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Previous work led to the proposal that the precision feeding of a high-concentrate diet may represent a potential method with which to enhance feed efficiency (FE) when rearing dairy heifers. However, the physiological and metabolic mechanisms underlying this approach remain unclear. This study used metabolomics analysis to investigate the changes in plasma metabolites of heifers precision-fed diets containing a wide range of forage to concentrate ratios. Twenty-four half-sib Holstein heifers, with a similar body condition, were randomly assigned into four groups and precision fed with diets containing different proportions of concentrate (20%, 40%, 60% and 80% based on DM). After 28 days of feeding, blood samples were collected 6 h after morning feeding and gas chromatography time-of-ﬂight/MS was used to analyze the plasma samples. Parameters of oxidative status were also determined in the plasma. The FE (after being corrected for gut fill) increased linearly (P < 0.01) with increasing level of dietary concentrate. Significant changes were identified for 38 different metabolites in the plasma of heifers fed different dietary forage to concentrate ratios. The main pathways showing alterations were clustered into those relating to carbohydrate and amino acid metabolism; all of which have been previously associated with FE changes in ruminants. Heifers fed with a high-concentrate diet had higher (P < 0.01) plasma total antioxidant capacity and superoxide dismutase but lower (P ≤ 0.02) hydroxyl radical and hydrogen peroxide than heifers fed with a low-concentrate diet, which might indicate a lower plasma oxidative status in the heifers fed a high-concentrate diet. Thus, heifers fed with a high-concentrate diet had higher FE and antioxidant capacity but a lower plasma oxidative status as well as changed carbohydrate and amino acid metabolism. Our findings provide a better understanding of how forage to concentrate ratios affect FE and metabolism in the precision-fed growing heifers.
Big data provides high volume of data to inform product customisation. Understanding which data is relevant remains a challenge. A method is proposed to identify relevant data to inform data-driven customisation. A case study regarding customisation of orthoses was conducted. Verbal protocol analysis was employed to extract time spent on major fabrication phases. Data related to patients, therapists and fabrication time was analysed. Results showed that the number of stabilised joints, experience of therapists and whether the design is for in- or out-patient are key factors for customisation.
Gold nanoparticles (AuNPs) are one of the most versatile and accessible classes of nanomaterials. Their chemical stability, ease of colloidal synthesis, surface functionalization, and plasmonic resonance—tunable from the visible through the near-infrared—have made AuNPs the metal nanoparticle of choice for many applications. This article summarizes the chemical synthesis of AuNPs, particularly gold nanorods, with a focus on recent developments in shape control and surface modifications. Current applications using the photothermal properties of AuNPs, as well as AuNP connections to biology and the environmental sciences, will be discussed.
Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.
Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.
The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control.
Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.
We describe an analytical method of SH-SY5Y cell membrane chromatography (SH-SY5Y/CMC) for recognition, separation and identification of active components from traditional Chinese medicines (TCMs). SH-SY5Y cells by means of culture with SH-SY5Y cell lines were used for preparation of the stationary phase in the CMC model. Retention components by the SH- SY5Y/CMC model were collected and active components then analyzed by SH-SY5Y/CMC under the optimized conditions. After investigating the suitability and reliability of the SH-SY5Y /CMC method using risperidone, sertraline and clozapine as standard compounds, this method was applied in screening active components from the extracts of TCMs such as Radix Gentianae, Radix Bupleuri, stir-baked semen ziziphi spinosae, rehmannia dride rhizome, uncaria rhynchophylla. Retention components from the extracts in the SH-SY5Y/CMC model were gentiopicrin and rosmarinci acid identified by the GC/MS method. In vitro pharmacological trials indicated that gentiopicrin and rosmarinci acid could concentration dependently protect the SH-SY5Y pre-treated by H2O2 (P < 0.05). The SH-SY5Y/CMC method is an effective screening system that can rapidly detect target components from a complex sample for antipsychotic candidate drug.
Electroconvulsive therapy (ECT) effectively treats severe depression, but not all patients remit. The aim of the study was to identify clinical factors that associate with ECT-induced remission in a community setting.
