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The "microbiota-gut-brain axis" which bridges the brain and gut microbiota is involved in the pathological mechanisms of bipolar disorder (BD), but rare is known about the exact association patterns and the potential for clinical diagnosis and treatment outcome prediction.At baseline, fecal samples and resting-state MRI data were collected from 103 BD depression patients and 39 healthy controls (HCs) for metagenomic sequencing and network-based functional connectivity (FC), grey matter volume (GMV) analyses. All patients then received 4-weeks quetiapine treatment and were further classified as responders and non-responders. Based on pre-treatment datasets, the correlation networks were established between gut microbiota and neuroimaging measures and the multimodal kernal combination support vector machine (SVM) classifiers were constructed to distinguish BD patients from HCs, and quetiapine responders from non-responders.The multi-modal pre-treatment characteristics of quetiapine responders, were closer to the HCs compared to non-responders. And the correlation network analyses found the substantial correlations existed in HC between the Anaerotruncus_ unclassified，Porphyromonas_asaccharolytica，Actinomyces_graevenitzii et al. and the functional connectomes involved default mode network (DMN),somatomotor (SM), visual, limbic and basal ganglia networks were disrupted in BD. Moreover, in terms of the multimodal classifier, it reached optimized area under curve (AUC-ROC) at 0.9517 when classified BD from HC, and also acquired 0.8292 discriminating quetiapine responders from non-responders, which consistently better than even using the best unique modality.Lack post-treatment and external validation datasets; size of HCs is modest.Multi-modalities of combining pre-treatment gut microbiota with neuroimaging endophenotypes might be a superior approach for accurate diagnosis and quetiapine efficacy prediction in BD.

The intricate processes of microbiota-gut-brain communication in modulating human cognition and emotion, especially in the context of mood disorders, have remained elusive. Here we performed faecal metagenomic, serum metabolomics and neuroimaging studies on a cohort of 109 unmedicated patients with depressed bipolar disorder (BD) patients and 40 healthy controls (HCs) to characterise the microbial-gut-brain axis in BD. Across over 12,000 measured metabolic features, we observed a large discrepancy (73.54%) in the serum metabolome between BD patients and HCs, spotting differentially abundant microbial-derived neuroactive metabolites including multiple B-vitamins, kynurenic acid, gamma-aminobutyric acid and short-chain fatty acids. These metabolites could be linked to the abundance of gut microbiota presented with corresponding biosynthetic potentials, including Akkermansia muciniphila, Citrobacter spp. (Citrobacter freundii and Citrobacter werkmanii), Phascolarctobacterium spp., Yersinia spp. (Yersinia frederiksenii and Yersinia aleksiciae), Enterobacter spp. (Enterobacter cloacae and Enterobacter kobei) and Flavobacterium spp. Based on functional neuroimaging, BD-related neuroactive microbes and metabolites were discovered as potential markers associated with BD-typical features of functional connectivity of brain networks, hinting at aberrant cognitive function, emotion regulation, and interoception. Our study combines gut microbiota and neuroactive metabolites with brain functional connectivity, thereby revealing potential signalling pathways from the microbiota to the gut and the brain, which may have a role in the pathophysiology of BD.

Preliminary studies have indicated metabolic dysfunction and gut dysbiosis in patients with bipolar disorder (BD). In this study, we aimed to clarify the impact of the gut microbial composition and function on metabolic dysfunction in BD patients with an acute depressive episode.Fresh fecal samples were provided from 58 patients with BD depression, including 29 with normal weight (NW) and 29 with overweight/obesity (OW), and 31 healthy controls (HCs). The hypervariable region of 16 S rRNA gene (V3-V4) sequencing was performed using IonS5TMXL platform to evaluate the bacterial communities. Differences of microbial community and correlation to clinical parameters across different groups were analyzed.Compared to NW and HCs, the OW group showed a decreased tendency in alpha diversity index. Beta diversity was markedly different among these groups (PERMANOVA: RSpecific bacterial taxa involved in pathways regulating the lipid, energy, and amino acid metabolisms may underlie the weight concerns in depressed BD patients. Potential targeting gut microbial therapy is provided for overweight/obesity patients with BD, which still need further studies in the future.

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.

