Hippocampal Dynamic Functional Connectivity, HPA Axis Activity, and Personality Trait in Bipolar Disorder with Suicidal Attempt.

INTRODUCTION: Suicide in bipolar disorder (BD) is a multifaceted behavior, involving specific neuroendocrine and psychological mechanisms. According to previous studies, we hypothesized that suicidal BD patients may exhibit impaired dynamic functional connectivity (dFC) variability of hippocampal subregions and hypothalamic-pituitary-adrenal (HPA) axis activity, which may be associated with suicide-related personality traits. The objective of our study was to clarify this. METHODS: Resting-state functional magnetic resonance imaging data were obtained from 79 patients with BD, 39 with suicidal attempt (SA), and 40 without SA, and 35 healthy controls (HCs). The activity of the HPA axis was assessed by measuring morning plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels. All participants underwent personality assessment using Minnesota Multiphasic Personality Inventory-2 (MMPI-2). RESULTS: BD patients with SA exhibited increased dFC variability between the right caudal hippocampus and the left superior temporal gyrus (STG) when compared with non-SA BD patients and HCs. BD with SA also showed significantly lower ACTH levels in comparison with HCs, which was positively correlated with increased dFC variability between the right caudal hippocampus and the left STG. BD with SA had significantly higher scores of Hypochondriasis, Depression, and Schizophrenia than non-SA BD. Additionally, multivariable regression analysis revealed the interaction of ACTH × dFC variability between the right caudal hippocampus and the left STG independently predicted MMPI-2 score (depression evaluation) in suicidal BD patients. CONCLUSION: These results suggested that suicidal BD exhibited increased dFC variability of hippocampal-temporal cortex and less HPA axis hyperactivity, which may affect their personality traits.

Sex-differential cognitive performance on MCCB of youth with BD-II depression.

BACKGROUND: Recent evidences have shown sex-differential cognitive deficits in bipolar disorder (BD) and differences in cognitions across BD subtypes. However, the sex-specific effect on cognitive impairment in BD subtype II (BD-II) remains obscure. The aim of the current study was to examine whether cognitive deficits differ by gender in youth with BD-II depression. METHOD: This cross-sectional study recruited 125 unmedicated youths with BD-II depression and 140 age-, sex-, and education-matched healthy controls (HCs). The Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) was used to assess cognitive functions. Mood state was assessed using the 24-item Hamilton Depression Rating Scale (24-HDRS) and the Young Mania Rating Scale (YMRS). Multivariate analysis of covariance (MANCOVA) was conducted. RESULT: ​Compared with HCs, patients with BD-II depression had lower scores on MCCB composite and its seven cognitive domains (all p < 0.001). After controlling for age and education, MANCOVA revealed significant gender-by-group interaction on attention/vigilance (F = 6.224, df = 1, p = 0.013), verbal learning (F = 9.847, df = 1, p = 0.002), visual learning (F = 4.242, df = 1, p = 0.040), and composite (F = 8.819, df = 1, p = 0.003). Post hoc analyses suggested that males performed worse in the above-mentioned MCCB tests than females in BD-II depression. CONCLUSION: Our study demonstrated generalized cognitive deficits in unmedicated youths with BD-II depression. Male patients performed more serious cognitive impairment on attention/vigilance, verbal learning, and visual learning compared to female patients.

A chromosome-scale genome assembly of Malus domestica, a multi-stress resistant apple variety.

Hanfu apple is the main cultivar grown in the cool areas of Northeast, Northwest, and North China. Here, we proposed a chromosome-level Hanfu genome assembly using PacBio, Illumina and Hi-C sequencing data. The total contig length was 628.99 Mb, with scaffold and contig N50 sizes of 36.18 Mb and 1.25 Mb, respectively. The Hanfu genome had a total of 39,617 genes, of which we predicted the function for 38,816. Evolutionary analysis showed that Hanfu may have undergone a γ-event, a recent whole-genome duplication. A comparative analysis was conducted on the genomes of Hanfu and homozygous triploid HFTH1, which were cultured using the anthers of diploid Hanfu apples. Three variants were identified, including 2,155,184 single nucleotide polymorphisms (SNPs), 413,108 insertions/deletions (indels), and 7,587 structural variants (SVs).This high-quality genome will provide a reference for the genetic improvement of apples and the breeding of more varieties with high resistance and high quality.

