Role of intestinal flora and 5-HT in depression- and anxiety-like behaviors in mice exposed to PM2.5

BackgroundSome studies have shown that PM2.5 exposure is closely related to central nervous system diseases that lead to cognitive dysfunction and change the composition of intestinal flora. However, there are few studies on the role of intestinal flora in PM2.5-induced depression- and anxiety-like behaviors in mice. ObjectiveTo observe the effects of PM2.5 exposure on depression- and anxiety-like behaviors and the composition of intestinal flora in mice, and to explore the role of intestinal flora in regulating 5-hydroxytryptamine (5-HT) in depression- and anxiety-like behaviors in mice exposed to PM2.5. MethodsEight-week-old male SPF C57BL/6J mice were randomly divided into control group (NS group), probiotic group (LGG group), PM2.5 group (PM group), and combined exposure group (PML group), 6 mice in each group. Mice in the PM group and the PML group were exposed to PM2.5 in a dynamic exposure cabinet for 6 h per day, 6 d a week for 7 consecutive weeks, and the PM2.5 concentrations were approximately 8 times higher than the outdoor concentration. The LGG group and the PML group were orally administered with Lactobacillus rhamnosus while the NS group and the PM group were orally administered with the same amount of saline. Elevated plus maze test and open field test were used to detect depression and anxiety in mice. Fecal samples of mice were collected to evaluate intestinal flora abundance, diversity, and structure between groups using high-throughput sequencing of 16S rRNA. ELISA was employed to detect the levels of 5-HT in serum and hippocampus. Spearman correlation was used to analyze the correlations of differential intestinal flora with 5-HT level in hippocampus and depression- and anxiety-like behavior indicators in mice. ResultsThe percentage of open-arm entry [M(P25, P75)] in the PM group was 0.0% (0.0%, 33.3%), lower than those in the NS group [47.7% (25.0%, 50.8%) ] and the PML group [46.9% (40.0%, 50.0%)], and the differences were statistically significant (P<0.05). The total travelled distance and the time spent in central area (\begin{document}$\bar x \pm s$\end{document}) in the PM group were (2.01±0.90) m and (10.31±1.99) s respectively, shorter than those of the NS group [(3.80±0.89) m, (14.47±3.07) s], the total travelled distance in the PML group [(2.73±1.12) m] was shorter than those of the NS group and the LGG group [(4.21±1.08) m], and the differences were statistically significant (P<0.05). Compared to the NS group, the Simpson index of the PM group significantly increased (P<0.05). Compared to the LGG group, the Simpson index of the PML group significantly decreased (P<0.05). The results of Beta diversity analysis showed that there were differences in the composition of intestinal flora among the four groups of mice. Compared with the NS group and the LGG group, the abundances of Erysipelotrichaceae and Dubosiella in the PM group and the PML group increased, while the abundances of Prevotellaceae_UCG-001 decreased, and the differences were statistically significant (P<0.05). In hippocampus, the level of 5-HT in the PM group [(135.02±10.31) μg·g−1] was lower than those in the NS group [(178.77±43.15) μg·g−1] and the LGG group [(224.85±22.98) μg·g−1], and the level of 5-HT in the PML group [(161.27±15.81) μg·g−1] was lower than that in the LGG group (P<0.05). 5-HT level in hippocampus was significantly positively correlated with the relative abundance of Prevotellaceae_UCG-001 (r=0.6090, P=0.012). The percentage of open-arm entry was significantly negatively correlated with the relative abundance of Dubosiella (r=−0.4630, P=0.023). ConclusionAtmospheric PM2.5 exposure may cause depression- and anxiety-like behaviors in mice. The observed behavior dysfunction may be associated with the changes in diversity and relative abundance of intestinal flora as well as the decrease of 5-HT level. Such depression- and anxiety-like behaviors are alleviated after adding probiotics

Causal association of blood cell traits with inflammatory bowel diseases: a Mendelian randomization study

