National prevalence of atopic dermatitis in Korean adolescents from 2009 to 2022.

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 ß difference (ßdiff) 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.

Machine Learning-Based Prediction of Suicidal Thinking in Adolescents by Derivation and Validation in 3 Independent Worldwide Cohorts: Algorithm Development and Validation Study.

BACKGROUND: Suicide is the second-leading cause of death among adolescents and is associated with clusters of suicides. Despite numerous studies on this preventable cause of death, the focus has primarily been on single nations and traditional statistical methods. OBJECTIVE: This study aims to develop a predictive model for adolescent suicidal thinking using multinational data sets and machine learning (ML). METHODS: We used data from the Korea Youth Risk Behavior Web-based Survey with 566,875 adolescents aged between 13 and 18 years and conducted external validation using the Youth Risk Behavior Survey with 103,874 adolescents and Norway's University National General Survey with 19,574 adolescents. Several tree-based ML models were developed, and feature importance and Shapley additive explanations values were analyzed to identify risk factors for adolescent suicidal thinking. RESULTS: When trained on the Korea Youth Risk Behavior Web-based Survey data from South Korea with a 95% CI, the XGBoost model reported an area under the receiver operating characteristic (AUROC) curve of 90.06% (95% CI 89.97-90.16), displaying superior performance compared to other models. For external validation using the Youth Risk Behavior Survey data from the United States and the University National General Survey from Norway, the XGBoost model achieved AUROCs of 83.09% and 81.27%, respectively. Across all data sets, XGBoost consistently outperformed the other models with the highest AUROC score, and was selected as the optimal model. In terms of predictors of suicidal thinking, feelings of sadness and despair were the most influential, accounting for 57.4% of the impact, followed by stress status at 19.8%. This was followed by age (5.7%), household income (4%), academic achievement (3.4%), sex (2.1%), and others, which contributed less than 2% each. CONCLUSIONS: This study used ML by integrating diverse data sets from 3 countries to address adolescent suicide. The findings highlight the important role of emotional health indicators in predicting suicidal thinking among adolescents. Specifically, sadness and despair were identified as the most significant predictors, followed by stressful conditions and age. These findings emphasize the critical need for early diagnosis and prevention of mental health issues during adolescence.

National prevalence of smoking among adolescents at tobacco tax increase and COVID-19 pandemic in South Korea, 2005-2022.

Prior research has predominantly focused on the overall effects of the tobacco tax increase and the COVID-19 pandemic on adolescent smoking behavior. However, there is a need to examine both the immediate and sustained associations of these two factors on subgroups of adolescents, employing an interrupted time-series model. We aimed to investigate the immediate and sustained association of tobacco tax increase and the COVID-19 pandemic on adolescent smoking prevalence. This study utilized data from the Korea Youth Risk Behavior Web-Based Survey to analyze the prevalence of current smoking among all participants (CSP) and the prevalence of daily smoking among current smokers (DSP) of Korean adolescents (n = 1,159,995; mean, age 14.99; male 51.5%) over 18 years from 2005 to 2022. The study examined 18-year trends in CSP and DSP among Korean adolescents, emphasizing the influences of the 2015 tobacco tax increase and the COVID-19 pandemic, using ß coefficients and their differences (ßdiff) from an interrupted time-series ARIMA model. While CSP exhibited a decreasing trend, DSP exhibited an increasing trend. Tobacco tax increase was associated with both the short and long terms in smoking prevalence, however, the short-term association on prevalence (CSP, - 3.076 [95% CI, - 3.707 to - 2.445]; DSP, - 4.112 [95% CI, - 6.488 to - 1.735]) was stronger. The pandemic was associated with an immediate increase in DSP (9.345 [95% CI, 5.285-13.406]). These effects were strongest among adolescents from low economic status and those exposed to familial secondhand smoking. Supportive programs for adolescents in low-income families will help overcome the effects associated with the pandemic. As a tobacco tax increase was associated with a reduction in smoking prevalence, this could be one method to overcome the effects of the pandemic.

