SNP-based and haplotype-based genome-wide association on drug dependence in Han Chinese.

BACKGROUND: Drug addiction is a serious problem worldwide and is influenced by genetic factors. The present study aimed to investigate the association between genetics and drug addiction among Han Chinese. METHODS: A total of 1000 Chinese users of illicit drugs and 9693 healthy controls were enrolled and underwent single nucleotide polymorphism (SNP)-based and haplotype-based association analyses via whole-genome genotyping. RESULTS: Both single-SNP and haplotype tests revealed associations between illicit drug use and several immune-related genes in the major histocompatibility complex (MHC) region (SNP association: log10BF = 15.135, p = 1.054e-18; haplotype association: log10BF = 20.925, p = 2.065e-24). These genes may affect the risk of drug addiction via modulation of the neuroimmune system. The single-SNP test exclusively reported genome-wide significant associations between rs3782886 (SNP association: log10BF = 8.726, p = 4.842e-11) in BRAP and rs671 (SNP association: log10BF = 7.406, p = 9.333e-10) in ALDH2 and drug addiction. The haplotype test exclusively reported a genome-wide significant association (haplotype association: log10BF = 7.607, p = 3.342e-11) between a region with allelic heterogeneity on chromosome 22 and drug addiction, which may be involved in the pathway of vitamin B12 transport and metabolism, indicating a causal link between lower vitamin B12 levels and methamphetamine addiction. CONCLUSIONS: These findings provide new insights into risk-modeling and the prevention and treatment of methamphetamine and heroin dependence, which may further contribute to potential novel therapeutic approaches.

Exploration of the radiosensitivity-related prognostic risk signature in patients with glioma: evidence from microarray data.

BACKGROUND: Gene expression signatures can be used as prognostic biomarkers in various types of cancers. We aim to develop a gene signature for predicting the response to radiotherapy in glioma patients. METHODS: Radio-sensitive and radio-resistant glioma cell lines (M059J and M059K) were subjected to microarray analysis to screen for differentially expressed mRNAs. Additionally, we obtained 169 glioblastomas (GBM) samples and 5 normal samples from The Cancer Genome Atlas (TCGA) database, as well as 80 GBM samples and 4 normal samples from the GSE7696 set. The "DESeq2" R package was employed to identify differentially expressed genes (DEGs) between the normal brain samples and GBM samples. Combining the prognostic-related molecules identified from the TCGA, we developed a radiosensitivity-related prognostic risk signature (RRPRS) in the training set, which includes 152 patients with glioblastoma. Subsequently, we validated the reliability of the RRPRS in a validation set containing 616 patients with glioma from the TCGA database, as well as an internal validation set consisting of 31 glioblastoma patients from the Nanfang Hospital, Southern Medical University. RESULTS: Based on the microarray and LASSO COX regression analysis, we developed a nine-gene radiosensitivity-related prognostic risk signature. Patients with glioma were divided into high- or low-risk groups based on the median risk score. The Kaplan-Meier survival analysis showed that the progression-free survival (PFS) of the high-risk group was significantly shorter. The signature accurately predicted PFS as assessed by time-dependent receiver operating characteristic curve (ROC) analyses. Stratified analysis demonstrated that the signature is specific to predict the outcome of patients who were treated using radiotherapy. Univariate and multivariate Cox regression analysis revealed that the predictor was an independent predictor for the prognosis of patients with glioma. The prognostic nomograms accompanied by calibration curves displayed the 1-, 2-, and 3-year PFS and OS in patients with glioma. CONCLUSION: Our study established a new nine-gene radiosensitivity-related prognostic risk signature that can predict the prognosis of patients with glioma who received radiotherapy. The nomogram showed great potential to predict the prognosis of patients with glioma treated using radiotherapy.

The potential capability of substituting chemical fertilizers with crop straw and human-livestock-poultry manure in areas with different topographic characteristics.

Agricultural production and lifestyle are constrained by topography, causing notable under disparities in the composition, distribution, and environmental benefits of crop straw and human-livestock-poultry manure (CSHLPM) in areas with different topographic characteristics. Under the premise of the international consensus on sustainable development, it has become an objective requirement to improve the use of CSHLPM as fertilizer, and minimize the use of chemical fertilizers. Thus, an investigation was conducted to assess the difference in the quantity and composition of CSHLPM in plain, hill, and mountainous areas, taking Anhui Province of China as a case study, to evaluate the potential contribution of CSHLPM to farmland and identify the environmental benefits. The results show that the composition of CSHLPM in plain, hill, and mountainous areas varied greatly, and the reuse of CSHLPM in farmland could supplement, but not completely replace the use of chemical fertilizer to meet the needs of nutrients. In plain areas, CSHLPM did not provide the necessary amount of N and P2O5 for crop growth, whereas in mountainous areas, P2O5 was not available in adequate amounts for crop growth. Only in hilly areas can CSHLPM be used to completely replace chemical fertilizers and supply the necessary amounts of nutrients for crop growth. Based on the characteristics of different topographies, two constructive suggestions for improving the management strategy of CSHLPM were put forward: adjust the industrial structure of husbandry and planting, and specify the recommended ratios for mixing organic chemical fertilizers.

