Rapid turnover and short-term blooms of Escherichia coli in the human gut.

Escherichia coli (E. coli) is a common microorganism that is widely present in the environment and closely related to human health. The extent of E. coli presence in the human gut has been a subject of ongoing debate. Through whole-genome shotgun metagenomic sequencing, our study revealed that E. coli exists in the human body at a low abundance (average abundance 1.21%), with occasional short-term bursts leading to temporary increases in abundance, with the highest recorded at 50.91%. Further investigations into the factors contributing to these short-term blooms of E. coli showed significant variations in strain types and genomes within fecal samples collected from the same individuals at different time points. Evolutionary tree analysis indicated that samples from different individuals crossed, suggesting a change in the dominant E. coli strains within the human gut. Therefore, it can be inferred that E. coli in the human body are more likely to be transient bacteria rather than permanent residents in the gut. The rapid rate of turnover among months (87.5% within a month) and short-term blooms of E. coli in the human body can establish "latent infections" of nonpathogenic strains in healthy individuals while also posing a potential risk of introducing pathogenic strains, thereby impacting human health. In summary, our study revealed the variation in E. coli abundance and strains within the human gut, influenced by geographic area and temporal factors. These findings contribute to a better understanding of the relationship between E. coli, the gut microbiota, and human health. IMPORTANCE Escherichia coli (E. coli) is a microorganism closely linked to human health, and its presence in the human gut has been a topic of debate. Our study, using whole-genome shotgun metagenomic sequencing, revealed that E. coli exists at a low abundance in the human body, with occasional short-term bursts leading to temporary increases. Strain and genome variations were observed within fecal samples from the same individuals at different time points, suggesting transient rather than permanent residence of E. coli in the gut. The rapid turnover rate and short-term blooms of E. coli can establish latent infections while also posing a risk of introducing pathogenic strains. These findings enhance our understanding of the relationship between E. coli, the gut microbiota, and human health.

Maternal inulin supplementation ameliorates prenatal methamphetamine exposure-induced hepatotoxicity and restores gut microbiota in mouse offspring.

Prenatal exposure to methamphetamine (METH) is an issue of global concern due to its adverse effects on offspring, particularly its impact on liver health, an area still not fully understood. Inulin, a recognized prebiotic, is thought to potentially ameliorate these developmental disorders and toxic injuries in progeny. To investigate the effects of prenatal METH exposure on the liver and the role of gut microbiota, we established a murine model, the subjects of which were exposed to METH prenatally and subsequently treated with inulin. Our findings indicate that prenatal METH exposure causes liver damage in offspring, as evidenced by a decreased liver index, histopathological changes, diminished glycogen synthesis, hepatic dysfunction, and alterations in mRNA profiles. Furthermore, it impairs the antioxidant system and induces oxidative stress, possibly due to changes in cecal microbiota and dysregulation of bile acid homeostasis. However, maternal inulin supplementation appears to restore the gut microbiota in offspring and mitigate the hepatotoxic effects induced by prenatal METH exposure. Our study provides definitive evidence of METH's transgenerational hepatotoxicity and suggests that maternal inulin supplementation could be an effective preventive strategy.

The gut microbiota contributes to methamphetamine-induced reproductive toxicity in male mice.

Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.

Causal effect of cerebral small vessel disease on unexplained dizziness: A Mendelian randomization study.

