Integrative multiomics profiling of passion fruit reveals the genetic basis for fruit color and aroma.

Passion fruit (Passiflora edulis) possesses a complex aroma and is widely grown in tropical and subtropical areas. Here, we conducted the de novo assembly, annotation, and comparison of PPF (P. edulis Sims) and YPF (P. edulis f. flavicarpa) reference genomes using PacBio, Illumina, and Hi-C technologies. Notably, we discovered evidence of recent whole-genome duplication events in P. edulis genomes. Comparative analysis revealed 7.6∼8.1 million single nucleotide polymorphisms, 1 million insertions/deletions, and over 142 Mb presence/absence variations among different P. edulis genomes. During the ripening of yellow passion fruit, metabolites related to flavor, aroma, and color were substantially accumulated or changed. Through joint analysis of genomic variations, differentially expressed genes, and accumulated metabolites, we explored candidate genes associated with flavor, aroma, and color distinctions. Flavonoid biosynthesis pathways, anthocyanin biosynthesis pathways, and related metabolites are pivotal factors affecting the coloration of passion fruit, and terpenoid metabolites accumulated more in PPF. Finally, by heterologous expression in yeast (Saccharomyces cerevisiae), we functionally characterized 12 terpene synthases. Our findings revealed that certain TPS homologs in both YPF and PPF varieties produce identical terpene products, while others yield distinct compounds or even lose their functionality. These discoveries revealed the genetic and metabolic basis of unique characteristics in aroma and flavor between the 2 passion fruit varieties. This study provides resources for better understanding the genome architecture and accelerating genetic improvement of passion fruits.

Three enigmatic BioH isoenzymes are programmed in the early stage of mycobacterial biotin synthesis, an attractive anti-TB drug target.

Tuberculosis (TB) is one of the leading infectious diseases of global concern, and one quarter of the world's population are TB carriers. Biotin metabolism appears to be an attractive anti-TB drug target. However, the first-stage of mycobacterial biotin synthesis is fragmentarily understood. Here we report that three evolutionarily-distinct BioH isoenzymes (BioH1 to BioH3) are programmed in biotin synthesis of Mycobacterium smegmatis. Expression of an individual bioH isoform is sufficient to allow the growth of an Escherichia coli ΔbioH mutant on the non-permissive condition lacking biotin. The enzymatic activity in vitro combined with biotin bioassay in vivo reveals that BioH2 and BioH3 are capable of removing methyl moiety from pimeloyl-ACP methyl ester to give pimeloyl-ACP, a cognate precursor for biotin synthesis. In particular, we determine the crystal structure of dimeric BioH3 at 2.27Å, featuring a unique lid domain. Apart from its catalytic triad, we also dissect the substrate recognition of BioH3 by pimeloyl-ACP methyl ester. The removal of triple bioH isoforms (ΔbioH1/2/3) renders M. smegmatis biotin auxotrophic. Along with the newly-identified Tam/BioC, the discovery of three unusual BioH isoforms defines an atypical 'BioC-BioH(3)' paradigm for the first-stage of mycobacterial biotin synthesis. This study solves a long-standing puzzle in mycobacterial nutritional immunity, providing an alternative anti-TB drug target.

New Loss-of-Function Mutations in PCSK9 Reduce Plasma LDL Cholesterol.

BACKGROUND: Lower plasma levels of LDL (low-density lipoprotein) cholesterol (LDL-C) can reduce the risk of atherosclerotic cardiovascular disease. The loss-of-function mutations in PCSK9 (proprotein convertase subtilisin/kexin type 9) have been known to associate with low LDL-C in many human populations. PCSK9 genetic variants in Chinese Uyghurs who are at high risk of atherosclerotic cardiovascular disease due to their dietary habits have not been reported. METHODS: The study involved the whole-exome and target sequencing of college students from Uyghur and other ethnic groups in Xinjiang, China, for the association of PCSK9 loss-of-function mutations with low plasma levels of LDL-C. The mechanisms by which the identified mutations affect the function of PCSK9 were investigated in cultured cells using biochemical and cell assays. The causal effects of the identified PCSK9 mutations on LDL-C levels were verified in mice injected with adeno-associated virus expressing different forms of PCSK9 and fed a high-cholesterol diet. RESULTS: We identified 2 PCSK9 mutations-E144K and C378W-in Chinese Uyghurs with low plasma levels of LDL-C. The E144K and C378W mutations impaired the maturation and secretion of the PCSK9 protein, respectively. Adeno-associated virus-mediated expression of E144K and C378W mutants in Pcsk9 KO (knockout) mice fed a high-cholesterol diet also hampered PCSK9 secretion into the serum, resulting in elevated levels of LDL receptor in the liver and reduced levels of LDL-C in the serum. CONCLUSIONS: Our study shows that E144K and C378W are PCSK9 loss-of-function mutations causing low LDL-C levels in mice and probably in humans as well.

