Direct Identification of O─O Bond Formation Through Three-Step Oxidation During Water Splitting by Operando Soft X-ray Absorption Spectroscopy.

Anionic redox allows the direct formation of O─O bonds from lattice oxygens and provides higher catalytic in the oxygen evolution reaction (OER) than does the conventional metal ion mechanism. While previous theories have predicted and experiments have suggested the possible O─O bond, it has not yet been directly observed in the OER process. In this study, operando soft X-ray absorption spectroscopy (sXAS) at the O K-edge and the operando Raman spectra is performed on layered double CoFe hydroxides (LDHs) after intercalation with [Cr(C2O4)3]3-, and revealed a three-step oxidation process, staring from Co2+ to Co3+, further to Co4+ (3d6L), and ultimately leading to the formation of O─O bonds and O2 evolution above a threshold voltage (1.4 V). In contrast, a gradual oxidation of Fe is observed in CoFe LDHs. The OER activity exhibits a significant enhancement, with the overpotential decreasing from 300 to 248 mV at 10 mA cm-2, following the intercalation of [Cr(C2O4)3]3- into CoFe LDHs, underscoring a crucial role of anionic redox in facilitating water splitting.

Long-term effects on growth in preterm and small for gestational age infants: A national birth cohort study.

BACKGROUND: Premature and small-for-gestational-age (SGA) infants tend to have long-term growth morbidities such as short stature, failure to thrive, and obesity. Although most of these infants show catch-up growth at 2-4 years of age, they are still more susceptible to childhood obesity and related metabolic disorders. Those who fail to achieve catch-up will suffer from pathological short stature and neurodevelopmental impairment through adulthood. This study aims to depict the growth pattern of premature or SGA infants and their growth morbidities in Taiwan. METHODS: Data were obtained from a nationally representative cohort of 24,200 pairs of postpartum women and newborns in the Taiwan Birth Cohort Study (TBCS), using structured questionnaire interviews. A total of 16,358 infants were included and three follow-up surveys were completed at 6, 18, and 36 months after the deliveries. We constructed growth curves to conduct an in-depth investigation into anthropometric data, applying a linear mixed model. Logistic regression was used to model the relevant outcomes, with adjustment for various potential confounding factors. RESULTS: Despite being born shorter and lighter, preterm and SGA infants generally showed catch-up growth and had no higher odds ratios (ORs) of developing short stature or failure to thrive compared to appropriate-for-gestational-age (AGA) term infants before 3 years of age. Preterm SGA infants, particularly females, had higher ORs for obesity at the 36-month follow-up. CONCLUSION: This is the first nationwide population-based study depicting the growth of SGA infants in Taiwan. The growth patterns of preterm and term SGA infants are different from those of preterm and term AGA infants. Further research is necessary to understand the growth trajectories of preterm and SGA infants and their associations with later diseases.

Dehydration Achieving the Iron Spin State Regulation of Prussian Blue for Boosted Sodium-Ion Storage Performance.

Prussian blue analogs (PBAs) show promise as cathodes for sodium-ion batteries due to their notable cycle stability, cost-effectiveness, and eco-friendly nature, yet the presence of interstitial water limits the specific capacity and obstructs Na+ mobility within the material. Although considerable experimental efforts are focused on dehydrating water for capacity enhancement, there is still a deficiency of a comprehensive understanding of the low capacity of low-spin Fe resulting from interstitial water, which holds significance in Na+ storage. This study introduces a novel gas-assisted heat treatment method to efficiently remove interstitial water from Fe-based PBA (NaFeHCF) electrodes and combines experiments and theoretical calculations to reveal the iron spin state regulation that is related to the capacity enhancement mechanism. This dehydration strategy significantly enhances battery capacity, especially the portion at higher voltages (3.4-4.0 V). The increase in capacity is attributed to the following factors: an enhanced proportion of Fe2+, reduced water content which facilitates faster charge transfer, and the activation of low spin Fe2+. The optimized NaFeHCF demonstrated impressive half-cell performance of retaining 87.3% capacity after 2000 cycles at a 5 C rate and achieving 100 mAh g-1 capacity over 200 cycles when being paired with hard carbon, exhibiting its practical potential.

"Warrior who transcends adversity": A qualitative examination of resilience among mothers caring for adolescents with congenital heart disease.

