Mechanical properties and deformation mechanisms of nanocrystalline u-10mo alloys by molecular dynamics simulation

U-Mo alloys were considered to be the most promising candidates for high-density nuclear fuel. The uniaxial tensile behavior of nanocrystalline U-10Mo alloys with average grain sizes of 8–23 nm was systematically studied by molecular dynamics (MD) simulation, mainly focusing on the influence of average grain size on the mechanical properties and deformation mechanisms. The results show that Young’s modulus, yield strength and ultimate tensile strength follow as average grain size increases. During the deformation process, localized phase transitions were observed in samples. Grain boundary sliding and grain rotation, as well as twinning, dominated the deformation in the smaller and larger grain sizes samples, respectively. Increased grain size led to greater localized shear deformation, resulting in greater stress drop. Additionally, we elucidated the effects of temperature and strain rate on tensile behavior and found that lower temperatures and higher strain rates not only facilitated the twinning tendency but also favored the occurrence of phase transitions in samples. Results from this research could provide guidance for the design and optimization of U-10Mo alloys materials

Combination of thymosin α1 with conventional therapy improves APC and IL-1R1 levels in children with severe pneumonia

Purpose: To investigate the effect of a combination of thymosin α1 with  conventional regimen on APC and IL-1R1 levels in children with severe pneumonia, and to provide a reference for its clinical treatment.Methods: A total of 96 children with severe pneumonia over a period of two years were divided into control and observation groups (48 cases per  group) by random number table method. The patients consisted of 46 males and 50 females within the age range of 0.1 - 6 years (mean age = 3.0 ± 1.2 years), and mean duration of 13.4 ± 2.2 days). Their acute physiology and chronic health evaluation II (APACHE II) was 20.3 ± 3.2 points. Patients in the control group were placed on conventional treatment programs, while those in the observation group, in addition to the  conventional treatments, received thymosin α1 (subcutaneous injection of thymosin α1 at a dose of 1.5 mg per injection) twice daily for the first 3 days, then once daily until the 7th day, after which the adverse reactions were observed and treated. Pulmonary function indices, and levels of APC, and IL-1R1 were also determined in the patients’ sera before and after the treatment regime.Results: The clinical efficacy of the observation group was significantly better (p < 0.05) than that of control. There were no significant differences (p > 0.05) in the indices of pulmonary function (maximal inspiratory and expiratory pressure, and peak expiratory flow) between the two groups before treatment. However, after treatment they were significantly higher (p < 0.05) in the observation group than in control. There were no significant differences (p > 0.05) in APC and IL-1R1 levels between the two groups before treatment, but after treatment, while the level of APC in the observation group was significantly increased (p < 0.05), the IL-1R1 level was significantly decreased (p < 0.05), when compared to the control group. Both groups showed no obvious adverse reactions during the treatmentregime.Conclusion: Combining thymosin α1 with routine treatment in the  management of children with severe pneumonia can significantly alleviate the symptoms of patients, greatly stimulate recovery of pulmonary function, improve APC and IL-1R1 levels, and prevent inflammation.Keywords: Pneumonia, Thymosin α1, Routine treatment, Inflammatory factors, Pulmonary functio

High Human Bocavirus Viral Load Is Associated with Disease Severity in Children under Five Years of Age

Human bocavirus (HBoV) is a parvovirus and detected worldwide in lower respiratory tract infections (LRTIs), but its pathogenic role in respiratory illness is still debatable due to high incidence of co-infection with other respiratory viruses. To determine the prevalence of HBoV infection in patients with LRTI in Shanghai and its correlation with disease severity, we performed a 3-year prospective study of HBoV in healthy controls, outpatients and inpatients under five years of age with X-ray diagnosed LRTIs. Nasopharyngeal aspirates were tested by PCR for common respiratory viruses and by real time PCR for HBoV subtypes 1–4. Nasopharyngeal swabs from healthy controls and serum samples and stools from inpatients were also tested for HBoV1-4 by real time PCR. Viral loads were determined by quantitative real time PCR in all HBoV positive samples. HBoV1 was detected in 7.0% of inpatients, with annual rates of 5.1%, 8.0% and 4.8% in 2010, 2011 and 2012, respectively. Respiratory syncytial virus (RSV) subtype A was the most frequent co-infection detected; HBoV1 and RSVA appeared to co-circulate with similar seasonal variations. High HBoV viral loads (>10(6) copies/ml) were significantly more frequent in inpatients and outpatients than in healthy controls. There was a direct correlation of high viral load with increasing disease severity in patients co-infected with HBoV1 and at least one other respiratory virus. In summary, our data suggest that HBoV1 can cause LRTIs, but symptomatic HBoV infection is only observed in the context of high viral load

Remdesivir for 5 or 10 Days in Patients With Severe Covid-19

Background: Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). Methods: We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale. Results: In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P = 0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P = 0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%). Conclusions: In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899.)

Intensive Cytokine induction in Pandemic H1N1 Influenza Virus Infection Accompanied by Robust Production of IL-10 and IL-6

BACKGROUND: The innate immune system is the first line of defense against viruses by inducing expression of cytokines and chemokines. Many pandemic influenza H1N1 virus [P(H1N1)] infected severe cases occur in young adults under 18 years old who were rarely seriously affected by seasonal influenza. Results regarding host cytokine profiles of P(H1N1) are ambivalent. In the present study we investigated host cytokine profiles in P(H1N1) patients and identified cytokines related to disease severity. METHODS AND PRINCIPAL FINDINGS: We retrieved 77, 59, 26 and 26 sera samples from P(H1N1) and non-flu influenza like illness (non-ILIs) cases with mild symptoms (mild patients), P(H1N1) vaccinees and healthy individuals, respectively. Nine and 16 sera were from hospitalized P(H1N1) and non-ILIs patients with severe symptoms (severe patients). Cytokines of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were assayed by cytokine bead array, IL-17 and IL-23 measured with ELISA. Mild P(H1N1) patients produced significantly elevated IL-2, IL-12, IFN-γ, IL-6, TNF-α, IL-5, IL-10, IL-17 and IL-23 versus to healthy controls. While an overwhelming IL-6 and IL-10 production were observed in severe P(H1N1) patients. Higher IL-10 secretion in P(H1N1) vaccinees confirmed our observation that highly increased level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression. CONCLUSION AND SIGNIFICANCE: A comprehensive innate immune response was activated at the early stage of P(H1N1) infection with a combine Th1/Th2/Th3 cytokines production. As disease progression, a systemic production of IL-6 and IL-10 were observed in severe P(H1N1) patients. Further analysis found a strong correlation between IL-6 and IL-10 production in the severe P(H1N1) patients. IL-6 may be served as a mediator to induce IL-10 production. Highly elevated level of sera IL-6 and IL-10 in P(H1N1) patients may lead to disease progression, but the underlying mechanism awaits further detailed investigations

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications