Stratum affects the distribution of soil selenium bioavailability by modulating the soil physicochemical properties: A case study in a Se-enriched area, China.

The soil selenium (Se) content and bioavailability are important for human health. In this regard, knowing the factors driving the concentration of total Se and bioavailable Se in soils is essential to map Se, enhance foodstuffs' Se content, and improve the Se nutritional status of humans. In this study, total Se and Se bioavailability (i.e., phosphate extracted Se) in surface soils (0-20 cm) developed on different strata were analyzed in a Se-enriched region of Southwest China. Furthermore, the interaction between the stratum and soil properties was assessed and how did the stratum effect on the concentration and spatial distribution of Se bioavailability in soils was investigated. Results showed that the median concentration of total Se in soils was 0.308 mg/kg, which is higher than China's soil background. The mean proportion of phosphate extracted Se in total Se was 12.2 %. The values of total Se, phosphate extracted Se, and soil organic matter (SOM) in soils increased with the increasing stratum age. In contrast, the coefficient of weathering and eluviation (BA) values decreased. The analysis of statistics and Geodetector revealed that the SOM, stratum, and BA were the dominant controlling factors for the contents and distributions of soil total Se and phosphate extracted Se. This study provided strong evidence that the soil properties that affected the total Se and Se bioavailability were modulated by the local geological background, and had important practical implications for addressing Se malnutrition and developing the Se-rich resource in the study region and similar geological settings in different parts of the globe.

Prevalence and factors associated with overweight, obesity and central obesity among adults in Shenmu City, Shaanxi Province, China.

Objectives: This research aimed to explore the prevalence and determinants of overweight, obesity, and central obesity in Shenmu City, Shaanxi Province, China and to offer guidance for preventative health measures. Methods: We conducted a multi-stage, stratified random sampling survey among 4,565 residents of Shenmu City. Data collection included questionnaires and anthropometric assessments to gather socio-demographic data and to identify cases of overweight, obesity, and central obesity. Multivariable logistic regression analysis was utilized to assess the association between various factors and these conditions. Results: The observed prevalence rates for overweight, obesity, central obesity, and the combination of overweight/obesity with central obesity were 39.9%, 18.2%, 48.0%, 32.8%, and 22.8%, respectively. Notably, the incidence of these conditions was significantly higher in men compared to women. The prevalence of overweight and obesity initially increased and then decreased with age, whereas the prevalence of central obesity consistently rose. Furthermore, a higher educational level correlated with lower prevalence rates. Additionally, our analysis indicated that hypertension, dyslipidemia, and hyperuricemia are risk factors for these conditions. Conclusions: The findings of this study offer crucial insights for formulating effective strategies to prevent and manage obesity in Shenmu City.

The prevalence of obesity and relationship between obesity indicators and chronic diseases in Northern Shaanxi, China.

INTRODUCTION: Obesity not only affects human health but also is an important risk factor for a variety of chronic diseases. Therefore, it is particularly important to analyse the epidemic trend of obesity and actively carry out the prevention and control of obesity in the population. MATERIAL AND METHODS: A total of 4565 adults were selected by multi-stage stratified random sampling in Shenmu, Shaanxi Province, China. Univariate analysis was used to explore the epidemic characteristics of obesity in this region. Multivariate logistic regression was used to analyse the relationship between obesity and chronic diseases. Finally, the prediction efficiency of different obesity indexes was analysed by drawing receiver operator characteristic curves (ROC). All statistical analysis was completed by SPSS 26.0 software. RESULTS: The prevalence rates of overweight, obesity, and central obesity were 39.9%, 18.2%, and 48.0%, respectively. After adjusting for other confounding factors, multivariate logistic regression analysis showed that overweight and obesity were risk factors for hypertension, dyslipidaemia, and hyperuricaemia. Central obesity is a risk factor for dyslipidaemia and hyperuricaemia. High level of waist-to-height ratio (WHtR) was a risk factor for dyslipidaemia and hyperuricaemia (p < 0.05). Obesity-related indicators: body mass index (BMI), waist circumference (WC), and WHtR, are strongly correlated with the increased risk of chronic diseases in northern Shaanxi, China. The optimal BMI cut-off values for predicting hypertension, dyslipidaemia, and hyperuricaemia were 24.27, 24.04, and 25.54, respectively. The optimal WC cut-off values for predicting dyslipidaemia and hyperuricaemia were 84.5 and 90.5, and WHtR cut-off values were 0.52 and 0.54, respectively. CONCLUSION: The problem of overweight, obesity, and central obesity in adults is serious in northern Shaanxi, China. Obesity of all types will increase the risk of chronic diseases. Therefore, a variety of preventive and therapeutic measures should be adopted to curb obesity and reduce the incidence of related chronic diseases.

