessibility of senior citizen centers and the number of apartments in each administrative district were set as independent variables. This selection was made to verify the effectiveness of the physical factors by conducting an independent sample t-test, normality test, Friedman test, and two-way ANOVA. The chief findings of this study are as follows. (1) The spatial awareness of each administrative district was low, and there were large disparities in the land development density relative to the spatial scale of the administrative districts. (2) Regarding the physical factors affecting the distribution density of senior citizen centers, the spatial accessibility of senior residences was more significant than the number of small apartment complexes nearby. (3) Personal and social factors may have indirectly influenced the distribution density of senior citizen centers more than physical factors, depending on the type of house in which the older adults live. The findings will provide a theoretical basis for determining the location and distribution density of senior citizen centers in urban planning considering physical factors, as well as serve as a reference for public policy decisions related to the allocation of such centers in the future.

Abstract This study analyzed HGA and SFTS in patients with suspected tick-borne infection by focusing on key differences that clinicians can easily recognize. A retrospective analysis was performed on confirmed patients with HGA or SFTS in 21 Korean hospitals from 2013 to 2020. A scoring system was developed by multivariate regression analysis and accuracy assessment of clinically easily discriminable parameters was performed. The multivariate logistic regression analysis revealed that sex (especially male sex) (odds ratio [OR] 11.45, P = 0.012), neutropenia ( 1) in a 5-point scoring system (0–4 points) was analyzed to evaluate the accuracy of differentiation between HGA and SFTS. The system showed 94.5% sensitivity, 92.6% specificity, and an area under the receiver-operating characteristic curve of 0.971 (0.949–0.9). Where HGA and SFTS are endemic, the scoring system based on these four parameters such as sex, neutrophil count, activated partial thromboplastin time, and C-reactive protein concentration will facilitate the differential diagnosis of HGA and SFTS in the emergency room in patients with suspected tick-borne infectious diseases.

Abstract The beginning of human immunodeficiency virus (HIV) infection treatment depends on various factors, which are significantly correlated with the initial CD4 cell number. However, a covariate correlation between these factors may not reflect the correct outcome variable. Thus, we evaluated the effects of a combination of fixed factors (reduced dimensions), which determine when to start treatment for the first time, on short-term outcome, long-term outcome, and survival, considering correlations between factors. Multiple correspondence analysis was performed on variables obtained from 925 patients who participated in a Korean HIV/acquired immunodeficiency syndrome cohort study (2006–2017). Five reduced dimension groups were derived according to clinical data, viral load, CD4 cell count at diagnosis, initial antiretroviral therapy, and others. The dimension group with high initial viral loads (55,000 copies/mL) and low CD4 cell counts ( 350 cells/mm3) that did not require immediate treatment according to previous guidelines had a higher failure rate for long-term relative CD4 recovery. Our results highlight the importance of early diagnosis and treatment to positively influence long-term disease outcomes, even if the initial immune status is poor, given the patient’s combination of early diagnostic symptoms.

To overcome the limitation of conventional cancer treatments, photodynamic therapy (PDT) has been introduced as another treatment option. PDT provides a non-invasive, non-surgical way with reduced toxicity. To improve the antitumor efficacy of PDT, we synthesized a novel photosensitizer, a 3-substituted methyl pyropheophorbide-a derivative (Photomed). The purpose of the study was to evaluate the antitumor effect of PDT with Photomed comparing with the clinically approved photosensitizers Photofrin and Radachlorin. The cytotoxicity assay against SCC VII cells (murine squamous cell carcinoma) was performed to determine whether Photomed is safe without PDT and whether Photomed is effective against cancer cells with PDT. An in vivo anticancer efficacy study was also performed using SCC VII tumor-bearing mice. The mice were divided into small-tumor and large-tumor groups to identify whether Photomed-induced PDT is effective for not only small tumors but also large tumors. From in vitro and in vivo studies, Photomed was confirmed to be (1) a safe photosensitizer without laser irradiation, (2) the most effective photosensitizer with PDT against cancers compared to Photofrin and Radachlorin and (3) effective with PDT in treating not only small tumors but also large tumors. In conclusion, Photomed may contribute as a novel, potential photosensitizer for use in PDT cancer treatment.