Pressure Control of Nonferroelastic Ferroelectric Domains in ErMnO3.

Mechanical pressure controls the structural, electric, and magnetic order in solid-state systems, allowing tailoring of their physical properties. A well-established example is ferroelastic ferroelectrics, where the coupling between pressure and the primary symmetry-breaking order parameter enables hysteretic switching of the strain state and ferroelectric domain engineering. Here, we study the pressure-driven response in a nonferroelastic ferroelectric, ErMnO3, where the classical stress-strain coupling is absent and the domain formation is governed by creation-annihilation processes of topological defects. By annealing ErMnO3 polycrystals under variable pressures in the MPa regime, we transform nonferroelastic vortex-like domains into stripe-like domains. The width of the stripe-like domains is determined by the applied pressure as we confirm by three-dimensional phase field simulations, showing that pressure leads to oriented layer-like periodic domains. Our work demonstrates the possibility to utilize mechanical pressure for domain engineering in nonferroelastic ferroelectrics, providing a lever to control their dielectric and piezoelectric responses.

Alterations of insular dynamic functional connectivity and psychological characteristics in unmedicated bipolar depression patients with a recent suicide attempt.

BACKGROUND: Mounting evidence showed that insula contributed to the neurobiological mechanism of suicidal behaviors in bipolar disorder (BD). However, no studies have analyzed the dynamic functional connectivity (dFC) of insular Mubregions and its association with personality traits in BD with suicidal behaviors. Therefore, we investigated the alterations of dFC variability in insular subregions and personality characteristics in BD patients with a recent suicide attempt (SA). METHODS: Thirty unmedicated BD patients with SA, 38 patients without SA (NSA) and 35 demographically matched healthy controls (HCs) were included. The sliding-window analysis was used to evaluate whole-brain dFC for each insular subregion seed. We assessed between-group differences of psychological characteristics on the Minnesota Multiphasic Personality Inventory-2. Finally, a multivariate regression model was adopted to predict the severity of suicidality. RESULTS: Compared to NSA and HCs, the SA group exhibited decreased dFC variability values between the left dorsal anterior insula and the left anterior cerebellum. These dFC variability values could also be utilized to predict the severity of suicidality (r = 0.456, p = 0.031), while static functional connectivity values were not appropriate for this prediction. Besides, the SA group scored significantly higher on the schizophrenia clinical scales (p < 0.001) compared with the NSA group. CONCLUSIONS: Our findings indicated that the dysfunction of insula-cerebellum connectivity may underlie the neural basis of SA in BD patients, and highlighted the dFC variability values could be considered a neuromarker for predictive models of the severity of suicidality. Moreover, the psychiatric features may increase the vulnerability of suicidal behavior.

Abnormal dynamic functional connectivity of hippocampal subregions associated with working memory impairment in melancholic depression.

