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Antipsychotic-induced metabolic dysfunction (AIMD) is an intractable clinical challenge worldwide. The situation is becoming more critical as second-generation antipsychotics (SGAs), to a great extent, have replaced the role of first-generation antipsychotics in managing major psychiatric disorders. Although the exact mechanisms for developing AIMD is intricate, emerging evidence has indicated the involvement of the microbiota-gut-brain axis in AIMD. SGAs treatment may change the diversity and compositions of intestinal flora (e.g., decreased abundance of Bacteroidetes and Akkermansia muciniphila, and increased Firmicutes). Short-chain fatty acids and other metabolites derived from gut microbiota, on the one hand, can regulate the activity of intestinal endocrine cells and their secretion of satiety hormones (e.g., glucagon-like peptide 1, peptide YY, cholecystokinin and ghrelin); on the other hand, can activate the vagus nerve or transport into the brain to exert a central modulation of foraging behaviors via binding to neuropeptide receptors. Interestingly, metformin, a classical antidiabetic agent, is capable of alleviating AIMD possibly by regulating the microbiota-gut-brain axis. That is, metformin can not only partially reverse the alterations of gut microbial communities due to SGAs treatment, but also play a positive role in rectifying the disturbances of peripheral and central satiety-related neuropeptides. Current evidence has indicated a promising role for metformin on ameliorating AMID, but further verifications in well-designed clinical trials are still warranted. more...

Background Reward circuit dysfunction underlies the pathogenesis of bipolar disorder (BD). This study aims to investigate whether nucleus accumbens (NAcc) and ventromedial prefrontal cortex (vmPFC), two key reward regions for BD, have resting-state dysfunctional connectivity with other brain regions in depressed and euthymic BD. Methods 40 bipolar depressive (DE), 20 euthymic patients (EU) and 20 healthy controls (HC) were recruited to undergo resting-state functional MRI (rs-fMRI) scanning. Seed-based functional connectivity (FC) was calculated between NAcc/vmPFC and the whole brain. Group differences were calculated and their correlations with clinical characteristics were analyzed. Support vector machine was applied to classify BD patients and HC based on the FC between the cluster of group difference and NAcc/vmPFC. Results Whole brain networks of FC identified right anterior insular cortex (AIC) as a significant region with bilateral NAcc when compared among three groups. The right AIC-NAcc FC elevated in both patient groups and was highest in the EU group. Interestingly, vmPFC-based networks also identified the right AIC as a significant cluster. The right AIC-vmPFC FC elevated in both patient groups. However, FC between NAcc and vmPFC did not significantly differ BD patients from HC. Furthermore, the strength of FC between bilateral NAcc and the right AIC was positively associated with the illness course of BD. Notably, the NAcc/vmPFC-right AIC classifier acquired an accuracy of 68.75% and AUC-ROC of 78.17%. Limitations Our sample size is modest. Conclusions Our findings indicated that elevated NAcc/vmPFC-right AIC connectivity within the reward circuit could be a neuroimaging endophenotype of BD. more...

Preclinical studies have shown that the gut microbiota can play a role in schizophrenia (SCH) pathogenesis via the gut-brain axis. However, its role in the antipsychotic treatment response is unclear. Here, we present a 24-week follow-up study to identify gut microbial biomarkers for SCH diagnosis and treatment response, using a sample of 107 first-episode, drug-naïve SCH patients, and 107 healthy controls (HCs). We collected biological samples at baseline (all participants) and follow-up time points after risperidone treatment (SCH patients). Treatment response was assessed using the Positive and Negative Symptoms Scale total (PANSS-T) score. False discovery rate was used to correct for multiple testing. We found that SCH patients showed lower α-diversity (the Shannon and Simpson’s indices) compared to HCs at baseline (p = 1.21 × 10−9, 1.23 × 10−8, respectively). We also found a significant difference in β-diversity between SCH patients and HCs (p = 0.001). At baseline, using microbes that showed different abundance between patients and controls as predictors, a prediction model can distinguish patients from HCs with an area under the curve (AUC) of 0.867. In SCH patients, after 24 weeks of risperidone treatment, we observed an increase of α-diversity toward the basal level of HCs. At the genus level, we observed decreased abundance of Lachnoclostridium (p = 0.019) and increased abundance Romboutsia (p = 0.067). Moreover, the treatment response in SCH patients was significantly associated with the basal levels of Lachnoclostridium and Romboutsia (p = 0.005 and 0.006, respectively). Our results suggest that SCH patients may present characteristic microbiota, and certain microbiota biomarkers may predict treatment response in this patient population. more...

