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Menaquinone-7 (MK-7), a multipotent vitamin K2, possesses a wide range of biological activities, a precise curative effect and excellent safety. A simple and rapid LC-APCI-MS/MS method for the determination of MK-7 in human plasma with single liquid–liquid extraction (LLE) extraction and 4·5-min analysis time has been developed and validated. Four per cent bovine serum albumin (BSA) was used as surrogate matrix for standard curves and endogenous baseline subtraction. This method was reproducible and reliable and was used to analyse of MK-7 in human plasma. The endogenous circadian rhythm and bioavailability of MK-7 were investigated in two randomised single-dose, open, one-way clinical trials (Study I and Study II). A total of five healthy male subjects were enrolled in Study I and 12 healthy male subjects in Study II. Single-dose (1 mg) of MK-7 was given to each subject under fasting condition, and all eligible subjects were given a restricting VK2 diet for 4 d prior to drug administration and during the trial. The experiment results of Study I demonstrated that endogenous MK-7 has no circadian rhythm in individuals. Both studies showed MK-7 are absorbed with peak plasma concentrations at about 6 h after intake and has a very long half-life time.
Porous materials have many applications for laser–matter interaction experiments related to inertial confinement fusion. Obtaining new knowledge about the properties of the laser-produced plasma of porous media is a challenging task. In this work, we report, for the first time to the best of our knowledge, the time-dependent measurement of the reflected light of a terawatt laser pulse from the laser-produced plasma of low-Z foam material of overcritical density. The experiments have been performed with the ABC laser, with targets constituted by foam of overcritical density and by solid media of the same chemical composition. We implemented in the MULTI-FM code a model for the light reflection to reproduce and interpret the experimental results. Using the simulations together with the experimental results, we indicate a criterion for estimating the homogenization time of the laser-produced plasma, whose measurement is challenging with direct diagnostic techniques and still not achieved.
N6-Methyladenosine (m6A) regulates oocyte-to-embryo transition and the reprogramming of somatic cells into induced pluripotent stem cells. However, the role of m6A methylation in porcine early embryonic development and its reprogramming characteristics in somatic cell nuclear transfer (SCNT) embryos are yet to be known. Here, we showed that m6A methylation was essential for normal early embryonic development and its aberrant reprogramming in SCNT embryos. We identified a persistent occurrence of m6A methylation in embryos between 1-cell to blastocyst stages and m6A levels abruptly increased during the morula-to-blastocyst transition. Cycloleucine (methylation inhibitor, 20 mM) treatment efficiently reduced m6A levels, significantly decreased the rates of 4-cell embryos and blastocysts, and disrupted normal lineage allocation. Moreover, cycloleucine treatment also led to higher levels in both apoptosis and autophagy in blastocysts. Furthermore, m6A levels in SCNT embryos at the 4-cell and 8-cell stages were significantly lower than that in parthenogenetic activation (PA) embryos, suggesting an abnormal reprogramming of m6A methylation in SCNT embryos. Correspondingly, expression levels of m6A writers (METTL3 and METTL14) and eraser (FTO) were apparently higher in SCNT 8-cell embryos compared with their PA counterparts. Taken together, these results indicated that aberrant nuclear transfer-mediated reprogramming of m6A methylation was involved in regulating porcine early embryonic development.
TLR3 and IL-10 play a crucial role in antiviral defence. However, there is a controversy between TLR3 rs3775291 and IL-10 rs1800871 polymorphisms and the risk of hepatitis B virus (HBV) infection. The purpose of this study is to explore the relationship between the two single nucleotide mutations and the risk of HBV infection by meta-analysis. Medline, EMBASE, Web of Science, CNKI, China Wanfang database were searched for the case-control studies on the relationship between TLR3 rs3775291 and IL-10 rs1800871 polymorphism and susceptibility to HBV, updated to June 2020. The data were analysed by Stata 15.0 software. A total of 22 articles were included. The results showed that in the analysis of IL10 rs1800871 polymorphism and the risk of HBV infection, the pooled OR was 1.21 (95% CI 1.06–1.37), 1.28 (95% CI 1.04–1.56) and 1.20 (95% CI 1.06–1.37) and 1.40 (95% CI 1.07–1.83) in the allele model (C vs. T), dominant model (CC+CT vs. TT), recessive model (CC vs. CT+TT) and homozygous model (CC vs. TT), respectively. There was no statistical significance in the heterozygote model. A subgroup analysis of the Asian population showed similar results. The analysis of TLR3 rs3775291 polymorphism and the risk of HBV showed that in the allele model (T vs. C), the pooled OR was 1.30 (95% CI 1.05–1.61). Except for the recessive model, no significances were found in other genetic models. In conclusion, TLR3 rs3775291 and IL-10 rs1800871 polymorphisms are associated with the risk of HBV. Allele C and genotype CC at IL10 rs1800871 loci, as well as allele T and genotype TT at TLR rs3775291 loci, may increase susceptibility to Hepatitis B infection.
