Host A-to-I RNA editing signatures in intracellular bacterial and single-strand RNA viral infections.

Background: Microbial infection is accompanied by remodeling of the host transcriptome. Involvement of A-to-I RNA editing has been reported during viral infection but remains to be elucidated during intracellular bacterial infections. Results: Herein we analyzed A-to-I RNA editing during intracellular bacterial infections based on 18 RNA-Seq datasets of 210 mouse samples involving 7 tissue types and 8 intracellular bacterial pathogens (IBPs), and identified a consensus signature of RNA editing for IBP infections, mainly involving neutrophil-mediated innate immunity and lipid metabolism. Further comparison of host RNA editing patterns revealed remarkable similarities between pneumonia caused by IBPs and single-strand RNA (ssRNA) viruses, such as altered editing enzyme expression, editing site numbers, and levels. In addition, functional enrichment analysis of genes with RNA editing highlighted that the Rab GTPase family played a common and vital role in the host immune response to IBP and ssRNA viral infections, which was indicated by the consistent up-regulated RNA editing of Ras-related protein Rab27a. Nevertheless, dramatic differences between IBP and viral infections were also observed, and clearly distinguished the two types of intracellular infections. Conclusion: Our study showed transcriptome-wide host A-to-I RNA editing alteration during IBP and ssRNA viral infections. By identifying and comparing consensus signatures of host A-to-I RNA editing, our analysis implicates the importance of host A-to-I RNA editing during these infections and provides new insights into the diagnosis and treatment of infectious diseases.

Transplantation of Gut Microbiota From High-Fat-Diet-Tolerant Cynomolgus Monkeys Alleviates Hyperlipidemia and Hepatic Steatosis in Rats.

Emerging evidence has been reported to support the involvement of the gut microbiota in the host's blood lipid and hyperlipidemia (HLP). However, there remains unexplained variation in the host's blood lipid phenotype. Herein a nonhuman primate HLP model was established in cynomolgus monkeys fed a high-fat diet (HFD) for 19 months. At month 19%, 60% (3/5) of the HFD monkeys developed HLP, but surprisingly 40% of them (2/5) exhibited strong tolerance to the HFD (HFD-T) with their blood lipid profiles returning to normal levels. Metagenomic analysis was used to investigate the compositional changes in the gut microbiota in these monkeys. Furthermore, the relative abundance of Megasphaera remarkably increased and became the dominant gut microbe in HFD-T monkeys. A validation experiment showed that transplantation of fecal microbiota from HFD-T monkeys reduced the blood lipid levels and hepatic steatosis in HLP rats. Furthermore, the relative abundance of Megasphaera significantly increased in rats receiving transplantation, confirming the successful colonization of the microbe in the host and its correlation with the change of the host's blood lipid profiles. Our results thus suggested a potentially pivotal lipid-lowering role of Megasphaera in the gut microbiota, which could contribute to the variation in the host's blood lipid phenotype.

Hybrid de novo Genome Assembly of Erwinia sp. E602 and Bioinformatic Analysis Characterized a New Plasmid-Borne lac Operon Under Positive Selection.

Our previous study identified a new ß-galactosidase in Erwinia sp. E602. To further understand the lactose metabolism in this strain, de novo genome assembly was conducted by using a strategy combining Illumina and PacBio sequencing technology. The whole genome of Erwinia sp. E602 includes a 4.8 Mb chromosome and a 326 kb large plasmid. A total of 4,739 genes, including 4,543 protein-coding genes, 25 rRNAs, 82 tRNAs and 7 other ncRNAs genes were annotated. The plasmid was the largest one characterized in genus Erwinia by far, and it contained a number of genes and pathways responsible for lactose metabolism and regulation. Moreover, a new plasmid-borne lac operon that lacked a typical ß-galactoside transacetylase (lacA) gene was identified in the strain. Phylogenetic analysis showed that the genes lacY and lacZ in the operon were under positive selection, indicating the adaptation of lactose metabolism to the environment in Erwinia sp. E602. Our current study demonstrated that the hybrid de novo genome assembly using Illumina and PacBio sequencing technologies, as well as the metabolic pathway analysis, provided a useful strategy for better understanding of the evolution of undiscovered microbial species or strains.

[Effect of Tiaoshen needling on plasma melatonin and cortisol in patients with chronic insomnia].

