Advances in DNA-based electrochemical biosensors for the detection of foodborne pathogenic bacteria.

The detection of foodborne pathogenic bacteria is critical in preventing foodborne diseases. DNA-based electrochemical biosensors, with the merits of high sensitivity and short detection time, provide an effective detecting method for foodborne pathogens, attracting significant interest for the past few years. This review mainly describes the important research progress of DNA-based electrochemical biosensors for the detection of foodborne pathogenic bacteria through four perspectives: representative foodborne pathogens detection using electrochemical approaches, DNA immobilization strategies of aptamers, DNA-based signal amplification strategies used in electrochemical DNA sensors, and functional DNA used in electrochemical DNA sensors. Finally, perspectives and challenges are presented in this field. This review will contribute to DNA-based electrochemical biosensor in enhancing the nucleic acid signal amplification.

Reference interval establishment and correlation research of urine thromboxane metabolites: Unveiling new possibilities in platelet activation.

BACKGROUND: Thromboxane metabolites could indirectly reflect platelet activation, among which 11-dehydro-thromboxane B2 (11dhTxB2) and 11-dehydro-2, 3-dinor thromboxane B2 (11dh23dinorTxB2) are two stable metabolites that are abundant in urine, and both are closely related to disease progression and drug use. However, most clinical application studies have focused on the single indicator of 11dhTxB2. We propose an LC-MS/MS method suitable for routine clinical screening with simultaneous determination of both metabolites and conduct preliminary studies in different populations. METHODS AND RESULTS: The thromboxane metabolites were extracted by liquid-liquid extraction and determined by LC-MS/MS. Reference intervals (RI) were established in 333 healthy adults and validated in 25 patients with coronary atherosclerosis (CA). This LC-MS/MS method was over a wide quantitative range (0.1-10 µmol/L), the imprecision and accuracy were 5.2 %-11 % and 89.3 %-106.5 %, and was suitable for clinical routine quantitative screening. The 95th percentile RI of unire 11dhTxB2 was 1220 (95 % CI: 1048, 1376) pg mg Cr -1, for 11dh23dinorTxB2, RI was 908 (95 % CI: 821, 1102) pg mg Cr -1. For the first time, we found a significant correlation between 11dhTxB2 and 11dh23dinorTxB2 in both healthy adults (r = 0.67, P < 0.001) and CA patients (r = 0.77, P < 0.001). CONCLUSION: The establishment of RI provides a reference for diseases related to platelet activation and the use of drugs, and the first discovery of the correlation between 11dhTxB2 and 11dh23dinorTxB2 in urine provides a new possibilitie for the diagnostic and prognostic of cardiovascular diseases.

An ultra performance liquid chromatography method for transthyretin variants screening and heart failure assisting diagnosis.

BACKGROUND: Transthyretin (TTR) gene mutations are associated with hereditary amyloidosis (ATTR) caused by mutant TTR protein dissociation, misfolding, aggregation, and insoluble fibrils deposition. Herein, we reported a chromatographic approach for quantification and identification of TTR tetramer in human blood serum by ultra performance liquid chromatography (UPLC). METHODS: TTR proteins and serum were incubated with a fluorescent TTR tetramer sensor (A2). The A2 sensor specifically reacted with tetrameric TTR and released stoichiometric fluorescence that was detected by fluorescence detector coupled to UPLC. The external standard was used for quantification, the chromatographic peak parameters were used to identification certain mutation types. RESULTS: UPLC correctly distinguished 18 types of mutant TTR proteins from wild type. The results were consistent with follow-up analysis of two ATTR patients' blood serum samples. In addition, the tetrameric TTR of 30 heart failure (HF) patients showed strongly correlation (r = -0.63, p < 0.00) with NT-proBNP, a HF clinical biomarker. CONCLUSIONS: UPLC method has sufficient accuracy to eliminate the necessity of sequencing for certain types of TTR mutations and allows for facile initial screening of ATTR amyloidosis patients, carriers, and healthy individuals for time-saving and economical purposes. TTR tetramer may serve as a diagnostic biomarker to evaluate the risk of HF diseases.