Depressed patients who underwent ECT in 2011–2014 were identified from the Swedish National Quality Register for ECT. Remission was defined as self-rated Montgomery-Åsberg Depression Rating Scale scores of 0–10 after ECT. Other registers provided data on previous antidepressant use, comorbidities, and demographics.
Of 1671 patients fulfilling the inclusion criteria, 42.8% achieved remission. Older age, education length over 9 years, psychotic symptoms, shorter duration of preceding antidepressant use, pulse width stimulus ≥ 0.50 ms, absence of substance use disorders, anxiety diagnosis, lamotrigine, and benzodiazepines, were associated with remission.
This study shows that psychotic subtype of depression and older age are clinically relevant predictors of a beneficial ECT effect. Additionally, ECT outcomes can be further improved by optimizing the treatment technique and concomitant medication.
Although the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke caused by intracranial anterior circulation large vessel occlusion (LVO) is proven, demonstration of local effectiveness is critical for health system planning and resource allocation because of the complexity and cost of this treatment.
Using our prospective registry, we identified all patients who underwent EVT for out-of-hospital LVO stroke from February 1, 2013 through January 31, 2017 (n = 44), and matched them 1:1 in a hierarchical fashion with control patients not treated with EVT based on age (±5 years), prehospital functional status, stroke syndrome, severity, and thrombolysis administration. Demographics, in-hospital mortality, discharge disposition from acute care, length of hospitalization, and functional status at discharge from acute care and at follow-up were compared between cases and controls.
For EVT-treated patients (median age 66, 50% women), the median onset-to-recanalization interval was 247 min, and successful recanalization was achieved in 30/44 (91%). Alteplase was administered in 75% of cases and 57% of controls (p = 0.07). In-hospital mortality was 11% among the cases and 36% in the control group (p = 0.006); this survival benefit persisted during follow-up (p = 0.014). More EVT patients were discharged home from acute care (50% vs. 18%, p = 0.002). Among survivors, there were nonsignificant trends in favor of EVT for median length of hospitalization (14 vs. 41 days, p = 0.11) and functional independence at follow-up (51% vs. 32%, p = 0.079).
EVT improved survival and decreased disability. This demonstration of single-center effectiveness may help facilitate expansion of EVT services in similar health-care jurisdictions.
Endovascular thrombectomy (EVT) is efficacious for ischemic stroke caused by proximal intracranial large-vessel occlusion involving the anterior cerebral circulation. However, evidence of its cost-effectiveness, especially in a real-world setting, is limited. We assessed whether EVT ± tissue plasminogen activator (tPA) was cost-effective when compared with standard care ± tPA at our center.
We identified patients treated with EVT ± tPA after the Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with Emphasis on minimizing computed tomography to recanalization times trial from our prospective stroke registry from February 1, 2013 to January 31, 2017. Patients admitted before February 2013 and treated with standard care ± tPA constitute the controls. The sample size was 88. Cost-effectiveness was assessed using the net monetary benefit (NMB). Differences in average costs and quality-adjusted life years (QALYs) were estimated using the augmented inverse probability weighted estimator. We accounted for sampling and methodological uncertainty in sensitivity analyses.
Patients treated with EVT ± tPA had a net gain of 2.89 [95% confidence interval (CI): 0.93–4.99] QALYs at an additional cost of $22,200 (95% CI: −28,902–78,244) per patient compared with the standard care ± tPA group. The NMB was $122,300 (95% CI: −4777–253,133) with a 0.85 probability of being cost-effective. The expected savings to the healthcare system would amount to $321,334 per year.
EVT ± tPA had higher costs and higher QALYs compared with the control, and is likely to be cost-effective at a willingness-to-pay threshold of $50,000 per QALY.
