Crystallization mechanism of the Pt50Au50 alloy with grain boundary segregation during the solidification process.

The crystalline mechanism of the Pt50Au50 alloy with grain boundary (GB) segregation during the rapid solidification process is investigated using molecular dynamics simulations. The cluster evolution and phase transformation processes during the GB segregation are analyzed by means of the energy temperature (E-T) curve, the pair distribution function (g(r)) curves, common neighborhood analysis (CNA), cluster-type index method (CTIM) and three-dimensional visualizing analyses. It is found that the GB segregation phenomenon of the Pt50Au50 alloy comes from various solidification temperatures of Pt- and Au-centered clusters. Four critical temperatures T1 (1153 K), T2 (1073 K), T3 (853 K) and T4 (753 K) are discovered during the liquid-solid transition, corresponding to the supercooled liquid, Pt-centered atom nucleation, Pt-centered cluster growth, Au-centered atom nucleation and grain growth process, respectively, which is observably different to the solidification process of other alloys. The Pt atoms begin to gather together in the high-temperature liquid before the liquid-solid transition. It is also found that the CTIM proposed by us would provide an effective tool to investigate the GB segregation process.

[Safety and feasibility of stereotactic radiation therapy on porcine ventricular septum: a preliminary study].

Objective: To explore the safety and feasibility of stereotactic radiation therapy (SBRT) strategy for irradiating porcine ventricular septum, see if can provide a preliminary experimental evidence for clinical SBRT in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Five male pigs (39-49 kg, 6 months old) were used in this study. Pigs were irradiated at doses of 25 Gy (n=2) or 40 Gy (n=3). Delineation of the target volume was achieved under the guidance of 3-dimensional CT image reconstruction, and SBRT was then performed on defined target volume of porcine ventricular septum. Blood biomarkers, electrocardiogram and echocardiography parameters were monitored before and after SBRT. Pathological examination (HE staining, Masson staining) was performed on the target and non-target myocardium at 6 months post SBRT. Results: SBRT was successful and all animals survived to the designed study endpoint (6 months) after SBRT. Serum cardiac troponin T (cTnT) level was significantly higher than the baseline level at 1 day post SBRT, and reduced at 1 week after SBRT, but was still higher than the baseline level(P<0.05). Serum N-terminal pro-B type natriuretic peptide (NT-proBNP) was also significantly increased at 1 day post SBRT (P<0.05) and returned to baseline level at 1 week post SBRT. The serum NT-proBNP level was (249±78), (594±37) and (234±46) pg/ml, respectively, and the cTnT was (14±7), (240±40) and (46±34) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 40 Gy dose group. The serum NT-proBNP level was (184±20), (451±49) and (209±36) pg/ml, respectively, the cTnT values ​​were (9±1), (176±29) and (89±27) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 25 Gy dose group. Both NT-proBNP and cTnT values tended to be higher post SBRT in the 40 Gy dose group as compared with the 25 Gy dose group, but the difference was not statistically significant (P>0.05). The left ventricular ejection fraction and the left ventricular end-diastolic diameter remained unchanged before and after SBRT (P>0.05). The interventricular septum thickness showed a decreasing trend at 6 months after SBRT, but the difference was not statistically significant ((9.54±0.24) mm vs. (9.82±8.00) mm, P>0.05). The flow velocity of the left ventricular outflow tract, and the valve function and morphology were not affected by SBRT. At 6 months after SBRT, HE staining revealed necrosis in the irradiated target area of ​​the myocardium in the 40 Gy dose group and the 25 Gy dose group, and the degree of necrosis in the irradiated interventricular septum was more obvious in the 40 Gy dose group as compared with the 25 Gy group. The combined histological analysis of the two groups showed that the necrotic area of ​​the irradiated target area accounted for (26±9)% of the entire interventricular septum area, which was higher than that of the non-irradiated area (0) (P<0.05). There was no damage or necrosis of myocardial tissue outside the target irradiation area in both groups. The results of Masson staining showed that the percentage area of myocardial fibrosis was significantly higher in the irradiated target area than non-irradiated area ((12.6±5.3)% vs. (2.5±0.8)%, P<0.05). Conclusion: SBRT is safe and feasible for irradiating porcine ventricular septum.

Coordination of primary metabolism and virulence factors expression mediates the virulence of Vibrio parahaemolyticus towards cultured shrimp (Penaeus vannamei).