PURPOSE: Parenting resilience is essential for the well-being and development of children with chronic illnesses. Given the importance of parenting resilience in this context, this study explored the nature of parenting resilience among mothers caring for adolescents with congenital heart disease (CHD). DESIGN AND METHODS: We adopted Husserl's phenomenological approach and conducted semistructured in-depth interviews. In addition, we conducted purposive sampling at the pediatric cardiology outpatient departments of 2 medical centers in Taiwan to recruit 11 mothers of adolescents with CHD; all of these adolescents had received open-heart surgery. Furthermore, we analyzed data by using Colaizzi's approach, and we adhered to the COnsolidated criteria for REporting Qualitative research checklist. RESULTS: Mothers caring for adolescents with CHD was a dynamic process involving problem solving. The 11 mothers in this study employed resilience to remain strong, provided a sense of normalcy for their children, and approached challenges calmly and bravely. We uncovered three major themes among these mothers: "providing support for the child, "facing challenges with equanimity," and "overcoming adversity through positivity and gratitude." CONCLUSIONS: The present results provide a deeper understanding of how mothers caring for adolescents with CHD can cultivate resilience. PRACTICE IMPLICATIONS: The study's findings can inform transitional programs for adolescents with CHD and their families, with nursing professionals supporting mothers' resilience.

Strong support effect induced by MXene for the synthesis of metal sulfides nanosheet arrays with sulfur vacancies towards selective CO2-to-CO photoreduction.

Selective CO2-to-CO photoreduction is under intensive research and requires photocatalysts with tuned microstructures to accelerate the reaction kinetics. Here, we report CuInS2 nanosheet arrays with sulfur vacancies (VS) grown on the two-dimensional (2D) support of Ti3C2Tx MXene for CO2-to-CO photoreduction. Our results reveal that the use of Ti3C2Tx induces strong support effect, which causes the hierarchical nanosheet arrays growth of CuInS2 and simultaneously leads to charge transfer from CuInS2 to Ti3C2Tx support, resulting in VS formed in CuInS2. The strong support effect based on Ti3C2Tx is proven to be applicable to prepare a series of different metal indium sulfide arrays with VS. CuInS2 nanosheet arrays with VS supported on Ti3C2Tx benefit the photocatalytic selective reduction of CO2 to CO, manifesting a remarkable over 14.8-fold activity enhancement compared with pure CuInS2. The experimental and computational investigations pinpoint that VS of CuInS2 resulting from the support effect of Ti3C2Tx lowers the barrier of the rate-limiting step of *COOH → *OH + *CO, which is the key to the photoactivity enhancement. This work demonstrates MXene support effects and offers an effective approach to regulate the atomic microstructure of metal sulfides toward enhancing photocatalytic performance.

Neural evidence of core foundations and conceptual change in preschool numeracy.

Symbolic numeracy first emerges as children learn the meanings of number words and how to use them to precisely count sets of objects. This development starts before children enter school and forms a foundation for lifelong mathematics achievement. Despite its importance, exactly how children acquire this basic knowledge is unclear. Here we test competing theories of early number learning by measuring event-related brain potentials during a novel number word-quantity comparison task in 3-4-year-old preschool children (N = 128). We find several qualitative differences in neural processing of number by conceptual stage of development. Specifically, we find differences in early attention-related parietal electrophysiology (N1), suggesting that less conceptually advanced children process arrays as individual objects and more advanced children distribute attention over the entire set. Subsequently, we find that only more conceptually advanced children show later-going frontal (N2) sensitivity to the numerical-distance relationship between the number word and visual quantity. The nature of this response suggested that exact rather than approximate numerical meanings were being associated with number words over frontal sites. No evidence of numerical distance effects was observed over posterior scalp sites. Together these results suggest that children may engage parallel individuation of objects to learn the meanings of the first few number words, but, ultimately, create new exact cardinal value representations for number words that cannot be defined in terms of core, nonverbal number systems. More broadly, these results document an interaction between attentional and general cognitive mechanisms in cognitive development. RESEARCH HIGHLIGHTS: Conceptual development in numeracy is associated with a shift in attention from objects to sets. Children acquire meanings of the first few number words through associations with parallel attentional individuation of objects. Understanding of cardinality is associated with attentional processing of sets rather than individuals. Brain signatures suggest children attribute exact rather than approximate numerical meanings to the first few number words. Number-quantity relationship processing for the first few number words is evident in frontal but not parietal scalp electrophysiology of young children.

