Crosstalk between human immunodeficiency virus infection and salivary bacterial function in men who have sex with men.

Background: Engaging in anal sexual intercourse markedly increases the risk of developing HIV among men who have sex with men (MSM); oral sexual activities tend to uniquely introduce gut-derived microbes to salivary microbiota, which, combined with an individual's positive HIV status, may greatly perturb oral microecology. However, till date, only a few published studies have addressed this aspect. Methods: Based on 16S rRNA sequencing data of bacterial taxa, MicroPITA picks representative samples for metagenomic analysis, effectively revealing how the development and progression of the HIV disease influences oral microbiota in MSM. Therefore, we collected samples from 11 HIV-negative and 44 HIV-positive MSM subjects (stage 0 was defined by HIV RNA positivity, but negative or indeterminate antibody status; stages 1, 2, and 3 were defined by CD4+ T lymphocyte counts ≥ 500, 200-499, and ≤ 200 or opportunistic infection) and selected 25 representative saliva samples (5 cases/stage) using MicroPITA. Metagenomic sequencing analysis were performed to explore whether positive HIV status changes salivary bacterial KEGG function and metabolic pathway in MSM. Results: The core functions of oral microbiota were maintained across each of the five groups, including metabolism, genetic and environmental information processing. All HIV-positive groups displayed KEGG functions of abnormal proliferation, most prominently at stage 0, and others related to metabolism. Clustering relationship analysis tentatively identified functional relationships between groups, with bacterial function being more similar between stage 0-control groups and stage 1-2 groups, whereas the stage 3 group exhibited large functional changes. Although we identified most metabolic pathways as being common to all five groups, several unique pathways formed clusters for certain groups; the stage 0 group had several, while the stage 2 and 3 groups had few, such clusters. The abundance of K03046 was positively correlated with CD4 counts. Conclusion: As HIV progresses, salivary bacterial function and metabolic pathways in MSM progressively changes, which may be related to HIV promoting abnormal energy metabolism and exacerbate pathogen virulence. Further, infection and drug resistance of acute stage and immune cell destruction of AIDS stage were abnormally increased, predicting an increased risk for MSM individuals to develop systemic and oral diseases.

Clinical evaluation of droplet digital pcr for suspected ascites infection in patients with liver cirrhosis.

BACKGROUND: Droplet digital PCR (ddPCR) is increasingly used in diagnosing clinical pathogens, but its effectiveness in cirrhosis patients with suspected ascites infection remains uncertain. METHODS: The diagnostic performance of ddPCR was assessed in 305 ascites samples, utilizing culture and clinical composite standards. The quantitative value and potential clinical impact of ddPCR were further analyzed in patients with spontaneous bacterial peritonitis. RESULTS: With culture standards, ddPCR demonstrated a sensitivity of 86.5% and specificity of 83.2% for bacterial or fungal detection. After adjustment of clinical composite criteria, specificity increased to 96.4%. Better diagnostic performance for all types of targeted pathogens, particularly fungi, was observed with ddPCR compared to culture, and more polymicrobial infections were detected (30.4% versus 5.7%, p < 0.001). Pathogen loads detected by ddPCR correlated with white blood cell count in ascites and blood, as well as polymorphonuclear cell (PMN) count in ascites, reflecting infection status rapidly. A positive clinical impact of 55.8% (43/77) was observed for ddPCR, which was more significant among patients with PMN count ≤ 250/mm3 in terms of medication adjustment and new diagnosis. ddPCR results for fungal detection were confirmed by clinical symptoms and other microbiological tests, which could guide antifungal therapy and reduce the risk of short-term mortality. CONCLUSIONS: ddPCR, with appropriate panel design, has advantages in pathogen detection and clinical management of ascites infection, especially for patients with fungal and polymicrobial infections. Patients with atypical spontaneous bacterial peritonitis benefited more from ddPCR.

Development of a droplet digital polymerase chain reaction assay for the sensitive detection of total and integrated HIV-1 DNA.

BACKGROUND: Total human immunodeficiency virus (HIV) DNA and integrated HIV DNA are widely used markers of HIV persistence. Droplet digital polymerase chain reaction (ddPCR) can be used for absolute quantification without needing a standard curve. Here, we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA. METHODS: The limit of detection, dynamic ranges, sensitivity, and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat (LTR) and human CD3 gene (for total HIV DNA) and ACH-2 cells (for integrated HIV DNA). Forty-two cases on stable suppressive antiretroviral therapy (ART) were assayed in total HIV DNA and integrated HIV DNA. Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive (CD4 + ) T-cell counts, CD8 + T-cell counts and CD4/CD8 T-cell ratio, respectively. The assay linear dynamic range and lower limit of detection (LLOD) were also assessed. RESULTS: The assay could detect the presence of HIV-1 copies 100% at concentrations of 6.3 copies/reaction, and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction (95% confidence intervals [CI]: 3.6-6.5 copies/reaction) with linearity over a 5-log 10 -unit range in total HIV DNA assay. For the integrated HIV DNA assay, the LLOD was 8.0 copies/reaction (95% CI: 5.8-16.6 copies/reaction) with linearity over a 3-log 10 -unit range. Total HIV DNA in CD4 + T cells was positively associated with integrated HIV DNA ( r = 0.76, P <0.0001). Meanwhile, both total HIV DNA and integrated HIV DNA in CD4 + T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8 + T-cell counts. CONCLUSIONS: This ddPCR assay can quantify total HIV DNA and integrated HIV DNA efficiently with robustness and sensitivity. It can be readily adapted for measuring HIV DNA with non-B clades, and it could be beneficial for testing in clinical trials.

Analysis of Immune and Inflammatory Microenvironment Characteristics of Noncancer End-Stage Liver Disease.

Chronic liver injury eventually progresses to cirrhosis and end-stage liver disease (ESLD), which are the leading causes of death in patients with liver disease worldwide. ESLD has a variety of etiologies and a complex pathogenesis. This study analyzed the characteristics of ESLD by studying the immune microenvironment and inflammatory microenvironment of ESLD caused by 4 noncancer diseases, including HBV-ALF, ALF, AILD, and AH. We collected transcriptome data from noncancer ESLD patients, collected liver tissue samples and blood samples from ESLD liver transplant patients, and analyzed the immune and inflammatory microenvironments in the liver and blood. The results showed that with the exception of HBV-induced ESLD, there were no significant differences in immune microenvironment scores among patients with ESLD caused by other noncancer diseases. Moreover, there were no significant differences in the inflammatory microenvironment in the liver and blood of patients with ESLD caused by the 4 noncancer diseases. Furthermore, we found that the cytokine, IL-15, could predict the prognosis of ESLD patients.

Regional urbanicity levels modify the association between ambient air pollution and prevalence of obesity: A nationwide cross-sectional survey.

Ambient air pollution exposure may increase the risk of obesity, but the population susceptibility associated with urbanicity has been insufficiently investigated. Based on a nationwide representative cross-sectional survey on 44,544 adults, high-resolution night light satellite remote sensing products, and multi-source ambient air pollution inversion data, the present study evaluated the associations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) concentrations with the prevalence of obesity and abdominal obesity. We further calculated the associations in regions with different urbanicity levels characterized by both administrative classification of urban/rural regions and night light index (NLI). We found that 10 µg/m3 increments in PM2.5 at 1-year moving average and in NO2 at 5-year moving average were associated with increased prevalence of obesity [odds ratios (OR) = 1.16 (1.14, 1.19); 1.12 (1.09, 1.15), respectively] and abdominal obesity [OR = 1.08 (1.07, 1.10); 1.07 (1.05, 1.09), respectively]. People in rural regions experienced stronger adverse effects than those in urban regions. For instance, a 10 µg/m3 increment in PM2.5 was associated with stronger odds of obesity in rural regions than in urban regions [OR = 1.27 (1.23, 1.31) vs 1.10 (1.05, 1.14), P for interaction <0.001]. In addition, lower NLI values were associated with constantly amplified associations of PM2.5 and NO2 with obesity and abdominal obesity (all P for interaction <0.001). In summary, people in less urbanized regions are more susceptible to the adverse effects of ambient air pollution on obesity, suggesting the significance of collaborative planning of urbanization development and air pollution control, especially in less urbanized regions.

Clinical Evaluation of Metagenomic Next-Generation Sequencing Method for the Diagnosis of Suspected Ascitic Infection in Patients with Liver Cirrhosis in a Clinical Laboratory.

Metagenomic next-generation sequencing (mNGS), mostly carried out in independent clinical laboratories, has been increasingly applied in clinical pathogen diagnosis. We aimed to explore the feasibility of mNGS in clinical laboratories and analyze its potential in the diagnosis of infectious ascites. Two reference panels composed of 12 strains commonly appearing in peritonitis were constructed to evaluate the performance metrics based on in-house mNGS protocols. The mNGS clinical detection value was analyzed in 211 ascitic samples and compared with culture and composite standards. Finally, eight patients with cirrhosis were prospectively enrolled to verify the clinical value of mNGS in peritoneal infection diagnosis. The mNGS analytical performance showed that the assay had great linearity, specificity, stability, interference, and limits of detection of 33 to 828 CFU/mL. The sensitivity and specificity of mNGS for bacterial or fungal detection using culture standards were 84.2% and 82.0%, respectively. After adjustment using digital PCR and clinical judgment, the sensitivity and specificity increased to 87.2% and 90.1%, respectively. Compared with culture, mNGS detected a broad range of pathogens and more polymicrobial infections (49% versus 9%, P < 0.05). The pathogen results were obtained within 24 h using mNGS in eight prospective cases, which effectively guided antibiotics therapy. mNGS testing in clinical laboratories affiliated with a hospital has certain advantages. It has unique superiority in pathogens detection, particularly in patients with polymicrobial infections. However, considering spectrum characteristics and test cost, pertinent pathogen panels should be developed in clinical practice. IMPORTANCE This study established and evaluated a complete metagenomics next-generation sequencing assay to improve the diagnosis of suspected ascitic infection in a clinical laboratory affiliated with a hospital. The assay is superior to traditional culture testing and will aid in the early and accurate identification of pathogens, particularly in patients with polymicrobial infections. This assay is also essential for precision therapy and can reduce the incidence of drug resistance stemming from irrational use of antibiotics.

A Method of Evaluating Safe Operating Space: Focus on Geographic Regions, Income Levels and Developing Pathway.

Safe and Just Space (SJS) is a framework for determining the range where the use of natural resources within the Earth's carrying capacity can maintain human well-being. However, there has been no systematic monitoring and evaluation of their sustainability across time and space. Here we developed and applied a model and a sustainable development human safe operation space (SDHSOS) index to assess the sustainability capacity and development path of 149 countries from 2000 to 2018. The results demonstrate that (1) The overall sustainable development capacity of all countries is at the middle or lower level and that it has increased over time. (2) The sustainability of natural and socio-economic dimensions and their degree of change show obvious geographic differences and income differences. (3) The national development path divided by income is characterized by a decline in natural environment dimensions and an increase in socio-economic dimensions, which mainly reflects a traditional development path model that promotes social welfare at the expense of the natural environment. This study suggests that nations can accurately identify development characteristics, expand their comparative advantages is the key to improving sustainable development capabilities.

The effects of rhein on D-GalN/LPS-induced acute liver injury in mice: Results from gut microbiome-metabolomics and host transcriptome analysis.

Background: Rhubarb is an important traditional Chinese medicine, and rhein is one of its most important active ingredients. Studies have found that rhein can improve ulcerative colitis by regulating gut microbes, but there are few reports on its effects on liver diseases. Therefore, this study aims to investigate these effects and underlying mechanisms. Methods: Mice were given rhein (100 mg/kg), with both a normal control group and a model group receiving the same amount of normal saline for one week. Acute liver injury was induced in mice by intraperitoneal injection of D-GalN (800 mg/kg)/LPS (10 ug/kg). Samples (blood, liver, and stool) were then collected and assessed for histological lesions and used for 16S rRNA gene sequencing, high-performance liquid chromatography-mass spectrometry (LC-MS) and RNA-seq analysis. Results: The levels of ALT and AST in the Model group were abnormal higher compared to the normal control group, and the levels of ALT and AST were significantly relieved in the rhein group. Hepatic HE staining showed that the degree of liver injury in the rhein group was lighter than that in the model group, and microbiological results showed that norank_o:Clostridia_UCG-014, Lachnoclostridium, and Roseburia were more abundant in the model group compared to the normal control group. Notably, the rhein treatment group showed reshaped disturbance of intestinal microbial community by D-GalN/LPS and these mice also had higher levels of Verrucomicrobia, Akkermansiaceae and Bacteroidetes. Additionally, There were multiple metabolites that were significantly different between the normal control group and the model group, such as L-α-amino acid, ofloxacin-N-oxide, 1-hydroxy-1,3-diphenylpropan-2-one,and L-4-hydroxyglutamate semialdehyde, but that returned to normal levels after rhein treatment. The gene expression level in the model group also changed significantly, various genes such as Cxcl2, S100a9, Tnf, Ereg, and IL-10 were up-regulated, while Mfsd2a and Bhlhe41 were down-regulated, which were recovered after rhein treatment. Conclusion: Overall, our results show that rhein alleviated D-GalN/LPS-induced acute liver injury in mice. It may help modulate gut microbiota in mice, thereby changing metabolism in the intestine. Meanwhile, rhein also may help regulate genes expression level to alleviate D-GalN/LPS-induced acute liver injury.

Clinical evaluation of bacterial DNA using an improved droplet digital PCR for spontaneous bacterial peritonitis diagnosis.

Objective: Bacterial DNA (bactDNA) detection can be used to quickly identify pathogenic bacteria and has been studied on ascitic fluid. We aimed to retrospectively analyze the diagnostic value and applicational prospect of the bactDNA load in spontaneous bacterial peritonitis (SBP). Method: We extracted viable bactDNA from ascitic samples of 250 patients with decompensated cirrhosis collected from October 2019 to April 2021 and detected the bactDNA by droplet digital polymerase chain reaction (ddPCR). We used ascitic samples of a baseline cohort of 191 patients to establish diagnostic thresholds for SBP and analyze the patients' diagnostic performance based on ascites polymorphonuclear (PMN) and clinical manifestation. We performed bactDNA quantification analysis on 13 patients with a PMN less than 250 cells/mm3 but with clinical symptoms. The dynamic changes of the bactDNA load from eight patients (before, during, and after SBP) were analyzed. Results: After the removal of free DNA, the bactDNA detected by ddPCR was generally decreased (1.75 vs. 1.5 log copies/µl, P < 0.001). Compared with the traditional culture and PMN count in the SBP diagnosis, the bactDNA showed that the ddPCR sensitivity was 80.5%, specificity was 95.3%, positive predictive value was 82.5%, and negative predictive value was 94.7%, based on clinical composite criteria. In patients with a PMN less than 250 cells/mm3, the bactDNA load of 13 patients with symptoms was significantly higher than those without symptoms (2.7 vs. 1.7 log copies/µl, P < 0.001). The bactDNA in eight patients had SBP that decreased by 1.6 log copies/µl after 48 h of antibiotic treatment and by 1.0 log copies/µl after 3 days of continued treatment. Conclusion: BactDNA detection can be used to further enhance the diagnostic efficiency of SBP. Therefore, the application of ddPCR assay not only can be used to discriminate and quantify bacteria but also can be used in the clinical assessment for antibiotics treatment.

How do precipitation events modify the stable isotope ratios in leaf water at Lhasa on the southern Tibetan Plateau?

Serving as a medium between source water and cellulose, leaf water contributes to the isotope ratios (δ18O, δ2H) of plant organic matter, which can be used for paleoclimate reconstruction. This study is the first to examine the diurnal variations in the δ18O and δ2H of leaf water on the southern Tibetan Plateau. The δ18O and δ2H of leaf water were relatively low when precipitation events occurred. In particular, 18O and 2H of leaf water became extremely depleted 5 h after the precipitation event. Our findings demonstrate that precipitation can modify the isotope ratios of leaf water from external and internal causes. First, precipitation events affect meteorological elements, lead to decreases in leaf transpiration, and immediately weaken the isotope enrichment of leaf water ('rapid effect' of precipitation). Second, precipitation events affect the internal plant-soil water cycle process, causing the plant to preferentially use deeper soil water, and the corresponding isotope ratios of leaf water exhibit extremely low values 5 h after precipitation events ('delay effect' of precipitation). This study suggests that researchers need to be cautious in separating the signals of precipitation and hydrological processes when interpreting isotope records preserved in tree-ring cellulose archives from the Tibetan Plateau.

Exploring complex water stress-gross primary production relationships: Impact of climatic drivers, main effects, and interactive effects.

The dominance of vapor pressure deficit (VPD) and soil water content (SWC) for plant water stress is still under debate. These two variables are strongly coupled and influenced by climatic drivers. The impacts of climatic drivers on the relationships between gross primary production (GPP) and water stress from VPD/SWC and the interaction between VPD and SWC are not fully understood. Here, applying statistical methods and extreme gradient boosting models-Shapley additive explanations framework to eddy-covariance observations from the global FLUXNET2015 data set, we found that the VPD-GPP relationship was strongly influenced by climatic interactions and that VPD was more important for plant water stress than SWC across most plant functional types when we removed the effect of main climatic drivers, e.g. air temperature, incoming shortwave radiation and wind speed. However, we found no evidence for a significant influence of elevated CO2 on stress alleviation, possibly because of the short duration of the records (approximately one decade). Additionally, the interactive effect between VPD and SWC differed from their individual effect. When SWC was high, the SHAP interaction value of SWC and VPD on GPP was decreased with increasing VPD, but when SWC was low, the trend was the opposite. Additionally, we revealed a threshold effect for VPD stress on GPP loss; above the threshold value, the stress on GPP was flattened off. Our results have important implications for independently identifying VPD and SWC limitations on plant productivity, which is meaningful for capturing the magnitude of ecosystem responses to water stress in dynamic global vegetation models.

Peripheral immune phenotypes and T cell receptor repertoire in pneumocystis pneumonia in HIV-1 infected patients.

BACKGROUND: The host immune response to pneumocystis pneumonia (PCP) involves interactions among immune cell subsets and cytokines. However, the definite pathogenesis and immunological influences of P. jirovecii have not been fully elucidated. METHODS: Mass cytometry and high-throughput sequencing of the T cell receptor (TCR) were used to profile the host immune response to human immunodeficiency virus-1 (HIV-1) and P. jirovecii infection. RESULTS: Our findings demonstrated that patients with PCP showed different immune cell proportions when compared to healthy controls. Changes in cytokines were found after anti-PCP treatment, suggested that cytokines may play an important role in controlling the pathogen. Furthermore, PCP patients showed marked reduction of TCR repertoire diversity. The diversity of TCR repertoire was restored by the anti-PCP treatment. CONCLUSION: In summary, we profiled the composition and characteristics of immune environment in response to HIV-1 and P. jirovecii infection, which may contribute to elucidating host immunity.

Residential greenness and prevalence of chronic kidney disease: Findings from the China National Survey of Chronic Kidney Disease.

Green space is associated with many health benefits, but evidence concerning the effects on chronic kidney disease (CKD) has not been investigated. Using the nationwide cross-sectional study of 47,204 adults from the China National Survey of Chronic Kidney Disease dataset and residential greenness assessed by the normalized difference vegetation index (NDVI), this study evaluated the association between residential greenness and CKD prevalence. An interquartile range increase in NDVI1000m (0.26) was associated with decreased odds of CKD for all participants with an odds ratio (OR) of 0.79 (95% confidence interval [CI]: 0.73-0.86). Subgroup analyses demonstrated more apparent inverse associations in younger adults <65 years, male participants, people in higher socio-economic status, as well as people with smoking and alcohol drinking habit. In addition, more apparent inverse associations were found in regions with higher fine particulate matter (PM2.5) concentration levels, with OR of 0.56 (95% CI: 0.49, 0.65) for higher pollution regions, and OR of 0.95 (95% CI: 0.83, 1.09) for lower pollution regions (P for interaction <0.001). The exposure-response curves captured more apparent declines in OR of CKD when in lower NDVI1000m exposure ranges (<0.6), even controlling for the PM2.5 concentration. Our results indicated that residential greenness might be beneficial for the prevention and control of CKD at the population level, suggesting the positive significance of strengthening green space construction, particularly in regions with low greenness.

Green water appropriation of the cropland ecosystem in China.

Despite the awareness that green water is the main source of water to produce food, studies on green water use in cropland ecosystems are still rather limited, and almost no research has so far explored the relationship between green water utilization and socioeconomic development. In this study, with the help of CropWat 8.0, the green water footprint (GWF) of main crops in China was estimated from 1979 to 2016. On this basis, a novel concept, i.e., green water appropriation rate (GWar), was introduced to reveal the relationship between GWF and precipitation. Then, for the first time, the center of gravity trajectory of the GWar and the correlation between GWar and socioeconomic factors were further investigated. The results show that the provinces with the largest increases of GWF were Inner Mongolia (223%), Xinjiang (127%), and Ningxia (123%), while the GWF of 11 provinces has decreased, and 9 of them were municipalities or coastal areas. Generally, the GWar in the eastern and central provinces was higher than that in the western provinces. The center of gravity of the GWar has always been in Henan Province, but it has moved westward from Kaifeng City in 1979 to Sanmenxia City in 2016 and may further move to Shanxi Province soon. The total power of agricultural machinery and the effective irrigation rate had a positive correlation with the GWar, while the agricultural GDP was negatively correlated with the GWar. It is expected that the results will explicitly provide a scientific basis for the development of water-appropriate agriculture and the full utilization of rainwater.

The Underrated Salivary Virome of Men Who Have Sex With Men Infected With HIV.

Salivary virome is important for oral ecosystem, but there are few reports on people living with HIV. We performed metagenomic sequencing to compare composition and functional genes of salivary virobiota between one HIV-negative and four HIV-positive groups in which participants were all men who have sex with men (MSM) with different immunosuppression statuses (five samples per group) to find the evidence that salivary virobiota plays a role in the pathogenesis of oral disease. Acute-stage subjects achieved a positive result of HIV RNA, but HIV antibody negative or indeterminate, whereas individuals with mild, moderate, and severe immunosuppression exhibited CD4+ T-lymphocyte counts of at least 500, 200-499, and less than 200 cells/µL or opportunistic infection, respectively. The results showed the composition of salivary virus genera in subjects with mild immunosuppression was the most similar to that in healthy people, followed by that in the acute stage; under severe immunosuppression, virus genera were suppressed and more similar to that under moderate immunosuppression. Furthermore, abnormally high abundance of Lymphocryptovirus was particularly obvious in MSM with HIV infection. Analysis of KEGG Pathway revealed that Caulobacter cell cycle, which affects cell duplication, became shorter in HIV-positive subjects. It is worth noting that in acute-stage participants, protein digestion and absorption related to the anti-HIV-1 activity of secretory leukocyte protease inhibitor was increased. Moreover, in the severely immunosuppressed subjects, glutathione metabolism, which is associated with the activation of lymphocytes, was enhanced. Nevertheless, the ecological dysbiosis in HIV-positive salivary virobiota possibly depended on the changes in blood viral load, and salivary dysfunction of MSM infected with HIV may be related to CD4 counts. Ribonucleoside diphosphate reductase subunit M1 in purine metabolism was negatively correlated, though weakly, to CD4 counts, which may be related to the promotion of HIV-1 DNA synthesis in peripheral blood lymphocytes. 7-Cyano-7-deazaguanine synthase in folate biosynthesis was weakly positively correlated with HIV viral load, suggesting that this compound was produced excessively to correct oral dysfunction for maintaining normal cell development. Despite the limited number of samples, the present study provided insight into the potential role of salivary virome in the oral function of HIV infected MSM.

Urbanization, ambient air pollution, and prevalence of chronic kidney disease: A nationwide cross-sectional study.

An increasing number of studies have linked ambient air pollution to chronic kidney disease (CKD) prevalence. However, its potential effect modification by urbanization has not been investigated. Based on data of 47,204 adults from the China National Survey of Chronic Kidney Disease (CKSCKD) dataset, night light satellite remote sensing data and high-resolution air pollution inversion products, the present cross-sectional study investigated the association between fine particulate matter <2.5 mm in diameter (PM2.5), nitrogen dioxide (NO2), night light index (NLI) and CKD prevalence in China, and the effect modification by urbanization characterized by administrative classification and NLI on the pollutant-health associations. Our results showed that a 10-µg/m3 increase in PM2.5 at 3-year moving average, a 10-µg/m3 increase in NO2 at 5-year moving average, and a 10-U increase in NLI at 5-year moving average were significantly associated with increased odds of CKD prevalence [OR = 1.24 (95 %CI:1.14, 1.35); OR = 1.12 (95 %CI:1.09, 1.15); OR = 1.05 (95 %CI:1.02, 1.07)]. Meanwhile, the pollutant-health associations were more apparent in medium-urbanized areas compared to low- and high-urbanized areas. For instance, a 10-µg/m3 increase in PM2.5 concentration at 2-year moving average was associated with increased odds of CKD in the areas with NLI level in the second [OR = 2.78 (95 %CI:1.77, 4.36)] and third quartiles [OR = 1.49 (95 %CI:1.14, 1.95)], compared to the lowest [OR = 0.96 (95% CI: 0.73, 1.26)] and highest [OR = 0.63 (95% CI: 0.39-1.02)] quartiles. PM2.5 and NO2 were associated with increased odds of CKD prevalence, especially in areas with medium NLI levels, suggesting the necessity of strengthening environmental management in medium-urbanized regions.

Salivary microbial diversity at different stages of human immunodeficiency virus infection.

Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) disrupts the host microbial balance. During disease progression, the oral microbial environment is altered in untreated people living with HIV/AIDS (PLWHA); however, no studies have reported changes in salivary microbial diversity during different stages of HIV infection. Therefore, in this study, we aimed to assess the relationships between immune dysfunction and changes in saliva microbiota. To this end, we collected saliva samples from 11 HIV-negative individuals and 44 PLWHA during different stages based on the Centers for Disease Control and Prevention criteria (stage 0, early stage during the first 6 months after infection; stages 1, 2, and 3 associated with CD4+ T-lymphocyte counts of ≥500, 200-499, and ≤200 or opportunistic infection, respectively). We analyzed salivary microbial community diversity using polymerase chain reaction amplification and Illumina MiSeq sequencing. We found that HIV-positive individuals had significantly greater alpha-diversity in the microbial community composition compared with HIV-negative controls (P < 0.05) except for AIDS (stage 3); however, the predominant salivary microbiota in the five groups remained similar. Porphyromonas in the four positive groups was the only genus that was significantly less abundant in the HIV-positive groups than in the control group (P < 0.05). There were some consistencies between the general abundance of salivary microbiota and AIDS disease progression. Lots of bacterial abundances in the saliva increased dramatically during the acute HIV infection (stage 0), and some of the negligible and abnormally proliferating bacteria in the asymptomatic stage showed a downward trend. Additionally, in the AIDS stage, partial inhibition was observed. Notably, Porphyromonas was closely related to the immune activation of HIV, showing a decline in abundance once infected with HIV. Solobacterium, which induces inflammation, was negatively correlated with CD4 counts. Overall, our findings provided important insights into changes in salivary microbial diversity in PLWHA.

