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Abstract Oxidative stress plays an essential role in the progression of Alzheimer’s disease (AD), the most common age-related neurodegenerative disorder. Streptozotocin (STZ)-induced abnormal brain insulin signaling and oxidative stress play crucial roles in the progression of Alzheimer’s disease (AD)-like pathology. Peroxiredoxins (Prxs) are associated with protection from neuronal death induced by oxidative stress. However, the molecular mechanisms underlying Prxs on STZ-induced progression of AD in the hippocampal neurons are not yet fully understood. Here, we evaluated whether Peroxiredoxin 1 (Prx1) affects STZ-induced AD-like pathology and cellular toxicity. Prx1 expression was increased by STZ treatment in the hippocampus cell line, HT-22 cells. We evaluated whether Prx1 affects STZ-induced HT-22 cells using overexpression. Prx1 successfully protected the forms of STZ-induced AD-like pathology, such as neuronal apoptosis, synaptic loss, and tau phosphorylation. Moreover, Prx1 suppressed the STZ-induced increase of mitochondrial dysfunction and fragmentation by down-regulating Drp1 phosphorylation and mitochondrial location. Prx1 plays a role in an upstream signal pathway of Drp1 phosphorylation, cyclin-dependent kinase 5 (Cdk5) by inhibiting the STZ-induced conversion of p35 to p25. We found that STZ-induced of intracellular Ca2+ accumulation was an important modulator of AD-like pathology progression by regulating Ca2+-mediated Calpain activation, and Prx1 down-regulated STZ-induced intracellular Ca2+ accumulation and Ca2+-mediated Calpain activation. Finally, we identified that Prx1 antioxidant capacity affected Ca2+/Calpain/Cdk5-mediated AD-like pathology progress. Therefore, these findings demonstrated that Prx1 is a key factor in STZ-induced hippocampal neuronal death through inhibition of Ca2+/Calpain/Cdk5-mediated mitochondrial dysfunction by protecting against oxidative stress.

Introduction Cigarette package inserts that describe quitting benefits and tips may promote cessation; however, research is needed to understand better their effects, including potentially enhancing the effects of pictorial health warning labels (PHWLs). Methods A randomized trial with a 2×2 factorial design was conducted with adult smokers (n=356) assigned to either small text-only health warning labels (HWLs; control); inserts with cessation messages, and the small text-only HWLs (insertsonly); large PHWLs (PHWLs-only); both inserts and PHWLs (inserts + PHWLs). Participants received a 14-day supply of their preferred cigarettes with packs labeled to reflect their group. Upon finishing the trial, participants reported their past 14-day frequency of noticing, reading, thinking about smoking harms and cessation benefits, talking about labels, and forgoing cigarettes because of the labels. Ordered logistic models regressed these outcomes on labeling groups, and mediation analyses assessed whether attention (i.e. noticing, reading) to labels mediated effects of labeling exposure on other outcomes (i.e. thinking about harms/benefits, talking, forgoing). Results The inserts + PHWLs group reported higher frequencies than the control group for all outcomes. Compared to the control group, both the inserts-only and PHWLs-only groups reported higher frequency of noticing (AOR=3.53 and 2.46, respectively) and reading labels (AOR=2.89 and 1.71), thinking about smoking risks because of the labels (AOR=1.93 and 1.82), and talking about labels (AOR=2.30 and 2.70). Participants in the inserts-only group also reported more frequent thinking about quitting benefits (AOR=1.98). Attention mediated all labeling effects except for the contrast between PHWLs only and control. Conclusions Compared to text-only HWLS, cigarette labeling that involves inserts, PHWLs, or both appears more effective at drawing attention to warnings, which mediated the effects on cessation-related psychosocial and behavioral outcomes.

Abstract Background Maternal diet during pregnancy might influence the development of childhood allergic disorders. There are few studies on the association between processed food intake and infant atopic dermatitis (AD) during pregnancy. The aim of the present study was to investigate the association of ultra-processed food (UPF) intake during pregnancy with infantile AD. Methods This study involved 861 pairs of pregnant women and their offspring from the Mothers’ and Children’s Environmental Health (MOCEH) study, a multi-center birth cohort project conducted in Korea. Dietary intake was estimated using a 24-h recall method at 12−28 weeks gestation. The NOVA classification was used to identify UPF, and UPF intake was calculated as the percentage of total energy consumption and categorized into quartiles. Infantile AD was assessed based on medical history and the criteria of the International Study of Asthma and Allergies in Childhood (ISAAC). Associations were assessed by logistic regression with adjustment for confounding factors. Results Children born to mothers in the highest quartile of UPF consumption (15.5% or more of the total energy) compared to the lowest quartile (6.8% or less) showed a higher risk of AD within 12 months [odds ratio (OR) = 1.69; 95% confidence interval (CI): 1.07−2.66, P for trend 0.0436]. After adjustment for the confounding factors under study, the association was strengthened; the adjusted OR between extreme quartiles was 2.19 (95% CI: 1.11–4.32, P for trend = 0.0418). This association was maintained even after an additional adjustment based on the Korean Healthy Eating Index (KHEI), an indicator of diet quality. Conclusions Higher maternal consumption of UPF during pregnancy was associated with a greater risk of infantile AD within the first year of life.

Purpose This study aimed to identify changes in the prevalence of obesity and related diseases among children and adolescents during the coronavirus disease 2019 (COVID-19) pandemic. Methods This study was conducted using data from the 2016–2021 Korean National Health and Nutrition Examination Survey and included 3,861 children and adolescents aged 10–18 years. The prevalence of obesity and related diseases was adjusted for age, sex, and income. We also analyzed the socioeconomic, nutritional, and physical activity items in the survey. Results During the COVID-19 pandemic, there was a significant increase in the prevalence of obesity (p=0.02), central obesity (p=0.001), mean body mass index (BMI, p=0.03), and hemoglobin A1c (p=0.005) among children and adolescents aged 10–18 years. The intake of food and calories was significantly reduced in the normal-weight group (p=0.001 and