AIMS: Acute hepatopancreatic necrosis disease (AHPND) caused by Vibrio parahaemolyticus has emerged as a severe bacterial disease of cultured shrimp. To identify the key virulence factors, two AHPND-causing V. parahaemolyticus (VpAHPND ) strains (123 and 137) and two non-VpAHPND strains (HZ56 and ATCC 17082) were selected. METHODS AND RESULTS: Challenge tests showed that the four strains exhibited different virulence towards shrimp with cumulative mortalities at 48 h postinfection (hpi) ranging from 10 to 92%. The expression of pirABVP in strain 123 and 137 was not significantly different. Genomic analysis revealed that the two VpAHPND strains contain a plasmid with the PirABVP toxins (pirABVP ) flanked by the insertion sequence (ISVal1) that has been identified in various locations of chromosomes in VpAHPND strains. The two VpAHPND strains possessed almost identical virulence factors, while ISVal1 disrupted three genes related to flagellar motility in strain 137. Phenotype assay showed that strain 123 possessed the highest growth rate and swimming motility, followed by strain 137, suggesting that the disruption of essential genes mediated by ISVal1 significantly affected the virulence level. Transcriptome analysis of two VpAHPND strains (123 and 137) further suggested that virulence genes related to the capsule, flagella and primary metabolism were highly expressed in strain 123. CONCLUSIONS: Here for the first time, it is demonstrated that the virulence of VpAHPND is not only determined by the expression of pirABVP , but also is mediated by ISVal1 which affects the genes involved in flagellar motility and primary metabolism. SIGNIFICANCE AND IMPACT OF THE STUDY: The genomic and transcriptomic analysis of VpAHPND strains provides valuable information on the virulence factors affecting the pathogenicity of VpAHPND.

Engagement among physicians fighting COVID-19: the mediating role of autonomy.

BACKGROUND: Keeping and improving work engagement among physicians fighting COVID-19 is important to healthy medical systems. In line with the job demands-resources model, optimism was expected to positively relate with job resources, leading to higher work engagement. However, the underlying mechanism between optimism, autonomy and work engagement has not been explored. AIMS: To examine whether optimism has a positive impact on work engagement via autonomy among physicians fighting COVID-19 in China. METHODS: This study was conducted among physicians in March 2020. A convenience sample was used to recruit physicians from the Wuhan Leishenshan Hospital and Wuhan Jinyintan Hospital. One hundred and four Chinese physicians working in the COVID-19 epidemic completed a survey measuring levels of autonomy, optimism and work engagement. The PROCESS macro (model 4) was used to test hypotheses about mediation. RESULTS: This current study found that optimism was related to increased autonomy, and autonomy was related to increased work engagement. The results of the bias-corrected bootstrap method suggested the indirect effect of optimism on work engagement via autonomy (Effect = 0.16, SE = 0.08, lower level confidence interval = 0.04, upper level confidence interval = 0.37), indicating a mediated relationship, in which autonomy is one mechanism to explain the link between optimism and increased work engagement. CONCLUSIONS: This study follows an observational design, with in-depth analysis of the relationship between optimism, autonomy and work engagement. When management implements strategies to improve work engagement among physicians working in the COVID-19 epidemic, the mediating impact of autonomy on the association between optimism and work engagement should be considered.

[Clinical observation of single-segment cervical adjacent segment disease treated with artificial cervical disc replacement].

Objective: To investigate the clinical outcomes and radiographic results of artificial cervical disc replacement (ACDR) for cervical adjacent segment disease (ASD). Methods: The clinical data of 28 patients with single-segment cervical ASD treated with ACDR in Xi 'an Honghui Hospital from December 2013 to July 2016 were retrospectively analyzed. There were 19 males and 9 females with a mean age of (46±7) years (36-63 years). Preoperative, postoperative 1 month and postoperative 24 months of clinical and radiographic outcomes were recorded and compared. The clinical outcome mainly includes Japanese orthopedic association (JOA), Neck Disability Index (NDI%), Odom score and complications. Imaging assessment mainly included range of motion (ROM) of cervical spine, surgical segment ROM, Cobb angle of surgical segment, degree of adjacent disc degeneration, heterotopic ossification, and prosthesis related image parameters. Results: In terms of clinical outcome, the average JOA score was 12.7±1.5 before surgery, 14.0±1.0 one month after surgery, 15.8±0.9 24 months after surgery, and the improvement rate of JOA was 75%±19%. The mean NDI% was 27.0%±2.8% before surgery, 20.5%±1.6% one month after surgery, and 15.3%±2.8% 24 months after surgery; the difference before and after treatment was statistically significant (F=159.101, P<0.01). Twenty patients were classified with excellent Odom score and 8 patients with good Odom score at the final follow-up. The total ROM of cervical spine, operation segment ROM, operation segment Cobb angle were all improved significantly after the operation (F=4.633, 6.063, 26.952, all P<0.05). There was a statistical difference in Miyazaki classification between adjacent discs above ACDR and below the fusion segment 24 months after surgery (µ(c)=2.12, P=0.034). The incidence of heterotopic ossification was 14.3%. The results of displacement degree of prosthesis were as follow: coronal plane (0.30±0.11) mm, sagittal plane (0.28±0.10) mm; subsidence of the prosthesis: (0.27±0.09) mm. No prosthesis loosening was observed. Conclusions: The clinical outcome of revision of cervical ASD by ACDR is satisfactory. The risk of intervertebral disc degeneration in adjacent segments is significantly lower than that of ACDF due to the presence of certain motor function postoperatively.