Blood Lipid Metabolic Profiles and Causal Links to Site-Specific Cancer Risks: A Mendelian Randomization Study.

Observational and Mendelian randomization (MR) studies have established links between dyslipidemia and select cancer susceptibilities. However, there is a lack of comprehensive exploration of causal relationships spanning diverse cancer types. Here, we conducted a two-sample MR analysis to elucidate the causative connections between 9 blood lipid metabolic profiles (namely, adiponectin, leptin, lipoprotein A, apolipoprotein A1, apolipoprotein B, cholesterol, triglycerides, LDL-cholesterol, and HDL-cholesterol) and 21 site-specific cancer risks. Our findings reveal genetically predicted adiponectin levels to be associated with a reduced ovarian cancer risk, while genetically determined leptin increases bladder cancer risk but decreases prostate cancer risk. Lipoprotein A elevates risk of prostate cancer while diminishing risk of endometrial cancer, while apolipoprotein A1 heightens risks of breast and cervical cancers. Furthermore, elevated levels of cholesterol are positively correlated with kidney cancer, and triglycerides demonstrate a positive association with non-melanoma skin cancer but a negative association with breast cancer. Protective effects of genetically predicted LDL-cholesterol on endometrial cancer and adverse effects of HDL-cholesterol on breast cancer are also observed. Our study conclusively establishes that blood lipid metabolic profiles exert causal effects on cancer susceptibility, providing more robust evidence for cancer prevention and prompting contemplation regarding the future health of the human populace.

Bulk RNA-sequencing, single-cell RNA-sequencing analysis, and experimental validation reveal iron metabolism-related genes CISD2 and CYP17A1 are potential diagnostic markers for recurrent pregnancy loss.

BACKGROUND: Recurrent pregnancy loss (RPL) is associated with variable causes. Its etiology remains unexplained in about half of the cases, with no effective treatment available. Individuals with RPL have an irregular iron metabolism. In the present study, we identified key genes impacting iron metabolism that could be used for diagnosing and treating RPL. METHODS: We obtained gene expression profiles from the Gene Expression Omnibus (GEO) database. The Molecular Signatures Database was used to identify 14 gene sets related to iron metabolism, comprising 520 iron metabolism genes. Differential analysis and a weighted gene co-expression network analysis (WGCNA) of gene expression revealed two iron metabolism-related hub genes. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were used on clinical samples to confirm our results. The receiver operating characteristic (ROC) analysis and immune infiltration analysis were conducted. In addition, we analyzed the distribution of genes and performed CellChat analysis by single-cell RNA sequencing. RESULTS: The expression of two hub genes, namely, CDGSH iron sulfur domain 2 (CISD2)and Cytochrome P450 family 17 subfamily A member 1 (CYP17A1), were reduced in RPL, as verified by both qPCR and immunohistochemistry. The Gene Ontology (GO) analysis revealed the genes predominantly engaged in autophagy and iron metabolism. The area under the curve (AUC) demonstrated better diagnostic performance for RPL using CISD2 and CYP17A1. The single-cell transcriptomic analysis of RPL demonstrated that CISD2 is expressed in the majority of cell subpopulations, whereas CYP17A1 is not. The cell cycle analysis revealed highly active natural killer (NK) cells that displayed the highest communications with other cells, including the strongest interaction with macrophages through the migratory inhibitory factor (MIF) pathway. CONCLUSIONS: Our study suggested that CISD2 and CYP17A1 genes are involved in abnormal iron metabolism, thereby contributing to RPL. These genes could be used as potential diagnostic and therapeutic markers for RPL.

The Assessment of TLR1 Gene Polymorphism Association with the Risk of Allergic Rhinitis in the Chinese Han Population from Northern China.

