Causal relationship between thyroid dysfunction and gastric cancer: a two-sample Mendelian randomization study.

Backgroud: Gastric cancer is one of the most common cancers worldwide, and its development is associated with a variety of factors. Previous observational studies have reported that thyroid dysfunction is associated with the development of gastric cancer. However, the exact relationship between the two is currently unclear. We used a two-sample Mendelian randomization (MR) study to reveal the causal relationship between thyroid dysfunction and gastric cancer for future clinical work. Materials and methods: This study is based on a two-sample Mendelian randomization design, and all data are from public GWAS databases. We selected hyperthyroidism, hypothyroidism, free thyroxine (FT4), and thyroid-stimulating hormone (TSH) as exposures, with gastric cancer as the outcome. We used three statistical methods, namely Inverse-variance weighted (IVW), MR-Egger, and weighted median, to assess the causal relationship between thyroid dysfunction and gastric cancer. The Cochran's Q test was used to assess the heterogeneity among SNPs in the IVW analysis results, and MR-PRESSO was employed to identify and remove IVs with heterogeneity from the analysis results. MR-Egger is a weighted linear regression model, and the magnitude of its intercept can be used to assess the horizontal pleiotropy among IVs. Finally, the data were visualized through the leave-one-out sensitivity test to evaluate the influence of individual SNPs on the overall causal effect. Funnel plots were used to assess the symmetry of the selected SNPs, forest plots were used to evaluate the confidence and heterogeneity of the incidental estimates, and scatter plots were used to assess the exposure-outcome relationship. All results were expressed as odds ratios (OR) and 95% confidence intervals (95% CI). P<0.05 represents statistical significance. Results: According to IVW analysis, there was a causal relationship between hypothyroidism and gastric cancer, and hypothyroidism could reduce the risk of gastric cancer (OR=0.936 (95% CI:0.893-0.980), P=0.006).This means that having hypothyroidism is a protective factor against stomach cancer. This finding suggests that hypothyroidism may be associated with a reduced risk of gastric cancer.Meanwhile, there was no causal relationship between hyperthyroidism, FT4, and TSH and gastric cancer. Conclusions: In this study, we found a causal relationship between hypothyroidism and gastric cancer with the help of a two-sample Mendelian randomisation study, and hypothyroidism may be associated with a reduced risk of gastric cancer, however, the exact mechanism is still unclear. This finding provides a new idea for the study of the etiology and pathogenesis of gastric cancer, and our results need to be further confirmed by more basic experiments in the future.

Characteristic analysis of BZR genes family and their responses to hormone treatments and abiotic stresses in Carya illinoinensis.

As the core of Brassinosteroids (BR) signaling pathway, BR-resistant (BZR) transcription factor regulates thousands of targeted genes mediating photomophogenesis, pollen sterility, cell expansion and stress response. Pecan (Carya illinoinensis) is a famous trees species of Carya, and its nut has high nutritional and economic values. However, there has no report on BZR genes family in pecan yet. Herein, totals of seven CiBZR members were identified in pecan genome, which were predicted to be hydrophilic unstable proteins and located in the nucleus. CiBZR genes had close evolutionary relationships with CcBZRs and JrBZRs in both Carya cathayensis and Juglans regia. These seven CiBZR genes were located independently on 7 chromosomes without doubling or tandem duplication. Based on the analysis of conserved motifs and gene structures, CiBZR genes were divided into three categories. More than 40 cis-acting elements were found in the 2 kb promoter regions of CiBZRs, which were mainly involved in hormone, light, and stress response, and plant growth and development. Notably, some of these CiBZR proteins were mainly located in the nucleus, had the self-activation ability and interaction relationship with BIN2 kinase, and negatively regulated the expression of CiCPD and CiDWF4. Gene expressions analysis further showed that CiBZR genes could express in many tissues and shared similar expression trends during embryo development. Moreover, most CiBZR genes responded to BR, Gibberellin (GA), Strigolactone (SL), salt, acid and osmotic stress. This study provides theoretical basis for the subsequent study on the role of CiBZR family genes in plant growth, development and stress responses.

Comparison of two different integrated method of pharmacokinetics by the integrated pharmacokinetic research of fangji huangqi decoction.