Altered Effective Connectivity Among the Cerebellum and Cerebrum in Patients with Major Depressive Disorder Using Multisite Resting-State fMRI.

Major depressive disorder (MDD) is a serious and widespread psychiatric disorder. Previous studies mainly focused on cerebrum functional connectivity, and the sample size was relatively small. However, functional connectivity is undirected. And, there is increasing evidence that the cerebellum is also involved in emotion and cognitive processing and makes outstanding contributions to the symptomology and pathology of depression. Therefore, we used a large sample size of resting-state functional magnetic resonance imaging (rs-fMRI) data to investigate the altered effective connectivity (EC) among the cerebellum and other cerebral cortex in patients with MDD. Here, from the perspective of data-driven analysis, we used two different atlases to divide the whole brain into different regions and analyzed the alterations of EC and EC networks in the MDD group compared with healthy controls group (HCs). The results showed that compared with HCs, there were significantly altered EC in the cerebellum-neocortex and cerebellum-basal ganglia circuits in MDD patients, which implied that the cerebellum may be a potential biomarker of depressive disorders. And, the alterations of EC brain networks in MDD patients may provide new insights into the pathophysiological mechanisms of depression.

Relationship between childhood maltreatment and cognitive function in medication-free patients with major depressive disorder.

This study aimed to elucidate the contribution of childhood maltreatment (CM) and the disease of major depressive disorder (MDD) on cognitive function in medication-free patients in a current depressive episode, and to examine the effect of CM on the improvement of cognitive function after treatment with antidepressants. One hundred and fifty-three unmedicated patients with MDD and 142 healthy controls (HCs) underwent clinical interviews. CM assessment was performed using the Childhood Trauma Questionnaire (CTQ), and a battery of comprehensive neurocognitive tests was used to assess the participants' executive function, processing speed, attention, and memory. After 6 months of treatment with antidepressants, the neurocognitive tests were reperformed in patients with MDD and HCs. There was a significant main effect of MDD on all four cognitive domains, while the main effect of CM was only significant on memory. No significant interactive effect was found between MDD and CM on any of the cognitive domains. In the MDD group, higher CTQ total score was predictive of poorer memory performance. After treatment, significant main effects of treatment and MDD were found on all four cognitive domains in remitted patients with MDD. No significant main effect of CM or three-way interaction effect of treatment × MDD × CM was found on any of the cognitive domains. The disease of MDD contributed to impairments in all four cognitive domains. CM independently contributed to memory impairment in patients in a current depressive episode, with higher severity of CM predictive of poorer memory performance.

D-Xylose Blocks the Broad Negative Regulation of XylR on Lipid Metabolism and Affects Multiple Physiological Characteristics in Mycobacteria.

D-xylose is the most abundant fermentable pentose, which usually represents an architectural component of the bacterial cell wall. However, its regulatory function and the involved signaling pathway in bacteria remain largely unclear. Here, we show that D-xylose can act as a signaling molecule to regulate the lipid metabolism and affect multiple physiological characteristics in mycobacteria. D-xylose directly interacts with XylR and inhibits its DNA-binding ability, thus blocking XylR-mediated repression. The xylose inhibitor, XylR, plays a global regulatory role and affects the expression of 166 mycobacterial genes that are involved in lipid synthesis and metabolism. Furthermore, we show that the xylose-dependent gene regulation of XylR affects the multiple physiological characteristics of Mycobacterium smegmatis, including bacterial size, colony phenotype, biofilm formation, cell aggregation, and antibiotic resistance. Finally, we found that XylR inhibited the survival of Mycobacterium bovis BCG in the host. Our findings provide novel insights into the molecular mechanism of lipid metabolism regulation and its correlation with bacterial physiological phenotypes.