BACKGROUND: Previous cohort studies have suggested an association between cerebral small vessel disease (cSVD) and "unexplained dizziness". The causality of this link remains uncertain, but it would be of significant clinical importance, considering the substantial number of patients presenting with unexplained dizziness is large. We aimed to investigate the causal effect of cSVD-related phenotypes on unexplained dizziness using a Mendelian randomization approach. METHODS: Genetic instruments for each cSVD-related phenotype - white matter hyperintensity (WMH) volume, lacunar stroke (LS), perivascular spaces (PVS), and cerebral microbleeds (CMBs) - as well as unexplained dizziness were identified through large-scale genome-wide association studies. We conducted 2-sample Mendelian randomization analyses. The random-effects inverse-variance weighted (IVW) method was chosen for the primary analysis. For sensitivity analyses, we employed the weighted-median, MR-Egger, MR pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out analysis methods were implemented for the sensitivity analyses. RESULTS: We successfully identified a significant causal effect of WMH volume on unexplained dizziness (odds ratio [95% CI], 1.12 [1.01-1.23]). However, we were unable to detect any significant causal effects of the other cSVD-related phenotypes on unexplained dizziness, with odds ratios [95% CI] of 1.03 [0.98-1.09] for LS, 0.75 [0.55-1.02] for white matter PVS, 1.02 [0.68-1.52] for basal ganglia PVS, 0.80 [0.43-1.51] for hippocampal PVS, 0.95 [0.90-1.00] for lobar CMBs, and 0.97 [0.92-1.01] for mixed CMBs respectively. The results from the sensitivity analyses were generally consistent with those of the primary analyses. CONCLUSIONS: This MR study supports a causal relationship between WMH, a phenotype associated with cSVD, and the risk of unexplained dizziness, but does not support such a relationship between other cSVD-related phenotypes and unexplained dizziness. These findings require further validation through randomized controlled trials, larger cohort studies, and MR studies based on more extensive GWASs.

Occurrence and risk assessment of azole fungicides during the urban water cycle: A year-long study along the Yangtze River, China.

Azole fungicides (AFs) play an important role in the prevention and treatment of fungal diseases in agricultural crops. However, limited studies are addressing the fate and ecological risk of AFs in the urban water cycle at a large watershed scale. To address this gap, we investigated the spatiotemporal distribution and ecological risk of twenty AFs in the lower reaches of the Yangtze River across four seasons. Carbendazim (CBA), tebuconazole (TBA), tricyclazole (TCA), and propiconazole (PPA) were found to be the dominant compounds. Their highest concentrations were measured in January (188.3 ng/L), and November (2197.1 ng/L), July (162.0 ng/L), and November (1801.9 ng/L), respectively. The comparison between wastewater treatment plants (WWTPs) effluents and surface water suggested that industrial WWTPs are major sources of AFs in the Yangtze River. In particular, TBA and PPA were found to be the most recalcitrant AFs in industrial WWTPs, while difenoconazole (DFA) was found to be the most potent pollutant in municipal WWTPs, with an average removal rate of less than 60%. The average risk quotient (RQ) for the entire AFs was 6.45 in the fall, which was higher than in January (0.98), April (0.61), and July (0.40). This indicates that AFs in surface water posed higher environmental risks during the dry season. Additionally, the exposure risk of AFs via drinking water for sensitive populations deserves more attention. This study provides benchmark data on the occurrence of AFs in the lower reaches of the Yangtze River, and offers suggestions for better reduction of AFs.

Estrogen promotes Epithelial ovarian cancer cells proliferation via down-regulating expression and activating phosphorylation of PTEN.

Epithelial ovarian cancer (EOC) is the most common of cancer death among malignant tumors in women, its occurrence and development are strongly linked to estrogen. Having identified the phosphatase and tensin homologue (PTEN) is a potent tumor suppressor regulating cell proliferation, migration, and survival. Meanwhile, there is a correlation between PTEN protein expression and estrogen receptor expression in EOC. However, no study has amplified on the molecular regulatory mechanism and function between estrogen and PTEN in the development of EOC. In this research, we found that PTEN shows a low expression level in EOC tissues and estrogen decreased PTEN expression via the estrogen receptor 1 (ESR1) in EOC cells. Knockdown of PTEN enhanced the proliferation and migration level of EOC cells driven by estrogen. Moreover, PTEN was also phosphorylated by G protein-coupled receptor 30 (GPR30)-Protein kinase C (PKC) signaling pathway upon estrogen stimulation. Inhibiting the phosphorylation of PTEN weakened the proliferation and migration of estrogen induced-EOC cells estrogen and decreased the phosphorylation of Protein kinase B (AKT) and Mammalian target of rapamycin (mTOR). These results indicated that estrogen decreased PTEN expression level via the ESR1 genomic pathway and phosphorylated PTEN via the GPR30-PKC non-genomic pathway to activate the PI3K/AKT/mTOR signaling pathway, thereby determining the fate of EOC cells.

Childhood maltreatment and subsequent depressive symptoms: a prospective study of the sequential mediating role of self-esteem and internalizing/externalizing problems.

