Experimental Verification of Demon-Involved Fluctuation Theorems.

The limit of energy saving in the control of small systems has recently attracted much interest due to the concept refinement of the Maxwell demon. Inspired by a newly proposed set of fluctuation theorems, we report the first experimental verification of these equalities and inequalities in an ultracold ^{40}Ca^{+} ion system, confirming the intrinsic nonequilibrium in the system due to involvement of the demon. Based on elaborately designed demon-involved control protocols, such as the Szilard engine protocol, we provide experimentally quantitative evidence of the dissipative information and observe tighter bounds of both the extracted work and the demon's efficacy than the limits predicted by the Sagawa-Ueda theorem. Our results substantiate a close connection between the physical nature of information and nonequilibrium processes at the microscale, which help to further understand the thermodynamic characteristics of information and the optimal design of nanoscale and smaller systems.

Response of microbial community and biological nitrogen removal to the accumulation of nonylphenol in sequencing batch reactor.

The widespread existence of nonylphenol in the environmental rendered from wastewater discharge has become a growing concern for its endocrine disrupting effects on microorganisms. In this study, the performance of nitrifying and denitrifying microbial community in a sequencing batch reactor (SBR) was investigated under different nonylphenol concentrations. The SBR was shown to be less effective in nitrogen removal at higher concentration of nonylphenol. Proteobacteria, Bacteroidetes, and Actinobacteria were characterized by 454 pyrosequencing as the dominant bacteria, nitrogen removal functional bacteria in these three phyla were inhibited by nonylphenol, and Proteobacteria and Actinobacteria were more sensitive to nonylphenol. With the accumulation of nonylphenol, the population of the most abundant denitrifying bacteria (Thauera spp.) and nitrifying bacteria (Nitrosomonas spp.) significantly reduced. Microbial diversity increased due to nonylphenol perturbation, which is indicated by the changes in microbial alpha diversity. Principal component analysis showed high similarity between microbial community in low and high concentration of nonylphenol, and the core genera involved in nitrogen removal had a low correlation with other genera shown in co-occurrence network. Moreover, linear discriminant analysis effect size analysis revealed intergroup differences in microorganisms. The mechanism of accumulated NP on the diversity and metabolism of the microbial community was examined. This paper established a theoretical foundation for the treatment of NP-containing wastewater and provided hints for further research about NP impact on biological nitrogen removal. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-023-04825-9.

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer.

BACKGROUND: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. PATIENTS AND METHODS: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. RESULTS: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. CONCLUSION: With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals.

Longitudinal investigations of anatomical and morphological development of the gastrointestinal tract in goats from colostrum to postweaning.

The digestive tract development in goat kids around weaning is vital to the establishment of digestion and absorption function, growth, and health of adults. The objective was to explore the effects of age and solid feed on the anatomical and morphological development of the gastrointestinal tract of Laiwu Black goat kids. Forty-eight female Laiwu Black goats at 8 ages (1, 7, 14, 28, 42, 56, 70, and 84 d; 6 goats per group) were selected and killed for anatomical and morphological analysis. The goats experienced the following 4 diet phases: maternal colostrum (MC; d 1, d 7), maternal milk (MM; d 14, d 28), maternal milk plus solid diet (MMSD; d 42, d 56) and only solid diet (OSD; d 70, d 84). The body and carcass weights were not significantly changed during MC and MM phases but changed during the MMSD phase. The absolute growth of body and carcass weights were higher in the MMSD phase than in MM phase. In addition, the dressing percentage was the highest in the MMSD phase. The body size indices evolved progressively and increased over time. The percentage of internal and external organs to body weight decreased over time, whereas the percentage to complex stomach percentage increased. The rumen and omasum weight experienced synchronous absolute growth over time, especially in the OSD phase. In contrast, the absolute growth of the reticulum and abomasum was the highest in MMSD and MC phases, respectively. After weaning, the goats showed the highest papillae height, lamina propria, muscle layer thickness, and epithelial thickness. The OSD phase showed the highest colonic mucosa thickness, ileal villus height, and ileal muscle layer thickness. The crypt depth was higher in the MMSD phase than in the MM phase. Moreover, the crypt depth and muscle layer thickness of jejunum increased over time. Furthermore, duodenal crypt depth, muscle layer thickness, and epithelial thickness increased in the OSD phase compared with other stages. In conclusion, the histological investigation supports the improvement of the morphological development of the digestive tract and the growth performance in the solid feed phase. It is recommended to add solid food as early as 4 wk old.

