Association of hypertension and depression with mortality: an exploratory study with interaction and mediation models.

BACKGROUND: The association of hypertension and depression with mortality has not been fully understood. We aimed to explore the possible independent or joint association of hypertension and depression with mortality. Their interaction effects on mortality and possible mediating role were also investigated. METHODS: Associations of hypertension, depression, and their interaction with all-cause and cardiovascular disease (CVD) mortality were evaluated using multivariate Cox proportional hazards regression models. The mediation analysis was conducted with a Sobel test. RESULTS: A total of 35152 participants were included in the final analysis. Hypertension and depression were independently associated with increased risk of all-cause and CVD mortality. The co-existence of hypertension and depression resulted in a 1.7-fold [95% confidence interval (CI): 1.3-2.1] increase in all-cause mortality and a 2.3-fold (95% CI: 1.4-3.7) increase in CVD mortality compared to those with neither of them. Hypertension and depression showed no significant multiplicative (P for interaction, 0.587) and additive interaction (P for relative excess risk of interaction, 0.243; P for Interaction on additive scale, 0.654) on all-cause mortality, as well as on CVD mortality. Depression did not mediate the relationship between hypertension and all-cause (Z=1.704, P=0.088) and CVD mortality (Z=1.547, P=0.122). Hypertension did not mediate the relationship between all-cause and CVD mortality as well. CONCLUSION: Hypertension and depression were related to all-cause and CVD mortality independently and the co-existence of them increased the risk of mortality. However, there is no interaction effect of them on mortality, and hypertension or depression did not mediate the association of each other with mortality.

Differentiation between depression and bipolar disorder in child and adolescents by voice features.

OBJECTIVE: Major depressive disorder (MDD) and bipolar disorder (BD) are serious chronic disabling mental and emotional disorders, with symptoms that often manifest atypically in children and adolescents, making diagnosis difficult without objective physiological indicators. Therefore, we aimed to objectively identify MDD and BD in children and adolescents by exploring their voiceprint features. METHODS: This study included a total of 150 participants, with 50 MDD patients, 50 BD patients, and 50 healthy controls aged between 6 and 16 years. After collecting voiceprint data, chi-square test was used to screen and extract voiceprint features specific to emotional disorders in children and adolescents. Then, selected characteristic voiceprint features were used to establish training and testing datasets with the ratio of 7:3. The performances of various machine learning and deep learning algorithms were compared using the training dataset, and the optimal algorithm was selected to classify the testing dataset and calculate the sensitivity, specificity, accuracy, and ROC curve. RESULTS: The three groups showed differences in clustering centers for various voice features such as root mean square energy, power spectral slope, low-frequency percentile energy level, high-frequency spectral slope, spectral harmonic gain, and audio signal energy level. The model of linear SVM showed the best performance in the training dataset, achieving a total accuracy of 95.6% in classifying the three groups in the testing dataset, with sensitivity of 93.3% for MDD, 100% for BD, specificity of 93.3%, AUC of 1 for BD, and AUC of 0.967 for MDD. CONCLUSION: By exploring the characteristics of voice features in children and adolescents, machine learning can effectively differentiate between MDD and BD in a population, and voice features hold promise as an objective physiological indicator for the auxiliary diagnosis of mood disorder in clinical practice.

The prevalence of SCT in China, its comorbidity with ADHD and its association with life events and parental-rearing behaviors.