BACKGROUND: Depression among adolescents is a seriously disabling public health problem with an extremely high prevalence. Identifying risk factors of depression at an early stage is important to reduce the disease burden. Childhood maltreatment (CM) is one of the major risk factors for depression. The key mediating processes that how CM affects the development of depression, however, still need further clarification. The present study tested the mediating effect of self-esteem, internalizing problems, and externalizing problems between CM and depressive symptoms. Potential sex differences in the foregoing associations were also explored. METHODS: A three-wave longitudinal study was carried out among 1,957 middle and high school students from 69 classes in 10 public schools in the Guangdong province of China. Data collection started when students were in grades 7 and 10 (median age: 13.0, range: 11-18) between January and April 2019, and the students were followed up once a year thereafter. Self-reported CM, depressive symptoms, self-esteem, internalizing and externalizing problems, and other demographics were collected. The multiple serial mediation analysis was conducted. RESULTS: We found that CM was positively related to subsequent internalizing and externalizing problems, as well as depressive symptoms, while self-esteem was negatively related to depressive symptoms. Serial mediation analysis indicated that self-esteem (mediator 1) and internalizing problems (mediator 2) sequentially mediated the path from CM to depressive symptoms in the overall and male population. Moreover, with externalizing problems as mediator 2, self-esteem (mediator 1) acted as a partial mediator in the association between CM and depressive symptoms in males, whereas externalizing problems played a complete mediating role in females. CONCLUSION: Findings revealed that self-esteem and internalizing problems sequentially mediated the influence of CM on depressive symptoms whereas externalizing problems played an independent mediating role. In addition, sex differences need to be taken into consideration when designing prevention and intervention strategies, given the different psychosocial processes between boys and girls.

Genetic characteristics of Blastocystis sp. ST3 at the genome level in the Chinese population.

The gut microbiota comprises the collective genomes of microbial symbionts and is composed of bacteria, fungi, viruses, and protists within the gastrointestinal tract of a host. Although the literature associated with gut microbiota is increasing, studies on eukaryotes in the human gut are just beginning to surface. Blastocystis is one of the most common intestinal parasites of humans and animals and is estimated to colonise more than 1 billion people on a global scale. However, the understanding of the genetic characteristics of Blastocystis subtype (ST) at the genome level and its relationship with other members of the gut microbiota is still limited. In this study, by surveying the prevalence and genome characteristics of Blastocystis sp. ST3 in a Chinese population (prevalence % = 6.09%), the association of Blastocystis sp. ST3 with region and time and the structure of the resident gut bacterial population was clarified. We identified novel sequences (50 mitochondrial and 41 genome sequences) and determined their genetic diversity amongst strains within Blastocystis sp. ST3 (4.14 SNPs/kb). Furthermore, we found that colonisation of Blastocystis was strongly associated with increased bacterial richness and higher abundance of several anaerobes. Finally, we performed time series sampling on two Blastocystis-positive individuals and confirmed that Blastocystis could exist continually in the human gut microbiota and persist for a long time, even for 4 years.

Inulin alleviates neuroinflammation and oxidative stress induced by perinatal 2-ethylhexyl diphenyl phosphate (EHDPHP) exposure in female mice and offspring.

Organophosphorus flame retardants (OPFRs), including 2-ethylhexyl diphenyl phosphate (EHDPHP), are prevalent in everyday life due to their broad usage in fields such as healthcare, electronics, industry, and sports. These compounds, added to polymers through physical mixing, can leach into the environment, posing a risk to humans through direct contact or the food chain. Despite known associations with health issues like endocrine disruption, neurotoxicity, and reproductive toxicity, the implications of perinatal EHDPHP exposure on both mothers and offspring are still unclear. This study aimed to investigate the neuroinflammatory effects of EHDPHP and the potential mitigating role of inulin. Pregnant C57 mice were administered either a corn oil control or an EHDPHP solution (300 µg/kg bw/d) from gestation day 7 (GD7) to postnatal day 21 (PND21). Concurrently, mice were provided either regular drinking water or water supplemented with 1% inulin. We found that EHDPHP significantly increased the serum levels of IL-1ß, IL-6, and MDA, but decreased SOD levels in both mothers and pups. These effects were reversed by inulin supplementation. RNA-sequencing revealed that EHDPHP induced inflammation and oxidative stress through the TLR4/NF-κB pathway, which was mitigated by inulin. In conclusion, inulin ameliorated EHDPHP-induced neuroinflammation and oxidative stress in both mothers and offspring, highlighting its potential therapeutic role.