Bipolar disorder (BD) is a severe affective disorder, mainly characterized by alternative depressive and manic or hypomanic episodes, yet the pathogenesis of BD has not been fully elucidated. Recent researches have implicated the altered kynurenine (KYN) metabolism involved in the neurobiology of BD. Excessive activation of the immune system also occurs in patients with BD, which further accelerates the KYN pathway for tryptophan metabolism. Changes of the KYN metabolites have effects on neuronal receptors and are involved in neuroendocrine transmissions. Interactions between KYN metabolism and the immune system may contribute to the neuropathogenesis of BD. Various studies have shown that alterations of the KYN metabolites were associated with mood, psychotic symptoms, and cognitive functions in patients with BD. In this review, we briefly introduce the KYN pathway and describe the immune dysregulation in BD as well as their interactions. We then focus on the research advances on the KYN metabolism in BD, which hold promise for identifying novel treatment targets in patients stricken with this disorder. more...

Trillions of microorganisms inhabiting in the human gut play an essential role in maintaining physical and mental health. The connections between gut microbiome and neuropsychiatric diseases have been recently identified. The pathogenesis of bipolar disorder, a spectrum of diseases manifesting with mood and energy fluctuations, also seems to be involved in the bidirectional modulation of the microbiome‐gut‐brain (MGB) axis. In this review, we briefly introduce the concept of MGB axis, and then focus on the previous findings in human studies associated with bipolar disorder. These studies provided preliminary evidences on the gut microbial alterations in bipolar disorder. Limitations in these studies and future directions in this research field, such as fecal microbiome transplantation and microbiome‐targeted therapy, were discussed. A research framework linking gut microbiome to determinants and health‐related outcomes in BD was also proposed. Better characterizing and understanding of gut microbial biosignatures in bipolar patients contribute to clarify the etiology of this intractable disease and pave the new way for treatment innovation., Previous studies have provided preliminary evidence that gut microbiome is closely linked to mental health in patients with bipolar disorder. Microbiome‐wide association studies help to illuminate the relationship between gut microorganisms and bipolar disorder. Manipulating the gut microbiome appears to be a promising strategy for treating bipolar disorder in the future. more...

This study was to examine the alterations in metabolic parameters, anti-oxidant superoxide dismutase (SOD), inflammatory marker high-sensitivity C-reactive protein (hs-CRP) and microbiota after 24-week risperidone treatment in drug naïve, normal weight, first episode schizophrenia patients; the study further examined the relationship between metabolic changes and changes in microbiota.Forty-one patients completed the 24-week study and 41 controls were enrolled in this study. Metabolic parameters, SOD, hs-CRP and the copy numbers of 5 fecal bacteria were measured at baseline (both groups) and at different time points (patients only).Patients had significantly lower numbers of fecal Bifidobacterium spp., Escherichia coli, Lactobacillus spp. compared with healthy controls (HC) (ps 0.001); in contrast, the numbers of fecal Clostridium coccoides group were significantly higher in the patient group compared with HC (p 0.001). After 24-week risperidone treatment, there were significant increases in body weight, BMI, fasting blood-glucose, triglycerides, LDL, hs-CRP, SOD and HOMA-IR (p 0.001), significant increases in the numbers of fecal Bifidobacterium spp. and E. coli (ps 0.001), and significant decreases in the numbers of fecal Clostridium coccoides group and Lactobacillus spp. (ps 0.001). Hierarchical multiple linear regression analysis shows that after controlling for potential confounding variables, only the changes in fecal Bifidobacterium spp., among 4 types of fecal bacteria, entered into the model and significantly correlated with the changes in weight (unstandardized coefficient B = 4.413, RDrug naïve, first episode schizophrenia patients show abnormalities in microbiota composition. Risperidone treatment causes significant changes in certain fecal bacteria, which are likely associated with antipsychotic medication induced metabolic changes. more...