Introduction Heated tobacco products (HTPs) are promoted as less harmful than cigarettes; nonetheless, whether HTPs help smokers quit is uncertain. Methods Data from 4067 Mexican adult smokers surveyed longitudinally every four months (November 2019–March 2021) were analyzed. Mixed-effects multinomial models regressed HTP use frequency (no use=reference; monthly; weekly; and daily use) on sociodemographics and tobacco/nicotine-related variables. Among participants who completed at least two surveys (n=2900) over four months, the duration of their longest smoking quit attempt (SQA) between surveys (SQAs: 5 cigarettes (ARRR=1.69 [95% CI: 1.12–2.55], 1.88 [95% CI: 1.26–2.81] and 6.46 [95% CI: 3.33–12.52], respectively); e-cigarette use (ARRR =5.68 [95% CI: 3.38–9.53], 6.54 [95% CI: 4.06–10.55] and 2.59 [95% CI: 1.26–5.30]); lower HTP risk perceptions (ARRR=2.12 [95% CI: 1.50–30.00], 2.25 [95% CI: 1.63–3.10] and 2.00 [95% CI: 1.25–3.22]); exposure to HTP information inside (ARRR=2.13 [95% CI: 1.44–3.15], 2.13 [95% CI: 1.49–3.05] and 3.72 [95% CI: 2.28–6.09]) and outside stores (ARRR=2.36 [95% CI: 1.56– 3.57], 2.32 [95% CI: 1.65–3.25] and 2.44 [95% CI: 1.41–4.24]) where tobacco is sold; having family (ARRR=2.46 [95% CI: 1.54–3.91], 2.90 [95% CI: 1.93–4.37] and 2.96 [95% CI: 1.52–5.77]) and friends (ARRR=5.78 [95% CI: 3.60–9.30], 4.98 [95% CI: 3.22–7.72] and 6.61 [95% CI: 2.91–15.01]) who use HTPs. HTP use frequency was not associated with quit attempts, except for monthly HTP use predicting SQAs lasting ≥30 days (ARRR=2.12 [95% CI: 1.17–3.85]). Initiation of HTP use was not associated with changes in smoking frequency. Limiting analysis to those who intend to quit smoking also yielded null results. Conclusions Among Mexican adult smokers, frequency of HTP use was mostly not associated with either cessation behaviors or changes in cigarette consumption, suggesting that HTPs have limited to no effectiveness for smoking cessation.

Abstract Previous studies have examined the prevalence of allergic diseases in adolescents 1–2 years after the emergence of the COVID-19 pandemic. However, more data is needed to understand the long-term impact of COVID-19 on allergic diseases. Thus, we aimed to examine the trend of the atopic dermatitis prevalence in Korean adolescents before and during the COVID-19 pandemic across 14 years. Additionally, we analyze the risk factors of atopic dermatitis (AD) based on the results. The Korean Disease Control and Prevention Agency conducted the Korea Youth Risk Behavior Web-based Survey from 2009 to 2022, from which the data for this study were obtained. Prevalence trends were compared across subgroups, and the β difference (βdiff) was calculated. We computed odds ratios to examine changes in the disease prevalence before and during the pandemic. This study included a total of 917,461 participants from 2009 to 2022. The prevalence of atopic dermatitis increased from 6.79% (95% CI 6.66–6.91) in 2009–2011 to 6.89% (95% CI 6.72–7.05) in 2018–2019, then decreased slightly to 5.82% (95% CI 5.60–6.04) in 2022. Across the 14 years, middle school student status, low parent’s highest education level, low household income, non-alcohol consumption, non-smoker smoking status, no suicidal thoughts, and no suicide attempts were associated with increased risk of atopic dermatitis, while female sex, rural residence, high BMI, low school performance, low household income, and no feelings of sadness and despair was associated with a small increase. This study examined the prevalence of atopic dermatitis across an 18-year, and found that the prevalence increased in the pre-pandemic then decreased during the start of the pandemic and remained constant throughout the pandemic. This trend could be explained mainly by the large scale social and political changes that occurred during the COVID-19 pandemic.

Abstract The physiological changes caused by the decline in estrogen levels due to menopause are linked to an increased risk of depression. This study investigated the antidepressant effects of hyperoside (HYP), a natural flavonol glycoside, and its associated molecular mechanisms in primary hippocampal neurons and ovariectomized (OVX) mice. HYP treatment increased nitric oxide (NO) production and neuronal nitric oxide synthase (nNOS) expression in primary hippocampal neurons; additionally, it upregulated the expression of brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin receptor kinase B (TrkB). In OVX mice, HYP treatment significantly improved depression-like behaviors in an open field test to a level comparable to estrogen treatment. Furthermore, HYP treatment upregulated OVX-induced decreased nNOS expression and BDNF-TrkB signaling in the hippocampus. Therefore, this study suggests that HYP exhibits antidepressant potential by addressing estrogen deficiency-induced alterations, specifically by restoring nNOS expression, promoting NO production, and concurrently enhancing BDNF-TrkB signaling in OVX mice.

Abstract As mounting evidence suggests a higher incidence of adverse consequences, such as disruption of the immune system, among patients with a history of COVID-19, we aimed to investigate post-COVID-19 conditions on a comprehensive set of allergic diseases including asthma, allergic rhinitis, atopic dermatitis, and food allergy. We used nationwide claims-based cohorts in South Korea (K-CoV-N; n = 836,164; main cohort) and Japan (JMDC; n = 2,541,021; replication cohort A) and the UK Biobank cohort (UKB; n = 325,843; replication cohort B) after 1:5 propensity score matching. Among the 836,164 individuals in the main cohort (mean age, 50.25 years [SD, 13.86]; 372,914 [44.6%] women), 147,824 were infected with SARS-CoV-2 during the follow-up period (2020−2021). The risk of developing allergic diseases, beyond the first 30 days of diagnosis of COVID-19, significantly increased (HR, 1.20; 95% CI, 1.13−1.27), notably in asthma (HR, 2.25; 95% CI, 1.80−2.83) and allergic rhinitis (HR, 1.23; 95% CI, 1.15−1.32). This risk gradually decreased over time, but it persisted throughout the follow-up period (≥6 months). In addition, the risk increased with increasing severity of COVID-19. Notably, COVID-19 vaccination of at least two doses had a protective effect against subsequent allergic diseases (HR, 0.81; 95% CI, 0.68−0.96). Similar findings were reported in the replication cohorts A and B. Although the potential for misclassification of pre-existing allergic conditions as incident diseases remains a limitation, ethnic diversity for evidence of incident allergic diseases in post-COVID-19 condition has been validated by utilizing multinational and independent population-based cohorts.

