Association between red cell distribution width and hypertension: Results from NHANES 1999-2018.

The relationship between red cell distribution width (RDW) and hypertension remains a contentious topic, with a lack of large-scale studies focusing on the adults in the United States. This study aimed to investigate the association between RDW and hypertension among US adults from 1999 to 2018. METHODS: Data were derived from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. RDW values were obtained from the Laboratory Data's Complete Blood Count with 5-part Differential-Whole Blood module. Hypertension data were obtained through hypertension questionnaires and blood pressure measurements. Multivariable weighted logistic regression analyses were conducted to assess the association between RDW and hypertension, followed by subgroup and smooth curve analyses. RESULTS: Compared to the non-hypertensive group, the hypertensive group exhibited higher RDW values (13.33±1.38 vs. 12.95±1.27, P <0.001). After adjusting for covariates, weighted multivariable logistic regression analysis revealed a positive correlation between RDW and hypertension prevalence (OR: 1.17, 95% CI 1.13, 1.21, P <0.001). When RDW was included as a categorical variable, participants in the fourth quartile had the highest risk of hypertension (OR: 1.86, 95% CI 1.70, 2.03, P <0.001). Subgroup analysis showed that, except for age, BMI and weak/failing kidneys, gender, race, education level, smoking, alcohol use, congestive heart failure, and stroke did not significantly influence this correlation (all P-values for interaction >0.05).Smooth curve fitting analysis revealed a reverse J-shaped relationship between RDW and hypertension prevalence, with an inflection point at 12.93%. CONCLUSION: We first explored the relationship between RDW and hypertension among US adults and discovered a reverse J-shaped association, providing further insights into the relationship between blood cell counts and hypertension and offering a new foundation for hypertension prevention and control.

Prevention or ex-post forcing? The impact of dual environmental regulation on corporate environmental behavior.

Corporate reactions to environmental regulation are the hottest topics in research on corporate environmental behavior. However, a few studies incorporate other environmental behavior into the same framework. By constructing a comprehensive indicator system of dual environmental regulation, this paper uses a comparative analysis to discuss Chinese A-listed corporations' environmental behavior from 2009 to 2017, which were influenced by dual environmental regulation. The study's results show that formal environmental regulation (FER) has a significant U-shaped effect on pre-emptive environmental behavior (PEB) but an insignificant impact on ex-post environmental behavior (NEB). After categorizing the various forms of FER, this study finds that market-incentive environmental regulation has a significant inverted U-shaped effect on NEB but an insignificant impact on PEB, voluntary-participation regulation have a significant U-shaped effect on PEB and an inverted U-shaped effect on their NEB, and command-control regulation has significant influence on neither PEB nor NEB. In addition, informal environmental regulation (IER) has a significantly positive and negative effect on PEB and NEB. This study shows that corporate perceptions of policies can have a positive impact on the interaction between the FER and PEB but a negative impact on the interaction between the IER and PEB, and no impact on the interaction between FER or IER and NEB. Moreover, the impact of FER and IER on corporate environmental behavior (CEB) varies depending on factors like ownership, industry characteristics, the market environment, and regional development. Therefore, governments should understand the choices related to corporate environmental behavior under the dual environmental regulation-formal and informal-and prioritize the synergistic impact of these dual environmental regulation, highlighting their enforceability, and take into account the heterogeneity of their targets and the market to stimulate PEB and decrease NEB to help enterprises align their short-term economic objectives with their long-term social goals.

Distinctive Lipid Characteristics of Colorectal Cancer Revealed through Non-targeted Lipidomics Analysis of Tongue Coating.