OBJECTIVE: To observe the clinical efficacy of Tiaoshen needling (dredging Governor Vessel and regulating mind)in the treatment of chronic insomnia (CI) and its effect on plasma melatonin (MT) and cortisol (CORT) levels, so as to explore its underlying mechanism. METHODS: Sixty patients with CI were randomly divided into the treatment group and the control group, with 30 cases in each group. Both groups were given sleep hygiene education before treatment. Patients in the treatment group received acupuncture or electroacupuncture at Baihui (GV20), Shenting (GV24), Yintang (GV29), bilateral Shenmen (HT7) and Sanyinjiao (SP6). Patients in the control group received acupuncture or electroacupuncture at bilateral Shousanli (LI10), Futu (ST32) and Feiyang(BL58). Both groups were treated every other day, 3 times a week, for a total of 4 weeks. Before and after treatment, Pittsburgh sleep quality index (PSQI) and fatigue severity scale (FSS) were used to evaluate sleep qua-lity and daytime fatigue, the plasma MT and CORT levels were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with before treatment, the PSQI scores and total FSS score of the treatment group decreased significantly (P<0.01，P<0.05), and the plasma MT content increased and CORT decreased significantly in the treatment group (P<0.01)，while the sleep-onset time score, sleep disturbance score and the PSQI total score of the control group decreased significantly (P<0.05). Compared with the control group, the PSQI sleep disorder score and total score, and the total FSS score as well as plasma CORT level were significantly down-regulated (P<0.01，P<0.05), while the plasma MT content was up-regulated (P<0.05) in the treatment group. CONCLUSION: Tiaoshen acupuncture can significantly improve the sleep quality of patients with CI and relieve daytime fatigue, which may be related to the increase of plasma MT content in patients with CI, thereby inhibiting the excessive activation of the hypothalamic-pituitary-adrenal axis.

[Effect of electroacupuncture on serum melatonin and dopamine in aged insomnia].

OBJECTIVE: To observe the clinical effect of electroacupuncture (EA) on aged insomnia, and explore its possible mechanism. METHODS: A total of 60 patients with aged insomnia were randomly divided into an EA group (30 cases) and a sham EA group (30 cases, 1 case dropped off). The patients in the EA group were treated with acupuncture at Baihui (GV 20), Yintang (GV 29), Shenmen (HT 7), Sanyinjiao (SP 6), Xinshu (BL 15) and Shenshu (BL 23), and EA was used at Baihui (GV 20) and Yintang (GV 29), with intermittent wave, 2 Hz in frequency. In the sham EA group, the acupoints and the EA connection acupoints were the same as those in the EA group, 2-3 mm in depth, but no current was connected. The intervention was given 30 min each time, once every other day, 3 times a week for 4 weeks in the both groups. Before and after treatment, the Pittsburgh sleep quality index (PSQI) and Montreal cognitive assessment (MoCA) scale were used to assess sleep quality and cognitive function, and serum melatonin (MT) and dopamine (DA) levels were detected. RESULTS: After treatment, the total score and sub-item scores of PSQI in the EA group were lower than those before treatment (P<0.01, P<0.05), among them, the sub-item scores of sleep quality, time to fall asleep, sleep time and sleep efficiency, daytime dysfunction and total score were all lower than those in the sham EA group (P<0.01, P<0.05). After treatment, the MoCA score and serum MT and DA levels in the EA group were higher than those before treatment (P<0.01), and the MoCA score and serum MT level in the EA group were higher than the sham EA group (P<0.01, P<0.05). CONCLUSION: Electroacupuncture can improve sleep quality and cognitive function in aged insomnia patients, and its mechanism may be related to regulating serum MT and DA levels.

[Effect of acupuncture at Tiaoshen acupoints on hyperarousal state in chronic insomnia].