Laboratory-based characterization and traceback of Clostridium butyricum isolates linked to outbreak cases of neonatal necrotizing enterocolitis (NEC) in a hospital in China.
In total, 37 samples were collected during the NEC outbreak. Classical bacteriological methods were applied to isolate and identify Clostridium spp. Meanwhile, 24 samples collected after an outbreak were similarly tested. All Clostridium isolates were identified to species level as either C. butyricum or C. sporogenes. These isolates were subsequently subtyped using pulsed-field gel electrophoresis (PFGE). Genomic DNA was purified from 2 representative C. butyricum isolates and sequenced to completion.
Of 37 samples collected during the NEC outbreak, 17 (45.95%) were positive for Clostridium spp. One species, C. butyricum, was cultured from 10 samples. Another species cultured from 2 other samples was identified as C. sporogenes. Both of these species were cocultured from 5 samples. Pulsotyping showed that the 15 C. butyricum and the 7 C. sporogenes isolates produced indistinguishable DNA profiles. No NEC cases were reported after disinfection following the outbreak, and all samples collected after the outbreak were negative for Clostridium spp. Whole-genome sequencing (WGS) indicated that sialidase, hemolysin, and enterotoxin virulence factors were located on the chromosomes of 2 C. butyricum isolates.
The outbreak of NEC was epidemiologically linked to C. butyricum contamination within the hospital. This is the first report of an NEC outbreak associated with C. butyricum infection in China.
We aimed to investigate the associations between school-level characteristics and obesity among Chinese primary school children with consideration of individual-level characteristics.
This cross-sectional study was conducted in 2015/2016. School-level characteristics were assessed using an interviewer-administered school questionnaire, and a ‘school-based obesity prevention index’ was further developed. Individual-level characteristics were collected by self-administered questionnaires. Objectively measured height and weight of students were collected, and obesity status was classified according to the International Obesity Task Force criteria for Asian children. Generalised linear mixed models were used to estimate the associations among the school- and individual-level characteristics and obesity of students.
Thirty-seven primary schools from an urban and a rural district of Beijing, China.
School staffs, 2201 students and their parents.
The school-based obesity prevention index involved the number of health professionals, availability of students’ health records, monitoring students’ nutrition status, frequency of health education activities, reporting achievements of obesity prevention activities to parents, duration of physical activity during school time and availability of playground equipment. The prevalence of obesity was lower in schools with the higher index value compared with that in schools with the lower index value (OR 0·56; 95 % CI 0·40, 0·79). Some individual-level characteristics were negatively associated with childhood obesity: liking sports, duration of screen time ≤2 h/d, perceived lower eating speed, parental non-overweight/obesity.
Irrespective of individual-level characteristics, the specific school-level characteristics had a cumulative effect on obesity among Chinese primary school children. Further school-based obesity intervention should consider these characteristics simultaneously.
Improving the production traits and resistance against mastitis in dairy cattle is a challenge for animal scientists across the globe. The present study was designed to investigate the genetic effects of single nucleotide polymorphisms (SNPs) in Janus kinase 2 (JAK2) and diacylglycerol acyltransferase (DGAT1) genes with production and mastitis-related traits. Four SNPs in JAK2 and one in DGAT1 were analyzed through Chinese Cow's SNPs Chip-I (CCSC-I) and genotyped in a population of 312 Chinese Holsteins. Our findings demonstrated that milk fat percentage, somatic cell count (SCC), somatic cell score (SCS), serum cytokines interleukin 6 (IL-6) and interferon gamma (IFN-γ) showed significant associations (P < 0.05) with at least one or more identified SNPs. Consequently, the analysis based on haplotypes amongst the SNPs in JAK2 revealed noteworthy (P < 0.05) association with SCC and IL-6. Collectively, our results verified the pleiotropic ability of detected SNPs in bovine JAK2 and DGAT1 for milk fat percentage as well as mastitis-related traits. The significant SNPs in both the genes could serve as powerful genetic markers to minimize mastitis risk. In addition, besides SCC and SCS, the IFN-γ and IL-6 could also be used as indicators of improved genetic resistance against mastitis.