[Seroepidemiological investigation of hepatitis C virus in Zhejiang Province: a hospital-based study].

Objective: To study serum HCV antibody (anti-HCV) with geographic distribution characteristics in Zhejiang Province. Methods: A stratified random cluster sampling method was used. Serum samples of the surveyed population were collected from selected hospitals, anti-HCV antibodies were examined, then hepatitis C infection rates among different genders, regions and age groups were analyzed. The anti-HCV rate was compared using the χ (2) test. Results: The average anti-HCV positive rate in Zhejiang Province was 0.24% [95% confidence interval (CI): 0.16% ~ 0.32%]. The antibody positive rate in the plain area was 0.32% (95% CI: 0.19% ~ 0.45%), which was significantly higher than the coastal islands 0.05%(95% CI: 0.00% ~ 0.12%, χ (2) = 7.638, P < 0.05). There was no significant difference between plain area and hilly area 0.22% (95% CI: 0.03% - 0.41%). There was no statistically significant difference in anti-HCV positive rates between males and females (χ (2) = 2.238, P = 0.135). The highest positive rate of anti-HCV (0.93%) was in the population aged 56-60 years and the lowest in the population aged less than 20 years. Anti-HCV positive rate of all age groups in 2017 was lower than that of 2006 seroepidemiological study of hepatitis C. Conclusion: Zhejiang Province is a region with low anti-HCV positive rate and the disease prevalence further reduced than 10 years ago. The positive rate of anti-HCV in plain areas is higher than islands. Middle-aged and elderly people are the age group with high prevalence, and the anti-HCV positive rate in people under 20 years old is exceptionally low. Gender differences in anti-HCV positive rate have little effect.

[The clinical analysis of frontline nilotinib vs imatinib therapies for newly diagnosed chronic myeloid leukemia in chronic phase].

Objective: To compare the clinical efficacy and safety of nilotinib and imatinib as frontline therapy in newly diagnosed patients with chronic myeloid leukemia in chronic phase(CML-CP). Methods: Until December 31st 2016, 18 patients using nilotinib and 83 using imatinib were recruited in our study. The efficacy and safety of two groups were evaluated. Results: A total of 101 patients with CML-CP included 18 receiving nilotinib and 83 imatinib. The optimal response rates at 3, 6, 12 and 18 months in nilotinib and imatinib group were 88.9% (16/18) vs 57.3% (47/82) (P=0.012), 82.4% (14/17) vs 55.7% (44/79) (P=0.041), 9/12 vs 63.9% (39/61) (P=0.460), 6/9 vs 68.9% (31/45) (P=0.896) respectively. The optimal response rates by 3 months in low sokal risk group on nilotinib and imatinib were 9/9 vs 76.5%(26/34) (P=0.107), in intermediate and high sokal risk group were 7/8 vs 45.2%(14/31) (P=0.032). At the end of follow-up, the rate of major molecular response (MMR) in nilotinib group was 72.2%, which was higher than 56.6% in imatinib group (P=0.021). The rate of complete cytogenetic response (CCyR) in nilotinib group was 100%, which was higher than 71.1% in imatinib group (P = 0.002). Progression free survival (PFS) rates in nilotinib and imatinib groups were 94.4% and 98.8% (P=0.019) respectively; whereas event free survival (EFS) rates were 88.9% and 48.2% (P=0.045). The incidence of drug related adverse reactions in nilotinib and imatinib was similar with only minor proportion of grade 3/4 adverse reactions. Conclusions: Nilotinib achieves a deeper molecular response in a shorter time than imatinib in newly diagnosed patients with CML-CP, especially in patients with high risk outcome. Good safety is obtained in both groups so as to ensure a long-term administration and improving prognosis.

[Silencing of vacuolar ATPase c subunit ATP6V0C inhibits invasion of prostate cancer cells].

