Biochemical Characterization and Phylogenetic Analysis of the Virulence Factor Lysine Decarboxylase From Vibrio vulnificus

Cadaverine is produced in organisms from the amino acid lysine in a decarboxylation reaction catalyzed by lysine decarboxylase (EC 4.1.1.18). The inducible lysine decarboxylase CadA plays a vital role in acid stress response for enteric bacteria. Vibrio vulnificus is an extremely virulent human pathogen causing gastroenteritis when the acid conditions that prevent survival of V. vulnificus in the stomach or small intestine are overcome. A gene encoding CadA was identified from V. vulnificus. Subsequent analyses showed that CadA from V. vulnificus (VvCadA) is a decamer with a 82-kDa subunit. Homogenous VvCadA was purified from Escherichia coli and used for lysine decarboxylation with an optimal pH of 6.0 and optimal temperature of 37°C. The apparent Vmax and Km for lysine were 9.45 ± 0.24 μM/min and 0.45 ± 0.05 mM, respectively. Mutation analysis suggested that the amino-acid-binding pyridoxal phosphate, the cofactor of the enzyme, plays a vital role in the reaction. Mutation of the negatively charged residues interacting with lysine also affected the activity of the enzyme to some extent. Quantitative RT-PCR showed that expression of VvcadA was up-regulated under low pH, low salinity, and oxidative stresses. Furthermore, the concentration of cadaverine released to the cell exterior also increased under these stresses. Protein sequence similarity network (SSN) analysis indicated that lysine decarboxylases with ornithine decarboxylases and arginine decarboxylases shared a common ancestor, and that lysine decarboxylases are more conserved during evolution. Our data provide evidence for the biochemical characteristics and important roles of VvCadA under stress conditions

A Canonical Correlation Analysis of AIDS Restriction Genes and Metabolic Pathways Identifies Purine Metabolism as a Key Cooperator

Human immunodeficiency virus causes a severe disease in humans, referred to as immune deficiency syndrome. Studies on the interaction between host genetic factors and the virus have revealed dozens of genes that impact diverse processes in the AIDS disease. To resolve more genetic factors related to AIDS, a canonical correlation analysis was used to determine the correlation between AIDS restriction and metabolic pathway gene expression. The results show that HIV-1 postentry cellular viral cofactors from AIDS restriction genes are coexpressed in human transcriptome microarray datasets. Further, the purine metabolism pathway comprises novel host factors that are coexpressed with AIDS restriction genes. Using a canonical correlation analysis for expression is a reliable approach to exploring the mechanism underlying AIDS

Structural Condition Assessment and Temperature Effect Analysis of Cable–Pylon Anchorage Zone Using Long-Term SHM Data

To study the temperature effect in the anchorage zone of a long-span cable-stayed bridge, a wavelet multiresolution analysis and layered stripping method were used in this paper. Based on long-term structural health monitoring data, the signals were decomposed and reconstructed at multiple time scales, confirming temperature to be the main factor causing the stress change in the anchorage zone. The results of structural condition during operation showed that the general compressive stress level of the anchorage zone was low. However, the tensile stress level of the sidewall was high, which led to a severe concrete cracking. Excluding the influence of the seasonal temperature, the compressive stress increased slightly, the horizontal tensile stress in the upstream inner pylon wall increased, and the crack width increased gradually. By analysing the daily temperature effect on the upstream and downstream pylon walls, the regression model proposed in this study can be used to predict the daily temperature effect at any time in the diurnal cycle. The accuracy of the model is reliable within 6 days, but for the location of severe cracks, the monitoring data should be updated in real time to ensure the precision