Psychosocial crisis intervention for coronavirus disease 2019 patients and healthcare workers. / æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žæ‚£è€ å’ŒåŒ»åŠ¡äººå‘˜çš„å¿ƒç†ç¤¾ä¼šå±æœºå¹²é¢„ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Shelter hospital was an alternative way to provide large-scale medical isolation and treatment for people with mild coronavirus disease 2019 (COVID-19). Due to various reasons, patients admitted to the large shelter hospital was reported high level of psychological distress, so did the healthcare workers. This study aims to introduce a comprehensive and multifaceted psychosocial crisis intervention model. METHODS: The psychosocial crisis intervention model was provided to 200 patients and 240 healthcare workers in Wuhan Wuchang shelter hospital. Patient volunteers and organized peer support, client-centered culturally sensitive supportive care, timely delivery of scientific information about COVID-19 and its complications, mental health knowledge acquisition of non-psychiatric healthcare workers, group activities, counseling and education, virtualization of psychological intervention, consultation and liaison were exhibited respectively in the model. Pre-service survey was done in 38 patients and 49 healthcare workers using the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Patient Health Questionnaire 2-item (PHQ-2) scale, and the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (PC-PTSD-5). Forty-eight healthcare workers gave feedback after the intervention. RESULTS: The psychosocial crisis intervention model was successfully implemented by 10 mental health professionals and was well-accepted by both patients and healthcare workers in the shelter hospital. In pre-service survey, 15.8% of 38 patients were with anxiety, 55.3% were with stress, and 15.8% were with depression; 16.3% of 49 healthcare workers were with anxiety, 26.5% were with stress, and 22.4% were with depression. In post-service survey, 62.5% of 48 healthcare workers thought it was very practical, 37.5% thought more practical; 37.5% of them thought it was very helpful to relief anxiety and insomnia, and 27.1% thought much helpful; 37.5% of them thought it was very helpful to recognize patients with anxiety and insomnia, and 29.2% thought much helpful; 35.4% of them thought it was very helpful to deal with patients' anxiety and insomnia, and 37.5% thought much helpful. CONCLUSIONS: Psychological crisis intervention is feasible, acceptable, and associated with positive outcomes. Future tastings of this model in larger population and different settings are warranted.

SUMOylation of the ubiquitin ligase IDOL decreases LDL receptor levels and is reversed by SENP1.

Inducible degrader of the low-density lipoprotein receptor (IDOL) is an E3 ubiquitin ligase mediating degradation of low-density lipoprotein (LDL) receptor (LDLR). IDOL also controls its own stability through autoubiquitination, primarily at lysine 293. Whether IDOL may undergo other forms of posttranslational modification is unknown. In this study, we show that IDOL can be modified by small ubiquitin-like modifier 1 at the K293 residue at least. The SUMOylation of IDOL counteracts its ubiquitination and augments IDOL protein levels. SUMOylation and the associated increase of IDOL protein are effectively reversed by SUMO-specific peptidase 1 (SENP1) in an activity-dependent manner. We further demonstrate that SENP1 affects LDLR protein levels by modulating IDOL. Overexpression of SENP1 increases LDLR protein levels and enhances LDL uptake in cultured cells. On the contrary, loss of SENP1 lowers LDLR levels in an IDOL-dependent manner and reduces LDL endocytosis. Collectively, our results reveal SUMOylation as a new regulatory posttranslational modification of IDOL and suggest that SENP1 positively regulates the LDLR pathway via deSUMOylation of IDOL and may therefore be exploited for the treatment of cardiovascular disease.

High efficiency of left superior frontal gyrus and the symptom features of major depressive disorder. / å·¦ä¾§é¢ä¸Šå›žç½‘ç»œèŠ‚ç‚¹é«˜æ•ˆçŽ‡å€¼ä¸ŽæŠ‘éƒç—‡ç—‡çŠ¶ç‰¹å¾çš„å ³ç³».

