Effects of genetic polymorphisms in INTS10 and their interaction with environmental factors on progression from persistent HBV infection to hepatocellular carcinoma.

Genome-wide association study recently identified a novel antiviral gene INTS10 (index rs7000921) in suppression of hepatitis B virus (HBV) replication. However, data were lacking on single nucleotide polymorphisms (SNPs) of INTS10 in the context of hepatocellular carcinoma (HCC) induced by HBV infection. Herein, we conducted a case-control study, including 737 HBV-related HCC cases and 750 persistently HBV-infected controls, to investigate the effect of INTS10 SNPs and their gene-environment interactions on HBV-related HCC. In multivariate analysis, the CT genotype of rs7000921 conferred a decreased risk of HBV-related HCC compared to the TT genotype (adjusted odds ratio [OR] = 0.79, 95% confidence interval [CI] = 0.64-0.98, p for permutation test = .038). Among the 12 tagSNPs, the rs4268139 yielded a borderline significant association with disease risk under the additive model (adjusted OR = 0.80, 95% CI = 0.63-1.00, p for permutation test = .061). Random forest model further suggested the rs7000921 and rs7822495 as the two-top ranked important SNPs, and thus a weighted genetic risk score (wGRS) was generated from these two SNPs plus rs4268139. The highest tertile of wGRS was associated with an increased risk, with an adjusted OR of 1.36 (95% CI = 1.05-1.75, p for permutation test = .016) compared to the lowest wGRS. Furthermore, an additive interaction was seen between wGRS and drinking (attributable proportion due to interaction [AP] = 0.21, 95% CI = 0.02-0.43, p = .016). The additive interaction between wGRS and smoking approached near significance (AP = 0.15, 95% CI = 0.00-0.32, p = .045). INTS10 polymorphisms may contribute to the progression from HBV infection to HCC. More importantly, INTS10 polymorphisms interact with drinking and smoking to affect the progression.

Impact factors of the accumulation, migration and spread of antibiotic resistance in the environment.

Antibiotic resistance is a great concern, which leads to global public health risks and ecological and environmental risks. The presence of antibiotic-resistant genes and antibiotic-resistant bacteria in the environment exacerbates the risk of spreading antibiotic resistance. Among them, horizontal gene transfer is an important mode in the spread of antibiotic resistance genes, and it is one of the reasons that the antibiotic resistance pollution has become increasingly serious. At the same time, free antibiotic resistance genes and resistance gene host bacterial also exist in the natural environment. They can not only affect horizontal gene transfer, but can also migrate and aggregate among environmental media in many ways and then continue to affect the proliferate and transfer of antibiotic resistance genes. All this shows the seriousness of antibiotic resistance pollution. Therefore, in this review, we reveal the sensitive factors affecting the distribution and spread of antibiotic resistance through three aspects: the influencing factors of horizontal gene transfer, the host bacteria of resistance genes and the migration of antibiotic resistance between environmental media. This review reveals the huge role of environmental migration in the spread of antibiotic resistance, and the environmental behavior of antibiotic resistance deserves wider attention. Meanwhile, extracellular antibiotic resistance genes and intracellular antibiotic resistance genes play different roles, so they should be studied separately.

A visible light-activated azo-fluorescent switch for imaging-guided and light-controlled release of antimycotics.

Azo switches are widely employed as essential components in light-responsive systems. Here, we develop an azo-fluorescent switch that is visible light-responsive and its light-responsive processes can be monitored using fluorescence imaging. Visible light irradiation promotes isomerization, accompanied by changes in fluorescence that enable the process to be monitored through fluorescence imaging. Furthermore, we document that the nanocavity size of liposome encapsulated nanoparticles containing azo changes in the isomerization process and show that this change enables construction of a light-responsive nanoplatform for optically controlled release of antimycotics. Also, natural light activation of nanoparticles of the switch loaded with an antimycotic agent causes death of Rhizoctonia solani. The results show that these nanoparticles can double the holding period in comparison to small molecule antimycotics. The strategy used to design the imaging-guided light-controlled nano-antimycotic release system can be applicable to protocols for controlled delivery of a wide variety of drugs.