Objectives: The hematopoietic stem cells transplantation (HSCT) is the only curable treatment in current for thalassemia major (TM).The quantity of auto stem cell of TM patients are very important for rescue the patients in case of failure of HSCT, and auto stem cells of TM will be used as target cells for gene therapy (GT) in the near future. Iron overload (IOL) can damage the hematopoiesis of TM. How to collect the auto stem cells in TM patients? How about the affects of iron overload in the mobilization and collection of auto stem cell? The aim of this study was to analyze quantity of auto stem cells in the TM and the affects of iron overload (IOL). Methods: We retrospectively analyzed a total of 134 patients and 25 normal donors undergoing PBSCs collection between January 2012 and December 2019. Patients with serum ferritin levels over 1,000 ng/mL and with a history of red blood cell transfusions prior to stem cell collection were defined as a group having transfusion-associated iron overload (IOL). In total one hundred and thirty-four patients and twenty-five donors were subcutaneous administrated G-CSF (Granulocyte Colony Stimulating Factor) 10 mg/kg/d Injection for 5 days, PBSCs was collected using a large volume leukapheresis (LVL) procedure. The data of WBC, MNC and CD34+ in product were analyzed by SPSS 20 software. Results: In 134 patients, median age is 8.60 range: (1-17),and 25 Normal donors, median age is 7.5 range: (1-18). The results demonstrated that cells either in patients with thalassemia or normal donors were effectively mobilized by G-CSF (10 mg / kg/d),as these children showed a marked increase in white blood cells and MNC cells in peripheral blood, reaching a peak in 4 to 5 days after the injection of G- CSF alone. Comparison of the MNC [(6.7±3.5) ×10⁸/kg vs (7.2±4.77) ×10⁸/kg] and CD34+cells [(10.29±4.5)×10⁶/kg vs (10.9±6.8)×10⁶/kg] in collected product in TM patients and normal donors groups revealed no significant difference. There was no significant difference between different Ferritin level (Mild, Intermediate and Severe) on WBC, MNC, and CD34+ in each group at the time point studied. But there was significant difference on MNC number (Normal liver iron (7.73±2.69)×10⁸/kg, Mild liver iron overload (7.66±4.64)×10⁸/kg, Intermediate (6.18± 2.84) ×10⁸/kg compared to Severe liver iron (4.45±3.34)×10⁸/kg, P=0.039. Significant difference was also can be seen in number of MNC of product in patients with intermediate cardiac iron overload compared to normal cardiac iron overload and mild cardiac iron overload (2.76±0.97) ×10⁶/kg vs(6.86±3.39) ×10⁶/kg and (6.88±3.72)×10⁶/kg, P=0.030. There was a statistically significant difference positive correlation between median age (P=0.011) and MNC/Kg (P=0.030). Conclusion:The quantity of mobilization of PBSC in TM patients had no significant difference compare to normal donor. The MNC in product was statistically decreased in intermediate cardiac iron overload and severe liver iron overload (IOL) subgroup. It indicated that iron overload (IOL) in organs may negatively relate to proliferation and mobilization of stem cells in TM. Further quality study of PBSC such as stem cell culture and ability of proliferation should be more evaluated. The sufficient quantity and high quality auto stem cell from TM patient can be more used in the future. Disclosures No relevant conflicts of interest to declare. more...

Rationale: Rapid eye movement sleep behavior disorder (RBD) is a kind of sleep disturbance characterized by a loss of normal paralysis of REM sleep with dream enactment behavior during REM sleep. The pharmacotherapy options for treating RBD are limited and the use of antidepressants remains controversial. Further, the role of vortioxetine in RBD has not been evaluated so far. Patient concerns: A 72-year-old woman presented with recurrent peculiar behaviors such as shouting, punching, kicking or even walking around her bedroom during sleep for over 3 years. Diagnosis: Clinical examinations and polysomnography indicated the diagnosis of RBD. Interventions: The patient received treatment with paroxetine and melatonin for 1 year and then paroxetine was discontinued and vortioxetine was initiated in a daily dose of 10 mg. Outcomes: Treatment with paroxetine and melatonin for one year was ineffective. A trial of vortioxetine 10 mg per day over 3 months resulted in significant clinical improvement. Lessons: To our knowledge, this is the first reported case of effective treatment of RBD with vortioxetine. Well-designed studies with large samples are needed to verify the clinical benefits. more...