Although sluggish cognitive tempo (SCT) symptoms are often observed in children with attention deficit hyperactivity disorder (ADHD), an increasing number of studies have highlighted its uniqueness. Nevertheless, no national survey on SCT among children and adolescents has been conducted in China. Hence, this research aims to study SCT in China and to evaluate the differences between SCT and ADHD symptoms by comparing their risk factors in terms of life events (LE) and parental rearing behaviors (PRB). This cross-sectional study used data from a survey on 71,929 children and adolescents in 5 province-level regions in China to study the incidence and demographic information of SCT in the Chinese population. Subsequently, the study investigated the comorbidity of ADHD and SCT, and conducted three logistic regressions on the LE and PRB scores to predict whether participants develop symptoms of ADHD or SCT, or neither symptom. 6658 participants were allocated into the SCT group, and the weighted point prevalence of SCT was 9.78%. 36.34% of participants with ADHD (n = 676) were found to demonstrate SCT symptoms, whereas no statistically significant difference was observed in its comorbidity to the three ADHD subtypes (χ2 = 1.668, p > 0.05, Δ = 2). The regression results on the presence or absence of ADHD revealed paternal excessive-interference and rejection, and maternal favoring were associated with ADHD diagnosis, whereas paternal punishment and favoring and maternal emotional warmth was related to the absence of ADHD symptoms. Academic stress and maternal excessive-interference were associated with SCT symptoms, and maternal emotional warmth associated with SCT absence. Concerning the presence of ADHD-only or SCT-only symptoms, LE adaptation was found to relate to SCT-only symptoms, while PRB paternal rejection and maternal favoring were associated with ADHD-only symptoms. While evidencing the high prevalence of SCT in China, our findings supported that although ADHD and SCT were highly comorbid, they may be considered two independent disorders with different risk factors. Specifically, participants with SCT symptoms are more vulnerable to stress from LE and tend to face more maladjustment than ADHD and normally-developing participants, and maternal rearing behaviours are the key factors to SCT symptoms. SCT brings global challenges in its diagnosis and treatment, and the challenge is more severe in a mentally stressful environment. Therefore, stress management and SCT etiology studies are recommended.

Comprehensive analysis of circRNA expression profile and circRNA-miRNA-mRNA network susceptibility to very early-onset schizophrenia.

To explore the potential role of circular RNAs (circRNAs) in children developing very early-onset schizophrenia (VEOS). Total RNA was extracted from the plasma samples of 10 VEOS patients and eight healthy controls. Expression profiles of circRNAs, micro RNAs (miRNAs), and messenger RNAs (mRNAs) were analyzed using RNA-seq. The interaction networks between miRNAs and targets were predicted using the miRanda tool. A differentially expressed circRNA-miRNA-mRNA (ceRNA) network was further constructed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the target mRNAs in the ceRNA network were performed to predict the potential functions of their host genes. The patient group and the control group were also compared on the regulatory patterns of circRNAs on mRNAs. 1934 circRNAs were identified from the samples and reported for the first time in schizophrenia. The circRNA expression levels were lower in the VEOS group than in the healthy control group, and 1889 circRNAs were expressed only in the control group. Differential expression analysis (i.e., log2fold change > 1.5, p 0.05) identified 235 circRNAs (1 up-regulated, 234 down-regulated), 11 miRNAs (7 up-regulated, 4 down-regulated), and 2,308 mRNAs (1906 up-regulated, 402 down-regulated) respectively. In VEOS, a ceRNA network with 10 down-regulated circRNA targets, 6 up-regulated miRNAs, and 47 down-regulated mRNAs was constructed. The target genes were involved in the membrane, the signal transduction, and the cytoskeleton and transport pathways. Finally, different expression correlation patterns of circRNA and mRNA in the network were observed between the patient group and the control group. The current research is the first to reveal the differentially expressed circRNAs in the plasma of VEOS patients. A circRNA-miRNA-mRNA network was also conducted in this study. It may be implied that the circRNAs in this network are potential diagnostic biomarkers for VEOS and they play an important role in the onset and development of VEOS symptoms.

Multidimensional voiceprint feature assessment system for identifying the depression in children and adolescents: a diagnostic test.

Objective: We designed a diagnostic test to evaluate the effectiveness and accuracy of a multidimensional voiceprint feature diagnostic assessment (MVFDA) system vs. the 24-item Hamilton Rating Scale for Depression (HAMD-24) for adjunctive diagnosis of children and adolescents with major depressive disorder (MDD). Methods: This study included 55 children aged 6-16 years who were clinically diagnosed with MDD according to the DSM-5 and analyzed by professional physicians, and 55 healthy children (typically developing). Each subject completed a voice recording and was scored on the HAMD-24 scale by a trained rater. We calculated the validity indices, including sensitivity, specificity, Youden's index, likelihood ratio, and other indices including predictive value, diagnostic odds ratio, diagnostic accuracy, and area under the curve (AUC), to assess the effectiveness of the MVFDA system in addition to the HAMD-24. Results: The sensitivity (92.73 vs. 76.36%) and the specificity (90.91 vs. 85.45%) of the MVFDA system are significantly higher than those of the HAMD-24. The AUC of the MVFDA system is also higher than that of the HAMD-24. There is a statistically significant difference between the groups (p < 0.05), and both of them have high diagnostic accuracy. In addition, the diagnostic efficacy of the MVFDA system is higher than that of HAMD-24 in terms of the Youden index, diagnostic accuracy, likelihood ratio, diagnostic odds ratio, and predictive value. Conclusion: The MVFDA has performed well in clinical diagnostic trials for the identification of MDD in children and adolescents by capturing objective sound features. Compared with the scale assessment method, the MVFDA system could be further promoted in clinical practice due to its advantages of simple operation, objective rating, and high diagnostic efficiency.