Background: Environmental factors and genetic predisposition can influence the occurrence and development of AR. Toll-like receptor 1 (TLR1) belongs to the TLR receptor family, which plays a fundamental role in the activation of innate immunity. This study aimed to explore the association between TLR1 genetic loci and AR susceptibility in the Han Chinese from northern China. Methods: Genotyping of three SNPs in the TLR1 has proceeded using the Agena MassARRAY platform. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the correlation between candidate SNPs and AR susceptibility. Using FPRP (false-positive report probability analysis) to detect whether the positive results are noteworthy findings. The SNP-SNP interactions were detected by multifactor dimensionality reduction (MDR). Results: TLR1-rs72493538 (Allele "G": OR=0.77, p = 0.034) and -rs76600635 (Allele "G": OR=0.75, p = 0.024) were associated with reducing the risk of AR among Han Chinese in northern China. In addition, we found evidence that TLR1-rs72493538 (males, participants with aging > 43 years, or coming from the wind-blown sand region) and -rs76600635 (males, participants with BMI ≤ 24 kg/m2, or coming from the wind-blown sand region) were associated with AR risk in stratified analyses. FPRP showed that all positive results are noteworthy findings. MDR analysis showed that a two-loci genetic model composed of rs72493538 and rs76600635 can be chosen as the best genetic model to predict the risk of AR. Conclusion: TLR1-rs72493538 and -rs76600635 have a close association with reducing the risk of AR.

Simulation and prediction for the spatial heterogeneity of soil selenium bioavailability at different stratigraphic scales.

Stratigraphic lithology strongly influences the spatial heterogeneity of soil available selenium (ASe), however, it is often neglected in regional simulation. Therefore, taking the Jiangjin District, where the soil is richer in selenium (Se), as the research area, the changes of soil ASe at different spatial scales have been simulated by combining Geodetector and three popular models (Multiple linear regression (MLR), Random forest (RF) and BP neural network (BPN)). The results showed that modelling with 'Formation' as the spatial scale could reduce the influence of stratum lithology difference on the spatial heterogeneity of soil ASe and improve the model's prediction accuracy. Compared with the MLR (R2 = 0.52, root mean squares error (RMSE) = 13.217 µg kg-1) and BPN (R2 = 0.55, RMSE = 13.79 µg kg-1), the RF (R2 = 0.67, RMSE = 10.85 µg kg-1) exhibited higher R2 and smaller RMSE, and the simulation effect of soil ASe is the best in the Middle Jurassic Shaximiao Formation (J2s). The outcomes of variable importance analysis revealed that soil total selenium (TSe) and soil organic matter (SOM) were the imperative factors for predicting ASe. The scenario simulation prediction showed that in the next 40 years, due to the combined influence of SOM and pH, the content of ASe in soil developed in the J2s would decrease from 40.8 µg kg-1 to 37.8 µg kg-1, a 7.8 percent drop. The main areas of soil ASe loss were in the western farming areas. The ASe content in dry land and paddy fields decreased by 12.0% and 4.9%, respectively. Therefore, long-term agricultural production activities would lead to soil ASe loss. The present results could provide a new scheme for the simulation and prediction of regional soil ASe, which is helpful for scientific planning, utilization of selenium-rich soil resources, and development of regional agricultural economy.

Synthesis of acrylic resin and methacrylic resin microspheres by suspension polymerization.

The process of suspension polymerization was utilized to create acrylate resin microspheres with mesh numbers of 140-200 µm and particle sizes of 100 µm for implementation in mesh coating technology. The copolymer of methyl methacrylate (MMA) and methyl acrylate (MA) served as the primary polymer, with dibenzoyl peroxide (DBPO) functioning as the initiator, and a mixture of calcium carbonate and deionized water served as the dispersion medium. The surface morphology of the synthesized microspheres was analyzed through Fourier-transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) to confirm successful synthesis. The optimal reaction conditions for the synthesis of these microspheres were determined to be a dispersant dosage of 30 g of calcium carbonate with a monomer ratio of 4:1, a reaction time of 1 h, an initiator dosage of 1.2 g of BPO, and a reaction temperature of approximately 75-80 C, resulting in microspheres with a regular spherical shape and smooth surface.

Hyperoside alleviates postmenopausal osteoporosis via regulating miR-19a-5p/IL-17A axis.