Sulfur: a neglected driver of the increased abundance of antibiotic resistance genes in agricultural reclaimed subsidence land located in coal mines with high phreatic water levels.

Due to the shallow burial of groundwater in coal mines with a high phreatic water level, a large area of subsidence lakes is formed after the mine collapses. Agricultural and fishery reclamation activities have been carried out, which introduced antibiotics and exacerbated the contamination of antibiotic resistance genes (ARGs), but this has received limited attention. This study analyzed ARG occurrence in reclaimed mining areas, the key impact factors, and the underlying mechanism. The results show that sulfur is the most critical factor impacting the abundance of ARGs in reclaimed soil, which is due to changes in the microbial community. The species and abundance of ARGs in the reclaimed soil were higher than those in the controlled soil. The relative abundances of most ARGs increased with the depth of reclaimed soil (from 0 to 80 cm). In addition, the microbial structures of the reclaimed and controlled soils were significantly different. Proteobacteria, was the most dominant microbial phylum in the reclaimed soil. This difference is likely related to the high abundance of sulfur metabolism functional genes in the reclaimed soil. Correlation analysis showed that the differences in ARGs and microorganisms in the two soil types were highly correlated with the sulfur content. High levels of sulfur promoted the proliferation of sulfur-metabolizing microbial populations such as Proteobacteria and Gemmatimonadetes in the reclaimed soils. Remarkably, these microbial phyla were the main antibiotic-resistant bacteria in this study, and their proliferation created conditions for the enrichment of ARGs. Overall, this study underscores the risk of the abundance and spread of ARGs driven by high-level sulfur in reclaimed soils and reveals the mechanisms.

Removal of Sulfonamide Resistance Genes in Fishery Reclamation Mining Subsidence Area by Zeolite.

A majority of subsidence lakes were reclaimed as fish ponds, but the widespread use of antibiotics has caused the pollution of antibiotic resistance genes (ARGs). This paper uses zeolite as a filter material to construct a horizontal submersible wastewater treatment device and explores its effect on the removal of conventional pollutants and sulfonamide ARGs in wastewater. The results showed that the removal of total nitrogen and ammonia nitrogen by the zeolite filter media were 59.0% and 63.8%, respectively, which were higher than the removal of total phosphorus and COD. The absolute abundances of sul1 and sul2 in wastewater were 2.81 × 104 copies·L-1 and 2.42 × 103 copies·L-1. On average, 60.62% of sul1 and 75.84% of sul2 can be removed, and more than 90% of sul1 and sul2 can be removed. Experiments showed that the residence time of wastewater in the treatment device had a significant impact on removal. The microbial community structure of aquaculture wastewater was quite different before and after wastewater treatment. The abundance changes of Saccharimonadales and Mycobacterium affect the removal of sulfonamide ARGs.

Establishment of a no-notice drill mode evaluation system for public health emergencies.

OBJECTIVE: At present, there are some no-notice drill mode evaluation systems for public health emergencies in Chinese hospitals, which are the subjects of assessment in this study. However, there is a lack of CDC. This study builds a set of no-notice drill mode evaluation systems for public health emergencies that involve the CDC. METHODS: The indexes for these systems were based on the performance of two no-notice drills for public health emergencies in Guangdong Province. Twenty experts were invited to screen the indicators during two rounds of the Delphi method to determine the weight of first- and second-level indexes through the analytic hierarchy process, and the weight of the third-level index was calculated using the percentage method. RESULTS: After two rounds of expert consultation, we obtained four first-level indicators, twenty-six second-level indicators and eighty-six third-level indicators. According to the weight calculated by analytic hierarchy process, the weights of the first-level indicators are emergency preparation (0.2775), verification and consultation regarding an epidemic situation (0.165), field investigation and control (0.3925) and summary report (0.165). Sensitivity analysis shows that the stability of the index is good. CONCLUSION: The no-notice drill mode evaluation system for public health emergencies constructed in this study can be applied to public health departments such as the CDC. Through promotion, it can provide a scientific basis for epidemiological investigation assessment.

A potentially functional variant of ARID1B interacts with physical activity in association with risk of hepatocellular carcinoma.