[Benefits and risks of prolonged dual antiplatelet therapy after percutaneous coronary intervention with drug-eluting stent in patients with stable coronary artery disease and diabetes].

Objective: To compare the efficacy and safety of prolonged dual antiplatelet therapy (DAPT>1 year) in patients with stable coronary artery disease (CAD) and diabetes who were event-free at 1 year after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) in a large and contemporary PCI registry. Methods: A total of 1 661 eligible patients were selected from the Fuwai PCI Registry, of which 1 193 received DAPT>1 year and 468 received DAPT ≤1 year. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding, MACCE was defined as a composite of all-cause death, myocardial infarction or stroke. Multivariate Cox regression analysis and inverse probability of treatment weighting (IPTW) Cox regression analysis were performed. Results: After a median follow-up of 2.5 years, patients who received DAPT>1 year were associated with lower risks of MACCE (1.4% vs. 3.2%; hazard ratio (HR) 0.412, 95% confidence interval (CI) 0.205-0.827) compared with DAPT ≤1 year, which was primarily caused by the lower all-cause mortality (0.1% vs. 2.6%; HR 0.031, 95%CI 0.004-0.236). Risks of cardiac death (0.1% vs. 1.5%; HR 0.051, 95%CI 0.006-0.416) and definite/probable ST (0.3% vs. 1.1%; HR 0.218, 95%CI 0.052-0.917) were also lower in patients received DAPT>1 year than those received DAPT ≤ 1 year. No difference was found between the two groups in terms of BARC type 2, 3, or 5 bleeding (5.3% vs. 4.1%; HR 1.088, 95%CI 0.650-1.821). Conclusions: In patients with stable CAD and diabetes who were event-free at 1 year after PCI with DES, prolonged DAPT (>1 year) provides a substantial reduction in ischemic cardiovascular events, including MACCE, all-cause mortality, cardiac mortality, and definite/probable ST, without increasing the clinically relevant bleeding risk compared with ≤ 1-year DAPT. Further well-designed, large-scale randomized trials are needed to verify the beneficial effect of prolonged DAPT in this population.

[Significance of microRNA 216a, 324-5p and 29a expression in peripheral blood in patients with acute pancreatitis and their correlation with liver injury].

Objective: To investigate the significance of microRNA (miR)-216a, miR-324-5p, miR-29a expression in peripheral blood in patients with acute pancreatitis (AP) and their correlation with liver injury. Methods: It was a case-control study design. To select 130 AP patients admitted from June 2017 to May 2019 in the First People's Hospital of Shangqiu, and the patients were divided into mild AP group (MAP group) and moderately severe AP group (SAP group) according to the disease severity, or 54 patients in the liver injury group (20 were MAP and 34 were SAP) and 76 in the non-liver injury group(all were MAP) according to liver injury. And another 40 healthy volunteers were selected as the healthy group. The expressions of miR-216a, miR-324-5p and miR-29a in peripheral blood of MAP group, SAP group, healthy group and liver injury group, non-liver injury group were compared, and the correlation between the miRNA levels and clinical indexes was analyzed. The predictive value of miRNA levels in peripheral blood for AP complicated with liver injury was analyzed by receiver operating characteristic (ROC) curve. Results: The levels of miR-216a and miR-29a in MAP group and SAP group were higher than those in healthy group, and the level of miR-324-5p was lower than that in healthy group (all P<0.01). The levels of miR-216a and miR-29a in SAP group were higher than those in MAP group, and the level of miR-324-5p was lower than that in healthy group (all P<0.01). Balthazar CT Score, acute physiology and chronic health evaluations (APACHE Ⅱ) score, C-reactive protein level, length of hospital stay were positively correlated with the levels of miR-216a and miR-29a in peripheral blood (all P<0.05), and negatively correlated with the levels of miR-324-5p (P<0.05). The levels of miR-216a and miR-29a in the peripheral blood in the liver injury group were higher than those in the non-liver injury group, and they were higher inSAP patients than those in MAP patients in the liver injury group (all P<0.05). The level of miR-324-5p in the peripheral blood in the liver injury group was lower than that in the non-liver injury group, and it was lower in SAP patients than that in MAP patientsin the liver injury group (all P<0.05). The area under ROC curve of miR-216a, miR-324-5p, and miR-29a in peripheral blood to predicate the AP complicated with liver damage was 0.694, 0.750 and 0.814, respectively. Conclusions: The levels of miR-216a and miR-29a increase in peripheral blood and the level of miR-324-5p decreases in patients with AP, and they are closely related to Balthazar CT score, APACHEⅡ score, C-reactive protein and length of hospital stay. The levels of miR-216a, miR-324-5p, miR-29a has certain predictive value for AP with liver injury, of which miR-29a has the highest predictive value.

Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib.

BACKGROUND: Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. PATIENTS AND METHODS: Patients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. RESULTS: Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [-2.47; 95% confidence interval (CI) -7.27, 2.33; P = 0.31]. Analysis of physical functioning scores showed a significant between-group difference (-4.45 points; 95% CI -8.75, -0.16; P = 0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P = 0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P = 0.32; HR 1.38; 95% CI 0.73, 2.63). CONCLUSIONS: HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer. CLINCALTRIALS.GOV NUMBER: NCT02184195.

[Mechanism of androgen in improving erectile dysfunction in castrated rats by regulating androgen receptor/vascular endothelial growth factor].

Objective: To explore the mechanism of androgen in improving erectile dysfunction in castrated rats. Methods: Forty 8-week-old male Sprague-Dawley (SD) rats were randomly divided into 4 groups:normal control group (Group A); castration group (Group B, in which rats were castrated); intervention groups (group C and D), in which rats were treated with different concentrations of testosterone undecanoate orally every day at 10 mg/kg (low dose) and 20 mg/kg (high dose), respectively after being castrated. Animals in group A and B were given 0.9% NS instead. After 8-week treatment, the level of serum testosterone, intra cavernous pressure (ICP) and mean arterial pressure (MAP) were detected, and the expression of androgen receptor (AR)and vascular endothelial growth factor (VEGF) were detected in the penis by Immunohistochemistry and Western blot. Results: The level of serum testosterone was significantly lower in group B [(1.3±0.6) nmol/L] than in group A [(17.1±1.5) nmol/L] (P<0.05).After testosterone supplementation, serum testosterone levels in group C [(8.7±1.2) nmol/L] and group D [(15.5±1.6) nmol/L] were higher than that in group B (all P<0.05). Max ICP/MAP of group C and D were higher than that in group B (all P<0.05). Immunohistochemistry and Western blot showed that the expression levels of AR and VEGF in group B were significantly lower than those in group A, C and D, and group D > group C (all P<0.05). Conclusion: Androgen replacement therapy with testosterone undecanoate can improve the erectile function of castrated rats by protecting the integrity of endothelial cells through AR/VEGF pathway.

[Association between resting heart rate trajectory pattern and risk of cardiovascular and cerebrovascular diseases].

Objective: To examine whether the long-term resting heart rate (RHR) pattern can predict the risk of cardiovascular and cerebrovascular diseases (CVDs). Methods: This prospective cohort study included 63 040 participants who took part in the health examination in 2006 and one of the health examinations on 2008 or 2010 and were free of myocardial infarction, stroke, arrhythmia, cancer and not treated with ß-recepter blocker. The outcomes were the first occurrence of myocardial infarction and stroke during the follow up ended on December 31, 2015. RHRs were measured in 2006, 2008, and 2010. We used latent mixture modeling SAS Proc procedure to identify RHR trajectories. We identified 4 distinct RHR trajectory patterns based on the data derived from 2006 and on the pattern change during 2006 to 2010 (low-stable, moderate-stable, moderate-increasing, elevated-decreasing). Collected the general clinical data of the patients. Cox regression model was used to determine the association between RHR trajectory patterns and the risk of CVDs during follow up. Hazard ratio (HR) with 95% confidence intervals (CI) were calculated using Cox regression modeling. Results: There were statistical significance among the 4 distinct RHR trajectory patterns on the following variables: age, gender, smoking status, drinking status, physical activity, education status, history of use antihypertensive drugs, history of hypertension,history of diabetes, body mass index, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting blood glucose, and the level of high-sensitivity C-reactive protein (all P<0.01). The moderate-increasing pattern experienced the highest risk of developing stroke and CVDs among all 4 patterns. The cumulative incidence of cerebral infarction, cerebral hemorrhage and CVDs in the order of low-stable trajectory, moderate-stable trajectory and moderate-increasing trajectory. The cumulative incidences of cerebral infarction, cerebral hemorrhage and CVDs in elevated-decreasing trajectory group were significantly lower than those in moderate-increasing trajectory group, but higher than those in moderate-stable trajectory group. Compared to the low-stable pattern, adjusted HR was 1.3 (95%CI 1.0-1.6) for the moderate-increasing pattern after adjustment for potential confounders. Conclusion: Our study finds that individuals with moderate-increasing RHR trajectory pattern are associated with higher risk of cardiovascular and CVDs.