OBJECTIVES: Major depressive disorder (MDD) patients with anhedonia tend to have a poor prognosis. The underlying imaging basis for anhedonia in MDD remains largely unknown. The relationship between nodal properties and anhedonia in MDD patients need to be further investigated. Herein, this study aims to explore differences of cerebral functional node characteristics in MDD patients with severe anhedonia (MDD-SA) and MDD patients with mild anhedonia (MDD-MA) before and after the antidepressant treatment. METHODS: Ninety participants with current MDD were recruited in this study. 24-Item Hamilton Depression Scale (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess the severity of depression and anhedonia at baseline and the end of 6-months treatment. The MDD patients who scored above the 25th percentile on the SHAPS were assigned to an MDD-SA group (n=19), while those who scored below the 25th percentile were assigned to an MDD-MA group (n=18). All patients in the 2 groups received antidepressant treatment. Functional magnetic resonance imaging (fMRI) images of all the patients were collected at baseline and the end of 6-months treatment. Graph theory was applied to analyze the patients' cerebral functional nodal characteristics, which were measured by efficiency (ei) and degree (ki). RESULTS: Repeated measures 2-factor ANCOVA showed significant main effects on group on the ei and ki values of left superior frontal gyrus (LSFG) (P=0.003 and P=0.008, respectively), and on the ei and ki values of left medial orbital-frontal gyrus (LMOFG) (P=0.004 and P=0.008, respectively). Compared with the MDD-MA group, the significantly higher ei and ki values of the LSFG (P=0.015 and P=0.021, respectively), and the significantly higher ei and ki values of the LMOFG (P=0.015 and P=0.037, respectively) were observed in the MDD-SA group at baseline. Meanwhile, higher SHAPS scores could result in higher ei and ki values of LSFG (P=0.019 and P=0.026, respectively), and higher ei value of LMOFG (P=0.040) at baseline; higher SHAPS scores could result in higher ei values of LSFG (P=0.049) at the end of 6-months treatment. The multiple linear regression analysis revealed that sex were negatively correlated with the ei and ki values of LSFG (r= -0.014, P=0.004; r=-1.153, P=0.001, respectively). The onset age of MDD was negatively correlated with the ki value of LSFG (r=-0.420, P=0.034) at the end of 6-months treatment. We also found that SHAPS scores at baseline were positively correlated with the HAMD-24 scores (r=0.387, P=0.022) at the end of 6-months treatment. CONCLUSIONS: There are obvious differences in nodal properties between the MDD-SA and the MDD-MA patients, such as the high ei of LSFG in the MDD-SA patients, which may be associated with the severity of anhedonia. These nodal properties could be potential biomarkers for the prognosis of MDD. The increased ei and ki values in the LSFG of MDD-SA patients may underlie a compensatory mechanism or protective mechanism. The mechanism may be an important component of the pathological mechanism of MDD-SA. The poor prognosis in the MDD-SA patients suggests that anhedonia may predict a worse prognosis in MDD patients. Sex and onset age of MDD may affect the nodal properties of LSFG at baseline and the end of 6-months treatment.

A novel stress-inducible CmtR-ESX3-Zn2+ regulatory pathway essential for survival of Mycobacterium bovis under oxidative stress.

Reactive oxygen species (ROS) are an unavoidable host environmental cue for intracellular pathogens such as Mycobacterium tuberculosis and Mycobacterium bovis; however, the signaling pathway in mycobacteria for sensing and responding to environmental stress remains largely unclear. Here, we characterize a novel CmtR-Zur-ESX3-Zn2+ regulatory pathway in M. bovis that aids mycobacterial survival under oxidative stress. We demonstrate that CmtR functions as a novel redox sensor and that its expression can be significantly induced under H2O2 stress. CmtR can physically interact with the negative regulator Zur and de-represses the expression of the esx-3 operon, which leads to Zn2+ accumulation and promotion of reactive oxygen species detoxication in mycobacterial cells. Zn2+ can also act as an effector molecule of the CmtR regulator, using which the latter can de-repress its own expression for further inducing bacterial antioxidant adaptation. Consistently, CmtR can induce the expression of EsxH, a component of esx-3 operon involved in Zn2+ transportation that has been reported earlier, and inhibit phagosome maturation in macrophages. Lastly, CmtR significantly contributes to bacterial survival in macrophages and in the lungs of infected mice. Our findings reveal the existence of an antioxidant regulatory pathway in mycobacteria and provide novel information on stress-triggered gene regulation and its association with host-pathogen interaction.