OBJECTIVE: To observe the clinical effect of acupuncture at Tiaoshen (regulating the spirit) acupoints on chronic insomnia and hyperarousal state, and explore its possible mechanism. METHODS: A total of 60 patients with chronic insomnia were randomly divided into an acupuncture group (30 cases, 1 case dropped off) and a sham acupuncture group (30 cases, 1 cases dropped off). Both groups were given basic sleep health education. The acupuncture group was treated with acupuncture at Tiaoshen acupoints including Baihui (GV 20), Shenting (GV 24), Yintang (GV 29), Shenmen (HT 7) and Sanyinjiao (SP 6). The sham acupuncture group was treated with non-effective point shallow acupuncture. Both groups were treated once every other day, 3 times a week for 4 weeks. The Pittsburgh sleep quality index (PSQI) score, pre-sleep arousal scale (PSAS) score, hyperarousal scale (HAS) score, and serum gamma-aminobutyric acid (GABA) level before and after treatment were compared between the two groups. RESULTS: Compared before treatment, the sleep quality, time to fall asleep, sleep time, sleep efficiency, sleep disturbance, daytime dysfunction scores and total score of PSQI, various scores and total score of PSAS, and HAS score in the acupuncture group after treatment were decreased (P<0.05, P<0.01); in the sham acupuncture group, the time to fall asleep, daytime dysfunction scores and total score of PSQI, and cognitive arousal score of PSAS after treatment were decreased (P<0.05). After treatment, the sleep quality, time to fall asleep, sleep time, sleep efficiency, sleep disturbance, daytime dysfunction scores and total score of PSQI, various scores and total score of PSAS, and HAS score in the acupuncture group were lower than those in the sham acupuncture group (P<0.05, P<0.01). Compared before treatment, the serum GABA level in the acupuncture group were increased (P<0.05), and the serum GABA level in the acupuncture group was higher than that in the sham acupuncture group after treatment (P<0.05). CONCLUSION: Acupuncture at Tiaoshen acupoints can obviously improve the sleep and hyperarousal state of patients with chronic insomnia, and up-regulating serum GABA content is one of its possible mechanisms.

Perinatal depression: Data-driven subtypes derived from life history and mindfulness and personality.

BACKGROUND: Perinatal depression is the most prevalent mental disorder during the perinatal period, and research suggests that it presents heterogeneously. We aimed to explore how subtypes of perinatal depression present in terms of multivariate patterns of stable characteristics. METHODS: A cohort study was conducted from March 2016 to March 2018 with Chinese women in the prenatal period (n = 3186). Of the participants, 682 (21.41%) women with Edinburgh Postnatal Depression Scale scores ≥10, indicating probable depression, were included, with the remaining 2504 (78.59%) representing the control group. We assessed mood distress, cognition, life history, emotional regulation, and personality, and used latent class analysis and latent transition analysis to identify perinatal depression subtypes. Of the 682 women with probable depression, only 598 were included in the full analyses, as they completed at least 10 questionnaires. A second, non-overlapping sample and a follow-up cohort were used. RESULTS: We identified four subtypes: 1) a highly distressed type characterized by distress across all domains, high levels of rumination and neuroticism, and reduced trait mindfulness; 2) two moderately distressed types: one with high trauma and low perceived social support, and another with low trauma, high perceived social support, and expressive suppression; and 3) a slightly distressed subtype. LIMITATIONS: We only collected cost and time spent in hospital from medical records. We only had a small follow-up sample. CONCLUSIONS: This multidimensional subtyping of women with perinatal depression could help reduce the apparent heterogeneity of perinatal depression. Distinguishing the subtype characteristics facilitates identifying underlying causes of perinatal depression.

Childhood Neglect and Psychological Distress Among Pregnant Women: The Chain Multiple Mediation Effect of Perceived Social Support and Positive Coping.

This study aimed to investigate the association between childhood neglect and psychological distress in pregnant women and to assess whether perceived social support and coping styles mediated this association. Pregnant women (N = 276) recruited from the prenatal clinic of a comprehensive hospital in China participated in this study. Participants reported their experiences of childhood neglect and abuse, depression, anxiety, perceived social support, and coping styles. Childhood neglect was positively associated with psychological distress. Perceived social support mediated the relationship between childhood neglect and psychological distress. Perceived social support and positive coping acted as chain mediators between childhood neglect and psychological distress. Childhood neglect is a risk factor for psychological distress during pregnancy independent of childhood abuse; perceived social support and positive coping can influence this relationship.

[Effect of Tongdu Tiaoshen needling in treatment of chronic insomnia by regulating the hypothalamic-pituitary-adrenal axis].

