Genome-wide association study on serum alkaline phosphatase levels in a Chinese population

Background: Serum alkaline phosphatase (ALP) is a complex phenotype influenced by both genetic and environmental factors. Recent Genome-Wide Association Studies (GWAS) have identified several loci affecting ALP levels; however, such studies in Chinese populations are limited. We performed a GWAS analyzing the association between 658,288 autosomal SNPs and serum ALP in 1,461 subjects, and replicated the top SNPs in an additional 8,830 healthy Chinese Han individuals. The interactions between significant locus and environmental factors on serum ALP levels were further investigated. Results: The association between ABO locus and serum ALP levels was replicated (P = 2.50 × 10-21, 1.12 × 10-56 and 2.82 × 10-27 for SNP rs8176720, rs651007 and rs7025162 on ABO locus, respectively). SNP rs651007 accounted for 2.15% of the total variance of serum ALP levels independently of the other 2 SNPs. When comparing our findings with previously published studies, ethnic differences were observed across populations. A significant interaction between ABO rs651007 and overweight and obesity was observed (FDR for interaction was 0.036); for individuals with GG genotype, those with normal weight and those who were overweight or obese have similar serum ALP concentrations; minor allele A of rs651007 remarkably reduced serum ALP levels, but this effect was attenuated in overweight and obese individuals. Conclusions: Our findings indicate that ABO locus is a major determinant for serum ALP levels in Chinese Han population. Overweight and obesity modifies the effect of ABO locus on serum ALP concentrations

Genome-Wide Analysis of DNA Methylation and Cigarette Smoking in a Chinese Population

Background: Smoking is a risk factor for many human diseases. DNA methylation has been related to smoking, but genome-wide methylation data for smoking in Chinese populations is limited. Objectives: We aimed to investigate epigenome-wide methylation in relation to smoking in a Chinese population. Methods: We measured the methylation levels at > 485,000 CpG sites (CpGs) in DNA from leukocytes using a methylation array and conducted a genome-wide meta-analysis of DNA methylation and smoking in a total of 596 Chinese participants. We further evaluated the associations of smoking-related CpGs with internal polycyclic aromatic hydrocarbon (PAH) biomarkers and their correlations with the expression of corresponding genes. Results: We identified 318 CpGs whose methylation levels were associated with smoking at a genome-wide significance level (false discovery rate < 0.05), among which 161 CpGs annotated to 123 genes were not associated with smoking in recent studies of Europeans and African Americans. Of these smoking-related CpGs, methylation levels at 80 CpGs showed significant correlations with the expression of corresponding genes (including RUNX3, IL6R, PTAFR, ANKRD11, CEP135 and CDH23), and methylation at 15 CpGs was significantly associated with urinary 2-hydroxynaphthalene, the most representative internal monohydroxy-PAH biomarker for smoking. Conclusion: We identified DNA methylation markers associated with smoking in a Chinese population, including some markers that were also correlated with gene expression. Exposure to naphthalene, a byproduct of tobacco smoke, may contribute to smoking-related methylation. Citation: Zhu X, Li J, Deng S, Yu K, Liu X, Deng Q, Sun H, Zhang X, He M, Guo H, Chen W, Yuan J, Zhang B, Kuang D, He X, Bai Y, Han X, Liu B, Li X, Yang L, Jiang H, Zhang Y, Hu J, Cheng L, Luo X, Mei W, Zhou Z, Sun S, Zhang L, Liu C, Guo Y, Zhang Z, Hu FB, Liang L, Wu T. 2016. Genome-wide analysis of DNA methylation and cigarette smoking in Chinese. Environ Health Perspect 124:966–973; http://dx.doi.org/10.1289/ehp.150983

Enrichment of Trypsin Inhibitor from Soybean Whey Wastewater Using Different Precipitating Agents and Analysis of Their Properties

Recovering valuable active substances from the by-products of agricultural processing is a crucial concern for scientific researchers. This paper focuses on the enrichment of soybean trypsin inhibitor (STI) from soybean whey wastewater using either ammonium sulfate salting or ethanol precipitation, and discusses their physicochemical properties. The results show that at a 60% ethanol content, the yield of STI was 3.983 mg/mL, whereas the yield was 3.833 mg/mL at 60% ammonium sulfate saturation. The inhibitory activity of STI obtained by ammonium sulfate salting out (A-STI) was higher than that obtained by ethanol precipitation (E-STI). A-STI exhibited better solubility than E-STI at specific temperatures and pH levels, as confirmed by turbidity and surface hydrophobicity measurements. Thermal characterization revealed that both A-STI and E-STI showed thermal transition temperatures above 90 °C. Scanning electron microscopy demonstrated that A-STI had a smooth surface with fewer pores, while E-STI had a rough surface with more pores. In conclusion, there was no significant difference in the yield of A-STI and E-STI (p < 0.05); however, the physicochemical properties of A-STI were superior to those of E-STI, making it more suitable for further processing and utilization. This study provides a theoretical reference for the enrichment of STI from soybean whey wastewater

