Unveiling the overlooked threat: antibiotic resistance in groundwater near an abandoned sulfuric acid plant in Xingyang, China.

Groundwater near a sulfuric acid plant in Xingyang, Henan, China was sampled from seven distinct sites to explore the prevalence of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs). Results showed that genes aadA, blaCTX-M, tetA, qnrA, and sul1 were detected with 100% frequency followed by aac(6')-Ib (85.71%), ermB (85.71%), and tetX (71.42%). Most abundant ARGs were sul1 in LSA2 (1.15 × 1011 copies/mL), tetA in LSA6 (4.95 × 1010 copies/mL), aadA in LSA2 (4.56 × 109 copies/mL), blaCTX-M in LSA4 (1.19 × 109 copies/mL), and ermB in LSA5 (1.07 × 109 copies/mL). Moreover, in LSA2, intl1 as a marker of class 1 integron emerged as the most abundant gene as part of MGE (2.25 × 1011 copies/mL), trailed by ISCR1 (1.57 × 109 copies/mL). Environmental factors explained 81.34% of ARG variations, with a strong positive correlation between the intl2 and blaCTX-M genes, as well as the ISCR1 gene and qnrA, tetA, intl2, and blaCTX-M. Furthermore, the intI1 gene had a strong positive connection with the aadA, tetA, and sul1 genes. Moreover, the aac(6')-Ib gene was associated with As, Pb, Mg, Ca, and HCO3-. The intl2 gene was also shown to be strongly associated with Cd. Notably, network analysis highlighted blaCTX-M as the most frequently appearing gene across networks of at least five genera. Particularly, Lactobacillus, Plesiomonas, and Ligilactobacillus demonstrated correlations with aadA, qnrA, blaCTX-M, intI2, and ISCR1. Based on 16S rRNA sequencing, the dominant phyla were Proteobacteria, Firmicutes, Bacteroidota, Acidobacteriota, and Actinobacteriota, with dominant genera including Pseudomonas, Ligilactobacillus, Azoarcus, Vogesella, Streptococcus, Plesiomonas, and Ferritrophicum. These findings enhance our understanding of ARG distribution in groundwater, signaling substantial contamination by ARGs and potential risks to public health.

Removal of estrogen pollutants using biochar-pellet-supported nanoscale zero-valent iron.

Nanoscale zero-valent iron-supported biochar pellets (nZVI)-(BP) were synthesized via liquid-phase reduction and applied to estrogen removal, including estrone (E1), 17ß-estradiol (E2), and estriol (E3). The performance of nZVI-BP, with respect to its characterization, removal kinetics, and isotherms, was investigated. The results showed that the adsorption equilibrium was reached within 10 min of exposure. The adsorption capacity of estrogen decreased with increasing solute pH and nZVI-BP dosage. The adsorptivity increased with increasing initial estrogen concentration. The estrogen behavior followed a pseudo-second-order kinetic model. The adsorption data of different initial estrogen concentrations fitted to Freundlich adsorption isotherms. In addition, a preliminary discussion of the adsorption mechanism of nZVI-BP for estrogens was provided.

Mechanism investigation of Forsythoside A against esophageal squamous cell carcinoma in vitro and in vivo.

CONTEXT: Forsythoside A (FSA) was extracted from Forsythia suspensa, a traditional Chinese medicine, which has been demonstrated to exert anti-inflammatory, antibacterial, and other pharmacological effects. However, the anticancer effect of FSA in esophageal squamous cell carcinoma (ESCC) has not been documented. OBJECTIVE: The present study aimed to elucidate the mechanism of FSA against ESCC. MATERIALS AND METHODS: Network pharmacology and molecular docking were employed to predict the mechanism. FSA was utilized to treat ESCC cell lines KYSE450 and KYSE30, followed by CCK-8 assay, cell cloning formation assay, flow cytometry, Western blot, RNA-seq analysis, and subsequent in vivo experiments. RESULTS: Network pharmacology and molecular docking predicted that the therapeutic effect of FSA in ESCC is mediated through proteins such as BCL2 and BAX, influencing KEGG pathways associated with apoptosis. In vitro experiments showed that FSA inhibited cell proliferation and plate clone formation, promoted cell apoptosis and impacted the cell cycle distribution of G2/M phase by regulating BCL2, BAX, and p21. Further RNA-seq in KYSE450 cells showed that FSA regulated the expression of 223 genes, specifically affecting the biological process of epidermal development. In vivo experiments showed that gastric administration of FSA resulted in notable reductions in both tumor volume and weight by regulating BCL2, BAX, and p21. 16S rRNA sequencing showed that FSA led to significant changes of beta diversity. Abundance of 11 specific bacterial taxa were considerably changed following administration of FSA. CONCLUSIONS: This study presents a novel candidate drug against ESCC and establishes a foundation for future clinical application.