The Arabidopsis Information Resource (TAIR; http://arabidopsis.org) is a comprehensive web resource of Arabidopsis biology for plant scientists. TAIR curates and integrates information about genes, proteins, gene function, orthologs, gene expression, mutant phenotypes, biological materials such as clones and seed stocks, genetic markers, genetic and physical maps, genome organization, images of mutant plants, protein sub-cellular localizations, publications, and the research community. The various data types are extensively interconnected and can be accessed through a variety of web-based search and display tools. This article primarily focuses on some basic methods for searching, browsing, visualizing, and analyzing information about Arabidopsis genes and genomes. Additionally, we describe how members of the community can share data via JBrowse and the Generic Online Annotation Submission Tool (GOAT) in order to make their published research more accessible and visible. © 2022 Wiley Periodicals LLC. Basic Protocol 1: TAIR homepage, sitemap, and navigation Basic Protocol 2: Finding comprehensive information about Arabidopsis genes Basic Protocol 3: Using the Arabidopsis genome browser: JBrowse Basic Protocol 4: Using the Gene Ontology annotations for gene discovery and gene function analysis Basic Protocol 5: Using gene lists to download bulk datasets Basic Protocol 6: Using TAIR's analysis tools to find short sequences and motifs Basic Protocol 7: Using the TAIR generic online annotation tool (GOAT) to submit functional annotations for Arabidopsis (or any other species) genes Basic Protocol 8: Using PhyloGenes to visualize gene families and predict functions Basic Protocol 9: Using TAIR to browse Arabidopsis literature Basic Protocol 10: Using the synteny viewer to find and display syntenic regions from Arabidopsis and other plant species.

Bipolar disorder (BD) is a common psychiatric illness with high prevalence and disease burden. Accumulating susceptibility genes for BD have been identified in recent years. However, the exact functions of these genes remain largely unknown. Despite its high heritability, gene and environment interaction is commonly accepted as the major contributing factor to BD pathogenesis. Intestine microbiota is increasingly recognized as a critical environmental factor for human health and diseases via the microbiota‐gut‐brain axis. BD individuals showed altered diversity and compositions in the commensal microbiota. In addition to pro‐inflammatory factors, such as interleukin‐6 and tumour necrosis factor‐α, type 1 interferon signalling pathway is also modulated by specific intestinal bacterial strains. Disruption of the microbiota‐gut‐brain axis contributes to peripheral and central nervous system inflammation, which accounts for the BD aetiology. Administration of type 1 interferon can induce the expression of TRANK1, which is associated with elevated circulating biomarkers of the impaired blood‐brain barrier in BD patients. In this review, we focus on the influence of intestine microbiota on the expression of bipolar gene TRANK1 and propose that intestine microbiota‐dependent type 1 interferon signalling is sufficient to induce the over‐expression of TRANK1, consequently causing the compromise of BBB integrity and facilitating the entrance of inflammatory mediators into the brain. Activated neuroinflammation eventually contributes to the occurrence and development of BD. This review provides a new perspective on how gut microbiota participate in the pathogenesis of BD. Future studies are needed to validate these assumptions and develop new treatment targets for BD.

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.

This study aimed to explore the gender specificity of gut microbiome in patients with unipolar and bipolar depression disorder by analyzing the data of gut microbiome in this two mental disorders and healthy people.A case-control study using 16S ribosomal RNA gene sequencing from fecal samples of MDD (male set, n = 43; female set, n = 77) and BD (male set, n = 82; female set, n = 83) compared with HCs (male set, n = 71; female set, n = 100) was conducted. Linear discriminant analysis was used to identify microbial characteristics. Through cooccurrence analysis, the potential correlations of the differential gut microbiota in different genders was explored. Finally, the gender-specific distinguishing microorganisms were identified as biomaker, and the diagnostic performance was verified by five-fold cross validation.A specific cluster was found enriched only in female MDD set, including 4 Bacteroideae OTUs. Similarly, 3 Lachnospiraceae OTUs was found significantly increased in female BD compared with other groups. In addition, the consistent enrichment of Pseudomonadacea in male and female may be the characteristic disease-related gut microbiota of BD. Besides, the diagnostic potential of gender specific biomarker panel in male (male validation AUC: 0.758-0.874, accurancy: 0.693-0.792; female validation AUC: 0.727-0.883, accurancy: 0.678-0.781) and female (male validation AUC: 0.787-0.883, accurancy: 0.719-0.784; female validation AUC: 0.795-0.898, accurancy: 0.689-0.838) has also been identified and confirmed.The microbiological changes in both MDD and BD are sex specific, and gender specific biomarker panel has better diagnostic performance, which provide a certain reference in sex difference for future clinical differentiation and microbial intervention.

