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Background Previous studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis. Results The study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved natural killer (NK) cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased the levels of Interferon gamma (IFN-γ), Interleukin-6 (IL-6), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in plasma. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for immune-related entries and pathways such as Tumor Necrosis Factor (TNF) and Toll-like receptor (TLR) signaling pathways, and upregulated expression levels of immune-related genes such as Complement 1q B chain (C1qb), Complement 4B (C4b), Tetracyclin Resistant (TCR) and Regulatory Factor X, 5 (RFX5). Conclusions BS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity.

In our previous study, we identified a metabolite of Bacillus subtilis BS-Z15 (a strain with probiotic characteristics) that could improve immunity in mice. In the present study, we examined the effects of B. subtilis BS-Z15 and its metabolites on body weight gain and the intestinal microbiota of mice. Sixty 25-day-old male Kunming white mice were selected and randomly divided into four groups: control group (A), daily saline gavage; B. subtilis -treated group (B), single gavage (1 × 10 9  CFU/time/animal/day); group D, 14 consecutive gavages (1 × 10 9  CFU/time/animal/day); and B. subtilis metabolite-treated group (E), 30 consecutive gavages (90 mg kg −1 /time/animal/day). High-throughput sequencing technology was used to analyze intergroup differences in the mouse intestinal microbiota. The results showed that the three treated groups had significantly slower body weight gain compared with the control group, which lasted until the 45 days ( P  < 0.05), and the daily food intake of the treated mice was higher ( P  < 0.05). The intestinal microbiota structure of the mice in the treated groups was significantly altered compared with that in the control group, suggesting that B. subtilis BS-Z15 may regulate the weight gain of animals by affecting their intestinal bacterial composition. After stopping the gavage of B. subtilis BS-Z15, the abundance of this strain in the small intestine of the mice gradually decreased and its presence was undetectable at 45 days, indicating that B. subtilis BS-Z15 could not colonize the intestine of these mice. These findings suggest that B. subtilis BS-Z15 may regulate intestinal microbiota through its metabolites to reduce weight gain.

Previous studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis. The study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved natural killer (NK) cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased the levels of Interferon gamma (IFN-[gamma]), Interleukin-6 (IL-6), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in plasma. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for immune-related entries and pathways such as Tumor Necrosis Factor (TNF) and Toll-like receptor (TLR) signaling pathways, and upregulated expression levels of immune-related genes such as Complement 1q B chain (C1qb), Complement 4B (C4b), Tetracyclin Resistant (TCR) and Regulatory Factor X, 5 (RFX5). BS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity.

R734.2; 小细胞肺癌(SCLC)是高度恶性肿瘤,具有增殖速度快、早期转移及预后差的特点,5年生存率仅7.2％.DNA损伤应答(DDR)是机体在面对DNA损伤及复制应激时,通过激活细胞周期检查点、阻滞细胞周期来促进DNA损伤修复,避免未修复的DNA损伤诱导程序性死亡的过程.SCLC具有突变负荷高、基因组不稳定的特征,普遍存在p53及RB1功能失活,致使细胞周期G1/S检查点缺陷,因而更加依赖后续的S、G2/M检查点进行周期阻滞和DNA损伤修复以确保基因组的稳定性及染色体的正确分离.因此,在基于致DNA损伤的放化疗应用背景下,抑制周期检查点以促进周期进程、增加DNA损伤及抑制DNA损伤修复成为SCLC治疗的新策略.本文就靶向DDR及其通路关键分子(PARP、ATR、CHK1/2、WEE1、ATM、Aurora A)抑制剂在SCLC中的研究进展进行综述,以期为SCLC的治疗策略提供思考.

To evaluate the effect of statins for erectile dysfunction （ED）, a systematic review of the literature was conducted in the Cochrane Library, Embase and PubMed from the inception of each database to June 2013. Only randomized controlled trials （RCTs） comparing treatment for ED with statins were identified. Placebo RCTs with the International Index of Erectile Function （IIEF） as the outcome measure were eligible for meta-analysis. A total of seven RCTs including two statins with a total of 586 patients strictly met our criteria for systematic review and five of them qualified for the meta-analysis. A meta-analysis using a random effects model showed that statins were associated with a significant increase in IIEF-5 scores （mean difference （MD）： 3.27; 95% confidential interval （CI）：1.51 to 5.02; P〈 0.01） and an overall improvement of lipid profiles including total cholesterol （MD： -1.08; 95% Ch -1.68 to -0.48; P 〈 0.01）, low-density lipoprotein （LDL） cholesterol （MD： -1.43; 95% Ch -2.07 to -0.79; P 〈 0.01）, high-density lipoprotein （HDL） cholesterol （MD： 0.24; 95% Ch 0.13 to 0.35; P〈 0.01） and triglycerides （TGs） （MD. -0.55; 95% Ch -0.61 to -0.48; P 〈 0.01）. In summary, our study revealed positive consequences of these lipid-lowering drugs on erectile function, especially for nonresponders to phosphodiesterase type 5 inhibitors （PDE51s）. However, it has been reported that statin therapy may reduce levels of testosterone and aggravate symptoms of ED. Therefore, larger, well-designed RCTs are needed to investigate the double-edged role of statins in the treatment of ED.