Abstract Adipose tissue (AT) adapts to overnutrition in a complex process, wherein specialized immune cells remove and replace dysfunctional and stressed adipocytes with new fat cells. Among immune cells recruited to AT, lipid-associated macrophages (LAMs) have emerged as key players in obesity and in diseases involving lipid stress and inflammation. Here, we show that LAMs selectively express transmembrane 4 L six family member 19 (TM4SF19), a lysosomal protein that represses acidification through its interaction with Vacuolar-ATPase. Inactivation of TM4SF19 elevates lysosomal acidification and accelerates the clearance of dying/dead adipocytes in vitro and in vivo. TM4SF19 deletion reduces the LAM accumulation and increases the proportion of restorative macrophages in AT of male mice fed a high-fat diet. Importantly, male mice lacking TM4SF19 adapt to high-fat feeding through adipocyte hyperplasia, rather than hypertrophy. This adaptation significantly improves local and systemic insulin sensitivity, and energy expenditure, offering a potential avenue to combat obesity-related metabolic dysfunction.

Abstract Dietary patterns may be a crucial modifiable factor in colorectal cancer (CRC) risk. This study aimed to examine the associations of dietary patterns derived from two methods with CRC risk in Korea. In a study of 1420 CRC patients and 2840 control participants, we obtained dietary patterns by principal component analysis (PCA) and reduced rank regression (RRR) using 33 predefined food groups. The associations between dietary patterns and CRC risk were assessed using unconditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs). We identified two similar dietary patterns, derived from PCA 1 (prudent) and RRR (healthy), characterized by higher consumption of green/yellow vegetables, light-colored vegetables, fruits, eggs, and milk in both men and women. In women, higher prudent and healthy pattern scores were significantly associated with a lower risk of CRC (prudent, ORQ4 vs. Q1 = 0.59, 95% CI 0.40–0.86, P for trend = 0.005; healthy, ORQ4 vs. Q1 = 0.62, 95% CI 0.43–0.89, P for trend = 0.007). In men, a significant inverse association between dietary pattern and risk of rectal cancer was found only for the healthy dietary pattern (ORQ4 vs. Q1 = 0.66, 95% CI 0.45–0.97, P for trend = 0.036). Compared with the dietary pattern derived by PCA, the RRR dietary pattern had a slightly stronger association with a lower risk of distal colon cancer (ORQ4 vs. Q1 = 0.58, 95% CI 0.35–0.97, P for trend = 0.025) and rectal cancer (ORQ4 vs. Q1 = 0.29, 95% CI 0.15–0.57, P for trend

Abstract Kdm1a is a histone demethylase linked to intellectual disability with essential roles during gastrulation and the terminal differentiation of specialized cell types, including neurons, that remains highly expressed in the adult brain. To explore Kdm1a’s function in adult neurons, we develop inducible and forebrain-restricted Kdm1a knockouts. By applying multi-omic transcriptome, epigenome and chromatin conformation data, combined with super-resolution microscopy, we find that Kdm1a elimination causes the neuronal activation of nonneuronal genes that are silenced by the polycomb repressor complex and interspersed with active genes. Functional assays demonstrate that the N-terminus of Kdm1a contains an intrinsically disordered region that is essential to segregate Kdm1a-repressed genes from the neighboring active chromatin environment. Finally, we show that the segregation of Kdm1a-target genes is weakened in neurons during natural aging, underscoring the role of Kdm1a safeguarding neuronal genome organization and gene silencing throughout life.

Contrastive learning of sentence representations has achieved great improvements in several natural language processing tasks. However, the supervised contrastive learning model trained on the natural language inference (NLI) dataset is insufficient to elucidate the semantics of sentences since it is prone to make a prediction based on heuristics. Herein, by using the ParsEVAL and the word overlap metric, it is shown that sentence pairs in the NLI dataset have strong syntactic similarity and propose a framework to compensate for this problem in two aspects. 1) Apply simple syntactic transformations to the hypothesis and 2) expand the objective to SupCon Loss to leverage variants of sentences. The method is evaluated on semantic textual similarity (STS) tasks and transfer tasks. The proposed methods improve the performance of the BERT‐based baseline in STS Benchmark and SICK Relatedness by 1.48% and 2.2%. Furthermore, the model achieves 82.65% on the HANS benchmark dataset, to the best of our knowledge, which is a state‐of‐the‐art performance demonstrating that our approach is effective in grasping semantics without heuristics in the NLI dataset at supervised contrastive learning. The code is available at https://github.com/whnhch/Break-the-Similarity.

Summary: The isolation of a natural product conventionally precedes its chemical synthesis. Often, the isolation and structure determination of a natural product present in minute quantities in its natural source pose formidable challenges, akin to finding “a needle in a haystack.” On the other hand, leveraging plausible biosynthetic insights and biomimetic synthetic expertise would allow for the prior synthesis of presumed natural products, followed by their verification in natural sources. In this study, we unveil two novel securinega alkaloids, securingines H and I, employing the natural product anticipation through synthesis approach. Structural analysis of securingines H and I suggests that they are biosynthetic derivatives of secu’amamine E and securinol A, respectively. We posit that this “synthesis first” strategy represents a valuable approach to the discovery of new natural products.

BackgroundUnderstanding the association between hypertension prevalence and socioeconomic and behavioral variables during a pandemic is essential, and this analysis should extend beyond short-term trends. ObjectiveThis study aims to examine long-term trends in the prevalence of participants diagnosed with and receiving treatment for hypertension, using data collected by a nationally representative survey from 2009 to 2022, which includes the COVID-19 pandemic era. MethodsA nationwide, population-based, cross-sectional study used data collected from the South Korea Community Health Survey between 2009 and 2022. The study sample comprised 3,208,710 Korean adults over a period of 14 years. We aimed to assess trends in the prevalence of participants diagnosed with and receiving treatment for hypertension in the national population from 2009 to 2022, with a specific focus on the COVID-19 pandemic, using weighted linear regression models. ResultsAmong the included 3,072,546 Korean adults, 794,239 (25.85%) were aged 19-39 years, 1,179,388 (38.38%) were aged 40-59 years; 948,097 (30.86%) were aged 60-79 years, and 150,822 (4.91%) were aged 80 years or older. A total of 1,426,379 (46.42%) were men; 761,896 (24.80%) and 712,264 (23.18%) were diagnosed with and received treatment for hypertension, respectively. Although the overall prevalence over the 14-year period increased, the upward trends of patients diagnosed with and receiving treatment for hypertension decreased during the COVID-19 pandemic era compared with the prepandemic era (β difference for trend during vs before the pandemic –.101, 95% CI –0.107 to –0.094 vs –.133, 95% CI –0.140 to –0.127). Notably, the trends in prevalence during the pandemic were less pronounced in subgroups of older adults (≥60 years old) and individuals with higher alcohol consumption (≥5 days/month). ConclusionsThis nationwide representative study found that the national prevalence of participants diagnosed with and receiving treatment for hypertension increased during the prepandemic era. However, there was a marked decrease in these trends during the prepandemic era, compared with the pandemic era, particularly among specific subgroups at increased risk of negative outcomes. Future studies are needed to evaluate the factors associated with changes in the prevalence of hypertension during the COVID-19 pandemic.