Longitudinal associations between problematic Internet use, self-esteem, and depressive symptoms among Chinese adolescents.

Problematic Internet use (PIU) has a negative impact on self-esteem among adolescents, thereby making them be vulnerable to developing depressive symptoms. However, there is a lack of longitudinal studies focusing on the process. This study aimed to explore the longitudinal associations between PIU, self-esteem, and depressive symptoms. A total of 1,736 adolescents completed this longitudinal study. The baseline survey was conducted in 2019, and the follow-up surveys were performed at 1-year and 2-year later. PIU, self-esteem, and depressive symptoms were measured. A cascade model was used to examine the longitudinal associations between PIU, self-esteem, and depressive symptoms. The mean age of participants was 13.6 (1.5) years at baseline. The final results observed significant within-time associations between PIU, self-esteem, and depressive symptoms at each time point. PIU and low level of self-esteem could predict subsequent depressive symptoms among adolescents, and depressive symptoms were also associated with subsequent PIU and self-esteem. Both PIU and self-esteem show bidirectional predictions with depressive symptoms among Chinese adolescents. Schools and parents should give more attention to adolescents prone to developing depressive symptoms and more social support to reduce their negative emotions. Health-related professionals should incorporate practical knowledge and skills into the education of adolescents to help them better control Internet use, attenuating the risk of future depressive symptoms.

GATA-binding protein 4 promotes neuroinflammation and cognitive impairment in Aß1-42 fibril-infused rats through small nucleolar RNA host gene 1/miR-361-3p axis.

Aging with dysregulated metabolic and immune homeostasis stimulates pyroptosis, neuroinflammation, and cellular senescence, thus contributing to etiopathogenesis of Alzheimer's disease. GATA-binding protein 4 (GATA4) functions as a transcriptional factor in response to DNA damage, and is associated with neuroinflammation and cellular senescence. The role of GATA4 in Alzheimer's disease was investigated. GATA4 was elevated in hippocampus of Aß1-42 fibril-infused rats. Injection with shRNA targeting GATA4 reduced escape latency with increase of time in target quadrant and number of platform crossings in Aß1-42 fibril-infused rats. Moreover, knockdown of GATA4 ameliorated morphological changes of hippocampus and reduced amyloid plaque deposition in Aß1-42 fibril-infused rats. Silence of GATA4 repressed neuroinflammation and apoptosis in Aß1-42 fibril-infused rats. Loss of GATA4 in Aß1-42 fibril-infused rats reduced the expression of specificity protein 1 (Sp1) to downregulate long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) and upregulated miR-361-3p. Loss of SNHG1 ameliorated learning and memory impairments in Aß1-42 fibril-infused rats. Overexpression of Sp1 attenuated GATA4 silence-induced decrease of escape latency, increase of time in target quadrant, and number of platform crossings in Aß1-42 fibril-infused rats. In conclusion, silence of GATA4 ameliorated cognitive dysfunction and inhibited hippocampal inflammation and cell apoptosis through regulation of Sp1/SNHG1/miR-361-3p.

The association of FKBP5 gene methylation, adolescents' sex, and depressive symptoms among Chinese adolescents: a nested case-control study.

