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.

Characteristics of flight delays during solar flares.

Solar flares are one of the severest solar activities that have important effects on near-Earth space. Previous studies have shown that flight arrival delays increase as a result of solar flares, but the intrinsic mechanism behind this relationship is still unknown. In this study, we conducted a comprehensive analysis of flight departure delays during 57 solar X-ray events by using a huge amount of flight data (~ 5 × 106 records) gathered over a 5-year period. It is found that the average flight departure delay time during solar X-ray events increased by 20.68% (7.67 min) compared to quiet periods. Our analysis also revealed apparent time and latitude dependencies, with flight delays being more serious on the dayside than on the nightside and longer (shorter) delays tending to occur in lower (higher) latitude airports during solar X-ray events. Furthermore, our results suggest that the intensity of solar flares (soft X-ray flux) and the Solar Zenith Angle directly modulate flight departure delay time and delay rate. These results indicate that communication interferences caused by solar flares directly affect flight departure delays. This work expands our conventional understanding of the impacts of solar flares on human society and provides new insights for preventing or coping with flight delays.

Additional flight delays and magnetospheric-ionospheric disturbances during solar storms.

Although the sun is really far away from us, some solar activities could still influence the performance and reliability of space-borne and ground-based technological systems on Earth. Those time-varying conditions in space caused by the sun are also called solar storm or space weather. It is known that aviation activities can be affected during solar storms, but the exact effects of space weather on aviation are still unclear. Especially how the flight delays, the top topic concerned by most people, will be affected by space weather has never been thoroughly researched. By analyzing huge amount of flight data (~ 4 × 106 records), for the first time, we quantitatively investigate the flight delays during space weather events. It is found that compared to the quiet periods, the average arrival delay time and 30-min delay rate during space weather events are significantly increased by 81.34% and 21.45% respectively. The evident negative correlation between the yearly flight regularity rate and the yearly mean total sunspot number during 22 years also confirms such correlation. Further studies show that the flight delay time and delay rate will monotonically increase with the geomagnetic field fluctuations and ionospheric disturbances. These results indicate that the interferences in communication and navigation during space weather events may be the most probable reason accounting for the increased flight delays. The above analyses expand the traditional field of space weather research and could also provide us with brand new views for improving the flight delay predications.

[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.

Pretreatment Normal WM Magnetization Transfer Ratio Predicts Risk of Radiation Necrosis in Patients with Medulloblastoma.

BACKGROUND AND PURPOSE: Radiation necrosis, for which abnormal WM enhancement is a hallmark, is an uncommon complication of craniospinal irradiation in children with medulloblastoma. The magnetization transfer ratio measures macromolecular content, dominated by myelin in the WM. We investigated whether the pretreatment supratentorial (nonsurgical) WM magnetization transfer ratio could predict patients at risk for radiation necrosis after radiation therapy for medulloblastoma. MATERIALS AND METHODS: Ninety-five eligible patients with medulloblastoma (41% female; mean age, 11.0 [SD, 5.4] years) had baseline balanced steady-state free precession MR imaging before proton or photon radiation therapy. Associations among baseline supratentorial magnetization transfer ratio, radiation necrosis (spontaneously resolving/improving parenchymal enhancement within the radiation field)3, age, and the presence of visible brain metastases were explored by logistic regression and parametric/nonparametric techniques as appropriate. RESULTS: Twenty-three of 95 (24.2%) children (44% female; mean age, 10.7 [SD, 6.7] years) developed radiation necrosis after radiation therapy (19 infratentorial, 1 supratentorial, 3 both). The mean pretreatment supratentorial WM magnetization transfer ratio was significantly lower in these children (43.18 versus 43.50, P = .03). There was no association between the supratentorial WM magnetization transfer ratio and age, sex, risk/treatment stratum, or the presence of visible brain metastases. CONCLUSIONS: A lower baseline supratentorial WM magnetization transfer ratio may indicate underlying structural WM susceptibility to radiation necrosis and may identify children at risk for developing radiation necrosis after craniospinal irradiation for medulloblastoma.

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.

Research on changes in cognitive function, ß-amyloid peptide and neurotrophic factor in stroke patients.