Abstract Brown algae are gaining traction as biorefinery feedstocks due to their advantages such as rapid growth and carbon dioxide sequestration. Saccharina japonica has high potential due to its high carbohydrate content, especially mannitol (26.7%). In this study, a biorefinery process for S. japonica was designed, with focusing on sugar conversion and bioconversion into lactic acid, a valuable platform chemical utilized in various industries. The existing sugar conversion process of S. japonica has been investigated by focusing on enzymatic or acid‐catalyzed hydrolysis, but not hot water extraction although mannitol can be easily recovered using water. The effect of temperature (60–120°C) on the mannitol yield from S. japonica was investigated, and a mannitol yield of 208 g/kg biomass was achieved at the optimal temperature of 100°C (about 78% of the theoretical maximum yield). This study emphasizes that this simple process has considerable potential for application as over 80% of the fermentable carbohydrates in S. japonica were mannitol. Then, S. japonica extract was applied to lactic acid production. First, lactic acid production of four bacterial strains was tested in a mannitol medium, and Lacticaseibacillus rhamnosus was selected as the superior producer, showing 1.93 to 2.92 times better lactic acid titer than others. Next, the optimal feeding concentration of mannitol was determined to be 20 g/L, which was all consumed by L. rhamnosus. Finally, S. japonica extract was applied to lactic acid production by L. rhamnosus, and the results showed similar fermentation profiles with the control medium: lactic acid production, 18.81 g/L (control: 18.97 g/L); lactic acid conversion, 95.1% (control: 95.9%); cell growth (OD600 nm), 8.9 (control: 7.4). The lactic acid yield in the designed biorefinery process was estimated to be 195.6 g/kg biomass, thus S. japonica has high potential as a biorefinery feedstock to produce valuable bioproducts, including lactic acid.

Abstract In Japan, Japanese Black cattle, known for their exceptional meat quality owing to their abundant intramuscular fat, undergo a unique three-stage feeding system with varying concentrate ratios. There is limited research on physiological and rumen microbial changes in Japanese Black cattle during these stages. Therefore, this study aimed to examine Japanese Black steers in these three stages: early (T1, 12–14 months), middle (T2, 15–22 months), and late (T3, 23–30 months). The rumen bacteria of 21 cattle per phase was analyzed using 16S rRNA gene sequencing. Rumen bacterial diversity was significantly higher in T1, with a distinct distribution, than in T2 and T3. Specific phyla and genera were exclusive to each stage, reflecting the shifts in feed composition. Certain genera dominated each stage: T1 had Flexilinea, Streptococcus, Butyrivibrio, Selenomonas, and Kandleria; T2 had Bifidobacterium, Shuttleworthia, and Sharpea; and T3 had Acetitomaculum, Mycoplasma, Atopobium, and Howardella. Correlation analysis revealed significant associations between certain microbial populations and physiological parameters. These findings indicate that changes in energy content and feed composition are associated with physiological and ruminal alterations. This study may guide strategies to improve rumen health and productivity in Japanese Black cattle by modifying diets to specific fattening stages.

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

In this paper, we conducted a simulation of an indium-gallium-zinc oxide (IGZO)-based neuromorphic system and proposed layer-by-layer membrane capacitor (Cmem) optimization for integrate-and-fire (I&F) neuron circuits to minimize the accuracy drop in spiking neural network (SNN). The fabricated synaptic transistor exhibited linear 32 synaptic weights with a large dynamic range $(\sim 846$ ), and an n-type-only IGZO I&F neuron circuit was proposed and verified by HSPICE simulation. The network, consisting of three fully connected layers, was evaluated with an offline learning method employing synaptic transistor and I&F circuit models for three datasets: MNIST, Fashion-MNIST, and CIFAR-10. For offline learning, accuracy drop can occur due to information loss caused by overflow or underflow in neurons, which is largely affected by Cmem. To address this problem, we introduced a layer-by-layer ${\mathrm{ C}}_{\mathrm{ mem}}$ optimization method that adjusts appropriate ${\mathrm{ C}}_{\mathrm{ mem}}$ for each layer to minimize the information loss. As a result, high SNN accuracy was achieved for MNIST, Fashion-MNIST, and CIFAR-10 at 98.42%, 89.16%, and 48.06%, respectively. Furthermore, the optimized system showed minimal accuracy degradation under device-to-device variation.

Abstract Formalin-fixed, paraffin-embedded (FFPE) tissue specimens are routinely used in pathological diagnosis, but their large number of artifactual mutations complicate the evaluation of companion diagnostics and analysis of next-generation sequencing data. Identification of variants with low allele frequencies is challenging because existing FFPE filtering tools label all low-frequency variants as artifacts. To address this problem, we aimed to develop DEEPOMICS FFPE, an AI model that can classify a true variant from an artifact. Paired whole exome sequencing data from fresh frozen and FFPE samples from 24 tumors were obtained from public sources and used as training and validation sets at a ratio of 7:3. A deep neural network model with three hidden layers was trained with input features using outputs of the MuTect2 caller. Contributing features were identified using the SHapley Additive exPlanations algorithm and optimized based on training results. The performance of the final model (DEEPOMICS FFPE) was compared with those of existing models (MuTect filter, FFPolish, and SOBDetector) by using well-defined test datasets. We found 41 discriminating properties for FFPE artifacts. Optimization of property quantification improved the model performance. DEEPOMICS FFPE removed 99.6% of artifacts while maintaining 87.1% of true variants, with an F1-score of 88.3 in the entire dataset not used for training, which is significantly higher than those of existing tools. Its performance was maintained even for low-allele-fraction variants with a specificity of 0.995, suggesting that it can be used to identify subclonal variants. Different from existing methods, DEEPOMICS FFPE identified most of the sequencing artifacts in the FFPE samples while retaining more of true variants, including those of low allele frequencies. The newly developed tool DEEPOMICS FFPE may be useful in designing capture panels for personalized circulating tumor DNA assay and identifying candidate neoepitopes for personalized vaccine design. DEEPOMICS FFPE is freely available on the web ( http://deepomics.co.kr/ffpe ) for research.