Objectives The coronavirus disease 2019 (COVID-19) pandemic has continued since its first detection in the Republic of Korea on January 20, 2020. This study describes the early countermeasures used to minimize the risk of COVID-19 outbreaks during cohort quarantine and compares the epidemiological characteristics of 2 outbreaks in long-term care facilities (LTCFs) in Gwangju Metropolitan City in summer 2020. Methods An epidemiological investigation was conducted via direct visits. We investigated epidemiological characteristics, including incidence, morbidity, and mortality rates, for all residents and staff members. Demographic characteristics were analyzed using a statistical program. Additionally, the method of managing infection in LTCFs is described. Results Residents and caregivers had high incidence rates in LTCF-A and LTCF-B, respectively. LTCF-B had a longer quarantine period than LTCF-A. The attack rate was 20.02% in LTCF-A and 27.9% in LTCF-B. The mortality rate was 2.3% (1/43) in LTCF-B, the only facility in which a COVID-19 death occurred. Conclusion Extensive management requires contact minimization, which involves testing all contacts to mitigate further transmission in the early stages of LTCF outbreaks. The findings of this study can help inform and prepare public health authorities for COVID-19 outbreaks, particularly for early control in vulnerable facilities.

The diversity of workloads drives studies to use GPU more effectively to overcome the limited memory of GPUs. Precisely, it is essential to understand and utilize data locality of workloads to utilize the memory and cache efficiently, which is relatively smaller than CPU ’ s. It is important to understand GPU memory hierarchy to efficiently use with multi-thread environment. Although there have been previous approaches to analyzing data locality on GPUs, these approaches focused on global memory and L2 cache levels with profiling at thread block levels. Data locality study in warp level in GPU has not been studied much. Especially, the concept of coalescing has been defined but the method of measuring the degree of coalescing has not been discussed. Our study focused on analyzing data locality in L1 cache levels, which is the smallest but fastest in cache level to analyze the impact of data locality. To achieve this analysis, our study profiles data locality in warp level, which is smallest segment in GPU thread groups. This paper introduces a novel perspective by introducing a quantitative measure for coalescing alongside static profiling of data locality. Furthermore, it offers a means of refining locality estimates by scrutinizing access patterns of L1 cache. To substantiate our approach, our study validates the estimated data locality against a range of real-world GPU benchmarks, including Rodina and Polybench. Through empirical experimentation, our results reveal a substantial correlation between the metrics of data locality and cache utilization, affirming the efficacy of our proposed method.

Abstract Studies of mouse models of Alzheimer's disease (AD) have demonstrated that nitric oxide synthase 2 (NOS2) is involved in AD pathology. However, the effects of NOS2 on the pathology of Parkinson’s disease (PD) are not well studied. To address this gap, we examined the impact of NOS2 on disease-associated phenotypes in a mouse model of PD. Transgenic mice carrying the A53T mutation of α-synuclein (SynA53T) and newly generated double transgenic mice with deletion of NOS2 (SynA53T/NOS2−/−) were used. Compared with SynA53T mice, the loss of nos2 decreased α-synuclein phosphorylation at serine 129 and reduced α-synuclein-induced microglial and astrocyte activation in SynA53T/NOS−/− mice. Additionally, neuroinflammation-related gene clusters in the deep mesencephalic nucleus (DpMe) were altered in SynA53T/NOS−/− mice compared with SynA53T mice. Taken together, our results suggest that deletion of nos2 alleviates α-synuclein pathology and α-synuclein-associated neuroinflammatory responses in the brain.

Abstract The objective of this study is to determine the trend and diversity of binary toxin-positive Clostridioides difficile over 10 years in Korea. Binary toxin-positive strains were selected from a tertiary hospital in Korea in 2009–2018. The multi-locus sequence typing and antibiotic susceptibility test were performed. Among the 3278 isolates in 2009–2018, 58 possessed binary toxin genes (1.7%). The proportion of CDT- positive isolates was 0.51–4.82% in 2009–2018, which increased over the 10-year period (P = 0.023). Thirteen sequence types (STs) were identified; ST5 (14 [24%]), ST11 (11 [19%]), ST221 (10 [17%]), ST201 (7 [12%]) and ST1 (5 [9%]) were popular. All 58 isolates were susceptible to vancomycin and piperacillin/tazobactam, and clindamycin and moxifloxacin were active in 69.0% and 62% of isolates, respectively. ST1 strains were resistant to several antibiotics, including moxifloxacin (80%), clindamycin (60%) and rifaximin (60%). Moreover, four of five ST1 presented a metronidazole minimum inhibitory concentration of 4 µg/mL. Moxifloxacin resistance was highest (72.3%) for ST11. In conclusion, binary toxin-positive strains are non-prevalent in Korea and involve diverse STs. ST1 strains were resistant to several antibiotics.

