Evaluation of Organic Hydride/Acid Pairs as a Type of Thermodynamic-Potential-Regulated Multisite Proton-Coupled Electron Transfer Reagents.

Organic hydride/acid pairs have been reported as multisite proton-coupled electron transfer (MS-PCET) reagents in reductive MS-PCET reactions recently. Since the key step for an organic hydride/acid pair acting as an MS-PCET reagent is a chemical process of the organic hydride/acid pair releasing a formal hydrogen atom, the bond dissociation free energy of the organic hydride/acid pair releasing a formal hydrogen atom is a valuable thermodynamic parameter for objectively evaluating the thermodynamic potential for an organic hydride/acid pair to act as an MS-PCET reagent. Now, organic hydride/acid pairs of 216 organic hydrides have been demonstrated to be a potential type of thermodynamically potential-regulated MS-PCET reagent. Without a doubt, organic hydride/acid pairs reflect the change of N-substituted organic hydrides from simple hydride reductants to thermodynamically-regulated MS-PCET reagents, which could significantly expand the availability of novel MS-PCET reagents.

Synergy of Oxygen Vacancy and Surface Modulation Endows Hollow Hydrangea-like MnCo2O4.5 with Enhanced Capacitive Performance.

Surface chemistry and bulk structure jointly play crucial roles in achieving high-performance supercapacitors. Here, the synergistic effect of surface chemistry properties (vacancy and phosphorization) and structure-derived properties (hollow hydrangea-like structure) on energy storage is explored by the surface treatment and architecture design of the nanostructures. The theoretical calculations and experiments prove that surface chemistry modulation is capable of improving electronic conductivity and electrolyte wettability. The structural engineering of both hollow and nanosheets produces a high specific surface area and an abundant pore structure, which is favorable in exposing more active sites and shortens the ion diffusion distance. Benefiting from its admirable physicochemical properties, the surface phosphorylated MnCo2O4.5 hollow hydrangea-like structure (P-MnCoO) delivers a high capacitance of 425 F g-1 at 1 A g-1, a superior capability rate of 63.9%, capacitance retention at 10 A g-1, and extremely long cyclic stability (91.1% after 10,000 cycles). The fabricated P-MnCoO/AC asymmetric supercapacitor achieved superior energy and power density. This work opens a new avenue to further improve the electrochemical performance of metal oxides for supercapacitors.

Halobacterium wangiae sp. nov. and Halobacterium zhouii sp. nov., two extremely halophilic archaea isolated from sediment of a salt lake and saline soil of an inland saltern.

Two novel halophilic archaeal strains, Gai3-17T and XZYJT26T, were isolated from the sediment of Gaize salt lake and the saline soil of Mangkang ancient solar saltern in Tibet, PR China, respectively. Strains Gai3-17T and XZYJT26T were related to each other (96.5 and 89.7% similarity, respectively) and showed 97.5-95.4 and 91.5-87.7% similarities to the current members of Halobacterium based on 16S rRNA and rpoB' genes. The phylogenomic analysis indicated that strains Gai3-17T and XZYJT26T formed two distinct clades and clustered with the Halobacterium species. The two strains can be differentiated from the type strains of the six species with validly published names based on several phenotypic characteristics. The phospholipids of the two strains were phosphatidic acid, phosphatidylglycerol and phosphatidylglycerol phosphate methyl ester. One major glycolipid, sulphated galactosyl mannosyl glucosyl diether, was detected in strain Gai3-17T, while four glycolipids, mannosyl glucosyl diether, sulphated mannosyl glucosyl diether, disulphated mannosyl glucosyl diether and sulphated galactosyl mannosyl glucosyl diether were observed in strain XZYJT26T. The average nucleotide identity, digital DNA-DNA hybridization and amino acid identity values among the two strains and the members of Halobacterium were no more than 81, 25 and 77 %, respectively. These overall genome-related indices were below the threshold values for species boundary, indicating that strains Gai3-17T and XZYJT26T represent two novel species of Halobacterium. Thus, two novel species, Halobacterium wangiae sp. nov. and Halobacterium zhouii sp. nov., are proposed to accommodate strains Gai3-17T (=CGMCC 1.16101T=JCM 33551T) and XZYJT26T (=CGMCC 1.16682T=JCM 33556T), respectively.