Plant Disease Resistance-Related Signaling Pathways: Recent Progress and Future Prospects.

Plant-pathogen interactions induce a signal transmission series that stimulates the plant's host defense system against pathogens and this, in turn, leads to disease resistance responses. Plant innate immunity mainly includes two lines of the defense system, called pathogen-associated molecular pattern-triggered immunity (PTI) and effector-triggered immunity (ETI). There is extensive signal exchange and recognition in the process of triggering the plant immune signaling network. Plant messenger signaling molecules, such as calcium ions, reactive oxygen species, and nitric oxide, and plant hormone signaling molecules, such as salicylic acid, jasmonic acid, and ethylene, play key roles in inducing plant defense responses. In addition, heterotrimeric G proteins, the mitogen-activated protein kinase cascade, and non-coding RNAs (ncRNAs) play important roles in regulating disease resistance and the defense signal transduction network. This paper summarizes the status and progress in plant disease resistance and disease resistance signal transduction pathway research in recent years; discusses the complexities of, and interactions among, defense signal pathways; and forecasts future research prospects to provide new ideas for the prevention and control of plant diseases.

Association between acrylamide exposure and the odds of developmental disabilities in children: A cross-sectional study.

Background: The association between acrylamide exposure and the odds of developmental disabilities (DDs) is unclear. We conducted this analysis to explore whether acrylamide exposure is related to DDs. Methods: We analyzed a sample of 1,140 children aged 6-17 years old from the US National Health and Nutrition Examination Survey 2013-2014 to 2015-2016. DDs were determined by reports of parents. Acrylamide exposure was evaluated by the hemoglobin adducts of acrylamide (HbAA) and its major metabolite glycidamide (HbGA). We investigated the association using binomial logistic regression analysis by taking HbAA and HbGA as continuous or quartile variables. Restricted cubic splines (RCS) were used to explore the non-linear relationship between HbAA or HbGA and the odds of DDs. Interaction analysis and propensity score matching (PSM) were used to validate the results. Results: A total of 134 participants were reported to have DDs. The median level of HbAA and HbGA was 41.6 and 40.5 pmol/g Hb, respectively. HbAA and HbGA were not associated with the odds of DDs when taken as continuous variables. When divided into quartiles, there was no evidence for a linear trend for HbAA and HbGA. RCS showed that there was a J-shaped association between HbGA and the odds of DDs (P for non-linearity, 0.023). The results were consistent in interaction analysis by age, gender, and race, and after PSM. Conclusion: HbGA level was associated with the odds of DDs in a J-shaped manner among children. Further investigation is warranted to determine the causality and underlying mechanisms.

The Prevalence and Comorbidity of Tic Disorders and Obsessive-Compulsive Disorder in Chinese School Students Aged 6-16: A National Survey.