A greater understanding of the rumen microbiota and its function may help find new strategies to improve feed efficiency in cattle. This study aimed to investigate whether the cattle breed affects specific ruminal taxonomic microbial groups and functions associated with feed conversion ratio (FCR), using two genetically related Angus breeds as a model. Total RNA was extracted from 24 rumen content samples collected from purebred Black and Red Angus bulls fed the same forage diet and then subjected to metatranscriptomic analysis. Multivariate discriminant analysis (sparse partial least square discriminant analysis (sPLS-DA)) and analysis of composition of microbiomes were conducted to identify microbial signatures characterizing Black and Red Angus cattle. Our analyses revealed relationships among bacterial signatures, host breeds and FCR. Although Black and Red Angus are genetically similar, sPLS-DA detected 25 bacterial species and 10 functions that differentiated the rumen microbial signatures between those two breeds. In Black Angus, we identified bacterial taxa Chitinophaga pinensis, Clostridium stercorarium and microbial functions with large and small subunits ribosomal proteins L16 and S7 exhibiting a higher abundance in the rumen microbiome. In Red Angus, nonetheless, we identified the poorly characterized bacterial taxon Oscillibacter valericigenes with a higher abundance and pathways related to carbohydrate metabolism. Analysis of composition of microbiomes revealed that C. pinensis and C. stercorarium exhibited a higher abundance in Black Angus compared to Red Angus associated with FCR, suggesting that these bacterial species may play a key role in the feed conversion efficiency of forage-fed bulls. This study highlights how the discovery of signatures of bacterial taxa and their functions can be used to harness the full potential of the rumen microbiome in Angus cattle.
Some studies have shown that the excessive metabolic heat production is the primary cause for dead chicken embryos during late embryonic development. Increasing heat shock protein (HSP) expression and adjusting metabolism are important ways to maintain body homeostasis under heat stress. This study was conducted to investigate the effects of in ovo injection (IOI) of vitamin C (VC) at embryonic age 11th day (E11) on HSP and metabolic genes expression. A total of 320 breeder eggs were randomly divided into normal saline and VC injection groups. We detected plasma VC content and rectal temperature at chick’s age 1st day, and the mRNA levels of HSP and metabolic genes in embryonic livers at E14, 16 and 18, analysed the promoter methylation levels of differentially expressed genes and predicted transcription factors at the promoter regions. The results showed that IOI of VC significantly increased plasma VC content and decreased rectal temperature (P < 0.05). In ovo injection of VC significantly increased heat shock protein 60 (HSP60) and pyruvate dehydrogenase kinase 4 (PDK4) genes expression at E16 and PDK4 and secreted frizzled related protein 1 (SFRP1) at E18 (P < 0.05). At E16, IOI of VC significantly decreased the methylation levels of total CpG sites and −336 CpG site in HSP60 promoter and −1137 CpG site in PDK4 promoter (P < 0.05). Potential binding sites for nuclear factor-1 were found around −389 and −336 CpG sites in HSP60 promoter and potential binding site for specificity protein 1 was found around −1137 CpG site in PDK4 promoter. Our results suggested that IOI of VC increased HSP60, PDK4 and SFRP1 genes expression at E16 and 18, which may be associated with the demethylation in gene promoters. Whether IOI of VC could improve hatchability needs to be further verified by setting uninjection group.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Nitroethane (NE), 2-nitroethanol (NEOH) and 2-nitro-1-propanol (NPOH) were investigated in order to determine their inhibitory effects on in vitro ruminal fermentation and methane (CH4) production of a hay-rich substrate (alfalfa hay: maize meal = 4:1, w/w). The rumen liquor collected from cannulated Holstein dairy cows was incubated at 39 °C for 72 h. The addition of NE, NEOH and NPOH slowed down the fermentation process and notably decreased molar CH4 proportion by 96.8, 96.4 and 35.0%, respectively. The abundance of total methanogen and methanogens from the order Methanobacteriales were all decreased with NE, NEOH and NPOH supplementation. Meanwhile, the nitrocompound addition reduced mcrA gene expression, coenzyme F420 and F430 contents. The correlation analysis showed that CH4 production was correlated positively with the population abundance of total methanogens, Methanobacteriales, mcrA gene expression, coenzyme contents of F420 and F430. The nitrocompound addition decreased acetate concentration and increased propionate and butyrate concentrations in the culture fluid. In summary, both NE and NEOH addition presented nearly the same inhibitory effectiveness on in vitro CH4 production; they were more effective than NPOH. The results of the current study provide evidence that NE, NEOH and NPOH can dramatically decrease methanogen population, mcrA gene expression and the coenzyme content of F420 and F430 in ruminal methanogenesis.