The metabolites and microbiota in tongue coating display distinct characteristics in certain digestive disorders, yet their relationship with colorectal cancer (CRC) remains unexplored. Here, we employed liquid chromatography coupled with tandem mass spectrometry to analyze the lipid composition of tongue coating using a nontargeted approach in 30 individuals with colorectal adenomas (CRA), 32 with CRC, and 30 healthy controls (HC). We identified 21 tongue coating lipids that effectively distinguished CRC from HC (AUC = 0.89), and 9 lipids that differentiated CRC from CRA (AUC = 0.9). Furthermore, we observed significant alterations in the tongue coating lipid composition in the CRC group compared to HC/CRA groups. As the adenoma-cancer sequence progressed, there was an increase in long-chain unsaturated triglycerides (TG) levels and a decrease in phosphatidylethanolamine plasmalogen (PE-P) levels. Furthermore, we noted a positive correlation between N-acyl ornithine (NAOrn), sphingomyelin (SM), and ceramide phosphoethanolamine (PE-Cer), potentially produced by members of the Bacteroidetes phylum. The levels of inflammatory lipid metabolite 12-HETE showed a decreasing trend with colorectal tumor progression, indicating the potential involvement of tongue coating microbiota and tumor immune regulation in early CRC development. Our findings highlight the potential utility of tongue coating lipid analysis as a noninvasive tool for CRC diagnosis.

Screening of specific binding peptide for ß-lactoglobulin using phage display technology.

ß-lactoglobulin (ß-Lg) is a major food allergen, there is an urgent need to develop a rapid method for detecting ß-Lg in order to avoid contact or ingestion by allergic patients. Peptide aptamers have high affinity, specificity, and stability, and have broad prospects in the field of rapid detection. Using ß-Lg as the target, this study screened 11 peptides (P1-11) from a phage display library. Using molecular docking technology to predict binding energy and binding mode of proteins and peptides. Select the peptides with the best binding ability to ß-Lg (P5, P7, P8) through ELISA. Combining them with whey protein, casein, and bovine serum protein, it was found that P7 has the best specificity for ß-Lg, with an inhibition rate of 87.99%. Verified by molecular dynamics that P7 binds well with ß-Lg. Therefore, this peptide can be used for the recognition of ß-Lg, becoming a new recognition element for detecting ß-Lg.

Coumarin-Furoxan Hybrid Suppressed the Proliferation and Metastasis of Triple-Negative Breast Cancer by Activating Mitochondrial Stress and Cell Apoptosis.

Triple-negative breast cancer (TNBC) typically manifests as higher invasive carcinoma correlated with a worse prognosis that primarily relies on chemotherapy. There is growing evidence that nitric oxide (NO) donor drugs have the potential for anticancer therapy. On this basis, we constructed and evaluated a novel coumarin-furoxan hybrid 4A93 as an effective antitumor candidate drug. 4A93 exhibits low IC50 values in three TNBC cell lines and inhibits colony formation and DNA synthesis, probably due to the release of high concentrations of NO in mitochondria, which induces oxidative stress, mitochondrial dysfunction, and apoptosis. Further research suggests that 4A93 might destroy mitochondria by opening the mitochondrial permeability transition pore (mPTP), depolarizing the mitochondrial membrane potential (MMP), and promoting the release of cytochrome c into the cytoplasm. Intrinsic apoptosis is induced finally, along with Akt/Erk signaling suppression. Additionally, 4A93 underregulates the Epithelial-mesenchymal transition process to inhibit cell migration and invasion. In 4T1 subcutaneous and hematogenous models of mice, 4A93 therapy suppresses the tumor growth and prevented lung metastasis with favorable biosafety. Our results provide insights into 4A93 in TNBC treatment and validate the contribution of NO donors in tumor therapy.

Optical enhancement mode 2 improves the detection rate of gastric neoplastic lesion in high-risk populations: A multicenter randomized controlled clinical study.

OBJECTIVES: Detection of early neoplastic lesions is crucial for improving the survival rates of patients with gastric cancer. Optical enhancement mode 2 is a new image-enhanced endoscopic technique that offers bright images and can improve the visibility of neoplastic lesions. This study aimed to compare the detection of neoplastic lesions with optical enhancement mode 2 and white-light imaging (WLI) in a high-risk population. METHODS: In this prospective multicenter randomized controlled trial, patients were randomly assigned to optical enhancement mode 2 or WLI groups. Detection of suspicious neoplastic lesions during the examinations was recorded, and pathological diagnoses served as the gold standard. RESULTS: A total of 1211 and 1219 individuals were included in the optical enhancement mode 2 and WLI groups, respectively. The detection rate of neoplastic lesions was significantly higher in the optical enhancement mode 2 group (5.1% vs. 1.9%; risk ratio, 2.656 [95% confidence interval, 1.630-4.330]; p < 0.001). The detection rate of neoplastic lesions with an atrophic gastritis background was significantly higher in the optical enhancement mode 2 group (8.6% vs. 2.6%, p < 0.001). The optical enhancement mode 2 group also had a higher detection rate among endoscopists with different experiences. CONCLUSIONS: Optical enhancement mode 2 was more effective than WLI for detecting neoplastic lesions in the stomach, and can serve as a new method for screening early gastric cancer in clinical practice. CLINICAL REGISTRY: United States National Library of Medicine (https://www. CLINICALTRIALS: gov), ID: NCT040720521.

