Autism Spectrum Disorder (ASD) is a severe neurodevelopmental disorder. To enhance the understanding of the gut microbiota structure in ASD children at different ages as well as the relationship ...between gut microbiota and fecal metabolites, we first used the 16S rRNA sequencing to evaluate the gut microbial population in a cohort of 143 children aged 2-13 years old. We found that the α-diversity of ASD group showed no significant change with age, while the TD group showed increased α-diversity with age, which indicates that the compositional development of the gut microbiota in ASD varies at different ages in ways that are not consistent with TD group. Recent studies have shown that chronic constipation is one of the most commonly obvious gastrointestinal (GI) symptoms along with ASD core symptoms. To further investigate the potential interaction effects between ASD and GI symptoms, the 30 C-ASD and their aged-matched TD were picked out to perform metagenomics analysis. We observed that C-ASD group displayed decreased diversity, depletion of species of Sutterella, Prevotella, and Bacteroides as well as dysregulation of associated metabolism activities, which may involve in the pathogenesis of C-ASD. Consistent with metagenomic analysis, liquid chromatography-mass spectrometry (LC/MS) revealed some of the differential metabolites between C-ASD and TD group were involved in the metabolic network of neurotransmitters including serotonin, dopamine, histidine, and GABA. Furthermore, we found these differences in metabolites were associated with altered abundance of specific bacteria. The study suggested possible future modalities for ASD intervention through targeting the specific bacteria associated with neurotransmitter metabolism.
Extensive changes of circRNA expression underscore their essential contributions to multiple hallmarks of cancers; however, their functions and mechanisms of action in esophageal squamous cell ...carcinoma (ESCC) remain undetermined. Here, we adopted a three-stage approach by first screening for significantly differentially expressed circRNAs in ESCC and performing an external validation study, followed by the functional analyses. The properties of circRNAs were evaluated using Sanger sequencing, RNase R digestion, actinomycin D treatment, subcellular localization analysis, and fluorescence in situ hybridization. Target transcripts were predicted using online tools and verified by dual-luciferase, RNA immunoprecipitation, qRT-PCR, and western blot. Biotin-labeled RNA-protein pull-down, mass spectrometry, and RNA immunoprecipitation were employed to identify proteins interacting with circRNAs. Gain- and loss-of-function experiments were performed to uncover the roles of circRNAs, their target genes, and binding proteins in the proliferation, metastasis, and invasion. We observed that circFAM120B (hsa_circ_0001666) was frequently downregulated in cancer tissues and patient plasma, and its expression level was related to overall survival in ESCC patients. Overexpression of circFAM120B inhibited the proliferation, metastasis, and invasion of ESCC while silencing it enhanced malignant phenotypes. Mechanistically, circFAM120B was predominantly located in the cytoplasm, guarantying its sponging for miR-661 to restore the expression of PPM1L, a tumor suppressor. We observed that circFAM120B could reduce the stability of RNA-dependent protein kinase (PKR) by promoting its ubiquitination-dependent degradation and subsequently regulating the p38 MAPK signaling pathway, resulting in the repression of EMTs in ESCC cells. Our findings suggest that circFAM120B is a promising biomarker of ESCC, which acts as a tumor suppressor via the circFAM120B/miR-661/PPM1L axis and PKR/p38 MAPK/EMT pathway, supporting its significance as a candidate therapeutic target.
The onset of hepatocellular carcinoma (HCC) ranked fifth malignancies all over the world. Increasing evidences showed that the distribution of HCC was related to the incidence of chronic hepatitis B ...virus (HBV) infection and other factors, such as alcoholism, aflatoxin B1 ingestion and obesity. Recent studies demonstrated that gut dysbiosis plays an important role in liver diseases. However, the researches on gut microbiota of HBV and non-HBV non-HCV related HCC have not been reported. In this study, we investigated the differences between the gut microbiota of HBV related HCC (B-HCC) and non-HBV non-HCV related HCC (NBNC-HCC), finally found some potential bacteria, linking different pathological mechanism of both types of HCCs.