OBJECTIVE: To investigate the changes as well as the related mechanism in cognitive function and levels of serum ß-amyloid peptide (Aß) and brain-derived neurotrophic factor (BDNF) in stroke patients. PATIENTS AND METHODS: A total of 30 patients with acute stroke treated in our hospital from June 2015 to September 2016 were selected as stroke group, while 30 volunteers during the same period were enrolled as control group. Changes in cognitive function of patients were evaluated using the Montreal Cognitive Assessment (MoCA) and mini-mental state examination (MMSE) before and after the treatment. At the same time, the concentrations of serum Aß1-40 and BDNF were detected, and their correlations with the MMSE score were analyzed. Finally, levels of serum cyclic adenosine monophosphate (cAMP) and phosphorylated-cAMP-response element binding protein (p-CREB), and the phosphorylation level of Tau protein were detected by Western blotting. RESULTS: MoCA and MMSE scores of patients in stroke group were significantly lower than those in control group (p < 0.01), and the scores were significantly higher in stroke patients after treatment than those before treatment (p < 0.01). Compared with those in control group, the serum Aß1-40 concentration in patients in stroke group was significantly increased (p < 0.01), but the BDNF level was significantly decreased (p < 0.01). Compared with those before treatment, the serum Aß1-40 concentration in patients was significantly decreased after treatment (p < 0.01), but the BDNF concentration was significantly increased (p < 0.01). Correlation analysis showed that the MMSE score was negatively correlated with the concentration of Aß1-40 (r2 = 0.764, p < 0.01), but positively related to the level of BDNF (r2 = 0.827, p < 0.01). Compared with those in control group, the content of serum cAMP and p-CREB in stroke patients was significantly decreased (p < 0.01), but the expression of p-Tau was statistically increased (p < 0.01). CONCLUSIONS: The cognitive function in stroke patients is impaired, with the rising content of serum Aß1-40 and reduction of BDNF, the mechanism of which is related to the decrease of cAMP and p-CREB and the increase of p-Tau. This provides a theoretical basis for searching the new therapeutic targets and new drugs for stroke.

[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.

Dietary Approach to Stop Hypertension with Sodium Reduction for Chinese Canadians (DASHNa-CC): A Pilot Randomized Controlled Trial.

BACKGROUND: There is a lack of culturally sensitive dietary interventions targeting Chinese Canadians despite unhealthy dietary behaviours being identified as the most important modifiable risk factor for hypertension in the Chinese population. AIMS: To determine the feasibility of a culturally sensitive dietary intervention for hypertension control; to examine the potential effects of the intervention on blood pressure and health-related quality of life among Chinese Canadians in community. METHODS: This study was a two-group pilot randomized controlled trial with 8 weeks follow up. Sixty self-identified Chinese Canadians, older than 45 years old and with grade one hypertension but not on antihypertensive medications were recruited in community. The control group received usual care and the intervention group received usual care plus newly developed DASHNa-CC intervention. The DASHNa-CC intervention consisted of a written manual, two classroom sessions, and one telephone booster call to provide healthy dietary and sodium reduction advice, integrated with Traditional Chinese Medicine food therapy recommendations for hypertension control. RESULTS: 618 Chinese Canadians participated in blood pressure screening, and 60 eligible participants recruited. Participants were highly satisfied with the intervention and adhered to the trial protocol. The lost to follow-up rate was 5%. At 8 weeks post-randomization, those in the intervention group had greater reductions in systolic blood pressure [3.8mmHg, t (55) = -1.58, p = 0.12] and higher physical health scores [t (55) = 2.13, p = 0.04] compared to those of the control group. There were no group differences in health care utilization. CONCLUSIONS: It is feasible to deliver the DASHNa-CC intervention in a Chinese Canadian community. The DASHNa-CC intervention may decrease blood pressure and improve health-related quality of life for Chinese Canadians.

[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.

[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.

[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.

A rare case of trisomy 11q23.3-11q25 and trisomy 22q11.1-22q11.21.

Partial duplication of the long arm of chromosome 11 and the partial trisomy of 22q are uncommon karyotypic abnormalities. Here, we report the case of a 6-year-old girl who showed partial trisomy of 11q and 22q, as a result of a maternal balanced reciprocal translocation (11;22), and exhibited dysmorphic features, severe intellectual disability, brain malformations, and speech delay related to this unique chromosomal abnormality. Array comparative genomic hybridization (array CGH) revealed a gain in copy number on the long arm of chromosome 11, spanning at least 18.22 Mb. Additionally, there was a gain in copy number on the long arm of chromosome 22, spanning at least 3.46 Mb. FISH analysis using a chromosome 11 short arm telomere probe (11p14.2), a chromosome 11 long arm telomere probe (11q24.3), and a chromosome 22 long arm telomere probe (22q13.33) confirmed the origin of the marker chromosome. It has been confirmed by the State Key Laboratory of Medical Genetics of China that this is the first reported instance of the karyotype 47,XX, +der(22)t(11;22)(q23.3;q11.1)mat in the world. Our study reports an additional case that can be used to further characterize and delineate the clinical ramifications of partial trisomy of 11q and 22q.

Tamoxifen reduces fat mass by boosting reactive oxygen species.