Free electrons excited SPASER.

Surface plasmon amplification by stimulated emission of radiation (SPASER) is discovered and used for realizing lasers at nanometer scale. The conventional gain media that are applied in SPASER are solid materials, such as organic dye or semiconductor, which limits the frequency range of SPASER. The free electrons could be considered as a kind of gain medium for emitting radiation. Here, we investigate theoretically the SPASER, which is excited by free electrons. We also demonstrate the tunable, deep-ultraviolet, and ultracompact laser numerically by having free electrons interact with surface plasmon polariton mode supported on metal surface. The output power density could reach about 30 W/µm2 and the wavelength in deep ultraviolet could be widely tuned by varying the electron energy. This work offers a way of realizing integrated free electron laser in the ultraviolet frequency region.

Androgen deficiency impairs erectile function in rats through promotion of corporal fibrosis.

The aim of this study was to investigate the underlying mechanism of androgen deficiency inducing corporal fibrosis, thereby causing erectile dysfunction (ED). Forty 12-week-old healthy male rats were divided randomly into four groups: normal control group (Control); castration group (Castration); the other 20 rats were castrated followed by testosterone (T) (orally) each day: castration + 10mg/kg T group (Castration + 10T) and castration + 20 mg/kg T group (Castration + 20T). After 8 weeks' treatment, the main outcome measures were the following: serum levels of T; the ratios of intracavernous pressure (ICP) to mean arterial pressure (MAP); histologic changes in penile smooth muscle cells; the Smad and non-Smad pathways; and extracellular matrix (ECM) protein deposition. Castration group showed lower level of T and ratio of ICP/MAP, reduced ratio of penile smooth muscle cells/collagen, increased extracellular matrix protein deposition, and a higher expression of the Smad and non-Smad pathways. Castration + 10T partially preserved erectile function and histology stabilisation. However, the Castration + 20T group showed significantly better erectile function and molecular changes. Better efficacy could be expected with ART of adequate dose. Androgen deficiency induces corporal fibrosis through activation of the Smad and non-Smad pathways, and accumulation of ECM proteins.

[The influence of Thymidine Phosphorylase genetic variation on clinical outcomes and safety of colorectal cancer patients received adjuvant chemotherapy after R0 resection].

Objective: To study the association between Thymidine Phosphorylase (TYMP) genetic variation and clinical outcomes and safety of postoperative colorectal cancer (CRC) patients. Methods: A total of 235 patients with colorectal cancer underwent surgical treatment were included in this retrospective analysis. Peripheral blood and the postoperative tissue specimen of the CRC patients were collected for the genotyping of polymorphism and TYMP mRNA expression, respectively. The correlation between polymorphism and clinical outcomes and safety of postoperative CRC patients were analysed. Results: Located in the upstream, 5633C>T was of clinical significance. The prevalence of 5633C>T in TYMP among the CRC patients were as follows: CC genotype 149 cases (63.40%), CT genotype 73 cases (31.06%), TT genotype 13 cases (5.54%), minor allele frequency of 5633C>T is 0.21. The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.313). CT genotype and TT genotype patients were merged in the comparison of prognosis. The survival analysis of patients with different genotypes found that the median Overall Survival (OS) of CT/TT genotype and CC genotype were 5.8 and 4.5 year, which was statistically significant (P=0.009). Adjusted in multivariate Cox regression analysis, CT/TT genotype was an independent favorable factor for OS (HR=0.67, P=0.015). Additionally, of the 87 postoperative tissue specimens, the results showed that the expression of TYMP in cancer tissues of the patients with CT or TT genotypes were significantly higher than those of the wild type CC genotype patients (P=0.019). And the safety analysis showed that the incidence of grade 3 hand-foot syndrome among CT/TT genotype patients were higher than that of CC genotype patients (33.72% vs 20.13%, OR=1.68, P=0.021). Conclusion: The polymorphism 5633C>T of TYMP may impact the prognosis of CRC patients received adjuvant chemotherapy by influencing the mRNA expression of TYMP.