MmbR, a master transcription regulator that controls fatty acid ß-oxidation genes in Mycolicibacterium smegmatis.

An unusually high lipid content and a complex lipid profile are the most distinctive features of the mycobacterial cell envelope. However, our understanding of the regulatory mechanism underlying mycobacterial lipid metabolism is limited, and the major regulators responsible for lipid homeostasis remain to be characterized. Here, we identified MmbR as a novel master regulator that is essential for maintaining lipid homeostasis in Mycolicibacterium smegmatis. We found that MmbR controls fatty acid ß-oxidation and modulates biofilm formation in Mycolicibacterium smegmatis. Although MmbR possesses the properties of nucleoid-associated proteins, it acts as a TetR-like transcription factor, directly regulating and intensively repressing the expression of a group of core genes involved in fatty acid ß-oxidation. Furthermore, both long-chain acyl-Coenzyme A and fatty acids appear to regulate the signal molecules modulated by MmbR. The deletion of mmbR led to a significant reduction in intracellular fatty acid content and a decrease in the relative lipid composition of the biofilm. The lack of mmbR led to morphological changes in the mycobacterial colony, defects in biofilm formation and enhanced sensitivity to anti-tuberculosis drugs. Our study is the first to establish a link between the transcriptional regulation of fatty acid ß-oxidation genes and lipid homeostasis in mycobacteria.

Cyclic di-GMP co-activates the two-component transcriptional regulator DevR in Mycobacterium smegmatis in response to oxidative stress.

Cyclic di-GMP (c-di-GMP) is an important second messenger in bacteria, and its regulatory network has been extensively studied. However, information regarding the activation mechanisms of its receptors remains limited. In this study, we characterized the two-component regulator DevR as a new c-di-GMP receptor and further uncovered a novel co-activation mechanism for effective regulation of DevR in mycobacteria. We show that high c-di-GMP levels induce the expression of the devR operon in Mycobacterium smegmatis and increase mycobacterial survival under oxidative stress. The deletion of either DevR or its two-component kinase DevS significantly weakened the stimulating effect of c-di-GMP on oxidative-stress tolerance of mycobacteria. We also found that DevR senses the c-di-GMP signal through its C-terminal structure and that c-di-GMP alone does not directly affect the DNA-binding activity of DevR. Strikingly, c-di-GMP stimulated DevR phosphorylation by the kinase DevS, thereby activating DevR's DNA-binding affinity. In summary, our results indicated that c-di-GMP triggers a phosphorylation-dependent mechanism that co-activates DevR's transcriptional activity. Our findings suggest a novel paradigm for the cross-talk between c-di-GMP signaling and two-component regulatory systems that activates transcription of stress-response genes in bacteria.

China's mental health support in response to COVID-19: progression, challenges and reflection.

The continued spread of the coronavirus disease 2019 (COVID-19) has a serious impact on everyone across the globe, both physically and psychologically. In addition to proactive measures addressing physical survival needs and health protection, China has launched a mental health support system to cope with the widespread psychological stress during the pandemic and its aftermath. In this debate, the authors attempted to depict and reflect upon the overall framework of China's mental health support, with particular reference to the psychological intervention in response to COVID-19 over the last few months. Although a lot of effort has been made to meet the mental health needs, the accessibility, acceptability and effectiveness of the support system still have much room for improvement. Therefore, it is very important to re-think the predicament and challenge on ways of enhancing public mental health emergency responses in China. The concepts of universality, timeliness and scientific rigour were proposed as a possible reform in preparation for large-scale natural or man-made disasters in the coming future.

HpoR, a novel c-di-GMP effective transcription factor, links the second messenger's regulatory function to the mycobacterial antioxidant defense.