Metagenomic profiles of the antimicrobial resistance in traditional Chinese fermented meat products: Core resistome and co-occurrence patterns.

Antimicrobial resistance (AMR) poses a significant challenge to global health, and the presence of antibiotic resistance genes (ARGs) in food poses a potential threat to public health. Traditional Chinese fermented meat products (FMPs) are highly favored because of their unique flavors and cultural value. However, microbial safety and the potential distribution and composition of AMR in these products remain unclear. In this study, a comprehensive analysis of bacterial composition and antibiotic-resistant populations in 216 samples of traditional fermented meat products from different regions of China was conducted using a metagenomic approach. Staphylococcus was the most abundant genus in the samples, accounting for an average abundance of 29.9 %, followed by Tetragenococcus (17.1 %), and Latilactobacillus (3.6 %). A core resistome of FMP samples was constructed for the first time using co-occurrence network analysis, which revealed the distribution and interrelationships of ARGs and bio/metal-resistant genes (BMRGs). Random forest analysis identified the lincosamide nucleotidyltransferase lnuA and the multidrug and toxic compound extrusion (MATE) transporter abeM as potential indicators for assessing the overall abundance of the core resistome. Additionally, Staphylococcus, Acinetobacter, and Pseudomonas were identified as hosts constituting the core resistome. Despite their low abundance, the latter two still serve as major reservoirs of antibiotic resistance genes. Notably, Lactococcus cremoris was identified as the key host for tetracycline resistance genes in the samples, highlighting the need for enhanced resistance monitoring in lactic acid bacteria. Based on our findings, in the microbial safety assessment of fermented meat products, beyond common foodborne pathogens, attention should be focused on detecting and controlling coagulase-negative Staphylococcus, Acinetobacter, and Pseudomonas, and addressing bacterial resistance. The quantitative detection of lnuA and abeM could provide a convenient and rapid method for assessing the overall abundance of the core resistome. Our findings have important implications for the control of bacterial resistance and prevention of pathogenic bacteria in fermented meat products.

Development of a Prognostic Risk Model Based on Oxidative StressRelated Genes for Platinum-Resistant Ovarian Cancer Patients.

INTRODUCTION: Ovarian Cancer (OC) is a heterogeneous malignancy with poor outcomes. Oxidative stress plays a crucial role in developing drug resistance. However, the relationships between Oxidative Stress-related Genes (OSRGs) and the prognosis of platinum-resistant OC remain unclear. This study aimed to develop an OSRGs-based prognostic risk model for platinum-resistant OC patients. METHODS: Gene Set Enrichment Analysis (GSEA) was performed to determine the expression difference of OSRGs between platinum-resistant and -sensitive OC patients. Cox regression analyses were used to identify the prognostic OSRGs and establish a risk score model. The model was validated by using an external dataset. Machine learning was used to determine the prognostic OSRGs associated with platinum resistance. Finally, the biological functions of selected OSRG were determined via in vitro cellular experiments. RESULTS: Three gene sets associated with oxidative stress-related pathways were enriched (p < 0.05), and 105 OSRGs were found to be differentially expressed between platinum-resistant and - sensitive OC (p < 0.05). Twenty prognosis-associated OSRGs were identified (HR: 0:562-5.437; 95% CI: 0.319-20.148; p < 0.005), and seven independent OSRGs were used to construct a prognostic risk score model, which accurately predicted the survival of OC patients (1-, 3-, and 5-year AUC=0.69, 0.75, and 0.67, respectively). The prognostic potential of this model was confirmed in the validation cohort. Machine learning showed five prognostic OSRGs (SPHK1, PXDNL, C1QA, WRN, and SETX) to be strongly correlated with platinum resistance in OC patients. Cellular experiments showed that WRN significantly promoted the malignancy and platinum resistance of OC cells. CONCLUSION: The OSRGs-based risk score model can efficiently predict the prognosis and platinum resistance of OC patients. This model may improve the risk stratification of OC patients in the clinic.