BACKGROUND: Depressive symptoms among adolescents are a serious health concern around the world. Altered DNA methylation in the FK506 binding protein 5 (FKBP5) gene has been reported to regulate stress response, which has been reported to be closely associated with depressive symptoms. However, most of the contributing studies have been conducted among adults and relatively few studies have considered the effect of disparate social influences and sex differences on the DNA methylation of FKBP5 in persons with depressive symptoms. The present study aimed to test the associations of FKBP5 DNA methylation and depressive symptoms among adolescents and explore possible sex differences in the foregoing associations. METHODS: This study was conducted using a nested case-control design within a longitudinal cohort study from January 2019 to December 2019. Adolescents aged 12 to 17 years from 69 classes in 10 public high schools located in Guangdong province of China participated in this research. Students with persistent depressive symptoms that reported having depressive symptoms at both baseline and follow-up were treated as the case group, and those without depressive symptoms were randomly selected as the control group. Our study finally included 87 cases and 151 controls. Quantitative methylation analyses of the selected gene were carried out by MassARRAY platform System. RESULTS: The overall DNA methylation trend of FKBP5 CpG sites in the case group was lower in comparison to the control group. Compared to healthy controls, lower methylation percentage of FKBP5-12 CpG 1 was observed in adolescents with persistent depressive symptoms after adjusting for covariates (case: 0.94 ± 2.00, control: 0.47 ± 0.92; F = 5.41, P = 0.021), although the statistical significance of the difference was lost after false discovery rate correction (q > 0.05). In addition, the hypomethylation of FKBP5-12 CpG 1 was approaching significance after adjustment for social-environmental factors (aOR = 0.77; P = 0.055), which indicated that no independent association was detected between hypomethylation of FKBP5 CpG sites and persistent depressive symptoms. Furthermore, in the present study, we were unable to identify sex differences in the association of FKBP5 gene methylation with depressive symptoms. CONCLUSION: The decreased methylation level of FKBP5 was observed in adolescents with persistent depressive symptoms, albeit non-significant after correction for multiple testing. Our results presented here are preliminary and underscore the complex gene-environment interactions relevant to the risk for depressive symptoms.

mRNA microarray analysis for the identification of potential biomarkers for vital reaction in burned skin: a preliminary pilot study.

The identification of ante- and post-mortem burns is challenging in forensic pathology. In this study, microarray analysis was used to detect the mRNA expression profiles in the skin of an experimental burn mouse model; the results were validated using RT-qPCR. Differentially expressed mRNAs (DE-mRNAs) were assessed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Our results revealed that mRNA expression of 501 genes was significantly different, of which 273 were upregulated and 228 were downregulated in ante-mortem burned mice skin. The expression levels of eight random mRNAs were consistent when measured using the microarray assay-based method and RT-qPCR. Genes from different functional categories and signalling pathways were enriched, including interleukin-20 binding, type IV hypersensitivity, negative regulation of acute inflammatory response, sensory organ development, endocytosis, neuroactive ligand-receptor interaction, and Jak-STAT signalling pathway. Only five of the eight mRNAs exhibited consistent changes in expression between burned skin samples of mice and human autopsy specimens. Our findings showed that DE-mRNAs revealed using microarray are potential biomarkers of ante-mortem burns. However, DE-mRNAs identified from experimental animal models cannot be directly extended to autopsy specimens without careful validation.

Single and combined effects of carbamazepine and copper on nervous and antioxidant systems of zebrafish (Danio rerio).

Various pollutants co-exist in the aquatic environment such as carbamazepine (CBZ) and copper (Cu), which can cause complex effects on inhabiting organisms. The toxic impacts of the single substance have been studied extensively. However, the studies about their combined adverse impacts are not enough. In the present study, zebrafish were exposed to environmental relevant concentrations of CBZ (1, 10, and 100 µg/L), Cu (0.5, 5, and 10 µg/L) and the mixtures (1 µg/L CBZ + 0.5 µg/L Cu, 10 µg/L CBZ + 5 µg/L Cu, 100 µg/L CBZ + 10 µg/L Cu) for 45 days, the effects on nervous and antioxidant systems of zebrafish were investigated. The results demonstrated that, in comparison with single exposure group, the combined presence of CBZ and Cu exacerbated the effect of antioxidant system (the ability of inhibition of hydroxyl radicals (IHR), superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST)) but not nervous system (Acetylcholinesterase [AChE]). The qPCR results supported the changes of corresponding enzymes activities. Hepatic histopathological analysis verified the results of biomarkers. Our work illustrated that the toxicity of mixed pollutants is very complicated, which cannot simply be inferred from the toxicity of single pollutant, and calls for more co-exposure experiments to better understanding of the co-effects of pollutants on aquatic organisms.

Distributed Field Estimation Using Sensor Networks Based on H∞ Consensus Filtering.

This paper is concerned with the distributed field estimation problem using a sensor network, and the main purpose is to design a local filter for each sensor node to estimate a spatially-distributed physical process using the measurements of the whole network. The finite element method is employed to discretize the infinite dimensional process, which is described by a partial differential equation, and an approximate finite dimensional linear system is established. Due to the sparsity on the spatial distribution of the source function, the ℓ 1 -regularized H ∞ filtering is introduced to solve the estimation problem, which attempts to provide better performance than the classical centralized Kalman filtering. Finally, a numerical example is provided to demonstrate the effectiveness and applicability of the proposed method.

