Trends of mental health care utilization among US adults from 1999 to 2018.

BACKGROUND: Mental health disorders affect millions of US adults, however, the trends and related factors for mental health care utilization in the US remain unknown. AIMS: Our study aimed to assess the trend of mental health utilization and related socio-demographic factors in the US. METHODS: The study included 55,052 individuals from the National Health and Nutrition Examination Survey (NHANES) in 1999-2018. Temporal trends in the percentages of mental health care utilizers were estimated across survey cycles. Trends and linked factors of mental health care utilization were assessed by a logistic regression model, while the non-linearity was estimated by restricted cubic splines. RESULTS: From 1999 to 2018, the percentage of mental health care utilizers in the US adult population increased from 7.0 to 11.3% (P < 0.001); meanwhile, the trends in males and females were consistent. The percentage increased positively with age in individuals aged 20-39 (P < 0.001) or aged 60 and over (P = 0.003). The trends were consistent in three race/ethnicity groups (P < 0.05). The logistic regression analysis revealed that several disparities existed in the subpopulations. Older age, female, lower family poverty-income ratio (PIR), chronic diseases, higher educational level, and smoking were estimated to be associated with a higher percentage of mental health care. CONCLUSIONS: The percentage of mental health care utilizers took on an increasing trend in the US adult population from 1999 to 2018. These trends were also observed in the subpopulations, but with disparities. Future research for exploring factors associated with mental health care utilizations is necessary.

Inhibition of KMO Ameliorates Myocardial Ischemia Injury via Maintaining Mitochondrial Fusion and Fission Balance.

Looking for early diagnostic markers and therapeutic targets is the key to ensuring prompt treatment of myocardial ischemia (MI). Here, a novel biomarker xanthurenic acid (XA) was identified based on metabolomics and exhibited high sensitivity and specificity in the diagnosis of MI patients. Additionally, the elevation of XA was proved to induce myocardial injury in vivo by promoting myocardial apoptosis and ferroptosis. Combining metabolomics and transcriptional data further revealed that kynurenine 3-monooxygenase (KMO) profoundly increased in MI mice, and was closely associated with the elevation of XA. More importantly, pharmacological or heart-specific inhibition of KMO obviously suppressed the elevation of XA and profoundly ameliorated the OGD-induced cardiomyocytes injury and the ligation-induced MI injury. Mechanistically, KMO inhibition effectively restrained myocardial apoptosis and ferroptosis by modulating mitochondrial fission and fusion. In addition, virtual screening and experimental validation were adopted to identify ginsenoside Rb3 as a novel inhibitor of KMO and exhibited great cardioprotective effects by regulating mitochondrial dynamical balance. Taken together, targeting KMO may provide a new approach for the clinical treatment of MI through maintaining mitochondrial fusion and fission balance, and ginsenoside Rb3 showed great potential to be developed as a novel therapeutic drug targeting KMO.

Inhibition of OAT1/3 and CMPF uptake attenuates myocardial ischemia-induced chronic heart failure via decreasing fatty acid oxidation and the therapeutic effects of ruscogenin.

Chronic heart failure (CHF) as a long-term disease is highly prevalent in elder people worldwide. Early diagnosis and treatments are crucial for preventing the development of CHF. Herein, we aimed to identify novel diagnostic biomarker, therapeutic target and drug for CHF. Untargeted metabolomic analysis has been used to characterize the different metabolomic profile between CHF patients and healthy people. Meanwhile, the targeted metabolomic study demonstrated the elevation of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) in the serum of CHF patients and coronary artery ligation-induced CHF mice. Subsequently, we firstly observed that elevation of CMPF impaired cardiac function and aggravated myocardial injury by enhancing fatty acid oxidation (FAO). Interestingly, inhibition of responsible transporters organic anion transporter 1/3 (OAT1/3) has been found to decrease the CMPF level, and suppress FAO-related key protein expressions including peroxisome proliferator-activated receptor alpha, peroxisome proliferative activated receptor-α, carnitine palmitoyl transferase 1, and malonyl CoA decarboxylase in coronary artery ligation-induced CHF mice. Meanwhile, the inhibitor of OAT1/3 presented an excellent improvement in cardiac function and histological injury. Based on the above findings, molecular docking was adopted to screen the potential therapeutic drug targeting OAT1/3, and ruscogenin (RUS) exhibited a great binding affinity with OAT1 and OAT3. Next, it was verified that RUS could remarkedly decrease the expression of OAT1/3 and CMPF levels in heart tissue of CHF mice, as well as suppress the expression of FAO-related proteins. What's more, RUS can effectively improve cardiac function, myocardial fibrosis and morphological damage. Collectively, this study provided a potential metabolic marker CMPF and novel target OAT1/3 for CHF, which were demonstrated to be involved in FAO. And RUS was identified as a potential anti-FAO drug for CHF by regulating OAT1/3.