PROBLEM: Postmenopausal osteoporosis (PMO) is a common osteoporosis. Hyperoside (Hyp), a natural flavonoid compound, has anti-osteoporotic effects, but the underlying mechanisms remain poorly understood. Inflammatory cytokine IL-17A is upregulated in PMO and plays vital roles in bone loss, but the upstream regulatory factors and mechanisms are still unknown. METHOD OF STUDY: Twenty PMO patients and 20 healthy control subjects were included to analyze IL-17A expression changes and screen dys-regulated miRNAs in the peripheral blood of PMO patients. miR-19a-5p mimics and inhibitor were transfected into RAW264.7 osteoclasts, and injected into bilateral ovariectomized (OVX) mice to explore the regulatory effect of miR-19a-5p on IL-17A. OVX mice were randomly grouped and treated with different doses of Hyp to uncover the effective targets for the medicine in PMO disease. RESULTS: MiR-19a-5p was downregulated in PMO patients and the expression level was negatively correlated with that of IL-17A. miR-19a-5p could directly bind to the 3'UTR of IL-17A and regulate its expression. Both in vitro and in vivo studies demonstrated that miR-19a-5p mimics decreased the expression of IL-17A, RANK and Cathepsin K, while miR-19a-5p inhibitor significantly increased the expression of IL-17A, RANK, and Cathepsin K. Importantly, the Hyp could improve bone structure of OVX mice by enhancing miR-19a-5p-mediated IL-17A downregulation. CONCLUSION: Overall, these data demonstrated that miR-19a-5p/IL-17A axis might serve as novel therapeutic candidate for PMO. Hyp could relieve bone resorption by targeting the miR-19a-5p/IL-17A axis in OVX mice and exhibited prospective for the treatment of PMO.

[Analysis of Change and Driving Factors of River Environmental Quality in China from 2002 to 2020].

According to the river environmental quality, pollutant emission, and investment in environmental pollution control from 2002-2020, the change law and driving factors of river environmental quality in China were evaluated using canonical correlation analysis and the Spearman correlation coefficient to analyze the influence between environmental and pollutant emission/investment in environmental pollution control. The results indicated that the river environmental quality was improved significantly based on the proportion of Class Ⅰ-Ⅲ increasing from 29.1% to 87.4% and the proportion of inferior Class Ⅴ decreasing from 40.9% to 0.2% from 2002-2020. The emission of wastewater and domestic wastewater increased from 4.395×1010 tons and 2.323×1010 tons to 8.491×1010 tons and 6.598×1010 tons, respectively. However, emissions of industrial wastewater decreased from 2.072×1010 tons to 1.680×1010 tons. Investment in environmental pollution control increased from 110.66 billion yuan to 1063.89 billion yuan. The proportion of Class Ⅰ-Ⅲ in seven major river basins, river basins in Zhejiang and Fujian, southwest river basins, and northwest river basins showed a negative correlation for industrial pollutant emissions and a positive correlation for investment in environmental pollution control. The primary measure for the seven major river basins, river basins in Zhejiang and Fujian, and northwest river basins cut down the industrial pollutant emissions, in the order of COD>NH4+-N>total wastewater. The primary measure for southwest river basins increased the investment in environmental pollution control, in the order of industrial investment in environmental pollution control>urban environmental infrastructure construction investment and environmental protection investment in construction projects. These results can provide theoretical and policy suggestions for the improvement of river environmental quality during the "14th Five-Year Plan" period.

A rapid magnetic-based purification of Cd2+ and Pb2+ prior to portable electrochemical determination for grain.

How to quickly separate and detect cadmium (Cd2+) and lead (Pb2+) from solid samples is a difficult problem that needs to be solved. For this, Fe3O4@agarose@iminodiacetic acid (IDA) was synthesized and used for rapid purification of Cd2+ and Pb2+. This material can remove complex matrix interference completely within a short time of 15 min. The mechanism of the adsorption kinetics fit well to a pseudo-second-order model. A portable screen-printed electrodes (SPEs)-based electrochemical detection platform was established. After coupling with the pretreatment, the whole detection process only took within 30 min. The limits of detection (LOD) were ten times lower than those of the Codex general standard, with values of 0.02 and 0.01 mg/kg for Pb2+ and Cd2+, respectively. The recoveries ranged from 84.1% to 109.7% in naturally contaminated grain, in good agreement with the ICP-MS, demonstrating great prospects for the rapid screening and monitoring of Cd2+ and Pb2+ in grain.

Emerging role of miRNAs, lncRNAs, and circRNAs in pregnancy-associated diseases.