Background: Obsessive-compulsive disorder (OCD) and tic disorders (TDs) are closely related and considered to etiologically overlap. Both disorders are characterized by repetitive behaviors. TD and OCD often co-occur. The high comorbidity between OCD and TD individuals suggests that we also need to pay more attention to the homogeneity and heterogeneity between TS and OCD. To date, there has been no systematic nationwide epidemiological survey of the mental health (including tic disorders and obsessive-compulsive disorder) of children and adolescents in China. Methods: A two-stage epidemiological study of psychiatric point prevalence was conducted. We used the multistage cluster stratified random sampling strategy to assess five provinces of China. The Child Behavior Checklist was used to identify behavioral problems among the enrolled students in the first stage. The results from the Mini-International Neuropsychiatric Interview for Children and Adolescents and evaluations from two psychiatrists based on the Diagnostic and Statistical Manual-IV were used to make a diagnosis. Point weighted prevalence for TD and OCD was estimated. We adjusted prevalence estimates with the product of sampling weights and poststratification weights. Standard error values and 95% confidential intervals were generated with Taylor series linearization. Rao−Scott adjusted chi-square (χ2) tests were employed to compare the prevalence estimates of different age and sex groups. Results: In the first stage, 73,992 participants aged 6−16 years old were selected. The prevalence rates of OCD and TDs were 1.37% (95% CI: 1.28−1.45) and 2.46% (95% CI: 2.35−2.57), respectively. The prevalence of OCD was found to be higher in girls (p < 0.001) and higher in boys with transient tic disorder (TTD) (p < 0.001) and Tourette's syndrome (TS) (p < 0.001). The most common comorbidity of TS was OCD (40.73%), and for OCD, it was TS (11.36%). Conclusions: Our study is the first nationwide survey on the prevalence of TD (2.46%) and OCD (1.37%) in school students aged 6−16 years old in China. The high comorbidity between OCD and TD individuals suggested overlap based on the prevalence dimensions, which might be influenced by age and sex. This result suggested that we also need to pay more attention to the homogeneity and heterogeneity between TS and OCD.

MAPK pathway-related tyrosine phosphatases regulate development, secondary metabolism and pathogenicity in fungus Aspergillus flavus.

Mitogen-activated protein kinase (MAPK) cascades are highly conserved in eukaryotic cells and are known to play crucial roles in the regulation of various cellular processes. However, compared with kinase-mediated phosphorylation, dephosphorylation catalysed by phosphatases has not been well characterized in filamentous fungi. In this study, we identified five MAPK pathway-related phosphatases (Msg5, Yvh1, Ptp1, Ptp2 and Oca2) and characterized their functions in Aspergillus flavus, which produces aflatoxin B1 (AFB1 ), one of the most toxic and carcinogenic secondary metabolites. These five phosphatases were identified as negative regulators of MAPK (Slt2, Fus3 and Hog1) pathways. Deletion of Msg5 and Yvh1 resulted in significant defects in conidiation, sclerotia formation, aflatoxin production and crop infection. Additionally, double knockout mutants (ΔMsg5/ΔPtp1, ΔMsg5/ΔPtp2 and ΔMsg5/ΔOca2) displayed similar defects to those observed in the ΔMsg5 single mutant, indicating that Msg5 plays a major role in the regulation of development and pathogenicity in A. flavus. Importantly, we found that the active site at C439 is essential for the function of the Msg5 phosphatase. Furthermore, the MAP kinase Fus3 was found to be involved in the regulation of development, aflatoxin biosynthesis and pathogenicity, and its conserved phosphorylation residues (Thr and Tyr) were critical for the full range of its functions in A. flavus. Overall, our results reveal that MAPK related tyrosine phosphatases play important roles in the regulation of development, secondary metabolism and pathogenicity in A. flavus, and could be developed as potential targets for preventing damage caused by this fungal pathogen.

The furofuran-ring selectivity, hydrogen peroxide-production and low Km value are the three elements for highly effective detoxification of aflatoxin oxidase.

AFO (aflatoxin oxidase), an enzyme from Armillariella tabescens previously named aflatoxin detoxifizyme, exhibits oxidative detoxification activity toward aflatoxin B1 and sterigmatocystin. Bioinformatics reveals that AFO is a newly discovered oxidase because AFO does not share any significant similarities with any known oxidase. It is critically important to understand how AFO acts on aflatoxin B1. In this study, in addition to aflatoxin B1 (AFB1) and sterigmatocystin (ST), five other chemicals that have furan or pyran structures were investigated. The results indicated that in addition to AFB1 and ST, AFO is also able to act on versicolorin A, 3,4-dihydro-2H-pyran and furan. These results suggested that 8,9-unsaturated carboncarbon bond of aflatoxin B1 is the potential reactive site for AFO. Further findings indicated that the action of AFO is oxygen-dependent and hydrogen peroxide-producing. The simultaneously produced-hydrogen peroxide possibly plays the essential role in detoxification of AFO. In addition, the extremely low Km value of 0.33 µmol/l for AFO-AFB1 and 0.11 µmol/l for AFO-ST signifies that AFO is highly selective for AFB1 as well as ST.