We carried out 16S rRNA analyses in a cohort of 33 healthy controls, 35 individuals with HBV related HCC (B-HCC) and 22 individuals with non-HBV non-HCV (NBNC) related HCC (NBNC-HCC). We found that the species richness of fecal microbiota of B-HCC patients was much higher than other two groups. Interestingly, the feces of NBNC-HCC patients harbored more potential pro-inflammatory bacteria (
-
,
) and reduced levels of
,
,
which results in decrease potential of anti-inflammatory short-chain fatty acids. The feces of NBNC-HCC patients had relatively fewer abundance of multiple biological pathways related to amino acid and glucose metabolism, but high level of transport and secretion in some types. However, the B-HCC patients had opposite results of bacterial composition and associated multiple biological pathways versus NBNC-HCC patients. Meanwhile, we found that aberrant network of gut microbiota occurred differently in B-HCC and NBNC-HCC patients.
Our study indicated that B-HCC and NBNC-HCC patients showed differential abundance of bacteria involved in different functions or biological pathways. We suggested the modification of specific gut microbiota may provide the therapeutic benefit for B-HCC and NBNC-HCC.
Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been rapidly developed and widely used as an analytical technique in clinical laboratories with high ...accuracy in microorganism identification.
To validate the efficacy of MALDI-TOF MS in identification of clinical pathogenic anaerobes.
Twenty-eight studies covering 6685 strains of anaerobic bacteria were included in this meta-analysis. Fixed-effects models based on the P-value and the I-squared were used for meta-analysis to consider the possibility of heterogeneity between studies. Statistical analyses were performed by using STATA 12.0.
The identification accuracy of MALDI-TOF MS was 84% for species (I
= 98.0%, P < 0.1), and 92% for genus (I
= 96.6%, P < 0.1). Thereinto, the identification accuracy of Bacteroides was the highest at 96% with a 95% CI of 95-97%, followed by Lactobacillus spp., Parabacteroides spp., Clostridium spp., Propionibacterium spp., Prevotella spp., Veillonella spp. and Peptostreptococcus spp., and their correct identification rates were all above 90%, while the accuracy of rare anaerobic bacteria was relatively low. Meanwhile, the overall capabilities of two MALDI-TOF MS systems were different. The identification accuracy rate was 90% for VITEK MS vs. 86% for MALDI biotyper system.
Our research showed that MALDI-TOF-MS was satisfactory in genus identification of clinical pathogenic anaerobic bacteria. However, this method still suffers from different drawbacks in precise identification of rare anaerobe and species levels of common anaerobic bacteria.
•Exposure to ambient PM2.5, PM10, SO2, and NO2 contributes to an increased risk of active tuberculosis.•The effect of ambient air PM10 and NO2 in the risk of tuberculosis remains significant in the ...multi-pollutant models.•This is the first DLNM-based time-series study exploring the long-term effect of ambient air pollution on the risk of tuberculosis.•Reducing the concentration of ambient air pollutants is likely to bring about health benefits in tuberculosis-endemic areas.
To explore the long-term effect of exposure to ambient air pollution on the risk of active tuberculosis (TB).
We constructed a distributed-lag nonlinear model (DLNM) to evaluate the relatively long-term influence of outdoor PM2.5, PM10, SO2 and NO2 exposure on active TB risk in the city of Lianyungang in Jiangsu Province, China.
There were 7,282 TB cases reported in the study area during 2014–2017, with annual median (interquartile range) concentrations of PM2.5, PM10, SO2 and NO2 at 45.86 (34.57–64.14) μg/m3, 85.43 (62.86–116.14) μg/m3, 22.00 (15.71–30.86) μg/m3 and 30.00 (23.29–38.57) μg/m3, respectively. The single-pollutant model showed that for each 10 μg/m3 increase in concentration, the cumulative relative risk of TB was 1.12 (lag 0–24 weeks, 95% CI: 1.03–1.22) for PM2.5 with reference to 35 μg/m3; 1.11 (lag 0–21 weeks, 95% CI: 1.06–1.17) for PM10 with reference to 70 μg/m3; 1.37 (lag 0–20 weeks, 95% CI: 1.16–1.62) for SO2 with reference to 60 μg/m3; and 1.29 (lag 0–22 weeks, 95% CI: 1.11–1.49) for NO2 with reference to 40 μg/m3. In the multipollutant model considering both PM10 and NO2, the association remained significant.