ABSTRACT: Accumulating studies have demonstrated that non-coding RNAs (ncRNAs), functioning as important regulators of transcription and translation, are involved in the establishment and maintenance of pregnancy, especially the maternal immune adaptation process. The endometrial stromal cells (ESCs), trophoblast cells, and decidua immune cells that reside at the maternal-fetal interface are thought to play significant roles in normal pregnancy and pregnancy-associated diseases. Here, we reviewed the up-to-date evidence on how microRNA, long non-coding RNA, and circular RNA regulate ESCs, trophoblast cells, and immune cells and discussed the potential applications of these ncRNAs as diagnostic and therapeutic markers in pregnancy complications.

Association between polymorphisms of the GSDMB gene and allergic rhinitis risk in the Chinese population: a case-control study.

BACKGROUND: Allergic rhinitis (AR) is a great risk factor for developing asthma, and its pathogenesis is affected by various factors, such as gene and environment. GSDMB is related to allergic diseases. Our purpose is to explore the correlation of single nucleotide polymorphisms (SNPs) in GSDMB and AR risk in the Chinese population. METHODS: We performed a case-control study including 1005 cases and 1004 controls. Rs2305479, rs4795400, and rs12450091 in GSDMB were geneotyped using Agena MassARRAY. The relationships between GSDMB SNPs and AR risk were assessed by logistic regression analysis in PLINK1.9. RESULTS: Our study showed that rs4795400 was a protective factor for AR in overall (TT vs. CC: OR = 0.66, p = 0.009; TT vs. CC/TC: OR = 0.67, p = 0.008; additive: OR = 0.87, p = 0.042 males, people with BMI ≤ 24, and living in wind-blown sand area. Rs2305479 was associated with a reduced AR risk in males (TT vs. CC: OR = 0.47, p = 0.014; TT vs. CC/TC: OR = 0.43, p = 0.004). However, rs12450091 was a risk factor for AR in people living in the loess hilly region (CC: OR = 4.75, p = 0.047). The levels of EO and EO_per in the case group were significantly higher than those in the control group (p < 0.05). CONCLUSION: This study indicated that GSDMB polymorphisms (rs4795400, rs2305479, and rs12450091) were associated with AR susceptibility. Further studies are required to confirm our findings and to clarify the functional relationship.

[Soil Heavy Metal Content, Pollution, and Influencing Factors in Typical Farming Area of Sichuan Basin].

In order to identify heavy metal contents, the pollution characteristics and influencing factors of soil in typical farming areas in the Sichuan basin were analyzed, with Jiangjin District of Chongqing City chosen as the study area. Two hundred and forty-seven topsoil samples were collected and analyzed using the Nemerow index (NPI), geographical information system (GIS), and geodetector method. The results demonstrated that: 1 the arithmetic means of Cd, Cu, and Zn in the topsoil were 1.22, 1.10, and 1.98 times that of the soil background values in western Chongqing, respectively. 2 The high-value areas of the six heavy metals were mainly distributed in the northern, western, and central Jiangjin district, whereas the low-value areas were distributed in the eastern and southern Jiangjin district. 3 The NPI showed that the polluted sample points accounted for 22.1% of the total sample points, indicating that the overall soil pollution was mainly safety and vigilance in general. The high value of NPI was distributed in Dingshan street in the northern Jiangjin district. 4 The explanatory power of stratum on the distribution of heavy metal contents in the topsoil was the strongest, followed by that of the topographic factor. The interaction effect of the stratum and topographic factors on the distribution of heavy metal content in soil was the strongest. The results showed that the stratum and topographic factors were the key factors affecting the distribution of soil heavy metal contents in the study area.

Automated and Rapid Easy-to-Use Magnetic Solid-Phase Extraction System for Five Heavy Metals in Cereals and Feeds.

