20(R)-ginsenoside Rg3 attenuates cerebral ischemia-reperfusion injury by mitigating mitochondrial oxidative stress via the Nrf2/HO-1 signaling pathway.

Reducing mitochondrial oxidative stress has become an important strategy to prevent neuronal death in ischemic stroke. Previous studies have shown that 20(R)-ginsenoside Rg3 can significantly improve behavioral abnormalities, reduce infarct size, and decrease the number of apoptotic neurons in cerebral ischemia/reperfusion injury rats. However, it remains unclear whether 20(R)-ginsenoside Rg3 can inhibit mitochondrial oxidative stress in ischemic stroke and the potential molecular mechanism. In this study, we found that 20(R)-ginsenoside Rg3 notably inhibited mitochondrial oxidative stress in middle cerebral artery occlusion/reperfusion (MCAO/R) rats and maintained the stability of mitochondrial structure and function. Treatment with 20(R)-ginsenoside Rg3 also decreased the levels of mitochondrial fission proteins (Drp1 and Fis1) and increased the levels of fusion proteins (Opa1, Mfn1, and Mfn2) in MCAO/R rats. Furthermore, we found that 20(R)-ginsenoside Rg3 promoted nuclear aggregation of nuclear factor erythroid2-related factor 2 (Nrf2) but did not affect Kelch-like ECH-associated protein-1 (Keap1), resulting in the downstream expression of antioxidants. In in vitro oxygen-glucose deprivation/reperfusion stroke models, the results of PC12 cells treated with 20(R)-ginsenoside Rg3 were consistent with animal experiments. After transfection with Nrf2 short interfering RNA (siRNA), the protective effect of 20(R)-ginsenoside Rg3 on PC12 cells was reversed. In conclusion, the inhibition of mitochondrial oxidative stress plays a vital position in the anti-cerebral ischemia-reperfusion injury of 20(R)-ginsenoside Rg3, and its neuroprotective mechanism is related to the activation of the nuclear factor erythroid2-related factor 2/heme oxygenase 1 signaling pathway.

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.

Comprehensive Analysis of the Effect of 20(R)-Ginsenoside Rg3 on Stroke Recovery in Rats via the Integrative miRNA-mRNA Regulatory Network.

MicroRNAs (miRNAs) are a class of small, endogenous, noncoding RNAs. Recent research has proven that miRNAs play an essential role in the occurrence and development of ischemic stroke. Our previous studies confirmed that 20(R)-ginsenosideRg3 [20(R)-Rg3] exerts beneficial effects on cerebral ischemia-reperfusion injury (CIRI), but its molecular mechanism has not been elucidated. In this study, we used high-throughput sequencing to investigate the differentially expressed miRNA and mRNA expression profiles of 20(R)-Rg3 preconditioning to ameliorate CIRI injury in rats and to reveal its potential neuroprotective molecular mechanism. The results show that 20(R)-Rg3 alleviated neurobehavioral dysfunction in MCAO/R-treated rats. Among these mRNAs, 953 mRNAs were significantly upregulated and 2602 mRNAs were downregulated in the model group versus the sham group, whereas 437 mRNAs were significantly upregulated and 35 mRNAs were downregulated in the 20(R)-Rg3 group in contrast with those in the model group. Meanwhile, the expression profile of the miRNAs showed that a total of 283 differentially expressed miRNAs were identified, of which 142 miRNAs were significantly upregulated and 141 miRNAs were downregulated in the model group compared with the sham group, whereas 34 miRNAs were differentially expressed in the 20(R)-Rg3 treatment group compared with the model group, with 28 miRNAs being significantly upregulated and six miRNAs being significantly downregulated. Furthermore, 415 (391 upregulated and 24 downregulated) differentially expressed mRNAs and 22 (17 upregulated and 5 downregulated) differentially expressed miRNAs were identified to be related to 20(R)-Rg3's neuroprotective effect on stroke recovery. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that 20(R)-Rg3 could modulate multiple signaling pathways related to these differential miRNAs, such as the cGMP-PKG, cAMP and MAPK signaling pathways. This study provides new insights into the protective mechanism of 20(R)-Rg3 against CIRI, and the mechanism may be partly associated with the regulation of brain miRNA expression and its target signaling pathways.

Factor structure and sex invariance of the temporal experience of pleasure scale (TEPS) in Chinese university students and clinical population.