Roles of trained immunity in the pathogenesis of periodontitis.

Periodontitis is a chronic, inflammatory, and destructive disease caused by the imbalance of host immune response and dental biofilm, and has strong epidemiological and pathogenesis correlations with systemic diseases. The immune response in periodontitis involves both innate and adaptive immunity, with numerous immune cells and inflammatory pathways participating in a complex network of interactions. In the past decade, the concept of "trained immunity" has emerged, which highlights the memory characteristics of innate immunity, thus opening up a new avenue of research. There is growing interest in exploring the role of trained immunity in chronic inflammatory and metabolic diseases such as atherosclerosis and diabetes mellitus. Evidence suggests that trained immunity may also regulate the onset and progression of periodontitis, serving as a bridge between periodontitis-related comorbidities. In this review, we summarize concepts related to trained immunity and its development. Furthermore, we present current evidence that endorses the notion of trained immunity in periodontitis and analyze possible roles it may assume regarding periodontitis-associated inflammatory reactions from a cellular perspective. Finally, we discuss various clinical therapeutic strategies for periodontitis and its associated comorbidities that target trained immunity. We hope that more researchers will pay attention to this emerging concept, thereby providing deeper insights into this novel field.

Eriodictyol regulated ferroptosis, mitochondrial dysfunction, and cell viability via Nrf2/HO-1/NQO1 signaling pathway in ovarian cancer cells.

This study aimed to investigate the antitumor effect and the underlying molecular mechanism of eriodictyol on ovarian cancer cells. CaoV3 and A2780 were exposed to eriodictyol at different concentrations of 0-800 µM. Cell apoptosis and viability were determined by TdT-mediated dUTP Nick-End Labeling (TUNEL) assay and Cell Counting Kit-8 (CCK-8) assay, respectively. Mitochondrial membrane potential was evaluated by flow cytometers with a JC-1 detection kit. Fe2+ content was evaluated using an iron assay kit. The section of tumor tissues was observed using hematoxylin-eosin (H&E) staining and nuclear factor erythroid 2-related factor 2 (Nrf2) expression was detected by immunohistochemistry (IHC) staining. Eriodictyol suppressed cell viability and induced cell apoptosis of CaoV3 and A2780 cells. Half maximal inhibitory concentration (IC50 ) value of CaoV3 at 24 and 48 h was (229.74 ± 5.13) µM and (38.44 ± 4.68) µM, and IC50 value of A2780 at 24 and 48 h was (248.32 ± 2.54) µM and (64.28 ± 3.19) µM. Fe2+ content and reactive oxygen species production were increased and protein levels of SLC7A11 and GPX4 were decreased by eriodictyol. Besides, eriodictyol reduced the ratio of JC-1 fluorescence ratio, glutathione and malondialdehyde contents but elevated Cytochrome C level. Nrf2 phosphorylation were obviously downregulated by eriodictyol. Finally, eriodictyol suppressed tumor growth, aggravated mitochondrial dysfunction and downregulated Nrf2 expression in tumor tissue in mice. Eriodictyol regulated ferroptosis, mitochondrial dysfunction and cell viability via Nrf2/HO-1/NQO1 signaling pathway in ovarian cancer.

Risk factors of multidrug-resistant bacteria infection in patients with ventilator-associated pneumonia: A systematic review and meta-analysis.