Abstract In recent years, rapid economic growth and a rising personal income have increased the demand for personalized services. To address this demand, the fashion industry and academia are increasingly analyzing and developing methods to provide personalized fashion design products. This study investigated an emotional data and data visualization-based design method for personalized fashion products. By visualizing emotions and involving consumers, we generated experimental designs to encourage interpersonal and emotional communication. In addition, we proposed methods for visualizing 28 levels of emotion in design elements, as well as a generative design process based on emotional and personal text messages. In fashion products, we used color and print to match the emotion and intensity of the emotion. As a result, 40 design experiment participants rated personalized fashion design tools, outcomes, and purchase intention positively. The highest score was received by the average value for expression of personality (4.43), purchase intention (4.38), and preference and recommendation (4.42). Consequently, this study could be applied to the use of personal data in generative fashion design, as well as the systemization of the data-driven design method for personalized and participatory fashion design.

Background/Objectives: In a collaborative effort, FAO, the International Federation of Beekeepers’ Association “Apimondia”, the Appalachian State University, and the Istituto Zooprofilattico Sperimentale del Lazio e Toscana (IZSLT), the FAO Reference Centre for Animal Health and Food Security Discipline Apiculture, health, and biosecurity, designed an online international survey (“Knowledge, Awareness and Practice”-KAP) as a risk assessment tool to validate biosecurity measures able to prevent and control the main honeybee (Apis mellifera subsp.) infectious diseases. Methods: The KAP survey was disseminated through various channels for 14 months (January 2019–March 2020). Beekeepers’ knowledge on nosemosis, American foulbrood (AFB), and European foulbrood (EFB) management was assessed. Beekeepers’ attitudes were investigated by asking them to provide a score called “Acceptance by beekeepers”. Results: Of the 410 respondents, the majority of them (68.3%, n = 252) were from Europe. European beekeepers (n = 252) considered “Highly acceptable” the following practices: removing combs that show signs of dysentery and feeding colonies for nosemosis; the quick identification and management of affected hives for American foulbrood and European foulbrood. Instead, the following practices were considered as not acceptable by beekeepers: for nosemosis, the use of antibiotics and sampling of hive debris for early detection; for American foulbrood and European foulbrood, the shook swarm, the destruction of the whole apiary, as well as their treatment with antibiotics. Conclusion: This study demonstrated the validity of the present “Knowledge, Awareness and Practice” (KAP) survey to validate the best practices for the main infectious honeybee diseases, considering the pragmatic point of view of beekeepers. Sustainable practices for disease control are preferred by the European beekeepers. While having an adequate knowledge base for the early detection of the investigated honeybee diseases, European beekeepers tend to be aware of the health status of their hives, embracing advanced, practice-oriented training. Authors highlight that the selection of practices and their validation should be revised on a regular basis, to be adapted in a timely manner to the current infectious honeybee disease situation, in order to build up a resilient and effective stock of practices.

Dietary protein sources and protein adequacy are crucial modulators of muscle quality and body composition. We investigated the association between dietary protein sources (and their adequacy) and body composition and the risk of sarcopenic obesity (SO) in South Korean populations. The participants (n = 1967) were classified into SO, obese, sarcopenia, and normal groups. A cross-sectional survey was conducted using the KS-15 questionnaire, short-form food frequency questionnaire, and anthropometric measurements. The percentage of body fat (male: 35.36 ± 0.51%; female: 44.14 ± 0.36%) was significantly high, while appendicular skeletal muscle (ASM; male: 36.39 ± 0.30%, female: 30.32 ± 0.19%) was low in the SO group. Beef and pork consumption was negatively associated with ASM (%) but positively associated with body fat (%) in the normal group and positively associated with ASM (kg/m2: beta = 0.002, p = 0.02) and BFM (kg: beta = 0.012, p = 0.03) in the SO group, respectively. The highest quintile (Q5: 173.6 g/day) showed a decreased risk of SO prevalence (AORs: 0.46, CI: 0.22–0.94) compared with that in the lowest quintile (Q1: 21.6 g/day) among the people with inadequacy protein intake. Daily poultry and egg intake was positively linked with body composition in the participants with SO, while red meat showed a negative effect on imbalanced body composition in participants in the normal and SO groups. Furthermore, a lower intake of poultry and eggs was strongly associated with SO prevalence in people who consumed inadequate amounts of daily dietary protein.