BACKGROUND: A motivation dimension of the core psychiatric symptom anhedonia additional has been suggested. The Temporal Experience of Pleasure Scale (TEPS) has been reported to assess anticipatory and consummatory pleasure separately in multiple factor-structure models. This study explored the factor structure of a Chinese version of the 18-item TEPS and further explored the measurement invariance of the TEPS across sex and clinical status (non-clinical, psychiatric). METHODS: Best-fit factor structure of the TEPS was examined in a non-clinical cohort of 7410 undergraduates, randomized into sample 1 (N = 3755) for exploratory factor analysis (EFA) and sample 2 (N = 3663) for confirmatory factor analysis (CFA). Additionally, serial CFA was conducted to evaluate measurement invariance across sex and between clinical (N = 313) and non-clinical (N = 341) samples. RESULTS: EFA supported a new four-factor structure with a motivation component, based on the original two-factor model (consummatory pleasure with/without motivation drive, anticipatory pleasure with/without motivation drive). CFA confirmed the four-factor model as the best-fit structure and revealed a second-order hierarchy in non-clinical and clinical samples. Full scalar invariance was observed across clinical and non-clinical samples and across sex in the clinical sample; only partial scalar invariance was observed across sex in the non-clinical sample. CONCLUSIONS: A four-factor structured TEPS can assess motivation-driving dimensions of anticipatory and consummatory pleasure, consistent with the recently advanced multidimensional structure of anhedonia. CFA and measurement invariance results support application of the TEPS for assessing motivation aspects of anhedonia.

Personality inventory for DSM-5 brief form(PID-5-BF) in Chinese students and patients: evaluating the five-factor model and a culturally informed six-factor model.

BACKGROUND: The Personality Inventory for DSM-5 Brief Form (PID-5-BF) is a 25-item measuring tool evaluating maladaptive personality traits for the diagnosis of personality disorders(PDs). As a promising scale, its impressive psychometric properties have been verified in some countries, however, there have been no studies about the utility of the PID-5-BF in Chinese settings. The current study aimed to explore the maladaptive personality factor model which was culturally adapted to China and to examine psychometric properties of the PID-5-BF among Chinese undergraduate students and clinical patients. METHODS: Seven thousand one hundred fifty-five undergraduate students and 451 clinical patients completed the Chinese version of the PID-5-BF. Two hundered twenty-eight students were chosen randomly for test-retest reliability at a 4-week interval. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted to discover the most suitable factor structure in China, measurement invariance(MI), internal consistency, and external validity were also calculated. RESULTS: The theoretical five-factor model was acceptable, but the exploratory six-factor model was more applicable in both samples (Undergraduate sample: CFI = 0.905, TLI = 0.888, RMSEA = 0.044, SRMR = 0.039; Clinical sample: CFI = 0.904, TLI = 0.886, RMSEA = 0.047, SRMR = 0.060). In the Chinese six-factor model, the Negative Affect domain was divided into two factors and the new factor was named "Interpersonal Relationships", which was in line with the Big-Six Personality model in Chinese. Measurement invariance across non-clinical and clinical sample was established (configural, weak, strong MI, and partial strict MI). Aside from acceptable internal consistency (Undergraduate sample: alpha = 0.84, MIC = 0.21; Clinical sample: alpha = 0.86, MIC = 0.19) and test-retest reliability(0.73), the correlation between the 25-item PID-5-BF and the 220-item PID-5 was significant(p < 0.01). The six PDs measured by Personality diagnostic questionnaire-4+ (PDQ-4+) were associated with and predicted by expected domains of PID-5-BF. CONCLUSIONS: Both the theoretical five-factor model and the exploratory six-factor model of the PID-5-BF were acceptable to the Chinese population. The five-factor model could allow for comparison and integration with other work on the original theoretical model. However, the Chinese six-factor structure may be more culturally informed in East Asian settings. In sum, the PID-5-BF is a convenient and useful screening tool for personality disorders.

CpxR regulates the colistin susceptibility of Salmonella Typhimurium by a multitarget mechanism.

