Spatial analysis of the prevalence of abdominal obesity in middle-aged and older adult people in China: exploring the relationship with meteorological factors based on gender differences.

Background: In recent years, the incidence of abdominal obesity among the middle-aged and older adult population in China has significantly increased. However, the gender disparities in the spatial distribution of abdominal obesity incidence and its relationship with meteorological factors among this demographic in China remain unclear. This gap in knowledge highlights the need for further research to understand these dynamics and inform targeted public health strategies. Methods: This study utilized data from the 2015 China Health and Retirement Longitudinal Study (CHARLS) to analyze the incidence of abdominal obesity among the middle-aged and older adult population in China. Additionally, meteorological data were collected from the National Meteorological Information Center. Using Moran's I index and Getis-Ord Gi* statistical methods, the spatial distribution characteristics of abdominal obesity incidence were examined. The influence of various meteorological factors on the incidence of abdominal obesity in middle-aged and older adult males and females was investigated using the q statistic from the Geodetector method. Furthermore, Multi-Scale Geographically Weighted Regression (MGWR) analysis was employed to explore the impact of meteorological factors on the spatial heterogeneity of abdominal obesity incidence from a gender perspective. Results: The spatial distribution of abdominal obesity among middle-aged and older adult individuals in China exhibits a decreasing trend from northwest to southeast, with notable spatial autocorrelation. Hotspots are concentrated in North and Northeast China, while cold spots are observed in Southwest China. Gender differences have minimal impact on spatial clustering characteristics. Meteorological factors, including temperature, sunlight, precipitation, wind speed, humidity, and atmospheric pressure, influence incidence rates. Notably, temperature and sunlight exert a greater impact on females, while wind speed has a reduced effect. Interactions among various meteorological factors generally demonstrate bivariate enhancement without significant gender disparities. However, gender disparities are evident in the influence of specific meteorological variables such as annual maximum, average, and minimum temperatures, as well as sunlight duration and precipitation, on the spatial heterogeneity of abdominal obesity incidence. Conclusion: Meteorological factors show a significant association with abdominal obesity prevalence in middle-aged and older adults, with temperature factors playing a prominent role. However, this relationship is influenced by gender differences and spatial heterogeneity. These findings suggest that effective public health policies should be not only gender-sensitive but also locally adapted.

Negative Emotions Are Associated With Older Self-perceived Age: A Cross-section Study From the UK Biobank.

BACKGROUND: Prior research has indicated a potential connection between psychological stress and how individuals perceive their own age. Building on this foundation, the current study explores the relationship between negative emotions and self-perceived age. METHODS: We conducted a cross-sectional analysis using data from the UK Biobank, a comprehensive cohort study representing the UK population. The analysis included 347 892 participants, aged between 39 and 73 years, of which 184 765 were women, accounting for 53.1% of the sample. Participants were categorized into three groups based on their self-perceived age: feeling younger than their chronological age (group Younger), feeling older than their chronological age (group Older), and feeling as old as their actual age (group Same). To investigate the relationship between negative emotions and self-perceived age, we utilized a multinomial logistic regression model with the Younger group serving as the reference category. RESULTS: Of 347 892 participants, after adjusted for covariates, the results showed that participants with irritability, nervous feelings, worrier/anxious feelings or fed-up feelings, worry too long and loneliness/isolation are more likely to be rated as "about your age" or "older than you are," with "younger than you are" as the reference group, indicating that negative emotions may influence one's self-perceived age. Among those negative emotions, irritability has the most significant impact self-perceived age, with the odds ratios (ORs) being 1.44 (95% CI: 1.35-1.54) and 1.11 (95% CI: 1.09-1.14). CONCLUSION: Negative emotions are associated with older self-perceived age, and irritability has the greatest impact. Further studies analyzing self-perceived age are needed to take psychological factors into consideration.

Combination of monensin and erlotinib synergistically inhibited the growth and cancer stem cell properties of triple-negative breast cancer by simultaneously inhibiting EGFR and PI3K signaling pathways.