Abstract Colloidal crystallization serves as one of the most economic and scalable production methods for photonic crystals. However, insufficient optical performance, nonuniformity and low reproducibility remain challenges for advanced high-value applications. In this study, we optimally formulate a photocurable dispersion of silica particles and apply shear flow to unify the orientation of the colloidal crystals, ensuring high optical performance and uniformity. The silica particles experience strong repulsion at ultrahigh volume fractions of 50% but demonstrate low mobility, leading to polycrystalline structures. Applying shear flow to the dispersions allows the silica particles to rearrange into larger crystalline domains with a unidirectional orientation along the flow. This shear-induced structural change produces absolute reflectivity at the stopband as high as 90% and a high transparency of 90% at off-resonant wavelengths with minimal diffusive scattering. Furthermore, the strong interparticle repulsion ensures a uniform volume fraction of particles throughout the dispersion, reducing deviations in the optical properties. We intricately micropattern the photocurable dispersions using photolithography. Additionally, the photonic films and patterns can be stacked to form multiple layers, displaying mixed structural colors and multiple reflectance peaks without sacrificing reflectivity. These superior photonic materials hold promise for various optical applications, including optical components and anticounterfeiting patches.

Abstract Novel hypoglycemic agents, sodium-glucose cotransporter 2 inhibitors (SGLT2i), have shown protective effects against anthracycline (AC)-induced cardiotoxicity and exhibit partial anticancer effects in animal models. However, clinical evidence for this is scarce. This study aimed to evaluate whether SGLT2i improve the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) undergoing AC-containing chemotherapy. A total of 81,572 patients who underwent AC chemotherapy between 2014 and 2021 were recruited from a nationwide Korean cohort. Patients were classified into three groups: patients with T2DM taking SGLT2i (n = 780) and other hypoglycemic agents excluding SGLT2i (non-SGLT2i; n = 3,455) during AC chemotherapy, and the non-DM group (n = 77,337). The clinical outcome was a composite of heart failure hospitalization, acute myocardial infarction, ischemic stroke, and death. After propensity score matching, 779 SGLT2i users were compared with 7800 non-DM patients and 2,337 non-SGLT2i users. The SGLT2i group had better composite outcomes compared with the non-DM group (adjusted hazard ratio [HR] = 0.35, 95% confidence interval [95% CI] = 0.25–0.51) and compared with the non-SGLT2i group (adjusted HR = 0.47, 95% CI = 0.32–0.69). In conclusion, SGLT2i may contribute to improving clinical outcomes in patients with T2DM undergoing AC-containing chemotherapy, through an emulated target trial using Korean nationwide cohort data.

Dictionary learning (DL), implemented via matrix factorization (MF), is commonly used in computational biology to tackle ubiquitous clustering problems. The method is favored due to its conceptual simplicity and relatively low computational complexity. However, DL algorithms produce results that lack interpretability in terms of real biological data. Additionally, they are not optimized for graph-structured data and hence often fail to handle them in a scalable manner. In order to address these limitations, we propose a novel DL algorithm called online convex network dictionary learning (online cvxNDL). Unlike classical DL algorithms, online cvxNDL is implemented via MF and designed to handle extremely large datasets by virtue of its online nature. Importantly, it enables the interpretation of dictionary elements, which serve as cluster representatives, through convex combinations of real measurements. Moreover, the algorithm can be applied to data with a network structure by incorporating specialized subnetwork sampling techniques. To demonstrate the utility of our approach, we apply cvxNDL on 3D-genome RNAPII ChIA-Drop data with the goal of identifying important long-range interaction patterns (long-range dictionary elements). ChIA-Drop probes higher-order interactions, and produces data in the form of hypergraphs whose nodes represent genomic fragments. The hyperedges represent observed physical contacts. Our hypergraph model analysis has the objective of creating an interpretable dictionary of long-range interaction patterns that accurately represent global chromatin physical contact maps. Through the use of dictionary information, one can also associate the contact maps with RNA transcripts and infer cellular functions. To accomplish the task at hand, we focus on RNAPII-enriched ChIA-Drop data from Drosophila Melanogaster S2 cell lines. Our results offer two key insights. First, we demonstrate that online cvxNDL retains the accuracy of classical DL (MF) methods while simultaneously ensuring unique interpretability and scalability. Second, we identify distinct collections of proximal and distal interaction patterns involving chromatin elements shared by related processes across different chromosomes, as well as patterns unique to specific chromosomes. To associate the dictionary elements with biological properties of the corresponding chromatin regions, we employ Gene Ontology (GO) enrichment analysis and perform multiple RNA coexpression studies.

BackgroundMicroglia, brain resident macrophages, play multiple roles in maintaining homeostasis, including immunity, surveillance, and protecting the central nervous system through their distinct activation processes. Identifying all types of microglia-driven populations is crucial due to the presence of various phenotypes that differ based on developmental stages or activation states. During embryonic development, the E8.5 yolk sac contains erythromyeloid progenitors that go through different growth phases, eventually resulting in the formation of microglia. In addition, microglia are present in neurological diseases as a diverse population. So far, no individual biomarker for microglia has been discovered that can accurately identify and monitor their development and attributes.SummaryHere, we highlight the newly defined biomarker of mouse microglia, UGT1A7C, which exhibits superior stability in expression during microglia development and activation compared to other known microglia biomarkers. The UGT1A7C sensing chemical probe labels all microglia in the 3xTG AD mouse model. The expression of Ugt1a7c is stable during development, with only a 4-fold variation, while other microglia biomarkers, such as Csf1r and Cx3cr1, exhibit at least a 10-fold difference. The UGT1A7C expression remains constant throughout its lifespan. In addition, the expression and activity of UGT1A7C are the same in response to different types of inflammatory activators’ treatment in vitro.ConclusionWe propose employing UGT1A7C as the representative biomarker for microglia, irrespective of their developmental state, age, or activation status. Using UGT1A7C can reduce the requirement for using multiple biomarkers, enhance the precision of microglia analysis, and even be utilized as a standard for gene/protein expression.