Traditional Chinese medicine (TCM) is characterized by its multiple components. The utilization of mathematical statistical methods to integrate the pharmacokinetics of monomer components can provide a comprehensive understanding of the holistic pharmacokinetic process of TCM. Two distinct integrated methods, namely the correlation coefficient method and the AUC-based weight coefficient method, were employed in this study to elucidate and compare their differences in the integrated pharmacokinetic research of Fangji Huangqi decoction (FHD). FHD is commonly used in clinical practice to treat the nephrotic syndrome. Firstly, one-dose FHD was given to doxorubicin-induced nephropathy (DN) rats, and the prototype compounds of FHD and their metabolites in plasma were qualitatively and semi-quantitatively analyzed by UHPLC-MS/MS. Secondly, the efficacy of FHD was quantitatively characterized by the relative distance method based on metabolomics. The correlation coefficients were obtained by analyzing the correlation between efficacy (relative distance values) and the content of compound, and they were subsequently used for the model integration (correlation coefficient method). Thirdly, the effective compounds of FHD treating DN were screened by integrating network pharmacology and molecular docking, and they were used for another integrated pharmacokinetic model by AUD-based weight coefficient method. Finally, the 2 integrated methods and the 2 integrated pharmacokinetic models were compared. In this study, 30 prototype compounds and 41 metabolites of FHD in plasma were identified, and the pharmacokinetic curve of 18 prototype compounds were built. The efficacy of FHD in the treatment of DN has been relatively quantitation. The 2 established integrated pharmacokinetic models of FHD indicated that the correlation coefficient method was the optimal approach for conducting the integrated pharmacokinetic research on the TCM with unknown effective compounds, whereas the AUC-based coefficient method was suitable for the TCM with the clear effective compounds. The integrated pharmacokinetic models indicated that FHD had high bioavailability and an absorption peak at about 6 h after administration, indicating that the 6 h after administration was the critical period of FHD treating DN. This research would be helpful for the pharmacological and pharmacokinetic research of FHD, and provide a method reference for the integrated pharmacokinetic research of TCM.

Exploration of the main effective constituent and the mechanism in Astragali Radix in the treatment for doxorubicin-induced nephropathy by integrating metabolomics and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragali Radix (AR) is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or A. membranaceus (Fisch.) Bge. AR was the main medicine in a Chinese traditional prescription called Fangji Huangqi Decoction, and it has been used to treating nephrotic syndrome (NS) for thousands of years in China. In recent years, AR has been evidenced to have anti-inflammatory activity, antihyperglycemic activity, antioxidant activity, etc. There are two mainstream commodities for ARs in the market including the imitation wild AR and transplanted AR. However, it is not clear whether the imitation wild AR or transplanted AR and which kind of component, astragalus saponin, astragalus flavonoid or astragalus polysaccharide, makes a bigger contribution in treating NS. And the exact molecular mechanism is not fully understood. AIM OF THE STUDY: To explore which kind of AR and which kind of component in AR makes the bigger contribution in treating NS, and exploring the molecular mechanism. MATERIALS AND METHODS: Firstly, HPLC-UV/ELSD was used for quantitative determination of the constituents in different ARs. Secondly, the efficacy of different ARs treating doxorubicin-induced nephropathy (DN) was compared by metabolomics. Thirdly, the protective effects of different constituents from ARs on the damage of MPC5 cells induced by adriamycin are validated. Finally, the effective constituents and mechanism of ARs against doxorubicin-induced nephropathy were investigated by network pharmacology and molecular docking. RESULTS: Quantitative determination experiment and pharmacological experiment indicated that the AR produced from Gansu province (China) (transplanted AR) with a higher proportion of total saponins, has better efficacy in the treatment for DN. And the cell experiment validated the result that astragalus saponins has the better efficacy in protecting the podocyte against injury than astragalus flavonoids and polysaccharides. The network pharmacology and molecular docking study indicated that astragalus saponins were the main constituent of AR in the treatment for DN. The mechanism may involve in GnRH signaling pathway, VEGF signaling pathway and metabolic pathways, especially of bilirubin metabolism. CONCLUSIONS: Transplanted AR has better efficacy in the treatment for NS than imitation wild AR, astragalus saponins have better efficacy in the treatment for NS than astragalus flavonoids and polysaccharides.