OBJECTIVE: To investigate the clinical effect of Tongdu Tiaoshen needling in the treatment of chronic insomnia and its mechanism based on the hypothalamic-pituitary-adrenal (HPA) axis. METHODS: A total of 60 patients with chronic insomnia were randomly divided into treatment group and control group, with 30 patients in each group. In addition to the health education on sleep, the patients in the treatment group were given Tongdu Tiaoshen needling, i．e., electroacupuncture at Baihui (GV20), Shenting (GV24), Yintang (EX-HN3), bilateral Shenmen (HT7), and bilateral Sanyinjiao (SP6), and those in the control group were given superficial acupuncture at Shousanli (LI10), Futu (ST32), and Feiyang (BL58) at both sides, once every other day and three times a week for 4 consecutive weeks. Before and after treatment, the Pittsburgh Sleep Quality Index (PSQI) was used to assess the quality and efficiency of sleep, and ELISA was used to measure the serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT). RESULTS: After treatment, the treatment group had significant reductions in the total PSQI score and the score of each component of PSQI (P<0.01), and the control group had significant reductions in the total PSQI score (P<0.01) and the scores of all components except sleep duration (P<0.05); compared with the control group, the treatment group had significantly lower total PSQI score and the score of each component (P<0.01). After treatment, the treatment group had significant reductions in the serum levels of CRH, ACTH and CORT (P<0.05，P <0.01), and compared with the control group, the treatment group had significant reductions in the serum levels of CRH, ACTH and CORT (P<0.01，P<0.05). CONCLUSION: Tongdu Tiaoshen needling has a good clinical effect in the treatment of chronic insomnia and can significantly improve the sleep condition of patients with chronic insomnia, possibly by reducing the hormones associated with the HPA axis.

[Insomnia treated with three acupuncture combinations guided by theory of Tongdu Tiaoshen: a randomized controlled trial].

OBJECTIVE: To compare the clinical therapeutic effect and safety on insomnia among three acupuncture combinations, named Tongdu Tiaowei (promoting the circulation of the governor vessel and regulating the defensive system), Tongdu Yangxin (promoting the circulation of the governor vessel and nourishing the heart) and Tongdu Tiaozang (promoting the circulation of the governor vessel and regulating zang functions). METHODS: A total of 90 patients with insomnia were randomized into a Tongdu Tiaowei group (30 cases, 1 case dropped off ), a Tongdu Yangxin group (30 cases, 2 cases dropped off ) and a Tongdu Tiaozang group (30 cases, 1 case dropped off ). Besides electroacupuncture (EA) applied to Baihui (GV 20) and Yintang (GV 29) in all of the three groups, acupuncture was added at Shenmai (BL 62) and Zhaohai (KI 6), Shenmen (HT 7) and Sanyinjiao (SP 6) as well as back-shu points of five zang organs [Feishu (BL 13), Xinshu (BL 15), Ganshu (BL 18), Pishu (BL 20) and Shenshu (BL 23)] in the Tongdu Tiaowei group, the Tongdu Yangxin group and the Tongdu Tiaozang group successively. The treatment was given once every two days, 3 times weekly, consecutively for 4 weeks. The score of Pittsburgh sleep quality index (PSQI) before and after treatment was observed, the therapeutic effect was evaluated and the adverse reactions were recorded in the patients of each group. RESULTS: After treatment, the score of each of 6 factors, named sleep quality, sleep latency, sleep time, sleep efficiency, sleep disturbance and daytime dysfunction, as well as the total score of PSQI scale were all reduced as compared with the scores before treatment in the patients of each group (P<0.05). After treatment, the scores of sleep latency and daytime dysfunction in the Tongdu Tiaowei group were lower than the other two groups (P<0.05). The score of sleep time in the Tongdu Yangxin group was lower than the other two groups (P<0.05) and the score of sleep quality in the Tongdu Tiaozang group was lower than the other two groups (P<0.05). After treatment, the total effective rates were 96.6% (28/29), 96.4% (27/28) and 96.6% (28/29) in the Tongdu Tiaowei group, the Tongdu Yangxin group and the Tongdu Tiaozang group successively, without significant difference in comparison among the three groups (P>0.05). During treatment, 1 case of mild adverse reaction occurred in each group. CONCLUSION: All of the three acupuncture combinations, named Tongdu Tiaowei, Tongdu Yangxin and Tongdu Tiaozang can effectively improve the sleep conditions in the patients with insomnia and are satisfactory in safety. The acupuncture combinations of Tongdu Tiaowei has the potential advantage in shortening sleep latency and relieving daytime dysfunction, the combinations of Tongdu Yangxin has the potential advantage in increasing sleep time and the combinations of Tongdu Tiaozang has the potential advantage in improving sleep quality.