The epidermal growth factor receptor (EGFR), also known as ErbB1 and HER1, belongs to the receptor tyrosine kinase family. EGFR serves as the primary driver in non-small-cell lung cancer (NSCLC) and is a promising therapeutic target for NSCLC. In this study, we synthesized a novel chemical library based on a benzofuran–indole hybrid scaffold and identified 8aa as a potent and selective EGFR inhibitor. Interestingly, 8aa not only showed selective anticancer effects against NSCLC cell lines, PC9, and A549, but it also showed significant inhibitory effects against the double mutant L858R/T790M EGFR, which frequently occurs in NSCLC. In addition, in PC9 and A549 cells, 8aa potently blocked the EGFR signaling pathway, cell viability, and cell migration. These findings suggest that 8aa, a benzofuran–indole hybrid derivative, is a novel EGFR inhibitor that may be a potential candidate for the treatment of NSCLC patients with EGFR mutations.

The number of design patents has grown significantly in the last 140 years. However, a data-driven approach for design patents has been overlooked and underutilised in the design management and innovation research communities. Through the prism of a patent professional, data analyst and designer, this photo essay demystifies the complexity of design patent data and sheds light on the underlying value of design as it features among a range of diverse innovation activities. Patent network analysis and visualisation techniques enable the building of a series of patent citation maps and co-inventor networks. Cases from renowned companies—Apple, Dyson, Samsung, and LG electronics— reveal different shapes of innovation activities, focusing on product diversification strategies, collaboration patterns and design-technology cross-pollination flows.

Many researchers are attempting to identify drugs that can be repurposed as effective therapies for Alzheimer’s disease (AD). Several recent studies have highlighted epidermal growth factor receptor (EGFR) inhibitors approved for use as anti-cancer drugs as potential candidates for repurposing as AD therapeutics. In cancer, EGFR inhibitors target cell proliferation and angiogenesis, and studies in AD mouse models have shown that EGFR inhibitors can attenuate amyloid-beta (Aβ) pathology and improve cognitive function. In this review, we discuss the different functions of EGFR in cancer and AD and the potential of EGFR as a dual molecular target for AD diseases. In addition, we describe the effects of anti-cancer EGFR tyrosine kinase inhibitors (TKIs) on AD pathology and their prospects as therapeutic interventions for AD. By summarizing the physiological functions of EGFR in cancer and AD, this review emphasizes the significance of EGFR as an important molecular target for these diseases.

Abstract Low‐cost Fe can be used for forming cation‐disordered rocksalt Li‐excess (DRX) materials instead of high‐cost d0‐species and then the Fe‐based DRX can be promising electrode materials because they can theoretically achieve high capacity, resulting from additional oxygen redox reaction and stable cation‐disordered structure. However, Fe‐based DRX materials suffer from large voltage hysteresis, low electrochemical activity, and poor cyclability, so it is highly challenging to utilize them as practical electrode materials for a cell. Here, novel high‐capacity Li‐Fe‐Ti‐Mo electrode materials (LFTMO) with high average discharge voltage and reasonable stability are reported. The effect of Ti/Mo on electrochemical reactions in Fe‐based DRX materials (LFTMO) is studied by controlling its composition ratio and using techniques for analyzing the local environment to find the key factors that improve its activity. It is found out that the introduction of appropriate quantity of redox‐active Mo4+/5+ to Fe‐based DRX materials can help stabilize the oxygen redox reaction via changing a local structure and can suppress a Fe redox reaction, which can cause poor performance. The understandings will help develop high capacity and long cyclability Fe‐based DRX electrode materials.