Several first-line anti-hypertensives act on fibrosarcoma progression and PD1ab blockade therapy

Abstract Purpose Patients are typically diagnosed with both hypertension and fibrosarcoma. Medical oncologists must prescribe suitable anti-hypertensive medications while considering anti-tumor drugs. Recently, immunotherapy has become prominent in cancer treatment. Nonetheless, it is unknown what role anti-hypertensive medications will play in immunotherapy. Methods We examined the effects of six first-line anti-hypertensive medications on programmed cell death protein 1 antibody (PD1ab) in tumor treatment using a mouse model of subcutaneous fibrosarcoma. The drugs examined were verapamil, losartan, furosemide, spironolactone, captopril, and hydrochlorothiazide (HCTZ). The infiltration of CD8+ T cells was examined by immunohistochemistry. Additionally, several in vitro and in vivo assays were used to study the effects of HCTZ on human fibrosarcoma cancer cells to explore its mechanism. Results Verapamil suppressed tumor growth and showed an improved effect on the tumor inhibition of PD1ab. Captopril did not affect tumor growth but brought an unexpected benefit to PD1ab treatment. In contrast, spironolactone and furosemide showed no effect on tumor growth but had an offset effect on the PD1ab therapy. Consequently, the survival time of mice was also significantly reduced. Notably, losartan and HCTZ, especially HCTZ, promoted tumor growth and weakened the effect of PD1ab treatment. Consistent results were observed in vivo and in vitro using the human fibrosarcoma cell line HT1080. We determined that the Solute Carrier Family 12 Member 3 (SLC12A3), a known target of HCTZ, may be the principal factor underlying its effect-enhancing properties through mechanism studies employing The Cancer Genome Atlas (TCGA) data and in vivo and in vitro assays. Conclusion Verapamil and captopril potentiated the anti-tumor effect of PD1ab, whereas spironolactone and furosemide weakened the effect of PD1ab on tumor inhibition. Alarmingly, losartan and HCTZ promoted tumor growth and impaired the effect of PD1ab. Furthermore, we preliminarily found that HCTZ may promote tumor progression through SLC12A3. Based on this study, futher mechanism researches and clinical trials should be conducted in the future

An Experimental Evaluation of Toxicity Effects of Sodium Chloride on Oviposition, Hatching and Larval Development of Aedes albopictus

Dengue virus, one of the most important mosquito-borne viruses, has shown a sharp upward trend, spreading around the world in recent years. Control of vectors Aedes aegypti and Ae. albopictus remains crucial for blocking dengue transmission. The lethal ovitrap (LO) is one of the cost-effective traps based on the classic &ldquo;lure and kill&rdquo; strategy, and finding a proper long-lasting effective toxin is key to achieving the desired effect. The concentration of inorganic salts of habitat environment plays a strong role in affecting oviposition, hatching, and development of mosquitoes, but the potential insecticide activity of Sodium Chloride (NaCl) in habitat water as well as LO still lacks research. In this study, we carried out laboratory experiments to systematically explore the effects of different concentrations of NaCl solutions on oviposition, egg hatching, and larval development of Ae. albopictus. Consequently, Ae. albopictus was found to prefer freshwater to lay eggs; whereas 48.8 &plusmn; 2.6% eggs were laid in freshwater and 20% in &ge;1.0% brackish water, few eggs were laid in 3.0% NaCl solution. Compared with egg hatching, larval development of Ae. albopictus presented a higher sensibility to NaCl concentration. The mortality of the 3rd&ndash;4th larvae in 1.0% NaCl solution was 83.8 &plusmn; 8.7%, while in 3.0% it reached 100%. Considering the cumulative effect of NaCl, when NaCl concentration was &ge;1.0%, no eggs could successfully develop into adults. These data suggested that NaCl solutions with a concentration &ge;1.0% can be used as an effective cheap insecticide for Ae. albopictus in subtropical inland aquatic habitats, and also as the &ldquo;kill&rdquo; toxin in LOs. Meanwhile, the concentration range from 0 to 2.0% of NaCl solution has the potential to be used as the &ldquo;lure&rdquo; in LOs. The technological processes of how to use NaCl as insecticide or in LOs still needs further in-depth exploration

CircZNF609 regulates pulmonary fibrosis via miR-145-5p/KLF4 axis and its translation function