NOD2 contributes to Parvimonas micra-induced bone resorption in diabetic rats with experimental periodontitis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) may affect the oral microbial community, exacerbating periodontal inflammation; however, its pathogenic mechanisms remain unclear. As nucleotide-binding oligomerization domain 2 (NOD2) plays a crucial role in the activation during periodontitis (PD), it is hypothesized that changes in the oral microbial community due to diabetes enhance periodontal inflammation through the activation of NOD2. METHODS: We collected subgingival plaque from 180 subjects who were categorized into two groups based on the presence or absence of T2DM. The composition of oral microbiota was detected by 16S rRNA high-throughput sequencing. In animal models of PD with or without T2DM, we assessed alveolar bone resorption by micro-computerized tomography and used immunohistochemistry to detect NOD2 expression in alveolar bone. Primary osteoblasts were cultured in osteogenic induction medium with high or normal glucose and treated with inactivated bacteria. After 24 h of inactivated bacteria intervention, the osteogenic differentiation ability was detected by alkaline phosphatase (ALP) staining, and the expressions of NOD2 and interleukin-12 (IL-6) were detected by western blot. RESULTS: The relative abundance of Parvimonas and Filifactor in the T2DM group was increased compared to the group without T2DM. In animal models, alveolar bone mass was decreased in PD, particularly in T2DM with PD (DMPD) group, compared to controls. Immunohistochemistry revealed NOD2 in osteoblasts from the alveolar bone in both the PD group and DMPD group, especially in the DMPD group. In vitro, intervention with inactivated Parvimonas significantly reduced ALP secretion of primary osteoblasts in high glucose medium, accompanied by increased expression of NOD2 and IL-6. CONCLUSIONS: The results suggest that T2DM leading to PD may be associated with the activation of NOD2 by Parvimonas.

One and five-year efficacy of tension-free vaginal tape (TVT) abbrevo and TVT-obturator in the treatment of stress urinary incontinence: a retrospective study.

BACKGROUND: Surgical interventions are more effective than nonsurgical approaches in providing a cure for stress urinary incontinence (SUI). In this study, we aimed to assess the benefits of tension-free vaginal tape (TVT) abbrevo by comparing its efficacy and complications to those of TVT obturator. METHODS AND RESULTS: 49 and 47 patients at The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University between January 2013 and December 2016 were included in the TVT-O and TVT-A groups, respectively. We evaluate the success rate and perioperative complications associated with TVT-O and TVT-A. A questionnaire that utilized the Patient Global Impression of Improvement (PGI-I) Scale was employed to assess the impact of surgery. Patients were followed up at 1 year, and 5 years after surgery. There were no statistically significant differences found in the efficacy of the TVT-A group and TVT-O group during both the one-year (p = 0.4) and five-year (p = 0.32) follow-up periods. In the period of one-year follow-up, 95.9% (n = 47) of patients in the TVT-O group and 95.8% (n = 45) of patients in the TVT-A group demonstrated improvement. During the period of five-year follow-up, 87.8% (n = 43) of patients in the TVT-O group and 93.6% (n = 44) of patients in the TVT-A group demonstrated improvement. CONCLUSIONS: Based on our findings, TVT-A and TVT-O procedures exhibited similarly high success rates and low frequencies of complications.

The incidence and risk factors of proximal lower extremity deep vein thrombosis without pharmacologic prophylaxis in critically ill surgical Taiwanese patients: A prospective study.

