Growth trajectories of children born preterm and full term with low birth weight to preschool ages: A nationwide study.

CONTEXT: Preterm (PT) and full term with low birth weight (FT-LBW) children are at a high-risk of poor growth outcomes. OBJECTIVE: To investigate the growth trajectories of PT and FT-LBW children from birth to preschool ages. METHODS: This study included 1,150,508 infants (PT, 41,454; FT-LBW, 38,250) who underwent the first three rounds (4-6, 9-12, and 18-24 months) of the National Health Screening Program for Infants and Children (NHSPIC). Growth measurements were obtained from the NHSPIC database and converted into Z-scores. Growth data at 2, 4, and 6 years old were measured as outcome variables. The impact of being born small on poor growth outcomes was investigated using a generalized estimating equation and Cox proportional-hazards regression analysis. RESULTS: The median birth weights of the PT, FT-LBW, and full term (FT) groups were 2.3, 2.4, and 3.2 kg, respectively. The incidence of short stature (height Z-score < -2 standard deviation score [SDS]) and failure to thrive (FTT) (body mass index (BMI) Z-score < -2 SDS) was the highest in the FT-LBW group, followed by the PT and FT groups. At 4 years old, the incidence rates were 6.0% vs. 5.2% vs. 1.9% for short stature and 4.6% vs. 3.9% vs. 1.7% for FTT. The ß estimate of height outcome was lower in both the PT (-0.326 SDS) and FT-LBW (-0.456 SDS) groups. CONCLUSIONS: The FT-LBW group was consistently shorter and lighter throughout the preschool period than the PT group, highlighting the significance of growth monitoring in high-risk populations.

Reliability of the DI-60 Digital Image Analyzer for Detecting Platelet Clumping and Obtaining Accurate Platelet Counts.

Pseudothrombocytopenia caused by platelet clumping (PC) can lead to unnecessary platelet transfusions or underdiagnosis of hematologic neoplasms. To overcome these limitations, we assessed the capacity of the Sysmex DI-60 digital morphology analyzer (Sysmex, Kobe, Japan) for detecting PC and determining an accurate platelet count in the presence of PC. For this purpose, 135 samples with or without PC (groups Y and N, respectively) were processed by an examiner (a hematologic specialist) using both the Sysmex XN-9000 and DI-60 analyzers. Although the platelet aggregate (PA) and giant platelet (GP) counts reported by the DI-60 and the examiner exhibited strong correlations, they proved inadequate as effective indicators for screening samples containing PC. Between the PA and GP counts and four platelet indices (the platelet distribution width [PDW], mean platelet volume [MPV], platelet large cell ratio [P_LCR], and plateletcrit [PCT]) reported by the XN-9000, we observed statistically significant correlations (both overall and with group Y), but they were relatively weak. The platelet counts determined using the DI-60 and light microscopy in group Y showed substantial variations. Although the performance of the DI-60 was reliable for detecting PA and GP in smear images, such fixed areas are not representative of whole samples. Further, in the presence of PC, the resulting platelet counts determined using the DI-60 were not sufficiently accurate to be accepted as the final count.

Advancing cancer immunotherapy through siRNA-based gene silencing for immune checkpoint blockade.