BACKGROUND: Multidrug-resistant (MDR) bacteria-induced VAP often has high lethality. We present this systematic review and meta-analysis to assess the risk factors for MDR bacterial infection in patients with VAP. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library were searched for studies regarding MDR bacterial infection in VAP patients, from Jan 1996 to Aug 2022. Study selection, data extraction, and quality assessment of included studies were conducted by two reviewers independently, and potential risk factors for MDR bacterial infection were identified. RESULTS: Meta-analysis showed that the score of the Acute Physiology and Chronic Health Evaluation II (APACHE-II) [OR = 1.009, 95% (CI 0.732, 1.287)], Simplified Acute Physiology Score II (SAPS-II) [OR = 2.805, 95%CI (0.854, 4.755)], length of hospital-stay before VAP onset (days) [OR = 2.639, 95%CI (0.387, 4.892)], in-ICU duration [OR = 3.958, 95%CI (0.894, 7.021)], Charlson index [OR = 1.000, 95%CI (0.889, 1.111)], overall hospital-stay [OR = 20.742, 95%CI (18.894, 22.591)], Medication of Quinolones [OR = 2.017, 95%CI (1.339, 3.038)], medication of carbapenems [OR = 3.527, 95%CI (2.476, 5.024)], combination of more than 2 prior antibiotics [OR = 3.181, 95%CI (2.102, 4.812)], and prior use of antibiotics [OR 2.971, 95%CI (2.001, 4.412)] were independent risk factors of MDR bacterial infection in VAP patients. Diabetes and mechanical ventilation duration before VAP onset showed no association with risk for MDR bacterial infection. CONCLUSIONS: This study has identified 10 risk factors associated with MDR bacterial infection in VAP patients. Identification of these factors would be able to facilitate the treatment and prevention of MDR bacterial infection in clinical practice.

Haladaptatus halobius sp. nov. and Haladaptatus salinisoli sp. nov., two extremely halophilic archaea isolated from Gobi saline soil.

Two extremely halophilic archaeal strains, PSR5T and PSR8T, were isolated from a saline soil sample collected from the Tarim Basin, Xinjiang, PR China. Both strains had two copies of the 16S rRNA genes rrn1 and rrn2, showing 2.6 and 3.9% divergence, respectively. The rrn1 gene of PSR5T showed 98.4 and 95.3% similarity to the rrn1 and rrn2 genes of strain PSR8T; the rrn2 gene of PSR5T displayed 97.4 and 96.7% similarity to those of strain PSR8T, respectively. Phylogenetic analyses based on the 16S rRNA and rpoB' genes revealed that strains PSR5T and PSR8T formed a single cluster, and then tightly clustered with the current four Haladaptatus species (93.5-97.1% similarities for the 16S rRNA gene and 89.3-90.9% similarities for the rpoB' gene, respectively). Several phenotypic characteristics differentiate strains PSR5T and PSR8T from current Haladaptatus members. The polar lipids of the two strains are phosphatidic acid, phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester phosphatidylglycerol sulphate and three glycolipids. One of the glycolipids is sulphated mannosyl glucosyl diether, and the remaining two glycolipids are unidentified. The average nucleotide identity, in silico DNA-DNA hybridization, amino acid identity and percentage of conserved proteins values between the two strains were 88.5, 39.1, 89.3 and 72.8 %, respectively, much lower than the threshold values proposed as a species boundary. These values among the two strains and Haladaptatus members were 77.9-79.2, 22.0-23.5, 75.1-78.2 and 56.8-69.9 %, respectively, much lower than the recommended threshold values for species delimitation. These results suggested that strains PSR5T and PSR8T represent two novel species of Haladaptatus. Based on phenotypic, chemotaxonomic, genomic and phylogenetic properties, strains PSR5T (=CGMCC 1.16851T=JCM 34141T) and PSR8T (=CGMCC 1.17025T=JCM 34142T) represent two novel species of the genus Haladaptatus, for which the names Haladaptatus halobius sp. nov. and Haladaptatus salinisoli sp. nov. are proposed.

Natrinema halophilum sp. nov., Natrinema salinisoli sp. nov., Natrinema amylolyticum sp. nov. and Haloterrigena alkaliphila sp. nov., four extremely halophilic archaea isolated from salt mine, saline soil and salt lake.