BACKGROUND: The two-component signalling systems PmrAB and PhoPQ of Salmonella have been extensively studied with regard to colistin resistance. We previously showed that overexpressed CpxR could significantly increase the colistin susceptibility (16-fold compared with the WT strain) of Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) through PmrAB and PhoPQ. OBJECTIVES: To identify the potential target genes of CpxR in PmrAB- and PhoPQ-related signalling pathways. METHODS: His6-CpxR was prokaryotically expressed and purified by Ni-NTA resin affinity chromatography. ß-Galactosidase activity assays were conducted to investigate whether CpxR could regulate the promoters of colistin resistance-related genes (CRRGs). Electrophoretic mobility shift assays (EMSAs) were used to further detect His6-CpxR complexes with promoters of CRRGs. RESULTS: We demonstrated for the first time (to the best of our knowledge) that CpxR and the AcrAB-TolC efflux pump have reciprocal effects on CRRG transcription. Additionally, CpxR could regulate the colistin susceptibility of Salmonella Typhimurium by binding directly to the promoters of phoPQ, pmrC, pmrH and pmrD at the CpxR box-like sequences or indirectly through other regulators including pmrAB and mgrB. CONCLUSIONS: CpxR could regulate the colistin susceptibility of Salmonella Typhimurium by a multitarget mechanism.

A novel construct of anhedonia revealed in a Chinese sample via the Revised Physical and Social Anhedonia Scales.

BACKGROUND: Anhedonia is a core clinical symptom of mental disorders. The Revised Physical Anhedonia Scale (RPAS) and the Revised Social Anhedonia Scale (RSAS) have been applied in clinical and non-clinical samples since 1980s. However, the construct of a unified RPAS&RSAS for comprehensive measurement of anhedonia has never been explored. Therefore, the purpose of our study was to examine the factor structure of the unified RPAS&RSAS among undergraduates and clinical patients. METHODS: A total of 3435 undergraduates from two universities and 294 clinical patients with mental disorders had completed the Chinese version of the RPAS and the RSAS. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were each conducted to reveal the constructs of the RPAS and the RSAS. CFA was used to evaluate first- and second-order models for the unified RPAS&RSAS in undergraduates and clinical patients. The internal consistency and test-retest reliability of the RPAS and the RSAS were also evaluated. RESULTS: EFA and CFA indicated 2-factor structures for RPAS and RSAS, with the factors being defined as anticipatory anhedonia and consummatory anhedonia. The second-order model of the unified RPAS&RSAS in the undergraduates and clinical patients both had satisfactory fit index values (Undergraduate sample: CFI = 0.901, TLI = 0.899, RMSEA = 0.055, SRMR = 0.086; Clinical sample: CFI = 0.922, TLI = 0.911, RMSEA = 0.052, SRMR = 0.078). The psychometric robustness of the RPAS&RSAS were confirmed by high internal consistency and test-retest reliability values. CONCLUSIONS: The unified RPAS&RSAS with a second-order structure was confirmed in both undergraduates and clinical samples in Chinese. The construct of anhedonia was refreshed as covering physical and social domains, and each of them includes both anticipatory and consummatory components.

Effectiveness of an Assertive Community Treatment program for people with severe schizophrenia in mainland China - a 12-month randomized controlled trial.

BACKGROUND: Assertive Community Treatment (ACT) is an evidence-based treatment program for people with severe mental illness developed in high-income countries. We report the first randomized controlled trial of ACT in mainland China. METHODS: Sixty outpatients with schizophrenia with severe functional impairments or frequent hospitalizations were randomly assigned to ACT (n = 30) or standard community treatment (n = 30). The severity of symptoms and level of social functioning were assessed at baseline and every 3 months during the 1-year study. The primary outcome was the duration of hospital readmission. Secondary outcomes included a pre-post change in symptom severity, the rates of symptom relapse and gainful employment, social and occupational functioning, and quality of life of family caregivers. RESULTS: Based on a modified intention-to-treat analysis, the outcomes for ACT were significantly better than those of standard community treatment. ACT patients were less likely to be readmitted [3.3% (1/30) v. 25.0% (7/28), Fisher's exact test p = 0.023], had a shorter mean readmission time [2.4 (13.3) v. 30.7 (66.9) days], were less likely to relapse [6.7% (2/30) v. 28.6% (8/28), Fisher's exact test p = 0.038], and had shorter mean time in relapse [3.5 (14.6) v. 34.4 (70.6) days]. The ACT group also had significantly longer times re-employed and greater symptomatic improvement and their caregivers experienced a greater improvement in their quality of life. CONCLUSION: Our results show that culturally adapted ACT is both feasible and effective for individuals with severe schizophrenia in urban China. Replication studies with larger samples and longer duration of follow up are warranted.