Seed reserves play vital roles in seed germination and seedling growth and their variation may be related to various environment factors, plant traits and phylogenetic history. Here, the evolutionary correlation associated with seed mass and altitude and carbon (C), nitrogen (N) and phosphorus (P) allocation of seeds among 253 alpine herbaceous plants was tested. In this study, phylogeny had strong limitations on nutrient allocation of seeds across species, and species from younger phylogenetic groups tended to have higher N and P contents, which might be considered as the evolutionary selection of seed plants. Higher seed N and P content would help seedlings to gain more survival chance and stronger competitive capacity, and their progeny would be more likely to be preserved. When phylogeny was considered, altitude only had a significant positive effect on P content, but the negative effects on seed mass were all expressed. The independent effects of altitude and seed mass suggest that the nutrient allocation of seeds might be affected by both environment and plant traits. In addition, altitude and seed mass displayed partial overlapping effects on nutrient allocation of seeds. The negative effects of seed mass were affected slightly by altitude, whereas altitude only had a significant positive effect on P content when seed mass was controlled. Above all, seed P content showed obvious and general correlations with seed mass, altitude and age of clade, which indicated that higher seed P content might be an adaptive selection of species associated with growth and survival of progeny.
The sharp-interface limits of a phase-field model with a generalized Navier slip boundary condition for binary fluids with moving contact lines are studied by asymptotic analysis and numerical simulations. The effects of the mobility number as well as a phenomenological relaxation parameter on the boundary condition are considered. In asymptotic analysis, we consider both the cases that the mobility number is proportional to the Cahn number and the square of the Cahn number, and derive the sharp-interface limits for several set-ups of the boundary relaxation parameter. It is shown that the sharp-interface limit of the phase-field model is the standard two-phase incompressible Navier–Stokes equations coupled with several different slip boundary conditions. Numerical results are consistent with the analysis results and also illustrate the different convergence rates of the sharp-interface limits for different scalings of the two parameters.
In the past few years, we have performed a 22 GHz H2O maser survey towards hundreds of BGPS sources using the 25-meter Nanshan Radio Telescope (NSRT) of the Xinjiang Astronomical Observatory, and detected more than one hundred masers. Our aim is to study star formation activities associated with these sources, as well as search for any correlations that may exist between 22 GHz H2O masers and the evolutionary stage of high-mass star formation regions. The NSRT has been upgraded and have now an effective diameter of 26 meter. Besides, cryogenically cooled dual-beam receiver systems covering seven millimeter-wave observing bands have been installed on the NSRT. For the next step of maser observation, we will continue to do H2O and SiO masers survey of massive dust clumps and monitor some maser sources.
In this work, the high-performance silicon carbide particle SiCp[carbon nanotube (CNT)] hybrid reinforcement is currently explored to develop the advanced metal matrix composites. 17 wt% SiCp(CNT)/Al composites were fabricated by a powder metallurgy technique, in which SiCp(CNT) hybrid reinforcement with various CNT contents (e.g., 3, 6 and 9 wt%) were applied. Effects of CNT content on the morphology of SiCp(CNT) hybrid reinforcement, the microstructural characteristics, and the tensile mechanical behavior of SiCp(CNT)/Al composites were studied as well. Especially, the SiCp(CNT)/Al composites with 6 wt% CNT in SiCp(CNT) hybrid reinforcement exhibited the most significant enhancing effects in the elastic modulus and tensile strength. Meanwhile, the SiCp(CNT)/Al composites produced a synergistic strengthening effect of SiCp and CNT compared to SiCp/Al composites, while the SiCp(CNT)/Al composites with high CNT content in SiCp(CNT) hybrid reinforcement provided weak improvement in the tensile strength and ductility due to the forming agglomeration of CNT in the matrix.