BACKGROUND: Previous studies have demonstrated structural and functional changes of the hippocampus in patients with major depressive disorder (MDD). However, no studies have analyzed the dynamic functional connectivity (dFC) of hippocampal subregions in melancholic MDD. We aimed to reveal the patterns for dFC variability in hippocampus subregions - including the bilateral rostral and caudal areas and its associations with cognitive impairment in melancholic MDD. METHODS: Forty-two treatment-naive MDD patients with melancholic features and 55 demographically matched healthy controls were included. The sliding-window analysis was used to evaluate whole-brain dFC for each hippocampal subregions seed. We assessed between-group differences in the dFC variability values of each hippocampal subregion in the whole brain and cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB). Finally, association analysis was conducted to investigate their relationships. RESULTS: Patients with melancholic MDD showed decreased dFC variability between the left rostral hippocampus and left anterior lobe of cerebellum compared with healthy controls (voxel p < 0.005, cluster p < 0.0125, GRF corrected), and poorer cognitive scores in working memory, verbal learning, visual learning, and social cognition (all p < 0.05). Association analysis showed that working memory was positively correlated with the dFC variability values of the left rostral hippocampus-left anterior lobe of the cerebellum (r = 0.338, p = 0.029) in melancholic MDD. CONCLUSIONS: These findings confirmed the distinct dynamic functional pathway of hippocampal subregions in patients with melancholic MDD, and suggested that the dysfunction of hippocampus-cerebellum connectivity may be underlying the neural substrate of working memory impairment in melancholic MDD.

Hepatitis B antibody levels after different doses of hepatitis B vaccination: a retrospective study based on hospitalized children.

Many studies have investigated the positivity rate of hepatitis B surface antibody (HBsAb) after hepatitis B vaccine (HepB) immunization. However, the antibody level, assessed monthly or at more frequent intervals after each of the three doses, particularly within the first year after birth, has not been previously reported. To elucidate the level of antibody formation at various times after vaccination, the current study used the available detection data of HBsAb in hospitalized children to analyze the HBsAb level after immunization combined with their vaccination history. Both the positivity rate and geometric mean concentration (GMC) increased sequentially with immunization doses, reaching their peaks earlier after the third dose than after the first two doses, and the rate of HBsAb positivity was able to reach 100% between 11 and 90 days after completing the three doses of HepB. Within one year after receiving the three doses, the antibody positivity rate and GMC were maintained above 90% and 100 mIU/mL, respectively, and subsequently steadily declined, reaching the lowest value in the 9th and 10th years. The current findings reveal, in more detail, the level of antibody formation at different times following each dose of HepB in hospitalized children, particularly in the age group up to one year after vaccination. For the subjects of this study, we prefer to believe that the proportion of HBsAb non-response should be less than 5% after full immunization with HepB, provided that the appropriate time for blood collection is chosen.

Instruments for assessing the spiritual needs of cancer patients: A systematic review of psychometric properties.

AIMS AND OBJECTIVES: To identify available instruments for assessing cancer patients' spiritual needs and to examine their psychometric properties using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology. BACKGROUND: Cancer patients frequently have significant spiritual needs. The nurse plays an integral role in assessing the patient's spiritual needs as part of providing holistic care. It is crucial to assess these needs using appropriate and reliable instruments. DESIGN: A systematic review based on COSMIN methodology. METHODS: Seven electronic databases (PubMed, EMBASE, CINAHL, Web of Science, ProQuest, CNKI and WANFANG) were systematically searched from inception until 14 February 2023. Two authors independently screened eligible literature, extracted data and evaluated methodological and psychometric quality. This systematic review was conducted following the PRISMA checklist. RESULTS: Sixteen studies have reported 16 different versions of the instruments. None of the instruments were properly assessed for all psychometric properties, nor were measurement error, responsiveness and cross-cultural validity/measurement invariance reported. All of the instruments failed to meet the COSMIN quality criteria for content validity. The quality of evidence for structural validity and/or internal consistency in five instruments did not meet the COSMIN criteria. Eventually, five instruments were not recommended, and 11 were only weakly recommended. CONCLUSION: Instruments to assess spiritual needs exhibited limited reliability and validity. The Spiritual Care Needs Scale is provisionally recommended for research and clinical settings, but its limitations regarding content validity and cross-cultural application must be considered in practice. Future research should further revise the content of available instruments and comprehensively and correctly test their psychometric properties. RELEVANCE TO CLINICAL PRACTICE: The review findings will provide evidence for healthcare professionals to select instruments for recognising spiritual needs in cancer patients. NO PATIENT OR PUBLIC CONTRIBUTION: This study is a systematic review with no patient or public participation.