BACKGROUND: Cancer stem cells (CSCs) in triple-negative breast cancer (TNBC) are recognized as a highly challenging subset of cells, renowned for their heightened propensity for relapse and unfavorable prognosis. Monensin, an ionophoric antibiotic, has been reported to exhibit significant therapeutic efficacy against various cancers, especially CSCs. Erlotinib is classified as one of the EGFR-TKIs and has been previously identified as a promising therapeutic target for TNBC. Our research aims to assess the effectiveness of combination of monensin and erlotinib as a potential treatment strategy for TNBC. METHODS: The combination of monensin and erlotinib was assessed for its potential anticancer activity through various in vitro assays, including cytotoxicity assay, colony formation assay, wound healing assay, transwell assay, mammosphere formation assay, and proportion of CSCs assay. Additionally, an in vivo study using tumor-bearing nude mice was conducted to evaluate the inhibitory effect of the monensin and erlotinib combination on tumor growth. RESULTS: The results indicated that combination of monensin with erlotinib synergistically inhibited cell proliferation, the migration rate, the invasion ability and decreased the CSCs proportion, and CSC markers SOX2 and CD133 in vivo and in vitro. Furthermore, the primary proteins involved in the signaling pathways of the EGFR/ERK and PI3K/AKT are simultaneously inhibited by the combination treatment of monensin and erlotinib in vivo and in vitro. CONCLUSIONS: The simultaneous inhibition of the EGFR/ERK and PI3K/AKT/mTOR signaling pathways by the combination of monensin and erlotinib exhibited a synergistic effect on suppressing tumor proliferation and cancer cell stemness in TNBC.

Characterization of biomass burning tracers in particulate matter at 12 sites in China: Significant increase of coal combustion emitted levoglucosan in northern China during winter.

Biomass burning (BB) is the largest contributor to carbonaceous aerosols globally. Specific organic tracers can track BB particles and identify BB types. At present, there is limited information on the composition of BB tracers on a continental scale. In this study, we conducted year-round sampling of particulate matter (PM) at 12 sites in China. Nine BB tracers were measured in PM with aerodynamic diameters <1.1 µm (PM<1.1), in the range of 1.1-3.3 µm (PM1.1-3.3), and > 3.3 µm (PM>3.3). The annual average concentration of these nine BB tracers (∑9 BB tracers) in the total PM was 366 ng m-3 with the majority of levoglucosan (66 %). The concentration of ∑9 BB tracers was higher in northern China than in southern China, especially in winter. ∑9 BB tracers were most enriched in PM<1.1 (50-61 % in mass), followed by PM1.1-3.3 and PM>3.3. The highest concentrations of ∑9 BB tracers were observed in winter, while satellite-recorded fire spots were intensive in autumn and spring. The mismatch of seasonal trends between them indicated that the high levels of BB tracers in winter was not due to open BB. The composition of 4-hydroxybenzoic acid, syringic acid and vanillic acid suggested that the burning of crop residues and softwoods were the major BB types in China. The ratio of levoglucosan to mannosan could neither identify the major BB types in China nor distinguish between BB and coal combustion. Correlation analysis and the PMF model demonstrated that non-BB sources contributed 7 %-58 % to levoglucosan at the 12 sites, with coal combustion being the predominant non-BB source in China, especially in northern urban sites during winter. Our findings suggest that caution should be taken in application of these organic tracers to identify BB types and estimate BB aerosols.

A clustering mining method for sports behavior characteristics of athletes based on the ant colony optimization.

