Down-regulating nuclear factor of activated T cells 1 alleviates cognitive deficits in a mouse model of sepsis-associated encephalopathy, possibly by stimulating hippocampal neurogenesis.

Sepsis-associated encephalopathy (SAE) is a common complication of sepsis, and has been associated with increased morbidity and mortality. Nuclear factor of activated T cells (NFATs) 1, a transcriptional factor that regulates T cell development, activation and differentiation, has been implicated in neuronal plasticity. Here we examined the potential role of NFAT1 in sepsis-associated encephalopathy in mice. Adult male C57BL/6J mice received intracerebroventricular injections of short interfering RNA against NFAT1 or sex-determining region Y-box 2 (SOX2), or a scrambled control siRNA prior to cecal ligation and perforation (CLP). A group of mice receiving sham surgery were included as an additional control. CLP increased escape latency and decreased the number of crossings into, and total time spent within, the target quadrant in the Morris water maze test. CLP also decreased the freezing time in context-dependent, but not context-independent, fear conditioning test. Knockdown of either NFAT1 or SOX2 attenuated these behavioral deficits. NFAT1 knockdown also attenuated CLP-induced upregulation of SOX2, increased the numbers of nestin-positive cells and newborn astrocytes, reduced the number of immature newborn neurons, and promoted the G1 to S transition of neural stem cells in hippocampus. These findings suggest that NFAT1 may contribute to sepsis-induced behavioral deficits, possibly by promoting SOX2 signaling and neurogenesis.

Effects of intrauterine and post-natal exposure to air pollution on children's pneumonia: Key roles in different particulate matters exposure during critical time windows.

BACKGROUND: Despite mounting evidence linked pneumonia with air pollution, it is unclear what main pollutant(s) exposure in which critical window(s) play a key role in pneumonia. OBJECTIVE: To examine effects of intrauterine and post-natal exposure to air pollution on children's doctor-diagnosed pneumonia (DDP). METHODS: A combination of cross-sectional and retrospective cohort study was conducted at Changsha, China during 2019-2020. Personal exposure to outdoor air pollutants at each child's home address was estimated using inverse distance weighted (IDW) method based on data from 10 air quality monitoring stations. Associations between personal air pollution exposure and DDP were evaluated. RESULTS: Children's DDP was associated with intrauterine and post-natal exposure to PM2.5, PM2.5-10, and PM10, adjusted ORs (95% CI) of 1.17 (1.04-1.30), 1.09 (1.01-1.17), and 1.07 (1.00-1.14) for IQR increase in intrauterine exposure and 1.12 (1.02-1.22), 1.13 (1.06-1.21), and 1.28 (1.16-1.41) for post-natal exposure. Intrauterine PM2.5 exposure and post-natal PM10 exposure were associated with a higher risk of pneumonia. We identified the 2nd trimester, 3rd trimester, and first year as critical windows respectively for PM2.5, PM2.5-10, and PM10 exposure. Daytime exposure to traffic-related air pollution especially during early life increased DDP. CONCLUSION: Intrauterine and post-natal exposure to particulate matters played a dominant role in children's DDP.

[Phosphate and tension homology-induced kinase 1/Parkin signaling mediates cognitive dysfunction in sepsis-associated encephalopathy through activation of hippocampal mitochondrial autophagy].

OBJECTIVE: To investigate the effects of gene of phosphate and tension homology (PTEN)-induced putative kinase 1 (PINK1)/Parkin pathway on hippocampal mitophagy and cognitive function in mice with sepsis-associated encephalopathy (SAE) and its possible mechanism. METHODS: A total of 80 male C57BL/6J mice were randomly divided into Sham group, cecal ligation puncture (CLP) group, PINK1 plasmid transfection pretreatment groups (p-PINK1+Sham group, p-PINK1+CLP group), empty vector plasmid transfection control group (p-vector+CLP group), with 16 mice in each group. The mice in CLP groups were treated with CLP to reproduce SAE models. The mice in the Sham groups were performed laparotomy only. Animals in the p-PINK1+Sham and p-PINK1+CLP groups were transfected with PINK1 plasmid through the lateral ventricle at 24 hours before surgery, while mice in the p-vector+CLP group were transfected with the empty plasmid. Morris water maze experiment was performed 7 days after CLP. The hippocampal tissues were collected, the pathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining, and the mitochondrial autophagy was observed under a transmission electron microscopy after uranyl acetate and lead citrate staining. The expressions of PINK1, Parkin, Beclin1, interleukins (IL-6, IL-1ß) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blotting. RESULTS: Compared with the Sham group, CLP group mice in Morris water maze experiment had longer escape latency, shorter target quadrant residence time, and fewer times of crossing the platform at 1-4 days. Under the light microscope, the hippocampal structure of the mouse was injured, the neuronal cells were arranged in disorder, and the nuclei were pyknotic. Under the electron microscope, the mitochondria appeared swollen, round, and wrapped by bilayer or multilayer membrane structures. Compared with the Sham group, CLP group had higher expressions of PINK1, Parkin, Beclin1, LC3II/LC3I ratio, IL-6 and IL-1ß in hippocampus, indicating that sepsis induced by CLP could activated inflammatory response and caused PINK1/Parkin-mediated mitophagy. Compared with the CLP group, p-PINK1+CLP group had shorter escape latencies, spent more time in the target quadrant and had more number of crossings in the target quadrant at 1-4 days. Under the light microscope, the hippocampal structures of mice was destroyed, the neurons were arranged disorderly, and the nuclei were pyknotic. Under transmission electron microscope, swollen and rounded mitochondria and mitochondrial structure wrapped by double membrane or multilayer membrane structure were observed. Compared with the CLP group, the levels of PINK1, Parkin, Beclin1 and LC3II/LC3 ratio in the p-PINK1+CLP group were significantly increased [PINK1 protein (PINK1/ß-actin): 1.95±0.17 vs. 1.74±0.15, Parkin protein (Parkin/ß-actin): 2.06±0.11 vs. 1.78±0.12, Beclin1 protein (Beclin1/ß-actin): 2.11±0.12 vs. 1.67±0.10, LC3II/LC3I ratio: 3.63±0.12 vs. 2.27±0.10, all P < 0.05], while the levels of IL-6 and IL-1ß were significantly decreased [IL-6 protein (IL-6/ß-actin): 1.69±0.09 vs. 2.00±0.11, IL-1ß protein (IL-1ß/ß-actin): 1.11±0.12 vs. 1.65±0.12, both P < 0.05], suggesting that overexpression of PINK1 protein could further activate mitophagy and reduce the inflammatory response caused by sepsis. There was no statistically significant difference in the above pathological changes and related indicators between Sham group and p-PINK1+Sham group, CLP group and p-vector+CLP group. CONCLUSIONS: PINK1 overexpression can further activate CLP-induced mitophagy by upregulating Parkin, thereby inhibiting inflammation response and alleviate cognitive function impairment in SAE mice.

Intrauterine and early postnatal exposure to air pollution associated with childhood allergic rhinitis.

BACKGROUND: Despite mounting evidence linking allergic rhinitis (AR) to air pollution, it remains unclear which major air pollutant(s) and critical window(s) of exposure play important roles in children's AR. OBJECTIVE: To examine the effects of intrauterine and early postnatal exposure to outdoor air pollution on children with doctor-diagnosed allergic rhinitis (DDAR). METHODS: A retrospective cohort study involving 8689 kindergarten children was conducted in Changsha, China, from 2019 to 2020. A questionnaire survey was conducted to collect information on the health status of children and their family members, as well as their living habits and home environment. Personal exposure to daily outdoor air pollutants (PM2.5, PM2.5-10, PM10, SO2, NO2, and CO) was estimated during 40 gestational weeks, three trimesters, the entire pregnancy, and the first year after birth. Multiple logistic regression models were used to assess the associations between air pollution and children's DDAR. RESULTS: Children's DDAR was associated with intrauterine CO exposure, with adjusted ORs (95% CI) of 1.18 (1.03-1.34) for each IQR increase in CO exposure. The second and third trimesters were critical windows for PM2.5 and CO exposure in relation to DDAR. Furthermore, early postnatal exposure to PM2.5-10 and PM10 in first year of life was associated with DDAR development, with adjusted ORs (95% CI) of 1.11 (1.01-1.22) and 1.27 (1.09, 1.47). The entire pregnancy and the first year of life were critical windows for CO and PM10 exposure. Some children were predisposed to DDAR risk due to exposure to traffic-related air pollution (TRAP). CONCLUSION: Our findings support the hypothesis of "fetal origin of allergic rhinitis" by demonstrating that intrauterine and early postnatal exposure to air pollution plays an important role in children's DDAR.

Interaction of high temperature and NO2 exposure on asthma risk: In vivo experimental evidence of inflammation and oxidative stress.

Allergic asthma is a complicated respiratory disease with many concerns. Mounting epidemiological evidence linked temperature (T) and NO2 with allergic asthma, yet toxicological studies remain scarce. We conducted an in vivo study to explore toxicological evidence in T-NO2 interaction on allergic asthma, to investigate underlying toxicological mechanisms. 90 male Balb/c mice were randomly and equally divided into 6 groups including saline control, ovalbumin (OVA)-sensitized, OVA + 35 °C, OVA + NO2, OVA + 35 °C + NO2, and OVA + 35 °C + NO2 + capsazepine (CZP), adopting treatment for 38 days. We measured pulmonary functions of inspiratory resistance (Ri), expiratory resistance (Re) and airway compliance (Cldyn), serum protein biomarkers, indexes of pulmonary inflammation, histopathological changes and protective effects of CZP. Airway hyperresponsiveness (AHR) was aggravated by high T (35 °C) and NO2 (5 ppm) co-exposure with a series of aggravating asthmatic symptoms including airway wall thickening, lumen stenosis, goblet cell proliferation, mucus hypersecretion, and subepithelial fibrotic hyperplasia, providing evidence in the toxicological impact of high T-NO2 interaction. The biomarkers of serum immune functions (Total-IgE, OVA-sIgE and IL-4), pro-inflammation (IL-6 and TNF-α), oxidative stress cytokines (8-OHdG, ROS and MDA), airway resistance (Ri and Re), and TRPV1 expression significantly increased, while IFN-γ, GSH and airway compliance (Cldyn) significantly decreased with co-exposure to high T and NO2. We observed that CZP addition significantly ameliorated these toxicological effects and biomarker levels induced by heat-NO2 interaction. Our results suggest a toxicity of heat-NO2 interaction on asthma with clear mechanisms, which can be ameliorated by CZP, indicating that both oxidative stress and TRPV1 expression may be primarily responsible for asthma of heat-NO2-induced toxicity.

Effects of short-term and long-term exposure to ambient air pollution and temperature on long recovery duration in COVID-19 patients.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has spread rapidly around the world since December 8, 2019. However, the key factors affecting the duration of recovery from COVID-19 remain unclear. OBJECTIVE: To investigate the associations of long recovery duration of COVID-19 patients with ambient air pollution, temperature, and diurnal temperature range (DTR) exposure. METHODS: A total of 427 confirmed cases in Changsha during the first wave of the epidemic in January 2020 were selected. We used inverse distance weighting (IDW) method to estimate personal exposure to seven ambient air pollutants (PM2.5, PM2.5-10, PM10, SO2, NO2, CO, and O3) at each subject's home address. Meteorological conditions included temperature and DTR. Multiple logistic regression model was used to investigate the relationship of air pollution exposure during short-term (past week and past month) and long-term (past three months) with recovery duration among COVID-19 patients. RESULTS: We found that long recovery duration among COVID-19 patients was positively associated with short-term exposure to CO during past week with OR (95% CI) = 1.42 (1.01-2.00) and PM2.5, NO2, and CO during past month with ORs (95% CI) = 2.00 (1.30-3.07) and 1.95 (1.30-2.93), and was negatively related with short-term exposure to O3 during past week and past month with ORs (95% CI) = 0.68 (0.46-0.99) and 0.41 (0.27-0.62), respectively. No association was observed for long-term exposure to air pollution during past three months. Furthermore, increased temperature during past three months elevated risk of long recovery duration in VOCID-19 patients, while DTR exposure during past week and past month decreased the risk. Male and younger patients were more susceptible to the effect of air pollution on long recovery duration, while female and older patients were more affected by exposure to temperature and DTR. CONCLUSION: Our findings suggest that both TRAP exposure and temperature indicators play important roles in prolonged recovery among COVID-19 patients, especially for the sensitive populations, which provide potential strategies for effective reduction and early prevention of long recovery duration of COVID-19.

Combined effect of preconceptional and prenatal exposure to air pollution and temperature on childhood pneumonia: A case-control study.

Mounting evidence have linked ambient air pollution and temperature with childhood pneumonia, but it is unclear whether there is an interaction between air pollution and temperature on childhood pneumonia. We aim to assess the combined effect of ambient air pollution and temperature exposure during preconception and pregnancy on pneumonia by a case-control study of 1510 children aged 0-14 years in Changsha, China. We obtained the data of childhood pneumonia from XiangYa Hospital electrical records. We estimated personal exposure to outdoor air pollution (PM10, SO2 and NO2) by inverse distance weighted (IDW) method and temperature indicators. Multiple logistic regression models were used to evaluate associations of childhood pneumonia with air pollution, temperature (T), and diurnal temperature variation (DTV). We found that exposure to industry-related air pollution (PM10 and SO2) during preconception and pregnancy were associated with childhood pneumonia, with ORs (95% CI) of 1.72 (1.48-1.98) and 2.96 (2.50-3.51) during 1 year before pregnancy and 1.83 (1.59-2.11) and 3.43 (2.83-4.17) in pregnancy. Childhood pneumonia was negatively associated with T exposure during 1 year before pregnancy and pregnancy, with ORs (95% CI) of 0.57 (0.41-0.80) and 0.85 (0.74-0.98). DTV exposure during pregnancy especially during the 1st and 2nd trimesters significantly increased pneumonia risk, with ORS (95% CI) of 1.77 (1.19-2.64), 1.47 (1.18-1.83), and 1.37 (1.07-1.76) respectively. We further observed interactions of PM10 and SO2 exposure with low T and high DTV during conception and pregnancy in relation to childhood pneumonia. This study suggests that there were interactions air pollution with temperature and DTV on pneumonia development.

Early life exposure to outdoor air pollution and indoor environmental factors on the development of childhood allergy from early symptoms to diseases.

BACKGROUND: The prevalence of childhood allergies has increased during past decades leading to serious hospitalization and heavy burden worldwide, yet the key factors responsible for the onset of early symptoms and development of diagnosed diseases are unclear. OBJECTIVE: To explore the role of early life exposure to ambient air pollution and indoor environmental factors on early allergic symptoms and doctor diagnosed allergic diseases. METHODS: A retrospective cohort study of 2598 preschool children was conducted at 36 kindergartens in Changsha, China from September of 2011 to February of 2012. A questionnaire was developed to survey each child's early onset of allergic symptoms (wheeze and rhinitis-like symptoms) and doctor diagnosis of allergic diseases (asthma and rhinitis) as well as home environments. Each mother's and child's exposures to ambient air pollutants (PM10, SO2, and NO2) and temperature were estimated for in utero and postnatal periods. The associations of early symptoms and diagnosed diseases with outdoor air pollution and indoor environmental variables were examined by logistic regression models. RESULTS: Childhood early allergic symptoms (33.9%) including wheeze (14.7%) and rhinitis-like symptoms (25.4%) before 2 years old were not associated with outdoor air pollution exposure but was significantly associated with maternal exposure of window condensation at home in pregnancy with ORs (95% CI) of 1.33 (1.11-1.59), 1.30 (1.01-1.67) and 1.27 (1.04-1.55) respectively, and was associated with new furniture during first year after birth with OR (95% CI) of 1.43 (1.02-2.02) for early wheeze. Childhood diagnosed allergic diseases (28.4%) containing asthma (6.7%) and allergic rhinitis (AR) (7.2%) were significantly associated with both outdoor air pollutants (mainly for SO2 and NO2) during first 3 years and indoor new furniture, redecoration, and window condensation. We found that sex, age, parental atopy, maternal productive age, environmental tobacco smoke (ETS), antibiotics use, economic stress, early and late introduction of complementary foods, and outdoor air pollution modified the effects of home environmental exposure in early life on early allergic symptoms and diagnosed allergic diseases. CONCLUSION: Our study indicates that early life exposure to indoor environmental factors plays a key role in early onset of allergic symptoms in children, and further exposure to ambient air pollution and indoor environmental factors contribute to the later development of asthma and allergic rhinitis.

Disrupted metabolic and spontaneous neuronal activity of hippocampus in sepsis associated encephalopathy rats: A study combining magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging.

Background: The diagnosis of sepsis associated encephalopathy (SAE) remains challenging in clinical settings because of a lack of specific biomarkers. Functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1H-MRS) can be used to aid in the diagnosis of cognition related diseases. This study investigated changes in functional activities and brain metabolites in the hippocampus in SAE rats by fMRI and 1H-MRS. Materials and methods: Sepsis associated encephalopathy rats underwent cecal ligation and perforation (CLP) surgery. The Morris water maze (MWM) test was then used to evaluate cognitive function. Resting state-fMRI and 1H-MRS scanning were performed 7 and 14 days after CLP surgery to reveal spontaneous neuronal activity and metabolite changes in the hippocampus. The amplitude of low-frequency fluctuation (ALFF) was used to evaluate spontaneous neuronal activity in the hippocampus. Creatine (Cr), Myo-inositol (mI), and glutamine/glutamate (Glx) levels were measured with 1H-MRS scanning. Immunofluorescence and levels of interleukin (IL)-1ß, interleukin (IL)-6, and C-reactive protein (CRP) in the hippocampus were additionally detected to evaluate microglial mediated inflammatory responses. Statistical analysis was performed to evaluate correlations between hippocampal metabolism and behavioral findings. Results: Cecal ligation and perforation treated rats exhibited impaired learning and memory function in the MWM test at days 7 and 14. Elevation of IL-1ß in the hippocampus, as well as immunofluorescence results, confirmed severe neuro inflammation in the hippocampus in SAE rats. Compared with the sham group, the ALFF of the right CA-1 area of the hippocampus was higher at day 7after CLP surgery. The Glx/Cr and mI/Cr ratios were enhanced at day 7 after CLP surgery and slightly lower at day 14 after CLP surgery. The ALFF value, and Glx/Cr and mI/Cr ratios were negatively correlated with time spent in the target quadrant in the MWM test. Conclusion: Spontaneous neuronal activity and metabolites showed significant alterations in SAE rats. The elevated ALFF value, Glx/Cr ratio, and mI/Cr ratio in the hippocampus were positively associated with cognitive deficits. Changes in ALFF and metabolites in hippocampus may serve as potential neuroimaging biomarkers of cognitive disorders in patients with SAE.

Effects of early life exposure to home environmental factors on childhood allergic rhinitis: Modifications by outdoor air pollution and temperature.

BACKGROUND: There is growing evidence that allergic rhinitis (AR) is associated with indoor environmental factors, but their role in childhood AR during early life remains unclear. OBJECTIVE: To investigate the association of preconceptional, prenatal, early postnatal, and current exposure to home environmental factors with childhood AR, and to further explore whether this association can be interacted by outdoor air pollution and temperature. METHODS: A retrospective cohort study of 8689 preschool children was conducted during 2019-2020 in Changsha, China. A standard questionnaire was used to collect data on each family's health outcomes and home environments. We considered home environmental exposures during one year before conception, pregnancy, first year of life, and past year. Associations of indoor air pollution and allergens with AR were assessed by multiple logistic regression models. RESULTS: Pre-birth exposure to indoor air pollution emitted by new furniture or redecoration and dampness related allergen derived from mold/damp stains and mold/damp clothes or bedding during 1 year before conception and pregnancy was significantly associated with increased AR, with adjusted ORs (95% CI) ranging from 1.35 (1.05-1.75) to 1.87 (1.55-2.27). Childhood AR was also significantly related with post-birth exposure to dampness related indoor allergen including mold/damp stains and mold/damp clothes or bedding in first year and past year and pollen allergen including total and nonflowing plants in past year, with a range of ORs (95% CI) from 1.20 (1.01-1.42) to 1.79 (1.42-2.27). We identified that pre-birth, particularly in utero exposure to both indoor air pollution from renovation and dampness related allergens, played a key role in AR development compared to post-birth exposures, and accumulative effect was observed with the highest risk of AR. High exposure to traffic-related air pollution (TRAP) including outdoor PM2.5, NO2, CO, and O3, as well as living near traffic road not only significantly increased adverse effect of home environmental factors but also decreased protective effect of household dogs on childhood AR. Early life exposure to low temperature in pregnancy and high temperature in first year significantly increased AR risk of home environmental exposure. Sensitivity analysis indicated that some sub-groups were more susceptible to AR risk of home environmental exposure. CONCLUSION: Our study suggests that pre-birth exposure to home environmental factors played an important role in AR development and this effect can be interacted by TRAP and temperature, which supports a hypothesis of "(pre)fetal origin of childhood AR".

Effect of preconceptional, prenatal and postnatal exposure to home environmental factors on childhood pneumonia: A key role in early life exposure.

BACKGROUND: Increasing evidence have associated pneumonia with early exposure to ambient air pollution. However, the role of indoor environmental factors exposure in early life on childhood pneumonia remains unclear. OBJECTIVE: To examine the association between indoor environmental factors exposure during different timing windows and childhood pneumonia, and to identify the key indoor factor(s) in different critical window(s). METHODS: A retrospective cohort study of 8689 pre-schoolers was performed in Changsha, China during 2019-2020. Our questionnaire survey was designed to collect information on pre-schooler's outcome and residential environmental exposure containing indoor pollution and allergens during 1 year before pregnancy, pregnancy, first year, and past year. The associations were further estimated stratified by personal exposure level of outdoor NO2, CO, temperature (T) and different covariates. Associations were assessed by multiple logistic regression model in terms of odds ratio (OR) of 95% confidence interval (CI). RESULTS: Pre-schooler's pneumonia was significantly related with exposure of new furniture, redecoration, mold/damp stains, and mold or damp clothing or bedding exposure during the four periods, with the strongest associations observed during 1 year before pregnancy based on multi-window model, with ORs (95% CI) of 1.27 (1.12-1.44), 1.26 (1.09-1.46), 1.34 (1.14-1.57), and 1.28 (1.05-1.56) respectively. Environmental tobacco smoke (ETS) including both parental and grandparental smoking were significantly related with increased risk of pre-schooler's pneumonia, and ETS played a more important role in early life, with ORs (95% CI) of 1.17 (1.01-1.36) and 1.19 (1.02-1.39) in pregnancy and first year. Indoor plants particularly nonflowering plants significantly elevated pneumonia risk but only in past year, with ORs (95% CI) of 1.17 (1.05-1.30) and 1.14 (1.03-1.26). Higher pneumonia risk was observed for renovation exposure in pre-birth compared to post-birth, while mold/dampness exerted an accumulative effect with the highest risk for exposure during both pre- and post-birth. Living near traffic road and exposure to high level of traffic-related air pollution and high temperature significantly increased pneumonia risk. Sensitivity analysis found that some sub-groups were more susceptible to pneumonia risk of home environment exposure. CONCLUSION: Early life exposure to indoor environmental factors plays an important role in pneumonia development, supporting the hypothesis of "Preconceptional and Fetal Origin of Childhood Pneumonia" and "Developmental Origins of Health and Pneumonia".

Short Chain Fatty Acids Protect the Cognitive Function of Sepsis Associated Encephalopathy Mice via GPR43.

