Nanostructured high-strength molybdenum alloys with unprecedented tensile ductility.

The high-temperature stability and mechanical properties of refractory molybdenum alloys are highly desirable for a wide range of critical applications. However, a long-standing problem for these alloys is that they suffer from low ductility and limited formability. Here we report a nanostructuring strategy that achieves Mo alloys with yield strength over 800 MPa and tensile elongation as large as ~ 40% at room temperature. The processing route involves a molecular-level liquid-liquid mixing/doping technique that leads to an optimal microstructure of submicrometre grains with nanometric oxide particles uniformly distributed in the grain interior. Our approach can be readily adapted to large-scale industrial production of ductile Mo alloys that can be extensively processed and shaped at low temperatures. The architecture engineered into such multicomponent alloys offers a general pathway for manufacturing dispersion-strengthened materials with both high strength and ductility.

Bayesian methods for estimating GEBVs of threshold traits.

Estimation of genomic breeding values is the key step in genomic selection (GS). Many methods have been proposed for continuous traits, but methods for threshold traits are still scarce. Here we introduced threshold model to the framework of GS, and specifically, we extended the three Bayesian methods BayesA, BayesB and BayesCπ on the basis of threshold model for estimating genomic breeding values of threshold traits, and the extended methods are correspondingly termed BayesTA, BayesTB and BayesTCπ. Computing procedures of the three BayesT methods using Markov Chain Monte Carlo algorithm were derived. A simulation study was performed to investigate the benefit of the presented methods in accuracy with the genomic estimated breeding values (GEBVs) for threshold traits. Factors affecting the performance of the three BayesT methods were addressed. As expected, the three BayesT methods generally performed better than the corresponding normal Bayesian methods, in particular when the number of phenotypic categories was small. In the standard scenario (number of categories=2, incidence=30%, number of quantitative trait loci=50, h² = 0.3), the accuracies were improved by 30.4%, 2.4%, and 5.7% points, respectively. In most scenarios, BayesTB and BayesTCπ generated similar accuracies and both performed better than BayesTA. In conclusion, our work proved that threshold model fits well for predicting GEBVs of threshold traits, and BayesTCπ is supposed to be the method of choice for GS of threshold traits.

The frequency and nature of drug administration error during anaesthesia in a Chinese hospital.

BACKGROUND: Throughout the world, drug administration error remains a known and significant threat to patients undergoing anaesthesia. Estimates of the extent of the problem vary, but few are based on large prospectively collected datasets. Furthermore, little is known about whether differences in work culture are important in error rates. METHODS: A prospective incident monitoring study was conducted at a large tertiary hospital in China to estimate the frequency of drug administration error during anaesthesia. Anaesthetists were asked to return a study form anonymously for every anaesthetic, indicating whether or not a drug administration error had occurred, including incident details if affirmative. RESULTS: From 24,380 anaesthetics, 16,496 study forms were returned (67.7% response rate), reporting 179 errors. The frequency (95% confidence interval) of drug administration error was 0.73% (0.63% to 0.85%) based on total study anaesthetics and 1.09% (0.93% to 1.26%) based on total forms returned. The largest categories of error were omissions (27%), incorrect doses (23%) and substitutions (20%). Errors resulted in prolonged stay in recovery for 21 patients, transfer to the ICU for five and one case each of haemorrhagic shock and asthmatic attack. More respondents who were not fully rested reported inattention as a contributing factor to error (21%) than those who were fully rested (7%, P = 0.04). CONCLUSION: Our results are comparable with other international prospective estimates indicating that drug administration error is of concern in China as elsewhere. These results will form a baseline from which to detect the effects of countermeasures.

Targeting rictor inhibits mouse vascular tumor cell proliferation and invasion in vitro and tumor growth in vivo.