Profiles and characteristics of clinical subtypes of perinatal depressive symptoms: A latent class analysis.

AIMS: To investigate clinically relevant subtypes of perinatal depressive symptoms. DESIGN: Cross-sectional study. METHODS: A sample of 2,783 women at different prenatal and postnatal periods was recruited between August 2015 - August 2017. The Patient Health Questionnaire-9 (PHQ-9) was used to assess depressive symptoms. Data analyses consisted of latent class analysis (LCA), analysis of variance and multinomial logistic regression. RESULTS: (a) Five latent subtypes (Classes 5/4/3/1/2) were identified: 'no symptoms', 'mild physio-somatic symptoms', 'severe physio-somatic symptoms and moderate anhedonia', 'moderate-to-severe symptoms' and 'severe symptoms'; (b) Postpartum women were more likely to belong to the severe depressive symptoms group, whereas pregnant women were likely to report severe physio-somatic symptoms; and (c) History of abortion and perinatal complications increased the likelihood of belonging to all moderate-to-severe classes. Lower levels of education increased the probability of belonging to Class 2. Younger women were more likely to be categorized into Classes 1 and 2. CONCLUSIONS: This is the first study to examine heterogeneity of perinatal depressive symptoms and delineate the characteristics of subtypes at different prenatal and postnatal periods via the PHQ-9, using LCA in a Chinese general population. IMPACT: This research details the heterogeneity of perinatal depressive symptoms and delineates the characteristics of subtypes at different prenatal and postnatal periods in a Chinese general population.

Discovery of novel chalcone-dithiocarbamates as ROS-mediated apoptosis inducers by inhibiting catalase.

Novel chalcone-dithiocarbamate hybrids were designed, synthesized and evaluated for antiproliferative activity against selected cancer cell lines (MGC803, MCF7, and PC3). Among these analogues, (E)-2-oxo-2-((4-(3-(3,4,5-trimethoxyphenyl)acryloyl)phenyl)amino)ethyl-4-(2-hydroxyethyl)piperazine-1-carbodithioate (12d) showed the best inhibitory activity against PC3 cells (IC50 = 1.05 µM). Cellular mechanism studies elucidated 12d could inhibit colony formation, arrest cell cycle at G2/M phase and induce DNA damage against PC3 cells. Compound 12d also induced mitochondrial apoptosis by caspase activation, MMP decrease, ROS production and catalase (CAT) inhibition. Importantly, 12d inhibited epithelial-mesenchymal transition (EMT) process by regulating EMT-related proteins (E-cadherin, N-cadherin, Vimentin, MMP2, MMP9). These results indicated that 12d is a promising lead compound and deserves further investigation for prevention and treatment of human prostate cancer.

A non-linear relationship between the cumulative exposure to occupational stressors and nurses' burnout and the potentially emotion regulation factors.

BACKGROUND: Stressful situations can increase the likelihood of nurses experiencing negative emotions, especially burnout. AIMS: To explore the association of cumulative exposure to occupational stressors and emotion regulation strategies with nurses' burnout. METHODS: Participants were 602 nurses from three general hospitals in Jinan, China. Social demographic characteristics, occupational stress, burnout, and emotion regulation strategies (cognitive reappraisal, expressive suppression, and rumination), were assessed. RESULTS: Nearly 70% of nurses reported that they were burnt out. Those with a moderate level and high level of stressors were 3.203 times and 26.444 times more likely to have burnout, respectively (x2trend = 62.732). Logistic regression revealed that nurses had higher cognitive reappraisal score (odds ratios (OR) = 0.941), scored lower for burnout. Those who had higher expressive suppression score (OR = 1.054), higher rumination score (OR = 1.037), and a higher level of stressors (OR = 2.779-18.259) scored higher for burnout. The results of sensitivity analysis were similar. CONCLUSIONS: A non-linear relationship exists between the cumulative exposure to occupational stressors and nurses' burnout. Those who less frequently use cognitive reappraisal, more frequently use rumination and expressive suppression, and have a high level of stressors may be more likely to experience burnout.

Clinical application of carbon nanoparticles in curative resection for colorectal carcinoma.