DPP9 regulates NQO1 and ROS to promote resistance to chemotherapy in liver cancer cells.

Chemotherapy has been the standard treatment for liver cancer. However, intrinsic or acquired drug resistance remains a major barrier to successful treatment. At present, the underlying molecular mechanisms of chemoresistance in liver cancer have not been elucidated. Dipeptidyl peptidase 9 (DPP9) is a member of the dipeptidyl peptidase IV family that has been found to be highly expressed in a variety of tumors, including liver cancer. It is unclear whether DPP9 affects chemoresistance in liver cancer. In this study, we find that DPP9 weakens the responses of liver cancer cells to chemotherapy drugs by up-regulating NQO1 and inhibiting intracellular ROS levels. In terms of mechanism, DPP9 inhibits ubiquitin-mediated degradation of NRF2 protein by binding to KEAP1, up-regulates NRF2 protein levels, promotes mRNA transcription of NQO1, and inhibits intracellular ROS levels. In addition, the NQO1 inhibitor dicoumarol can enhance the efficacy of chemotherapy drugs in liver cancer cells. Collectively, our findings suggest that inhibiting DPP9/NQO1 signaling can serve as a potential therapeutic strategy for liver cancer.

Substrate Charge Transfer Induced Ferromagnetism in MnSe/SrTiO3 Ultrathin Films.

The observation of superconductivity in MnSe at 12 GPa motivated us to investigate whether superconductivity could be induced in MnSe at ambient conditions. A strain-induced structural change in the ultrathin film could be one route to the emergence of superconductivity. In this report, we present the physical property of MnSe ultrathin films, which become tetragonal (stretched ab-plane and shortened c-axis) on a (001) SrTiO3 (STO) substrate, prepared by the pulsed laser deposition (PLD) method. The physical properties of the tetragonal MnSe ultrathin films exhibit very different characteristics from those of the thick films and polycrystalline samples. The tetragonal MnSe films show substantial conductivity enhancement, which could be associated with the presence of superparamagnetism. The optical absorption data indicate that the electron transition through the indirect bandgap to the conduction band is significantly enhanced in tetragonal MnSe. Furthermore, the X-ray Mn L-edge absorption results also reveal an increase in unoccupied state valance bands. This theoretical study suggests that charge transfer from the substrate plays an important role in conductivity enhancement and the emergence of a ferromagnetic order that leads to superparamagnetism.

Baseline viral load and on-treatment hepatocellular carcinoma risk in chronic hepatitis B: A multinational cohort study.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) risk persists in chronic hepatitis B (CHB) patients despite antiviral therapy. The relationship between pre-treatment baseline hepatitis B virus (HBV) viral load and HCC risk during antiviral treatment remains uncertain. METHODS: This multinational cohort study aimed to investigate the association between baseline HBV viral load and on-treatment HCC risk in 20,826 noncirrhotic, hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with baseline HBV DNA levels ≥2,000 IU/mL (3.30 log10 IU/mL) who initiated entecavir or tenofovir treatment. The primary outcome was on-treatment HCC incidence, stratified by baseline HBV viral load as a categorical variable. RESULTS: In total, 663 patients developed HCC over a median follow-up of 4.1 years, with an incidence rate of 0.81 per 100 person-years (95% confidence interval [CI], 0.75-0.87). Baseline HBV viral load was significantly associated with HCC risk in a non-linear parabolic pattern, independent of other factors. Patients with baseline viral load between 6.00 and 7.00 log10 IU/mL had the highest on-treatment HCC risk (adjusted hazard ratio, 4.28; 95% CI, 2.15-8.52; P < .0001) compared to those with baseline viral load ≥8.00 log10 IU/mL, who exhibited the lowest HCC risk. CONCLUSION: Baseline viral load showed a significant, non-linear, parabolic association with HCC risk during antiviral treatment in noncirrhotic CHB patients. Early initiation of antiviral treatment based on HBV viral load may help prevent irreversible HCC risk accumulation in CHB patients.

Association between frozen embryo transfer and childhood allergy: a retrospective cohort study.