Validation of the Dutch Eating Behavior Questionnaire (DEBQ) in a sample of Chinese adolescents.

We sought to validate the Dutch Eating Behavior Questionnaire (DEBQ) in a sample of Chinese adolescents and investigate differences in eating behaviors among Chinese normal weight, overweight, and obese adolescents. Chinese middle and high school students completed the DEBQ, Eating Disorder Inventory-1, and the Self-Control Scale. Result showed that the DEBQ had good internal consistency, test-retest reliability and criterion validity. Furthermore, the obese and overweight adolescents scored significantly higher than normal weight adolescents on three subscales. The DEBQ is effective for assessing eating behaviors in Chinese adolescents.

Reasons for living and hope as the protective factors against suicidality in Chinese patients with depression: a cross sectional study.

BACKGROUND: The risk factors of suicidal ideation and attempts have been discussed in many researches. Few studies have examined reasons for living and hope as protective factors against suicide in a clinical population. It is unclear if these factors help to reduce suicide rates in patients with depression. The study aimed to assess the role of reasons for living and hope in the identification and reduction of suicidality and explore the influence of reasons for living or hope in the transition from suicidal ideation to suicide attempts. METHODS: Patients with depression (N = 115) completed the Beck Depression Inventory, Reasons for Living Inventory, and Adult Suicidal Ideation Questionnaire. RESULTS: There were significant correlations among depression, hope, total reasons for living, and suicidal ideation and attempts. Further, after controlling for depression, reasons for living and hope had significant main effects on suicidal ideation. Hope also had a significant predictive effect in the transition of suicidal ideation to suicide attempt. CONCLUSIONS: We concluded that reasons for living and hope may protect against suicidal ideation and attempts in patients with depression. Especially hope could reduce the possibility of suicide attempt.

Chinese version of Impact of Weight on Quality of Life for Kids: psychometric properties in a large school-based sample.

BACKGROUND: The Impact of Weight on Quality of Life for Kids (IWQOL-Kids) is the first self-report questionnaire for assessing weight-related quality of life for youth. However, there is no Chinese version of IWQOL-Kids. Thus, the objective of this research was to translate IWQOL-Kids into Mandarin and evaluate its psychometric properties in a large school-based sample. METHODS: The total sample included 2282 participants aged 11-18 years old, including 1703 non-overweight, 386 overweight and 193 obese students. IWQOL-Kids was translated and culturally adapted by following the international guidelines for instrument linguistic validation procedures. The psychometric evaluation included internal consistency, test-retest reliability, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), convergent validity and discriminant validity. RESULTS: Cronbach's α for the Chinese version of IWQOL-Kids (IWQOL-Kids-C) was 0.956 and ranged from 0.891 to 0.927 for subscales. IWQOL-Kids-C showed a test-retest coefficient of 0.937 after 2 weeks and ranged from 0.847 to 0.903 for subscales. The original four-factor model was reproduced by EFA after seven iterations, accounting for 69.28% of the total variance. CFA demonstrated that the four-factor model had good fit indices with comparative fit index = 0.92, normed fit index = 0.91, goodness of fit index = 0.86, root mean square error of approximation = 0.07 and root mean square residual = 0.03. Convergent validity and discriminant validity were demonstrated with higher correlations between similar constructs and lower correlations between dissimilar constructs of IWQOL-Kids-C and PedsQL™ 4.0. The significant differences were found across the body mass index groups, and IWQOL-Kids-C had higher effect sizes than PedsQL™4.0 when comparing non-overweight and obese groups, supporting the sensitivity of IWQOL-Kids-C. CONCLUSIONS: IWQOL-Kids-C is a satisfactory, valid and reliable instrument to assess weight-related quality of life for Chinese children and adolescents aged 11-18 years old.

Self-control and parental control mediate the relationship between negative emotions and emotional eating among adolescents.

OBJECTIVES: The study was conducted to simultaneously investigate the mediating effects of parental control and adolescents' self-control on the relationship between adolescents' negative emotions and emotional eating, and to determine pathways with the greatest effect among these variables. METHODS: Negative emotions, emotional eating, parental control, and self-control were investigated in 594 high school students (average age=16.70, SD=1.09) in Changsha City, China. RESULTS: High levels of negative emotions and parental control and low levels of self-control were strongly related to high levels of emotional eating in adolescents. In addition to the direct relationship between negative emotions and emotional eating, there was a mediating effect observed through low self-control and high parental control. The mediational effect of parental control was non-significant in adolescent boys. Furthermore, negative emotions related to emotional eating through the effect of parental control on adolescents' self-control. The degree to which both mediators explained the relationship between negative emotions and emotional eating ranged from 52.6% to 66.8%, and self-control had a stronger mediational effect than did parental control. CONCLUSION: The results indicate that both self-control and parental control should be considered in designing preventative measures against emotional eating in adolescents. Adolescent self-control training could also assist in preventing emotional eating.