Vascular tumor is an abnormal buildup of blood vessels in the skin or internal organs that can lead to disfigurement and/or life-threatening consequences. The mechanism of hemangiogenesis remains unknown. The aim of this study was to assess the role of rapamycin-insensitive companion of mTOR (Rictor) in control of vascular tumor malignant biological behavior and cell signaling mechanism in Mouse Hemangioendothelioma Endothelial Cells (EOMA cells) and nude mouse model. Knocking down rictor was mediated by lentivirus shRNA. The role and mechanism of rictor in vascular tumor were assessed by western blotting, wst-1 proliferation assay, matrigel invasion assay and xenograft vascular tumor growth. Our results in vitro showed that loss of rictor down-regulated phosphorylation of AKT and S6 by which EOMA cells growth and proliferation were greatly suppressed. Knock down of rictor also inhibited the invasion of EOMA cells. Furthermore, we demonstrated that knock down of rictor inhibited xenograft vascular tumor growth in nude mice. Taken together, we purpose that rictor contributed to vascular tumor growth and progression. Targeting rictor becomes an effective strategy in vascular tumor treatment.

Genome-wide association studies for hematological traits in swine.

Improving immune capacity may increase the profitability of animal production if it enables animals to better cope with infections. Hematological traits play pivotal roles in animal immune capacity and disease resistance. Thus far, few studies have been conducted using a high-density swine SNP chip panel to unravel the genetic mechanism of the immune capability in domestic animals. In this study, using mixed model-based single-locus regression analyses, we carried out genome-wide association studies, using the Porcine SNP60 BeadChip, for immune responses in piglets for 18 hematological traits (seven leukocyte traits, seven erythrocyte traits, and four platelet traits) after being immunized with classical swine fever vaccine. After adjusting for multiple testing based on permutations, 10, 24, and 77 chromosome-wise significant SNPs were identified for the leukocyte traits, erythrocyte traits, and platelet traits respectively, of which 10 reached genome-wise significance level. Among the 53 SNPs for mean platelet volume, 29 are located in a linkage disequilibrium block between 32.77 and 40.59 Mb on SSC6. Four genes of interest are located within the block, providing genetic evidence that this genomic segment may be considered a candidate region relevant to the platelet traits. Other candidate genes of interest for red blood cell, hemoglobin, and red blood cell volume distribution width also have been found near the significant SNPs. Our genome-wide association study provides a list of significant SNPs and candidate genes that offer valuable information for future dissection of molecular mechanisms regulating hematological traits.

Molecular characterization and association analysis of porcine interferon regulatory factor 1 gene.

Interferon regulatory factor 1 (IRF1) is a member of IRF-family that was discovered to activate promoters in type I interferon (IFN) genes. It is shown to play functionally diverse role in the regulation of the immune system. In this report, the porcine IRF1 cDNA were cloned and a 7500 bp genomic DNA structure was identified. The putative IRF1 protein included 322 amino acids. Alignment and phylogenetic analysis of the predicted porcine IRF1 amino acids sequence with its homologies of other species show high identity (over 88%). Tissues expression of IRF1 mRNA was observed by RT-PCR, the results revealed IRF1 gene expressed widely in all analyzed tissues. Using the radiation hybrid panel, the porcine IRF1 gene was mapped to porcine chromosome 2 and closely linked to the locus IL4 (LOD = 7.09, 57cR). A SNP in exon2 of porcine IRF1 gene was demonstrated by sequencing and PCR-RFLP analysis. The further association analysis indicated that the SNP was significant associate with level of IFN-γ (day 20) in serum (P = 0.0001) and the ratio of IFN-γ to IL10 (day 20; day 35) in serum (P = 0.0165; P = 0.0095). The results suggested that the porcine IRF1 gene is strong candidate gene for these immune traits in pig.

Association analysis of polymorphisms of porcine LMP2 and LMP7 genes with haematological traits.