The alternation of halobenzoquinone disinfection byproduct on toxicogenomics of DNA damage and repair in uroepithelial cells.

Halobenzoquinones (HBQs) were recently discovered as an emerging class of drinking water disinfection byproducts with carcinogenic concern. However, the molecular mechanism underlying HBQs-induced DNA damage is not clear. In this study, we integrated in vitro genotoxicity, computational toxicology, and the quantitative toxicogenomic analysis of HBQs on DNA damage/repair pathways in human bladder epithelial cells SV-HUC-1. The results showed that HBQs could induce cytotoxicity with the descending order as 2,6-DIBQ > 2,6-DCBQ ≈ 2,6-DBBQ. Also, HBQs can increase DNA damage in SV-HUC-1 cells and thus generate genotoxicity. However, there is no significant difference in genotoxicity among the three HBQs. The results of molecular docking and molecular dynamics simulation further confirmed that HBQs had high binding fractions and stability to DNA. Toxicogenomic analysis indicated that HBQs interfered with DNA repair pathways, mainly affecting base excision repair, nucleotide excision repair and homologous recombination repair. These results have provided new insights into the underlying molecular mechanisms of HBQs-induced DNA damage, and contributed to the understanding of the relationship between exposure to DBPs and risks of developing bladder cancer.

Occupational stress and associated risk factors among 13,867 industrial workers in China.

Objective: Occupational stress is a critical global public health problem. We aimed to evaluate the prevalence of occupational stress among the workers in the electricity, heat, gas, water production and supply (EHGWPS), manufacturing, and transportation industries in Beijing, China. We explored the demographic differences in occupational stress status among workers in industrial enterprises. Methods: A cross-sectional study was conducted on 13,867 workers. The self-administered New Brief Job Stress Questionnaire was used to evaluate high occupational stress status, which includes four sub-dimensions (job stressors, stress response, social support, job stressors & social support). Multiple regression and logistic regression models were used to estimate the association between high occupational stress and the four occupational stress sub-dimensions with risk factors. Results: A total of 13,867 workers were included. The prevalence of high occupational stress was 3.3% in the EHGWPS industries, 10.3% in manufacturing, and 5.8% in transportation. The prevalence of high occupational stress was higher than in the other two categories (p < 0.05) in manufacturing industries. Logistic regression analysis showed that male workers with lower educational status, more job experience, and working in manufacturing were vulnerable to high occupational stress. Further analysis of the four occupational stress sub-dimensions showed that male workers, older adult workers, workers with lower educational levels, and longer working time were associated with higher scores in job stressors, stress response, social support, and job stress & social support (all p < 0.05). Moreover, divorced or widowed workers had higher occupational stress scores. Conclusion: Male workers with lower educational levels and longer working time may have an increased risk of occupational stress.

Simultaneous determination of serum homocysteine, cysteine, and methionine in patients with schizophrenia by liquid chromatography-tandem mass spectrometry.

Schizophrenia is a debilitating psychiatric disorder affecting approximately 1% of the population worldwide. Disturbances in the homocysteine metabolism are an important factor in the pathophysiology of schizophrenia. In this research, a novel validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantification procedure was developed to investigate three significant compounds of homocysteine metabolism: homocysteine, cysteine, and methionine in patients with schizophrenia and healthy controls. Sample preparation involved a reduction with dithiothreitol followed by protein precipitation, and the chromatographic runtime was 2 min. The LC-MS/MS method was validated according to CLSI C62-A and the Chinese Guidance for Liquid Chromatography and Mass Spectrometry Clinical Application. The performance of the method was excellent with a coefficient of variation for precision in the range of 0.5-6.9%, an accuracy of 90.4-101.6%. In addition, the practical applicability of the method was demonstrated by applying it in the routine sample analysis for a schizophrenic patient. Increased homocysteine levels and decreased cysteine levels were observed in the patient with schizophrenia. These results indicate that the activity of the transsulfuration pathway may play a key role in the pathogenesis of schizophrenia.

Establishment of reference intervals of homocysteine, cysteine, and methionine in apparently healthy Chinese adults.