Features of anemia in patients coinfected with AIDS and talaromycosis marneffei

Objective To analyze the characteristics of anemia in patients with acquired immunodeficiency syndrome (AIDS) complicated with talaromycosis marneffei (TSM). Methods Patients coinfected with AIDS and TSM in Mengchao Hepatobiliary Hospital of Fujian Medical University between January 2016 and December 2020 were retrospectively included. Demographic data and anemia-related laboratory results were collected, and the type and degree of anemia of the patients were analyzed. Results A total of 383 patients were included and the prevalence of anemia was 84.33%(323/383).According to classification of anemia, mild, moderate and severe anemia accounted for 63.47%, 33.74% and 2.79%, respectively. According to erythrocyte morphology，microcytic anemia，normocytic anemia and macrocytic anemia accounted for 17.34%、80.80% and 1.86%, respectively. Compared with patients without anemia, patients with anemia had more women(14.24% vs 3.33%, χ2=5.492, P=0.019), more CD4+ ＜20 cells/μL(73.37% vs 60.00%, χ2=4.421, P=0.035), more white blood cell＜3×109/L(36.22% vs 16.67%, χ2=8.731, P=0.003)and more blood platelet ＜50×109/L(19.81% vs 8.33%, χ2=4.516, P=0.034). Conclusion The incidence of anemia in patients coinfected with AIDS and TSM is very high, especially in female patients with CD4+ ＜20 counts. For AIDS patients with anemia， physicians should pay more attention to these patients and treat them with fungi-medicine timely if necessary

Coexpression Analysis of Transcriptome on AIDS and Other Human Disease Pathways by Canonical Correlation Analysis

Acquired immune deficiency syndrome is a severe disease in humans caused by human immunodeficiency virus. Several human genes were characterized as host genetic factors that impact the processes of AIDS disease. Recent studies on AIDS patients revealed a series disease is complicating with AIDS. To resolve gene interaction between AIDS and complicating diseases, a canonical correlation analysis was used to identify the global correlation between AIDS and other disease pathway genes expression. The results showed that HLA-B, HLA-A, MH9, ZNED1, IRF1, TLR8, TSG101, NCOR2, and GML are the key AIDS-restricted genes highly correlated with other disease pathway genes. Furthermore, pathway genes in several diseases such as asthma, autoimmune thyroid disease, and malaria were globally correlated with ARGs. It suggests that these diseases are a high risk in AIDS patients as complicating diseases

Moderate/Severe hyponatremia increases the risk of death among hospitalized Chinese human immunodeficiency virus/acquired immunodeficiency syndrome patients.

OBJECTIVES: To evaluate whether the serum sodium concentration is associated with the progression and long-term prognosis of Chinese HIV/AIDS patients. METHODS: Three hundred and eighty seven hospitalized patients were recruited into this retrospective cohort study. The strata of serum sodium concentration were moderate/severe hyponatremia, mild hyponatremia and normonatremia. Disease progression was estimated using CD4 counts and the WHO clinical stage. Correlation analysis was used to evaluate the serum sodium concentration with disease progression. The Kaplan-Meier method and the Cox proportional hazards model were used to analyze the effect of different serum sodium levels on survival. RESULTS: In this study 206 patients (53.2%) had hyponatremia, including 10.6% patients with moderate/severe hyponatremia and 42.6% with mild hyponatremia. The serum sodium concentration was significantly correlated with the HIV/AIDS progression (P<0.001). During the follow-up, 100 patients (25.6%) died. The cumulative survival rates of HIV/AIDS patients were 47.8% ± 8.5% in patients with moderate/severe hyponatremia, 59.8% ± 5.0% with mild hyponatremia and 79.9% ± 3.4% with normonatremia (log-rank P<0.001). After adjusting for sex, age, WHO stage, CD4 count, hemoglobin and albumin, the relative hazard was 3.5 (95% CI: 1.9-6.5) for patients with moderate/severe hyponatremia (P<0.001), and 1.5 (95% CI: 0.9-2.4) for those with mild hyponatremia (P = 0.161), compared with normonatremic patients. CONCLUSIONS: The serum sodium level is closely correlated with the severity of patients. Only moderate/severe hyponatremia affects the prognosis of Chinese HIV/AIDS patients. Earlier intensive medical managements(including HAART)are necessary to increase the survival rates of Chinese HIV/AIDS patients with moderate/severe hyponatremia