The effect of psychological contract on turnover intention among nurses: a meta-analytic review.

BACKGROUND: The turnover intention (TI) of nurses is common, posing a threat to modern healthcare organizations. Psychological contract (PC) is a predictor of TI, affecting significantly nurse's TI. However, the extent of the association between PC and nurse's TI is unknown. We performed a meta-analysis to quantitatively analyze the relationship between PC and nurse's TI. METHODS: We searched nine electronic databases from inception to July 2023. Observational studies were included using a retrieval strategy related to PC and TI. Meta-analyses of common effect and random effect models were performed using R software with Spearman or Pearson correlation coefficients. Meta-regression, subgroup analysis, publication bias, and sensitivity analysis were also carried out . RESULTS: Eighteen studies including 8,908 nurses were identified. Based on various PC-related perspectives, 16 studies explored nurses' TI in terms of the content and three-dimensional structure of PC. Of these, 9 studies reported the negative direction of the correlation between PC and TI (r ranged from - 0.20 to -0.45), whereas 7 studies reported the positive direction of the correlation between PC and TI (r ranged from 0.32 to 0.50). The PC total and its dimensions were found to have moderately significant associations with TI, with the exception of the PCE and PCE-I. Additional, 2 studies reported the relationship between the outcome of PC and TI, the PCF, PCB, and PCV were powerful predictors of nurses' TI. Meta-regression and subgroup analysis found that only nurses working in specialized departments might be the source of heterogeneity. CONCLUSIONS: To our knowledge, this was the first meta-analysis to quantitatively examine the relationship between PC and TI among nurses. The findings reaffirmed the necessity for healthcare administrators and the medical profession to valued nurse' good interpersonal, social support, humanistic environment, and meet nurses' psychological and spiritual needs in addition to their material demands. Moderators of the connection between PC and TI, based on meta-regression and subgroup analyses, should be carefully explored as they may aid in identifying nurses' TI. Additional, longitudinal research, as well as mixed research, should be conducted to more comprehensively explore the relationship between PC and TI.

Transcriptome-based network analysis related to M2-like tumor-associated macrophage infiltration identified VARS1 as a potential target for improving melanoma immunotherapy efficacy.

RATIONALE: The M2-like tumor-associated macrophages (TAMs) are independent prognostic factors in melanoma. METHODS: We performed weighted gene co-expression network analysis (WGCNA) to identify the module most correlated with M2-like TAMs. The Cancer Genome Atlas (TCGA) patients were classified into two clusters that differed based on prognosis and biological function, with consensus clustering. A prognostic model was established based on the differentially expressed genes (DEGs) of the two clusters. We investigated the difference in immune cell infiltration and immune response-related gene expression between the high and low risk score groups. RESULTS: The risk score was defined as an independent prognostic value in melanoma. VARS1 was a hub gene in the M2-like macrophage-associated WGCNA module that the DepMap portal demonstrated was necessary for melanoma growth. Overexpressing VARS1 in vitro increased melanoma cell migration and invasion, while downregulating VARS1 had the opposite result. VARS1 overexpression promoted M2 macrophage polarization and increased TGF-ß1 concentrations in tumor cell supernatant in vitro. VARS1 expression was inversely correlated with immune-related signaling pathways and the expression of several immune checkpoint genes. In addition, the VARS1 expression level helped predict the response to anti-PD-1 immunotherapy. Pan-cancer analysis demonstrated that VARS1 expression negatively correlated with CD8 T cell infiltration and the immune response-related pathways in most cancers. CONCLUSION: We established an M2-like TAM-related prognostic model for melanoma and explored the role of VARS1 in melanoma progression, M2 macrophage polarization, and the development of immunotherapy resistance.