BACKGROUND: It has been widely reported that the key biomarkers of homocysteine metabolic pathways have emerged as markers or independent risk factors for cardiovascular disease and many other diseases. To improve the accuracy of evaluation in China, we establish the reference intervals of serum homocysteine (Hcy), cysteine (Cys), and methionine (Met) in apparently healthy Chinese adults. METHODS: We examined 1553 subjects aged ≥20 years who underwent Hcy metabolic pathway tests, in the Chaoyang Central Hospital between January 2019 and December 2020. The serum Hcy, Cys, and Met levels were simultaneously determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Multiple regression analysis was performed to identify sources of variation. A nonparametric method was used to establish the reference intervals. RESULTS: Gender differences were observed in Hcy and Met, with higher levels in males. Reference intervals for males were 6.09-17.00 µmol/L (Hcy) and 19.31-33.68 µmol/L (Met); conversely, the reference intervals for females were 4.61-14.61 µmol/L (Hcy) and 16.16-30.35 µmol/L (Met). The serum Cys reference intervals were seen to be gender-independent, but age-dependent reference intervals were needed; those for Cys were 188.85-334.27 µmol/L, 200.48-340.66 µmol/L, and 216.03-349.67 µmol/L in <40, 40-50, and ≥50 years, respectively. CONCLUSIONS: By this study, the gender- or age-specific reference intervals of Hcy, Cys, and Met that were matched with the Chinese population were established, providing valuable references for clinical work and laboratory researches.

The Association Between Leucine and Diabetic Retinopathy in Different Genders: A Cross-Sectional Study in Chinese Patients With Type 2 Diabetes.

Objective: To explore the association between serum leucine (leu) and diabetic retinopathy (DR) in patients with type 2 diabetes (T2D) and then to analyze the influence of gender on the association. Method: The electronic medical records of 1,149 T2D patients who met inclusion and exclusion criteria were retrieved from the Second Affiliated Hospital of Dalian Medical University and the First Affiliated Hospital of Jinzhou Medical University. Serum leu levels of all subjects were measured by liquid chromatography-mass spectrometry. Logistic regression was used to obtain the odds ratio (OR) and CI of leu-DR risk in multiple models. When using these models, restricted cubic spline (RCS) was used to test the potential non-linear relationship between multiple continuous independent variables, such as leu and DR (classification), and dependent variables. We also used the additive interaction method to evaluate the interaction effect between leu and gender on DR. Results: Leu was a protective factor of DR [0.78 (0.66, 0.92)]. When gender was divided into male and female, the above relationship was statistically significant only in men [0.73 (0.58, 0.94)]. Three indicators of additive interaction-RERI, AP, and S-suggested that there is no interaction between gender and leu on the risk of DR. Conclusions: Male T2D patients with high leu levels may have a lower risk of DR.

Acetylcarnitine Is Associated With Cardiovascular Disease Risk in Type 2 Diabetes Mellitus.

Objective: This study aimed to identify the association between specific short-chain acylcarnitines and cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM). Method: We retrieved 1,032 consecutive patients with T2DM who meet the inclusion and exclusion criteria from the same tertiary care center and extracted clinical information from electronic medical records from May 2015 to August 2016. A total of 356 T2DM patients with CVD and 676 T2DM patients without CVD were recruited. Venous blood samples were collected by finger puncture after 8 h fasting and stored as dried blood spots. Restricted cubic spline (RCS) analysis nested in binary logistic regression was used to identify possible cutoff points and obtain the odds ratios (ORs) and 95% confidence intervals (CIs) of short-chain acylcarnitines for CVD risk in T2DM. The Ryan-Holm step-down Bonferroni procedure was performed to adjust p-values. Stepwise forward selection was performed to estimate the effects of acylcarnitines on CVD risk. Result: The levels of C2, C4, and C6 were elevated and C5-OH was decreased in T2DM patients with CVD. Notably, only elevated C2 was still associated with increased CVD inT2DM after adjusting for potential confounders in the multivariable model (OR = 1.558, 95%CI = 1.124-2.159, p = 0.008). Furthermore, the association was independent of previous adjusted demographic and clinical factors after stepwise forward selection (OR = 1.562, 95%CI = 1.132-2.154, p = 0.007). Conclusions: Elevated C2 was associated with increased CVD risk in T2DM.