[Retracted] MicroRNA­599 targets high­mobility group AT­hook 2 to inhibit cell proliferation and invasion in clear cell renal carcinoma.

Following the publication of the above paper, it was drawn to the Editors' attention by a concerned reader that cell migration and invasion assay data shown in Fig. 5C were strikingly similar to data appearing in different form in other articles by different authors, which have been retracted. Owing to the fact that the contentious data in the above article were already under consideration for publication, or had already been published, elsewhere when it was submitted to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 7451­7459, 2018; DOI: 10.3892/mmr.2018.8755].

Observed causative impact of fine particulate matter on acute upper respiratory disease: a comparative study in two typical cities in China.

Association between fine particulate matter (PM2.5) and respiratory health has attracted great concern in China. Substantial epidemiological evidences confirm the correlational relationship between PM2.5 and respiratory disease in many Chinese cities. However, the causative impact of PM2.5 on respiratory disease remains uncertain and comparative analysis is limited. This study aims to explore and compare the correlational relationship as well as the causal connection between PM2.5 and upper respiratory tract infection (URTI) in two typical cities (Beijing, Shenzhen) with rather different ambient air environment conditions. The distributed lag nonlinear model (DLNM) was used to detect the correlational relationship between PM2.5 and URTI by revealing the lag effect pattern of PM2.5 on URTI. The convergent cross mapping (CCM) method was applied to explore the causal connection between PM2.5 and URTI. The results from DLNM indicate that an increase of 10 µg/m3 in PM2.5 concentration is associated with an increase of 1.86% (95% confidence interval: 0.74%-2.99%) in URTI at a lag of 13 days in Beijing, compared with 2.68% (95% confidence interval: 0.99-4.39%) at a lag of 1 day in Shenzhen. The causality detection with CCM quantitatively demonstrates the significant causative influence of PM2.5 on URTI in both two cities. Findings from the two methods consistently show that people living in low-concentration areas (Shenzhen) are less tolerant to PM2.5 exposure than those in high-concentration areas (Beijing). In general, our study highlights the adverse health effects of PM2.5 pollution on the general public in cities with various PM2.5 levels and emphasizes the needs for the government to provide appropriate solutions to control PM2.5 pollution, even in cities with low PM2.5 concentration.

Feasibility of machine learning methods for predicting hospital emergency room visits for respiratory diseases.

The prediction of hospital emergency room visits (ERV) for respiratory diseases after the outbreak of PM2.5 is of great importance in terms of public health, medical resource allocation, and policy decision support. Recently, the machine learning methods bring promising solutions for ERV prediction in view of their powerful ability of short-term forecasting, while their performances still exist unknown. Therefore, we aim to check the feasibility of machine learning methods for ERV prediction of respiratory diseases. Three different machine learning models, including autoregressive integrated moving average (ARIMA), multilayer perceptron (MLP), and long short-term memory (LSTM), are introduced to predict daily ERV in urban areas of Beijing, and their performances are evaluated in terms of the mean absolute error (MAE), root mean squared error (RMSE), mean absolute percentage error (MAPE), and coefficient of determination (R2). The results show that the performance of ARIMA is the worst, with a maximum R2 of 0.70 and minimum MAE, RMSE, and MAPE of 99, 124, and 26.56, respectively, while MLP and LSTM perform better, with a maximum R2 of 0.80 (0.78) and corresponding MAE, RMSE, and MAPE of 49 (33), 62 (42), and 14.14 (9.86). In addition, it demonstrates that MLP cannot detect the time lag effect properly, while LSTM does well in the description and prediction of exposure-response relationship between PM2.5 pollution and infecting respiratory disease.

Public Emotions and Rumors Spread During the COVID-19 Epidemic in China: Web-Based Correlation Study.