Cancer immunotherapy represents a revolutionary strategy, leveraging the patient's immune system to inhibit tumor growth and alleviate the immunosuppressive effects of the tumor microenvironment (TME). The recent emergence of immune checkpoint blockade (ICB) therapies, particularly following the first approval of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors like ipilimumab, has led to significant growth in cancer immunotherapy. The extensive explorations on diverse immune checkpoint antibodies have broadened the therapeutic scope for various malignancies. However, the clinical response to these antibody-based ICB therapies remains limited, with less than 15% responsiveness and notable adverse effects in some patients. This review introduces the emerging strategies to overcome current limitations of antibody-based ICB therapies, mainly focusing on the development of small interfering ribonucleic acid (siRNA)-based ICB therapies and innovative delivery systems. We firstly highlight the diverse target immune checkpoint genes for siRNA-based ICB therapies, incorporating silencing of multiple genes to boost anti-tumor immune responses. Subsequently, we discuss improvements in siRNA delivery systems, enhanced by various nanocarriers, aimed at overcoming siRNA's clinical challenges such as vulnerability to enzymatic degradation, inadequate pharmacokinetics, and possible unintended target interactions. Additionally, the review presents various combination therapies that integrate chemotherapy, phototherapy, stimulatory checkpoints, ICB antibodies, and cancer vaccines. The important point is that when used in combination with siRNA-based ICB therapy, the synergistic effect of traditional therapies is strengthened, improving host immune surveillance and therapeutic outcomes. Conclusively, we discuss the insights into innovative and effective cancer immunotherapeutic strategies based on RNA interference (RNAi) technology utilizing siRNA and nanocarriers as a novel approach in ICB cancer immunotherapy.

Fine tuning of CpG spatial distribution with DNA origami for improved cancer vaccination.

Multivalent presentation of ligands often enhances receptor activation and downstream signalling. DNA origami offers a precise nanoscale spacing of ligands, a potentially useful feature for therapeutic nanoparticles. Here we use a square-block DNA origami platform to explore the importance of the spacing of CpG oligonucleotides. CpG engages Toll-like receptors and therefore acts to activate dendritic cells. Through in vitro cell culture studies and in vivo tumour treatment models, we demonstrate that square blocks induce Th1 immune polarization when CpG is spaced at 3.5 nm. We observe that this DNA origami vaccine enhances DC activation, antigen cross-presentation, CD8 T-cell activation, Th1-polarized CD4 activation and natural-killer-cell activation. The vaccine also effectively synergizes with anti-PD-L1 for improved cancer immunotherapy in melanoma and lymphoma models and induces long-term T-cell memory. Our results suggest that DNA origami may serve as a platform for controlling adjuvant spacing and co-delivering antigens in vaccines.

Different particle sizes of Momordica charantia leaf powder modify the rheological and textural properties of corn starch-based 3D food printing ink.

The study determined the effect of incorporating Momordica charantia leaf powder (MCLP) into corn-starch 3D food-printing ink as a functional ingredient. The effects of the particle size (75, 131, and 200 µm) and quantity of MCLP on 3D printing performance, structural, textural, and rheological properties of corn starch gel were evaluated with different concentrations (5, 10, and 15 % (w/w)) of corn starch. The viscoelastic properties of food inks were determined considering their behavior during extrusion and self-recovery after printing. Scanning electron microscope was used to characterize the microstructure. Based on the results, a high starch content (15 %) with 5 % MCLP was more favorable for 3D food printing. In addition, 3D printing performance, textural and rheological properties of formulated ink was mainly governed by the particle size of MCLP. The food ink with a 5 % mass fraction of 200 µm MCLP had the highest printing precision and the best masticatory properties.

Association between smartphone usage and health outcomes of adolescents: A propensity analysis using the Korea youth risk behavior survey.

OBJECTIVES: We aimed to investigate the association between smartphone use and adverse behavioral health outcomes using nationwide Korea Youth Risk Behavior Web-based Survey data for 2017 and 2020. METHODS: The 2020 data (N = 54,809) were used to analyze the relationships between daily smartphone usage time (non-user, 0-2 h [hour], 2-4 h, 4-6 h, 6-8 h, and > 8 h), and adverse health outcomes (stress, sleep, depression, suicide, substance use, and smartphone overdependence). A 1:1 propensity score matching (PSM) was used to control for confounding variables. RESULTS: A total of 40,998 adolescents with < 4 h/day and > 4 h/day of usage were included. Adolescents' mean smartphone usage time in 2020 increased compared to that in 2017 (weighted % of > 2 h/day; 64.3% vs. 85.7%). The curvilinear relationships between smartphone usage time and adverse health outcomes were prominent after > 4 h/day. Adolescents using smartphones 2-4 h/day showed no increased adverse health outcomes compared to non-users, except for smartphone overdependence. Using a smartphone > 4 h/day was significantly associated with stress perception (1.16; 1.11-1.22), suicidal ideation (1.22; 1.13-1.31), and substance use (alcohol, 1.66; 1.57-1.75) after PSM. CONCLUSIONS: Our study demonstrated the curvilinear relationship between smartphone usage time and adverse health outcomes in adolescents. Our findings can help establish smartphone usage guidelines for adolescents.

The risk of pediatric cardiovascular diseases in offspring born to mothers with systemic lupus erythematosus: a nationwide study.

Background: Systemic lupus erythematosus (SLE), a common autoimmune disease predominantly affecting women, has been linked to various complications during pregnancy. The transfer of anti-Ro/SSA antibodies from SLE-affected mothers to their offspring can lead to neonatal lupus and cardiac issues. This study investigated the association between maternal SLE and the risk of pediatric cardiovascular disorders. Methods: The study utilized South Korea's National Health Insurance Service (NHIS) database, covering 3,505,737 children born between 2007 and 2017 and tracked until 2020. Maternal SLE cases were identified using the World Health Organization's International Classification of Diseases Tenth revision (ICD-10) codes and linked with delivery records. Cardiologic disorders were categorized into congenital heart disease (CHD), arrhythmic disorders, and acquired heart disease. Propensity score matching with 1:4 ratios was applied to the set control group. Results: Among 3,505,737 children, 0.7% (n = 23,330) were born to mothers with SLE. The incidence of preterm birth was significantly higher in the maternal SLE group (5.9% vs. 3.0%). Compared with the control group, children born to mothers with SLE exhibited a significantly elevated risk of overall CHDs (5.5%, adjusted odds ratio [aOR] 1.21; 95% confidence interval [CI] 1.14-1.29), including atrial septal defect (1.18; 1.09-1.28) and patent ductus arteriosus (1.15; 1.03-1.30). In addition, a notably higher risk was observed in arrhythmic disorders (complete atrioventricular block 7.20; 2.41-21.49) and acquired cardiac disorders, including cardiomyopathy (1.40; 1.17-1.68) and mucocutaneous lymph node syndrome (MCLS) (1.27; 1.15-1.43). Conclusions: Maternal SLE is associated with congenital and acquired cardiac disorders in offspring, including structural, arrhythmic, and MCLS. This study highlights the need for continuous cardiovascular monitoring from the prenatal stage to preadolescence in these children due to multifactorial influences involving maternal autoantibodies, genetic predisposition, and environmental factors.

Annual Change in Fungal Concentrations and Allergic Sensitization Rates to Alternaria and Cladosporium in Korea During the Period 1998-2022.

PURPOSE: Atmospheric fungi are associated with respiratory allergies in humans, and some fungal spores can cause allergic diseases. Environmental and biological factors influence the concentrations of atmospheric spores. In this study, we evaluated the climate change-induced annual variations in fungal spore concentrations and allergic sensitization rates in the Seoul Metropolitan Area over a period of 25 years. METHODS: Fungal spores and pollen were obtained from Hanyang University Seoul and Guri Hospitals; they were identified and counted for 25 years (1998-2022). The study participants included patients who underwent tests for allergic diseases in both hospitals. Their allergenic sensitization rates were determined via allergic skin prick and serum tests, after which their sensitization rates to allergenic fungi and pollens were calculated. The daily climatic variables were obtained from the Korea Meteorological Administration. RESULTS: The total annual atmospheric fungal concentrations decreased in both areas during the period. Simultaneously, we recruited 21,394 patients with allergies (asthma, 1,550; allergic rhinitis, 5,983; and atopic dermatitis, 5,422) from Seoul and Guri Hospitals for allergenic fungal sensitization evaluations over the period. The allergenic fungal sensitization rates decreased annually in both areas over that time `+(Alternaria [3.5%] and Cladosporium [4.4%] in 1998; Alternaria [0.2%] and Cladosporium [0.2%] in 2022). In contrast, the annual pollen concentrations increased with the sensitization rates to pollen in children. CONCLUSIONS: The atmospheric fungal concentrations decreased annually, with allergic sensitization rate decreasing over the period of 25 years. Allergenic fungal sporulation could decrease with climate changes, such as desertification and drought. Extended monitoring periods and further large-scale studies are required to confirm the causality and to evaluate the impact of climate change.

Salvia miltiorrhiza Bunge Ameliorates Benign Prostatic Hyperplasia through Regulation of Oxidative Stress via Nrf-2/ HO-1 Activation.

Oxidative stress is a key factor in the pathogenesis of benign prostatic hyperplasia (BPH) that leads to inflammation. This study aimed to evaluate the ameliorative effects of Salvia miltiorrhiza Bunge extract (HLT-101) on BPH through the regulation of oxidative stress and inflammation. A testosterone propionate (TP)-induced BPH rat model was orally administered HLT-101 (20, 40, or 80 mg/kg), and its effects on oxidative stress- and inflammation-related gene expression were examined. Further, HLT-101 was assessed for its effect on reactive oxygen species (ROS) levels and Nrf-2/HO-1 signaling pathways in BPH-1 cells. HLT-101 decreased testosterone-induced excessive free radical production and inflammatory factor activation. Moreover, HLT-101 treatment significantly decreased the intracellular ROS level in the TNF-α and IFN-γ treated BPH-1 cells through the activation of Nrf-2. In addition, HLT-101 treatment inhibited the NF-κB pathway and androgen receptor (AR) signaling, which is highly linked to the pathogenesis of BPH. Therefore, HLT-101 has the potential to be an effective treatment reagent for BPH because of its ability to reduce inflammation and oxidative stress via Nrf-2/HO-1 signaling.

Combined effect of heating temperature and content of pectin on the textural properties, rheology, and 3D printability of potato starch gel.

Three-dimensional (3D) printing is one of the emerging techniques which fabricates customized foods with desired sensory characteristics. Rheological properties of 3D printing materials are vitally important in printability which govern the flowability and structural stability. Due to its unique gel-forming characteristics, potato starch has been extensively used in myriad food applications, such as 3D printing. However, little attention has been paid to the combined effect of heating temperature and pectin addition on the properties of potato starch gels. Thus, this study investigated the impact of different pectin contents (1, 1.5, and 2 %) on printability and the rheological and textural properties of potato starch gels heated at different temperatures (70, 80, and 90 °C). The gel heating temperature governs pectin-driven modifications in potato starch gels. Pectin addition increased the 3D printability, viscosity, storage modulus, hardness, gumminess, and springiness of starch gel at higher temperatures (80 °C and 90 °C). In contrast, at lower temperatures (70 °C), pectin addition decreased printability, viscosity, storage modulus, hardness, gumminess, and springiness. Therefore, the gel heating temperature influences the impact of pectin on printability, rheology, and textural properties. Accordingly, the combined effects of pectin and heating temperature should be considered in pectin-based 3D food-printing ink formulations.

Pre-Pandemic Distribution of Bacterial Species in Nasopharyngeal Swab Specimens from Pediatric and Adult Patients Detected via RT-PCR Using the Allplex Respiratory Panel.

Background: Recently, panel-based molecular diagnostics for the simultaneous detection of respiratory viruses and bacteria in nasopharyngeal swab (NPS) specimens have been highlighted. We identified the distribution of bacterial species in NPS specimens collected from pediatric and adult patients by employing RT-PCR (Allplex respiratory panel 4, RP4, Seegene) to estimate its applicability in a panel-based assay for detecting respiratory viruses. Methods: We used 271 and 173 NPS specimens from pediatric and adult patients, respectively. The results of the Allplex RP4 panel using NPS (NPS-RP4) from adult patients were compared with those of the Seeplex PneumoBacter ACE Detection assay (Seegene), which used sputum for testing (sputum-Seeplex). Results: A total of 147 specimens (54.2%) were positive for the NPS-RP4 panel in pediatric patients. There were 94, 77, 10, 3, 3, and 2 specimens that were positive for Haemophilus influenzae (HI), Streptococcus pneumoniae (SP), Mycoplasma pneumoniae (MP), Chlamydia pneumoniae (CP), Bordetella pertussis (BP), and B. parapertussis (BPP), respectively. Among 173 adult patients, 39 specimens (22.5%) were positive in the NPS-RP4. Thirty specimens were positive for HI, and 13 were positive for SP. One specimen tested positive for both MP and Legionella pneumophila (LP). CP, BP, and BPP results were all negative. However, 126 specimens (72.8%) had positive results with sputum-Seeplex (99 SP, 59 HI, three LP, and two MP), and the overall percentage of agreement between the two assays was 39.3% in the adult patients. Conclusions: Bacterial species in NPS from more than half of pediatric patients were detected. Performing the Allplex RP4 assay with NPS revealed additional respiratory bacteria that are not detected in current clinical practices, which do not include bacterial testing, demanding the use of sputum specimens. However, the use of NPS showed low agreement with standard assays using sputum in adult patients. Thus, more research is needed to develop a reliable RT-PCR method using NPS specimens in adult patients.

Analysis of Watson for oncology and clinicians' treatment recommendations for patients with breast cancer in Korea: A single center experience.

Background: Various clinical applications have been attempted using artificial intelligence (AI) clinical decision support system (CDSS), and it has become a starting point for personalized cancer treatment. We aimed to identify the degree of agreement between the AI-CDSS, Watson for Oncology (WFO), and the clinician in treatment recommendations for Korean breast cancer patients and to provide guidelines for future improvement. Methods: One hundred and eighty-three breast cancer patients who underwent treatment at the Pusan National University Hospital between January 1, 2016 and May 31, 2017 were enrolled in this study. The concordance between WFO's and clinicians' treatment recommendations were examined according to various factors. Results: WFO gave the same treatment option recommendations as clinicians in 74 (40.4%) of the cases. According to the logistic regression, the difference in recommendation concordance between stage I and stage III was statistically significant (P = 0.004), and there was no difference among other factors. Conclusion: The concordance of treatment recommendations was low overall. However, this is largely attributable to the differences of medical insurance system and healthcare environment between the United States and Korea. In the future, region-specific features should be considered or reflected during the development of AI-CDSS.

Retrospective evaluation of the clinical utility of reconstructed computed tomography images using artificial intelligence in the oral and maxillofacial region.

The aim of this study was to convert medical images stored in 3 mm slices in the picture archiving and communication system (PACS) to 1 mm slices, using artificial intelligence (AI), and to analyze the accuracy of the AI. The original 1.0 mm CT slices of the facial bone were obtained from 30 patients and reformatted to a rough CT slice of 3.0 mm. CT slices of 1.0 mm were subsequently reconstructed from those of 3.0 mm using AI. The AI and rough CT images were superimposed on the original CT images. Fourteen hard-tissue and five soft-tissue landmarks were selected for measuring the discrepancy. The overall average differences in values for the hard-tissue landmarks were 1.31 ± 0.38 mm and 0.81 ± 0.17 mm for the rough and AI CT images, respectively. The values for the soft-tissue landmarks were 1.18 ± 0.35 mm and 0.54 ± 0.17 mm for the rough and AI CT images, respectively. The differences for all the landmarks, excluding point A and pogonion, were statistically significant. Within the limitations of the study it seems that CT images reconstructed using AI might provide more accurate clinical information with a discrepancy of less than 1.0 mm.

Association between long working hours and unmet dental needs in wage workers.