Introduction: The mortality of Parkinson’s disease (PD) and its associated risk factors among clinically definite PD patients in China has been rarely investigated. Our study aimed to identify the mortality rates and predictors of death in PD patients in China. Methods: 157 consecutive, clinically definite PD patients from the urban area of Shanghai were recruited from a central hospital based movement disorder clinic in 2006. All patients were regularly followed up at the clinic until December 31, 2011, or death. Mortality and associations with baseline demographics, health and medical factors were then determined within the cohort. Results: After 5 years, 11(7%) patients had died. The standardised mortality ratio was 0.62 (95% CI 0.32 to 1.07, P=0.104). The main causes of death were pneumonia (54.5%, 6/11) and digestive disorders (18.2%, 2/11), respectively. Age at onset, independent living, the mini mental state examination score, the Parkinson’s disease sleep scale score and the Epworth sleepiness scale score at baseline were statistically significantly different between the survival group and the deceased group (P<0.05). Across all participants, risk factors for death included low mini mental state examination score, and high Epworth sleepiness scale score according to a binary variable logistic regression analysis. Conclusions: This study confirms the similar survival of patients with PD to the control population up to a follow-up of 5 years. Interventions tailored to potential risk factors associated with death may offer further benefits.
An epigenetic mechanism has been suggested to explain the effects of the maternal diet on the development of disease in offspring. The present study aimed to observe the effects of a maternal high-lipid, high-energy (HLE) diet on the DNA methylation pattern of male offspring in mice. Female C57BL/6J mice were fed an HLE diet during gestation and lactation. The genomic DNA methylations at promoter sites of genes in the liver, mRNA and protein levels of selected genes related to lipid and glucose metabolism were measured by microarray, real-time PCR and Western blot. The results indicated that the percentage of methylated DNA in offspring from dams that were fed an HLE diet was significantly higher than that from dams that were fed a chow diet, and most of these genes were hypermethylated in promoter regions. The nuclear protein content and mRNA levels of hypermethylated genes, such as PPARγ and liver X receptor α (LXRα), were decreased significantly in offspring in the HLE group. The results suggested that the DNA methylation profile in adult offspring livers was changed by the maternal HLE diet during gestation and lactation.
Hypoxia inducible factor 1 (HIF-1) is a key transcriptional factor activated during cerebral ischemia, which regulates a great number of downstream genes, including those associated with cell death. In the present study, we aimed to test the hypothesis that post-ischemic HIF-1α up-regulation might promote autophagy activation; thereby, HIF-1α inhibitor 2ME2 might prevent neurons from ischemic injury through inhibiting autophagy.
Global ischemia was induced using the four-vessel occlusion model (4-VO) in Sprague-Dawley rats (male, 250-280g). 2-Methoxyestradiol (2ME2, 5mg/kg, i.p.) was administrated to down-regulate HIF-1α expression. Post-ischemic beclin-1 and LC3 protein expression was determined at different time points through Western blot assay. Neuronal injury was determined by cresyl violet staining and TUNEL staining in coronal histological sections.
The expression of beclin-1 and the ratio of LC3-II/LC3-I increased significantly at 12 and 24 h after ischemia. 2ME2 could remarkably inhibit the up-regulation of beclin-1 and the increase of LC3-II/LC3-I ratio during reperfusion. Moreover, 2ME2 and 3-MA exhibited powerful protective effects against ischemic/reperfusion induced neuronal injury.
This study confirmed that autophagy participated in post-ischemic neuronal injury. 2ME2, a HIF-1α inhibitor, might significantly decrease autophagy activation after cerebral ischemia and relieve post-ischemic neuronal injury. Our findings demonstrate that autophagy could be a potential target for neuronal protection after cerebral ischemia.
Ubiquitin proteasome system dysfunction is believed to play an important role in the development of Parkinson's disease (PD), and almost all studies till now have mainly focused on the susceptibility of dopaminergic neurons to proteasome inhibition. However, in fact, there are many other types of neurons such as cholinergic ones involved in PD. In our present study, we attempt to figure out what effect the failure of ubiquitin proteasome function would execute on cholinergic cells in culture.
We treated cholinergic cells in culture with various doses of lactacystin. Then MTT assay was used to evaluate the cellular viability and the Annexin V-PI method was used to detect apoptosis. Both cellular soluble and insoluble polyubiquitinated proteins were detected by western blot. Furthermore, the mitochondrial membrane potential was analyzed using JC-1 and the intracellular production of reactive oxygen species (ROS) was determined using the fluorescent probe CM-H2DCFDA.