This study aims to enhance the precision of analyzing athlete behavior characteristics, thereby optimizing sports training and competitive strategies. This study introduces an innovative Ant Colony Optimization (ACO) clustering model designed to address the high-dimensional clustering issues in athlete behavior data by simulating the path selection mechanism of ants searching for food. The development process of this model includes fine-tuning ACO parameters, optimizing for features specific to sports data, and comparing it with traditional clustering algorithms, and similar research models based on the neural network, support vector machines, and deep learning. The results indicate that the ACO model significantly outperforms the comparison algorithms in terms of silhouette coefficient (0.72) and Davies-Bouldin index (1.05), demonstrating higher clustering effectiveness and model stability. Particularly noteworthy is the recall rate (0.82), a key performance indicator, where the ACO model accurately captures different behavioral characteristics of athletes, validating its effectiveness and reliability in athlete behavior analysis. The innovation lies not only in the application of the ACO algorithm to address practical issues in the field of sports but also in showcasing the advantages of the ACO algorithm in handling complex, high-dimensional sports data. However, its generality and efficiency on a larger scale or different types of sports data still need further validation. In conclusion, through the introduction and optimization of the ACO clustering model, this study provides a novel and effective approach for a deeper understanding and analysis of athlete behavior characteristics. This study holds significant importance in advancing sports science research and practical applications.

Application of PLS-NN model based on mid-infrared spectroscopy in the origin identification of Cornus officinalis.

Mid-infrared spectroscopy has been increasingly used as a nondestructive analytical technique in Chinese herbal medicine identification in recent years. In this study, a new chemometric model named as PLS-NN model was proposed based on the mid-infrared spectral data of Cornus officinalis samples from 11 origins. It was realized by combining the partial least squares and neural networks for the identification of the origin of Chinese herbal medicines. First, we extracted features from the spectral data in 3448 bands using the partial least squares method, and extracted 122 components that contained more than 95% of the information. Then, we trained the PLS-NN model by neural network using the extracted components as inputs and the corresponding origin classes as outputs. Finally, based on an external test set, we evaluated the generalization ability of the PLS-NN model using metrics such as accuracy, F1-Score and Kappa coefficient. The results show that the PLS-NN model performs well in all three metrics when compared to models such as Decision trees, Support vector machine, Partial least squares Discriminant analysis, and Naive bayes. The model not only realizes the dimensionality reduction of full-spectrum data and improves the training efficiency of the model, but also has higher accuracy compared with the full-spectrum data model. The PLS-NN model was applied to identify the origin of Cornus officinalis with an accuracy of 91.9%.

The association between lower extremity function and cardiovascular diseases risk in older Chinese adults: Longitudinal evidence from a nationwide cohort.

BACKGROUND: Older adults in China are at a high risk of cardiovascular diseases (CVD), and impaired lower extremity function (LEF) is commonly observed in this demographic. This study aimed at assessing the association between LEF and CVD, thus providing valuable insights for clinical practice and public health policies. METHODS: A sample of 4,636 individuals was included from the China Health and Retirement Longitudinal Study (CHARLS) dataset. Logistic regression and cox proportional hazard regression model was utilized to study the association between LEF and CVD incidence. Cross-lagged panel models were utilized to investigate the potential causal association between LEF and CVD over time. RESULTS: Poor LEF was significantly associated with a higher risk of CVD in the total population [OR (95 % CI): 1.62 (1.27-2.05), P < 0.001]. Individuals with poor LEF demonstrated an increased risk of developing CVD [HR (95 % CI): 1.11 (1.02-1.23), P < 0.05], particularly stroke, compared to those with good LEF. And those with poor LEF had higher risks for heart disease [1.21 (1.00-1.45), P < 0.05] and stroke [1.98 (1.47-2.67), P < 0.001]. CONCLUSION: The results suggest the potential usefulness of the Short Physical Performance Battery (SPPB) for classifying stroke risk in older Chinese adults, which also suggested that preventing and/or improving LEF may be beneficial for reducing stroke incidence and promoting healthy aging for older adults.

Development and validation of prognostic nomograms for adult with papillary renal cell carcinoma: A retrospective study.