Non-invasive brain stimulation combined with psychosocial intervention for depression: a systematic review and meta-analysis.

OBJECTIVES: This review investigates the efficacy and safety of non-invasive brain stimulation (NIBS) combined with psychosocial intervention on depressive symptoms. MATERIALS AND METHODS: We systematically searched five electronic databases from their inception to June 2021: PubMed, Embase, PsycINFO, Web of Science, and Medline. Randomized or non-randomized clinical trials in which NIBS plus psychosocial intervention was compared to control conditions in people with depressive symptoms were included. RESULTS: A total of 17 eligible studies with 660 participants were included. The meta-analysis results showed that NIBS combined with psychosocial therapy had a positive effect on moderate to severe depression ([SMD = - 0.46, 95%CI (- 0.90, - 0.02), I2 = 73%, p < .01]), but did not significantly improve minimal to mild depression ([SMD = - 0.12, 95%CI (- 0.42, 0.18), I2 = 0%, p = .63]). Compared with NIBS alone, the combination treatment had a significantly greater effect in alleviating depressive symptoms ([SMD = - 0.84, 95%CI (- 1.25, - 0.42), I2 = 0%, p = .93]). However, our results suggested that the pooled effect size of ameliorating depression of NIBS plus psychosocial intervention had no significant difference compared with the combination of sham NIBS [SMD = - 0.12, 95%CI (- 0.31, 0.07), I2 = 0%, p = .60] and psychosocial intervention alone [SMD = - 0.97, 95%CI (- 2.32, 0.38), I2 = 72%, p = .01]. CONCLUSION: NIBS when combined with psychosocial intervention has a significant positive effect in alleviating moderately to severely depressive symptoms. Further well-designed studies of NIBS combined with psychosocial intervention on depression should be carried out to consolidate the conclusions and explore the in-depth underlying mechanism.

Predicting hand washing, mask wearing and social distancing behaviors among older adults during the covid-19 pandemic: an integrated social cognition model.

BACKGROUND: Older adults are at a higher risk from COVID-19. Individual preventive behaviors including frequent hand washing, mask wearing, and social distancing play important roles in reducing the transmission of COVID-19 in the community. This study aimed to identify the determinants of three preventive behaviors of older adults during the COVID-19 pandemic by using an Integrated Social Cognition Model. METHODS: Using a prospective study design, 516 Chinese older adults from Hubei province of China (mean age = 67.55 years, SD = 6.60, 57.9% females) completed two online questionnaire surveys. The demographics, social cognition constructs (motivational self-efficacy, risk perception, attitude, subjective norm, health knowledge, intention, volitional self-efficacy, planning, action control) and three preventive behaviors were measured during the first-wave online survey from 18 May 2020 to 7 June 2020. One month later, three preventive behaviors were measured again during the second-wave online survey. Data were analyzed by structural equation modelling. RESULTS: Models showed attitude, motivational self-efficacy and subjective norm were consistent predictors of intention, motivational self-efficacy was a consistent predictor of volitional self-efficacy, planning and volitional self-efficacy were consistent predictors of action control, and health knowledge was a consistent predictor of behaviors across all three preventive behaviors. In addition, mediating relationships were found in the model of hand washing behavior. In particular, planning (ß = .109, p = .042) and action control (ß = .056, p = .047) mediated between volitional self-efficacy and hand washing respectively. Action control also mediated between planning and hand washing (ß = .087, p = .044). Moreover, the inclusion of past behaviors in three models attenuated most of the structural relations. CONCLUSIONS: The current study's findings basically supported the Integrated Social Cognition Model and identified key modifiable determinants of preventive behaviors. Based on this model, future interventions aiming to promote COVID-19 preventive behaviors among older adults are warranted.

[In vitro screening of natural compounds with antitumor activity by trypsin].