Objective: This study aims to analyze the changes of fecal short chain fatty acids (SCFAs) content and gut microbiota composition in sepsis associated encephalopathy (SAE) mice, further evaluating the effect of SCFAs on cognitive function and the underlying mechanism in SAE mice. Methods: A total of 55 male adult C57BL/6 mice (2-3 months of age, 20-25 g) were divided into four groups randomly: sham group (n = 10), cecal ligation and puncture group (CLP group, n = 15), CLP+SCFAs group (n = 15), and CLP+SCFAs+GLPG0974 group (n = 15). Seven days after surgery, fecal samples were collected for microbiota composition and SCFA analysis from 6 mice in each group randomly. Behavioral test was applied to assess cognitive impairment at the same time. After that, mice were sacrificed and brain tissue was harvested for inflammatory cytokines analysis. Results: The levels of acetic acid (.57 ± 0.09 vs 2.00 ± 0.24, p < 0.001) and propionic acid (.32 ± 0.06 vs .66 ± 0.12, p = 0.002) were significantly decreased in the CLP group compared with the sham group. The administration of SCFAs significantly increased the levels of acetic acid (1.51 ± 0.12 vs. 0.57 ± 0.09, p < 0.001) and propionic acid (0.54 ± 0.03 vs. 0.32 ± 0.06, p = 0.033) in CLP+SCFAs group compared with CLP group. Relative abundance of SCFAs-producing bacteria, including Allobaculum (0.16 ± 0.14 vs. 15.21 ± 8.12, p = 0.037), Bacteroides (1.82 ± 0.38 vs. 15.21 ± 5.95, p = 0.002) and Bifidobacterium (0.16 ± 0.06 vs. 2.24 ± 0.48, p = 0.002), significantly decreased in the CLP group compared with the sham group. The behavioral tests suggested that cognitive function was impaired in SAE mice, which could be alleviated by SCFAs pretreatment. ELISA tests indicated that the levels of IL-1ß, IL-6, and TNF-α were elevated in SAE mice and SCFAs could lower them. However, the GPR43 antagonist, GLPG0974, could reverse the cognitive protective effect and anti-neuroinflammation effect of SCFAs. Conclusion: Our study suggested that in SAE, the levels of acetate and propionate decreased significantly, accompanied by gut microbiota dysbiosis, particularly a decrease in SCFAs-producing bacteria. GPR43 was essential for the anti-neuroinflammation and cognitive protective effect of SCFAs in SAE.

[Research progress of sepsis associated encephalopathy influenced by gut microbiota via efferocytosis].

Sepsis associated encephalopathy (SAE) is a severe disease secondary to sepsis, which is associated with increased mortality and causes long-term cognitive deficits in survivors. Recently, an increasing body of evidence has shown that gut microbiota is closely related to the central nervous system, and could influence brain function via microbiota-gut-brain axis. Therefore, in the occurrence and development of SAE, cholinergic anti-inflammatory pathway is one of the mechanisms by which gut microbiota could improve cognitive function. Efferocytosis, a process of eliminating apoptotic cells in the body, has anti-inflammatory effects and provides organ protection in sepsis. On the other hand, it could be enhanced by some metabolites of gut microbiota, making it another potential mechanism for gut microbiota regulating SAE. This review summarizes the mutual regulation of gut microbiota, efferocytosis and SAE, to explore potential mechanisms and therapeutic targets of SAE.

Cluster-Based Visual Abstraction for Multivariate Scatterplots.

The use of scatterplots is an important method for multivariate data visualization. The point distribution on the scatterplot, along with variable values represented by each point, can help analyze underlying patterns in data. However, determining the multivariate data variation on a scatterplot generated using projection methods, such as multidimensional scaling, is difficult. Furthermore, the point distribution becomes unclear when the data scale is large and clutter problems occur. These conditions can significantly decrease the usability of scatterplots on multivariate data analysis. In this study, we present a cluster-based visual abstraction method to enhance the visualization of multivariate scatterplots. Our method leverages an adapted multilabel clustering method to provide abstractions of high quality for scatterplots. An image-based method is used to deal with large scale data problem. Furthermore, a suite of glyphs is designed to visualize the data at different levels of detail and support data exploration. The view coordination between the glyph-based visualization and the table lens can effectively enhance the multivariate data analysis. Through numerical evaluations for data abstraction quality, case studies and a user study, we demonstrate the effectiveness and usability of the proposed techniques for multivariate data analysis on scatterplots.