Does the proximal humeral bone quality influence alignment after reverse total shoulder arthroplasty with short humeral stems?

PURPOSE: When compared to standard-length humeral stem in reverse total shoulder arthroplasty (RTSA), short humeral stems in RTSA require good proximal humeral metaphyseal bone quality to gain proper and secure fixation during prosthetic implantation. Shorter humeral stems potentially carry more risk of misalignment than standard or long humeral stems. The hypothesis was that misalignment of the short humeral stems is influenced by regional bone quality. METHODS: RTSA with a short curved humeral stem with neck-shaft angle (NSA) default of 132.5° was reviewed. The study group included 35 cases at a mean age of 75.97 (± 6.23) years. Deltoid-tuberosity index (DTI) was measured to evaluate proximal humeral bone quality. The deltoid tuberosity index was measured at immediately above position of the upper end of the deltoid tuberosity. Stem alignment was given by the angle measured in degrees between the intramedullary humeral shaft axis and the axis of the humeral implant stem. RESULTS: The patient's mean DTI was 1.37 ± 0.16 (median, 1.32; range, 1.12-1.80). 22 patients had poor bone quality (DTI < 1.4), compared to 13 patients with acceptable bone quality (DTI > 1.4). After RTSA, ten humeral components (29%) were neutrally aligned, whereas 25 humeral components (71%) were misaligned. There was no correlation between misalignment and DTI (r = 0.117; p = 0.504). But there was a strong correlation between misalignment and the patient's own NSA (r = - 0.47; p = 0.004). The postoperative stem position and stem misalignment are not associated with functional outcomes (p > 0.05). CONCLUSION: The misalignment of the short curved humeral stem frequently occurs. Poor reginal humeral bone quality does not influence misalignment after RTSA with a short humeral stem. Postoperative stem alignment is associated with the patient's preoperative NSA and method of neck cut. The misalignment does not affect functional outcomes for midterm follow-up. Further long-term follow-up studies are needed to confirm its clinical relevance.

Programmed Death Ligand 1 Regulatory Crosstalk with Ubiquitination and Deubiquitination: Implications in Cancer Immunotherapy.

Programmed death ligand 1 (PD-L1) plays a pivotal role in cancer immune evasion and is a critical target for cancer immunotherapy. This review focuses on the regulation of PD-L1 through the dynamic processes of ubiquitination and deubiquitination, which are crucial for its stability and function. Here, we explored the intricate mechanisms involving various E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) that modulate PD-L1 expression in cancer cells. Specific ligases are discussed in detail, highlighting their roles in tagging PD-L1 for degradation. Furthermore, we discuss the actions of DUBs that stabilize PD-L1 by removing ubiquitin chains. The interplay of these enzymes not only dictates PD-L1 levels but also influences cancer progression and patient response to immunotherapies. Furthermore, we discuss the therapeutic implications of targeting these regulatory pathways and propose novel strategies to enhance the efficacy of PD-L1/PD-1-based therapies. Our review underscores the complexity of PD-L1 regulation and its significant impact on the tumor microenvironment and immunotherapy outcomes.

Machine Learning-Based Prediction of Suicidality in Adolescents With Allergic Rhinitis: Derivation and Validation in 2 Independent Nationwide Cohorts.