The Qingchangligan Formula Alleviates Acute Liver Failure by Regulating Galactose Metabolism and Gut Microbiota.

The Qingchangligan formula (QCLGF) is a traditional Chinese medicine that has significant clinical potential for patients with acute liver failure (ALF). However, the experimental evidence of the effect of QCLGF on ALF and the associated mechanisms remain elusive. We aimed to evaluate the function of QCLGF in ALF and the underlying mechanism. ALF was induced in rats by intraperitoneal injection of D-GalN (1100 mg/kg). The Qingchangligan formula was administered to the rats (6.725 g/kg · d) for 5 days, and the model group and the control group were given the same amount of physiological saline. Then 16S rRNA gene sequencing, high performance gas chromatography-mass spectrometry (GC-MS), and RNA-seq analysis were performed on the samples. The levels of ALT and AST in the ALF rats were abnormal (5322.08 ± 566.27 U/L and 7655.95 ± 1238.08 U/L, respectively) compared with the normal control (98.98 ± 6.90 U/L and 99.63 ± 10.94 U/L, respectively). The levels of ALT and AST in the QCLGF rats (2997.67 ± 469.24 U/L and 4158.40 ± 596.07 U/L, respectively) were closer the normal control group. Liver HE staining showed that the degree of liver damage in the QCLGF rats was lighter than that in the ALF rats. The overall structure of the gut microbiota after ALF was significantly altered, including Proteobacteria, Blautia, Romboutsia, Parabacteroides, UCG-008, Parasutterella, Ruminococcus, norank_f:Lachnospiraceae, the Eubacterium_xylanophilum_group, Oscillibacter, and Eisenbergiella. QCLGF balanced the structure and abundance of intestinal flora. The levels of D(+)galactose, isopropyl beta-D-1-thiogalactopyranoside and D-mannitol were lighter in the plasma of the ALF rats than in the normal control rats, but there were significantly elevated levels of those metabolites in the QCLGF rats. The gene expression changed significantly in the ALF rats. QCLGF regulated the expression of THBS1 and the KEGG pathways of carbohydrate metabolism, lipid metabolism, signal transduction, the immune system, and infectious disease: bacterial. QCLGF may alleviating intestinal flora disorder, regulating galactose metabolism and downregulating the expression of THBS1 to alleviate D-GalN induced acute liver failure.

Corrigendum to "Usnea Acid as Multidrug Resistance (MDR) Reversing Agent against Human Chronic Myelogenous Leukemia K562/ADR Cells via an ROS Dependent Apoptosis".

[This corrects the article DOI: 10.1155/2019/8727935.].

Association of the IL-6 Rs1800796 SNP with Concentration/dose Ratios of Tacrolimus and Donor Liver Function after Transplantation.

Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a range of important roles such as in inflammation, immune response, and cell growth regulation. Here, we aimed to assess the potential influence of the IL-6 single nucleotide polymorphism (SNP) rs1800796 on the concentration/dose (C/D) ratios of tacrolimus and donor liver function in Chinese liver transplant patients. A total of 331 liver transplant patients were included in this study. The C/D ratios and the ALT, AST, T-BIL, ALP, and GGT levels were analyzed at different time points in patients with and without the IL-6 rs1800796 SNP. The IL-6 rs1800796 polymorphism in recipients was found to be correlated with the C/D ratios of tacrolimus at months 2 to month 6 after transplantation. Also, the rs1800796 SNP in donors was found to influence liver function (shown in the data of ALT, AST, T-BIL, ALP and GGT) in recipients at the early post-transplant stage after transplantation. In conclusion, the IL-6 rs1800796 polymorphism was associated with the C/D ratios of tacrolimus and post-transplant donor liver function.