A rapid, accurate, and ecofriendly pretreatment plays an extremely important role prior to ICP-MS for heavy metal analysis. In order to improve the pretreatment efficiency, a high-throughput and automatic magnetic solid-phase extraction of five heavy metals (Cd, Pb, Mn, Cu, and Zn) was carried out by a magnet-controlled pretreatment system with an ecofriendly diluted acid as an extracting agent and carboxyl-functionalized magnetic beads as a pretreatment material. Key conditions, including the pH, adsorption time, and eluent solution, were optimized. The time for purification and enrichment was only 8 min. The adsorption capacities of the carboxyl-functionalized magnetic beads were in the range of 152~426 mg g-1. The preconcentration factor of Cu was 40, and others were 200. In the optimal conditions, the limits of detection for Mn, Zn, Cd, Cu, and Pb by ICP-MS were 3.84, 2.71, 0.16, 11.54, and 6.01 ng L-1, respectively. The percentage recoveries were in the range of 80~110%, and the relative standard deviations were less than 3%. The developed method was in good agreement with traditional standard microwave digestion. Additionally, the designed system could simultaneously process up to 24 samples within 22 min, reducing the time to less than 1 min/sample. Thus, the proposed auto-MSPE-ICP-MS method was successfully applied to analyze five heavy metals in cereals and feeds with a simple operation and high precision, safety, and reliability.

Investigating genetic causal relationships between blood pressure and anxiety, depressive symptoms, neuroticism and subjective well-being.

Background: High blood pressure is a leading cardiovascular disease risk factor and considered to be associated with psychological factors. However, the causal relationships between blood pressure and anxiety, depressive symptoms, neuroticism and subjective well-being are not clear. Aims: The current study explored the genetic causal relationships between blood pressure and anxiety, depressive symptoms, neuroticism and subjective well-being. Methods: Mendelian randomisation (MR) analyses were performed using the generalised summary-data-based MR analysis method with eight large-scale genome-wide association study datasets for hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure, anxiety, depressive symptoms, neuroticism and subjective well-being. Results: A causal effect of DBP on neuroticism was found, and 1074 independent instrumental single nucleotide polymorphisms were identified by the incorporated Heterogeneity in Dependent Instruments-outlier test among the bidirectional causal relationship between blood pressure and the four psychological states. Conclusions: DBP has a causal effect on neuroticism. Appropriate management of blood pressure may reduce neuroticism, neuroticism-inducing mood disorders and cardiovascular diseases.

Evidence that the pituitary gland connects type 2 diabetes mellitus and schizophrenia based on large-scale trans-ethnic genetic analyses.

BACKGROUND: Previous studies on European (EUR) samples have obtained inconsistent results regarding the genetic correlation between type 2 diabetes mellitus (T2DM) and Schizophrenia (SCZ). A large-scale trans-ethnic genetic analysis may provide additional evidence with enhanced power. OBJECTIVE: We aimed to explore the genetic basis for both T2DM and SCZ based on large-scale genetic analyses of genome-wide association study (GWAS) data from both East Asian (EAS) and EUR subjects. METHODS: A range of complementary approaches were employed to cross-validate the genetic correlation between T2DM and SCZ at the whole genome, autosomes (linkage disequilibrium score regression, LDSC), loci (Heritability Estimation from Summary Statistics, HESS), and causal variants (MiXeR and Mendelian randomization, MR) levels. Then, genome-wide and transcriptome-wide cross-trait/ethnic meta-analyses were performed separately to explore the effective shared organs, cells and molecular pathways. RESULTS: A weak genome-wide negative genetic correlation between SCZ and T2DM was found for the EUR (rg = - 0.098, P = 0.009) and EAS (rg =- 0.053 and P = 0.032) populations, which showed no significant difference between the EUR and EAS populations (P = 0.22). After Bonferroni correction, the rg remained significant only in the EUR population. Similar results were obtained from analyses at the levels of autosomes, loci and causal variants. 25 independent variants were firstly identified as being responsible for both SCZ and T2DM. The variants associated with the two disorders were significantly correlated to the gene expression profiles in the brain (P = 1.1E-9) and pituitary gland (P = 1.9E-6). Then, 61 protein-coding and non-coding genes were identified as effective genes in the pituitary gland (P < 9.23E-6) and were enriched in metabolic pathways related to glutathione mediated arsenate detoxification and to D-myo-inositol-trisphosphate. CONCLUSION: Here, we show that a negative genetic correlation exists between SCZ and T2DM at the whole genome, autosome, locus and causal variant levels. We identify pituitary gland as a common effective organ for both diseases, in which non-protein-coding effective genes, such as lncRNAs, may be responsible for the negative genetic correlation. This highlights the importance of molecular metabolism and neuroendocrine modulation in the pituitary gland, which may be responsible for the initiation of T2DM in SCZ patients.

Integrating network pharmacology and an experimental validation strategy elucidates the protective effect and mechanism of callicarpa nudiflora against neuroinflammation.