Hyperlipidemia impairs erectile function in rats by causing cavernosal fibrosis.

Men with hyperlipidemia are more likely to have erectile dysfunction (ED) than those without hyperlipidemia, but the mechanisms are not fully understood. The aim of this study was to investigate the underlying mechanism of ED caused by hyperlipidemia. Fourteen 8-week-old Sprague-Dawley rats were randomly divided into two groups: a control group and a hyperlipidemia group (fed chow containing 4% cholesterol and 1% cholic acid). After 6 months, we assessed erectile function by performing cavernous nerve electrostimulation followed by intracavernosal pressure/mean arterial pressure measurements, as well as plasma lipid profile assessment in all rats. A transferase-mediated nick end labeling (TUNEL) assay, immunohistochemical staining and Western blotting were performed to determine the levels of apoptosis, autophagy and fibrosis in the penile tissue. Compared with the control group, the hyperlipidemia group exhibited: (i) increased plasma lipid levels; (ii) decreased erectile function; (iii) a decreased smooth muscle/collagen ratio; (iv) increased fibrosis; (v) increased apoptosis and decreased autophagy. Overall, hyperlipidemia may attenuate erectile function in rats by causing of cavernosal fibrosis.

Suberoylanilide hydroxamic acid, a novel histone deacetylase inhibitor, improves the development and acetylation level of miniature porcine handmade cloning embryos.

Histone deacetylase inhibitors (HDACis) can change the histone acetylation and significantly enhance the developmental competence of the pre-implantation SCNT embryo. To select a proper histone deacetylase inhibitor to improve the success rate and potentially developmental ability of handmade cloning (HMC) embryos of miniature porcine, we compared the effect of two histone deacetylase inhibitors (SAHA vs. VPA) on HMC embryo development, their histone acetylation level and the expression level of relevant genes. The blastocyst rate and number of blastocyst cells of HMC embryos treated with SAHA (SAHA-HMC) or VPA (VPA-HMC) were significantly higher than those of control (Control-HMC), respectively, but there were no significant difference between SAHA-HMC and VPA-HMC groups. In addition, the acetylation level (AcH4K8) of Control-HMC and VPA-HMC embryos at the blastocyst stage, respectively, was significantly lower than that of in vitro fertilized (IVF) and SAHA-HMC embryos. However, the acetylation H4K8 of the blastocysts had no significant difference between SAHA-HMC and the IVF groups. The SAHA-HMC blastocysts indicated comparative expression levels of Oct4 and HDAC1 (histone deacetyltransferase gene) with those of IVF blastocysts. In contrast, the expression levels of Oct4 were lower and those of HDAC1 were higher in the VPA-HMC and Control-HMC blastocysts, respectively, compared to those of the IVF blastocysts. Our results demonstrated that the HMC embryos treated by SAHA could promote the pre-implantation development and increase the levels of histone H4K8 acetylation and the expression of the OCT4 gene, yet decrease the expression of the HDAC1 gene to the comparable level of the IVF embryos. Our results proved that SAHA may be a better histone deacetylase inhibitor for porcine HMC compared to VPA, and furthermore, it may indicate that SAHA can effectively correct the abnormal histone acetylation during the HMC embryo development and subsequently improve the full-term developmental potential of the HMC embryos after embryo transplantation.

Prevalence and molecular characterization of Salmonella enterica isolates throughout an integrated broiler supply chain in China.