Four halophilic archaeal strains, YPL8T, SLN56T, LT61T and KZCA68T, were isolated from a salt mine, saline soil and a salt lake located in different regions of China. Sequence similarities of 16S rRNA and rpoB' genes among strains YPL8T, SLN56T, LT61T and the current members of Natrinema were 94.1-98.2 % and 89.3-95.1 %, respectively, while these values among strain KZCA68T and the current members of Haloterrigena were 97.2-97.4 % and 91.7-91.9 %, respectively. The average nucleotide identity, in silico DNA-DNA hybridization and average amino acid identity values among these four strains and their closely related species were all lower than the threshold values for species boundary. All four strains were unable to hydrolyse casein, gelatin, or Tween 80. Strain YPL8T contained phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylglycerol phosphate methyl ester (PGP-Me), sulfated mannosyl glucosyl diether (S-DGD-1), disulfated mannosyl glucosyl diether (S2-DGD) and sulfated mannosyl glucosyl diether-phosphatidic acid (S-DGD-PA). Strain SLN56T contained PA, PG, phosphatidylglycerol sulphate (PGS), PGP-Me, S-DGD-1, S2-DGD and S-DGD-PA. Strain LT61T contained PA, PG, PGS, PGP-Me, S-DGD-1 and S2-DGD. The phospholipids of strain KZCA68T were PA, PG and PGP-Me. These results showed that strains YPL8T (=CGMCC 1.13883T=JCM 31181T), SLN56T (=CGMCC 1.14945T=JCM 30832T) and LT61T (=CGMCC 1.14942T=JCM 30668T) represent novel species of the genus Natrinema, for which the names, Natrinema halophilum sp. nov., Natrinema salinisoli sp. nov. and Natrinema amylolyticum sp. nov. are proposed. Strain KZCA68T (=CGMCC 1.17211T=JCM 34158T) represents a novel species of Haloterrigena, for which the name Haloterrigena alkaliphila sp. nov. is proposed.

Discovering and Evaluating the Reducing Abilities of Polar Alkanes and Related Family Members as Organic Reductants Using Thermodynamics.

In this work, the pKa values of 69 polar alkanes (YH2) in acetonitrile were computed using the method developed by Luo and Zhang in 2020, and representative 69 thermodynamic network cards on 22 elementary steps of YH2 and related polar alkenes (Y) releasing or accepting H2 were naturally established. Potential electron reductants (YH-), hydride reductants (YH-), antioxidants (YH2 and YH-), and hydrogen molecule reductants (YH2) are unexpectedly discovered according to thermodynamic network cards. It is also found that there are great differences between YH2 and common hydrogen molecule reductants (XH2), such as Hantzsch ester (HEH2), benzothiazoline (BTH2), and dihydro-phenanthridine (PH2), releasing two hydrogen ions to unsaturated compounds. During the hydrogenation process, XH2 release hydrides first, then the oxidation state XH+ release protons. However, in the case of YH2, YH2 release protons first, then YH- release hydrides. It is the differences on acidic properties of YH2 and XH2 that result in the behavioral and thermodynamic differences on YH2 and XH2 releasing two hydrogen ions (H--H+). The redox mechanisms and behaviors of Y, YH-, and YH2 as electron, hydrogen atom, hydride, and hydrogen molecule donors or acceptors in the chemical reaction are reasonably investigated and discussed in this paper using thermodynamics.

Association of bone-related biomarkers with femoral neck bone strength.