RESEARCH QUESTION: Does frozen embryo transfer (FET) increase the risk of allergic diseases in offspring? DESIGN: This study followed up 653 singleton children: 166 born through FET and 487 born through natural conception. Demographic characteristics, perinatal information and allergic diseases of children and their parents were collected through clinical medical systems and questionnaires. Among these 653 children, allergen-specific immunoglobulin E (IgE) testing was performed using peripheral blood samples collected from 207 children: 145 in the FET group and 62 in the natural conception group. The prevalence of allergic diseases and positive rates of allergen-specific IgE testing were compared between the two groups with adjustments for confounding factors. RESULTS: The prevalence of food allergy was significantly higher in children born through FET compared with children born through natural conception (adjusted OR = 3.154, 95% CI 1.895-5.250; P < 0.001). In addition, positive rates of food allergen sensitization were higher in children in the FET group compared with children in the natural conception group (adjusted OR = 5.769, 95% CI 2.859-11.751, P < 0.001). Children in the FET group had a higher positive sensitization rate to at least one allergen compared with children in the natural conception group (adjusted OR = 3.127, 95% CI 1.640-5.961, P < 0.001). No association was observed between FET and other allergic diseases, including asthma (P = 0.136), atopic dermatitis (P = 0.130) and allergic rhinitis (P = 0.922). Allergen sensitization IgE testing indicated no differences between the two groups in terms of positive sensitization rates of other common allergens, including animal and insect allergens (P = 0.627), inhaled outdoor allergens (P = 0.915) and inhaled outdoor allergens (P = 0.544). CONCLUSION: This study suggests that children born through FET have increased risk of developing food allergy in early childhood.

Impact of HCV eradication by directly acting antivirals on glycemic indices in chronic hepatitis C patients -a nationwide Taiwan HCV registry.

BACKGROUND/AIMS: Hepatitis C virus (HCV) eradication using antiviral agents augments the metabolic profile. Changes in glycated hemoglobin (HbA1c) levels in chronic hepatitis C patients who receive glecaprevir/pibrentasvir (GLE/PIB) remain elusive. METHODS: Data from 2417 patients treated with GLE/PIB from the Taiwan HCV Registry were analyzed, and pretreatment HbA1c levels were compared with 3-months after the-end-of treatment levels. A sustained virological response (SVR) was defined as undetectable HCV RNA at 12 weeks after the end of treatment. A significant change in HbA1c level was defined as the 75th percentile of the change in the HbA1c level before and after treatment (decrement >0.2%). RESULTS: Serum HbA1c levels decreased significantly (6.0 vs 5.9%, P < 0.001). Post-treatment HbA1c levels decreased in all subgroups, except in non-SVR patients (5.7 vs 5.7%, P = 0.79). Compared to patients without significant HbA1c improvement (decrement >0.2%), those with HbA1c improvement were older (60.2 vs 58.6 years, P < 0.001), had higher serum creatinine levels (1.9 vs 1.6 mg/dL, P < 0.001), triglycerides (129.8 vs 106.2 mg/dL, P < 0.001), fasting glucose (135.8 vs 104.0 mg/dL, P < 0.001), and pretreatment HbA1c (7.1 vs 5.7%, P < 0.001) and had a higher proportion of male sex (57.9% vs 50.9%, P = 0.003), diabetes (84.3 vs 16.8%, P < 0.001), more advanced stages of chronic kidney disease (CKD) (15.7 vs 11.1 %, P < 0.001), anti-diabetic medication use (47.3 vs 16.4%, P < 0.001) and fatty liver (49.6 vs 38.3 %, P < 0.001). Multivariate analysis revealed that the factors associated with significant HbA1c improvement were age (odds ratio [OR]/95% confidence intervals [CI]: 1.01/1.00-1.02, P = 0.01), HbA1c level (OR/CI: 2.83/2.48-3.24, P < 0.001) and advanced CKD stages (OR/CI: 1.16/1.05-1.28, P = 0.004). If the HbA1c variable was not considered, the factors associated with significant HbA1c improvement included alanine aminotransferase level (OR/CI, 1.002/1.000-1.004, P = 0.01), fasting glucose level (OR/CI: 1.010/1.006-1.013, P < 0.001), and diabetes (OR/CI: 3.35/2.52-4.45, P < 0.001). CONCLUSIONS: The HbA1c levels improved shortly after HCV eradication using GLE/PIB. The improvement in glycemic control can be generalized to all subpopulations, particularly in patients with a higher baseline HbA1c level or diabetes.

TLR2 Derangements Likely Play a Significant Role in the Inflammatory Response and Thrombosis in Patients with Ph(-) Classical Myeloproliferative Neoplasm.