OBJECTIVE: The aim of the study was to create two consensus nomograms for predicting Overall Survival (OS) and Cancer-Specific Survival (CSS) in adults with papillary Renal Cell Carcinoma (pRCC). METHODS: Using the Surveillance, Epidemiology, and End Results databases, a retrospective analysis of 1,074 adults with pRCC from 2004 to 2015 was performed. These patients were then randomly divided into two independent cohorts with a ratio of 7:3 (training cohort: 752; validation cohort: 322). In a retrospective analysis of 752 patients from the training cohort, independent prognostic variables affecting OS and CSS were found. R software was used to create prognostic nomograms based on the findings of Cox regression analysis. The performance of the nomograms was assessed using the Concordance Index (C-index), the Area Under Curve (AUC), a calibration curve, and Decision Curve Analysis (DCA). Data from the 107 postoperative pRCC patients at the Affiliated Hospital of Xuzhou Medical University were used for external validation of the nomogram. RESULTS: For OS and CSS, the C-indices and AUCs of the training cohort and the validation cohort indicated that the model had excellent discrimination. The DCA demonstrated that the model was clinically applicable, and the calibration curves in the internal and external validations showed that the model's accuracy was high. CONCLUSION: The authors developed and validated a prognostic nomogram that accurately predicted the 3-, 5-, and 8-year OS and CSS of adults with pRCC. Clinicians can use this knowledge to direct the clinical management and counseling of patients with pRCC.

HHLA2 promotes hepatoma cell proliferation, migration, and invasion via SPP1/PI3K/AKT signaling pathway.

Hepatocellular carcinoma (HCC) stands as one of the most malignant tumors characterized by poor prognosis and high mortality rates. Emerging evidence underscores the crucial role of the B7 protein family in various cancers, including HCC. However, the involvement of the human endogenous retrovirus H long-terminal repeat-associated protein 2 (HHLA2, or B7-H5) in HCC remains unclear. Immunohistochemistry was employed to assess the differential expression of HHLA2 between HCC and normal liver tissues. A battery of assays, including CCK8, EdU, tablet clone-forming, Transwell, and wound healing assays, were conducted to elucidate the function and potential mechanisms of HHLA2 in the malignant biological behaviors of HCC. Additionally, a xenograft mouse model was established to evaluate the tumorigenicity of hepatoma cell lines exhibiting different HHLA2 expression levels in vivo. Western blot analysis was used to analyze HHLA2, secretory phosphoprotein 1 (SPP1), and PI3K/AKT/mTOR levels. HHLA2 exhibited elevated expression in HCC tissues, correlating with poor tumor differentiation and shortened overall survival in HCC patients. In vitro experiments demonstrated that HHLA2 overexpression (OE) promoted the proliferation, migration, and invasion of hepatoma cells, while in vivo experiments revealed that HHLA2 OE enhanced HCC tumor growth. Conversely, inhibition of HHLA2 expression yielded the opposite effect. Downregulation of SPP1 inhibited the proliferation, migration, and invasion induced by HHLA2 OE, and this effect was linked to the PI3K/AKT/mTOR signaling pathway. Our findings indicate that HHLA2 promotes the proliferation, migration, and invasion of hepatoma cells via the SPP1/PI3K/AKT signaling pathway, establishing it as a potential therapeutic target for HCC.

Interference with mitochondrial metabolism could serve as a potential therapeutic strategy for advanced prostate cancer.