Our results revealed a potential association between outdoor exposure to PM2.5, PM10, SO2, and NO2 and active TB. Considering that people from developing countries continue to be exposed to both severe outdoor air pollution and high rates of latent TB infection, the association between worsening air pollution and active TB deserves further attention.
The kynurenine pathway (KP) is abnormal in autistic patients and model animals. According to studies on the brain-gut axis, probiotics can help ameliorate the metabolic abnormalities of the KP in ...patients and model animals with neurological diseases. This study was aimed at evaluating the ability of
(
) CCFM077 to enhance the gut microbiome and KP metabolism and regulate the neurotransmitter levels and neuroinflammation of autistic rats. The KP metabolism of autistic rats was significantly disordered and significantly related to the regulation of neurotransmitter (excitation and inhibition) and neuroglia states.
CCFM1077 could effectively alleviate autistic-like behaviours (repetitive stereotyped behaviour, learning and memory ability, and despair mood) and regulate the KP metabolism in the periphery system (gut and blood) and brain. In particular,
CCFM1077 could significant regulate the quinolinic acid (QUIN) level in the brain and markedly regulate glutamic acid (Glu) and Glu/γ-aminobutyric acid (GABA) levels in the brain while alleviating microglia activity in the cerebellum. Through a correlation analysis, the QUIN level in the brain was strongly related with autistic-like behaviours and neurotransmitter levels (GABA and Glu). The QUIN level may thus be a potential therapeutic marker for treating autism through the intestinal and neural pathways.
Epitranscriptome studies have shown that critical RNA modifications drive tumorigenicity; however, the role of 5-methylcytosine (m
5
C) RNA methylation remains poorly understood. We extracted 17 m
5
...C regulators and clustered distinct m
5
C modification patterns by consensus clustering analysis. Gene set variation and single-sample gene set enrichment analysis were applied to quantify functional analysis and immune infiltration. The least absolute shrinkage and selection operator was employed to develop a prognostic risk score. Kaplan-Meier with log-rank test was used for survival analysis. Differential expression analysis was performed with the "limma" R package. Wilcoxon signed ranked test or Kruskal-Wallis test was used to compare groups. We observed that m
5
C RNA methylation was commonly upregulated in gastrointestinal cancer and related to prognosis. Clusters were identified for m
5
C patterns, with distinct immune infiltrations and functional pathways. The risk scores of m
5
C regulators were independent risk factors. Differentially expressed mRNAs (DEmRNAs) in m
5
C clusters were involved in cancer-related pathways. The methylation-based m
5
Cscore showed a significant effect on the prognosis. Patients with a lower m
5
Cscore exhibited more therapeutic efficiency on anti-CTLA4 therapy in liver cancer, while the combination of anti-CTLA4 therapy and pd1 was more efficient for patients with a lower m
5
Cscore in pancreatic cancer. We uncovered dysregulations of m
5
C-related regulators in gastrointestinal cancer and their associations with overall survival. Some immune cells were differently infiltrated in distinct m
5
C modification patterns, indicating their potential impacts on gastrointestinal cancer cell-immune. Moreover, an m
5
Cscore, derived from DEmRNAs in specific clusters, can serve as a classifier for immunotherapy.
The purpose of this study is to evaluate the prevalence, awareness, treatment and glycemic control of diabetes mellitus (DM) in a Chinese population. The findings from this study are expected to ...offer scientific evidence to better prevent and control the growing number of reported and untreated cases.
A cross-sectional survey was conducted in Jiangsu, China. We recruited permanent residents over 18 years of age from eight towns in Jintan (JT) and six towns in Yangzhong (YZ) using a three-stage stratified cluster sampling method. The rates of DM prevalence, awareness, treatment and control as well as their related factors were analyzed.