BACKGROUND: Femoral neck fractures are the worst consequence of osteoporosis (OP), and its early prevention and treatment have become a public health problem. This study aims to investigate the relationship of bone-related biomarkers, femoral neck bone mineral density (BMD) and maximum load (Lmax), selecting the indicator which can reflect femoral neck bone loss and reduced bone strength. METHODS: A total of 108 patients were recruited from January 2017 to December 2019. Venous blood samples were collected from patients before total hip replacement, and femoral neck samples were collected during the surgery. Femoral neck BMD, femoral neck Lmax, bone-related markers (serum levels of bone turnover markers, protein expression of type I collagen (COL-I) and osteopontin (OPN) in femoral neck) were all measured and analyzed. RESULTS: The expression of COL-I in femoral neck were significantly decreased, whereas other markers were all significantly increased with the decreasing of femoral neck BMD and Lmax (P < 0.05). Among them, serum C-terminal telopeptide of type I collagen (CTX) levels and OPN expression of femoral neck were increased in osteopenia. In multiple linear regression analysis, CTX and OPN were both negatively correlated with femoral neck BMD and Lmax, and they were independent factors of femoral neck BMD and Lmax, whereas COL-I was independent factor affecting Lmax (P < 0.05). Besides, CTX was negatively correlated with COL-I (ß = -0.275, P = 0.012) and positively correlated with OPN (ß = 0.295, P = 0.003). CONCLUSIONS: Compared with other indicators, serum CTX was more sensitive to differences in bone mass and bone strength of femoral neck, and could be considered as surrogate marker for OPN and COL-I.Early measurement of CTX could facilitate the diagnosis of osteopenia and provide a theoretical basis for delaying the occurrence of femoral neck OP and fragility fractures.

Racemic Norlignans as Diastereoisomers from Ferula sinkiangensis Resins with Antitumor and Wound-Healing Promotion Activities.

Ferulasinkins A-D (1-4), four new norlignans, were isolated from the resins of Ferula sinkiangensis, a medicinal plant of the Apiaceae family. All of them were obtained as racemic mixtures, chiral HPLC was used to produce their (+)- and (-)-antipodes. The structures of these new compounds, including their absolute configurations, were elucidated by spectroscopic and computational methods. This isolation provides new insight into the chemical profiling of F. sinkiangensis resins beyond the well-investigated structure types such as sesquiterpene coumarins and disulfides. Compounds 2a and 3a were found to significantly inhibit the invasion and migration of triple-negative breast cancer (TNBC) cell lines via CCK-8 assay. On the other hand, the wound-healing assay also demonstrated that compounds 4a and 4b could promote the proliferation of human umbilical vein endothelial cells (HUVECs). Notably, the promoting effects of 4a and 4b were observed as more significant versus a positive control using basic fibroblast growth factor (bFGF).

Haloprofundus salilacus sp. nov., Haloprofundus halobius sp. nov. and Haloprofundus salinisoli sp. nov.: three extremely halophilic archaea isolated from salt lake and saline soil.

Three halophilic archaeal strains, Gai1-5T, SEDH52T and SQT7-1T were isolated from Gaize salt lake and Xiadi salt lake in Tibet, and saline soil from Xinjiang, respectively. Phylogenetic analysis based on 16S rRNA gene and rpoB' gene sequences showed that these three strains formed different branches separating them from Haloprofundus halophilus NK23T (97.7-98.3% similarities for 16S rRNA gene and 94.7-94.8% similarities for rpoB' gene, respectively) and Haloprofundus marisrubri SB9T (94.7-96.4% similarities for 16S rRNA gene and 92.3-93.2% similarities for rpoB' gene, respectively). Several phenotypic characteristics distinguish the strains Gai1-5 T, SEDH52T and SQT7-1T from Haloprofundus halophilus NK23T and Haloprofundus marisrubri SB9T. The average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values among the three strains and current Haloprofundus members were in the range of 83.3-88.3% and 27.2-35.7%, respectively, far below the species boundary threshold values. The major polar lipids of three strains were phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylglycerol sulphate (PGS), phosphatidylglycerol phosphate methyl ester (PGP-Me), sulfated mannosyl glucosyl diether (S-DGD-1), mannosyl glucosyl diether-phosphatidic acid (DGD-PA) and sulfated mannosyl glucosyl diether-phosphatidic acid (S-DGD-PA). These results showed that strains Gai1-5T (= CGMCC 1.16079T = JCM 33561T), SQT7-1T (= CGMCC 1.16063T = JCM 33553 T) and SEDH52T (= CGMCC 1.17434T) represented three novel species in the genus Haloprofundus, for which the names Haloprofundus salilacus sp. nov., Haloprofundus salinisoli sp. nov., and Haloprofundus halobius sp. nov. are proposed.