Exploratory and confirmatory factor analysis of the sensitivity to punishment and sensitivity to reward questionnaire-revised and its psychometric evaluation among Chinese person with substance use disorder.

The Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ) is a self-report tool widely used to assess individuals' level of reinforcement sensitivity. Drug addiction is strongly associated with reinforcement sensitivity, but there is a lack of measurement tools to assess reinforcement sensitivity in drug users, necessitating the revision and application of the SPSRQ among drug users. This study recruited 819 drug users (mean age = 34.74; 56.41% female) from five compulsory rehabilitation centers in Hunan Province, China. The applicability of the SPSRQ among person with substance use disorder was assessed by conducting reliability analyses and validity analyses, with retesting performed by 127 individuals after 6 weeks. Exploratory factor analysis for the SPSRQ showed a stable two-factor structure in person with substance use disorder. Confirmatory factor analysis indicated acceptable goodness of fit indexes for the two-factor structure. The SPSRQ also demonstrated good reliability and convergent and discriminant validity evidence. The two-factor structure of the SPSRQ also demonstrated measurement invariance across gender. Further comparative analysis found that the degree of reward sensitivity was higher for males than for females. Generally, the SPSRQ has shown evidence of good reliability and validity in Chinese drug-dependent populations, and it is suitable for research and application with Chinese person with substance use disorder. These findings about the personality traits of people with substance use disorder provide a solid basis for further research.

Upregulation of outer membrane porin gene ompC contributed to enhancement of azithromycin susceptibility in multidrug-resistant Escherichia coli.

The outer membrane (OM) in gram-negative bacteria contains proteins that regulate the passive or active uptake of small molecules for growth and cell function, as well as mediate the emergence of antibiotic resistance. This study aims to explore the potential mechanisms for restoring bacteria to azithromycin susceptibility based on transcriptome analysis of bacterial membrane-related genes. Transcriptome sequencing was performed by treating multidrug-resistant Escherichia coli T28R with azithromycin or in combination with colistin and confirmed by reverse transcription-quantitative PCR (RT-qPCR). Azithromycin enzyme-linked immunosorbent assay (ELISA) test, ompC gene overexpression, and molecular docking were utilized to conduct the confirmatory research of the potential mechanisms. We found that colistin combined with azithromycin led to 48 differentially expressed genes, compared to azithromycin alone, such as downregulation of tolA, eptB, lpxP, and opgE and upregulation of ompC gene. Interestingly, the addition of colistin to azithromycin differentially downregulated the mph(A) gene mediating azithromycin resistance, facilitating the intracellular accumulation of azithromycin. Also, overexpression of the ompC elevated azithromycin susceptibility, and colistin contributed to further suppression of the Mph(A) activity in the presence of azithromycin. These findings suggested that colistin firstly enhanced the permeability of bacterial OM, causing intracellular drug accumulation, and then had a repressive effect on the Mph(A) activity along with azithromycin. Our study provides a novel perspective that the improvement of azithromycin susceptibility is related not only to the downregulation of the mph(A) gene and conformational remodeling of the Mph(A) protein but also the upregulation of the membrane porin gene ompC.IMPORTANCEUsually, active efflux via efflux pumps is an important mechanism of antimicrobial resistance, such as the AcrAB-TolC complex and MdtEF. Also, bacterial porins exhibited a substantial fraction of the total number of outer membrane proteins in Enterobacteriaceae, which are involved in mediating the development of the resistance. We found that the upregulation or overexpression of the ompC gene contributed to the enhancement of resistant bacteria to azithromycin susceptibility, probably due to the augment of drug uptakes caused and the opportunity of Mph(A) function suppressed by azithromycin with colistin. Under the combination of colistin and azithromycin treatment, OmpC exhibited an increased selectivity for cationic molecules and played a key role in the restoral of the antibiotic susceptibility. Investigations on the regulation of porin expression that mediated drug resistance would be important in clinical isolates treated with antibiotics.