BACKGROUND: Given the additional risk of suicide-related behaviors in adolescents with allergic rhinitis (AR), it is important to use the growing field of machine learning (ML) to evaluate this risk. OBJECTIVE: This study aims to evaluate the validity and usefulness of an ML model for predicting suicide risk in patients with AR. METHODS: We used data from 2 independent survey studies, Korea Youth Risk Behavior Web-based Survey (KYRBS; n=299,468) for the original data set and Korea National Health and Nutrition Examination Survey (KNHANES; n=833) for the external validation data set, to predict suicide risks of AR in adolescents aged 13 to 18 years, with 3.45% (10,341/299,468) and 1.4% (12/833) of the patients attempting suicide in the KYRBS and KNHANES studies, respectively. The outcome of interest was the suicide attempt risks. We selected various ML-based models with hyperparameter tuning in the discovery and performed an area under the receiver operating characteristic curve (AUROC) analysis in the train, test, and external validation data. RESULTS: The study data set included 299,468 (KYRBS; original data set) and 833 (KNHANES; external validation data set) patients with AR recruited between 2005 and 2022. The best-performing ML model was the random forest model with a mean AUROC of 84.12% (95% CI 83.98%-84.27%) in the original data set. Applying this result to the external validation data set revealed the best performance among the models, with an AUROC of 89.87% (sensitivity 83.33%, specificity 82.58%, accuracy 82.59%, and balanced accuracy 82.96%). While looking at feature importance, the 5 most important features in predicting suicide attempts in adolescent patients with AR are depression, stress status, academic achievement, age, and alcohol consumption. CONCLUSIONS: This study emphasizes the potential of ML models in predicting suicide risks in patients with AR, encouraging further application of these models in other conditions to enhance adolescent health and decrease suicide rates.

National Trends in Allergic Rhinitis and Chronic Rhinosinusitis and COVID-19 Pandemic-Related Factors in South Korea, from 1998 to 2021.

INTRODUCTION: Existing studies provide insights into the prevalence and environmental factors associated with allergic rhinitis (AR) and chronic rhinosinusitis (CRS) globally. However, limitations still persist in these studies, particularly regarding cohort sizes and the duration of follow-up periods, indicating a need for more comprehensive and long-term research in these fields. Our study aimed to investigate the prevalence, long-term trends, and underlying factors of these conditions in the general population of adult participants (≥19 years) in Korea. METHOD: We analyzed data from adult participants (≥19 years) from the Korea National Health and Nutrition Examination Survey (KNHANES) study to determine the prevalence of AR and CRS from 1998 to 2021. To analyze prevalence trends before and during the COVID-19 pandemic, we employed a weighted linear regression model and obtained ß-coefficients with 95% confidence intervals (CI). RESULTS: Between 1998 and 2021, over a span of 24 years, the comprehensive KNHANES study included 146,264 adult participants (mean age: 47.80 years, standard deviation: 16.49 years; 66,177, 49.3% men). The prevalence of AR and CRS increased from 1998 to 2021, with AR prevalence rising from 5.84% (95% CI, 5.57-6.10) in 1998-2005 to 8.99% (8.09-9.91) in 2021 and CRS from 1.84% (1.70-1.97) in 1998-2005 to 3.70% (3.18-4.23) in 2021. However, the increasing trend has slowed down during the COVID-19 pandemic era. CONCLUSIONS: The significance of continuous monitoring and focused interventions for AR and CRS is underscored by this study. The observed deceleration in the rising prevalence of AR and CRS during the pandemic indicates the possibility of beneficial impacts from lifestyle modifications triggered by the pandemic. These findings call for additional research to explore potential protective effects in greater depth.

Role of Carbohydrate response element-binding protein in mediating dexamethasone-induced glucose transporter 5 expression in Caco-2BBE cells and during the developmental phase in mice.

Glucose transporter 5 (GLUT5), the main fructose transporter in mammals, is primarily responsible for absorbing dietary fructose in the small intestine. The expression of this intestinal gene significantly increases in response to developmental and dietary cues that reach the glucocorticoid receptor and carbohydrate response element-binding protein (ChREBP), respectively. Our study demonstrates that ChREBP is involved in the dexamethasone (Dex)-induced expression of GLUT5 in Caco-2BBE cells and the small intestine of both wild-type and ChREBP-knockout mice. Dex, a glucocorticoid, demonstrated an increase in GLUT5 mRNA levels in a dose- and time-dependent manner. While the overexpression of ChREBP moderately increased GLUT5 expression, its synergistic increase in the presence of Dex was noteworthy, whereas the suppression of ChREBP significantly reduced Dex-induced GLUT5 expression. Dex did not increase ChREBP protein levels but facilitated its nuclear translocation, thereby increasing the activity of the GLUT5 promoter. In vivo experiments conducted on 14-day-old mice pups treated with Dex for three days revealed that only wild-type mice (not ChREBP-knockout mice) exhibited Dex-mediated Glut5 gene induction, which further supports the role of ChREBP in regulating GLUT5 expression. Collectively, our results provide insights into the molecular mechanisms involved in the regulation of GLUT5 expression in response to developmental and dietary signals mediated by glucocorticoids and ChREBP. General significance: The transcription factor ChREBP is important for Dex-mediated Glut5 gene expression in the small intestine.