The tumor suppressor role of AT-rich interactive domain containing protein 1B (ARID1B) has drawn much attention in area of cancer etiology. However, it had remained unknown whether or not genetic variants of ARID1B involved in development of hepatocellular carcinoma (HCC). In this study, three putatively functional variants in ARID1B (rs73013281C>T, rs167007A>G, and rs9397984C>T) were selected using bioinformatics tools, and a case-control study of 611 cases and 614 controls was conducted to investigate genetic associations with HCC risk in a Southern Chinese population. Two-dimensional gene-environment interactions were also explored using both multiplicative and additive scales. A dominant effect of the rs73013281 was found for HCC risk, with an adjusted odds ratio (OR) of 1.70 [95% confidence interval (CI) = 1.03-2.80] for the CT/TT genotypes compared to the CC genotype. In stratified analysis, the detrimental effect of the T allele on elevated HCC risk was attenuated by physical activity, with an adjusted OR of 2.75 (95% CI = 1.39-5.41) among inactive individuals against that of 0.89 (95% CI = 0.42-1.91) in those who exercised regularly. Expectably, the rs73013281 showed both multiplicative and additive interactions with physical activity (P = 0.037 and 0.006, respectively). In conclusion, these results highlighted the significant genetic contribution of the ARID1B variant, rs73013281, to susceptibility for HCC, especially in interaction with physical activity.

Preoperative glucose level has different effects on the endogenous extracellular matrix-related gene expression in saphenous vein of type 2 diabetic patients undergoing coronary surgery.

BACKGROUND: Type 2 diabetes mellitus (DM) severely reduces the benefits of coronary artery bypass grafting (CABG). However, few studies investigated the correlation between preoperative glucose level and endogenous extracellular matrix (ECM)-related gene expression of saphenous vein (SV) conduits in diabetic patients. METHODS: A total of 130 patients were divided into high-glucose (HG), low-glucose (LG) and control group according to the preoperative level of blood glucose. The expression of ECM-related genes was analysed by microarray. RESULTS: Compared with control group, 30 genes showed at least a threefold change in expression in HG group; up-regulation was observed in 24 genes. However, there were only 21 ECM-related genes showed at least a threefold change in expression between the LG and control group. Compared with HG group, matrix metalloproteinases' (MMPs) expression was significantly decreased in LG and control groups. In contrast to the decrease in MMPs' expression, expression of tissue inhibitors of metalloproteinases (TIMPs) was increased. CONCLUSION: This study suggested that different preoperative diabetic status affected the expression of ECM-related genes in SV. ECM-related genes were more significantly imbalanced in diabetic patients with uncontrolled preoperative blood glucose than those with well-controlled preoperative blood glucose.

Secondhand smoking and matrix metalloproteinase-2 and -9 gene expression in saphenous veins of women nonsmokers.

BACKGROUND: Active smoking upregulated matrix metalloproteinase-2 (MMP-2) and MMP-9 gene expression in saphenous veins (SVs) before coronary operation. However, little is known about the effects of secondhand smoke (SHS), a smoking status that is more widely harmful to the general population, on MMP gene expression in SVs. Health effects of SHS were investigated mainly in nonsmokers married to smokers. Because the vast majority of women are nonsmokers in China, we had an opportunity to evaluate the relations between SHS and MMP gene expression in SVs of women patients before operation. METHODS: A total of 258 woman patients were divided into three groups: control group, nonsmokers; SHS group, patients exposed to SHS until operation; active smoking group, patients who smoked a minimum of 1 package of cigarettes every day for more than 20 years. Messenger RNA and protein levels of MMP-2 and MMP-9 were analyzed. Saphenous vein graft patency after coronary operation was evaluated. RESULTS: The clinical backgrounds in the three groups were comparable. Compared with the control group, MMP-2 and MMP-9 gene expression was significantly increased in the SHS and active smoking groups (p<0.05). The degree of MMP gene expression changed by SHS or active smoking was comparable. A significant difference of SV graft patency was found among the three groups. An association of increased MMP gene expression with lowered SV graft patency was found in follow-up. CONCLUSIONS: Our data revealed that SHS had similar power as active smoking to affect MMP gene expression in SVs before operation and SV graft patency after coronary operation in women nonsmokers.