Study of Township Construction Land Carrying Capacity and Spatial Pattern Matching in Loess Plateau Hilly and Gully Region: A Case of Xifeng in China.

With the acceleration of urbanization, the construction land scale of urban and rural areas is constantly expanding, which leads to contradiction and conflict between territorial development and ecological protection becoming more and more serious. Therefore, as an important unit of county (district), and even urban and rural, development, the study on land resource carrying capacity and the rationality of the development can provide some basis for developing the optimal strategies of differential territorial space. Taking Xifeng, Gansu Province, China as the research area, this study constructs the evaluation index system of township construction land carrying capacity from the three dimensions of ecological protection, natural environment, and social economy. It evaluates the suitability of township construction land by the means of a comprehensive scoring method and discusses the carrying capacity and spatial pattern matching of township construction land based on the suitability evaluation results. The results showed that: (1) the spatial difference of suitability of construction land is obvious, which is higher in the city center than in the surrounding areas; (2) the comprehensive carrying capacity of township construction land is 52.62%, and different townships range from 3.78% to 13.15%. It is different between towns; (3) on the whole, the condition of township construction land is well-developed, and the main distribution forms are flaky, banded, and dotted. (4) There is a positive correlation between spatial matching and carrying capacity. The carrying capacity should be considered in regional development to avoid overdevelopment. It can provide a basis for optimizing the territorial spatial layout, strengthening the coordinated development among townships, and improving the comprehensive township carrying capacity in the Loess Plateau hilly and gully region.

Construction of an S-Scheme Ag2MoO4/ZnFe2O4 Nanofiber Heterojunction for Enhanced Photoelectrocatalytic Activity under Visible Light Irradiation.

The removal of organic dyes and pathogenic bacteria from contaminated water remains a significant challenge. In the present study, S-type heterojunction Ag2MoO4/ZnFe2O4 (AMO/ZFO) composite nanofibers were synthesized by electrospinning and co-precipitation and fabricated into photoanodes. It is found that the constructed S-type heterojunction of AMO/ZFO composites effectively inhibits the recombination of photogenerated carriers, in addition to the benefits of more exposed active sites and a greater specific surface area. When several properties are improved, AMO/ZFO composites exhibit excellent photoelectrocatalytic performance. The results demonstrate that under visible light irradiation, the photoelectrocatalytic degradation rate of AMO/ZFO-3 to methylene blue reached 76.2% within 50 min, and the killing rate of Salmonella was 83.6% within 80 min. The enhanced photoelectrocatalytic activity was due to the synergy of both electrochemical and photocatalytic effects. More importantly, after four testing cycles, AMO/ZFO-3 still has a better ability to kill pathogenic bacteria and degrade organic dyes due to its high stability. This work provides a feasible method for oxidizing organic dyes and pathogenic bacteria.

Global Transcriptome Analysis Revealed the Molecular Regulation Mechanism of Pigment and Reactive Oxygen Species Metabolism During the Stigma Development of Carya cathayensis.

Hickory (Carya cathayensis Sarg.) is a monoecious plant of the genus Carya of the Juglandaceae family. Its nuts contain a number of nutritional compounds and are deeply loved by consumers. Interestingly, it was observed that the color of hickory stigma changed obviously from blooming to mature. However, the molecular mechanism underlying color formation during stigma development and the biological significance of this phenomenon was mostly unknown. In this work, pigment content, reactive oxygen species (ROS) removal capacity, and transcriptome analysis of developing stigma of hickory at 4 differential sampling time points (S1, S2, S3, and S4) were performed to reveal the dynamic changes of related pigment, antioxidant capacity, and its internal molecular regulatory mechanism. It was found that total chlorophyll content was decreased slightly from S1 to S4, while total carotenoids content was increased from S1 to S3 but decreased gradually from S3 to S4. Total anthocyanin content continued to increase during the four periods of stigma development, reaching the highest level at the S4. Similarly, the antioxidant capacity of stigma was also gradually improved from S1 to S4. Furthermore, transcriptome analysis of developing hickory stigma identified 31,027 genes. Time-series analysis of gene expressions showed that these genes were divided into 12 clusters. Cluster 5 was enriched with some genes responsible for porphyrin and chlorophyll metabolism, carotenoid metabolism, and photosynthesis. Meanwhile, cluster 10 was enriched with genes related to flavonoid metabolism, including anthocyanin involved in ROS scavenging, and its related genes were mainly distributed in cluster 12. Based on the selected threshold values, a total of 10432 differentially expressed genes were screened out and enriched in the chlorophyll, carotenoid, anthocyanin, and ROS metabolism. The expression trends of these genes provided plausible explanations for the dynamic change of color and ROS level of hickory stigma with development. qRT-PCR analyses were basically consistent with the results of RNA-seq. The gene co-regulatory networks of pigment and ROS metabolism were further constructed and MYB113 (CCA0887S0030) and WRKY75 (CCA0573S0068) were predicted to be two core transcriptional regulators. These results provided in-depth evidence for revealing the molecular mechanism of color formation in hickory stigma and its biological significance.