We investigated the role of toll-like receptors (TLRs) in inflammatory pathways in Philadelphia chromosome-negative myeloproliferative neoplasms (Ph(-)MPNs). TLR2 expression was increased in ET, PV, and MPN (grouped as (PV + (ET) + MF)), whereas TLR4 was elevated only in MPN. TLR3, 7, and 9 were not elevated. Cultured monocyte-derived dendritic cells and plasma assays in TLR2-elevated patients were found to secrete more cytokines than those from TLR2-normal patients. These facts suggest that TLR2 is the major inflammatory pathways in MPN. We also measured S100A9 and reactive oxygen species (ROS), revealing increased S100A9 in PV, MF, and MPN, while ROS were only increased in MF. These data suggests that MPNs initially involve TLR2, with minor contributions from TLR4, and with S100A9, leading to ROS formation, JAK2 mutation, and progression to MF or leukemia. Furthermore, patients with JAK2 mutations or leukocytosis exhibited higher TLR2 expression. In leukocyte-platelet interactions, cells from MPN patients displayed a stronger response to a TLR2 agonist than TLR4 agonist. A TLR2 inhibitor (but not a TLR4 inhibitor) attenuated this response. Thrombosis incidence was higher in TLR2-elevated patients (29%) than in TLR2-normal patients (19%). These findings suggest that TLR2 likely contributes to thrombosis in MPN.

Complete genome sequence of Bacillus stercoris BST19, a soil isolate with potential anti-microbial properties using PacBio sequencing.

We report the complete genome sequence of Bacillus stercoris BST19, an isolate from the allotment soil in Tainan, Taiwan. The genome was obtained using the PacBio Sequel II platform, yielding a circular chromosome of 4,167,147 bp with a 43.9% GC content.

Age, sex, and pre-arrest comorbidities shape the risk trajectory of sudden cardiac death- Patterns highlighted by population data in Taiwan.

OBJECTIVES: Few reports have indicated the secular trend in the sudden cardiac death (SCD) incidence and pre-arrest comorbidities. This study aimed to comprehensively analyze the trend of SCD incidence and its association with pre-arrest comorbidities. METHODS: This population-based cohort study analyzed Taiwan's National Health Insurance (NHI) research database and identified SCD incidents by inspecting data from all emergency department visits from 2011 to 2018. The inclusion criteria were ICD-9:427.5 or 427.41, or ICD-10:I46.9, I46.8, or I46.2. Pre-existing comorbidities were confirmed based on medication use. Multivariable logistic regression was adopted with covariates age, sex, and pre-existing comorbidities. RESULTS: This study reviewed a total of 184,164,969 person-year records, and identified 92,138 SCD incidents. From 2011 to 2018, the SCD incidence rate increased from 36.3 to 55.4 per 100,000 enrollees in Taiwan. The top five pre-arrest comorbidities were stable, while the prevalence of chronic kidney disease rose significantly. Compared to those aged 20-29, enrollees aged >65 years had significantly higher odds of SCD (aOR:27.30, 95% CI:26.05-28.61). Higher odds of SCD were noted in the enrollees who had a seizure (aOR:2.24, 95% CI:2.12-2.38), parkinsonism (aOR:1.81, 95% CI:1.73-1.89), psychological disorders (aOR:1.59, 95% CI:1.56-1.62), diabetes mellitus (aOR:1.44, 95% CI:1.41-1.46), heart diseases (aOR:1.41, 95% CI:1.38-1.44). CONCLUSIONS: The incidence of SCD steadily increased in Taiwan from 2011 to 2018. Hypertension, diabetes mellitus, heart disease, psychological disorders, and arthritis were major pre-arrest comorbidities. Age is the most important risk factor for SCD. Further large-scaled population-based study that investigated in diverse ethnicities from countries in addition to Asians would be warranted.

The lived experience of mothers caring for school-age children with Pompe disease: A qualitative study.