Background: Venous thromboembolism (VTE) in critically ill patients has been well-studied in Western countries. Many studies have developed risk assessments and established pharmacological protocols to prevent deep venous thrombosis (DVT). However, the DVT rate and need for pharmacologic VTE prophylaxis in critically ill Taiwanese patients are limited. This study aimed to prospectively determine the DVT incidence, risk factors, and outcomes in critically ill Taiwanese patients who do not receive pharmacologic VTE prophylaxis. Methods: We conducted a prospective study in a surgical intensive care unit (SICU) of a tertiary academic medical center in Taiwan. Adult patients admitted to SICU from March 2021 to June 2022 received proximal lower extremities DVT surveillance with venous duplex ultrasound. No patient received pharmacologic VTE prophylaxis. The outcomes were the incidence and risk factors of DVT. Results: Among 501 enrolled SICU patients, 21 patients (4.2%) were diagnosed with proximal lower extremities DVT. In a multivariate regression analysis, hypoalbuminemia (odd ratio (OR) = 6.061, 95% confidence interval (CI): 1.067-34.421), femoral central venous catheter (OR = 4.515, 95% CI: 1.547-13.174), ICU stays more than 10 days (OR = 4.017, 95% CI: 1.270-12.707), and swollen leg (OR = 3.427, 95% CI: 1.075-10.930) were independent risk factors for DVT. In addition, patients with proximal lower extremities DVT have more extended ventilator days (p = 0.045) and ICU stays (p = 0.044). Conclusion: Our findings indicate critically ill Taiwanese patients have a higher incidence of DVT than results from prior retrospective studies in the Asian population. Physicians who care for this population should consider the specific risk factors for DVT and prescribe pharmacologic prophylaxis in high-risk groups.

Multi-spectral photoacoustic imaging combined with acoustic radiation force impulse imaging for applications in tissue engineering.

Tissue engineering is a dynamic field focusing on the creation of advanced scaffolds for tissue and organ regeneration. These scaffolds are customized to their specific applications and are often designed to be complex, large structures to mimic tissues and organs. This study addresses the critical challenge of effectively characterizing these thick, optically opaque scaffolds that traditional imaging methods fail to fully image due to their optical limitations. We introduce a novel multi-modal imaging approach combining ultrasound, photoacoustic, and acoustic radiation force impulse imaging. This combination leverages its acoustic-based detection to overcome the limitations posed by optical imaging techniques. Ultrasound imaging is employed to monitor the scaffold structure, photoacoustic imaging is employed to monitor cell proliferation, and acoustic radiation force impulse imaging is employed to evaluate the homogeneity of scaffold stiffness. We applied this integrated imaging system to analyze melanoma cell growth within silk fibroin protein scaffolds with varying pore sizes and therefore stiffness over different cell incubation periods. Among various materials, silk fibroin was chosen for its unique combination of features including biocompatibility, tunable mechanical properties, and structural porosity which supports extensive cell proliferation. The results provide a detailed mesoscale view of the scaffolds' internal structure, including cell penetration depth and biomechanical properties. Our findings demonstrate that the developed multimodal imaging technique offers comprehensive insights into the physical and biological dynamics of tissue-engineered scaffolds. As the field of tissue engineering continues to advance, the importance of non-ionizing and non-invasive imaging systems becomes increasingly evident, and by facilitating a deeper understanding and better characterization of scaffold architectures, such imaging systems are pivotal in driving the success of future tissue-engineering solutions.

Identification of B-cell epitope on the N protein of type 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) using monoclonal antibody and construction of epitope-mutated virus.

The escalating epidemic of PRRSV-1 in China has prompted widespread concern regarding the evolution of strains, disparities in pathogenicity to herds, and immunological detection of emerging strains. The nucleocapsid (N) protein, as a highly conserved protein with immunogenic properties in PRRSV, is a subject of intensive study. In this research, the recombinant His-N protein was expressed based on the N gene of PRRSV-1 using a prokaryotic expression system and then administered to BALB/c mice. A cell fusion protocol was implemented between SP2/0 cells and splenocytes, resulting in the successful screening of a monoclonal antibody against the N protein, designated as mAb 2D7, by indirect ELISA. Western Blot analysis and Indirect Immunofluorescence Assay (IFA) confirmed that mAb 2D7 positively responded to PRRSV-1. By constructing and expressing a series of truncated His-fused N proteins, a B-cell epitope of N protein, 59-AAEDDIR-65, was identified. A sequence alignment of two genotypes of PRRSV revealed that this epitope is relatively conserved in PRRSV, yet more so in genotype 1. Cross-reactivity analysis by Western blot analysis demonstrated that the B-cell epitope containing D62Y mutation could not be recognized by mAb 2D7. The inability of mAb 2D7 to recognize the epitope carrying the D62Y mutation was further determined using an infectious clone of PRRSV. This research may shed light on the biological significance of the N protein of PRRSV, paving the way for the advancement of immunological detection and development of future recombinant marker vaccine.