To characterize the fractional amplitude of low-frequency fluctuation (fALFF) in drug-naïve first-episode female patients with anorexia nervosa (AN) using resting-state functional magnetic resonance imaging (rs-fMRI). Whole brain rs-fMRI data were collected from 7 drug-naïve first-episode female patients with DSM-5 AN and 14 age-matched healthy female controls. fALFF values were calculated and compared between the two groups using a two-sample t test. Correlation analysis between the fALFF values in the entire brain and body mass index (BMI) was performed. Compared with the healthy controls, increased fALFF values were observed in the AN patients in their right hippocampus and left superior frontal gyrus, while decreased fALFF values were observed in their left rectus and left middle occipital gyrus. Moreover, low BMI was significantly associated with decreased fALFF in the left inferior frontal gyrus but increased fALFF in the left calcarine. In particular, the z-standardized fALFF (zfALFF) value of the left rectus was positive associated with BMI. Our findings suggest that spontaneous brain activity in the frontal region, hippocampus and rectus, characterized by fALFF values, was altered in drug-naïve, first-episode female patients with AN. more...

Background As metabolic pathway resources become more commonly available, researchers have unprecedented access to information about their organism of interest. Despite efforts to ensure consistency between various resources, information content and quality can vary widely. Two maize metabolic pathway resources for the B73 inbred line, CornCyc 4.0 and MaizeCyc 2.2, are based on the same gene model set and were developed using Pathway Tools software. These resources differ in their initial enzymatic function assignments and in the extent of manual curation. We present an in-depth comparison between CornCyc and MaizeCyc to demonstrate the effect of initial computational enzymatic function assignments on the quality and content of metabolic pathway resources. Results These two resources are different in their content. MaizeCyc contains GO annotations for over 21,000 genes that CornCyc is missing. CornCyc contains on average 1.6 transcripts per gene, while MaizeCyc contains almost no alternate splicing. MaizeCyc also does not match CornCyc’s breadth in representing the metabolic domain; MaizeCyc has fewer compounds, reactions, and pathways than CornCyc. CornCyc’s computational predictions are more accurate than those in MaizeCyc when compared to experimentally determined function assignments, demonstrating the relative strength of the enzymatic function assignment pipeline used to generate CornCyc. Conclusions Our results show that the quality of initial enzymatic function assignments primarily determines the quality of the final metabolic pathway resource. Therefore, biologists should pay close attention to the methods and information sources used to develop a metabolic pathway resource to gauge the utility of using such functional assignments to construct hypotheses for experimental studies. Electronic supplementary material The online version of this article (doi:10.1186/s12918-016-0369-x) contains supplementary material, which is available to authorized users. more...

Arabidopsis thaliana is the most widely-studied plant today. The concerted efforts of over 11 000 researchers and 4000 organizations around the world are generating a rich diversity and quantity of information and materials. This information is made available through a comprehensive on-line resource called the Arabidopsis Information Resource (TAIR) (http://arabidopsis.org), which is accessible via commonly used web browsers and can be searched and downloaded in a number of ways. In the last two years, efforts have been focused on increasing data content and diversity, functionally annotating genes and gene products with controlled vocabularies, and improving data retrieval, analysis and visualization tools. New information include sequence polymorphisms including alleles, germplasms and phenotypes, Gene Ontology annotations, gene families, protein information, metabolic pathways, gene expression data from microarray experiments and seed and DNA stocks. New data visualization and analysis tools include SeqViewer, which interactively displays the genome from the whole chromosome down to 10 kb of nucleotide sequence and AraCyc, a metabolic pathway database and map tool that allows overlaying expression data onto the pathway diagrams. Finally, we have recently incorporated seed and DNA stock information from the Arabidopsis Biological Resource Center (ABRC) and implemented a shopping-cart style on-line ordering system. more...

This paper introduces the composition and operating principle of a television signal generator based on CPLD, it explains the logic function design and basic principle in CPLD and the hardware configuration of this system in detail. This television signal generator has many advanced features such as high precision, high reliability, simple circuit and small equipment. Furthermore, programming with hardware description language VHDL makes it easy to expand software functions more...

In this paper, an intelligent mask with EPM7256AETC144-10 core is designed. The mask has the functions of judging, alert and counting of wrong conditions. And the mask has been used in practice to increase the electromagnetic compatibility of electronic products. It can help the operator to fit screws on the shield strictly by prescribed sequence. Through this, the performance of products is improved obviously. Hardware description language VHDL and graphic editor are used to programme. The program are compiled and simulated by MAX+PLUS II application. After testing, the performance of the designed mask is steady and the functions needed in production process are preferably accomplished more...