PURPOSE: To explore the lived experiences of mothers caring for school-age children with Pompe disease. DESIGN AND METHODS: A qualitative study using a descriptive phenomenology approach. Semi-structured interviews were conducted from October to December 2022 with 10 mothers of school-age children diagnosed with Pompe disease, which were identified through the Taiwan Pompe Disease Association. Colaizzi's phenomenological method was employed for data analysis. RESULTS: The study identified five themes in the caregiving experiences of mothers: 1. unwavering parenting beliefs; 2. child-centric approach; 3. focus on peer relationships and coping strategies; 4. integration of learning, treatment, and rehabilitation; and 5. embracing and navigating life's challenges. Mothers balanced education, treatment, and rehabilitation for their children with Pompe disease, offering perspectives into the caregiving experience. CONCLUSIONS: This study highlights the complex experiences of mothers caring for children with Pompe disease, emphasizing the importance of comprehensive support. PRACTICE IMPLICATIONS: Insights into the perspectives of mothers can aid health-care professionals in understanding the challenges faced by families with children diagnosed with Pompe disease and can enable the development of strategies for providing comprehensive psychological support to improve mental health outcomes for these children and their families. Increased awareness among health-care professionals and in the society leads to an informed and empathetic approach to addressing the unique challenges faced by children with Pompe disease and their families.

Implementing next-generation sequencing for diagnosis and management of hereditary hearing impairment: a comprehensive review.

INTRODUCTION: Sensorineural hearing impairment (SNHI), a common childhood disorder with heterogeneous genetic causes, can lead to delayed language development and psychosocial problems. Next-generation sequencing (NGS) offers high-throughput screening and high-sensitivity detection of genetic etiologies of SNHI, enabling clinicians to make informed medical decisions, provide tailored treatments, and improve prognostic outcomes. AREAS COVERED: This review covers the diverse etiologies of HHI and the utility of different NGS modalities (targeted sequencing and whole exome/genome sequencing), and includes HHI-related studies on newborn screening, genetic counseling, prognostic prediction, and personalized treatment. Challenges such as the trade-off between cost and diagnostic yield, detection of structural variants, and exploration of the non-coding genome are also highlighted. EXPERT OPINION: In the current landscape of NGS-based diagnostics for HHI, there are both challenges (e.g. detection of structural variants and non-coding genome variants) and opportunities (e.g. the emergence of medical artificial intelligence tools). The authors advocate the use of technological advances such as long-read sequencing for structural variant detection, multi-omics analysis for non-coding variant exploration, and medical artificial intelligence for pathogenicity assessment and outcome prediction. By integrating these innovations into clinical practice, precision medicine in the diagnosis and management of HHI can be further improved.

Progression of fertility-sparing treatment for atypical endometrial hyperplasia in a woman with lynch syndrome: a case report and review of the literature.

Endometrial cancer in Lynch syndrome is characterized by a higher incidence, younger age at onset, and increased recurrence rates compared to sporadic cases, while the safety and efficacy of fertility-sparing treatments remain uncertain. This case report presents the oncology outcome of fertility-preserving treatment in a 39-year-old woman diagnosed with Lynch syndrome and atypical endometrial hyperplasia. Initially, she responded favorably to fertility-preserving treatment but subsequently experienced disease relapse and rapid progression during retreatment. Final pathology revealed endometrial cancer with metastasis to the right ovary, categorized as FIGO 2023 stage IIIA1. This population's unique molecular mechanisms and genetic mutations warrant special consideration when opting for fertility-sparing treatment. We have reviewed and summarized the oncology and pregnancy outcomes among Lynch syndrome and MMR-deficient patients through previous literature. However, no studies have investigated retreatment after recurrence in Lynch syndrome. Our case highlights the potential risks associated with retreatment following relapse. Vigilant monitoring and prompt consideration of surgical intervention are recommended upon disease relapse.

Exposure-associated DNA methylation among people exposed to multiple industrial pollutants.