16SPIP: a comprehensive analysis pipeline for rapid pathogen detection in clinical samples based on 16S metagenomic sequencing.

BACKGROUND: Pathogen detection in clinical samples based on 16S metagenomic sequencing technology in microbiology laboratories is an important strategy for clinical diagnosis, public health surveillance, and investigations of outbreaks. However, the implementation of the technology is limited by its accuracy and the time required for bioinformatics analysis. Therefore, a simple, standardized, and rapid analysis pipeline from the receipt of clinical samples to the generation of a test report is needed to increase the use of metagenomic analyses in clinical settings. RESULTS: We developed a comprehensive bioinformatics analysis pipeline for the identification of pathogens in clinical samples based on 16S metagenomic sequencing data, named 16SPIP. This pipeline offers two analysis modes (fast and sensitive mode) for the rapid conversion of clinical 16S metagenomic data to test reports for pathogen detection. The pipeline includes tools for data conversion, quality control, merging of paired-end reads, alignment, and pathogen identification. We validated the feasibility and accuracy of the pipeline using a combination of culture and whole-genome shotgun (WGS) metagenomic analyses. CONCLUSIONS: 16SPIP may be effective for the analysis of 16S metagenomic sequencing data for real-time, rapid, and unbiased pathogen detection in clinical samples.

Temporal dynamics and species-level complexity of Prevotella spp. in the human gut microbiota: implications for enterotypes and health.

The concept of "enterotypes" in microbiome research has attracted substantial interest, particularly focusing on the abundance of Prevotella spp. in the human gut. In this study, the intricate dynamics of Prevotella spp. in the human gut microbiota was investigated, based on the metagenomic method. First, 239 fecal samples from individuals across four regions of China revealed a bimodal distribution, highlighting the abundance and variability in Prevotella spp. within the Chinese population. Second, the longitudinal cohort study included 184 fecal samples from 52 time points collected from seven individuals who demonstrated either the outbreaks or disappearances of Prevotella spp., emphasizing the transient nature of Prevotella abundance levels and suggesting shifts in Prevotella "enterotypes." Furthermore, a turnover of the dominant Prevotella spp. was observed, indicating the potential presence of diverse subtypes of Prevotella enterotype. Notably, the genomic analysis demonstrated the persistence of specific Prevotella strains within individuals over extended periods, highlighting the enduring presence of Prevotella in the human gut. In conclusion, by integrating the temporal and geographical scales in our research, we gained deeper insights into the dynamics of Prevotella, emphasizing the importance of considering the dynamics at the time and species level in gut microbiota studies and their implications on human health.

Prevalence of antibiotics, antibiotic resistance genes, and their associations in municipal wastewater treatment plants along the Yangtze River basin, China.

The overuse and misuse of antibiotics have resulted in the pollution of antibiotics and antibiotic resistance genes (ARGs) in municipal wastewater treatment plants (WWTPs), posing threats to ecological security and human health. Thus, a comprehensive investigation was conducted to assess the occurrence, removal efficiency, and ecological risk of antibiotics, along with the diversity, abundance, and co-occurrence of ARGs, and their correlations in 13 WWTPs along the Yangtze River Basin. Among 35 target antibiotics, 23 antibiotics within 6 categories were detected in all the samples. Amoxicillin (AMO), ofloxacin (OFL), and pefloxacin (PEF) were predominant in influents, while AMO exhibited dominance with the highest concentration of 1409 ng/L in effluents. Although antibiotic removal performance varied among different WWTPs, a significant decrease in each antibiotic category and overall antibiotics was observed in effluents compared with that in influents (p < 0.05). Remarkably, ecological risk assessment revealed high risks associated with AMO and ciprofloxacin (CIP) and medium risks linked to several antibiotics, notably including OFL, roxithromycin (ROX), clarithromycin (CLA), and tetracycline (TC). Furthermore, 96 ARG subtypes within 12 resistance types were detected in this study, and the total absolute abundance and diversity of ARGs were significantly decreased from influents to effluents (p < 0.05). Enrichment of 38 ARGs (e.g., blaNDM, ermA, vatA, mexA, and dfrA25) in effluents indicated potential health risks. Various mobile genetic elements (MGEs), exhibited significant correlations with a majority of ARGs in both influents and effluents, such as intⅠ1, tnpA1, tnpA5, and tp614, underscoring the important role of MGEs in contributing to the ARG dissemination. Many antibiotics displayed lower correlations with corresponding ARGs, but exhibited higher correlations with other ARGs, suggesting complex selective pressures influencing ARG propagation. Overall, the incomplete elimination of antibiotics and ARGs in WWTPs is likely to pose adverse impacts on aquatic ecosystems in the Yangtze River Basin.