IntroductionAcupuncture is a clinical intervention consisting of multiple stimulus components, including somatosensory stimulation and manipulation of therapeutic context. Existing findings in neuroscience consolidated cognitive modulation to somatosensory afferent process, which could differ from placebo mechanism in brain. Here, we aimed to identify intrinsic process of brain interactions induced by compound stimulus of acupuncture treatment.MethodsTo separately and comprehensively investigate somatosensory afferent and cognitive/affective processes in brain, we implemented a novel experimental protocol of contextual manipulation with somatosensory stimulation (real acupuncture: REAL) and only contextual manipulation (phantom acupuncture: PHNT) for fMRI scan, and conducted independent component (IC)-wise assessment with the concatenated fMRI data.ResultsBy our double (experimentally and analytically) dissociation, two ICs (CA1: executive control, CA2: goal-directed sensory process) for cognitive/affective modulation (associated with both REAL and PHNT) and other two ICs (SA1: interoceptive attention and motor-reaction, SA2: somatosensory representation) for somatosensory afference (associated with only REAL) were identified. Moreover, coupling between SA1 and SA2 was associated with a decreased heart rate during stimulation, whereas CA1 was associated with a delayed heart rate decrease post-stimulation. Furthermore, partial correlation network for these components demonstrated a bi-directional interaction between CA1 and SA1/SA2, suggesting the cognitive modulation to somatosensory process. The expectation for the treatment negatively affected CA1 but positively affected SA1 in REAL, whereas the expectation positively affected CA1 in PHNT.DiscussionThese specific cognitive-somatosensory interaction in REAL were differed from vicarious sensation mechanism in PHNT; and might be associated with a characteristic of acupuncture, which induces voluntary attention for interoception. Our findings on brain interactions in acupuncture treatment elucidated the underlying brain mechanisms for compound stimulus of somatosensory afferent and therapeutic contextual manipulation, which might be a specific response to acupuncture.

Abstract Background Numerous vaccine strategies are being advanced to control SARS-CoV-2, the cause of the COVID-19 pandemic. EuCorVac-19 (ECV19) is a recombinant protein nanoparticle vaccine that displays the SARS-CoV-2 receptor-binding domain (RBD) on immunogenic nanoliposomes. Methods Initial study of a phase 2 randomized, observer-blind, placebo-controlled trial to assess the immunogenicity, safety, and tolerance of ECV19 was carried out between July and October 2021. Two hundred twenty-nine participants were enrolled at 5 hospital sites in South Korea. Healthy adults aged 19–75 without prior known exposure to COVID-19 were vaccinated intramuscularly on day 0 and day 21. Of the participants who received two vaccine doses according to protocol, 100 received high-dose ECV19 (20 μg RBD), 96 received low-dose ECV19 (10 μg RBD), and 27 received placebo. Local and systemic adverse events were monitored. Serum was assessed on days 0, 21, and 42 for immunogenicity analysis by ELISA and neutralizing antibody response by focus reduction neutralization test (FRNT). Results Low-grade injection site tenderness and pain were observed in most participants. Solicited systemic adverse events were less frequent, and mostly involved low-grade fatigue/malaise, myalgia, and headache. No clinical laboratory abnormalities were observed. Adverse events did not increase with the second injection and no serious adverse events were solicited by ECV19. On day 42, Spike IgG geometric mean ELISA titers were 0.8, 211, and 590 Spike binding antibody units (BAU/mL) for placebo, low-dose and high-dose ECV19, respectively (p

Purpose: This study aimed to examine the changes in the characteristics of community-onset fluoroquinolone-resistant (FQ-R) Escherichia coli isolates causing community-acquired acute pyelonephritis (APN) in South Korea. Methods: Blood or urine samples were prospectively collected from patients aged ≥15 years with community-acquired APN who were admitted to one of the eight Korean hospitals included in this study between September 2017 and August 2018. Phylogenetic typing, multilocus sequence typing, and molecular characterization of β-lactamase resistance and plasmid-mediated quinolone resistance (PMQR) determinants were performed. The data were compared with those from a previous study with the same design conducted in 2010–2011. Results: A total of 300 and 346 isolates were identified in 2010–2011 and 2017–2018, respectively. Among them, 76 (22.0%) and 77 (25.7%) FQ-R isolates were identified in 2010–2011 and 2017–2018, respectively. A significantly higher antimicrobial resistance against third-to fourth-generation cephalosporins, including cefotaxime (23.9% vs. 77.9%, P