Profiling of intracellular and extracellular antibiotic resistance genes in municipal wastewater treatment plant and their effluent-receiving river.

The presence of antibiotic resistance genes (ARGs) and heavy metal resistance genes (MRGs) in extracellular and intracellular DNA (eDNA and iDNA) has received considerable attention in recent years owing to the potential threat to human health and the ecosystem. As a result, we investigated six ARGs, three MRGs, and two mobile genetic elements (MGEs) in the municipal wastewater treatment plant (MWWTP) and its adjacent environments. Results revealed that the absolute abundances of eARGs and eMRGs were lower than iARGs and iMRGs in MWWTP. By contrast, eARGs and eMRGs were higher in river sediments. Among ARGs, aminoglycoside resistance genes (aadA) was the most abundant gene (3.13 × 102 to 2.31 × 106 copies/mL in iDNA; 1.27 × 103 to 7.23 × 105 copies/mL in eDNA) in MWWTP, while zntA gene (9.4 × 102 to 3.97 × 106 copies/mL in iDNA; 3.2 × 103 to 6 × 105 copies/mL in eDNA) was amongst the MRGs. Notably, intI1 was enriched and positively correlated with iDNA (tetA, sul1, blaCTX-M, ermB, and merA) and eDNA (blaCTX-M, ermB, and merA), demonstrating its function in the proliferation of resistance genes. This widespread distribution of ARGs, MRGs, and MGEs in MWWTP and its adjacent river sediments will help clarify the transmission routes within these environments and provide a theoretical basis for better monitoring and mitigation of such dissemination.

NAT2 genetic polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in Chinese community population.

BACKGROUND: Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is one of the most prevalent and serious adverse drug reactions in the course of anti-tuberculosis (TB) treatment. Some researchers suggested that determination of N-acetyltransferase 2 (NAT2) genotype may be clinically useful to identify patients at high risk of developing ATDH. AIM: To evaluate whether the NAT2 genotype could be as a predictor for ATDH in Chinese community TB population. MATERIAL AND METHODS: A total of 4304 community-based TB patients were followed up six to nine months prospectively. A nested case-control study was designed. Each ATDH case was 1:4 matched with controls by age (within 5 years old), gender, treatment history, disease severity and drug dosage. The polymorphisms of NAT2 were determined using polymerase chain reaction with restriction fragment length polymorphism. Conditional Logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (CI), as well as corresponding P-values. RESULTS: A total of 89 ATDH cases and 356 controls were included in this study. Allele frequency of NAT2*5, NAT2*6 and NAT2*7 in cases and controls were 4.5 and 3.2%, 25.3 and 26.5%, and 13.5 and 13.5%, respectively. Frequencies of genotypes and alleles of NAT2*5, NAT2*6 and NAT2*7 did not differ significantly between cases and controls. The OR of intermediate acetylator and slow acetylator compared with rapid acetylator was 1.040 (95%CI 0.616-1.758) and 0.990 (95%CI 0.509-1.925), respectively. The NAT2 haplotype distribution in cases was similar to controls. CONCLUSIONS: In conclusion, we did not find significant association between NAT2 genotype and ATDH in community-based Chinese population. It may be deficient to take NAT2 genotype as a predictor for ATDH in Chinese community TB patients.

Effect of scheduled monitoring of liver function during anti-Tuberculosis treatment in a retrospective cohort in China.

BACKGROUND: Data on effect of regular liver function monitoring during anti-TB treatment is limited in China. This study aimed to evaluate the effects of scheduled liver function monitoring on identification of asymptomatic liver damage and anti-TB treatment outcomes during anti-TB treatment. METHODS: A retrospective analysis was performed based on a national-level cohort study. A total of 273 patients developing liver dysfunction were divided into two groups, 111 patients who were diagnosed through scheduled liver function test within two months after initiation of anti-TB treatment formed scheduled monitoring group, others who were diagnosed due to developing symptoms formed passive detection group (n = 162). The two groups were compared through clinical features, prognosis of liver dysfunction and impact on anti-TB treatment using propensity score weighting analysis. RESULTS: 33.3% of 273 patients did not have any clinical symptoms, including 8 with severe hepatotoxicity. 1.8% in scheduled monitoring group and 11.1% in passive detection group required hospitalization (P = 0.004). Regarding the prognosis of liver dysfunction, most patients recovered, no death happened in scheduled monitoring group while 3 died in passive detection group. In terms of impact on anti-TB treatment, 35.1% in scheduled monitoring group and 56.8% in passive detection group changed their anti-TB treatment (P = 0.001). CONCLUSIONS: Scheduled monitoring is effective in identifying asymptomatic liver damage, reducing hospitalization rate and improving compliance of anti-TB treatment.