Ribosome as a Translocase and Helicase.

During protein synthesis, ribosome moves along mRNA to decode one codon after the other. Ribosome translocation is induced by a universally conserved protein, elongation factor G (EF-G) in bacteria and elongation factor 2 (EF-2) in eukaryotes. EF-G-induced translocation results in unwinding of the intramolecular secondary structures of mRNA by three base pairs at a time that renders the translating ribosome a processive helicase. Professor Alexander Sergeevich Spirin has made numerous seminal contributions to understanding the molecular mechanism of translocation. Here, we review Spirin's insights into the ribosomal translocation and recent advances in the field that stemmed from Spirin's pioneering work. We also discuss key remaining challenges in studies of translocase and helicase activities of the ribosome.

Workplace bullying, personality traits and health among hospital nurses: The mediating effect of social support.

AIMS AND OBJECTIVES: This study aimed to explore the status of nursing staff's workplace bullying, personality traits, social support and mental health, to find out the predictors of nursing staff's health, and to explore whether social support is a mediator to regulate the impact of workplace bullying on mental health. BACKGROUND: Bullying could cause physical and psychological problems, and nursing workplace bullying causes not only health problems of nursing staff but also patient safety problems. "Workplace bullying" is a worthy topic to pay attention to. Only limited studies could be discovered about the mediating effects between workplace bullying and health. METHODS: Cross-sectional and correlation designs were used. The STROBE was used as a checklist for this study. RESULTS: The results showed that the frequency of poor sleep quality ≥3 days in recent 2 weeks (p < .001), external control personality traits (p = .016), workplace bullying (p < .001) and less social support (p = .001) were the main predictors of the health problems among nurses, and social support was the mediator between workplace bullying and health problems. CONCLUSION: It is recommended that hospital managers should apply regular sleep-wake schedule by designing a biological clock-compliant shift in order to promote good sleep hygiene of the nurses. Providing educational programmes and building up policies to decrease workplace bullying and increase social supports are suggested. RELEVANCE TO CLINICAL PRACTICE: Hospital managers should provide education and training related to the prevention of bullying and establish communication and consultation channels for the bullied. Nursing managers should also educate nurses to establish effective social networks with family, friends and colleagues to prevent health problems.

SIRT1 Activation Promotes ß-Cell Regeneration by Activating Endocrine Progenitor Cells via AMPK Signaling-Mediated Fatty Acid Oxidation.

Induction of ß-cell regeneration from endogenous cells represents a highly promising strategy in stem cell-based treatment for patients with diabetes. Recently, calorie restriction has been shown to affect the regulation of tissue and cell regeneration, including ß cells, via metabolic related mechanisms. Here, we examined the potential utility of sirtuin 1 (SIRT1), a calorie restriction mimetic, for stimulating ß-cell regeneration and the underlying mechanisms of such stimulation. The present results showed that SIRT1 activation with SRT1720 promoted ß-cell regeneration in streptozotocin (STZ)-induced ß-cell-deficient neonatal rats. This beneficial effect involved enhanced activation of neurogenin3 (NGN3)-positive endocrine progenitors from pancreatic ductal cells, rather than an expansion of residual ß cells. A dynamic expression profile of SIRT1 was observed in endocrine progenitors both during ß-cell regeneration in neonatal rats and in the second transition phase of mouse pancreas development. Consistently, SRT1720 treatment upregulated endocrine progenitor differentiation in cultured pancreatic rudiments. Upregulation of NGN3 by SIRT1 activation was through stimulating AMP-activated protein kinase (AMPK) signaling-mediated fatty acid oxidation (FAO) in human pancreatic progenitor cells; AMPK inhibition abolished these effects. The present findings demonstrate a promotional effect of SIRT1 activation on ß-cell restoration and endocrine progenitor differentiation that involves regulation of AMPK signaling-mediated FAO. Stem Cells 2019;37:1416-1428.