Metabolic reprogramming has been defined as a hallmark of malignancies. Prior studies have focused on the single nucleotide polymorphism (SNP) of POLG2 gene, which is reportedly responsible for encoding mitochondrial DNA genes and is implicated in the material and energy metabolism of tumor cells, whereas its function in prostate cancer has been elusive. Gene expression profile matrix and clinical information were downloaded from TCGA (The Cancer Genome Atlas) data portal, and GSE3325 and GSE8511 were retrieved from GEO (Gene Expression Omnibus) database. We conducted analysis of the relative expression of POLG2, clinical characterization, survival analysis, GO / KEGG and GSEA (Gene Set Enrichment Analysis) enrichment analysis in R and employed STRING portal to acquaint ourselves with the protein-protein interaction (PPI). IHC (Immunohistochemical) profiles of POLG2 protein between normal and cancerous tissues were consulted via HPA (Human protein atlas) database and the immunohistochemical POLG2 were verified between para-cancerous and cancerous tissues in tissue array. At the cellular level, Mitochondrial dysfunction assay, DNA synthesis test, wound healing assay, and invasion assay were implemented to further validate the phenotype of POLG2 knockdown in PCa cell lines. RT-qPCR and western blotting were routinely adopted to verify variations of molecular expression within epithelial mesenchymal transition (EMT). Results showed that POLG2 was over-expressed in most cancer types, and the over-expression of POLG2 was correlated with PCa progression and suggested poor OS (Overall Survival) and PFI (Progress Free Interval). Multivariate analysis showed that POLG2 might be an independent prognostic factor of prostate cancer. We also performed GO/KEGG, GSEA analysis, co-expression genes, and PPI, and observed the metabolism-related gene alterations in PCa. Furthermore, we verified that POLG2 knockdown had an inhibitory effect on mitochondrial function, proliferation, cell motility, and invasion, we affirmed POLG2 could affect the prognosis of advanced prostate cancer via EMT. In summary, our findings indicate that over-expressed POLG2 renders poor prognosis in advanced prostate cancer. This disadvantageous factor can serve as a potential indicator, making it possible to target mitochondrial metabolism to treat advanced prostate cancer.

Finite Element Analysis of Different Carbon Fiber Reinforced Polyetheretherketone Dental Implants in Implant-supported Fixed Denture.

OBJECTIVES: The purpose of this study is to determine the feasibility of polyetheretherketone-based dental implants, and analyze the stress and strain around different kinds of dental implants by finite element analysis. METHODS: The radiographic data was disposed to models in Mimics 19.0. 3D models of implants, crowns and jawbones were established and combined in SolidWorks 2018. Appling axial and oblique loads of 100 N, cloud pictures were exported in Ansys Workbench 18.0 to calculate and analyze the stress and strain in and around different implants. RESULTS: Oblique load tended to deliver more stress to bone tissue than axial load. The uniformity of stress distribution was the best for 30% short carbon fiber reinforced polyetheretherketone implants at axial and buccolingual directions. Stress shielding phenomenon occurred at the neck of 60% continuous carbon fiber reinforced polyetheretherketone and titanium implants. Stress concentration appeared in PEEK implants and the load of bone tissue would aggravate. CONCLUSIONS: 30% short carbon fiber reinforced polyetheretherketone implants demonstrate a more uniform stress distribution in bone-implant contact and surrounding bone than titanium. Stress shielding and stress concentration may be avoided in bone-implant interface and bone tissue. Bone disuse-atrophy may be inhibited in PEEK-based implants.

Synergistic targeting of TrxR1 and ATM/AKT pathway in human colon cancer cells.

Thioredoxin reductase 1 (TrxR1) has emerged as a promising target for cancer therapy. In our previous research, we discovered several new TrxR1 inhibitors and found that they all have excellent anti-tumor activity. At the same time, we found these TrxR1 inhibitors all lead to an increase in AKT phosphorylation in cancer cells, but the detailed role of AKT phosphorylation in TrxR1 inhibitor-mediated cell death remains unclear. In this study, we identified the combination of AKT and TrxR1 inhibitor displayed a strong synergistic effect in colon cancer cells. Furthermore, we demonstrated that the synergistic effect of auranofin (TrxR1 inhibitor) and MK-2206 (AKT inhibitor) was caused by ROS accumulation. Importantly, we found that ATM inhibitor KU-55933 can block the increase of AKT phosphorylation caused by auranofin, and exhibited a synergistic effect with auranofin. Taken together, our study demonstrated that the activation of ATM/AKT pathway is a compensatory mechanism to cope with ROS accumulation induced by TrxR1 inhibitor, and synergistic targeting of TrxR1 and ATM/AKT pathway is a promising strategy for treating colon cancer.

Plasmonic Gold Nanostar-Based Probes with Distance-Dependent Plasmon-Enhanced Fluorescence for Ultrasensitive DNA Methyltransferase Assay.