Construction of a novel two-dimensional AgBiO3/BiOBr step-scheme heterojunction for enhanced broad-spectrum photocatalytic performance.

Efficient S-scheme heterojunction photocatalysts were prepared through in situ growth of AgBiO3 on BiOBr. The self-assembled hierarchical structure of AgBiO3/BiOBr was formed from flower-like AgBiO3 and plate-like BiOBr. The optimized AgBiO3/BiOBr heterojunction possessed excellent visible-light photocatalytic degradation efficiency (83%) for ciprofloxacin (CIP) after 120 min, with 1.46- and 4.15-times higher activity than pure AgBiO3 and BiOBr, respectively. Furthermore, the removal ratio of multiple organic pollutants including tetracycline, Rhodamine B, Lanasol Red 5B and methyl orange was also investigated. Environmental interference experiments demonstrated that high pollutant concentrations, low photocatalyst dose and the addition of ions (SO4 2-, PO4 3-, HPO4 2-, H2PO4 -) inhibited the photocatalytic activities. Subsequently, a simultaneous degradation experiment showed the competitive actions between CIP and RhB for radicals, decreasing the photocatalytic activity of CIP. Furthermore, trapping and electron spin resonance experiments showed that h+ and ˙O2 - played a certain role in the degradation process and that ˙OH acted as assistant.

Association of polymorphisms in drug transporter genes (SLCO1B1 and SLC10A1) and anti-tuberculosis drug-induced hepatotoxicity in a Chinese cohort.

This study investigated the association between genetic variants in two hepatic uptake transporter genes (SLCO1B1 and SLC10A1) and the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH) in a Chinese cohort. The frequencies and distributions of single nucleotide polymorphisms (SNPs) and haplotypes of these genes were compared among 89 incident ATDH cases and 356 matched ATDH-free controls using a multivariate conditional logistic regression analysis. After correction for potential confounding factors, significant differences were found in polymorphism of rs4149014 under an addictive model (P = 0.008) and a recessive model (P = 0.016). The result of haplotype analysis suggested that patients carrying at least one SLCO1B1*15 haplotype had a higher risk of ATDH (odds ratio (OR) = 1.74, 95% confidence intervals (CI): 1.04-2.90, P = 0.034) in comparison with those carrying SLCO1B1*1a or SLCO1B1*1b haplotypes. These findings indicate that genetic variants of SLCO1B1 are associated with the development of ATDH in Chinese population.

Cytochrome P450 2E1 gene polymorphisms/haplotypes and anti-tuberculosis drug-induced hepatitis in a Chinese cohort.

OBJECTIVE: The pathogenic mechanism of anti-tuberculosis (anti-TB) drug-induced hepatitis is associated with drug metabolizing enzymes. No tagging single-nucleotide polymorphisms (tSNPs) of cytochrome P450 2E1(CYP2E1) in the risk of anti-TB drug-induced hepatitis have been reported. The present study was aimed at exploring the role of tSNPs in CYP2E1 gene in a population-based anti-TB treatment cohort. METHODS AND DESIGN: A nested case-control study was designed. Each hepatitis case was 14 matched with controls by age, gender, treatment history, disease severity and drug dosage. The tSNPs were selected by using Haploview 4.2 based on the HapMap database of Han Chinese in Beijing, and detected by using TaqMan allelic discrimination technology. RESULTS: Eighty-nine anti-TB drug-induced hepatitis cases and 356 controls were included in this study. 6 tSNPs (rs2031920, rs2070672, rs915908, rs8192775, rs2515641, rs2515644) were genotyped and minor allele frequencies of these tSNPs were 21.9%, 23.0%, 19.1%, 23.6%, 20.8% and 44.4% in the cases and 20.9%, 22.7%, 18.9%, 23.2%, 18.2% and 43.2% in the controls, respectively. No significant difference was observed in genotypes or allele frequencies of the 6 tSNPs between case group and control group, and neither of haplotypes in block 1 nor in block 2 was significantly associated with the development of hepatitis. CONCLUSION: Based on the Chinese anti-TB treatment cohort, we did not find a statistically significant association between genetic polymorphisms of CYP2E1 and the risk of anti-TB drug-induced hepatitis. None of the haplotypes showed a significant association with the development of hepatitis in Chinese TB population.

Expression analysis and binding experiments of chemosensory proteins indicate multiple roles in Bombyx mori.