BACKGROUND: Current research on the epigenetic repercussions of exposure to a combination of pollutants is limited. This study aims to discern DNA methylation probes associated with exposure to multiple pollutants, serving as early effect markers, and single-nucleotide polymorphisms (SNPs) as surrogate indicators for population susceptibility. The investigation involved the analysis of urine exposure biomarkers for 11 heavy metals (vanadium, arsenic, mercury, cadmium, chromium, nickel, lead, manganese, copper, strontium, thallium), polycyclic aromatic hydrocarbon (PAHs) (1-hydroxypyrene), genome-wide DNA methylation sequencing, and SNPs array on all study participants. The data were integrated with metabolomics information and analyzed both at a community level based on proximity to home addresses relative to the complex and at an individual level based on exposure biomarker concentrations. RESULTS: On a community level, 67 exposure-related CpG probes were identified, while 70 CpG probes were associated with urine arsenic concentration, 2 with mercury, and 46 with vanadium on an individual level. These probes were annotated to genes implicated in cancers and chronic kidney disease. Weighted quantile sum regression analysis revealed that vanadium, mercury, and 1-hydroxypyrene contributed the most to cg08238319 hypomethylation. cg08238319 is annotated to the aryl hydrocarbon receptor repressor (AHRR) gene, and AHRR hypomethylation was correlated with an elevated risk of lung cancer. AHRR was further linked to deregulations in phenylalanine metabolism, alanine, aspartate, and glutamate metabolism, along with heightened oxidative stress. Additionally, three SNPs (rs11085020, rs199442, and rs10947050) corresponding to exposure-related CpG probes exhibited significant interaction effects with multiple heavy metals and PAHs exposure, and have been implicated in cancer progression and respiratory diseases. CONCLUSION: Our findings underscore the pivotal role of AHRR methylation in gene-environment interactions and highlight SNPs that could potentially serve as indicators of population susceptibility in regions exposed to multiple heavy metals and PAHs.

Clinical Predictors of Nontuberculous Mycobacteria Lung Disease and Coisolates of Potential Pathogenic Microorganisms in Noncystic Fibrosis Bronchiectasis.

Background: In bronchiectasis, nontuberculous mycobacteria (NTM) lung disease (NTM-LD) is a well-known coexisting infection. However, microorganism coisolates and clinical NTM-LD predictors are poorly studied. Methods: Patients with bronchiectasis diagnosed by means of computed tomography between January 2017 and June 2020 were screened, using the date of computed tomography as the index date. Those with a major bronchiectasis diagnosis in ≥2 follow-up visits after the index date were enrolled in the study, and NTM-LD occurrence and its association with pneumonia and hospitalization within 1 year were analyzed. Results: Of the 2717 participants, 79 (2.9%) had NTM-LD diagnosed. The factors associated with NTM-LD included hemoptysis, postinfectious bronchiectasis, a tree-in-bud score ≥2, a modified Reiff score ≥4, and chronic obstructive pulmonary disease (adjusted odds ratios, 1.80, 2.36, 1.78, 2.95, and 0.51, respectively). Compared with patients in the non-NTM group, those with NTM-LD had higher rates of hospitalization (15.9% vs 32.9%; P < .001) and pneumonia (9.8% vs 20.3%; P = .003). Pseudomonas aeruginosa was the most common microorganism in those with NTM-LD and those in the non-NTM group (10.1% vs 7.8%; P = .40). However, compared with those in the non-NTM group, Acinetobacter baumannii and Escherichia coli were more prevalent in patients with NTM-LD (0.7% vs 3.8% [P = .03%] and 1.0% vs 3.8% [P = .05], respectively). Conclusions: Postinfectious bronchiectasis with hemoptysis, higher radiological involvement, and a tree-in-bud pattern were associated with NTM-LD risk. The rate of A baumannii and E coli coisolation was higher in bronchiectasis populations with NTM-LD.

The role of ALDH1A1 in glioblastoma proliferation and invasion.

High-grade gliomas, including glioblastoma multiforme (GBM), continue to be a leading aggressive brain tumor in adults, marked by its rapid growth and invasive nature. Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), an enzyme, plays a significant role in tumor progression, yet its function in high-grade gliomas is still poorly investigated. In this study, we evaluated ALDH1A1 levels in clinical samples of GBM. We also assessed the prognostic significance of ALDH1A1 expression in GBM and LGG (low grade glioma) patients using TCGA (The Cancer Genome Atlas) database analysis. The MTT and transwell assays were utilized to examine cell growth and the invasive capability of U87 cells, respectively. We quantitatively examined markers for cell proliferation (Ki-67 and cyclin D1) and invasion (MMP2 and 9). A Western blot test was conducted to determine the downstream signaling of ALDH1A1. We found a notable increase in ALDH1A1 expression in high-grade gliomas compared to their low-grade counterparts. U87 cells that overexpressed ALDH1A1 showed increased cell growth and invasion. We found that ALDH1A1 promotes the phosphorylation of AKT, and inhibiting AKT phosphorylation mitigates the ALDH1A1's effects on tumor growth and migration. In summary, our findings suggest ALDH1A1 as a potential therapeutic target for GBM treatment.