A total number of 15,404 people were entered into the analysis. The DM prevalence, awareness, treatment and control rates were 7.31%, 58.35%, 51.87% and 14.12%, respectively. Multivariable logistic regression analysis showed that being female was positively related to prevalence (OR=1.21, 95% CI: 1.07-1.37), awareness (OR=1.52, 95% CI: 1.19-1.93), treatment (OR=1.48, 95% CI: 1.17-1.88) and control (OR=1.87, 95% CI: 1.30-2.67) of DM. Having a family history of diabetes was significantly correlated with DM risk (OR=1.86, 95% CI: 1.37-2.54) and increased awareness (OR=3.12, 95% CI: 2.19-4.47), treatment (OR=3.47, 95% CI: 2.45-4.90) and control (OR=1.81, 95% CI: 1.22-2.68) of DM. Former smoking status (OR=1.82, 95% CI: 1.23-2.71), overweight (OR=2.11, 95% CI: 1.72-2.60) and obesity (OR=3.46, 95% CI: 2.67-4.50) were related to the risk of DM. Additionally, we found current drinking status to be positively correlated with DM risk (OR=1.30, 95% CI: 1.01-1.66) and negatively correlated with DM awareness (OR=0.41, 95% CI: 0.29-0.59) and treatment (OR=0.41, 95% CI: 0.29-0.59). Our study highlights the high prevalence and inadequate awareness, treatment and control of DM in the Chinese population.
Management and prevention of DM-related complications should be considered an essential strategy by governments and society. This study assessed the reasons why DM has been increasing and established the first step in determining where to start regarding preventative methods.
Abstract
Globally, air pollution is amongst the most significant causes of premature death. Nevertheless, studies on the relationship between fine particulate matter (PM
2.5
) exposure and blood ...lipids have typically not been population-based. In a large, community-based sample of residents in Yixing city, we assessed the relationship between short-term outdoor PM
2.5
exposure and blood lipid concentrations. Participants who attended the physical examination were enrolled from Yixing People’s hospital from 2015 to 2020. We collected general characteristics of participants, including gender and age, as well as test results of indicators of blood lipids. Data on daily meteorological factors were collected from the National Meteorological Data Sharing Center (
http://data.cma.cn/
) and air pollutant concentrations were collected from the China Air Quality Online Monitoring and Analysis Platform (
https://www.aqistudy.cn/
) during this period. We applied generalized additive models to estimate short-term effects of ambient PM
2.5
exposure on each measured blood lipid-related indicators and converted these indicators into dichotomous variables (non- hyperlipidemia and hyperlipidemia) to calculate risks of hyperlipidemia associated with PM
2.5
exposure. A total of 197,957 participants were included in the analysis with mean age 47.90 years (± SD, 14.28). The increase in PM
2.5
was significantly associated with hyperlipidemia (odds ratio (OR) 1.003, 95% CI 1.001–1.004), and it was still significant in subgroups of males and age < 60 years. For every 10 μg/m
3
increase in PM
2.5
, triglyceride levels decreased by 0.5447% (95% CI − 0.7873, − 0.3015), the low-density lipoprotein cholesterol concentration increased by 0.0127 mmol/L (95% CI 0.0099, 0.0156), the total cholesterol concentration increased by 0.0095 mmol/L (95% CI 0.0053, 0.0136), and no significant association was observed between PM
2.5
and the high-density lipoprotein cholesterol concentration. After excluding people with abnormal blood lipid concentrations, the associations remained significant except for the high-density lipoprotein cholesterol concentration. PM
2.5
was positively correlated with low-density lipoprotein cholesterol and total cholesterol, and negatively correlated with triglyceride, indicating PM
2.5
can potentially affect health through blood lipid levels.
Psychobiotics, a newly identified category of probiotics primarily targeting the gut–brain axis, exhibit tremendous potential in improving sleep quality. In this study, the clinical trial was ...registered in advance (identifier: NO. ChiCTR2300067806). Forty participants who were diagnosed with stress-induced insomnia were chosen and randomly divided into two groups: one received CCFM1025 at a dose of 5 × 109 CFU (n = 20), while the other was administered a placebo (n = 20), over a period of four weeks. The results revealed that compared to the placebo group (pre: M = 10.10, SD = 2.292; post: M = 8.650, SD = 2.793; pre vs. post: F (1, 38) = 15.41, p = 0.4316), the CCFM1025-treated group exhibited a significant decrease in Pittsburgh Sleep Quality Index (PSQI) scores from baseline (pre: M = 11.60, SD = 3.169; post: M = 7.750, SD = 3.697, F (1, 38) = 15.41, p = 0.0007). Furthermore, the administration of CCFM1025 was associated with a more pronounced reduction in stress marker concentrations. This effect could potentially be linked to changes in serum metabolites induced by the probiotic treatment, notably daidzein. In conclusion, B. breve CCFM1025 demonstrates promise as a psychobiotic strain for enhancing sleep quality.
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