BackgroundObservational studies have found associations between blood cell traits and inflammatory bowel diseases (IBDs), whereas the causality and dose-effect relationships are still undetermined.MethodsTwo-sample Mendelian randomization (MR) analyses using linear regression approaches, as well as Bayesian model averaging (MR-BMA), were conducted to identify and prioritize the causal blood cell traits for Crohn’s disease (CD) and ulcerative colitis (UC). An observational study was also performed using restricted cubic spline (RCS) to explore the relationship between important blood cell traits and IBDs.ResultsOur uvMR analysis using the random effects inverse variance weighted (IVW) method identified eosinophil (EOS) as a causal factor for UC (OR = 1.36; 95% CI: 1.13, 1.63). Our MR-BMA analysis further prioritized that high level of lymphocyte (LYM) decreased CD risk (MIP = 0.307; θ^MACE = −0.059; PP = 0.189; θ^λ = −0.173), whereas high level of EOS increased UC risk (MIP = 0.824; θ^MACE = 0.198; PP = 0.627; θ^λ = 0.239). Furthermore, the observational study clearly depicts the nonlinear relationship between important blood cell traits and the risk of IBDs.ConclusionUsing MR approaches, several blood cell traits were identified as risk factors of CD and UC, which could be used as potential targets for the management of IBDs. Stratified genome-wide association studies (GWASs) based on the concentration of traits would be helpful owing to the nonlinear relationships between blood cell traits and IBDs, as demonstrated in our clinical observational study. Together, these findings could shed light on the clinical strategies applied to the management of CD and UC

Study on the Disintegration Characteristics and Mechanism of Modified Dispersive Soil Based on the C-S-H Synthesis Principle

Since dispersive soil has the characteristic of dispersing and disappearing when making contact with water, lime, fly ash, and cement are often used to modify dispersive soil in engineering. This often causes environmental pollution. Current studies tend to search for environmentally friendly modification methods. A new Ca&minus;Si-modified dispersive soil method was proposed based on the synthesis principle of calcium silicate hydrate (C-S-H). Pinhole, mud ball, dispersion, and disintegration tests were used to investigate the modification effect and physical, chemical, and microscopic tests were used to investigate the mechanism. The results show that the dispersivity of soil can be eliminated by using 0.8% CaO or 4% nanosilica. The dispersivity of Ca&minus;Si-treated soil can be eliminated at a 0.5 C/S and a 1% solid dosage. The disintegration characteristics of CaO-modified and Ca&minus;Si-modified soils are different from those of dispersive soil. The final disintegration time of CaO-modified soil was shortened, and the disintegration rate was stable. The Ca&minus;Si-modified soil had the best disintegration resistance at a 0.5 C/S and a 2% solid dosage. With the increase in the C/S, the disintegration resistance was reduced. The mechanism of Ca&minus;Si-modified soil includes reducing the pH and exchangeable sodium percentage and generating calcium silicate hydrate cement. The results show that the Ca&minus;Si treatment method based on the C-S-H synthesis principle can effectively eliminate soil dispersivity and improve disintegration resistance, which can theoretically support the reduction in contamination caused by traditional materials and improve engineering safety

Study on the Disintegration Characteristics and Mechanism of Modified Dispersive Soil Based on the C-S-H Synthesis Principle

Since dispersive soil has the characteristic of dispersing and disappearing when making contact with water, lime, fly ash, and cement are often used to modify dispersive soil in engineering. This often causes environmental pollution. Current studies tend to search for environmentally friendly modification methods. A new Ca−Si-modified dispersive soil method was proposed based on the synthesis principle of calcium silicate hydrate (C-S-H). Pinhole, mud ball, dispersion, and disintegration tests were used to investigate the modification effect and physical, chemical, and microscopic tests were used to investigate the mechanism. The results show that the dispersivity of soil can be eliminated by using 0.8% CaO or 4% nanosilica. The dispersivity of Ca−Si-treated soil can be eliminated at a 0.5 C/S and a 1% solid dosage. The disintegration characteristics of CaO-modified and Ca−Si-modified soils are different from those of dispersive soil. The final disintegration time of CaO-modified soil was shortened, and the disintegration rate was stable. The Ca−Si-modified soil had the best disintegration resistance at a 0.5 C/S and a 2% solid dosage. With the increase in the C/S, the disintegration resistance was reduced. The mechanism of Ca−Si-modified soil includes reducing the pH and exchangeable sodium percentage and generating calcium silicate hydrate cement. The results show that the Ca−Si treatment method based on the C-S-H synthesis principle can effectively eliminate soil dispersivity and improve disintegration resistance, which can theoretically support the reduction in contamination caused by traditional materials and improve engineering safety

Fluoride and arsenic exposure impairs learning and memory and decreases mGluR5 expression in the hippocampus and cortex in rats.