Efficient and optimal penetration path planning for stealth unmanned aerial vehicle using minimal radar cross-section tactics and modified A-Star algorithm.

Penetration path planning for stealth unmanned aerial vehicles (SUAVs) in the integrated air defense system (IADS) has been a hot research topic in recent years. The present study examines penetration path planning in different threat environments. Firstly, for the complex terrain and static radar threats, a modified A-Star algorithm containing the bidirectional sector expansion and variable step search strategy is proposed to elude static threats rapidly. Then, with regard to bandit threats, the minimal radar cross-section (RCS) tactics are presented to achieve path replanning. Furthermore, the combinatorial methodology of the minimum RCS tactics and the modified A-Star algorithm is applied to achieve the dynamic path planning for SUAV. The simulation results indicate that the modified A-Star algorithm and minimal RCS tactics can significantly reduce the probability of radar system, which has better superiority in calculation efficiency, path cost and safety. And the minimal RCS tactics have better real-time performance and are more convenient in dealing with dynamic threats, which enhances the survivability of SUAV and verifies the effectiveness of the proposed methodology.

Distributed time-varying out formation-containment tracking of multi-UAV systems based on finite-time event-triggered control.

Considering the limited communication resources and slow convergence speed of multi-unmanned aerial vehicle (UAV) systems, this paper presents a finite-time even-triggered control framework for multi-UAV systems to achieve formation-containment tracking control. First, a virtual leader with time-varying output is introduced so that the trajectory of the whole system can be manipulated in real time. Second, the finite-time control enables that the systematic error converge to a small neighborhood of origin in finite time. Third, in order to save communication resources, an event-triggering function is developed to generate the control event sequences, which avoids continuous update of the controller. Rigorous proof shows the finite-time stability of the proposed control algorithm, and Zeno behavior is strictly excluded for each UAV. Finally, some numerical simulations are given to verify the effectiveness of the proposed controllers.

Efficient Informative Path Planning via Normalized Utility in Unknown Environments Exploration.

Exploration is an important aspect of autonomous robotics, whether it is for target searching, rescue missions, or reconnaissance in an unknown environment. In this paper, we propose a solution to efficiently explore the unknown environment by unmanned aerial vehicles (UAV). Innovatively, a topological road map is incrementally built based on Rapidly-exploring Random Tree (RRT) and maintained along with the whole exploration process. The topological structure can provide a set of waypoints for searching an optimal informative path. To evaluate the path, we consider the information measurement based on prior map uncertainty and the distance cost of the path, and formulate a normalized utility to describe information-richness along the path. The informative path is determined in every period by a local planner, and the robot executes the planned path to collect measurements of the unknown environment and restructure a map. The proposed framework and its composed modules are verified in two 3-D environments, which exhibit better performance in improving the exploration efficiency than other methods.

Ruscogenin Alleviates Myocardial Ischemia-Induced Ferroptosis through the Activation of BCAT1/BCAT2.