OBJECTIVE: Vacuolar ATPase (V-ATPase) was found within the membranes and internal organelles of a vast array of eukaryotic cells, and was related to various kinds of highly metastatic tumors. LASS2/TMSG1 gene was a novel tumor metastasis suppressor gene cloned from human prostate cancer cell line PC-3M in 1999 by our laboratory. It was found out that protein encoded by LASS2/TMSG1 could interact with the c subunit of V-ATPase (ATP6V0C). In this study, To use RNA interference to suppress the expression of ATP6V0C and try to further investigate the molecular mechanism of ATP6V0C in tumor metastasis and its relationship with LASS2/TMSG1 gene. METHODS AND RESULTS: The expression level of ATP6V0C mRNA and protein in high metastatic potential prostate cancer cell lines (PC-3M-1E8 and PC-3M) was significantly higher than that in low metastatic potential prostate cancer cell lines (PC-3M-2B4 and PC-3), the expression level in PC-3M-1E8 being the highest. Follow-up tests selected PC-3M-1E8 cells for gene silencing. The expression and secretion of MMP-2 and the expression of MMP-9 in ATP6V0C siRNA transfected PC-3M-1E8 cells displayed no obvious change, but the activity of secreted MMP-9 was abated noticeably compared with the controls (P<0.05). Extracellular hydrogen ion concentration and V-ATPase activity in interference group were both reduced significantly compared with the controls (P<0.05). The migration and invasion capacity of ATP6V0C siRNA interfered cells in vitro were diminished significantly compared with the controls (P<0.05). Furthermore, a dramatic reduction of LASS2/TMSG1 mRNA and protein level after transfection of siRNA in PC-3M-1E8 cells was discovered (P<0.05). Confocal immunofluorescence showed a vast co-localization of ATP6V0C protein and LASS2/TMSG1 protein in plasma and membrane. The co-localization signals of control group were much stronger than those of interference group. CONCLUSION: Specific siRNA silencing of ATP6V0C gene inhi-bits the invasion of human prostate cancer cells in vitro by mechanism of inhibiting V-ATPase activity and then reducing the extracellular hydrogen ion concentration, inhibiting MMP-9 activation and affecting ECM degradation and reconstruction. Meanwhile, ATP6V0C and LASS2/TMSG1 have interaction and it is likely that ATP6V0C functions as a feedback regulator of LASS2/TMSG1.

[Clinicopathologic and prognosis features of Claudin-low breast cancers].

Objective: To investigate the clinicopathologic and prognostic features of Claudin-low breast cancers (CLBC). Methods: Tissue microarray sections were scored semiquantitatively for the immunohistochemical expression of claudin-1, -3, -4, -7 and -8 in 233 cases of invasive breast cancers collected from Qingdao Central Hospital from January 2010 to December 2011. Results: The expression rate of Claudin-3 (72/212, 33.9%) and -4 (56/212, 45.2%) was most similar, and Claudin-4 showed the highest expression. Twenty one cases (21/212, 9.0%) were diagnosed as CLBC, with triple-negative breast cancer (TNBC) accounted for the highest proportion (11/21, 52.4%). Among the CLBC cases, the invasive carcinoma no special type (66.7%, 14/21) and metaplastic carcinoma (14.3%, 3/21) were mostly seen, while metaplastic squamous carcinoma did not show Claudin-low pattern. Compared to the non CLBC in this cohort, CLBC had higher proportion of histologic grade 3 and tumors larger than 2 cm, and the proportions were slightly lower than TNBC. Patients with CLBC had lower 5 year disease-free(P>0.05) and overall survival rates(P=0.018). Conclusion: CLBC shows distinct clinicopathologic and prognostic features comparing to other subtypes, and is associated with poor prognosis.

Identification of novel DYNC2H1 mutations associated with short rib-polydactyly syndrome type III using next-generation panel sequencing.

Short rib-polydactyly syndrome type III (SRPS3) is a perinatal lethal skeletal disorder with polydactyly and multisystem organ abnormalities. While ultrasound of the fetus can detect skeletal abnormalities characteristic of SRPS3, the syndrome is often difficult to diagnose before birth. As SRPS3 is an autosomal recessive disorder, identification of the gene mutations involved could lead to the development of prenatal genetic testing as an accurate method of diagnosis. In this study, we describe genetic screening approaches to identify potential abnormalities associated with SRPS3. Karyotype analysis, array comparative genomic hybridization (aCGH), and next-generation panel sequencing were each performed on a fetus showing signs of the disorder, as well as on the mother and father. Karyotype and aCGH results revealed no abnormalities. However, next-generation panel sequencing identified novel mutations in the DYNC2H1 gene. The fetus was compound heterozygous for both a missense mutation c.8313A > T and a frameshift mutation c.10711_10714delTTTA in the DYNC2H1 gene, which were inherited from the mother and father, respectively. These variants were further confirmed using Sanger sequencing and have not been previously reported. Our study indicates the utility of using next-generation panel sequencing in screening for novel disease-associated mutations.