A total of 1145 samples were collected from chicken breeder farms, hatcheries, broiler farms, a slaughterhouse and retail refrigerated chicken stores in an integrated broiler supply chain in Guangdong Province, China, in 2013. One-hundred and two Salmonella enterica strains were isolated and subjected to serotyping, antimicrobial susceptibility testing, virulence profile determination and molecular subtyping by pulsed field gel electrophoresis (PFGE). The contamination rates in samples from breeder farms, hatcheries, broiler farms, the slaughterhouse and retail stores were 1·46%, 4·31%, 7·00%, 62·86% and 54·67%, respectively. The isolated strains of S. enterica belonged to 10 serotypes; most of them were S. Weltevreden (46·08%, 47/102) and S. Agona (18·63%, 19/102). Isolates were frequently resistant to streptomycin (38·2%), tetracycline (36·3%), sulfisoxazole (35·3%) and gentamicin (34·3%); 31·4% of isolates were multidrug resistant. The isolates were screened for 10 virulence factors. The Salmonella pathogenicity island genes avrA, ssaQ, mgtC, siiD, and sopB and the fimbrial gene bcfC were present in 100% of the strains. PFGE genotyping of the 102 S. enterica isolates yielded 24 PFGE types at an 85% similarity threshold. The PFGE patterns show that the genotypes of S. enterica in the production chain are very diverse, but some strains have 100% similarity in different parts of the production chain, which indicates that some S. enterica persist throughout the broiler supply chain.

Exogenous Estradiol Benzoate Induces Spermatogenesis Disorder through Influencing Apoptosis and Oestrogen Receptor Signalling Pathway.

As the exact role for exogenous oestrogen in spermatogenesis is not fully understood, the aim of this study was to investigate the effect of estradiol benzoate (EB) exposure to male mice on their spermatogenesis and fertility. Sixty male mice aged 4 weeks were randomly divided into three groups, including a control group and two treatment groups. The mice of the control group were injected with 250 µl paraffin oil only by every other day subcutaneous injection for 4 weeks. Meantime, the mice of the treatment groups were injected with EB at the concentration of 5 or 10 mg/kg, respectively. Results showed that EB slowed down the body weight gains and generated testicular atrophy with spermatogenesis disorder compared with that of the control mice, and consequently induced their infertility. Moreover, the number of TUNEL-positive cells in the testis of EB-treated mice was significantly increased with the EB concentration rise. In comparison with controls, the mRNA expression level of pro-apoptosis factors (Fas, TNF, Cytochrome C, Apaf1, Chop, Caspase-3, Caspase-8, Caspase-9 and Caspase-12) and key genes in oestrogen receptor (ER) signalling pathway (ER α, ER ß, Erk1/2, Hsp90 and DAX-1) were upregulated in the testes of the treatment groups. Furthermore, Western blotting results proved the protein expression level of Fas, TNF, Cytochrome C, Chop, Caspase-3, cleaved Caspase-3, Caspase-9, Erk1/2 and Hsp90 were upregulated, and the phosphorylation level of Erk1/2 was also increased. These results indicate that EB may impair spermatogenesis through influencing the apoptosis and ER signalling pathway.

[Mechanism of RhoA/Rho-kinase signal pathway-induced erectile dysfunction in hyperlipidemic rats].

OBJECTIVE: To investigate the expression of RhoA/Rho-kinase (ROCK) in penile corpus cavernosum smooth muscles in rats of hyperlipidemia-induced erectile dysfunction and its molecular mechanism. METHODS: Forty male Sprague-Dawley rats were randomly divided into control and experimental groups using a random number table. Rats in the control group (n=20) were fed with regular diet for 24 weeks and those in the experimental group (n=20) with high-fat diet for the same period of time. The serum lipids profile was detected before and after the diet treatment. The ratio of intracavernosal pressure (ΔICP)/mean arterial pressure (MAP) was measured, and Western blot was used to detect the expression of total RhoA, ROCK1, and ROCK2 in penile corpus cavernosum smooth muscles, and RhoA protein in cell membrane and cytoplasm of smooth muscles after 24 weeks. RESULTS: After 24 weeks, the levels of cholesterol, triglyceride, and low-density lipoprotein were significantly higher in the experimental group compared with those before diet treatment and the control group (all P<0.01). ΔICP/MAP in the experimental group was greatly lower than in the control group (P<0.01). The protein expression of ROCK2 in penile corpus cavernosum smooth muscles was higher in the experimental group than in the control group (0.77±0.10 vs 0.27±0.08, P<0.01) after 24 weeks, while no statistically significant differences were observed in total RhoA and ROCK 1 protein expression between the two groups (both P>0.05). RhoA expression in cytoplasm was lower in the experimental than in the control group (1.66±0.09 vs 1.79±0.15, P<0.05). The ratio of RhoA expression in menmbrane/cytoplasm was higher in the experimental than in the control group (0.33±0.09 vs 0.26±0.07, P<0.05). CONCLUSION: Up-regulation of RhoA/ROCK may be involved in hyperlipidemia-induced erectile dysfunction in rats.