New Insights into the Role of KLF10 in Tissue Fibrosis.

Fibrosis, characterized by excessive extracellular matrix accumulation, disrupts normal tissue architecture, causes organ dysfunction, and contributes to numerous chronic diseases. This review focuses on Krüppel-like factor 10 (KLF10), a transcription factor significantly induced by transforming growth factor-ß (TGF-ß), and its role in fibrosis pathogenesis and progression across various tissues. KLF10, initially identified as TGF-ß-inducible early gene-1 (TIEG1), is involved in key biological processes including cell proliferation, differentiation, apoptosis, and immune responses. Our analysis investigated KLF10 gene and protein structures, interaction partners, and context-dependent functions in fibrotic diseases. This review highlights recent findings that underscore KLF10 interaction with pivotal signaling pathways, such as TGF-ß, and the modulation of gene expression in fibrotic tissues. We examined the dual role of KLF10 in promoting and inhibiting fibrosis depending on tissue type and fibrotic context. This review also discusses the therapeutic potential of targeting KLF10 in fibrotic diseases, based on its regulatory role in key pathogenic mechanisms. By consolidating current research, this review aims to enhance the understanding of the multifaceted role of KLF10 in fibrosis and stimulate further research into its potential as a therapeutic target in combating fibrotic diseases.

Enhancing air treatment through controlled fabrication of transition metal-doped titanium dioxide nanocomposites for photocatalytic toluene degradation.

Rapid industrial growth and urbanization have resulted in a significant rise in environmental pollution issues, particularly indoor air pollutants. As a result, it is crucial to design and develop technologies and/or catalysts that are not only cost-effective but also promising high performance and practical applicability. However, achieving this goal has been so far remained a challenging task. Herein, a series of transition metal M - TiO2 (M = W, Fe, Mn) nanocrystals was prepared for photocatalytic degradation of volatile organic compounds (VOCs), i.e., toluene. Of the nanocomposites tested, W-TiO2 showed significantly improved photocatalytic activity for VOC degradation under UV irradiation compared to the others. In particular, the optimized W dopant amount of 0.5 wt% resulted in the outstanding degradation performance of toluene (96%) for the obtained W-TiO2(0.5%) nanocomposite. Moreover, W-TiO2(0.5%) nanocomposite exhibited good stability for 32 h working under high toluene concentration (10 ppm) compared to the pristine TiO2. The current work demonstrates the potential usage of M - TiO2 nanocrystals, particularly W-TiO2(0.5%), as a promising photocatalyst for efficient VOCs degradation.

A Micrometric Transformer: Compositional Nanoshell Transformation of Fe3+ -Trimesic-Acid Complex with Concomitant Payload Release in Cell-in-Catalytic-Shell Nanobiohybrids.

Nanoencapsulation of living cells within artificial shells is a powerful approach for augmenting the inherent capacity of cells and enabling the acquisition of extrinsic functions. However, the current state of the field requires the development of nanoshells that can dynamically sense and adapt to environmental changes by undergoing transformations in form and composition. This paper reports the compositional transformation of an enzyme-embedded nanoshell of Fe3+ -trimesic acid complex to an iron phosphate shell in phosphate-containing media. The cytocompatible transformation allows the nanoshells to release functional molecules without loss of activities and biorecognition, while preserving the initial shell properties, such as cytoprotection. Demonstrations include the lysis and killing of Escherichia coli by lysozyme, and the secretion of interleukin-2 by Jurkat T cells in response to paracrine stimulation by antibodies. This work on micrometric Transformers will benefit the creation of cell-in-shell nanobiohybrids that can interact with their surroundings in active and adaptive ways.