While assessing the environmental impact of nuclear power plants, researchers have focused their attention on radiocarbon (14C) owing to its high mobility in the environment and important radiological impact on human beings. The 10 MW high-temperature gas-cooled reactor (HTR-10) is the first pebble-bed gas-cooled test reactor in China that adopted helium as primary coolant and graphite spheres containing tristructural-isotropic (TRISO) coated particles as fuel elements. A series of experiments on the 14C source terms in HTR-10 was conducted: (1) measurement of the specific activity and distribution of typical nuclides in the irradiated graphite spheres from the core, (2) measurement of the activity concentration of 14C in the primary coolant, and (3) measurement of the amount of 14C discharged in the effluent from the stack. All experimental data on 14C available for HTR-10 were summarized and analyzed using theoretical calculations. A sensitivity study on the total porosity, open porosity, and percentage of closed pores that became open after irradiating the matrix graphite was performed to illustrate their effects on the activity concentration of 14C in the primary coolant and activity amount of 14C in various deduction routes.
Two-dimensional particle-in-cell (PIC) simulations have been used to investigate the interaction between a laser pulse and a foil exposed to an external strong longitudinal magnetic field. Compared with that in the absence of the external magnetic field, the divergence of proton with the magnetic field in radiation pressure acceleration (RPA) regimes has improved remarkably due to the restriction of the electron transverse expansion. During the RPA process, the foil develops into a typical bubble-like shape resulting from the combined action of transversal ponderomotive force and instabilities. However, the foil prefers to be in a cone-like shape by using the magnetic field. The dependence of proton divergence on the strength of magnetic field has been studied, and an optimal magnetic field of nearly 60 kT is achieved in these simulations.
Copy number variations (CNVs), as an important source of genetic variation, can affect a wide range of phenotypes by diverse mechanisms. The somatostatin receptor 2 (SSTR2) gene plays important roles in cell proliferation and apoptosis. Recently, this gene was mapped to a CNV region, which encompasses quantitative trait loci of cattle economic traits including body weight, marbling score, etc. Therefore, SSTR2 CNV may exhibit phenotypic effects on cattle growth traits. In the current study, distribution of SSTR2 gene CNVs was investigated in six Chinese cattle breeds (XN, QC, NY, JA, LX and PN), and the results showed higher CNV polymorphisms in XN, QC and NY cattle. Next, association analysis between growth traits and SSTR2 CNV was performed for XN, QC and NY cattle. In NY, individuals with fewer copies showed better performance than those with more copies. Further, the effects of SSTR2 CNV on the SSTR2 mRNA level were also investigated, but revealed no significant correlation in either muscle or adipose tissue of adult NY cattle. The results suggested the potential for use of SSTR2 CNV as a marker for the molecular breeding of NY cattle.
The very high temperature reactor (VHTR) is a development of the high-temperature gas-cooled reactors (HTGRs) and one of the six proposed Generation IV reactor concept candidates. The 10 MW high temperature gas-cooled reactor (HTR-10) is the first pebble-bed gas-cooled test reactor in China. A sampling system for the measurement of carbon-14 (14C) was established in the helium purification system of the HTR-10 primary loop, which could sample 14C from the coolant at three locations. The results showed that activity concentration of 14C in the HTR-10 primary coolant was 1.2(1) × 102 Bq/m3 (STP). The production mechanisms, distribution characteristics, reduction routes, and release types of 14C in HTR-10 were analyzed and discussed. A theoretical model was built to calculate the amount of 14C in the core of HTR-10 and its concentration in the primary coolant. The activation reaction of 13C has been identified to be the dominant 14C source in the core, whereas in the primary coolant, it is the activation of 14N. These results can supplement important information for the source term analysis of 14C in HTR-10 and promote the study of 14C in HTGRs.