Anti-hyperuricemia bioactive peptides: a review on obtaining, activity, and mechanism of action.

Hyperuricemia, a disorder of uric acid metabolism, serves as a significant risk factor for conditions such as hypertension, diabetes mellitus, renal failure, and various metabolic syndromes. The main contributors to hyperuricemia include overproduction of uric acid in the liver or impaired excretion in the kidneys. Despite traditional clinical drugs being employed for its treatment, significant health concerns persist. Recently, there has been growing interest in utilizing protein peptides sourced from diverse food origins to mitigate hyperuricemia. This article provides a comprehensive review of bioactive peptides with anti-hyperuricemia properties derived from animals, plants, and their products. We specifically outline the methods for preparing these peptides from food proteins and elucidate their efficacy and mechanisms in combating hyperuricemia, supported by in vitro and in vivo evidence. Uric acid-lowering peptides offer promising prospects due to their safer profile, enhanced efficacy, and improved bioavailability. Therefore, this review underscores significant advancements and contributions in identifying peptides capable of metabolizing purine and/or uric acid, thereby alleviating hyperuricemia. Moreover, it offers a theoretical foundation for the development of functional foods incorporating uric acid-lowering peptides.

From Bulk to Interface: Solvent Exchange Dynamics and Their Role in Ion Transport and the Interfacial Model of Rechargeable Magnesium Batteries.

Multivalent battery chemistries have been explored in response to the increasing demand for high-energy rechargeable batteries utilizing sustainable resources. Solvation structures of working cations have been recognized as a key component in the design of electrolytes; however, most structure-property correlations of metal ions in organic electrolytes usually build upon favorable static solvation structures, often overlooking solvent exchange dynamics. We here report the ion solvation structures and solvent exchange rates of magnesium electrolytes in various solvents by using multimodal nuclear magnetic resonance (NMR) analysis and molecular dynamics/density functional theory (MD/DFT) calculations. These magnesium solvation structures and solvent exchange dynamics are correlated to the combined effects of several physicochemical properties of the solvents. Moreover, Mg2+ transport and interfacial charge transfer efficiency are found to be closely correlated to the solvent exchange rate in the binary electrolytes where the solvent exchange is tunable by the fraction of diluent solvents. Our primary findings are (1) most battery-related solvents undergo ultraslow solvent exchange coordinating to Mg2+ (with time scales ranging from 0.5 µs to 5 ms), (2) the cation transport mechanism is a mixture of vehicular and structural diffusion even at the ultraslow exchange limit (with faster solvent exchange leading to faster cation transport), and (3) an interfacial model wherein organic-rich regions facilitate desolvation and inorganic regions promote Mg2+ transport is consistent with our NMR, electrochemistry, and cryogenic X-ray photoelectron spectroscopy (cryo-XPS) results. This observed ultraslow solvent exchange and its importance for ion transport and interfacial properties necessitate the judicious selection of solvents and informed design of electrolyte blends for multivalent electrolytes.

Transcriptomic Insights into Different Stimulation Intensity of Electroacupuncture in Treating COPD in Rat Models.