As the pandemic of obesity is growing, a variety of animal models have been generated to study the mechanisms underlying the increased adiposity and development of metabolic disorders. Tamoxifen (Tam) is widely used to activate Cre recombinase that spatiotemporally controls target gene expression and regulates adiposity in laboratory animals. However, a critical question remains as to whether Tam itself affects adiposity and possibly confounds the functional study of target genes in adipose tissue. Here we administered Tam to Cre-absent forkhead box O1 (FoxO1) floxed mice (f-FoxO1) and insulin receptor substrate Irs1/Irs2 double floxed mice (df-Irs) and found that Tam induced approximately 30% reduction (P<0.05) in fat mass with insignificant change in body weight. Mechanistically, Tam promoted reactive oxygen species (ROS) production, apoptosis and autophagy, which was associated with downregulation of adipogenic regulator peroxisome proliferator-activated receptor gamma and dedifferentiation of mature adipocytes. However, normalization of ROS potently suppressed Tam-induced apoptosis, autophagy and adipocyte dedifferentiation, suggesting that ROS may account, at least in part, for the changes. Importantly, Tam-induced ROS production and fat mass reduction lasted for 4-5 weeks in the f-FoxO1 and df-Irs mice. Our data suggest that Tam reduces fat mass via boosting ROS, thus making a recovery period crucial for posttreatment study.

BCR-ABL1-positive microvesicles transform normal hematopoietic transplants through genomic instability: implications for donor cell leukemia.

Malignant transformation of normal hematopoietic transplants induced by residual leukemia cells is considered as a pivotal mechanism of donor cell leukemia (DCL). The effects of leukemia cell-derived microvesicles (MVs) in this transformation were examined. We found that MVs derived from K562 leukemia cells contained the breakpoint cluster region-Abelson leukemia gene human homolog 1 (BCR-ABL1) mRNA. Following incubation with BCR-ABL1-positive MVs, mononuclear cells derived from normal transplants exhibited a leukemia-like malignant phenotype both in vitro and in vivo. Horizontal transfer of BCR-ABL1 mRNA from MVs into the recipient cells was critical to the transformation. Relative genomic instability was observed and considered the main mechanism in the recipient cells. MVs contributed to genomic instability by two distinct pathways: via consequent overexpression of activation-induced cytidine deaminase and reactive oxygen species, which mediated DNA breakage and recombination; and via upregulation of methyltransferases and global DNA hypermethylation. We demonstrated that BCR-ABL1-positive MVs could initiate malignant transformation of normal hematopoietic transplants through genomic instability, which might serve as a convenient and operable model for investigating leukemogenesis, especially for DCL. Furthermore, MVs themselves could act as an early warning indicator and a novel tool to detect and prevent the occurrence of DCL.

Effect of pesticide 1-[6-chloro-3-methyl-pyridyl-8-nitro-7-methyl-1 2 3 5 6 7-hexahydro imidazo (1,2a)]-pyridine when responding to a wheat plant's antioxidant defense system.

The purpose of this research was to establish an analytical method for analysing the 1-[6-chloro-3-methyl-pyridyl-8-nitro-7-methyl-1 2 3 5 6 7-hexahydro imidazo-(1,2a)]-pyridine (IPP) residue levels and to evaluate the difference in plant growth and its physical condition. A high performance liquid chromatography connected to a diode array detector (HPLC-DAD) was also employed. The results showed that the content of protein and water soluble carbohydrate (WSC) treated by IPP were initially higher with a significant delayed decrease. The biomarker response showed, even at a lower dose rate, exposure to the IPP caused stress effects and modified the activity of superoxide dismutase (SOD), guaiacol peroxidase (POD), catalase (CAT) and polyphenol oxidase (PPO). Different patterns of biomarker responses were observed by an increase in SOD and malondialdehyde (MDA), and differential effects for antioxidant enzymes with a decrease in CAT, POD and PPO. The conclusions show that this profile of biomarker variation could represent a useful method to characterise exposure to IPP in a wheat plant.

Strategies for health education in North American immigrant populations.

AIM: This article is intended to stimulate critical thinking about barriers and strategies related to health education for immigrant populations. Its rationale is to promote an understanding and appreciation for the individuality and diversity of immigrant beliefs, values and culture, and how these contribute to health education through nursing practice, research and theory. BACKGROUND: Since 2005, over 1,250,000 immigrants annually have obtained legal permanent residence in North America [over 1 million annually in the United States of America (USA) and over 250,000 annually in Canada]. THE PROBLEM: While a broad immigration policy leads to population growth, cultural change and ethnic diversity, migration impacts immigrants' health status. In North America, the 'healthy immigrant effect', whereby immigrants generally tend to be healthier than individuals born in host countries, steadily declines after immigration. METHODS: Immigration statistics and reports on literacy and learning were sourced from official websites in Canada and the USA. These were reviewed and discussed in the context of scholarly published literature on health literacy, health education and health promotion. OPPORTUNITIES: Promoting health in immigrant populations is difficult due to cultural, linguistic, health literacy and socio-economic barriers. Cultural sensitivity, careful inquiry and comprehensive knowledge of immigrants' social circumstances are essential to every health education programme. CONCLUSION: Strategies for immigrant health education must be technologically diverse, involve partnerships with multidisciplinary professionals, elicit active community participation, and facilitate language transfer and interpretation. Future research must continue to explore these barriers and strategies, using both qualitative and quantitative methodologies.