Cyclic di-GMP (c-di-GMP) is a global signaling molecule that widely modulates diverse cellular processes. However, whether or not the c-di-GMP signal participates in regulation of bacterial antioxidant defense is unclear, and the involved regulators remain to be explored. In this study, we characterized HpoR as a novel c-di-GMP effective transcription factor and found a link between the c-di-GMP signal and the antioxidant regulation in Mycobacterium smegmatis. H2O2 stress induces c-di-GMP accumulation in M. smegmatis. High level of c-di-GMP triggers expression of a redox gene cluster, designated as hpoR operon, which is required for the mycobacterial H2O2 resistance. HpoR acts as an inhibitor of the hpoR operon and recognizes a 12-bp motif sequence within the upstream regulatory region of the operon. c-di-GMP specifically binds with HpoR at a ratio of 1:1. Low concentrations of c-di-GMP stimulate the DNA-binding activity of HpoR, whereas high concentrations of the signal molecule inhibit the activity. Strikingly, high level of c-di-GMP de-represses the intracellular association of HpoR with the regulatory region of the hpoR operon in M. smegmatis and enhances the mycobacterial H2O2 resistance. Therefore, we report a novel c-di-GMP effective regulator in mycobacteria, which extends the second messenger's function to bacterial antioxidant defense.

Cyclic di-GMP integrates functionally divergent transcription factors into a regulation pathway for antioxidant defense.

Cyclic diguanylate monophosphate (c-di-GMP) is a global signaling molecule that modulates diverse cellular processes through its downstream receptors. However, no study has fully clarified the mechanisms by which c-di-GMP organizes functionally divergent regulators to drive the gene expression for coping with environmental stress. Here, we reported that c-di-GMP can integrate two functionally opposite receptor transcription factors, namely, LtmA and HpoR, into a pathway to regulate the antioxidant processes in Mycobacterium smegmatis. In contrast to HpoR, LtmA is an activator that positively regulates the expression of redox gene clusters and the mycobacterial H2O2 resistance. LtmA can physically interact with HpoR. A high level of c-di-GMP stimulates the positive regulation of LtmA and boosts the physical interaction between the two regulators, further enhancing the DNA-binding ability of LtmA and reducing the inhibitory activity of HpoR. Therefore, upon exposure to oxidative stress, c-di-GMP can orchestrate functionally divergent transcription factors to trigger antioxidant defense in mycobacteria. This finding presents a noteworthy example of how a bacterium remodels its transcriptional network via c-di-GMP in response to environmental stress.

Psychiatric education in Greater China.

Multiple surveys have revealed that China has an immense mental health care needs predominantly related to common mental disorders like anxiety and depressive disorders. China has provided different training pathways with an aim of increasing the number of psychiatrists working to address such growing mental health care needs. Although this strategy has successfully doubled the total number of psychiatrists over a couple of years, there remains the problem of harmonising the training standards across different training pathways and across different training units. There is also a pressing need to enhance psychiatric education among other health professionals as it is increasingly recognised that many people with common mental disorders do not have or want to have access to psychiatric care, and need to be taken care of by medical practitioners of other specialties or health professionals. Despite Hong Kong having a different training system from Mainland China, the problems faced with training psychiatrists and other health professionals in Hong Kong are strikingly similar to those encountered by their counterparts in China. Given their different historical origins and subsequent diverse development of training systems, Mainland China and Hong Kong have much to learn from one another.

Somatic symptom disorder in the context of Chinese yin-yang culture: A case report and literature review. / 中国阴阳文化背景下的躯体症状障碍1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

Somatic symptom disorder (SSD) is a somatic disorder characterized by excessive anxiety over various somatic symptoms for a long time, which makes patients feel very painful and the quality of personal life significantly decreased. Previous studies have shown that there is a connection between the clinical manifestations of SSD patients and their cultural background. The patient in this case report was highly affected by Chinese yin-yang culture, displaying obvious Chinese characteristics.We report a patient with SSD, whose clinical manifestations were mainly sexual dysfunction and mood symptoms which were closely related to the Traditional Chinese culture of Yin and Yang. In this case, Hamilton Anxiety Scale, Hamilton Depression Scale, and International Erectile Function Questionnaire were used to evaluate the patients' anxiety, depression, and sexual function, and the scores were 32, 33, and 9, respectively. The patient was treated with a combination of venlafaxine and mirtazapine. After 5 weeks of treatment, the patient's clinical symptoms improved significantly.The clinical manifestations of some Chinese SSD patients have obvious characteristic relevance to Chinese theory of Yin and Yang, making SSD easily to be misdiagnosed. Therefore, clinicians should pay atlention to this situation. In addition, the combination of venlafaxine and mirtazapine may have a better effect on SSD patients with chronic pain and sexual dysfunction.