In order to investigate the feasibility of in vitro screening the antitumor activity of natural compounds by trypsin, porcine trypsin was used to for screening test, which is marked by inhibition of enzyme activity. Four compounds, namely daidzin, genistin, matrine and oxymatrine, were selected as test subjects. The natural antitumor drug camptothecin was used as the control. The inhibitory effect was detected by two experimental methods: direct detection of trypsin activity inhibition and hydrolysis of bovine serum albumin by trypsin. The results showed the inhibitory effects of the four natural compounds on trypsin, and the inhibition rates of the four natural compounds were significantly different. The enzyme activity assay showed that the inhibitory effect of matrine was better than that of oxymatrine, indicating that trypsin had a good screening resolution. The inhibitory effect was significantly increased with the increased ratio of sample to trypsin, suggesting the structure-activity correlation and dose-effect correlation of the screening methods. Altogether, the experimental method of screening antitumor activity of natural compounds by trypsin has good application values. Since porcine trypsin is similar to human trypsin in terms of molecular structure and performance, it is more applicable for screening of antitumor efficacy of natural pharmacodynamic compounds.

Urine proteomics identifies biomarkers for diabetic kidney disease at different stages.

BACKGROUND: Type 2 diabetic kidney disease is the most common cause of chronic kidney diseases (CKD) and end-stage renal diseases (ESRD). Although kidney biopsy is considered as the 'gold standard' for diabetic kidney disease (DKD) diagnosis, it is an invasive procedure, and the diagnosis can be influenced by sampling bias and personal judgement. It is desirable to establish a non-invasive procedure that can complement kidney biopsy in diagnosis and tracking the DKD progress. METHODS: In this cross-sectional study, we collected 252 urine samples, including 134 uncomplicated diabetes, 65 DKD, 40 CKD without diabetes and 13 follow-up diabetic samples, and analyzed the urine proteomes with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We built logistic regression models to distinguish uncomplicated diabetes, DKD and other CKDs. RESULTS: We quantified 559 ± 202 gene products (GPs) (Mean ± SD) on a single sample and 2946 GPs in total. Based on logistic regression models, DKD patients could be differentiated from the uncomplicated diabetic patients with 2 urinary proteins (AUC = 0.928), and the stage 3 (DKD3) and stage 4 (DKD4) DKD patients with 3 urinary proteins (AUC = 0.949). These results were validated in an independent dataset. Finally, a 4-protein classifier identified putative pre-DKD3 patients, who showed DKD3 proteomic features but were not diagnosed by clinical standards. Follow-up studies on 11 patients indicated that 2 putative pre-DKD patients have progressed to DKD3. CONCLUSIONS: Our study demonstrated the potential for urinary proteomics as a noninvasive method for DKD diagnosis and identifying high-risk patients for progression monitoring.

Exenatide and Renal Outcomes in Patients with Type 2 Diabetes and Diabetic Kidney Disease.

BACKGROUND: Cardiovascular outcomes in clinical trials with type 2 diabetes mellitus (T2DM) patients have shown that glucagon-like peptide-1 receptor agonist can have a beneficial effect on the kidney. This trial aimed to assess the effects of exenatide on renal outcomes in patients with T2DM and diabetic kidney disease (DKD). METHODS: We performed a randomized parallel study encompassing 4 general hospitals. T2DM patients with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 and macroalbuminuria, defined as 24-h urinary albumin excretion rate (UAER) >0.3 g/24 h were randomized 1:1 to receive exenatide twice daily plus insulin glargine (intervention group) or insulin lispro plus glargine (control group) for 24 weeks. The primary outcome was the UAER percentage change from the baseline after 24 weeks of intervention. The rates of hypoglycemia, adverse events (AEs), and change in eGFR during the follow-up were measured as safety outcomes. RESULTS: Between March 2016 and April 2019, 92 patients were randomized and took at least 1 dose of the study drug. The mean age of the participants was 56 years. At baseline, the median UAER was 1,512.0 mg/24 h and mean eGFR was 70.4 mL/min/1.73 m2. After 24 weeks of treatment, the UAER percentage change was significantly lower in the intervention group than in the control group (p = 0.0255). Moreover, the body weight declined by 1.3 kg in the intervention group (the difference between the 2 groups was 2.7 kg, p = 0.0001). Compared to the control group, a lower frequency of hypoglycemia and more gastrointestinal AEs were observed in the intervention group. CONCLUSION: Exenatide plus insulin glargine treatment for 24 weeks resulted in a reduction of albuminuria in T2DM patients with DKD.