Association of the TNF-α+489 G/A polymorphism with chronic obstructive pulmonary disease risk in Asians: meta-analysis.

The association between the TNF-α +489 G/A polymorphism and chronic obstructive pulmonary disease (COPD) remains controversial because of small group size and varied design among different studies. In the present study, a meta-analysis was conducted to assess the association between the +489 G/A polymorphism and COPD risk. A comprehensive search was conducted to identify articles that have reported an association between the TNF-α +489 G/A polymorphism and COPD risk. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated under both dominant (AA+GA vs GG genotypes) and allele (A vs G) models. Heterogeneity was assessed, as well as publication bias. Nine articles with ten eligible studies were included in this analysis. Significant association between the +489 G/A polymorphism and COPD was identified in Asians under the allele model (OR = 1.582, 95%CI = 1.035-2.419). However, no significant difference was found in the Caucasian groups. Strong evidence for between-study heterogeneity was identified under both models, and no publication bias was detected. Our results indicated a potential role of the A allele of the TNF-α +489 G/A polymorphism in increasing COPD risk in Asians, but not in Caucasians. Additional studies will be necessary to verify this conclusion.

Endogenous hormonal equilibrium linked to bamboo culm development.

Moso bamboo (Phyllostachys heterocycla) is the most important bamboo species in China and is famous for its fast-growing culms. To investigate the possible relationship between internode development and endogenous hormones, the concentrations of indole-3-acetic acid (IAA), zeatin riboside (ZR), gibberellins (GA3), and abscisic acid (ABA) were analyzed in culm samples from plants at different developmental stages during a single growing season and, at the same time, anatomical structure was closely monitored. Cell division was the dominant process in internode development during early development, while cell elongation predominated at later stages. There was a negative correlation between the rates of cell division and cell elongation. The four endogenous hormones (IAA, ZR, GA3, and ABA) displayed fluctuations in their levels at different developmental stages but their peak activities were not synchronous. Cell division rate had a significant positive correlation with ZR concentration. Cell elongation had a significant positive correlation with the ratio of promoting hormones (IAA, GA3, and ZR) to inhibitory hormone (ABA) concentrations. We conclude that hormonal equilibrium might regulate the division and elongation of bamboo culms.

Generation of Foxo3-targeted Mice by Injection of mRNAs Encoding Transcription Activator-like Effector Nucleases (TALENs) into Zygotes.

In this study, for exploring the mechanism of forkhead box O3(Foxo3) participating in regulation of the activation of primordial oocytes, Foxo3-targeted mice were generated by injection of mRNAs encoding transcription activator-like effector nucleases (TALENs) into mouse zygotes. The TALEN sites were designed with high conservative homologous region among pig, bovine, buffalo and mouse by commercial bio-companies. The TALENs mutagenic non-homologous end-joining (NHEJ) repair activity were determined to be 31.3% in human embryonic kidney 293T (HEK-293T) cells by dual luciferase reporter assay system. Then, we firstly injected TALEN-mRNAs into the cytoplasm of mouse zygotes by micromanipulation, and four of 48 mouse blastocysts were identified as mutation by sequencing. Subsequently, by the method of TALEN-mRNAs injected into the zygotes with pronucleus micromanipulation technique, we obtained seven Foxo3 mutants of 20 FVB/NJ backgrounds mice which were Foxo3-independent alleles with frameshift and deletion mutations. It was very interesting that all seven were heterozygous mutants (Foxo3(-/+) ), and the gene mutagenesis rates of the mice reached 35%. The five Foxo3 mutant females were all infertile in the following 6 months after birth. The histological examination results showed that there were rare primordial follicles and primary follicles in the ovary of Foxo3 mutant compared to that of wide-type female mice. Moreover, one of two mutant males was subfertile and another was fertile normally. Those results suggested that the mutant of Foxo3 severely affected the fertile ability of female and perhaps male in some degree; furthermore, an even more efficient TALENs-based gene mutation method has been established to be poised to revolutionize the study of mouse and other species genetics.