ABSTRACT: This study was performed to investigate supplementary effects of probiotic Lacticaseibacillus paracasei NSMJ56 strain on laying performance, egg quality, intestinal histology, antioxidant status, gut immunity and microbiota in laying hens. A total of ninety-six 21-wk-old Hy-Line Brown laying hens were randomly subjected to one of 2 dietary treatments: a control group fed a non-supplemented diet, or a probiotic group fed with a diet supplemented with 1 g of Lacticaseibacillus paracasei NSMJ56 (5 × 108 CFU/kg of diet). The trial lasted for 4 wk. Egg weight was increased (P < 0.05) in laying hens fed probiotic-fed diet compared with the control group. Dietary probiotics did not affect egg quality except for Haugh unit, which was improved (P < 0.05) in the probiotic-fed group. Neither jejunal histology nor cecal short-chain fatty acids were affected by dietary treatments. Dietary probiotics increased the activity of catalase compared with the control group. Flow cytometry analysis revealed that dietary probiotics elevated the CD4+ T cells, but not CD8+ T cells, in jejunal lamina propria. Based on the LEfSe analysis at the phylum and genus levels, Erysipelotrichales, Erysipelotrichia, Flintibater, Dielma, Hespellia, Coprobacter, Roseburia, Anaerotignum, and Coprococcus were enriched in the probiotic group compared with the control group. Taken together, our study showed that dietary probiotics could be used to improve some parameters associated with egg freshness and antioxidant capacity, and to partially alter T cell population and microbial community in laying hens.

Abstract Malignant melanoma is a fatal disease with an increasing global incidence. Despite numerous studies focused on anti-cancer drugs, a variety of side effects of cancer treatment remain challenging. Thus, there is a pressing need to identify novel anti-cancer agents with minimal cytotoxicity and side effects. DB3 (1,3,7,9-tetrahydroxy-2,8-dimethyl-4,6-di[ethanoyl]dibenzofuran) is a member of the dibenzofuran family and is extracted from Ramalina terebrata (Antarctic lichen). We investigated if DB3 exerted an antitumor effect on B16F10 melanoma cells. The results revealed that DB3 exerted time- and dose-dependent reduction of cell viability by inducing apoptosis and significantly suppressing cell proliferation through cell cycle arrest in the G0/G1 phase in B16F10 melanoma cells. Additionally, DB3 impeded the migration and invasiveness of B16F10 cells. Subsequently, we observed that DB3 decreased the expression levels of Cdk4/Cyclin D1 and the phosphorylation of p38, JNK, ERK, and AKT. Furthermore, DB3 decreased melanoma tumor growth in a mouse tumor syngraft model. Based on these findings, we propose that DB3 possesses potential for use as an anti-cancer agent for melanoma treatment.

Abstract The study aimed to identify critical factors associated with the surgical stability of pogonion (Pog) by applying machine learning (ML) to predict relapse following two-jaw orthognathic surgery (2 J-OGJ). The sample set comprised 227 patients (110 males and 117 females, 207 training and 20 test sets). Using lateral cephalograms taken at the initial evaluation (T0), pretreatment (T1), after (T2) 2 J-OGS, and post treatment (T3), 55 linear and angular skeletal and dental surgical movements (T2-T1) were measured. Six ML modes were utilized, including classification and regression trees (CART), conditional inference tree (CTREE), and random forest (RF). The training samples were classified into three groups; highly significant (HS) (≥ 4), significant (S) (≥ 2 and

Abstract Background Oviedomycin is one among several polyketides known for their potential as anticancer agents. The biosynthetic gene cluster (BGC) for oviedomycin is primarily found in Streptomyces antibioticus. However, because this BGC is usually inactive under normal laboratory conditions, it is necessary to employ systematic metabolic engineering methods, such as heterologous expression, refactoring of BGCs, and optimization of precursor biosynthesis, to allow efficient production of these compounds. Results Oviedomycin BGC was captured from the genome of Streptomyces antibioticus by a newly constructed plasmid, pCBA, and conjugated into the heterologous strain, S. coelicolor M1152. To increase the production of oviedomycin, clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system was utilized in an in vitro setting to refactor the native promoters within the ovm BGC. The target promoters of refactoring were selected based on examination of factors such as transcription levels and metabolite profiling. Furthermore, genome-scale metabolic simulation was applied to find overexpression targets that could enhance the biosynthesis of precursors or cofactors related to oviedomycin production. The combined approach led to a significant increase in oviedomycin production, reaching up to 670 mg/L, which is the highest titer reported to date. This demonstrates the potential of the approach undertaken in this study. Conclusions The metabolic engineering approach used in this study led to the successful production of a valuable polyketide, oviedomycin, via BGC cloning, promoter refactoring, and gene manipulation of host metabolism aided by genome-scale metabolic simulation. This approach can be also useful for the efficient production of other secondary molecules encoded by ‘silent’ BGCs.

AbstractThe nucleolus is the largest, membrane-less organelle within the nucleus of eukaryotic cell that plays a critical role in rRNA transcription and assembly of ribosomes. Recently, the nucleolus has been shown to be implicated in an array of processes including the formation of signal recognition particles and response to cellular stress. Such diverse functions of nucleolus are mediated by nucleolar proteins. In this study, we characterized a gene coding a putative protein containing a nucleolar localization sequence (NoLS) in the rice blast fungus, Magnaporthe oryzae. Phylogenetic and domain analysis suggested that the protein is orthologous to Rrp8 in Saccharomyces cerevisiae. MoRRP8-GFP (translational fusion of MoRRP8 with green fluorescence protein) co-localizes with a nucleolar marker protein, MoNOP1 fused to red fluorescence protein (RFP), indicating that MoRRP8 is a nucleolar protein. Deletion of the MoRRP8 gene caused a reduction in vegetative growth and impinged largely on asexual sporulation. Although the asexual spores of ΔMorrp8 were morphologically indistinguishable from those of wild-type, they showed delay in germination and reduction in appressorium formation. Our pathogenicity assay revealed that the MoRRP8 is required for full virulence and growth within host plants. Taken together, these results suggest that nucleolar processes mediated by MoRRP8 is pivotal for fungal development and pathogenesis.