Fluoride and arsenic are two common inorganic contaminants in drinking water that are associated with impairment in child development and retarded intelligence. The present study was conducted to explore the effects on spatial learning, memory, glutamate levels, and group I metabotropic glutamate receptors (mGluRs) expression in the hippocampus and cortex after subchronic exposure to fluoride, arsenic, and a fluoride and arsenic combination in rats. Weaned male Sprague-Dawley rats were assigned to four groups. The control rats drank tap water. Rats in the three exposure groups drank water with sodium fluoride (120 mg/L), sodium arsenite (70 mg/L), and a sodium fluoride (120 mg/L) and sodium arsenite (70 mg/L) combination for 3 months. Spatial learning and memory was measured in Morris water maze. mGluR1 and mGluR5 mRNA and protein expression in the hippocampus and cortex was detected using RT-PCR and Western blot, respectively. Compared with controls, learning and memory ability declined in rats that were exposed to fluoride and arsenic both alone and combined. Combined fluoride and arsenic exposure did not have a more pronounced effect on spatial learning and memory compared with arsenic and fluoride exposure alone. Compared with controls, glutamate levels decreased in the hippocampus and cortex of rats exposed to fluoride and combined fluoride and arsenic, and in cortex of arsenic-exposed rats. mGluR5 mRNA and protein expressions in the hippocampus and mGluR5 protein expression in the cortex decreased in rats exposed to arsenic alone. Interestingly, compared with fluoride and arsenic exposure alone, fluoride and arsenic combination decreased mGluR5 mRNA expression in the cortex and protein expression in the hippocampus, suggesting a synergistic effect of fluoride and arsenic. These data indicate that fluoride and arsenic, either alone or combined, can decrease learning and memory ability in rats. The mechanism may be associated with changes of glutamate level and mGluR5 expression in cortex and hippocampus

Effects of PM2.5 and high-fat diet on glucose and lipid metabolisms and role of MT-COX3 methylation in male rats

Both fine particulate matter (PM2.5) and high-fat diet (HFD) can cause changes in glucose and lipid metabolisms; however, the mechanism of their combined effects on glucose and lipid metabolisms is still unclear. This study aimed to investigate the effects of PM2.5 and HFD co-exposure on glucose and lipid metabolisms and mitochondrial DNA methylation in Wistar rats. PM2.5 and HFD co-treatment led to an increase in fasting blood glucose levels, an alteration in glucose tolerance, and a decrease in high density lipoprotein cholesterol (HDL-C) levels in Wistar rats. In the homeostasis model assessment (HOMA), HOMA-insulin resistance (HOMA-IR) increased and HOMA-insulin sensitivity (HOMA-IS) and HOMA-β cell function (HOMA-β) decreased in rats co-exposed to PM2.5 and HFD. Additionally, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were increased, and interleukin-6 (IL-6) and interleukin-10 (IL-10) mRNA expressions were upregulated in the brown adipose tissue following PM2.5 and HFD co-exposure. Bisulfite pyrosequencing was used to detect the methylation levels of mitochondrially-encoded genes (MT-COX1, MT-COX2 and MT-COX3), and MT-COX3 was hypermethylated in the PM2.5 and HFD co-exposure group. Moreover, MT-COX3-Pos.2 mediated 36.41 % (95 % CI: −27.42, −0.75) of the total effect of PM2.5 and HFD exposure on HOMA-β. Our study suggests that PM2.5 and HFD co-exposure led to changes in glucose and lipid metabolisms in rats, which may be related to oxidative stress and inflammatory responses, followed by mitochondrial stress leading to MT-COX3 hypermethylation. Moreover, MT-COX3-Pos.2 was found for the first time as a mediator in the impact of co-exposure to PM2.5 and HFD on β-cell function. It could serve as a potential biomarker, offering fresh insights into the prevention and treatment of metabolic diseases

Table_1_Aggrephagy-related patterns in tumor microenvironment, prognosis, and immunotherapy for acute myeloid leukemia: a comprehensive single-cell RNA sequencing analysis.xlsx