Effects of assertiveness and psychosocial work condition on workplace bullying among nurses: A cross-sectional study.

AIMS: This study aims to explore nurses' demographic data, assertiveness, psychosocial work condition, and workplace bullying, and find the predictors of workplace bullying. METHODS: This study adopted a cross-sectional design. A stratified sample comprising 241 nurses from a regi onal teaching hospitals in Taiwan was selected from the 10th to the 23rd September, 2018. Data were analysed by using the SPSS Statistics 17.0. Descriptive statistics (frequency, percentage, mean, and standard deviation), one-way Anova, t test, Pearson's correlation, and multiple linear regressions were used. RESULTS: The results showed that the participants with "past bullying experience," "lower self-assertiveness," "higher work psychological demands," "lower workplace justice," "lower labour participation," and "lower overall social support" are more likely to experience workplace bullying. CONCLUSIONS: Hospital managers should pay attention to the problem of nursing workplace bullying. First of all, hospital managers should encourage curriculum on nursing workplace bullying and incorporate nursing workplace bullying prevention training courses in curriculum planning.

Synthetic Studies on Enantioselective Total Synthesis of Cyathane Diterpenoids: Cyrneines A and B, Glaucopine C, and (+)-Allocyathin B2.

The details for the synthetic studies on enantioselective total synthesis of cyathane diterpenoids cyrneine A (1) and B (2), glaucopine C (3), and (+)-allocyathin B2 are presented. We established a mild Suzuki coupling for heavily substituted nonactivated cyclopentenyl triflates using a phosphinamide-derived palladacycle as precatalyst and a chelation-controlled highly regioselective Friedel-Crafts cyclization. The utilization of these two key reactions enabled a rapid construction of the 5-6-6 tricyclic skeleton. In the middle stage of the synthesis, a Birch reductive methylation, a modified Wolff-Kishner-Huang reduction, and a carbenoid-mediated ring expansion were employed as the key reactions to furnish the 5-6-7 tricyclic core bearing two antiorientated all-carbon quaternary stereocenters at the C6 and C9 ring junctions. By applying these key transformations, a more efficient total synthesis of cyrneine A and allocyathin B2, and the first total synthesis of cyrneine B and glaucopine C, were accomplished through a collective manner. The late-stage conversions involving a base-mediated double bond migration and a double bond migration/aerobic γ-CH oxidation cascade for the stereoselective synthesis of cyrneine B and glaucopine C were interesting.

Quantitative real-time PCR with high-throughput automatable DNA preparation for molecular screening of Nosema spp. in Antheraea pernyi.

Accurate diagnosis of pathogenic Nosema spp. in Antheraea pernyi samples is considered especially useful for reducing economic losses in sericulture and improving food safety by maintaining pathogen-free pupae. However, microscopy and immunologic methods have poor diagnostic sensitivity, while the more sensitive PCR methods remain costly and time-consuming for template preparation. To address this issue, we introduce a sensitive ALMS-qPCR method that combines fast, simple DNA extraction using Alkali Lysis followed by Magnetic bead Separation (ALMS) and quantitative real-time PCR (qPCR). This approach is especially fit for large-scale pathogen molecular screening, because the DNA preparation procedure is fast (<0.94 min per sample) and is high-throughput (performs on a 96-well plate). It is cost-effective, since the most expensive materials can be made in the lab and can be recycled, while the automated procedure can help to minimize labor cost. Though the DNA preparation procedure was substantially simplified, common PCR inhibitory factors were not observed. The sensitivity of ALMS-qPCR is high and the limit of detection is 0.045 parasites/µL. Large-scale screening of Nosema spp. in 3000 Antheraea pernyi samples confirmed the efficacy of the ALMS-qPCR method. Sensitivity is much higher than clinical microscopy, especially for host groups with low infection prevalence and levels. High-throughput ALMS-qPCR, combining automated DNA preparation and sensitive qPCR, provides an enhanced approach for pébrine screening and epidemiological studies. The application of ALMS-qPCR in the sericulture industry will help to strengthen pébrine control and breed pathogen-free species, which means much safer food provision and better genetic resource conservation.