Background: Venous thromboembolism (VTE) is a severe, life-threatening physical condition. However, the risk of developing VTE in patients with mental disorders has been insufficiently recognized.Methods: In this descriptive study, we retrospectively screened the hospital electronic medical record system and identified the asymptomatic VTE condition in hospitalized patients in the Mental Health Center, First Affiliated Hospital, Zhejiang University School of Medicine from January 2014 to January 2021. The diagnosis of VTE was made based on elevated plasma D-dimer levels and positive imaging findings, including arteriovenous color doppler ultrasonograpny of lower limbs and computed tomography angiography of pulmonary artery. For patients included, demographic and clinical profiles, and findings of laboratory and imaging examinations were collected. The anticoagulant therapy and clinical outcomes of these patients were also recorded.Results: A total of 8093 hospitalized patients were screened and eventually 24 psychiatric patients with asymptomatic VTE were included in the final analysis. The mean age of patients was 65.75±8.69 years old, with 20 patients (83.3%) older than 60 years. 18 (75%) patients were female and 6 (25%) were male. The number of patients with a history of smoking and previous pharmacotherapy was 3 and 19, respectively. And the average BMI of all subjects was 22.85±3.97, which was within the normal values. The average course of psychiatric disorders prior to the hospitalization was 9.15±10.38 years, the mean hospital stays were 23.17±9.14 days and the shortest hospital stay was 10 days. The average plasma levels of D-dimer before anticoagulant therapy was 4060.00±2824.88 ug/L FEU with a range of 920~10700 ug/L FEU (the normal range: 0~700 ug/L FEU). Following anticoagulant therapy, 83.3% (n=20) patients had a significant reduction in the plasma levels of D-dimer and the average reduced to 1678.25 ±1970.16 ug/L FEU, with a minimum level of 160 ug/L FEU. The plasma D-dimer levels between before and after anticoagulant treatment was significantly different (P＜0.05).Conclusion: Our data suggest the necessity screening the asymptomatic VTE among psychiatric patients, especially in those with advanced age, long duration of illness, and female with a long history of psychotropic treatment and high plasma levels of D-dimer. Once the diagnosis of asymptomatic VTE is confirmed, antithrombotic therapy should be initiated as early as possible to avoid fatal consequences.

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.

Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10−7 to 4.79 × 10−44). By incorporating the PRS into EBV-serology-based NPC screening, the test’s positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.

UNSTRUCTURED Biomedical data bears the potential to facilitate personalize diagnosis and precision treatment in the era of Big Data. Based on this, high-quality annotation of human specimens has become the primary mission of bio-bankers, especially for tumor bio-banks with large amounts of “omics” and clinical data. However, the lack of agreed-upon standardizations and the gap among heterogeneous databases make information application and communication a major challenge. International efforts are undergoing to develop national projects on informatics management. The aim of this paper is to provide references in data annotation and process to standardize and take full advantage of biomedical information. First, information categories that are vital for specimen applications, including sample attributes, external clinical and experimental data, are systematically listed to provide references for subsequent data mining. Second, commonly-used approaches in data collection, recording, extraction, transformation, integration and storage were summarized in support of data processes. In particular, a practical workflow of information annotation in daily bio-banking was drawn to help handling each step of the informatics management procedure. This review highlights the importance of informatics management of tumor specimens, presents the process of data standardization, and provides practical instructions for bio-bankers in specimen annotation and data management.