Proteomic analysis of serum proteins from HIV/AIDS patients with Talaromyces marneffei infection by TMT labeling-based quantitative proteomics

Abstract Background Talaromyces marneffei (TM) is an emerging pathogenic fungus that can cause a fatal systemic mycosis in patients infected with human immunodeficiency virus (HIV). Although global awareness regarding HIV/TM coinfection is increasing little is known about the mechanism that mediates the rapid progression to HIV/AIDS disease in coinfected individuals. The aim of this study was to analyze the serum proteome of HIV/TM coinfected patients and to identify the associated protein biomarkers for TM in patients with HIV/AIDS. Methods We systematically used multiplexed isobaric tandem mass tag labeling combined with liquid chromatography mass spectrometry (LC–MS/MS) to screen for differentially expressed proteins in the serum samples from HIV/TM-coinfected patients. Results Of a total data set that included 1099 identified proteins, approximately 86% of the identified proteins were quantified. Among them, 123 proteins were at least 1.5-fold up-or downregulated in the serum between HIV/TM-coinfected and HIV-mono-infected patients. Furthermore, our results indicate that two selected proteins (IL1RL1 and THBS1) are potential biomarkers for distinguishing HIV/TM-coinfected patients. Conclusions This is the first report to provide a global proteomic profile of serum samples from HIV/TM-coinfected patients. Our data provide insights into the proteins that are involved as host response factors during infection. These data shed new light on the molecular mechanisms that are dysregulated and contribute to the pathogenesis of HIV/TM coinfection. IL1RL1 and THBS1 are promising diagnostic markers for HIV/TM-coinfected patients although further large-scale studies are needed. Thus, quantitative proteomic analysis revealed molecular differences between the HIV/TM-coinfected and HIV-mono-infected individuals, and might provide fundamental information for further detailed investigations

Increased Serum Soluble Urokinase Plasminogen Activator Receptor Predicts Short-Term Outcome in Patients with Hepatitis B-Related Acute-on-Chronic Liver Failure

Aims. Soluble urokinase plasminogen activator receptor (suPAR) reflects the immune activation in circumstances of inflammation and infection. It has been considered as a risk biomarker associated with poor outcome in various low-grade inflammation and infectious diseases. The study is aimed at investigating whether suPAR has a predictive value with short-term survival in patients with hepatitis B-related acute-on-chronic liver failure (HB-ACLF). Methods. Serum suPAR expression was compared among patients with different states of chronic hepatitis B virus infection. Sixty HB-ACLF patients were recruited as the training cohort and followed up for 90 days. Serum suPAR level and the clinical relevance with short-term outcome were investigated. The temporal dynamics of suPAR were evaluated in 50 HB-ACLF patients with available serum sequentially at baseline, week 2 and week 4. Another 167 HB-ACLF patients were enrolled to validate the predictive value of suPAR with respect to the prognosis. Results. Serum suPAR level was significantly increased in HB-ACLF patients compared to non-ACLF patients. In the training set of HB-ACLF, we observed higher suPAR level, INR, MELD score, and more complications in nonsurvivors than survivors. Longitudinal analysis revealed an increased trend of suPAR level in nonsurvivors during week 0 to week 4 and the modest decline in survivors. It showed that the synchronous suPAR level was higher in nonsurvivors at all indicated time points. Elevated suPAR level at baseline was identified as a strong predictor of a 90-day mortality of HB-ACLF patients. It was confirmed suPAR>16.26 ng/ml had a positive predictive value of 72.22% and a negative predictive value of 77.88% for poor outcome in the validation cohort. Conclusions. Serum suPAR level increases significantly in HB-ACLF patients and associated with a 90-day mortality. It suggests that suPAR might be a potential biomarker to predict the prognosis of HB-ACLF patients