Background: Electroacupuncture (EA), with varying stimulation intensities, has demonstrated therapeutic potentials in both animal and clinical studies for the treatment of chronic obstructive pulmonary disease (COPD). However, a comprehensive investigation of the intensity-related effects, particularly 1mA and 3mA of EA, and the underlying mechanisms remains lacking. Methods: A COPD rat model was established by prolonged exposure to cigarette smoke and intermittent intratracheal instillation of lipopolysaccharide. EA treatment was administered at acupoints BL13 (Feishu) and ST36 (Zusanli), 20 minutes daily for 2 weeks, with intensities of 1mA and 3mA. EA effectiveness was evaluated by pulmonary function, histopathological change, serum level of inflammatory cytokines, and level of oxidative stress markers in serum and lung tissues. Transcriptome profiling and weighted gene co-expression network analysis (WGCNA) were performed to reveal gene expression patterns and identify hub genes. Real-time quantitative PCR (RT-qPCR) and Western blot (WB) were performed to detect the mRNA and protein expression levels, respectively. Results: EA at both 1mA and 3mA exerted differing therapeutic effects by improving lung function and reducing inflammation and oxidative stress in COPD rats. Transcriptome analysis revealed distinct expression patterns between the two groups, functionally corresponding to shared and intensity-specific (1mA and 3mA) enriched pathways. Eight candidate genes were identified, including Aqp9, Trem1, Mrc1, and Gpnmb that were downregulated by EA and upregulated in COPD. Notably, Msr1 and Slc26a4 exclusively downregulated in EA-1mA, while Pde3a and Bmp6 upregulated solely in EA-3mA. WGCNA constructed 5 key modules and elucidated the module-trait relationship, with the aforementioned 8 genes being highlighted. Additionally, their mRNA and protein levels were validated by RT-qPCR and WB. Conclusion: Our results demonstrated that 1mA and 3mA intensities induce distinct gene expression patterns at the transcriptional level, associated with shared and 1mA vs 3mA-specific enriched pathways. Genes Mrc1, Gpnmb, Trem1, and Aqp9 emerge as promising targets, and further studies are needed to elucidate their functional consequences in COPD.

ADHD classification with cross-dataset feature selection for biomarker consistency detection.

Objective.Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in children. While numerous intelligent methods are applied for its subjective diagnosis, they seldom consider the consistency problem of ADHD biomarkers. In practice, these data-driven approaches lead to varying learned features for ADHD classification across diverse ADHD datasets. This phenomenon significantly undermines the reliability of identified biomarkers and hampers the interpretability of these methods.Approach.In this study, we propose a cross-dataset feature selection (FS) module using a grouped SVM-based recursive feature elimination approach (G-SVM-RFE) to enhance biomarker consistency across multiple datasets. Additionally, we employ connectome gradient data for ADHD classification. In details, we introduce the G-SVM-RFE method to effectively concentrate gradient components within a few brain regions, thereby increasing the likelihood of identifying these regions as ADHD biomarkers. The cross-dataset FS module is integrated into an existing binary hypothesis testing (BHT) framework. This module utilizes external datasets to identify global regions that yield stable biomarkers. Meanwhile, given a dataset which waits for implementing the classification task as local dataset, we learn its own specific regions to further improve the performance of accuracy on this dataset.Main results.By employing this module, our experiments achieve an average accuracy of 96.7% on diverse datasets. Importantly, the discriminative gradient components primarily originate from the global regions, providing evidence for the significance of these regions. We further identify regions with the high appearance frequencies as biomarkers, where all the used global regions and one local region are recognized.Significance.These biomarkers align with existing research on impaired brain regions in children with ADHD. Thus, our method demonstrates its validity by providing enhanced biological explanations derived from ADHD mechanisms.

Source identification and driving factor apportionment for soil potentially toxic elements via combining APCS-MLR, UNMIX, PMF and GDM.

The contamination and quantification of soil potentially toxic elements (PTEs) contamination sources and the determination of driving factors are the premise of soil contamination control. In our study, 788 soil samples from the National Agricultural Park in Chengdu, Sichuan Province were used to evaluate the contamination degree of soil PTEs by pollution factors and pollution load index. The source identification of soil PTEs was performed using positive matrix decomposition (PMF), edge analysis (UNMIX) and absolute principal component score-multiple line regression (APCS-MLR). The geo-detector method (GDM) was used to analysis drivers of soil PTEs pollution sources to help interpret pollution sources derived from receptor models. Result shows that soil Cu, Pb, Zn, Cr, Ni, Cd, As and Hg average content were 35.2, 32.3, 108.9, 91.9, 37.1, 0.22, 9.76 and 0.15 mg/kg in this study area. Except for As, all are higher than the corresponding soil background values in Sichuan Province. The best performance of APCS-MLR was determined by comparison, and APCS-MLR was considered as the preferred receptor model for soil PTEs source distribution in the study area. ACPS-MLR results showed that 82.70% of Cu, 61.6% of Pb, 75.3% of Zn, 91.9% of Cr and 89.4% of Ni came from traffic-industrial emission sources, 60.9% of Hg came from domestic-transportation emission sources, 57.7% of Cd came from agricultural sources, and 89.5% of As came from natural sources. The GDM results showed that distance from first grade highway, population, land utilization and total potassium (TK) content were the main driving factors affecting these four sources, with q values of 0.064, 0.048, 0.069 and 0.058, respectively. The results can provide reference for reducing PTEs contamination in farmland soil.

CEBPB-mediated upregulation of SERPINA1 promotes colorectal cancer progression by enhancing STAT3 signaling.

Colorectal cancer (CRC) is a highly malignant carcinoma associated with poor prognosis, and metastasis is one of the most common causes of death in CRC. Serpin Family A Member 1 (SERPINA1) is a serine protease inhibitor from the Serpin family. Till now, the function and mechanism of SERPINA1 in CRC progression have not been fully illustrated. We established highly metastatic colorectal cancer cells named as RKO-H and Caco2-H by mice liver metastasis model. By integrative bioinformatic approaches, we analyzed the prognostic value and clinical significance of SERPINA1 in CRC, and predicted potential transcription factors. Colony formation, EDU, MTS, Transwell and wound healing assay were performed to evaluate the biological functions of SERPINA1 in CRC in vitro. Experiments in vivo were conducted to explore the effects of SERPINA1 on liver metastasis of CRC. ChIP and luciferase reporter gene assays were performed to identify the transcriptional regulatory mechanism of SERPINA1 by CEBPB. Our results show that SERPINA1 is highly expressed in CRC and correlated with poor clinical outcomes. SERPINA1 promotes the proliferation, migration by activating STAT3 pathway. Mechanistically, CEBPB binds SERPINA1 gene promoter sequence and promotes the transcription of SERPINA1. SERPINA1 drives CEBPB-induced tumor cell growth and migration via augmenting STAT3 signaling. Our results suggest that SERPINA1 is a potential prognostic marker and may serve as a novel treatment target for CRC.

Identification of Mitophagy-Associated Genes for the Prediction of Metabolic Dysfunction-Associated Steatohepatitis Based on Interpretable Machine Learning Models.

Background: This study aims to elucidate the role of mitochondrial autophagy in metabolic dysfunction-associated steatohepatitis (MASH) by identifying and validating key mitophagy-related genes and diagnostic models with diagnostic potential. Methods: The gene expression profiles and clinical information of MASH patients and healthy controls were obtained from the Gene Expression Omnibus database (GEO). Limma and functional enrichment analysis were used to identify the mitophagy-related differentially expressed genes (mito-DEGs) in MASH patients. Machine learning models were used to select key mito-DEGs and evaluate their efficacy in the early diagnosis of MASH. The expression levels of the key mito-DEGs were validated using datasets and cell models. A nomogram was constructed to assess the risk of MASH progression based on the expression of the key mito-DEGs. The mitophagy-related molecular subtypes of MASH were evaluated. Results: Four mito-DEGs, namely MRAS, RAB7B, RETREG1, and TIGAR were identified. Among the machine learning models employed, the Support Vector Machine demonstrated the highest AUC value of 0.935, while the Light Gradient Boosting model exhibited the highest accuracy (0.9189), kappa (0.7204), and F1-score (0.9508) values. Based on these models, MRAS, RAB7B, and RETREG1 were selected for further analysis. The logistic regression model based on these genes could accurately predict MASH diagnosis. The nomogram model based on these DEGs exhibited excellent prediction performance. The expression levels of the three mito-DEGs were validated in the independent datasets and cell models, and the results were found to be consistent with the findings obtained through bioinformatics analysis. Furthermore, our findings revealed significant differences in gene expression patterns, immune characteristics, biological functions, and enrichment pathways between the mitophagy-related molecular subtypes of MASH. Subtype-specific small-molecule drugs were identified using the CMap database. Conclusion: Our research provides novel insights into the role of mitophagy in MASH and uncovers novel targets for predictive and personalized MASH treatments.