Discriminating depressive episodes of bipolar disorder (BD) from major depressive disorder (MDD) is a major clinical challenge. Recently, gut microbiome alterations are implicated in these two mood disorders; however, little is known about the shared and distinct microbial characteristics in MDD versus BD. Here, using 16S ribosomal RNA (rRNA) gene sequencing, the microbial compositions of 165 subjects with MDD are compared with 217 BD, and 217 healthy controls (HCs). It is found that the microbial compositions are different between the three groups. Compared to HCs, MDD is characterized by altered covarying operational taxonomic units (OTUs) assigned to the Bacteroidaceae family, and BD shows disturbed covarying OTUs belonging to Lachnospiraceae, Prevotellaceae, and Ruminococcaceae families. Furthermore, a signature of 26 OTUs is identified that can distinguish patients with MDD from those with BD or HCs, with area under the curve (AUC) values ranging from 0.961 to 0.986 in discovery sets, and 0.702 to 0.741 in validation sets. Moreover, 4 of 26 microbial markers correlate with disease severity in MDD or BD. Together, distinct gut microbial compositions are identified in MDD compared to BD and HCs, and a novel marker panel is provided for distinguishing MDD from BD based on gut microbiome signatures., Gut microbiome alterations are implicated in major depressive disorder (MDD) and bipolar disorder (BD); however, little is known about the shared and distinct microbial characteristics in MDD versus BD. Here, the distinct microbial covarying units for MDD and BD are first identified, and microbial markers for distinguishing MDD from BD based on gut microbiome signatures are provided.

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.

We aimed to characterize gut microbial alterations in depressed patients with bipolar disorder (BD) following quetiapine monotherapy and explored its potential for disease diagnosis and outcome prediction.Fecal samples were obtained from 60 healthy individuals and 62 patients in acute depressive episodes. All patients received one-month quetiapine treatment after enrollment. The structure of gut microbiota was measured with metagenomic sequencing, and its correlation with clinical profiles and brain function as indicated by resting-state functional magnetic resonance imaging was analyzed. Random forest models based on bacterial species were constructed to distinguish patients from controls, and responders from non-responders, respectively.BD patients displayed specific alterations in gut microbial diversity and composition. Quetiapine treatment increased the diversity of microbial communities and changed the composition. The abundance of Clostridium bartlettii was negatively associated with age, baseline depression severity, while positively associated with spontaneous neural oscillation in the hippocampus. Tree-based classification models for (1) patients and controls and (2) responders and non-responders showed an area under the curve of 0.733 and 0.800, respectively.Our findings add new evidence to the existing literature regarding gut dysbiosis in BD and reveal the potential of microbe-based biomarkers for disease diagnosis and treatment outcome prediction.

Acoustic data transmission in drill string is one of the effective methods to solve the bottleneck of downhole information transmission speed, but its channel characteristics are mainly affected by the structural changes of string. In the process of drilling, the downhole BHA changes constantly according to the well condition, and the shape of drill string changes indefinitely under the condition of wear and force, which leads to the uncertainty of acoustic channel. Through the numerical simulation analysis, we can get the channel changes of drill string in different shapes, and analyze the main factors that affect the information transmission. The size inconsistency of multiple drill strings will lead to the deterioration of the channel characteristics to a certain extent, but the aperiodic drilling tool structure in the channel will cause a significant change in the transmission characteristics.

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.

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.

Acoustic telemetry technology while drilling may effectively solve the practical and speed bottleneck of downhole information transmission, but its channel characteristics are subject to the influence of drill string structure in the channel. According to the requirements of reservoir exploitation and drilling technology, the directional well technology is becoming more complex, and the changeable bottom hole assembly (BHA) in the well causes the aperiodicity of acoustic channel. Through the modeling and analysis of BHA under different drilling technology, the characteristics of various aperiodic channels are obtained, and compared with the characteristics of ideal periodic channels, the acoustic transmission characteristics of drill string in directional well are obtained. The aperiodicity brought by BHA makes the high frequency section of the channel seriously attenuated, so the number of aperiodic drilling tools used in the acoustic remote transmission channel needs to be strictly controlled. It can be excluded from the channel if necessary.

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.

The maize PI gene encodes a myb-homologous protein that regulates flavonoid pigment biosynthesis in floral organs including the kernel pericarp, cob glume and tassel glume. The Pl-rr allele coding sequence is flanked by long (5.2 kbp) direct repeats. To clarily the origin of the unusual P-rr gene structure, we isolated and characterized a second, tightly linked, maize gene {P2). and a related gene {P2-t) from teosinte parviglumis. the closest wild relative of maize. The maize P2 gene and the teosinte P2-t gene are homologous to the maize PI gene in the coding region and 3" flanking region, but not in the 5' flanking region. The 5" flanking regions of maize P2 and teosinte P2-t are similar to each other, but different from that of the maize PI gene. We propose that the maize PI and P2 genes were generated by a tandem (head-to-tail) gene duplication in which the 3" flanking sequence of the progenitor P gene was duplicated at the 5' side of the incipient PI gene, thereby generating the long direct repeats that flank the Pl-rr allele. This duplication event occurred approximately 2.75 MYA. and subsequent insertions of retroelements separated the PI and P2 genes. Pigmentation phenotypes and transcript analysis indicate that the two duplicated maize P genes and the teosinte P2-t gene have distinct tissue specific expression patterns. The