Ruscogenin (RUS), a natural steroidal sapogenin, exerts various biological activities. However, its effectiveness for preventing myocardial ischemia (MI) and its molecular mechanisms need further clarification. The model of MI mice and oxygen-glucose deprivation-induced cardiomyocytes injury was performed. RUS significantly alleviated MI, as evidenced by decreased infarct size, ameliorated biochemical indicators and cardiac pathological features, and markedly inhibited ferroptosis by means of the up-regulation of GPX4 and down-regulation of ACSL4 and FLC. Simultaneously, RUS notably mitigated cell injury and oxidative stress, and ameliorated ferroptosis in vitro. Subsequently, HPLC-Q-TOF/MS-based metabolomics identified BCAT1/BCAT2 as possible regulatory enzymes responsible for the cardioprotection of RUS. Importantly, RUS treatment significantly increased the expression of BCAT1 and BCAT2 in MI. Furthermore, we found that BCAT1 or BCAT2 siRNA significantly decreased cell viability, promoted ferroptosis, and increased Keap1 expression, and induced Nrf2 and HO-1 degradation in cardiomyocytes. Conversely, cardiac overexpression of BCAT1 or BCAT2 in MI mice activated the Keap1/Nrf2/HO-1 pathway. Moreover, RUS significantly activated the Keap1/Nrf2/HO-1 pathway in MI, whereas BCAT1 or BCAT2 siRNA partially weakened the protective effects of RUS, suggesting that RUS might suppress myocardial injury through BCAT1 and BCAT2. Overall, this study demonstrated that BCAT1/BCAT2 could alleviate MI-induced ferroptosis through the activation of the Keap1/Nrf2/HO-1 pathway and RUS exerted cardioprotective effects via BCAT1/BCAT2.

Isoorientin protects lipopolysaccharide-induced acute lung injury in mice via modulating Keap1/Nrf2-HO-1 and NLRP3 inflammasome pathways.

Acute lung injury (ALI) is a pulmonary disease with high mortality. The present study investigated the protective effect of isoorientin (ISO) on lipopolysaccharide (LPS)-induced ALI compared with Thalictrum minus L. (TML). The experimental ALI was achieved by LPS via endotracheal drip, ISO and TML (40 mg/kg) were administered orally 1 h prior to LPS. ISO treatment significantly protected mice from ALI and exhibited similar efficacy as TML. Administration of ISO markedly corrected weight loss and improved lung pathological damage caused by LPS. Meanwhile, a decline of lung wet to dry weight (W/D) ratios and total protein in bronchoalveolar fluid (BALF) demonstrated that ISO mitigated pulmonary edema and vascular leakage of ALI mice. Moreover, ISO also signally decreased oxidative stress and suppressed the content of interleukin-6 (IL-6) in BALF. Additionally, ISO significantly promoted the expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) and down-regulated kelch-like ECH-associated protein 1 (Keap1). Simultaneously, it suppressed the over-expression of NOD-, LRR- and pyrin domain-containing 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a CARD (ASC) and pro-inflammatory cytokines interleukin IL-1ß (pro-IL-1ß), and inhibited the expression of apoptotic related proteins induced by LPS challenge. Meanwhile, the results of molecular docking indicated the potential ability of ISO as a ligand binding with proteins Keap1, NLRP3 and cleaved-caspase-3 as well. These findings demonstrated that ISO might be one of the bioactive components of TML in the treatment of ALI and provided a rationale for future clinical applications and potential protective strategies for ALI.

1H NMR-based metabolomics analyses in children with Helicobacter pylori infection and the alteration of serum metabolites after treatment.

BACKGROUND AND AIMS: Helicobacter pylori (H. pylori) infection can occur in early childhood, without eradication therapies such infection can persist throughout life and cause many different diseases. This study investigated the metabolic characteristics and explored the underlying mechanism of children with H. pylori infection, and identified potential biomarkers for evaluating the efficacy of H. pylori eradication therapies. METHODS: We performed 1H NMR-based metabonomics coupled with multivariate analysis to investigate the metabolic profiling of serum samples between Children with and without H. pylori infection. In the same manner, we compared the alternations of metabolites in H. pylori-infected children before and after H. pylori eradication therapies. RESULTS: 21 metabolites from serum in H. pylori-infected and H. pylori-uninfected children were identified, which were mainly involved in energy, amino acid, lipid and microbial metabolism. We found that the serum levels of trimethylamine N-oxide and alanine were significantly higher in H. pylori-infected children compared to uninfected sera, whereas lactate was significantly lower. We also found that the levels of trimethylamine N-oxide and creatine in H. pylori-infected children was significantly decreased after H. pylori eradication therapies, whereas lactate and low-density lipoprotein/very low-density lipoprotein was significantly increased. CONCLUSIONS: This is the first study using 1H NMR-based metabolomics approach to explore the effects of H. pylori infection in children. Our results demonstrated that the disturbances of metabolism in energy, amino acids, lipids and microbiota could play an important role in the pathogenesis of gastrointestinal and extragastric diseases caused by H. pylori infection. Trimethylamine N-oxide and lactate might serve as potential serum biomarkers for evaluating the efficacy of H. pylori eradication therapies.