A qualitative study to explore views of patients', carers' and mental health professionals' to inform cultural adaptation of CBT for psychosis (CBTp) in China.

BACKGROUND: The evidence for effectiveness of Cognitive Behaviour Therapy (CBT) is robust and the national organizations in the United Kingdom and the United States recommend its use. It is not utilized to its full potential in low and middle-income countries. Adaptation of CBT treatment to the target culture may facilitate its uptake. This study explored views of patients with schizophrenia, their caregivers, and mental health professionals for the purpose of cultural adaptation of CBT. METHOD: The project was conducted in a teaching hospital in China. Systematic content and question analysis were the techniques we used to analyse the data generated in a series of qualitative interviews (N 45) in China. After identification of emerging themes and categories we compared and contrasted the themes across different interviews recursively. Triangulation of themes and concepts was undertaken to compare further and contrast the data from the different participating groups. RESULTS: This work highlighted the barriers in therapy as well as opportunities for use of CBT in that environment. Patients and their carers in China use a bio-psycho-spiritual-social model of illness. CBT is not commonly used to help those with schizophrenia in China. CONCLUSIONS: This study will facilitate the therapists using CBT for people with psychosis in China. These results require to be tested in clinical trials.

A longitudinal fMRI investigation in acute post-traumatic stress disorder (PTSD).

Background Neuroimaging studies have implicated limbic, paralimbic, and prefrontal cortex in the pathophysiology of chronic post-traumatic stress disorder (PTSD). However, little is known about the neural substrates of acute PTSD and how they change with symptom improvement. Purpose To examine the neural circuitry underlying acute PTSD and brain function changes during clinical recovery from this disorder. Material and Methods Nineteen acute PTSD patients and nine non-PTSD subjects who all experienced a devastating mining accident underwent clinical assessment as well as functional magnetic resonance imaging (fMRI) scanning while viewing trauma-related and neutral pictures. Two years after the accident, a subgroup of 17 patients completed a second clinical evaluation, of which 13 were given an identical follow-up scan. Results Acute PTSD patients demonstrated greater activation in the vermis and right posterior cingulate, and greater deactivation in the bilateral medial prefrontal cortex and inferior parietal lobules than controls in the traumatic versus neutral condition. At follow-up, PTSD patients showed symptom reduction and decreased activation in the right middle frontal gyrus, bilateral posterior cingulate/precuneus, and cerebellum. Correlation results confirmed these findings and indicated that brain activation in the posterior cingulate/precuneus and vermis was predictive of PTSD symptom improvement. Conclusion The findings support the involvement of the medial prefrontal cortex, inferior parietal lobule, posterior cingulate, and vermis in the pathogenesis of acute PTSD. Brain activation in the vermis and posterior cingulate/precuneus appears to be a biological marker of recovery potential from PTSD. Furthermore, decreased activation of the middle frontal gyrus, posterior cingulate/precuneus, and cerebellum may reflect symptom improvement.

DarR, a TetR-like transcriptional factor, is a cyclic di-AMP-responsive repressor in Mycobacterium smegmatis.

Cyclic dinucleotides, including cyclic di-AMP (c-di-AMP), are known to be ubiquitous second messengers involved in bacterial signal transduction. However, no transcriptional regulator has been characterized as a c-di-AMP receptor/effector to date. In the present study, using a c-di-AMP/transcription factor binding screen, we identified Ms5346, a TetR family regulator in Mycobacterium smegmatis, as a c-di-AMP receptor in bacteria. Ms5346 could specifically bind c-di-AMP with K(d) of 2.3 ± 0.5 µM. Using EMSA and DNase I footprinting assays, c-di-AMP was found to stimulate the DNA binding activity of Ms5346 and to enhance its ability to protect its target DNA sequence. A conserved 14-bp palindromic motif was identified as the DNA-binding site for Ms5346. Further, Ms5346 was found to negatively regulate expression of three target genes including Ms5347 (encoding a major facilitator family transporter), Ms5348 (encoding a medium chain fatty acyl-CoA ligase), and Ms5696 (encoding a cold shock protein, CspA). Ms5346 is the first cyclic di-AMP receptor regulator to be identified in bacteria, and we have designated it as DarR. Our findings enhance our understanding of the function and regulatory mechanism of the second messenger c-di-AMP in bacteria.