The eukaryotic cell has evolved a variety of stress responses against external stimuli, such as innate immunity, the formation of stress granules (SGs), and autophagy. We previously demonstrated that the innate immune adaptor IFN-β promoter stimulator 1 (IPS-1) plays an essential role in the formation of dsRNA-induced SGs, indicating a connection between SG formation and innate immunity. In this study, it was further demonstrated that melanoma differentiation-associated gene 5 (MDA5), an innate immune sensor, is involved in SG formation induced by carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial protonophore. MDA5 knockdown had no significant impact on the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) triggered by CCCP, and MDA5 itself was not recruited to SGs, suggesting that the regulation of MDA5 in the SG response occurs downstream of eIF2α. Furthermore, the depletion of MDA5 or G3BP1 led to reduced autophagy in CCCP-stimulated cells, implying that the regulatory effect of MDA5 with respect to autophagy depends on its role in SG formation. This study uncovered an unexpected role of the innate immune protein MDA5 in SG formation and autophagy triggered by the protonophore CCCP, further supporting a correlation between different stress responses.

The MetaCyc database (MetaCyc.org) is a comprehensive and freely accessible database describing metabolic pathways and enzymes from all domains of life. MetaCyc pathways are experimentally determined, mostly small-molecule metabolic pathways and are curated from the primary scientific literature. MetaCyc contains >2100 pathways derived from >37 000 publications, and is the largest curated collection of metabolic pathways currently available. BioCyc (BioCyc.org) is a collection of >3000 organism-specific Pathway/Genome Databases (PGDBs), each containing the full genome and predicted metabolic network of one organism, including metabolites, enzymes, reactions, metabolic pathways, predicted operons, transport systems and pathway-hole fillers. Additions to BioCyc over the past 2 years include YeastCyc, a PGDB for Saccharomyces cerevisiae, and 891 new genomes from the Human Microbiome Project. The BioCyc Web site offers a variety of tools for querying and analysis of PGDBs, including Omics Viewers and tools for comparative analysis. New developments include atom mappings in reactions, a new representation of glycan degradation pathways, improved compound structure display, better coverage of enzyme kinetic data, enhancements of the Web Groups functionality, improvements to the Omics viewers, a new representation of the Enzyme Commission system and, for the desktop version of the software, the ability to save display states.

Plant metabolism underpins many traits of ecological and agronomic importance. Plants produce numerous compounds to cope with their environments but the biosynthetic pathways for most of these compounds have not yet been elucidated. To engineer and improve metabolic traits, we need comprehensive and accurate knowledge of the organization and regulation of plant metabolism at the genome scale. Here, we present a computational pipeline to identify metabolic enzymes, pathways, and gene clusters from a sequenced genome. Using this pipeline, we generated metabolic pathway databases for 22 species and identified metabolic gene clusters from 18 species. This unified resource can be used to conduct a wide array of comparative studies of plant metabolism. Using the resource, we discovered a widespread occurrence of metabolic gene clusters in plants: 11,969 clusters from 18 species. The prevalence of metabolic gene clusters offers an intriguing possibility of an untapped source for uncovering new metabolite biosynthesis pathways. For example, more than 1,700 clusters contain enzymes that could generate a specialized metabolite scaffold (signature enzymes) and enzymes that modify the scaffold (tailoring enzymes). In four species with sufficient gene expression data, we identified 43 highly coexpressed clusters that contain signature and tailoring enzymes, of which eight were characterized previously to be functional pathways. Finally, we identified patterns of genome organization that implicate local gene duplication and, to a lesser extent, single gene transposition as having played roles in the evolution of plant metabolic gene clusters.