The ultrasensitive DNA methyltransferase (Dam MTase) assay is of high significance for biomedical research and clinical diagnosis because of its profound effect on gene regulation. However, detection sensitivity is still limited by shortcomings, including photobleaching and weak signal intensities of conventional fluorophores at low concentrations. Plasmonic nanostructures with ultrastrong electromagnetic fields and fluorescence enhancement capability that can overcome these intrinsic defects hold great potential for ultrasensitive bioanalysis. Herein, a silica-coated gold nanostars (Au NSTs@SiO2)-based plasmon-enhanced fluorescence (PEF) probe with 20 "hot spots" was developed for ultrasensitive detection of Dam MTase. Here, the Dam Mtase assay was achieved by detecting the byproduct PPi of the rolling circle amplification reaction. It is worth noting that, benefiting from the excellent fluorescence enhancement capability of Au NSTs originating from their 20 "hot spots", the detection limit of Dam Mtase was reduced by nearly 105 times. Moreover, the proposed Au NST-based PEF probe enabled versatile evaluation of Dam MTase inhibitors as well as endogenous Dam MTase detection in GW5100 and JM110 Escherichia coli cell lysates, demonstrating its potential in biomedical analysis.

A converged ubiquitin-proteasome pathway for the degradation of TOC and TOM tail-anchored receptors.

In plants, thousands of nucleus-encoded proteins translated in the cytosol are sorted to chloroplasts and mitochondria by binding to specific receptors of the TOC (translocon on the outer chloroplast membrane) and the TOM (translocon on the outer mitochondrial membrane) complexes for import into those organelles. The degradation pathways for these receptors are unclear. Here, we discovered a converged ubiquitin-proteasome pathway for the degradation of Arabidopsis thaliana TOC and TOM tail-anchored receptors. The receptors are ubiquitinated by E3 ligase(s) and pulled from the outer membranes by the AAA+ adenosine triphosphatase CDC48, after which a previously uncharacterized cytosolic protein, transmembrane domain (TMD)-binding protein for tail-anchored outer membrane proteins (TTOP), binds to the exposed TMDs at the C termini of the receptors and CDC48, and delivers these complexes to the 26S proteasome.

Sarcopenia is associated with leukopenia in urothelial carcinoma patients who receive tislelizumab combined with gemcitabine and cisplatin therapy.

BACKGROUND: In the era of combination therapy, there has been limited research on body composition. Specific body composition, such as sarcopenia, possesses the potential to serve as a predictive biomarker for toxic effects and clinical response in patients with urothelial carcinoma (UC) undergoing tislelizumab combined with gemcitabine and cisplatin (T + GC). MATERIALS AND METHODS: A total of 112 UC patients who received T + GC were selected at the Affiliated Hospital of Xuzhou Medical University from April 2020 to January 2023. Baseline patient characteristics and detailed hematological parameters were collected using the electronic medical system and laboratory examinations. The computed tomography images of patients were analyzed to calculate psoas muscle mass index (PMI). We evaluated the association between sarcopenia (PMI < 4.5 cm2/m2 in men; PMI < 3.3 cm2/m2 in women) and both hematological toxicity and tumor response. RESULTS: Overall, of the 112 patients (65.2% male, median age 56 years), 43 (38.4%) were defined as sarcopenia. Patients with sarcopenia were notably older (p = 0.037), more likely to have hypertension (p = 0.009), and had poorer ECOG-PS (p = 0.027). Patients with sarcopenia were more likely to develop leukopenia (OR 2.969, 95% CI 1.028-8.575, p = 0.044) after receiving at least two cycles of T + GC. However, these significant differences were not observed in thrombocytopenia and anemia. There were no significant differences in the tumor response and grade 3-4 hematological toxicity between patients with sarcopenia and those without sarcopenia. CONCLUSIONS: Patients with sarcopenia were more likely to develop leukopenia after receiving T + GC. There were no notable alterations observed in relation to anemia or thrombocytopenia. No significant difference was found between the sarcopenia group and non-sarcopenia group in terms of tumor response and grade 3-4 hematological toxicity.

Supervised contrastive learning enhances graph convolutional networks for predicting neurodevelopmental deficits in very preterm infants using brain structural connectome.