Machine learning-based exploration of molecular design descriptors for area-selective atomic layer deposition (AS-ALD) precursors.

CONTEXT: Area-selective atomic layer deposition (AS-ALD) is a thin film deposition technique developed using conventional ALD by considering the surface chemical nature of the substrate. Selecting appropriate precursors is a critical step in developing an efficient AS-ALD process with high deposition selectivity. However, the current efficiency of research on viable AS-ALD precursors is limited because of the absence of theoretical design rules for precursor chemical structures. In this study, our objective is to propose molecular design principle for precursors for AS-ALD, particularly focusing on achieving high deposition selectivity of oxides on diverse substrates. Current preliminary results suggest that ML-based prediction model may provide a fundamental molecular-level understanding of the reactivity of metal oxide precursors, that can be useful for efficient selection of suitable precursors for AS-ALD. METHODS: We employ density functional theory (DFT) calculations and machine learning (ML) techniques to analyze the relationship between the structure and the surface reactivity of the precursor. Considering DFT calculation data (M06L/def2-tzvp, Gaussian 09 and Orca 4.0) and information on precursor structures, artificial neural networks (ANN, neuralnet, R) are applied to identify critical descriptors of the AS-ALD process. Furthermore, we utilize this ANN model to predict precursor reactivity according to surface terminations.

Trends in hypertension prevalence, awareness, treatment, and control in South Korea, 1998-2021: a nationally representative serial study.

The impact of the pandemic on hypertension management is unknown, particularly regarding changes in demographic risk factors. We conducted a comprehensive study between 1998 and 2021 on the long-term trends in hypertension prevalence in South Korea, including a comparison of the pre-pandemic and pandemic eras. Data from 1998 to 2021 of 108,687 Korean adults were obtained through a nationwide, large-scale, and serial study. We conducted a weighted complex sampling analysis on the estimates of national prevalence and compared the slope of hypertension prevalence before and during the pandemic to determine the trend dynamics. We included 108,687 participants over 24 years, 1998-2021. While the prevalence of patients with hypertension consistently increased before the pandemic from 25.51% [95% CI: 24.27-26.75] in 1998-2005 to 27.81% [95% CI: 26.97-28.66] in 2016-2019, the increasing slope in hypertension prevalence slowed during the pandemic period (28.07% [95% CI: 26.16-29.98] for 2021; ßdiff, -0.012 [-0.023 to 0.000]). Hypertension awareness, treatment, control, and control rates among patients receiving treatment followed similar trends. Compared to the pre-pandemic era, individuals aged 19-59 years or male had significantly increased control rates among the treated patients during the pandemic. This study investigated long-term trends in hypertension prevalence, awareness, treatment, and control among Korean adults. The absence of a reduction in the health indicators associated with hypertension during the pandemic implies that medical services for individuals with hypertension remain unaffected.

Hand and Oral Hygiene Practices of South Korean Adolescents Before and During the COVID-19 Pandemic.