BACKGROUND: Various online rumors have led to inappropriate behaviors among the public in response to the COVID-19 epidemic in China. These rumors adversely affect people's physical and mental health. Therefore, a better understanding of the relationship between public emotions and rumors during the epidemic may help generate useful strategies for guiding public emotions and dispelling rumors. OBJECTIVE: This study aimed to explore whether public emotions are related to the dissemination of online rumors in the context of COVID-19. METHODS: We used the web-crawling tool Scrapy to gather data published by People's Daily on Sina Weibo, a popular social media platform in China, after January 8, 2020. Netizens' comments under each Weibo post were collected. Nearly 1 million comments thus collected were divided into 5 categories: happiness, sadness, anger, fear, and neutral, based on the underlying emotional information identified and extracted from the comments by using a manual identification process. Data on rumors spread online were collected through Tencent's Jiaozhen platform. Time-lagged cross-correlation analyses were performed to examine the relationship between public emotions and rumors. RESULTS: Our results indicated that the angrier the public felt, the more rumors there would likely be (r=0.48, P<.001). Similar results were observed for the relationship between fear and rumors (r=0.51, P<.001) and between sadness and rumors (r=0.47, P<.001). Furthermore, we found a positive correlation between happiness and rumors, with happiness lagging the emergence of rumors by 1 day (r=0.56, P<.001). In addition, our data showed a significant positive correlation between fear and fearful rumors (r=0.34, P=.02). CONCLUSIONS: Our findings confirm that public emotions are related to the rumors spread online in the context of COVID-19 in China. Moreover, these findings provide several suggestions, such as the use of web-based monitoring methods, for relevant authorities and policy makers to guide public emotions and behavior during this public health emergency.

Effect of total flavones of Clematis filamentosa Dunn on the oxLDL-induced injury of vascular smooth muscle cells by regulating miR-455-5p.

This experiment was conducted to investigate whether total flavones of Clematis filamentosa Dunn affect the inflammatory response and apoptosis of vascular smooth muscle cells induced by oxidized low-density lipoprotein (oxLDL) by regulating microRNA-455-5p (miR-455-5p). 50 mg/mL oxLDL was performed to stimulate the injury of vascular smooth muscle cells, and the total flavones of Clematis filamentosa Dunn were added at concentrations of 75, 150, and 300 µg/mL. The expressions of inflammatory factors IL-1ß and TNF-α were analyzed by ELISA, the apoptosis was evaluated by flow cytometry, the expression of Bcl-2 and Bax was determined by western blot, and the real-time fluorescence quantitative PCR (qRT-PCR) was applied to detect miR-455-5p expression. MiR-455-5p mimic was transfected into vascular smooth muscle cells and then induced injury with oxLDL; miR-455-5p inhibitor was transfected into vascular smooth muscle cells and treated with oxLDL and 300 µg/mL total flavones of Clematis filamentosa Dunn. The above methods were employed to investigate the inflammatory response and apoptosis of cells. The total flavones of Clematis filamentosa Dunn significantly inhibited the expression of IL-1ß, TNF-α, apoptosis rate, Bax protein expression of oxLDL induced vascular smooth muscle cells, and remarkably promoted the expression of Bcl-2 protein and miR-455-5p, which all showed concentration dependence (p<0.05). Overexpression of miR-455-5p reduced IL-1ß, TNF-α expression, apoptosis rate, Bax protein expression, and greatly increased Bcl-2 protein expression in oxLDL injured vascular smooth muscle cells (p<0.05). After interfering with the expression of miR-455-5p, the inhibitory effect of total flavones of Clematis filamentosa Dunn on the expression of IL-1ß, TNF-α, apoptosis, Bax protein expression of oxLDL-induced vascular smooth muscle cells was reversed, and its promotion effect on Bcl-2 protein expression was also reversed. Total flavones of Clematis filamentosa Dunn can reduce oxLDL-induced vascular smooth muscle cell inflammation and inhibit its apoptosis. The mechanism of action is related to the up-regulation of miR-455-5p expression.

Graph-based generative models for de Novo drug design.

The discovery of new chemical entities is a crucial part of drug discovery, which requires the lead compounds to have desired properties to be pharmaceutically active. De novo drug design aims to generate and optimize novel ligands for macromolecular targets from scratch. The development of graph-based deep generative neural networks has provided a new method. In this review, we gave a brief introduction to graph representation and graph-based generative models for de novo drug design, summarized them as four architectures, and concluded each's characteristics. We also discussed generative models for scaffold- and fragment-based design and graph-based generative models' future directions.

MicroRNA-599 targets high-mobility group AT-hook 2 to inhibit cell proliferation and invasion in clear cell renal carcinoma.