Very preterm (VPT) infants (born at less than 32 weeks gestational age) are at high risk for various adverse neurodevelopmental deficits. Unfortunately, most of these deficits cannot be accurately diagnosed until the age of 2-5 years old. Given the benefits of early interventions, accurate diagnosis and prediction soon after birth are urgently needed for VPT infants. Previous studies have applied deep learning models to learn the brain structural connectome (SC) to predict neurodevelopmental deficits in the preterm population. However, none of these models are specifically designed for graph-structured data, and thus may potentially miss certain topological information conveyed in the brain SC. In this study, we aim to develop deep learning models to learn the SC acquired at term-equivalent age for early prediction of neurodevelopmental deficits at 2 years corrected age in VPT infants. We directly treated the brain SC as a graph, and applied graph convolutional network (GCN) models to capture complex topological information of the SC. In addition, we applied the supervised contrastive learning (SCL) technique to mitigate the effects of the data scarcity problem, and enable robust training of GCN models. We hypothesize that SCL will enhance GCN models for early prediction of neurodevelopmental deficits in VPT infants using the SC. We used a regional prospective cohort of ∼280 VPT infants who underwent MRI examinations at term-equivalent age from the Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS). These VPT infants completed neurodevelopmental assessment at 2 years corrected age to evaluate cognition, language, and motor skills. Using the SCL technique, the GCN model achieved mean areas under the receiver operating characteristic curve (AUCs) in the range of 0.72∼0.75 for predicting three neurodevelopmental deficits, outperforming several competing models. Our results support our hypothesis that the SCL technique is able to enhance the GCN model in our prediction tasks.

Integrative analysis identifies oxidative stress biomarkers in non-alcoholic fatty liver disease via machine learning and weighted gene co-expression network analysis.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally, with the potential to progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. Given the absence of effective treatments to halt its progression, novel molecular approaches to the NAFLD diagnosis and treatment are of paramount importance. Methods: Firstly, we downloaded oxidative stress-related genes from the GeneCards database and retrieved NAFLD-related datasets from the GEO database. Using the Limma R package and WGCNA, we identified differentially expressed genes closely associated with NAFLD. In our study, we identified 31 intersection genes by analyzing the intersection among oxidative stress-related genes, NAFLD-related genes, and genes closely associated with NAFLD as identified through Weighted Gene Co-expression Network Analysis (WGCNA). In a study of 31 intersection genes between NAFLD and Oxidative Stress (OS), we identified three hub genes using three machine learning algorithms: Least Absolute Shrinkage and Selection Operator (LASSO) regression, Support Vector Machine - Recursive Feature Elimination (SVM-RFE), and RandomForest. Subsequently, a nomogram was utilized to predict the incidence of NAFLD. The CIBERSORT algorithm was employed for immune infiltration analysis, single sample Gene Set Enrichment Analysis (ssGSEA) for functional enrichment analysis, and Protein-Protein Interaction (PPI) networks to explore the relationships between the three hub genes and other intersecting genes of NAFLD and OS. The distribution of these three hub genes across six cell clusters was determined using single-cell RNA sequencing. Finally, utilizing relevant data from the Attie Lab Diabetes Database, and liver tissues from NASH mouse model, Western Blot (WB) and Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) assays were conducted, this further validated the significant roles of CDKN1B and TFAM in NAFLD. Results: In the course of this research, we identified 31 genes with a strong association with oxidative stress in NAFLD. Subsequent machine learning analysis and external validation pinpointed two genes: CDKN1B and TFAM, as demonstrating the closest correlation to oxidative stress in NAFLD. Conclusion: This investigation found two hub genes that hold potential as novel targets for the diagnosis and treatment of NAFLD, thereby offering innovative perspectives for its clinical management.

Synthesis and Anti-Inflammatory Activity of Ferulic Acid-Sesquiterpene Lactone Hybrids.