Abstract Background The deep learning-based nodule detection (DLD) system improves nodule detection performance of observers on chest radiographs (CXRs). However, its performance in different pulmonary nodule (PN) locations remains unknown. Methods We divided the CXR intrathoracic region into non-danger zone (NDZ) and danger zone (DZ). The DZ included the lung apices, paramediastinal areas, and retrodiaphragmatic areas, where nodules could be missed. We used a dataset of 300 CXRs (100 normal and 200 abnormal images with 216 PNs [107 NDZ and 109 DZ nodules]). Eight observers (two thoracic radiologists [TRs], two non-thoracic radiologists [NTRs], and four radiology residents [RRs]) interpreted each radiograph with and without the DLD system. The metric of lesion localization fraction (LLF; the number of correctly localized lesions divided by the total number of true lesions) was used to evaluate the diagnostic performance according to the nodule location. Results The DLD system demonstrated a lower LLF for the detection of DZ nodules (64.2) than that of NDZ nodules (83.2, p = 0.008). For DZ nodule detection, the LLF of the DLD system (64.2) was lower than that of TRs (81.7, p

Phedimus aizoon has been utilized as a medicinal plant in Asia. However, the production of phytochemical-rich extracts from P. aizoon and the evaluation of their bioactivity are limited. Herein, phytochemical-rich extracts were prepared by ultrasound-assisted extraction of P. aizoon, with a high extraction yield of 16.56%. The extracts contained about 126 mg of phenolics and 31 mg of flavonoids per g of the extracts. The chromatographic analysis (GC-MS and HPLC analyses) identified 19 notable phytochemicals of the extracts from P. aizoon, including pentacosane, hexadecanoic acid, gallic acid, vanillic acid, and quercetin. The gallic acid content of the extracts was relatively high at 2.75 mg/g. The identified compounds are known to have various bioactivities, such as antioxidant, antibacterial, and antifungal activities. In fact, the prepared extracts exhibited antioxidant activity at 24–28% of that of ascorbic acid. In addition, it showed antibacterial activity against both Escherichia coli (Gram-negative bacteria) and Staphylococcus aureus (Gram-positive bacteria). This study highlights that P. aizoon deserves attention as a natural bioactive substance and emphasizes the need for applications of the extracts from P. aizoon.

Temperature control is critical to prevent overfermentation during the storage, distribution, and export of kimchi. Studies to optimize the freezing conditions for kimchi are lacking. Thus, the present study aimed to evaluate the optimum freezing and storage temperature for kimchi during long-term storage. Kimchi was frozen at −18°C, −40°C, and −80°C for 4 months, followed by thawing at 2°C until the core temperature reached 0°C. Thawing loss was maximum for samples frozen at −18°C, with increased cell membrane disruption, thus considerably decreasing the hardness. Compared to kimchi stored at −18°C, those frozen at −40°C and −80°C resisted the changes in pH, titratable acidity, reducing sugar content, antioxidant activity, and total phenol content. However, the total aerobic count and total lactic acid bacteria values of samples frozen at −18°C sharply decreased among treatments. Therefore, freezing at freezer temperature, particularly −80°C is ideal to maintain the kimchi quality for long-term storage.

The immune-enhancing activity of the combination of Platycodon grandiflorum and Salvia plebeian extracts (PGSP) was evaluated through macrophage activation using RAW264.7 cells. PGSP (250-1000 μg/mL) showed a higher release of NO in a dose-dependent manner. The results showed that PGSP could significantly stimulate the production of PGE2, COX-2, TNF-α, IL-1β, and IL-6 in RAW264.7 cells and promote iNOS, COX-2, TNF-α, IL-1β, IL-4, and IL-6 mRNA expression. Western blot analysis demonstrated that the protein expression of iNOS and COX-2 and the phosphorylation of ERK, JNK, p38, and NF-κB p65 were greatly increased in PGSP-treated cells. PGSP also promoted the phagocytic activity of RAW264.7 cells. All these results indicated that PGSP might activate macrophages through MAPK and NF-κB signaling pathways. Taken together, PGSP may be considered to have immune-enhancing activity and might be used as a potential immune-enhancing agent.

Abstract Perturbed cellular protein homeostasis (proteostasis) and mitochondrial dysfunction play an important role in neurodegenerative diseases, however, the interplay between these two phenomena remains unclear. Mitochondrial dysfunction leads to a delay in mitochondrial protein import, causing accumulation of non-imported mitochondrial proteins in the cytosol and challenging proteostasis. Cells respond by increasing proteasome activity and molecular chaperones in yeast and C. elegans. Here, we demonstrate that in human cells mitochondrial dysfunction leads to the upregulation of a chaperone HSPB1 and, interestingly, an immunoproteasome-specific subunit PSMB9. Moreover, PSMB9 expression is dependent on the translation elongation factor EEF1A2. These mechanisms constitute a defense response to preserve cellular proteostasis under mitochondrial stress. Our findings define a mode of proteasomal activation through the change in proteasome composition driven by EEF1A2 and its spatial regulation, and are useful to formulate therapies to prevent neurodegenerative diseases.