Heavy alcohol use is pervasive and one of our most significant global health burdens. Early theories posited that certain alcohol response phenotypes, notably low sensitivity to alcohol (‘low-level response’) imparts risk for alcohol use disorder (AUD). However, other theories, and newer measures of subjective alcohol responses, have challenged that contention and argued that high sensitivity to some alcohol effects are equally important for AUD risk. This study presents results of a unique longitudinal study in 294 young adult non-dependent drinkers examined with alcohol and placebo testing in the laboratory at initial enrolment and repeated 5 years later, with regular follow-up intervals assessing AUD (trial registration: http://clinicaltrials.gov/ct2/show/NCT00961792). Findings showed that alcohol sedation was negatively correlated with stimulation across the breath alcohol curve and at initial and re-examination testing. A higher rather than lower alcohol response phenotype was predictive of future AUD. The findings underscore a new understanding of factors increasing vulnerability to AUD.
Beijing–Tianjin–Hebei is the largest urban agglomeration in northern China, but the spatiotemporal patterns and risk factors concerning hepatitis B virus (HBV) incidence in this area have been unclear. The present study aimed to reveal the spatiotemporal epidemiological features of HBV infection and quantify the association between HBV infection and socio-economic risk factors. The data on HBV cases in Beijing–Tianjin–Hebei from 2007 to 2012 was collected for each county. The Bayesian space–time hierarchy model and the GeoDetector method were used to reveal spatiotemporal patterns and detect risk factors. High-risk regions were mainly distributed in the underdeveloped rural areas in the north and mid-south of the study region, while low-risk regions were mainly distributed in the urban and western areas. The HBV annual incidence rate decreased substantially over the 6-year period, dropping from 7.34/105 to 5.51/105. Compared with this overall trend, 38.5% of high-risk counties showed a faster decrease, and 35.9% of high-risk counties exhibited a slower decrease. Meanwhile, 29.7% of low-risk counties had a faster decrease, and 44.6% of low-risk counties exhibited a slower decrease. Socio-economic factors were strongly associated with the spatiotemporal patterns and variation. The population density and gross domestic product per capita were negatively associated with HBV transmission, with determinant powers of 0.17 and 0.12, respectively. The proportion of primary industry and the number of healthcare workers were positively associated with the disease incidence, with determinant powers of 0.11 and 0.8, respectively. The interactive effect between population density and the other factors exerted a greater influence on HBV transmission than that of these factors measured independently.
Starch digestion in the small intestines of the dairy cow is low, to a large extent, due to a shortage of syntheses of α-amylase. One strategy to improve the situation is to enhance the synthesis of α-amylase. The mammalian target of rapamycin (mTOR) signalling pathway, which acts as a central regulator of protein synthesis, can be activated by leucine. Our objectives were to investigate the effects of leucine on the mTOR signalling pathway and to define the associations between these signalling activities and the synthesis of pancreatic enzymes using an in vitro model of cultured Holstein dairy calf pancreatic tissue. The pancreatic tissue was incubated in culture medium containing l-leucine for 3 h, and samples were collected hourly, with the control being included but not containing l-leucine. The leucine supplementation increased α-amylase and trypsin activities and the messenger RNA expression of their coding genes (P <0.05), and it enhanced the mTOR synthesis and the phosphorylation of mTOR, ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E-binding protein 1 (P <0.05). In addition, rapamycin inhibited the mTOR signal pathway factors during leucine treatment. In sum, the leucine regulates α-amylase and trypsin synthesis in dairy calves through the regulation of the mTOR signal pathways.
The strong-coupling mode, called the “quasimode”, is excited by stimulated Brillouin scattering (SBS) in high-intensity laser–plasma interactions. Also SBS of the quasimode competes with SBS of the fast mode (or slow mode) in multi-ion species plasmas, thus leading to a low-frequency burst behavior of SBS reflectivity. Competition between the quasimode and the ion-acoustic wave (IAW) is an important saturation mechanism of SBS in high-intensity laser–plasma interactions. These results give a clear explanation of the low-frequency periodic burst behavior of SBS and should be considered as a saturation mechanism of SBS in high-intensity laser–plasma interactions.