Vip3Aa from Bacillus thuringiensis subsp. kurstaki HD1 is toxic to Aedes aegypti (Diptera: Culicidae).

Bacillus thuringensis (Bt) vegetative insecticidal proteins share no sequence or structural homology with the known Cry proteins. The activity of Vip3Aa is generally considered to be restricted to lepidopteran insects. In this paper, the vip3Aa gene was cloned from Bt subsp. kurstaki HD1 and expressed in E. coli. It was found to be toxic to Aedes aegypti larvae - the first time that dipteran activity has been reported. Furthermore, the potential synergism of Vip3Aa with the Cry toxins was investigated. Although no significant synergism was observed, Vip3Aa could be used in combination with Cry toxins to prevent or delay the onset of resistance.

Persistent Pleural Lesions and Inflammation by Pulmonary Exposure of Multiwalled Carbon Nanotubes.

Translocation of multiwalled carbon nanotubes (MWCNTs) from the lung to the pleural cavity, deposition of the fibers in the pleural tissue, induction of pleural fibrosis, and mesothelial proliferation have been found in rodents administered MWCNTs by different pulmonary exposure methods. However, whether the translocation and deposition and the subsequent pleural inflammation are associated with the pleural lesions is unclear. In the present study, male F344 rats were given 250 µg of two types of MWCNTs, with crocidolite as a positive control, 2 times/week for 4 weeks by intratracheal spraying. At 24 h and at 3 months after the last spraying, the rats were sacrificed for histological examination of the lung and chest wall; pleural cavity lavage was also collected at sacrifice for observation of pleural inflammatory reactions. The results indicated that intratracheally sprayed MWCNTs, like crocidolite fibers, translocated into the pleural cavity, deposited in the pleura, and induced persistent infiltration of immune cells into the pleural cavity, persistent pleural fibrosis, and mesothelial proliferation. The number of MWCNT fibers detected in the pleural cavity lavage was parallel to the number of infiltrating immune cells, which were mainly composed of macrophages. Analysis of cytokines in the fluids of the pleural cavity lavages by suspension array indicated that levels of IL-2, IL-18, and IP-10 were significantly increased both at 24 h and at 3 months after the last spraying. In vitro proliferation assays revealed that a mixture of IL-2, IL-18, and IP-10, but not any of these cytokines alone, promoted cell proliferation of human fibroblasts and mesothelial cells. These results suggest that translocated and deposited MWCNTs induce subsequent pleural inflammation and that increased IL-2, IL-18, and IP-10 synergistically promote the development of pleural fibrosis and mesothelial proliferation.

The anxiolytic-like effects of puerarin are associated with the changes of monoaminergic neurotransmitters and biosynthesis of allopregnanolone in the brain.