Abstract Background In chronic myelogenous leukemia, reciprocal translocation between chromosome 9 and chromosome 22 generates a chimeric protein, Bcr-Abl, that leads to hyperactivity of tyrosine kinase-linked signaling transduction. The therapeutic agent nilotinib inhibits Bcr-Abl/DDR1 and can cross the blood–brain barrier, but its potential impact on neuroinflammatory responses and cognitive function has not been studied in detail. Methods The effects of nilotinib in vitro and in vivo were assessed by a combination of RT-PCR, real-time PCR, western blotting, ELISA, immunostaining, and/or subcellular fractionation. In the in vitro experiments, the effects of 200 ng/mL LPS or PBS on BV2 microglial cells, primary microglia or primary astrocytes pre- or post-treated with 5 µM nilotinib or vehicle were evaluated. The in vivo experiments involved wild-type mice administered a 7-day course of daily injections with 20 mg/kg nilotinib (i.p.) or vehicle before injection with 10 mg/kg LPS (i.p.) or PBS. Results In BV2 microglial cells, pre- and post-treatment with nilotinib altered LPS-induced proinflammatory/anti-inflammatory cytokine mRNA levels by suppressing AKT/P38/SOD2 signaling. Nilotinib treatment also significantly downregulated LPS-stimulated proinflammatory cytokine levels in primary microglia and primary astrocytes by altering P38/STAT3 signaling. Experiments in wild-type mice showed that nilotinib administration affected LPS-mediated microglial/astroglial activation in a brain region-specific manner in vivo. In addition, nilotinib significantly reduced proinflammatory cytokine IL-1β, IL-6 and COX-2 levels and P38/STAT3 signaling in the brain in LPS-treated wild-type mice. Importantly, nilotinib treatment rescued LPS-mediated spatial working memory impairment and cortical dendritic spine number in wild-type mice. Conclusions Our results indicate that nilotinib can modulate neuroinflammatory responses and cognitive function in LPS-stimulated wild-type mice.

The integration of artificial intelligence (AI) into drug discovery has markedly advanced the search for effective therapeutics. In our study, we employed a comprehensive computational–experimental approach to identify potential anti-SARS-CoV-2 compounds. We developed a predictive model to assess the activities of compounds based on their structural features. This model screened a library of approximately 700,000 compounds, culminating in the selection of the top 100 candidates for experimental validation. In vitro assays on human intestinal epithelial cells (Caco-2) revealed that 19 of these compounds exhibited inhibitory activity. Notably, eight compounds demonstrated dose-dependent activity in Vero cell lines, with half-maximal effective concentration (EC50) values ranging from 1 μM to 7 μM. Furthermore, we utilized a clustering approach to pinpoint potential nucleoside analog inhibitors, leading to the discovery of two promising candidates: azathioprine and its metabolite, thioinosinic acid. Both compounds showed in vitro activity against SARS-CoV-2, with thioinosinic acid also significantly reducing viral loads in mouse lungs. These findings underscore the utility of AI in accelerating drug discovery processes.

Recently, the extensive spread of some algae along coastlines has surged into unmanageable thick decomposition layers. This study aimed to demonstrate the use of Sargassum horneri as a biomass resource for ethanol production through the continuous hydrolysis, enzymatic saccharification, and fermentation process. Sugars from S. horneri were obtained using a combination of thermal acid hydrolysis and enzymatic saccharification. The optimal conditions for thermal acid hydrolysis involved a 10% (w/v) S. horneri slurry treated with 100 mM H2SO4 at 121 °C for 60 min; enzymatic saccharification using 16 U/mL Cellic CTec2 further boosted the monosaccharide concentration to 23.53 g/L. Fermentation experiments were conducted with mannitol-adapted Saccharomyces cerevisiae BY4741 using S. horneri hydrolysate. Enhanced ethanol production was observed in the hydrolysate, particularly with mannitol-adapted S. cerevisiae BY4741, which yielded 10.06 g/L ethanol. Non-adapted S. cerevisiae produced 8.12 g/L ethanol, as it primarily utilized glucose and not mannitol. Regarding ethanol fermentation using 5 L- and 500 L-scale fermenters, the ethanol concentrations reached 10.56 g/L and 7.88 g/L with yields of 0.51 and 0.45, respectively, at 48 h. This study confirmed the economic viability of ethanol production using waste seaweed with optimized pretreatment conditions and the adaptive evolution of S. cerevisiae to mannitol.