PURPOSE: To explore the potential of carbon nanoparticles (CNs) for the intraoperative detection of positive and negative lymph nodes in the treatment of colorectal cancer. PATIENTS AND METHODS: The clinical data of 470 patients undergoing surgical procedures for colorectal cancer from June 2010 to February 2013 were analyzed retrospectively. The patients were divided into the CN group (183 males and 161 females; mean age, 58.6±12.4 years), who were given a CN suspension, and the control group (78 males and 48 females; mean age, 59.1±12.2 years), who were not given a CN suspension. The operative time, blood loss, number of lymph nodes detected/positive lymph nodes, and prevalence of postoperative complications were compared between the two groups. Three years after surgery, 444 cases (327 cases in the CN group and 117 cases in the control group) were interviewed, with the remaining 26 cases lost to follow-up. With regard to tumor, node, metastasis staging, the survival and prevalence of recurrence in each group at 3 years were analyzed. RESULTS: The number of positive lymph nodes was higher and the prevalence of blood loss was lower in the CN group than in the control group (p<0.05). There were no significant differences in the operative time, number of lymph nodes detected, or the prevalence of postoperative complications, survival, metastasis, or recurrence between the two groups at 3 years (p>0.05). CONCLUSION: The application of CNs is convenient for the detection of lymph nodes to reduce blood loss and increase the probability of detecting positive lymph nodes accurately and rapidly.

Design and Antiproliferative Evaluation of Novel Sulfanilamide Derivatives as Potential Tubulin Polymerization Inhibitors.

A series of sulfanilamide-1,2,3-triazole hybrids were designed by a molecular hybridization strategy and evaluated for antiproliferative activity against three selected cancer cell lines (MGC-803, MCF-7 and PC-3). The detailed structure-activity relationships for these sulfanilamide-1,2,3-triazole hybrids were investigated. All these sulfanilamide-1,2,3-triazole hybrids exhibited moderate to potent activity against all cell lines. In particular 4-methyl-N-((1-(3-phenoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)benzenesulfonamide (11f) showed the most potent inhibitory effect against PC-3 cells, with an IC50 value of 4.08 µM. Furthermore, the tubulin polymerization inhibitory activity in vitro of compound 11f was 2.41 µM. These sulfanilamide hybrids might serve as bioactive fragments for developing more potent antiproliferative agents.

Discovery of 5,6-diaryl-1,2,4-triazines hybrids as potential apoptosis inducers.

A series of 5,6-diaryl-1,2,4-triazines hybrids bearing a 1,2,3-triazole linker were synthesized by molecular hybridization strategy and evaluated for antiproliferative activity against three selected cancer cell lines (MGC-803, EC-109 and PC-3). The first structure-activity relationship (SAR) for these 5,6-diaryl-1,2,4-triazines is explored in this report with evaluation of 15 variants of the structural class. Among these chemical derivatives, 3-(((1-(4-fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-5,6-diphenyl-1,2,4-triazine (11E) showed the more potent inhibitory effect against three cell lines than 5-Fu. Cellular mechanism studies in MGC-803 cells elucidated 11E inhibited colony formation and arrested cell cycle at G2/M phase. Furthermore, compound 11E caused morphological changes, decreased mitochondrial membrane potential, and induced apoptosis through the apoptosis-related proteins in MGC-803 cells. It was the first time, to our knowledge, that 5,6-diaryl-1,2,4-triazines bearing a 1,2,3-triazole linker were used as potential apoptosis inducers.

Molecular diversity of phenothiazines: design and synthesis of phenothiazine-dithiocarbamate hybrids as potential cell cycle blockers.

Novel phenothiazine-dithiocarbamate analogues were designed by molecular hybridization strategy and synthesized and evaluated for their anticancer activity in vitro against three selected cancer cell lines (EC-109, MGC-803, and PC-3). The preliminary structure-activity relationship (SAR) for this phenothiazine-dithiocarbamate hybrids is explored. Among all analogues, 2-oxo-2-(10H-phenothiazin-10-yl)ethyl 4-ethylpiperazine-1-carbodithioate (8a) showed the most potent inhibitory activity with an [Formula: see text] value of [Formula: see text] against PC-3 cells. In addition, compound 8a could arrest the cell cycle at the G1 phase and regulate the expression of G1 checkpoint-related proteins, suggesting that phenothiazine-dithiocarbamate hybrids might be useful as cell cycle blockers.