Effect of intensive care unit diary on incidence of posttraumatic stress disorder, anxiety, and depression of adult intensive care unit survivors: A systematic review and meta-analysis.

AIM: To systematically evaluate the effect of intensive care unit diary psychotherapy on the incidence of posttraumatic stress disorder, anxiety, and depression after discharge from intensive care unit. BACKGROUND: Many studies have reported the potential advantages and risks of intensive care unit diary psychotherapy in adult patients discharged from intensive care unit, but the results are divergent. DESIGN: Systematic review and meta-analysis of prospective randomized controlled or case-controlled studies. DATA SOURCE: Databases such as Cochran Library, Pubmed, Embase, CINAHL, and ProQuest databases, China national knowledge infrastructure (CNKI) were searched for literatures published from January 2000-March 2020. REVIEW METHODS: We use the Cochrane Risk of Bias Tool for quality assessment and audit manager 5.3 software for meta-analysis. The main result is the incidence of posttraumatic stress disorder, anxiety, and depression. RESULTS: Ten studies meeting the inclusion criteria were identified, including eight randomized controlled studies and two case-controlled studies, with a total of 1,210 patients. The pooled results of this meta-analysis indicated that the intensive care unit diary could reduce the incidence of posttraumatic stress disorder, anxiety, and depression. CONCLUSION: This study showed that an intensive care unit diary could improve the psychological symptoms of adult intensive care unit patients after discharge. However, due to limitations such as publication bias and case sample size, the results should be carefully considered. Researchers need to further clarify the multidisciplinary collaborative process of intensive care unit diary therapy, the real beneficiaries, and its impact on family members' psychological status by conducting large, robust studies in the future. IMPACT: This study's findings suggest that medical staff need to re-examine the role of intensive care unit diary therapy, its standardized implementation and provide effective intervention for reducing psychological stress-related symptoms of intensive care unit patients after discharge.

Hedging crash risk in optimal portfolio selection.

When almost all underlying assets suddenly lose a certain part of their nominal value in a market crash, the diversification effect of portfolios in a normal market condition no longer works. We integrate the crash risk into portfolio management and investigate performance measures, hedging and optimization of portfolio selection involving derivatives. A suitable convex conic programming framework based on parametric approximation method is proposed to make the problem a tractable one. Simulation analysis and empirical study are performed to test the proposed approach.

IL-21 Stimulates the expression and activation of cell cycle regulators and promotes cell proliferation in EBV-positive diffuse large B cell lymphoma.

The clinical features of EBV-positive diffuse large B cell lymphoma (DLBCL) indicate a poorer prognosis than EBV-negative DLBCL. Currently, there is no efficacious drug for EBV-positive DLBCL. The cytokine interleukin-21 (IL-21) has been reported to be pro-apoptotic in DLBCL cell lines and is being explored as a new therapeutic strategy for this type of lymphomas. However, our previous studies showed that IL-21 stimulation of EBV-positive DLBCL cell lines leads to increased proliferation. Here, analysis of a rare clinical sample of EBV-positive DLBCL, in combination with a NOD/SCID mouse xenograft model, confirmed the effect of IL-21 on the proliferation of EBV-positive DLBCL cells. Using RNA-sequencing, we identified the pattern of differentially-expressed genes following IL-21 treatment and verified the expression of key genes at the protein level using western blotting. We found that IL-21 upregulates expression of the host MYC and AP-1 (composed of related Jun and Fos family proteins) and STAT3 phosphorylation, as well as expression of the viral LMP-1 protein. These proteins are known to promote the G1/S phase transition to accelerate cell cycle progression. Furthermore, in NOD/SCID mouse xenograft model experiments, we found that IL-21 treatment increases glucose uptake and angiogenesis in EBV-positive DLBCL tumours. Although more samples are needed to validate these observations, our study reconfirms the adverse effects of IL-21 on EBV-positive DLBCL, which has implications for the drug development of DLBCL.