Low molecular weight polypeptides 2 (LMP2) and low molecular weight polypeptides 7 (LMP7) are located within the major histocompatibility complex and have been associated with autoimmune disease. In this study, polymorphisms of porcine LMP2 and LMP7 genes were analyzed by PCR-SSCP and DNA sequencing methods. Four SNPs (DQ659151:g.2115T>C; DQ659151:g.4343A>G; DQ872631:g.1232C>G; DQ872631:g.2847C>T) were identified. Four SNPs of genes were analyzed for association with 22 haematological traits in Large White (n = 195), Landrace (n = 84) and Songliao Black (n = 86) pig population. Of all the 22 traits, seven were significant associated with the SNPs of LMP2/LMP7 gene (P < 0.05). They included white blood cell count (WBC) (P = 0.028), neutrophilic granulocyte count (GRAN) (P = 0.037), monocytes percentage (MO%) (P = 0.015), red blood cell (RBC) (P = 0.004), red blood cell volume distribution width (RDW) (P = 0.004), mean platelet volume (MPV) (P = 0.016) and CD4(+)CD8(+)% (P = 0.045). These results suggest LMP2/LMP7 gene should be regarded as molecular marker to estimate animal's immune status for their effects on hematological traits.

[Short term effect of PM(2.5) on cardiovascular mortality in residents in Changping district, Beijing].

Objective: To make a quantitative evaluation on the short term effect of particulate matter with aerodynamic diameter no more than 2.5 µm (PM(2.5)) on cumulative excess mortality rate (CER) and years of life lost (YLL) in residents in Changping district of Beijing. Methods: The death data in local residents, daily mortality, meteorology data and air pollution data (PM(2.5), SO(2) and NO(2) concentrations) in Changping from 2014 to 2017 were collected. Distributed lag non-linear model was used to assess the age and gender specific cumulative lag effects of PM(2.5) on cardiovascular CER and daily YLL in Changping. Results: The effects of PM(2.5) on cardiovascular CER and YLL were obvious on lag 7 days and lag 9 days, respectively, peaking on day 14, and lasting for 21 days. On lag0-21 days, for a 10 µg/m(3) increase in PM(2.5), the population based CER of cardiovascular disease death was 0.021% (95%CI: 0.004%-0.038%), and the YLL was 1.47 (95%CI: 0.23-2.70) years. Greater PM(2.5) effect were observed in males and the elderly. Conclusion: PM(2.5) increased the risk of cardiovascular disease death and YLL.

MiR-122 inhibits cell proliferation and induces apoptosis by targeting runt-related transcription factors 2 in human glioma.

OBJECTIVE: Accumulating evidence has suggested that microRNAs play critical roles in the development and progression of human glioma. The role of miR-122 in glioma tumorigenesis has been poorly defined. The current study is designed to investigate whether and how miR-122 affects proliferation and apoptosis of human glioma cells. PATIENTS AND METHODS: 8 normal brain tissues and 19 glioma tissues (7 for low grade and 12 for high grade) were collected. The expressions of miR-122 and runt-related transcription factors (RUNX2) in normal brain/glioma tissues and normal astrocytes (NHA)/multiple glioma cell lines (U87, U251, and U118) were analyzed by Real-time polymerase chain reaction (PCR). Western blot and luciferase activity assays were performed to validate the predicted relationship between miR-122 and RUNX2. The effects of miR-122 on cell proliferation and apoptosis were assessed by cell counting kit-8 (CCK-8), colony forming, and Annexin V-FITC/PI apoptosis assays using both gain- and loss-of-function approaches. RESULTS: MiR-122 expression is downregulated in glioma tissues compared with normal brain tissues, and is negatively correlated with the WHO grade. In contrast, the RUNX2 expression is upregulated in glioma tissues, and is positively correlated with the WHO grade. In glioma cell lines, the miR-122 expression is also constantly downregulated. MiR-122 functions as a tumor suppressor by inhibiting proliferation and inducing apoptosis, which is achieved by directly targeting RUNX2. Overexpression of RUNX2 can partially abrogate the effect of miR-122 on glioma cells. CONCLUSIONS: These results demonstrate a crucial role of miR-122 in regulating cell proliferation and apoptosis. Identifying the miR-122/RUNX2 signaling provides novel insights into the development of therapeutic targets for glioma.

Comparative analysis of internal friction and natural frequency measured by free decay and forced vibration.