Atypical Antipsychotic Administration in Schizophrenic Patients Leads to Elevated Lipoprotein-Associated Phospholipase A2 Levels and Increased Cardiovascular Risk: A Retrospective Cohort Study.

The prevalence of cardiovascular disease (CVD) is higher in patients with schizophrenia than in the general population. We aimed to investigate whether atypical antipsychotics (AAP) increase the levels of lipoprotein-associated phospholipase A2 (Lp-PLA2), thereby increasing the risk of CVD. The data were from inpatients aged 18-60 years with a diagnosis of schizophrenia according to ICD-10 at the Affiliated Brain Hospital of Nanjing Medical University who underwent physical examination between 1 October 2014 and 30 September 2016. A retrospective cohort study was used to analyse the correlation between AAP, Lp-PLA2 levels and the CVD risk (it was determined that Lp-PLA2 values >200 ng/mL were defined as high CVD risk) in patients treated with monotherapy, olanzapine, clozapine or quetiapine. Data were collected for 452 patients with eligible schizophrenia: 163 treated with clozapine, 186 treated with olanzapine, 47 treated with quetiapine and 56 receiving no medication. Compared with the no-medication patients, AAP administration in patients with olanzapine, clozapine or quetiapine had higher serum Lp-PLA2 levels when age, sex, BMI and fasting glucose level were matched. AAP were significantly associated with serum Lp-PLA2 level by Spearman's correlation coefficients. The results of logistic regression analysis showed that AAP administration was an independent factor of CVD risk when adjusted by potential confounding factors. This study is the first to confirm that AAP administration, especially clozapine and olanzapine, could increase Lp-PLA2 levels and CVD risk, independent of drug-induced weight gain in schizophrenia. The extent and the factors of increasing Lp-PLA2 level and CVD risk in olanzapine, clozapine and quetiapine are discrepant. The possible effects of AAP on Lp-PLA2 in schizophrenia patients are involved in pro-inflammatory cytokines and hormones.

Interplay of transcription factors and microRNAs during embryonic hematopoiesis.

Hematopoietic stem cells (HSCs), which are localized in the bone marrow of adult mammals, come from hematopoietic endothelium during embryonic stages. Although the basic processes of HSC generation and differentiation have been described in the past, the epigenetic regulation of embryonic hematopoiesis remains to be fully described. Here, by utilizing an in vitro differentiation system of mouse embryonic stem cells (ESCs), we identified more than 20 microRNAs that were highly enriched in embryonic hematopoietic cells, including some (e.g. miR-10b, miR-15b, and miR-27a) with previously unknown functions in blood formation. Luciferase and gene expression assays further revealed combinational binding and regulation of these microRNAs by key transcription factors in blood cells. Finally, bioinformatics and functional analyses supported an interactive regulatory control between transcription factors and microRNAs in hematopoiesis.

The Complex Relationship Between Diet And Health.

The relationship between food and health is complex. Everyone needs food to live, but too little food, too much food, or the wrong type of food has negative consequences for health. To increase understanding of this relationship, we describe trends and patterns in food-related diseases among both adults and children. Using an ecological framework, we then describe why food intake is complex with a discussion of three broad levels--macro (including policy and social-cultural norms), local community, and individual environments--and their relationship to food consumption. Given the strong relationship between an individual's food choice and his or her surrounding environment, we end with examples of policy responses that aim to help people overcome environmental disincentives toward healthy eating. Finding ways to make eating healthfully easier and affordable for all populations is essential to shifting the average American diet toward one that promotes health.