ICEGpa1804, a novel integrative and conjugative element carrying eight resistance genes, identified in Glaesserella parasuis.

ICEGpa1804 was identified in the genome of a serovar 2, ST279 isolate EHP1804 carrying eight different resistance genes from 200 Glaesserella parasuis strains isolated from swine with lower respiratory tract infection in seven provinces of China. Susceptibility testing for EHP1804 was determined by broth microdilution, and its genetic profile was determined by whole-genome sequencing. The complete ICEGpa1804 was analysed by polymerase chain reaction, conjugation assay and bioinformatics tools. The conjugation assay was performed using EHP1804 as the donor and G. parasuis V43 (rifampicin-resistant) as the recipient. ICEGpa1804 has a size of 71,880 bp and contains 83 genes, including eight resistance genes [tet(B), blaRob-1, aphA1, strA, strB, aac(3)-IId, catA3 and sul2]. The conjugation assay showed that ICEGpa1804 could be transferred to G. parasuis V43 with frequencies of 4.3 × 10-7. To the best of the authors' knowledge, this is the first study to identify a novel integrative and conjugative element (ICE) carrying eight resistance genes and seven insertion sequence (IS) elements from a G. parasuis isolate. Tn6743, a novel transposon carrying six resistance genes, was identified. Moreover, ISGpa1, a novel IS256 family insertion element, is the first characterized example of a G. parasuis insertion element. Multiple mobile genetic elements involved in resistance genes were located in chromosomal ICEGpa1804, which showed that ICEs may serve as a vital platform for the accumulation of resistance genes.

Working memory processing deficit associated with a nonlinear response pattern of the anterior cingulate cortex in first-episode and drug-naïve schizophrenia.

Impaired working memory (WM) is a core neuropsychological dysfunction of schizophrenia, however complex interactions among the information storage, information processing and attentional aspects of WM tasks make it difficult to uncover the psychophysiological mechanisms of this deficit. Thirty-six first-episode and drug-naïve schizophrenia and 29 healthy controls (HCs) were enrolled in this study. Here, we modified a WM task to isolate components of WM storage and WM processing, while also varying the difficulty level (load) of the task to study regional differences in load-specific activation using mixed effects models, and its relationship to distributed gene expression. Comparing patients with HCs, we found both attentional deficits and WM deficits, with WM processing being more impaired than WM storage in patients. In patients, but not controls, a linear modulation of brain activation was observed mainly in the frontoparietal and dorsal attention networks. In controls, an inverted U-shaped response pattern was identified in the left anterior cingulate cortex. The vertex of this inverted U-shape was lower in patients than controls, and a left-shifting axis of symmetry was associated with better WM performance in patients. Both the above linear and U-shaped modulation effects were associated with the expressions of the genes enriched in the dopamine neurotransmitter system across all cortical brain regions. These findings indicate that a WM processing deficit is evident in schizophrenia from an early stage before antipsychotic treatment, and associated with a dopamine pathway related aberration in nonlinear response pattern at the cingulate cortex when processing WM load.

Prevalence of the optrA gene among Streptococcus suis isolates from diseased pigs and identification of a novel integrative conjugative element ICESsu988S.

Aim of this study was to investigate the prevalence and genetic environment of the oxazolidinone resistance gene optrA in Streptococcus suis (S. suis) isolates from diseased pigs in China. A total of 178 S. suis isolates were screened for the optrA gene by PCR. The phenotypes and genotypes of optrA-positive isolates were investigated by antimicrobial susceptibility testing, core genome Multilocus Sequence Typing (cgMLST), capsular serotypes determination and whole-genome sequencing (WGS). Fifty-one (28.7%) S. suis isolates were positive for optrA. Phylogenetic analysis indicated that the spread of the optrA among S. suis isolates was primarily due to horizontal transfer. Analysis of S. suis serotypes from diseased pigs revealed substantial diversity. The genetic environment of optrA was complex and diverse and could be divided into 12 different types. Interestingly, we identified a novel integrative and conjugative element ICESsu988S, carrying optrA and erm(T) genes. This is to the best of our knowledge the first report of the optrA and erm(T) co-located on an ICE in S. suis. Our results showed a high prevalence of optrA gene in S. suis isolates in China. Further research is needed to evaluate the importance of ICEs, as they horizontally propagate important clinical resistance genes.

Analysis of Regulatory Mechanism of AcrB and CpxR on Colistin Susceptibility Based on Transcriptome and Metabolome of Salmonella Typhimurium.