Relations between various values of the internal friction (tgdelta, Q(-1), Q(-1*), and Lambda/pi) measured by free decay and forced vibration are analyzed systemically based on a fundamental mechanical model in this paper. Additionally, relations between various natural frequencies, such as vibration frequency of free decay omega(FD), displacement-resonant frequency of forced vibration omega(d), and velocity-resonant frequency of forced vibration omega(0) are calculated. Moreover, measurement of natural frequencies of a copper specimen of 99.9% purity has been made to demonstrate the relation between the measured natural frequencies of the system by forced vibration and free decay. These results are of importance for not only more accurate measurement of the elastic modulus of materials but also the data conversion between different internal friction measurements.

Efficacy of type a botulinum toxin injections and infrared polarized light on treating chronic migraine.

OBJECTIVE: To investigate the clinical value of the combination of ultrasound-and-hyponome-guided type A botulinum toxin injection and infrared polarized light on treating chronic migraine. PATIENTS AND METHODS: Ninety-one patients with chronic migraine were randomly divided into four groups: in the control group (group A, 22 cases in total), nimodipine was used in the treatment of chronic migraine for two months; in the infrared polarized light therapy group (group B, 22 cases in total), infrared polarized light was adopted in the treatment of chronic migraine for 50-60d; in the botulinum toxin treatment group (group C, 24 cases in total), ultrasound-and-hyponome-guided type A botulinum toxin was injected into frontal, temporal, and occipital muscles in treating chronic migraine; in the joint treatment group (group D, 23 cases in total), ultrasound-and-hyponome-guided type A botulinum toxin injection in group C and infrared polarized light in group B were both used here in the treatment of chronic migraine. Infrared polarized light therapy lasted 50-60d and the time of study lasted six months. The survey would include the conditions of patients with chronic migraine three months before treatment and at one, three and six months after treatment. Patients were asked to fill the MIDAS (migraine disability assessment questionnaire) and were graded on the evaluation scale of life quality, so that the researchers would be able to compare attack frequency, duration of attack, attack severity, the use of painkillers and their recovery from chronic migraine, and then observe their adverse reactions. RESULTS: Eleven cases dropped out during the treatment, three cases in A group, two cases in group B, four cases in group C and two cases in group D. One, three and six months after treatment, the MIDAS scores in group A, B, C and D were significantly lower than before the treatment. Hence, the differences were statistically significant (p < 0.01). The scores in quality of life rating scale were significantly higher than pre-treatment scores, so the difference was statistically significant (p < 0.01). The MIDAS scores and quality of life rating scale scores in group D were compared with those in group A, B, and C respectively, and the differences were statistically significant (p < 0.05). Two patients were recorded with dizziness, and the dizziness disappeared after two weeks with no treatments at all. Forehead lines and crow's feet of 21 patients shallowed or disappeared in varying degrees after the injection. CONCLUSIONS: The combination of ultrasound-and-hyponome-guided type A botulinum toxin injection and infrared polarized light on treating chronic migraine demonstrated a significant clinical effect.

Efficacy analysis of ultrasound-guided local injection of botulinum toxin type A treatment with orthopedic joint brace in patients with cervical dystonia.

OBJECTIVE: To study the efficacy of ultrasound-guided local injection of botulinum toxin type A (BTX-A) treatment with orthopedic joint brace in patients with cervical dystonia (CD). PATIENTS AND METHODS: A total of 105 patients with cervical dystonia were selected and randomly divided into medication treatment group (A group), botulinum toxin treatment group under the guidance of ultrasound treatment (B group) and botulinum toxin under the guidance of ultrasound treatment combined with orthopedic joint brace treatment group (C group). Tsui scale and Spitzer quality of life index was applied to evaluate the spasm and quality of life. The scores of Tsui scale and Spitzer quality of life index were compared after ultrasound-guided local treatment for one month, three months and six months. RESULTS: The difference in Tsui and Spitzer scores before and after the treatment of oral medications were not statistically significant (p > 0.05). Whereas, the differences in Tsui and Spitzer scores before and after the treatment between local injection of BTX-A treatment group and orthopedic joint brace combined with BTX-A injection group were statistically significant (p < 0.05). Also, the difference in Tsui and Spitzer scores of orthopedic joint brace combined with BTX-A injection group at 3 months, and 6 months were statistically significant compared to local injection of BTX-A treatment group (p < 0.05). CONCLUSIONS: Ultrasound-guided local injection of BTX-A combined with orthopedic brace could significantly reduce muscle tension and improve quality of life.