Acute myeloid leukemia (AML) is a complex mixed entity composed of malignant tumor cells, immune cells and stromal cells, with intra-tumor and inter-tumor heterogeneity. Single-cell RNA sequencing enables a comprehensive study of the highly complex tumor microenvironment, which is conducive to exploring the evolutionary trajectory of tumor cells. Herein, we carried out comprehensive analyses of aggrephagy-related cell clusters based on single-cell sequencing for patients with acute myeloid leukemia. A total of 11 specific cell types (T, NK, CMP, Myeloid, GMP, MEP, Promono, Plasma, HSC, B, and Erythroid cells) using t-SNE dimension reduction analysis. Several aggrephagy-related genes were highly expressed in the 11 specific cell types. Using Monocle analysis and NMF clustering analysis, six aggrephagy-related CD8+ T clusters, six aggrephagy-related NK clusters, and six aggrephagy-related Mac clusters were identified. We also evaluated the ligand-receptor links and Cell–cell communication using CellChat package and CellChatDB database. Furthermore, the transcription factors (TFs) of aggrephagy-mediated cell clusters for AML were assessed through pySCENIC package. Prognostic analysis of the aggrephagy-related cell clusters based on R package revealed the differences in prognosis of aggrephagy-mediated cell clusters. Immunotherapy of the aggrephagy-related cell clusters was investigated using TIDE algorithm and public immunotherapy cohorts. Our study revealed the significance of aggrephagy-related patterns in tumor microenvironment, prognosis, and immunotherapy for AML.</p

Image_1_Aggrephagy-related patterns in tumor microenvironment, prognosis, and immunotherapy for acute myeloid leukemia: a comprehensive single-cell RNA sequencing analysis.docx

Acute myeloid leukemia (AML) is a complex mixed entity composed of malignant tumor cells, immune cells and stromal cells, with intra-tumor and inter-tumor heterogeneity. Single-cell RNA sequencing enables a comprehensive study of the highly complex tumor microenvironment, which is conducive to exploring the evolutionary trajectory of tumor cells. Herein, we carried out comprehensive analyses of aggrephagy-related cell clusters based on single-cell sequencing for patients with acute myeloid leukemia. A total of 11 specific cell types (T, NK, CMP, Myeloid, GMP, MEP, Promono, Plasma, HSC, B, and Erythroid cells) using t-SNE dimension reduction analysis. Several aggrephagy-related genes were highly expressed in the 11 specific cell types. Using Monocle analysis and NMF clustering analysis, six aggrephagy-related CD8+ T clusters, six aggrephagy-related NK clusters, and six aggrephagy-related Mac clusters were identified. We also evaluated the ligand-receptor links and Cell–cell communication using CellChat package and CellChatDB database. Furthermore, the transcription factors (TFs) of aggrephagy-mediated cell clusters for AML were assessed through pySCENIC package. Prognostic analysis of the aggrephagy-related cell clusters based on R package revealed the differences in prognosis of aggrephagy-mediated cell clusters. Immunotherapy of the aggrephagy-related cell clusters was investigated using TIDE algorithm and public immunotherapy cohorts. Our study revealed the significance of aggrephagy-related patterns in tumor microenvironment, prognosis, and immunotherapy for AML.</p

Trends in Research on Forest Ecosystem Services in the Most Recent 20 Years: A Bibliometric Analysis

Forest resources and the flow of ecosystem services they provide play a key role in supporting national and regional economies, improving people&rsquo;s lives, protecting biodiversity, and mitigating the impacts of climate change. Based on the ISI (Institute of Scientific Information) Web of Science (WoS) database, we used a bibliometric approach to analyze the research status, evolution process, and hotspots of forest ecosystem services (FES) from a compilation of 8797 documents published between 1997 and 2019. The results indicated that: (1) research on forest ecosystem services has developed rapidly over the past 23 years. Institutions in the United States and other developed countries have significantly contributed to undertake research on the topic of ecosystem services. (2) The 11 hotpot key focus areas of completed research were payments for ecosystem services, biodiversity conservation, forest governance, ecosystem approaches, climate change, nitrogen, ecosystem management, pollination, cities, ecological restoration, and policy. (3) The trade-off relationships among ecosystem services, ecosystem resilience and stability have become the research frontier in this field. (4) Future research on FES will likely focus on the formation and evolution mechanism of ecosystem services; the interaction, feedback and intrinsic connections of ecosystem services at different scales; analysis of the trade-offs and synergies; unified evaluation standards, evaluation systems, model construction and scenario analyses; in-depth studies of the internal correlation mechanism between forest ecosystem services and human wellbeing; and realization of cross-disciplinary and multi-method integration in sustainable forest management and decision-making