Importance: Only a few studies have examined the long-term trends of hand and oral hygiene, especially among adolescents. Objective: To investigate the 15-year trends in frequency of handwashing and toothbrushing and examine the factors associated with hand and oral hygiene, particularly during the COVID-19 pandemic. Design, Setting, and Participants: This cross-sectional study, performed from January 1, 2008, to December 31, 2022, used general population-based data from 963 644 individuals in a national representative survey (Korea Youth Risk Behavior Web-based Survey [KYRBS]). Exposure: COVID-19 pandemic. Main Outcomes and Measures: Trends in hand and oral hygiene practices were measured by how frequently adolescents washed their hands and whether they fulfilled the recommended guidelines for toothbrushing. An interrupted time series analysis using linear and logistic regression models was performed to assess any associations with the COVID-19 pandemic. Hand and oral hygiene behaviors before and during the pandemic in each sociodemographic subgroup were also compared. Results: In the 963 644 adolescents (495 697 [51.4%] male; mean [range] age, 15.01 [12-18] years) who participated in the KYRBS from 2008 to 2022, a 73.3% (95% CI, 59.4%-97.4%; P < .001) immediate increase was seen in overall hand hygiene behavior at the onset of the COVID-19 pandemic compared with the prepandemic period, with a sustained decrease thereafter (ß = -0.018; 95% CI, -0.022 to -0.015; P < .001). Meanwhile, no immediate increase was observed in terms of overall oral hygiene behavior (0.1%; 95% CI, -0.9% to 1.1%; P = .82); however, there was a sustained decrease during the pandemic (ß = -0.018; 95% CI, -0.020 to -0.016; P < .001). Older age, female sex, nonsmoking status, alcohol use, low household economic level, and poor school performance were significantly associated with poor hand hygiene during the pandemic. Conclusions and Relevance: In this cross-sectional study of South Korean adolescents, an increase in the prevalence of hand hygiene was observed during the early pandemic; however, this prevalence decreased over time. Meanwhile, the decrease in the prevalence of oral hygiene was more pronounced during the pandemic. This study recommends stronger guidelines for adolescent health coaches, such as teachers or public health advisers, regarding hygiene behaviors, even after the COVID-19 pandemic ends.

National trends in rheumatoid arthritis and osteoarthritis prevalence in South Korea, 1998-2021.

Studies on the trends in the prevalence of rheumatoid arthritis (RA) and osteoarthritis (OA) are limited, particularly during the COVID-19 pandemic. This study aimed to analyze the temporal trend of RA and OA in South Korean adults from 1998 to 2021, including the COVID-19 pandemic period. The Korea National Health and Nutrition Examination Survey (KNHANES) data on adults aged ≥ 19 years were analyzed to investigate the prevalence of RA and OA from 1998 to 2021. The prevalence trends were compared by the years, and ßdiff (ß difference) was calculated. Odds ratios (ORs) were computed for each disease to examine changes in disease prevalence before and during the pandemic in order to determine the impact of the pandemic on disease prevalence. Among 163,221 Korean adults, the prevalence of RA and OA showed a steady decrease from 2005 (RA: from 1.91% in 2005-2007 to 1.55% in 2016-2019 and OA: from 9.75% in 2005-2007 to 8.27% in 2016-2019), but there was a slight increased after the onset of the COVID-19 pandemic (RA: from 1.23% in 2020 to 1.36% in 2021 and OA: from 8.04% in 2020 to 8.27% in 2021). Vulnerable groups, including participants aged ≥ 60 years (versus 19-60 years, ratio of ORs: 1.222; 95% CI 1.011-1.477), urban residents (ratio of ORs: 1.289; 95% CI 1.007-1.650), and participants with higher education level (ratio of ORs: 1.360; 95% CI 1.119-1.653) showed higher ORs of OA, whereas no particularly vulnerable population was observed for RA. Our findings provide an insight into the long-term trends of RA and OA among adult population and highlight a novel perspective on the impact of COVID-19 on disease prevalence.

Global incidence and prevalence of autoimmune hepatitis, 1970-2022: a systematic review and meta-analysis.