Ultrasound-guided botulinum toxin injections and EMG biofeedback therapy the lower limb muscle spasm after cerebral infarction.

OBJECTIVE: To evaluate the clinical efficacy under ultrasound-guided injection of botulinum toxin-A (BTX-A) and EMG biofeedback treatment of the lower limb muscle spasm after cerebral infarction. PATIENTS AND METHODS: Thirty-six cases of lower limb muscle spasm after cerebral infarction hemiplegia were randomly divided into two groups, the treatment group and the control group respectively including 18 cases. Both groups of patients were injected with BTX-A at different sites on spastic muscles. Twenty-four hours later, the treatment group was administered EMG biofeedback. Then, the modified Ashworth scoring was employed to observe the curative effect of the two groups. RESULTS: After six weeks' injection, the treatment group scored better than the control group (p < 0.05). CONCLUSIONS: Ultrasound-guided injection of botulinum toxin type A at various sites with EMG biofeedback treatment of the lower limb muscle spasms after cerebral infarction is efficient and conducive to the rehabilitation of patients' motor functions.

Efficiency of ultrasound and water capsule-guided local injection of botulinum toxin type A treatment on patients with facial spasm.

OBJECTIVE: To study the efficacy of ultrasound and water capsule-guided local injection of botulinum toxin type A (BTX-A) treatment on patients with facial spasm. PATIENTS AND METHODS: One hundred and fifty-seven cases of facial spasm were randomly divided into oral drug treatment group (group A) (78 cases) and ultrasound and water capsule-guided local injection of botulinum toxin type A treatment group (group B) (79 cases). Cohen, Acbert spasm strength grade scores in each case with facial spasm were recorded. Therapeutic effect, duration, significant efficiency, and muscle spasm strength were compared before and three after treatment. RESULTS: The muscle spasm strength showed no significant change in group A after the treatment. However, the muscle spasm strength was decreased significantly in group B after treatment (p < 0.01). CONCLUSIONS: Ultrasound and water capsule-guided local injection of botulinum toxin type A treatment is a safe, effective, and simple treatment for patients with facial spasm.

Color Doppler ultrasound-guided botulinum toxin type A injection combined with an ankle foot brace for treating lower limb spasticity after a stroke.

OBJECTIVE: To explore the effectiveness of the color Doppler ultrasound-guided botulinum toxin type A (BTX-A) injection combined with an ankle foot brace (AFO) for treating lower limb spasticity after a stroke. PATIENTS AND METHODS: A total of 103 post-stroke patients with lower limb spasticity were divided into three groups: the control group treated with conventional therapy and rehabilitation training, the observation group treated with conventional therapy, rehabilitation training and botulinum toxin type A injection, the treatment group treated with AFO plus the same treatment received by the observation group. The muscle spasms were evaluated using the Clinic Spasticity Influx (CSI), movement with the Fugl-Meyer Assessment (FMA), dynamic and static balance with the Berg Balance Scale (BBS), and daily life activities with the Functional Independence Measure (FIM), respectively. RESULTS: Compared the first month after treatment with the prior treatment, there were significant differences in CSI, FMA and FIM scores in both control group and the observation group (p < 0.05). However, no differences were noticed in the control group (p > 0.05). Compared the third and sixth month after treatment with prior treatment, there were significant differences in these three groups (p < 0.05). In terms of treatment time, the BBS scores were always higher in all three groups after one month, three months and six months treatment than prior treatment (p < 0.05), and there were significant differences in third month and sixth month after treatment compared with the first month treatment (p < 0.05). Compared the third month after treatment with the sixth month, there were significant differences in all three groups (p < 0.05). CONCLUSIONS: The color Doppler ultrasound-guided BTX-A injection combined with AFO can effectively promote patients with post-stroke lower limb spasticity in lower limb muscle spasm, movement, balance and daily life activities.