Anxiety disorder is a serious and burdensome psychiatric illness that frequently turn into chronic clinical conditions. Puerarin have been shown to be effective in the therapy of depression. However, few studies are concerned about the anxiolytic-like effects of puerarin. The current study aimed to evaluate the anxiolytic-like effects of puerarin and its possible mechanism. To evaluate this, the behavioral tests, i.e. Vogel-type conflict test (VTCT), elevated plus-maze test (EPMT), and open-field test (OFT) were conducted. Data showed that similar to the positive-control drug sertraline (Ser) (15 mg/kg, i.g.), the anxiolytic-like effects were produced by puerarin (60 and 120 mg/kg, i.g.) in VTCT and EMPT respectively without affecting locomotor activity in OFT. Moreover, the present study also found that consistent with Ser, the levels of allopregnanolone and serotonin (5-HT) in the prefrontal cortex and hippocampus were increased by puerarin (60 and 120 mg/kg, i.g.), respectively. In summary, the present study indicated that puerarin exerted the anxiolytic-like effects, which maybe associated with normalization of 5-HT levels and biosynthesis of allopregnanolone in brain.

Anxiolytic-like effects of paeoniflorin in an animal model of post traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is the serious psychiatric disorder. Paeoniflorin (PF) produces the antidepressant-like properties. However, few studies are concerned about its anti-PTSD-like effects and mechanisms. To investigate these, the single prolonged stress (SPS) model was utilized. PTSD-like behavioral deficits in rats after exposure to SPS were improved by PF (10 and 20 mg/kg, i.p.), evidenced by blocking increased freezing time in contextual fear paradigm (CFP) and increased time and entries in open arms in elevated plus maze (EPM) test without affecting the locomotor activity in open field (OF) test. We also found that increased levels of corticosterone (Cort), corticotropin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) after exposure to SPS were reversed by PF (10 and 20 mg/kg, i.p.) in serum, respectively. Moreover, the decreased levels of serotonin (5-HT) and 5-Hydroxyindoleacetic acid (5-HIAA) in prefrontal cortex and hippocampus were reversed by PF (10 and 20 mg/kg, i.p.), respectively. In summary, the anti-PTSD-like activities of PF were associated with the modulation of HPA axis and 5-HT system activation.

Physiological and de novo transcriptome analysis of the fermentation mechanism of Cerasus sachalinensis roots in response to short-term waterlogging.

BACKGROUND: Cerasus sachalinensis is widely used in cool regions as a sweet cherry rootstock and is known for its sensitivity to soil waterlogging and waterlogging stress. However, the limited availability of Cerasus genomic resources has considerably restricted the exploration of its waterlogging response mechanism. To understand its reaction to short-term waterlogging, we analyzed the physiology and transcriptomes of C. sachalinensis roots in response to different waterlogging durations. RESULTS: In this study, 12,487 differentially expressed genes (DEGs) were identified from Cerasus sachalinensis roots under different waterlogging durations. Carbon metabolism and energy maintenance formed the first coping mechanism stage of C. sachalinensis in response to low oxygen conditions. Root energy processes, including root respiration and activities of the fermentation enzymes alcohol dehydrogenase, pyruvate decarboxylase, and lactate dehydrogenase, showed unique changes after 0 h, 3 h, 6 h, and 24 h of waterlogging exposure. Ribonucleic acid sequencing was used to analyze transcriptome changes in C. sachalinensis roots treated with 3 h, 6 h, and 24 h of waterlogging stress. After de novo assembly, 597,474 unigenes were recognized, of which 355,350 (59.47%) were annotated. To identify the most important pathways represented by DEGs, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used to compare these genes. The first stage of root reaction to waterlogging stress was activation of carbohydrate metabolism to produce more glucose and maintain energy levels. At 3 h, the glycolytic and fermentation pathways were activated to maintain adenosine triphosphate production. At 24 h, pathways involved in the translation of proteins were activated to further assist the plant in tolerating waterlogging stress. These findings will facilitate a further understanding of the potential mechanisms of plant responses to waterlogging at physiological and transcriptome levels. CONCLUSIONS: Carbon metabolism and energy maintenance formed the first coping mechanism C. sachalinensis in response to low oxygen conditions, and they may be responsible for its short-term waterlogging response. Our study not only provides the assessment of genomic resources of Cerasus but also paves the way for probing the metabolic and molecular mechanisms underlying the short-term waterlogging response in C. sachalinensis.