With the increasing and inappropriate use of colistin, the emerging colistin-resistant isolates have been frequently reported during the last few decades. Therefore, new potential targets and adjuvants to reverse colistin resistance are urgently needed. Our previous study has confirmed a marked increase of colistin susceptibility (16-fold compared to the wild-type Salmonella strain) of cpxR overexpression strain JSΔacrBΔcpxR::kan/pcpxR (simplified as JSΔΔ/pR). To searching for potential new drug targets, the transcriptome and metabolome analysis were carried out in this study. We found that the more susceptible strain JSΔΔ/pR displayed striking perturbations at both the transcriptomics and metabolomics levels. The virulence-related genes and colistin resistance-related genes (CRRGs) were significantly downregulated in JSΔΔ/pR. There were significant accumulation of citrate, α-ketoglutaric acid, and agmatine sulfate in JSΔΔ/pR, and exogenous supplement of them could synergistically enhance the bactericidal effect of colistin, indicating that these metabolites may serve as potential adjuvants for colistin therapy. Additionally, we also demonstrated that AcrB and CpxR could target the ATP and reactive oxygen species (ROS) generation, but not proton motive force (PMF) production pathway to potentiate antibacterial activity of colistin. Collectively, these findings have revealed several previously unknown mechanisms contributing to increased colistin susceptibility and identified potential targets and adjuvants for potentiating colistin treatment of Salmonella infections. IMPORTANCE Emergence of multidrug-resistant (MDR) Gram-negative (G-) bacteria have led to the reconsideration of colistin as the last-resort therapeutic option for health care-associated infections. Finding new drug targets and strategies against the spread of MDR G- bacteria are global challenges for the life sciences community and public health. In this paper, we demonstrated the more susceptibility strain JSΔΔ/pR displayed striking perturbations at both the transcriptomics and metabolomics levels and revealed several previously unknown regulatory mechanisms of AcrB and CpxR on the colistin susceptibility. Importantly, we found that exogenous supplement of citrate, α-ketoglutaric acid, and agmatine sulfate could synergistically enhance the bactericidal effect of colistin, indicating that these metabolites may serve as potential adjuvants for colistin therapy. These results provide a theoretical basis for finding potential new drug targets and adjuvants.

Multidrug Resistance Genes Carried by a Novel Transposon Tn7376 and a Genomic Island Named MMGI-4 in a Pathogenic Morganella morganii Isolate.

Antimicrobial resistance in Morganella morganii is increasing in recent years, which is mainly introduced via extra genetic and mobile elements. The aim of our study is to analyze the multidrug resistance (MDR) and characterize the mobile genetic elements (MGEs) in M. morganii isolates. Here, we report the characteristic of a pathogenic M. morganii isolate containing multidrug resistance genes that are mainly carried by a novel transposon Tn7376 and a genomic island. Sequence analysis suggested that the Tn7376 could be generated through homologous recombination between two different IS26-bounded translocatable units (TUs), namely, module A (IS26-Hp-IS26-mph(A)-mrx(A)-mphR-IS6100-chrA-sul1-qacEΔ1) and module B (ISCR1-sul1-qacEΔ1-cmlA1-aadA1-aadB-intI1-IS26), and the genomic island named MMGI-4 might derive from a partial structure of different original genomic islands that also carried IS26-mediated TUs. Notably, a 2,518-bp sequence linked to the module A and B contains a 570-bp dfrA24 gene. To the best of our knowledge, this is the first report of the novel Tn7376 possessing a complex class 1 integron that carried an infrequent gene dfrA24 in M. morganii. IMPORTANCE Mobile genetic elements (MGEs), especially for IS26-bounded translocatable units, may act as a reservoir for a variety of antimicrobial resistance genes in clinically important pathogenic bacteria. We expounded this significant genetic characteristic by investigating a representative M. morganii isolate containing multidrug resistance genes, including the infrequent dfrA24. Our study suggested that these acquired resistance genes were mainly driven by IS26-flanked important MGEs, such as the novel Tn7376 and the MMGI-4. We demonstrated that IS26-related MGEs contributed to the emergence of the extra gene dfrA24 in M. morganii through some potential genetic events like recombination, transposition, and integration. Therefore, it is of importance to investigate persistently the prevalence these MEGs in the clinical pathogens to provide risk assessment of emergence and development of novel resistance genes.