Predictors of occupational burnout among nurses: a dominance analysis of job stressors.

AIMS AND OBJECTIVES: To quantitatively compare dimensions of job stressors' effects on nurses' burnout. BACKGROUND: Nurses, a key group of health service providers, often experience stressors at work. Extensive research has examined the relationship between job stressors and burnout; however, less has specifically compared the effects of job stressor domains on nurses' burnout. DESIGN: A quantitative cross-sectional survey examined three general hospitals in Jinan, China. METHOD: Participants were 602 nurses. We compared five potential stressors' ability to predict nurses' burnout using dominance analysis and assuming that each stressor was intercorrelated. RESULTS: Strong positive correlations were found between all five job stressors and burnout. Interpersonal relationships and management issues most strongly predicted participants' burnout (11·3% of average variance). CONCLUSION: Job stressors, and particularly interpersonal relationships and management issues, significantly predict nurses' job burnout. RELEVANCE TO CLINICAL PRACTICE: Understanding the relative effect of job stressors may help identify fruitful areas for intervention and improve nurse recruitment and retention.

Design and synthesis of formononetin-dithiocarbamate hybrids that inhibit growth and migration of PC-3 cells via MAPK/Wnt signaling pathways.

A series of novel formononetin-dithiocarbamate derivatives were designed, synthesized and evaluated for antiproliferative activity against three selected cancer cell line (MGC-803, EC-109, PC-3). The first structure-activity relationship (SAR) for this formononetin-dithiocarbamate scaffold is explored in this report with evaluation of 14 variants of the structural class. Among these analogues, tert-butyl 4-(((3-((3-(4-methoxyphenyl)-4-oxo-4H-chromen-7-yl)oxy)propyl)thio)carbonothioyl)piperazine-1-carboxylate (8i) showed the best inhibitory activity against PC-3 cells (IC50 = 1.97 µM). Cellular mechanism studies elucidated 8i arrests cell cycle at G1 phase and regulates the expression of G1 checkpoint-related proteins in concentration-dependent manners. Furthermore, 8i could inhibit cell growth via MAPK signaling pathway and inhibit migration via Wnt pathway in PC-3 cells.

[Study on anti-tumor and anti-metastasis mechanism of alcohol extracts from pharbitidis semen against Lewis lung cancer].

OBJECTIVE: To observe the effect of alcohol extracts from Pharbitidis Semen on the proliferation and metastasis of Lewis lung cancer, and study its anti-tumor mechanism. METHOD: In vitro, MTT assay and scratch assay were adopted to detect the effect of alcohol extracts from Pharbitidis Semen on the proliferation and metastasis of Lewis lung cancer cells. The cell autophagy was detected by the acridine orange staining. The gap-junction intercellular communication (GJIC) was investigated by the fluorescent yellow transfer. The expression of aquaporin 1 (AQP1) was analyzed by the Western blotting. In vivo, the subcutaneous implant model and the experimental pulmonary metastasis model of Lewis lung cancer in mice were established to evaluate the anti-tumor and anti-metastasis effects of alcohol extract from Pharbitidis Semen. The serum carcinoembryonic antigen (CEA) and beta2 microglobulin (beta2-MG) of mice bearing Lewis lung cancer were detected by the electrochemiluminesence immunoassay. The expressions of lung AQP1 and Connexin 43 (Cx43) were examined by the immunohistochemical method. RESULT: In vitro, alcohol extracts from Pharbitidis Semen inhibited the cell proliferation in a dose-dependent matter, significantly prevented the cell migration, down-regulated AQP1 proteins of cells, promoted GJIC, and decreased the serum-free autophagy of tumor cells. In vivo, compared with untreated model mice, alcohol extracts from Pharbitidis Semen inhibited the tumor growth in a dose-dependent matter, prevented the tumor metastasis and prolonged the life span of mice bearing Lewis lung cancer, while decreasing serum CEA and beta2-MG of mice bearing Lewis lung cancer, enhancing the immumohistochemical staining intensity of Cx43 and weakening aquaporins AQP1 positive intensity. CONCLUSION: Alcohol extracts from Pharbitidis Semen could prevent the proliferation and metastasis in Lewis lung cancer cells. Its mechanism may be related to the promotion of GJIC and the down-regulation of AQP1.