Pharmacokinetic and Bioequivalence Evaluation of Dihydroxyaluminum Aminoacetate, Heavy Magnesium Carbonate, and Aspirin Tablets in Healthy Chinese Subjects in the Fasting and Postprandial Conditions.

Dihydroxyaluminum aminoacetate, heavy magnesium carbonate, and aspirin tablets is a new combined aspirin preparation, each containing aspirin (81 mg), dihydroxyaluminum aminoacetate (11 mg), and heavy magnesium carbonate (22 mg). This study was conducted to evaluate the pharmacokinetic (PK) and bioequivalence in healthy Chinese subjects. This randomized, open-label, single-dose, 2-sequence, and 2-period crossover study included 78 healthy volunteers (fasting, n = 36; postprandial, n = 42). Blood samples were collected for PK analysis. Aspirin and salicylic acid concentrations in human plasma were determined by liquid chromatography-tandem mass spectrometry. Safety and tolerability were monitored. There were no significant differences between the test and reference formulations in maximum plasma concentration, area under the plasma concentration-time curve (AUC) from time 0 to time t, or AUC from time 0 to infinity. The 90% confidence intervals of the test and reference formulations of maximum plasma concentration, AUC from time 0 to time t, and AUC from time 0 to infinity were within the acceptable range (80%-125%) under fasting and postprandial conditions. All adverse events were mild and no serious adverse events were observed in the study. Both compounds were well tolerated in healthy Chinese volunteers.

Pharmacokinetic Bioequivalence and Safety Assessment of Two Venlafaxine Hydrochloride Extended-Release Capsules in Healthy Chinese Subjects Under Fed Conditions: A Randomized, Open-Label, Single-Dose, Crossover Study.

BACKGROUND AND OBJECTIVE: Venlafaxine hydrochloride extended-release (ER) capsules are commonly used to treat depression and anxiety disorders. Evaluation of the bioequivalence of generic formulations with reference products is essential to ensure therapeutic equivalence. The objective of this study was to evaluate the bioequivalence, safety, and tolerability of Chinese-manufactured venlafaxine hydrochloride extended-release capsules compared with USA-manufactured EFFEXOR® XR in healthy Chinese volunteers under fed conditions. METHODS: A randomized, open-label, single-dose, crossover study was conducted. Subjects were randomly assigned to receive the test formulation (one 150-mg ER capsule manufactured in China) or the reference formulation (one 150-mg ER capsule manufactured in the USA). The bioequivalence of the two drugs was assessed using the area under the plasma concentration-time curve from time zero to the last sampling time (AUC0-t) and the maximum observed concentration (Cmax). RESULTS: A total of 28 subjects were enrolled and randomly assigned to receive a single dose of either the test or reference capsule. All the subjects completed the study and were included in the pharmacokinetic (PK) and safety analyses. The mean AUC0-t and Cmax of venlafaxine and its active metabolite O-desmethylvenlafaxine were comparable between the test and reference products with both parameters close to 100% and the corresponding 90% confidence intervals within the specified 80-125% bioequivalence boundary. Safety was also assessed between the two products and all adverse events (AEs) in this study were mild in severity. CONCLUSIONS: Both the test and reference venlafaxine hydrochloride ER capsules were bioequivalent and showed a similar safety and tolerability profile in the population studied. CLINICAL TRIALS REGISTRATION: This study was registered at the Drug Clinical Trial Registration and Information Publicity Platform ( http://www.chinadrugtrials.org.cn/index.html ) with registration number CTR20211243, date: June 1, 2021.