Dysregulation of microRNAs (miRNAs) is associated with the occurrence and development of clear cell renal cell carcinoma (ccRCC) through their participation in a number of critical biological processes. Therefore, an in­depth investigation into miRNAs and their biological roles within ccRCC may provide useful insights and lead to the identification of novel therapeutic methods for patients with ccRCC. miRNA­599 (miR­599) serves critical roles in different types of human cancer. However, the expression pattern, biological function and molecular mechanism of miR­599 in ccRCC remain unknown. The present study aimed to detect the expression level of miR­599 in ccRCC, examine its effect on ccRCC progression and further explore the possible underlying mechanisms. It was observed that miR­599 was significantly underexpressed in ccRCC tissues and cell lines compared with the control. Functional assays revealed that restored expression of miR­599 restricted the proliferation and invasion of ccRCC cells. Bioinformatics analysis, luciferase reporter assay, reverse transcription­quantitative polymerase chain reaction and western blot analysis demonstrated that high­mobility group AT­hook 2 (HMGA2) was a direct target of miR­599 in ccRCC. HMGA2 knockdown simulated the suppressive effects caused by miR­599 overexpression in ccRCC. Recovered HMGA2 expression partially rescued the miR­599­mediated inhibition of ccRCC proliferation and invasion. These results suggest that miR­599 may serve tumour suppressive roles in ccRCC by directly targeting HMGA2, indicating that miR­599 may have potential as a treatment for patients with ccRCC.

The Association between Air Pollution and Population Health Risk for Respiratory Infection: A Case Study of Shenzhen, China.

Nowadays, most of the research on air pollution and its adverse effects on public health in China has focused on megacities and heavily-polluted regions. Fewer studies have focused on cities that are slightly polluted. Shenzhen used to have a favorable air environment, but its air quality has deteriorated gradually as a result of development in recent years. So far, no systematic investigations have been conducted on the adverse effects of air pollution on public health in Shenzhen. This research has applied a time series analysis model to study the possible association between different types of air pollution and respiratory hospital admission in Shenzhen in 2013. Respiratory hospital admission was divided into two categories for comparison analysis among various population groups: acute upper respiratory infection and acute lower respiratory infection. The results showed that short-term exposure to ambient air pollution was significantly associated with acute respiratory infection hospital admission in Shenzhen in 2013. Children under 14 years old were the main susceptible population of acute respiratory infection due to air pollution. PM10, PM2.5 and NO2 were the primary air pollutants threatening respiratory health in Shenzhen. Though air pollution level is generally relatively low in Shenzhen, it will benefit public health to control the pollution of particulate matter as well as other gaseous pollutants.

A decreased micronucleus frequency in human lymphocytes after folate and vitamin B12 intervention: a preliminary study in a Yunnan population.

BACKGROUND: Micronucleus (MN) is a validated biomarker for DNA damage in peripheral blood lymphocytes (PBL) and is a reflection of the changes of human nutritional status. Folate (FA) and vitamin B(12) are one-carbon metabolism-related micronutrients, which play important roles in maintaining genomic stability. OBJECTIVE: To investigate the correcting effects of FA and B(12) intervention on DNA damage in PBL. METHOD: One hundred fifty-six volunteers without history of cancer were divided into 5 age groups (20 - 69 y, 47.4 % male) for establishing the baseline of chromosomal damage by means of cytokinesis-block micronucleus assay. Twelve individuals whose MN frequency was higher than the median value in each age group were selected for a four-month FA (200 - 400 µg/day)-B12 (3.125 - 25 µg/day) intervention dosed as to age and MTHFR genotypes. RESULTS: There were significantly positive correlations between age and MN frequency in all groups (p < 0.01). Among all age groups, the baseline MN frequencies were higher in females than that in males. The MN frequencies from 10 volunteers were reduced by 33.5 % after the intervention with the two micronutrients (p < 0.01), and two individuals did not show any changes. CONCLUSION: Dietary supplement intake of FA and B(12) based on MTHFR genotypes could protect the genome from damage and benefit genome health.

Analysis of the bioactive constituents of ChanSu in rat plasma by high performance liquid chromatography with mass spectrometric detection.

A plasma pharmacochemistry analysis of the bioactive constituents in rat plasma after oral administration of ChanSu was performed. High performance liquid chromatography coupled with the electrospray ionization mass spectrometry techniques of HPLC/ESI-IT-MS/MS and RRLC/ESI-Q-TOF-MS were used for the chemical profiling of samples of dosed plasma, control plasma and ChanSu extract. Comparative analysis of the resulting chemical profiles revealed 20 prototype compounds and 4 metabolites derived from ChanSu as potential bioactive components. By MS/MS analysis and accurate molecular weight assessments, the majority of these bioactive components (19 prototype compounds and 2 metabolites) were structurally identified. Moreover, seven were confirmed by comparing their retention behaviors using MS and MS/MS analysis. This study proposes a series of potential bioactive components of ChanSu, which we hope will lead to new drug discovery based on ChanSu and other traditional Chinese medicines.