Plain Language Summary In the context of pregnancy preparation, attention has recently shifted from the period just before pregnancy to the early years, or even throughout one’s life. The World Health Organization identifies adolescents as requiring specific attention. Adolescents’ health behaviors can impact their adulthood years and have significant repercussions on the health of the future generation. In addition, recent studies consistently report that the preparedness of both men and women is essential to pregnancy preparation. Therefore, it is now time to present a new strategy by identifying and grasping the different factors that influence the two genders. This study can raise awareness of healthy pregnancy preparation behavior from adolescence onwards of both genders. There were differences in factors affecting HPPB by gender. For healthy pregnancy preparation, interventions based on HBM constructs and smoking should be presented for both male and female adolescents. Imparting education to females on the importance of HPPB (β = 0.19, p = 0.005) and males on confidence in HPPB (β = 0.12, p = 0.401), gender equality related to pregnancy and childbirth (β = − 0.20, p = 0.001 for women’s responsibility variable, β = 0.14, p = 0.018 for men’s responsibility variable), and alcohol consumption (β = − 0.10, p = 0.022) should be emphasized; and effective healthy pregnancy preventive strategies should be developed based on these findings. Interventions to prepare for a healthy pregnancy from an early age can ensure the health of both mother and child.

Abstract Background The germline mutations of DDX41, also known as DEAD box RNA helicase 41, have been found in about 1.5% of myeloid neoplasms (MNs). Development of MDS/AML is relatively common in germline DDX41 mutations. However, a variety of hematological malignancies (HMs) have been reported. Case presentation We report a novel case of bi-alleleic DDX41 mutations in B-cell lymphoblastic leukemia (B-ALL), with unusual location of DDX41 mutations. The gene expression profile (GEP) of Ph + B-ALL with bi-alleleic DDX41 mutations showed heterogeneously transitional GEP and altered gene expression levels of genes involved in the process essential for red blood cells and myeloid cell differentiation were noted. Conclusions We report that DDX41 mutations are unusual but can be an underlying event in Ph + B-ALL and screening DDX41 mutations can be also informative for patients awaiting for haploidentical stem cell transplantation and choosing the therapy.

Plain English summary Starting in early adulthood, such as college students in the preconception stage, it is necessary to take care of one’s mental health (including depression) in order to have a healthy pregnancy in the future. The early identification of adults needing depression management is also a major challenge. In this study, an online survey was conducted to investigate levels of depression among Korean college students and their intention to manage depression for a healthy future pregnancy, as well as to identify the influencing factors. Convenience recruitment was conducted by e-mail at one university in Korea, and 828 male and female college students responded to the survey. An analysis of the factors affecting the intention to manage depression for a healthy future pregnancy identified the components of the Theory of Planned Behavior as influencing factors in both men and women. In particular, self-efficacy had the greatest influence. However, the current level of depression was only a significant factor among women. These findings could help nurses recognize differences in gender characteristics for the intention of preventive depression management for a healthy pregnancy, and provide evidence to develop and implement the intervention. These efforts will ultimately reduce high-risk pregnancies due to poor mental health.

Angioimmunoblastic T-cell lymphoma (AITL) is a lymphoproliferative disorder of mature T follicular helper cells. Atypical lymphoid cells were observed in the bone marrow of an 80-year-old woman, and the flow cytometric determined immunophenotypes of B-cells were unusual, that is, CD19+, CD20-, and CD22- with lambda light chain restriction. Initially, we suspected BM involvement of B-cell lymphoma based on the presence of abnormal B-cells. However, the patient was diagnosed with AITL involving BM. A re-analysis of flow cytometric immunophenotyping revealed a minor, aberrant T-cell population, and the lambda light chain restriction observed by surface staining was considered non-specific binding. This case demonstrates B-cells in patients with EBV-positive T-cell lymphoma may exhibit immunophenotypes resembling those of plasma cells, and that proliferation of abnormal B-cells or plasma cells could also potentially mask underlying T-cell lymphoma. A more integrated approach is required for accurate diagnosis.

It is assumed that mood can be inferred from one’s facial expression. While this association may prove to be an objective marker for mood disorders, few studies have explicitly evaluated this linkage.The facial movement responses of women with major depressive disorder (n = 66) and healthy controls (n = 46) under emotional stimuli were recorded using webcam. To boost facial movements, the naturalistic audio-visual stimuli were presented. To assess consistent global patterns across facial movements, scores for facial action units were extracted and projected onto principal component using principal component analysis. The associations of component for facial movements with functional brain circuitry was also investigated.Clusters of mouth movements, such as lip press and stretch, identified by principal component analysis, were attenuated in depressive patients compared to those in healthy controls. This component of facial movements was associated with depressive symptoms, and the strengths of resting brain functional connectivity between nucleus accumbens and both posterior insular cortex and thalamus.The evaluation of facial movements may prove to be a promising quantitative marker for assessing depressive symptoms and their underlying brain circuitry.