Solvent systems for intracarotid 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) infusion.

The agent, 1,3-bis(3-chloroethyl)-1-nitrosourea (BCNU), when given by arterial infusion for brain tumor chemotherapy is usually dissolved in an alcohol/saline solution. The authors compared the osmolality of and drug recovery from solvent systems of alcohol/saline, dimethyl sulfoxide (DMSO)/water, and dextrose/water. Recovery of drug was adequate from all solvent systems, although variability of drug recovery from the alcohol/saline and DMSO/water systems was greater than from the dextrose/water system. The alcohol/saline system was significantly hyperosmolar. The alcohol/saline and DMSO/water solvent systems offer no advantage over the dextrose/water system and may be associated with significant disadvantages.

Trace analysis for cis-platinum anti-cancer drugs via LCEC.

Liquid chromatography-electrochemical detection (LCEC) methods and instrumentation have been successfully applied for the trace determination of at least three separate platinum (Pt) anti-cancer (neoplastic) agents. All of these compounds have proven clinically effective in the treatment of human neoplasms. The three Pt derivatives studied were: cis-dichloro diammine platinum (cis-Pt); cis-diammine-1, 1-cyclobutane dicarboxylate platinum (CBDCA); and cis-dichloro-trans-dihydroxy diisopropylamine platinum (CHIP). The parent compound, cis-Pt (CDDP), can be determined via both oxidative and reductive LCEC, with differences in the minimum limits of detection. Calibration plots and minimum detection limits have been determined for all three derivatives. Both CBDCA and CHIP can be determined via direct LCEC, but the minimum detection limits for CBDCA are not practical for stability or clinical studies. A new method of derivatization for CBDCA and related Pt compounds has been developed, wherein this can be quantitatively converted to cis-Pt, and the final derivative is then determined as for the parent cis-Pt. CDDP can be determined via reductive LCEC at the 100-ppb level in plasma. The final methods of LCEC analysis have now been applied to a variety of stability studies with all three Pt drugs, in water, plasma, and saline infusion solutions. It is suggested that these LCEC methods are directly applicable and amenable to "real world" clinical settings and cancer-patient samples.

Precolumn derivatization for improved detection in liquid chromatography-photolysis-electrochemistry.

Precolumn, homogeneous chemical derivatization with Sanger's reagent (2,4-dinitrofluorobenzene) is utilized to improve the chromatographic and detection properties of amino alcohols and amino acids. The 2,4-dinitrophenyl derivatives are separated using reversed-phase liquid chromatography and are detected using the hybrid photolysis-electrochemical (hv-EC) detector in tandem with UV absorbance detection. Following optimization of reaction, chromatographic, and detection variables, the derivatization-detection approach provides limits of detection in the low parts-per-billion range, with a linearity of roughly three orders of magnitude. Selectivity is based on retention times as well as dual electrode response ratios and a "lamp on/off" responsiveness criterion unique to the hv-EC detector. The method is applied to the determination of serine in beer.

Measurement of shear strength for HOPG with scanning tunneling microscopy by thermal excitation method.

An experimental observation of force interactions in scanning tunneling microscopy (STM) is presented. A technique for measuring force interactions between a conventional STM probe and a sample by spectra analysis of its thermal fluctuations from tunneling current in STM is developed theoretically and experimentally. Thermally excited fluctuation of the STM probe is exactly discerned in air and then force gradient is determined from its corresponding eigen-frequency with a formula similar to that for a small-amplitude atomic force microscopy (AFM). The observed force interactions are consistent with forces in dynamic AFM. Shear strength of 7 GPa for highly oriented pyrolytic graphite (HOPG) under compressive stress is obtained from the experiment and using the elastic theory. We believe that this technique is of scientific significance as it enables accurate measurement of short-range force interactions at atomic scale under true STM conditions.