BACKGROUND: Many previous studies on the reasons behind unmet dental needs focus on economic issues. However, in this research, we aimed to investigate the relationship between long working hours and unmet dental needs while considering the influence of occupational factors in wage workers. METHODS: This study used data from the Korea National Health and Nutrition Examination Survey (2012-2018) and analyzed a sample of 12,104 wage workers. Unmet dental needs were defined as cases in which individuals did not receive dental care, despite their need for examination or treatment, within the last year. Long working hours were defined as exceeding 52 h per week, based on the standard working hours stipulated by the Labor Standards Act. A binomial model was applied to calculate the prevalence ratio through multivariate logistic regression analysis. RESULTS: The prevalence of unmet dental needs was observed in 3,948 cases (32.5%), among which 1,478 attributed their presence to lack of time. The prevalence of unmet dental needs showed an inverse relationship with the education level and household income. The wage workers who worked long hours had the highest prevalence of unmet dental needs. Long working hours were found to be 1.18 times (95% CI 1.07-1.29) more likely to result in unmet dental care compared to working less than 40 h. The relationship between long working hours and unmet dental needs were statistically significant only in men (PR 1.24, 95% CI 1.07-1.43). However, the relationship between long working hours and unmet dental needs owing to time were in both men and women (men: PR 1.59, 95% CI 1.20-2.11, women: PR 1.90, 95% CI 1.48-2.43). CONCLUSIONS: This study confirmed that long working hours and unmet dental needs are related when occupational factors are taken into consideration, despite the absence of oral health indicators. Using this study as a reference, further research is necessary to identify the underlying causes of unmet dental care and to improve access to dental services in the future.

Molecular Mechanism of Selective Al2O3 Atomic Layer Deposition on Self-Assembled Monolayers.

Area-selective atomic layer deposition (AS-ALD) of insulating metallic oxide layers could be a useful nanopatterning technique for making increasingly complex semiconductor circuits. Although the alkanethiol self-assembled monolayer (SAM) has been considered promising as an ALD inhibitor, the low inhibition efficiency of the SAM during ALD processes makes its wide application difficult. We investigated the deposition mechanism of Al2O3 on alkanethiol-SAMs using temperature-dependent vibrational sum-frequency-generation spectroscopy. We found that the thermally induced formation of gauche defects in the SAMs is the main causative factor deteriorating the inhibition efficiency. Here, we demonstrate that a discontinuously temperature-controlled ALD technique involving self-healing and dissipation of thermally induced stress on the structure of SAM substantially enhances the SAM's inhibition efficiency and enables us to achieve 60 ALD cycles (6.6 nm). We anticipate that the present experimental results on the ALD mechanism on the SAM surface and the proposed ALD method will provide clues to improve the efficiency of AS-ALD, a promising nanoscale patterning and manufacturing technique.

Controlled spatial characteristics of ligands on nanoparticles: Determinant of cellular functions.

Interactions of various ligands and receptors have been extensively investigated because they regulate a series of signal transduction leading to various functional cellular outcomes. The receptors on cell membrane recognize their specific ligands, resulting in specific binding between ligands and receptors. Accumulating evidence reveals that the receptors recognize the difference on the spatial characteristics of ligands as well as the types of ligands. Thus, control on spatial characteristics of multiple ligands presented on therapeutic nanoparticles is believed to impact the cellular functions. Specifically, the localized and multivalent distribution of ligands on nanoparticles can induce receptor oligomerization and receptor clustering, controlling intensity or direction of signal transduction cascades. Here, we will introduce recent studies on the use of material-based nanotechnology to control spatial characteristics of ligands and their effect on cellular functions. These therapeutic nanoparticles with controlled spatial characteristics of ligands may be a promising strategy for maximized therapeutic outcome.

Efficacy of pure beta tricalcium phosphate graft in dentoalveolar surgery: a retrospective evaluation based on serial radiographic images.

BACKGROUND: The use of beta-tricalcium phosphate (beta-TCP) in dental surgery is limited owing to its rapid absorption compared to mixed formulations of hydroxyapatite. However, newly developed pure beta-TCP crystals have demonstrated slow absorption; hence, they last longer within the defect and act as a scaffold until new bone formation. The oral environment is unique and can prove unfavorable for bone grafts due to the high infection rate in the oral cavity and the fragile condition of the oral mucosa. The aim of this study was to evaluate the feasibility of using pure beta-TCP bone grafts in various dental treatments. METHODS: Panoramic X-ray images of 25 patients who underwent bone grafting during dental surgery were analyzed. A specially treated pure beta-TCP crystal, Neo Bone® (Neo Bone®, SN Biologics Co., Ltd, Seoul, Korea), was used in this study. The bone density at the graft site was compared with that of the surrounding bone using the ImageJ software (Wayne Rasband, NIH USA). RESULTS: Six months after surgery, the bone graft density was similar to that of the surrounding bone in 20 patients and increased in 5 patients. No adverse effects, such as infection, dehiscence, or graft failure, were observed. CONCLUSION: The newly developed pure beta-TCP crystal was slowly absorbed and served as support until new bone formation at the defect site, thus demonstrating its potential for use in various oral conditions requiring bone grafting.