Acute lung injury (ALI) is a respiratory failure disease associated with high mortality rates in patients. The primary pathological damage is attributed to the excessive release of pro-inflammatory mediators in pulmonary tissue. However, specific therapy for ALI has not been developed. In this study, a series of novel ferulic acid-parthenolide (FA-PTL) and ferulic acid-micheliolide (FA-MCL) hybrid derivatives were designed, synthesized, and evaluated for their anti-inflammatory activities in vitro. Compounds 2, 4, and 6 showed pronounced anti-inflammatory activity against LPS-induced expression of pro-inflammatory cytokines in vitro. Importantly, compound 6 displayed good water solubility, and treatment of mice with compound 6 (10 mg/kg) significantly prevented weight loss and ameliorated inflammatory cell infiltration and edema in lung tissue, as well as improving the alveolar structure. These results suggest that compound 6 (((1aR,7aS,8R,10aS,10bS,E)-8-((dimethylamino)methyl)-1a-methyl-9-oxo-1a,2,3,6,7,7a,8,9,10a,10b-decahydrooxireno[2',3':9,10]cyclodeca[1,2-b]furan-5-yl)methyl (E)-3-(4-hydroxy-3-methoxyphenyl)acrylate 2-hydroxypropane-1,2,3-tricarboxylate) might be considered as a lead compound for further evaluation as a potential anti-ALI agent.

Effects of cage vs. net-floor mixed rearing system on goose spleen histomorphology and gene expression profiles.

Due to the demands for both environmental protection and modernization of the goose industry in China, the traditional goose waterside rearing systems have been gradually transitioning to the modern intensive dryland rearing ones, such as the net-floor mixed rearing system (MRS) and cage rearing system (CRS). However, the goose immune responses to different dryland rearing systems remain poorly understood. This study aimed to investigate and compare the age-dependent effects of MRS and CRS on the splenic histomorphological characteristics and immune-related genes expression profiles among three economically important goose breeds, including Sichuan White goose (SW), Gang goose (GE), and Landes goose (LD). Morphological analysis revealed that the splenic weight and organ index of SW were higher under CRS than under MRS (p < 0.05). Histological observations showed that for SW and LD, the splenic corpuscle diameter and area as well as trabecular artery diameter were larger under MRS than under CRS at 30 or 43 weeks of age (p < 0.05), while the splenic red pulp area of GE was larger under CRS than under MRS at 43 weeks of age (p < 0.05). Besides, at 43 weeks of age, higher mRNA expression levels of NGF, SPI1, and VEGFA in spleens of SW were observed under MRS than under CRS (p < 0.05), while higher levels of HSPA2 and NGF in spleens of LD were observed under MRS than under CRS (p < 0.05). For GE, there were higher mRNA expression levels of MYD88 in spleens under CRS at 30 weeks of age (p < 0.05). Moreover, our correlation analysis showed that there appeared to be more pronounced positive associations between the splenic histological parameters and expression levels of several key immune-related genes under MRS than under CRS. Therefore, it is speculated that the geese reared under MRS might exhibit enhanced immune functions than those under CRS, particularly for SW and LD. Although these phenotypic differences are assumed to be associated with the age-dependent differential expression profiles of HSPA2, MYD88, NGF, SPI1, and VEGFA in the goose spleen, the underlying regulatory mechanisms await further investigations.

Semipinacol Rearrangement of Iododifluorohomoallyl Alcohols and Its Application in the Allylic C-H Esterification Reactions.

We herein present a study on the Ag(I)-mediated semipinacol rearrangement of iododifluorohomoallyl alcohols, the resulting allylic difluoromethyl ketones underwent oxidative allylic C-H esterification under palladium catalysis in the absence of external ligand. This process yielded a range of difluoromethyl ketones derived from allyl esters in a single operation. The reaction features broad scope of o-nitrobenzoic acids and homoallylic iododifluoroalcohols affording the targeted molecules in synthetically useful yields. Control experiments illustrated that the silver salt acted as not only a Lewis acid to promote the cleavage of a C-I bond and furnish the semipinacol rearrangement but also a co-oxidant in the catalytic cycle for the allylic C-H esterification.