ENO1 contributes to 5-fluorouracil resistance in colorectal cancer cells via EMT pathway.

Introduction: Chemoresistance is a major barrier in the treatment of colorectal cancer (CRC) and many other cancers. ENO1 has been associated with various biological characteristics of CRC. This study aimed to investigate the function of ENO1 in regulating 5-Fluorouracil (5-FU) resistance in CRC. Methods: ENO1 level in 120 pairs of tumor tissues and adjacent normal tissues was examined by immunohistochemistry, and the correlation between ENO1 expression and prognosis was explored by survival analysis. Its role and potential mechanisms in regulating 5-FU resistance in CRC were studied by Western blotting, MTT assay, colony formation assay and transwell invasion assay. Murine xenograft assay was implied to verify the results in vivo. Results: Our study indicated that ENO1 was elevated in CRC tissues and was associated with poor patient prognosis. High levels of ENO1 expression were detected as a significant influencing factor for overall survival. Furthermore, ENO1 expression was found to have increased in drug-resistant cells (HCT116/5-FU and SW620/5-FU) constructed by increasing concentrations of 5-FU. Knockdown of ENO1 markedly increased the drug susceptibility and inhibited the proliferation and migration ability of HCT116/5-FU and SW620/5-FU cells. It was found that down-regulation of ENO1 inhibited the epithelial-mesenchymal transformation (EMT) signaling process. Finally, a murine xenograft assay verified that the depletion of ENO1 alleviated 5-FU resistance. Conclusion: This study identified that ENO1 regulated 5-FU resistance via the EMT pathway and may be a novel target in the prevention and treatment of 5-FUresistant CRC.

Novel starter cultures Virgibacillus spp. selected from grasshopper sub shrimp paste to inhibit biogenic amines accumulation.

Controlling the content of biogenic amines (BAs) is critical to guarantee the safety of fermented aquatic products. The degradation characteristics and application potential of amine-negative starter cultures (Virgibacillus halodenitrificans CGMCC 1.18601: G25, Virgibacillus pantothenticus CGMCC 1.18602: G38) screened from grasshopper sub shrimp paste (Gssp) were studied. The enzymes of the two strains G25 and G38 that degrade BAs were amine oxidases (AOs) located on their respective cell membranes. The conditions that promoted the AO activity of Virgibacillus spp. were NaCl concentrations 5-10%, temperature 37 °C, pH 7.0 and ethanol concentrations 0-2%. Safety assessments (antibiotic susceptibility, biofilm activity and hemolytic activity) indicated that Virgibacillus spp. do not present a risk to human health, and this isolate can be confidently recommended as safe starter cultures for the food industry. Then, the two strains were cultured separately as starters and applied to the Gssp to analyze their influence on the flavor and quality of the product. As far as the bad flavors in Gssp such as sulfur-organic and sulf-chlor were concerned, the response values in the starter groups by G25 and G38 were significantly reduced by 39% and 65%, respectively. For the ability of strains to degrade BAs in Gssp, G25 degraded 11.1% of histamine, 11.3% of tyramine, 15.5% of putrescine and 4.1% of cadaverine; G38 significantly degraded 10.1% of histamine, 21.8% of tyramine, 18.1% of putrescine and 5.0% of cadaverine. These results indicated that the selected species could be used as starter cultures for the control of BA accumulation and degradation in Gssp.

Diversity of bacterial communities in traditional sourdough derived from three terrain conditions (mountain, plain and basin) in Henan Province, China.