We found that low doses of lactacystin were enough to induce significant apoptotic cell death, disturb the mitochondrial membrane potential, and cause oxidative stress. We also found that the amounts of polyubiquitinated proteins dramatically increased with high doses, although the loss of cells did not increase accordingly.
Our results suggest that cholinergic cells are sensitive to ubiquitin proteasome system dysfunction, which exerts its toxic effect by causing mitochondrial dysfunction and subsequent oxidative stress, not through polyubiquitinated proteins accumulation.
We report a modified surgical technique for transplanting an ectopic, lingual thyroid to the submandibular space, in order to maintain thyroid function while relieving obstructive symptoms.
A 52-year-old woman complained of progressive dysphagia and dyspnoea. Ectopic lingual thyroid tissue was diagnosed. The ectopic thyroid gland was transplanted into the submandibular region via a lateral pharyngeal approach. A random muscle pedicle was prepared to provide a vascular supply to the transposed gland.
Twelve-month follow up confirmed the survival of the transplanted thyroid gland, with preserved thyroid function.
Surgical transplantation of a lingual thyroid to the submandibular region offers an alternative treatment method for this anomaly, which avoids the need for resection and lifelong thyroxine replacement.
KLa2Ti3O9.5 and KLa2Ti3O9.5:Er3+ nanocrystals were successfully synthesized using a hydrothermal method and a subsequent calcination treatment. The band gap (Eg) of the KLa2Ti3O9.5 nanocrystals was calculated to be about 2.56 eV by means of the reflectance diffusion technique. Under 980-nm excitation, the KLa2Ti3O9.5:Er3+ nanocrystals emitted intense green (2H11/2/4S3/2 → 4I15/2) and red (4F9/2 → 4I15/2) upconversion (UC) luminescence. In comparison with pure KLa2Ti3O9.5, the KLa2Ti3O9.5:Er3+ nanocrystals exhibited a higher activity for water splitting into H2 under simulated solar light irradiation. We suggest that the enhancement of photocatalytic activity is related to the Brunauer-Emmett-Teller (BET) surface area and UC luminescence of KLa2Ti3O9.5:Er3+.
The thermal dilation experiment and the martensite transformation features of modified high Cr ferritic heat-resistant steel upon continuous cooling were explored at various cooling rates. The “spread” martensite transformation model was introduced to investigate the influence of the cooling rate applied on the martensite transformation behaviors. The martensite fraction, martensite formation rate, and the density of martensite laths were obtained as a function of cooling rate. Both the onset and offset temperatures of the martensite transformation decrease with the increase of cooling rate, and the martensite formation rate bursts at the beginning of transformation and then reaches a peak rapidly. The fitted data based on the proposed kinetic model indicated that the aspect ratio of martensite lath decreases, instead the density of martensite laths increases, with the increase of cooling rate.
Contrary to concerns that fructose may have adverse metabolic effects, there is evidence that small, ‘catalytic’ doses ( ≤ 10 g/meal) of fructose decrease the glycaemic response to high-glycaemic index meals in human subjects. To assess the longer-term effects of ‘catalytic’ doses of fructose, we undertook a meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library. Analyses included all controlled feeding trials ≥ 7 d featuring ‘catalytic’ fructose doses ( ≤ 36 g/d) in isoenergetic exchange for other carbohydrates. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean differences (MD) with 95 % CI. Heterogeneity was assessed by the Q statistic and quantified by I2. The Heyland Methodological Quality Score assessed study quality. A total of six feeding trials (n 118) met the eligibility criteria. ‘Catalytic’ doses of fructose significantly reduced HbA1c (MD − 0·40, 95 % CI − 0·72, − 0·08) and fasting glucose (MD − 0·25, 95 % CI − 0·44, − 0·07). This benefit was seen in the absence of adverse effects on fasting insulin, body weight, TAG or uric acid. Subgroup and sensitivity analyses showed evidence of effect modification under certain conditions. The small number of trials and their relatively short duration limit the strength of the conclusions. In conclusion, this small meta-analysis shows that ‘catalytic’ fructose doses ( ≤ 36 g/d) may improve glycaemic control without adverse effects on body weight, TAG, insulin and uric acid. There is a need for larger, longer ( ≥ 6 months) trials using ‘catalytic’ fructose to confirm these results.