Background: Autoimmune hepatitis (AIH) varies significantly in incidence and prevalence across countries and regions. We aimed to examine global, regional, and national trends in incidence and prevalence of AIH from 1970 to 2022. Methods: We conducted a thorough search of the PubMed/MEDLINE, Embase, CINAHL, Google Scholar, and Cochrane databases from database inception to August 9, 2023, using the search term "autoimmune hepatitis" in combination with "incidence," "prevalence," or "trend." Only general population-based observational studies with larger samples sizes were considered for inclusion. Studies that recruited convenience samples, and those with fewer than 50 participants were excluded. Summary data were extracted from published reports. A random effects model was used and pooled estimates with 95% CI were used to calculate the incidence and prevalence of AIH. Heterogeneity was evaluated using the I2 statistic. The study protocol was registered with PROSPERO, CRD42023430138. Findings: A total of 37 eligible studies, encompassing more than 239 million participants and 55,839 patients with AIH from 18 countries across five continents, were included in the analysis. Global pooled incidence and prevalence of AIH were found to be 1.28 cases per 100,000 inhabitant-years (95% CI, 1.01-1.63, I2 = 99·51%; number of studies, 33; sample population, 220,673,674) and 15.65 cases per 100,000 inhabitants (95% CI, 13.42-18.24, I2 = 99·75%; number of studies, 26; sample population, 217,178,684), respectively. The incidence of AIH was greater in countries with high Human Development Index (>0.92), in North America and Oceania (compared with Asia), among females, adults (compared with children), and high latitude (>45°). Similar patterns in AIH prevalence were observed. Pooled AIH prevalence increased gradually from 1970 to 2019 (1970-1999; 9.95 [4.77-15.13], I2 = 95·58% versus 2015-2022; 27.91 [24.86-30.96], I2 = 99·32%; cases per 100,000 inhabitants). The overall incidence and prevalence of AIH, as well as some subgroup analyses of the studies, displayed asymmetry in the funnel plots, suggesting potential evidence of publication bias. Interpretation: AIH incidence and prevalence have increased significantly and exhibit substantial variation across regions worldwide. Further research is required to assess the incidence and prevalence of AIH, specifically in South America and Africa. Funding: National Research Foundation of Korea.

Tandem-biocatalysis reactors constructed by topological evolution of CaCO3 particles into hollow metal hydroxide spheres.

Despite remarkable advances in the design and synthesis of hollow inorganic spheres (HISs), the harsh synthetic conditions have precluded the applications of HISs to biochemical and biological fields. Herein we report a biocompatible strategy for synthesizing metal hydroxide HISs (MH-HISs) by simply mixing CaCO3 particles with metal ions in water. The ion-exchange reaction between Ca2+ and metal ions leads to the structural and chemical evolution from solid CaCO3 particles to hollow MH-HISs via core-shell and yolk-shell structures, while enabling the encapsulation of enzymes to the shells without loss of catalytic activities. The biocompatible protocol makes multienzymatic cascade reactions achievable, with great recyclability due to mechanical durability of MH-HISs.

KLF10 Inhibits TGF-ß-Mediated Activation of Hepatic Stellate Cells via Suppression of ATF3 Expression.

Liver fibrosis is a progressive and debilitating condition characterized by the excessive deposition of extracellular matrix proteins. Stellate cell activation, a major contributor to fibrogenesis, is influenced by Transforming growth factor (TGF-ß)/SMAD signaling. Although Krüppel-like-factor (KLF) 10 is an early TGF-ß-inducible gene, its specific role in hepatic stellate cell activation remains unclear. Our previous study demonstrated that KLF10 knockout mice develop severe liver fibrosis when fed a high-sucrose diet. Based on these findings, we aimed to identify potential target molecules involved in liver fibrosis and investigate the mechanisms underlying the KLF10 modulation of hepatic stellate cell activation. By RNA sequencing analysis of liver tissues from KLF10 knockout mice with severe liver fibrosis induced by a high-sucrose diet, we identified ATF3 as a potential target gene regulated by KLF10. In LX-2 cells, an immortalized human hepatic stellate cell line, KLF10 expression was induced early after TGF-ß treatment, whereas ATF3 expression showed delayed induction. KLF10 knockdown in LX-2 cells enhanced TGF-ß-mediated activation, as evidenced by elevated fibrogenic protein levels. Further mechanistic studies revealed that KLF10 knockdown promoted TGF-ß signaling and upregulated ATF3 expression. Conversely, KLF10 overexpression suppressed TGF-ß-mediated activation and downregulated ATF3 expression. Furthermore, treatment with the chemical chaperone 4-PBA attenuated siKLF10-mediated upregulation of ATF3 and fibrogenic responses in TGF-ß-treated LX-2 cells. Collectively, our findings suggest that KLF10 acts as a negative regulator of the TGF-ß signaling pathway, exerting suppressive effects on hepatic stellate cell activation and fibrogenesis through modulation of ATF3 expression. These results highlight the potential therapeutic implications of targeting the KLF10-ATF3 axis in liver fibrosis treatment.