Transcription factors (TFs) are proteins that regulate the expression of target genes by binding to specific cis-elements in promoter regions. Transcriptional regulators (TRs) also regulate the expression of target genes; however, they operate indirectly via interaction with the basal transcription apparatus (e.g. TFs), or by altering the accessibility of DNA to TFs via chromatin remodeling. Another type of regulatory proteins, protein kinases (PKs), function in signal transduction pathways and alter the activity of target proteins by phosphorylating them. These three important classes of regulatory proteins have been associated with numerous aspects of plant growth and development (Gapper et al., 2014; Xu and Zhang, 2015), and response to biotic and abiotic stimuli (Mickelbart et al., 2015; Zhang et al., 2013). Effective and accurate identification and classification of these genes is important for understanding their evolution, biological functions, and regulatory networks. Currently, more than 100 plant genomes have been sequenced and regulatory proteins have been systematically identified from several of these plant genomes. Databases presenting these regulatory proteins, especially TFs, have been developed, such as PlnTFDB (Pérez-Rodríguez et al., 2010) and PlantTFDB (Jin et al., 2013). However, annotations of TF/TR families and the associated classification rules have been inconsistent among different studies. For example, the PlantTFDB does not include TRs that are presented in PlnTFDB. As another example, the ?forbidden? domain (a domain that the specific TF families should not contain) of the C2H2 family is annotated as an RNase_T domain in PlantTFDB, but as a PHD domain in PlnTFDB. Presently, while the collection of genome sequences is rapidly expanding, cataloged and annotated TFs/TRs vary across different databases due to inconsistent identification and characterization criteria with serious consequences for genome scale and targeted analyses. Furthermore, in contrast to many studies focusing on specific families of plant regulators, computational tools for identification and classification of these regulatory proteins on a genome scale are very limited. Fil: Zheng, Yi. Boyce Thompson Institute; Estados Unidos Fil: Jiao, Chen. Boyce Thompson Institute; Estados Unidos Fil: Sun, Honghe. Boyce Thompson Institute; Estados Unidos Fil: Rosli, Hernan Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Fisiología Vegetal. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Fisiología Vegetal; Argentina. Boyce Thompson Institute; Estados Unidos Fil: Pombo, Marina Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Fisiología Vegetal. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Fisiología Vegetal; Argentina. Boyce Thompson Institute; Estados Unidos Fil: Zhang, Peifen. Carnegie Institution for Science; Estados Unidos Fil: Banf, Michael. Carnegie Institution for Science; Estados Unidos Fil: Dai, Xinbin. Samuel Roberts Noble Foundation; Estados Unidos Fil: Martin, Gregory B.. Boyce Thompson Institute; Estados Unidos. Cornell University; Estados Unidos Fil: Giovannoni, James J.. Boyce Thompson Institute; Estados Unidos. Center for Agriculture and Health; Estados Unidos Fil: Zhao, Patrick X.. Samuel Roberts Noble Foundation; Estados Unidos Fil: Rhee, Seung Y.. Carnegie Institution for Science; Estados Unidos Fil: Fei, Zhangjun. Boyce Thompson Institute; Estados Unidos. Center for Agriculture and Health; Estados Unidos

1. Insect oviposition behaviour is ecologically and physiologically plastic. For tephritid fruit flies, Bactrocera dorsalis Hendel, host availability varies spatially and temporally. Females are expected to adopt adaptive oviposition strategies to maximise lifetime reproductive fitness, including survival. Bactrocera dorsalis oviposition tactics in response to different host availabilities were investigated. 2. This study includes three treatments: (i) variable host densities (host density varied according to a fixed cycle from day to day over values of 1, 5, 10 and 20 hosts per cage), (ii) a fixed high host density (20 hosts per cage), and (iii) a fixed low host density (1 host per cage). 3. Daily egg-laying number per female over the course of 27 days was entirely independent of host density and highly dependent on female age. As host availability increased, females accepted significantly more hosts, generally laid small egg clutches, and more broadly distributed the eggs. 4. Tephritid fruit flies adaptively adjusted egg clutches in ways that reflected the variability of host availability. Egg- and time-limitation constraints appeared to drive these adjustments. Female egg maturation was triggered by oviposition activity and reflected marked lifetime trade-offs. Such strategies involved specific time schedules for egg laying. 5.This study defined the oviposition plasticity of the tephritid fruit fly. These results have general implications for the behavioural ecology of insect herbivores and parasitoids.