An adaptive behavioral control motif mediated by cortical axo-axonic inhibition.

Genetically defined subgroups of inhibitory interneurons are thought to play distinct roles in learning, but heterogeneity within these subgroups has limited our understanding of the scope and nature of their specific contributions. Here we reveal that the chandelier cell (ChC), an interneuron type that specializes in inhibiting the axon-initial segment (AIS) of pyramidal neurons, establishes cortical microcircuits for organizing neural coding through selective axo-axonic synaptic plasticity. We found that organized motor control is mediated by enhanced population coding of direction-tuned premotor neurons, with tuning refined through suppression of irrelevant neuronal activity. ChCs contribute to learning-dependent refinements by providing selective inhibitory control over individual pyramidal neurons rather than global suppression. Quantitative analysis of structural plasticity across axo-axonic synapses revealed that ChCs redistributed inhibitory weights to individual pyramidal neurons during learning. These results demonstrate an adaptive logic of the inhibitory circuit motif responsible for organizing distributed neural representations. Thus, ChCs permit efficient cortical computation in a targeted cell-specific manner.

Polygenic Variants Linked to Oxidative Stress and the Antioxidant System Are Associated with Type 2 Diabetes Risk and Interact with Lifestyle Factors.

Oxidative stress is associated with insulin resistance and secretion, and antioxidant systems are essential for preventing and managing type 2 diabetes (T2DM). This study aimed to explore the polygenic variants linked to oxidative stress and the antioxidant system among those associated with T2DM and the interaction of their polygenic risk scores (PRSs) with lifestyle factors in a large hospital-based cohort (n = 58,701). Genotyping, anthropometric, biochemical, and dietary assessments were conducted for all participants with an average body mass index of 23.9 kg/m2. Genetic variants associated with T2DM were searched through genome-wide association studies in participants with T2DM (n = 5383) and without T2DM (n = 53,318). The Gene Ontology database was searched for the antioxidant systems and oxidative stress-related genes among the genetic variants associated with T2DM risk, and the PRS was generated by summing the risk alleles of selected ones. Gene expression according to the genetic variant alleles was determined on the FUMA website. Food components with low binding energy to the GSTA5 protein generated from the wildtype and mutated GSTA5_rs7739421 (missense mutation) genes were selected using in silico analysis. Glutathione metabolism-related genes, including glutathione peroxidase (GPX)1 and GPX3, glutathione disulfide reductase (GSR), peroxiredoxin-6 (PRDX6), glutamate-cysteine ligase catalytic subunit (GCLC), glutathione S-transferase alpha-5 (GSTA5), and gamma-glutamyltransferase-1 (GGT1), were predominantly selected with a relevance score of >7. The PRS related to the antioxidant system was positively associated with T2DM (ORs = 1.423, 95% CI = 1.22-1.66). The active site of the GASTA proteins having valine or leucine at 55 due to the missense mutation (rs7739421) had a low binding energy (<-10 kcal/mol) similarly or differently to some flavonoids and anthocyanins. The PRS interacted with the intake of bioactive components (specifically dietary antioxidants, vitamin C, vitamin D, and coffee) and smoking status (p < 0.05). In conclusion, individuals with a higher PRS related to the antioxidant system may have an increased risk of T2DM, and there is a potential indication that exogenous antioxidant intake may alleviate this risk, providing insights for personalized strategies in T2DM prevention.