To elucidate the bacterial community composition of sourdoughs from different terrain conditions, thirty-two Chinese traditional sourdough samples were collected from three terrain conditions (mountain, plain and basin) in Henan Province. High-throughput sequencing and culture-dependent approaches were employed to identify the bacterial diversity of the sourdough samples. A total of two hundred and six isolates were characterized via 16S rRNA gene sequencing. Pediococcus pentosaceus was isolated from every sample and was the predominant species in the sourdough samples, accounting for 58% of the relative abundance. High-throughput sequencing revealed that the predominant genera (mainly Pediococcus) in the basin group were significantly different from those in the mountain and plain groups. The genus Lactobacillus was predominant in the plain and mountain sourdough samples. Pediococcus pentosaceus was the absolute dominant strain in the basin sourdough samples. Acetobacter, which was widely distributed only in mountain samples, was recognized as the representative genus of the mountain samples. Moreover, we first reported Gluconobacter oxydans in sourdough. This study provided insight into the bacterial diversity of sourdough from three terrain conditions (mountain, plain and basin) in Henan Province and could serve as a reference for the isolation of desired bacterial strains.

Alkaloids from nux vomica suppresses colon cancer cell growth through Wnt/ß-catenin signaling pathway.

Brucine and Strychnine are alkaloids isolated from the seeds of Strychnos nux vomica L., which have long been used as a traditional medicine for the treatment of tumor. However, the effect of Brucine and Strychnine on colorectal cancer (CRC) and the underlying molecular mechanism remain unclear. In the present study, Brucine and Strychnine displayed profound inhibitory effects on the growth of human colon cancer cells. The results of flow cytometric analysis demonstrated that the two alkaloids induced cellular apoptosis. Moreover, the growth of DLD1 xenografted tumors in nude mice was significantly suppressed in the Brucine or Strychnine treated group. Mechanistically, the Wnt/ß-catenin is involved in this phenomenon, which is characterized by significantly increased expression of DKK1 and APC, whereas decreased expression of ß-catenin, c-Myc, and p-LRP6 in CRC cells as well as tumor tissues. Collectively, Brucine and Strychnine have targeted inhibition for colon cancer proliferation both in vitro and in vivo, and it is valuable for future exploitation and utilization as an antitumor agent of CRC.

Localized surface plasmon resonance modulation of totally encapsulated VO2/Au/VO2 composite structure.

We design and fabricate a totally encapsulated VO2/Au/VO2 composite structure which is aimed to improve the tunability of the localized surface plasmon resonance (LSPR) peak. In this work, the structure will ensure all the Au NPs' resonant electric field area is filled with VO2. The modulation range of the totally encapsulated structure is larger than that of the semi-coated structure. To further improve the modulation range, we also explore the VO2 thickness dependence of the structure's LSPR modulation. With the increase of the top layer VO2 thin film thickness, the modulation range becomes larger. When the thickness is about 80 nm, the absorption peak achieves a largest shift of 112 nm. FDTD solution and equivalent model of series capacitor are used to explain the phenomenon. These results will contribute to the area of metamaterial electromagnetic wave absorber and other fields.

Differentially expressed genes between female and male adult Anopheles anthropophagus.

The aim of the present study was to identify sex-specific genes in adult Anopheles anthropophagus. As the major malaria vector and Brugia malayi vector in the Asian continent, female Anopheles mosquitoes take blood meals and transmit pathogens through this pathway, while males are nectar feeders. This complex behavior is controlled at several levels, but is probably initiated by the genetic background difference between these two groups. In our study, a subtractive cDNA library for female A. anthropophagus was constructed using the suppression subtractive hybridization (SSH) technique and then 3,074 clones from the female SSH library were analyzed using a microarray-based survey. Genes that were expressed differentially according to sex in A. anthropophagus were screened using real-time polymerase chain reaction and reverse transcription polymerase chain reaction. In our results, we report a series of genes which may be involved in female-specific mosquito behavior, including an inorganic phosphate transporter, a serine protease, the salivary protein GP35-2, and the D7 cluster salivary protein. These findings will provide clues to the nature of insect vectors and open up unprecedented opportunities to develop novel strategies for the control of mosquito-borne diseases.