Associations of work stress and humor with health status in hospital nurses-A cross-sectional study.

AIMS AND OBJECTIVES: To analyse the relationship among hospital nurses' socio-demographic data, work stress, humor and health conditions, and to determine the predictors of nurses' health status. BACKGROUND: Humor can decrease the feelings of helplessness, fear and anxiety, and that may result in the development of positive emotions, which might have a good impact on health. DESIGN: This research applied cross-sectional designs and used structured questionnaires which included socio-demographic data, an Effort-Reward Imbalance questionnaire (ERI), humor and 12-item Chinese health questionnaires (CHQ). A total of 236 nurses in a regional hospital in Taiwan were recruited. SPSS was used for the data analysis in the study. The STROBE was chosen as a checklist for this study. RESULTS: The results showed that the significant predictors of the participants' health were "whether experienced significant life events during the past 3 months," "the degree of work stress" and the level of "humor." CONCLUSIONS: It is recommended that administrators pay attention to the cultivation of nursing staff's humor, such as providing nurses with musical CDs or humorous books and providing stress management training courses to nurses. RELEVANCE TO CLINICAL PRACTICE: It is necessary for hospital managers to determine and deal with the causes of work stress to avoid the development of health problems in the nursing personnel. Furthermore, in order to develop stress-releasing strategies, it is necessary to provide nurses with stress management and resilience enhancement courses. Cultivating a humor competency of nurses is also recommended to alleviate the work stress.

Thalidomide Reduces Hemorrhage of Brain Arteriovenous Malformations in a Mouse Model.

BACKGROUND AND PURPOSE: Brain arteriovenous malformation (bAVM) is an important risk factor for intracranial hemorrhage. Current treatments for bAVM are all associated with considerable risks. There is no safe method to prevent bAVM hemorrhage. Thalidomide reduces nose bleeding in patients with hereditary hemorrhagic telangiectasia, an inherited disorder characterized by vascular malformations. In this study, we tested whether thalidomide and its less toxic analog, lenalidomide, reduce bAVM hemorrhage using a mouse model. METHODS: bAVMs were induced through induction of brain focal activin-like kinase 1 (Alk1, an AVM causative gene) gene deletion and angiogenesis in adult Alk1-floxed mice. Thalidomide was injected intraperitoneally twice per week for 6 weeks, starting either 2 or 8 weeks after AVM induction. Lenalidomide was injected intraperitoneally daily starting 8 weeks after AVM induction for 6 weeks. Brain samples were collected at the end of the treatments for morphology, mRNA, and protein analyses. The influence of Alk1 downregulation on PDGFB (platelet-derived growth factor B) expression was also studied on cultured human brain microvascular endothelial cells. The effect of PDGFB in mural cell recruitment in bAVM was explored by injection of a PDGFB overexpressing lentiviral vector to the mouse brain. RESULTS: Thalidomide or lenalidomide treatment reduced the number of dysplastic vessels and hemorrhage and increased mural cell (vascular smooth muscle cells and pericytes) coverage in the bAVM lesion. Thalidomide reduced the burden of CD68+ cells and the expression of inflammatory cytokines in the bAVM lesions. PDGFB expression was reduced in ALK1-knockdown human brain microvascular endothelial cells and in mouse bAVM lesion. Thalidomide increased Pdgfb expression in bAVM lesion. Overexpression of PDGFB mimicked the effect of thalidomide. CONCLUSIONS: Thalidomide and lenalidomide improve mural cell coverage of bAVM vessels and reduce bAVM hemorrhage, which is likely through upregulation of Pdgfb expression.