Abstract Background Pulmonary fibrosis is a growing clinical problem that develops as a result of abnormal wound healing, leading to breathlessness, pulmonary dysfunction and ultimately death. However, therapeutic options for pulmonary fibrosis are limited because the underlying pathogenesis remains incompletely understood. Circular RNAs, as key regulators in various diseases, remain poorly understood in pulmonary fibrosis induced by silica. Methods We performed studies with fibroblast cell lines and silica-induced mouse pulmonary fibrosis models. The expression of circZNF609, miR-145-5p, and KLF4 was determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. RNA immunoprecipitation (RIP) assays and m6A RNA immunoprecipitation assays (MeRIP), Western blotting, immunofluorescence assays, and CCK8 were performed to investigate the role of the circZNF609/miR-145-5p/KLF4 axis and circZNF609-encoded peptides in fibroblast activation. Results Our data showed that circZNF609 was downregulated in activated fibroblasts and silica-induced fibrotic mouse lung tissues. Overexpression of circZNF609 could inhibit fibroblast activation induced by transforming growth factor-β1 (TGF-β1). Mechanically, we revealed that circZNF609 regulates pulmonary fibrosis via miR-145-5p/KLF4 axis and circZNF609-encoded peptides. Furthermore, circZNF609 was highly methylated and its expression was controlled by N6-methyladenosine (m6A) modification. Lastly, in vivo studies revealed that overexpression of circZNF609 attenuates silica-induced lung fibrosis in mice. Conclusions Our data indicate that circZNF609 is a critical regulator of fibroblast activation and silica-induced lung fibrosis. The circZNF609 and its derived peptides may represent novel promising targets for the treatment of pulmonary fibrosis

MIMO: A Unified Spatio-Temporal Model for Multi-Scale Sea Surface Temperature Prediction

Sea surface temperature (SST) is a crucial factor that affects global climate and marine activities. Predicting SST at different temporal scales benefits various applications, from short-term SST prediction for weather forecasting to long-term SST prediction for analyzing El Niño–Southern Oscillation (ENSO). However, existing approaches for SST prediction train separate models for different temporal scales, which is inefficient and cannot take advantage of the correlations among the temperatures of different scales to improve the prediction performance. In this work, we propose a unified spatio-temporal model termed the Multi-In and Multi-Out (MIMO) model to predict SST at different scales. MIMO is an encoder–decoder model, where the encoder learns spatio-temporal features from the SST data of multiple scales, and fuses the learned features with a Cross Scale Fusion (CSF) operation. The decoder utilizes the learned features from the encoder to adaptively predict the SST of different scales. To our best knowledge, this is the first work to predict SST at different temporal scales simultaneously with a single model. According to the experimental evaluation on the Optimum Interpolation SST (OISST) dataset, MIMO achieves the state-of-the-art prediction performance

Metal Exposure-Related Welder&rsquo;s Pneumoconiosis and Lung Function: A Cross-Sectional Study in a Container Factory of China

Long-term inhalation of welding fume at high exposure can cause welder&rsquo;s pneumoconiosis, and metals in welding dust are associated with respiratory dysfunction. This cross-sectional study, which contains 384 Chinese male workers who were or had been working in a container factory, aimed to assess the potential risk of haemal and urinary metal content in welder&rsquo;s pneumoconiosis. Further, we investigated their effects on lung function parameters. Metal content and lung function were measured using inductively coupled plasma&ndash;mass spectrometry (ICP-MS) and spirometer, respectively. The concentration and metal content of respirable dust as well as total dust were collected at this container factory. Lung function of cases with welder&rsquo;s pneumoconiosis was significantly worse, as indicated by lower values of FVC, FVC% predicted, FEV1, FEV1% predicted, MEF25% predicted, and MMEF% predicted (p &lt; 0.05). Results of logistic regression models showed that haemal Cr and Zn were risk factors of welder&rsquo;s pneumoconiosis (OR = 4.98, 95%CI: 1.73&ndash;21.20, p = 0.009 for Cr; OR = 5.23, 95%CI: 1.56&ndash;41.08, p = 0.033 for Zn) after adjusted with age, BMI, working years, welding dust exposure years, and smoking status. Multiple linear regression models showed that several metals (haemal Cd and Pb; urinary Cd and Fe) were significantly associated with different lung function indices in the welder&rsquo;s pneumoconiosis group. Compared to non-welders, welders were exposed to considerably higher levels of respirable dust, total dust, and six kinds of metals (p &lt; 0.05). In conclusion, haemal Cr and Zn are positively related to welder&rsquo;s pneumoconiosis. Meanwhile, Cd and Pb might worsen lung function in welder&rsquo;s pneumoconiosis