Abstract Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are distinct clinicopathological subtypes of frontotemporal lobar degeneration. They both have atypical parkinsonism, and they usually have distinct clinical features. The most common clinical presentation of PSP is Richardson syndrome, and the most common presentation of CBD is corticobasal syndrome. In this report, we describe a patient with a five-year history of Richardson syndrome and a family history of PSP in her mother and sister. A tau PET scan (18F-APN-1607) revealed low-to-moderate uptake in the substantia nigra, globus pallidus, thalamus and posterior cortical areas, including temporal, parietal and occipital cortices. Neuropathological evaluation revealed widespread neuronal and glial tau pathology in cortical and subcortical structures, including tufted astrocytes in the motor cortex, striatum and midbrain tegmentum. The subthalamic nucleus had mild-to-moderate neuronal loss with globose neurofibrillary tangles, consistent with PSP. On the other hand, there were also astrocytic plaques, a pathological hallmark of CBD, in the neocortex and striatum. To further characterize the mixed pathology, we applied two machine learning-based diagnostic pipelines. These models suggested diagnoses of PSP and CBD depending on the brain region – PSP in the motor cortex and superior frontal gyrus and CBD in caudate nucleus. Western blots of insoluble tau from motor cortex showed a banding pattern consistent with mixed features of PSP and CBD, whereas tau from the superior frontal gyrus showed a pattern consistent with CBD. Real-time quaking-induced conversion (RT-QuIC) using brain homogenates from the motor cortex and superior frontal gyrus showed ThT maxima consistent with PSP, while reaction kinetics were consistent with CBD. There were no pathogenic variants in MAPT with whole genome sequencing. We conclude that this patient had an unclassified tauopathy and features of both PSP and CBD. The different pathologies in specific brain regions suggests caution in diagnosis of tauopathies with limited sampling.

Solar-terrestrial interaction is a dynamic process that manifests itself in the ionosphere. Interplanetary (IP) shocks or solar wind dynamic pressure pulses can generate enhanced brightening in dayside aurora. Foreshock transients are capable of inducing pressure changes, larger in magnitude than solar wind pressure pulses, which also contribute to intensifying dayside aurora. These pressure variations can accelerate particles into the ionosphere, generating field-aligned currents that produce magnetic impulse events and enhanced dayside auroral activity with periods of increased brightening. This study presents several dayside auroral brightening events that are not associated with IP shocks or solar wind dynamic pressure pulses. The dayside auroral brightening events are associated with a green (557.7 nm) to red (630.0 nm) ratio which is greater than 15. These extreme brightening events (EBEs) begin on the eastern or western end of a pre-existing dayside auroral arc. Periodic pulses of enhanced brightening are correlated with large sharp increases in the X-component (points toward the north-geographic pole) from ground magnetometers in the IMAGE network. EBEs occur predominately before magnetic noon and with X-component signatures from high-latitude stations. Ground-based data were obtained from the Kjell Henriksen Observatory in Longyearbyen and the IMAGE magnetometer network.

Abstract We retrospectively analyzed National Health Insurance claims data (January 2002–December 2018) to determine the asthma prevalence and risk factors among preterm infants born in Korea. Patients with asthma were defined as those with a history of asthma medication prescriptions at least twice per year with International Classification of Diseases, Tenth Edition codes J45 and J46. We enrolled 99,139 preterm infants. The prevalence of asthma among preterm and term infants was 32.7% and 26.9%, 21.2% and 19.1%, 6.7% and 5.9%, 2.0%, and 1.6%, and 2.4% and 1.6% at 2, 5, 10, 15, and 16 years of age, respectively. The relative risk (RR) of asthma in preterm infants was 1.1-fold that in female preterm infants. The RR of asthma medication prescriptions for infants with extreme prematurity was 1.92-fold that of infants with moderate/late pre-term status. Among preterm with bronchopulmonary dysplasia (BPD) and respiratory distress syndrome (RDS) without comorbidities, the RRs for the number of asthma medication prescriptions were 1.34 and 1.06, respectively. This study revealed a higher prevalence of asthma among preterm infants than that in term infants. Male sex, extreme prematurity, BPD, and RDS were identified as risk factors for asthma medication prescriptions in preterm infants.

BackgroundManaging complex vascular anomalies in pediatric care requires comprehensive approaches. Sirolimus, an mTOR inhibitor with immunosuppressive and anti-angiogenic properties, offers promise. We evaluated sirolimus's effectiveness and safety in pediatric patients with complex vascular anomalies at a tertiary children's hospital.MethodsOur study included 20 patients, aged 1 month to 19 years, with diverse vascular anomalies resistant to conventional therapies or located in high-risk areas precluding surgery. The evaluation of response encompassed measuring the reduction in the size of the targeted vascular or lymphatic lesions as observed on radiologic imaging, along with considering improvements reported by the patients.ResultsPatients used sirolimus for a median of 2.1 years, ranging from 0.6–4.3 years. Results indicated that 60% of patients achieved complete or partial response (CR/PR), whereas 40% had stable disease (SD). Notably, no disease progression occurred. Lesion size assessment was complex, yet patients' self-reported improvements were considered. Three patients reinitiated sirolimus after discontinuation due to worsening lesions. Sirolimus treatment demonstrated good tolerability, with minor complications except for one case of Pneumocystis jiroveci pneumonia. Group comparisons based on response highlighted better outcomes in patients with vascular tumors (CR/PR group 58.0% vs. SD group 0.0%, P = 0.015) or localized measurable lesions (83.3% vs. 12.5%, P = 0.005).ConclusionOur study underscores sirolimus's potential for treating complex vascular anomalies in pediatric patients. Challenges associated with optimal treatment duration and concurrent interventions necessitate a comprehensive approach and genetic testing to optimize outcomes.

IntroductionSince the analgesic effect of acupuncture stimulation is derived from different mechanisms depending on the type of pain, it is important to know which acupuncture points to stimulate. In this study, to confirm the effect of acupuncture stimulation on acute pain from a neurological point of view, somatosensory evoked potential and sensory threshold changes were evaluated to identify the nerve range that is affected by acupuncture stimulation on LI4 (Hapgok acupuncture point, of the radial nerve) during acute pain.MethodsThe subjects were 40 healthy men and women aged 19–35 years. The study was designed as a randomly controlled, crossover trial with acupuncture stimulation at LI4 as the intervention. The washout period for acupuncture stimulation was 2 weeks, and the subjects were divided into two groups, i.e., an acupuncture stimulation group and a nonstimulation group, with 10 men and 10 women in each group. Somatosensory evoked potential measurement was carried out for 5 min by alternately applying 2 HZ-pulse electrical stimulation to the thumb and the little finger of the hand acupunctured with a 64-channel electroencephalogram. The verbal rating scale was used before and after each acupuncture stimulation session.Result and discussionThe results of the study confirmed that the somatosensory evoked potential amplitude value of the thumb was significantly decreased and that the intensity of sensory stimulation corresponding to a verbal rating scale score of 6 was significantly increased only in the thumb after acupuncture stimulation. Therefore, the results show that acupuncture treatment for acute pain is more effective when direct acupuncture stimulation is applied to the painful area.