Abnormal activation of microglia promotes neuroinflammation (NI) in Alzheimer's disease (AD). Callicarpa nudiflora Hook et Arn. (CN) is a traditional Chinese herb with a wide range of clinical applications and definite anti-inflammatory effects. However, the anti-inflammatory action and mechanism of NI are not known. The purpose of this research was to survey whether CN could inhibit lipopolysaccharide (LPS)-induced inflammatory activation in BV-2 microglia. This study used a network pharmacology and pharmacophore model-based approach to explore the molecular mechanism of CN anti-NI by combining molecular docking and experimental validation. First, we screened the key active components and targets of CN anti-NI by network pharmacology. Then, the common structural features of these functional molecules in the treatment of neuroinflammation were predicted by 3D-QSAR pharmacodynamic modeling. Finally, the molecular mechanism of the active ingredient 5-hydroxy-3,7,4'-trimethoxyflavone (THF) against neuroinflammation was validated by molecular docking and in vitro experiments. In conclusion, this study established the structure-activity relationships of the active components of CN anti-NI and provided new insights into the pharmacological mechanisms of CN anti-NI at an integrative level.

Association between IL1RL1 gene polymorphisms and allergic rhinitis risk in the Chinese Han population.

BACKGROUND: Although it has been confirmed that IL1RL1 is involved in the occurrence of allergic rhinitis (AR), the role of IL1RL1 gene single nucleotide polymorphisms (SNPs) in AR is still unclear. METHODS: We performed a case-control study including 1000 AR patients and 1000 healthy controls. The four SNPs rs72823628 G > A, rs950881 G > T, rs72823641 T > A and rs3771175 T > A in IL1RL1 were chosen and genotyped using Agena MassARRAY platform. The relationship between IL1RL1 SNPs and AR risk was analyzed by logistic regression and assessed with odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs). RESULTS: Overall analysis revealed that IL1RL1 gene rs72823628, rs950881 and rs3771175 were associated with a reduced AR risk. Stratified analysis showed that the three SNPs (rs72823628, rs950881 and rs3771175) were obviously linked to a reduced risk of AR in males. Moreover, no correlation was observed between haplotypes and reduced AR risk after the false discovery rate (FDR) correction. The false positive report probability (FPRP) analysis was used to further validate significant findings. CONCLUSION: Our study is the first to indicate that IL1RL1 gene polymorphisms (rs72823628, rs950881 and rs3771175) may be correlated with decreased risk of AR in the Chinese Han population.

Genetic Loci in Phospholipase C-Like 1 (PLCL1) are Protective Factors for Allergic Rhinitis in Han Population of Northern Shaanxi, China.

Background: Allergic rhinitis (AR) is a common allergic disease in otolaryngology. Its pathogenesis is still unclear. PLC1 plays a key role in calcium homeostasis and immune response, which is potentially related to AR. We aimed to explore the association between PLCL1 genetic loci and susceptibility to AR. Methods: We recruited 1975 volunteers to perform an association analysis through SNPStats online software. False-positive report probability (FPRP) analysis was used to detect whether the positive findings were worth noting. Linkage disequilibrium and haplotype analysis were completed through Haploview and SNPStats. The influence of SNP-SNP interaction on AR susceptibility was evaluated through multifactor dimensionality reduction (MDR). Results: The results showed that four genetic loci in PLCL1 (rs2139049, rs212164068, rs2228135, and rs6738825) are associated with AR susceptibility under multiple genetic models. Allele "A" of PLCL1-rs2139049 (OR = 0.85, p = 0.031) or of -rs212164068 (OR = 0.85, p = 0.030), and allele "G" of PLCL1-rs6738825 (OR = 0.84, p = 0.022) are significantly associated with reduced AR risk. PLCL1-rs2228135 is associated with an increased risk of AR in males or participants older than 43 years of age. FPRP analysis showed that most of positive results are noteworthy findings. Three loci model composed of rs2139049, rs2164068, and rs2228135 is the best model for predicting AR risk (p = 0.0022). In addition, the haplotype "Grs2139049Ars6738825Ars2164068Ars2228135" (OR = 0.50, p = 0.033) can reduce the AR risk. Conclusion: Allele "A" of PLCL1-rs2139049, allele "A" of -rs212164068, and allele "G" of PLCL1-rs6738825 are protective factors of AR in Han population from northern Shaanxi, China.