BACKGROUND:Current studies on CD62 P have focused mainly on cardiovascular diseases,while only few studies have evaluated the effects of CD62 P on the development of sepsis and the association between endothelial cell injury with inflammation and coagulation.This study attended to explore the association between endothelial cell injury with inflammation and coagulation by evaluating the expression of soluble CD62P(s-CD62P) in plasma and its mechanism in patients with sepsis,thus to provide the evidence of effective treatment of sepsis with anti-adhesion therapy targeted CD62 P.METHODS:A total of 70 critically ill patients with systemic inflammatory response syndrome(SIRS) admitted to intensive care unit(ICU) between September 2009 and February 2010 were enrolled for a prospective and control study.According to the diagnostic criteria of sepsis/SIRS,the patients were divided into two groups:a sepsis group(n=38) and a SIRS group(n=32).Another 20 healthy volunteers served as a control group.Patients in the sepsis group and SIRS group were matched by clinical signs of high blood pressure,diabetes and its complications.The demographics of the patients including age,sex,body mass index(BMI),smoking and alcohol addict were compared among the groups.Six mL peripheral blood samples were collected within 24-hour admission in ICU for enzymelinked immunosorbent assay(ELISA) to detect the plasma levels of S-CD62 P,TNF-α,and hs-CRP.And variables of coagulation function such as platelet(PLT),prothrombin(PT),activated partial thromboplastin time(APTT),D-dimer and antithrombin-Ⅲ(AT-Ⅲ) were analyzed during 24 hours after admission to ICU.Meanwhile sequential organ failure assessment(SOFA) score of critically ill patients was evaluated.Data were expressed as meanistandard deviation and were statistically analyzed by using SPSS 17.0statistical software.The differences in plasma levels of S-CD62 P of patients in each group were analyzed by ANOVA and the Kruskal-Wallis test.The relations between S-CD62 P and inflammatory cytokines as well as with coagulation were determined by Pearson’s product moment correlation coefficient analysis.Changes were considered as statistically significant if P value was less than 0.05.RESULTS:Compared with the control group and SIRS group,the sepsis group demonstrated significantly higher levels of S-CD62 P,TNF-a and highly sensitive C-reactive protein(hs-CRP)(PO.05).The plasma levels of D-dimer,PT,and APTT in the sepsis and SIRS groups were significantly higher than those in the control group,while the platelet count and the activity of AT-Ⅲ were obviously lower(P<0.05).In the sepsis group,the plasma levels of hs-CRP and TNF-a were positively correlated with PT,APTT,and D-dimer,and negatively correlated with AT-Ⅲ and PLT(P<0.05).The plasma levels of S-CD62 P were significantly correlated with the plasma levels of TNF-a,hs-CRP,D-dimer,PT,and APTT,whereas they were correlated negatively well with PLT and AT-Ⅲ(P<0.05).CONCLUSIONS:The concentration of plasma S-CD62 P is elevated as a early biomarker in patients with sepsis,and it serves as one of the pathogenic factors responsible for endothelial cell damage.Coagulation and mediators of inflammation promote each other,aggravating the severity of sepsis.Plasma S-CD62 P may be an important factor for the development of coagulation and inflammatory reaction.

* A full scale biofilm process was developed for typical domestic wastewater treatment. * The HRT was 8 h and secondary sedimentation tank was omitted. * Candidatus Brocadia were enriched in the HBR with an abundance of 2.89%. * Anammox enabled a stable ammonium removal of ~15% in the anoxic zone. The slow initiation of anammox for treating typical domestic wastewater and the relatively high footprint of wastewater treatment infrastructures are major concerns for practical wastewater treatment systems. Herein, a 300 m 3/d hybrid biofilm reactor (HBR) process was developed and operated with a short hydraulic retention time (HRT) of 8 h. The analysis of the bacterial community demonstrated that anammox were enriched in the anoxic zone of the HBR process. The percentage abundance of Candidatus Brocadia in the total bacterial community of the anoxic zone increased from 0 at Day 1 to 0.33% at Day 130 and then to 2.89% at Day 213. Based upon the activity of anammox bacteria, the removal of ammonia nitrogen (NH 4 +-N) in the anoxic zone was approximately 15%. This showed that the nitrogen transformation pathway was enhanced in the HBR system through partial anammox process in the anoxic zone. The final effluent contained 12 mg/L chemical oxygen demand (COD), 0.662 mg/L NH 4 +-N, 7.2 mg/L total nitrogen (TN), and 6 mg/L SS, indicating the effectiveness of the HBR process for treating real domestic wastewater.

Aim： This study was to investigate the effect of dehydroevodiamine （DHED） on Alzheimer＇s disease （AD）-like tau hyperphosphorylation induced by calyculin A （CA）, an inhibitor of protein phosphatase （PP）-2A and PP- 1, and the involvement of PP-2A in metabolically competent rat brain slices. Methods： Rat brain slices were pre-incubated at 33 ℃ in the presence （10, 100, and 200 μtmol/L, respectively） or absence of DHED for 1 h. Then, CA 0.1 μmol/L was added and the slices were treated for another 2 h. Western blotting and/or immunohistochemistry were used to measure the phosphorylation level of tau and PP-2A. Results： CA treatment could remarkably increase the immunoreactivity of pS262 and decrease the staining of Tau-1, representing tau hyperphosphorylation at Ser262 （pS262） and Ser198/ 199/202 （Tan-1, as the antibody reacts with unphosphorylated tau, therefore, decreased staining represents increased phosphorylation）. Prencubation of the brain slices with DHED could efficiently attenuate the CA-induced tau hyperphosphorylation at the above AD-related sites. Additionally, DHED also decreased the basal phosphorylation level of tau at Ser396, although CA failed to induce tau hyperphosphorylation at this site. Furthermore, CA treatment induced an increased level of Tyr307-phosphorylated PP-2A, which represents inactivation of the phosphatase, whereas DHED arrested the elevation of the inhibitory modification of PP-2A. Conclusion： DHED can attenuate CA-induced tau hyperphosphorylation at multiple AD-related sites in metabolically active rat brain slices. The underlying mechanism may involve a decreased inhibitory phosphorylation of PP-2A at Tyr307.