Chemosensory proteins (CSPs) are a family of small soluble proteins that, in addition to the odorant-binding proteins (OBPs), are involved in chemical communication. To understand the physiological function of the 16 known CSPs in the silkworm Bombyx mori, we investigated the expression patterns in different tissues and developmental stages using quantitative real-time RT-PCR (Q-PCR) and Western blot analysis. The results indicated that most CSPs were widely expressed in embryos, larvae, pupae and adults but were developmentally regulated. Such broad spatial and temporal expression was inconsistent with a specific association with chemosensory function. We conclude that CSPs are multifunctional proteins that are involved in diverse cellular processes and that can play non-chemosensory as well as chemosensory roles. Binding experiments revealed different binding characteristics of CSP1 and CSP2, with retinal being the best ligand, suggesting a putative function of these CSPs as carriers.

Adverse reactions due to directly observed treatment strategy therapy in Chinese tuberculosis patients: a prospective study.

BACKGROUND: More than 1 million tuberculosis (TB) patients are receiving directly observed treatment strategy (DOTS) therapy in China every year. As to the profile of adverse drug reactions (ADRs) due to DOTS therapy, no consensus has been reached. There is no report regarding ADRs due to DOTS therapy with a large Chinese TB population. This study aimed to determine the incidence and prognosis of ADRs due to DOTS therapy, and to evaluate their impact on anti-TB treatment in China. METHODS: A prospective population-based cohort study was performed during 2007-2008. Sputum smear positive pulmonary TB patients who received DOTS therapy were included and followed up for six to nine months in 52 counties of four regions in China. The suspected ADRs were recorded and reviewed by Chinese State Food and Drug Administration. RESULTS: A total of 4304 TB patients were included in this study. 649 patients (15.08%) showed at least one ADR and 766 cases in total were detected. The incidence (count) of ADR based on affected organ was: liver dysfunction 6.34% (273), gastrointestinal disorders 3.74% (161), arthralgia 2.51% (108), allergic reactions 2.35% (101), neurological system disorders 2.04% (88), renal impairment 0.07% (3) and others 0.05% (2). Most cases of ADRs (95%) had a good clinical outcome, while two with hepatotoxicity and one with renal impairment died. Compared with patients without ADRs, patients with ADRs were more likely to have positive smear test results at the end of the intensive phase (adjusted OR, 2.00; 95%CI, 1.44-2.78) and unsuccessful anti-TB outcomes (adjusted OR, 2.58; 95%CI, 1.43-4.68). CONCLUSIONS: The incidence of ADRs due to DOTS therapy was 15.08%. Those ADRs had a substantial impact on TB control in China. This highlighted the importance of developing strategies to ameliorate ADRs both to improve the quality of patient care and to control TB safely.

Incidence, clinical features and impact on anti-tuberculosis treatment of anti-tuberculosis drug induced liver injury (ATLI) in China.

BACKGROUND: Anti-tuberculosis drug induced liver injury (ATLI) is emerging as a significant threat to tuberculosis control in China, though limited data is available about the burden of ATLI at population level. This study aimed to estimate the incidence of ATLI, to better understand its clinical features, and to evaluate its impact on anti-tuberculosis (TB) treatment in China. METHODOLOGY/PRINCIPAL FINDINGS: In a population-based prospective study, we monitored 4,304 TB patients receiving directly observed treatment strategy (DOTS) treatment, and found that 106 patients developed ATLI with a cumulative incidence of 2.55% (95% Confidence Interval [CI], 2.04%-3.06%). Nausea, vomiting and anorexia were the top three most frequently observed symptoms. There were 35 (33.02%) ATLI patients with no symptoms, including 8 with severe hepatotoxicity. Regarding the prognosis of ATLI, 84 cases (79.25%) recovered, 18 (16.98%) improved, 2 (1.89%) failed to respond to the treatment with continued elevation of serum alanine aminotransferase, and 2 (1.89%) died as result of ATLI. Of all the ATLI cases, 74 (69.81%) cases changed their anti-TB treatment, including 4 (3.77%) cases with medication administration change, 21 (19.81%) cases with drugs replacement, 54 (50.94%) cases with therapy interruption, and 12 (11.32%) cases who discontinued therapy. In terms of treatment outcomes, 53 (51.46%) cases had TB cured in time, 48 (46.60%) cases had therapy prolonged, and 2 (1.94%) cases died. Compared with non-ATLI patients, ATLI patients had a 9.25-fold (95%CI, 5.69-15.05) risk of unsuccessful anti-TB treatment outcomes and a 2.11-fold (95%CI, 1.23-3.60) risk of prolonged intensive treatment phase. CONCLUSIONS/SIGNIFICANCE: ATLI could considerably impact the outcomes of anti-TB treatment. Given the incidence of ATLI and the size of TB population in China, the negative impact is substantial. Therefore, more research and efforts are warranted in order to enhance the diagnosis and the prevention of ATLI.