Search

We present the results of the neutron star X-ray binary system Cen X-3 performed by Insight -HXMT with two observations during 2017 and 2018. During these two observations, the source reached a X-ray luminosity of ∼1038 erg s−1 from 2–105 keV. The analysis of the broadband X-ray spectrum reports the presence of two cyclotron resonance scattering features (CRSFs) with the fundamental line at ∼ 28 keV and the harmonic line at ∼47 keV. The multiple lines exist by fittings with different continuum models, like the absorbed negative and positive power-law with an exponential cutoff (NPEX) model and a power-law with high energy exponential cutoff model. This is the first time that both fundamental and harmonic lines are detected in Cen X-3. We also show evidence of two cyclotron lines in the phase-resolved spectrum of Cen X-3. The CRSF and continuum spectral parameters show evolution with the pulse profile, and the two line centroid energy ratio does not change significantly and locates in a narrow value range of 1.6−1.7 over the pulse phase. The implications of the discovering two cyclotron absorption features and phase-resolved spectral properties are discussed. [ABSTRACT FROM AUTHOR]

Milk fat determines the quality of milk and is also a main targeted trait in dairy cow breeding. Recent studies have revealed important regulatory roles of microRNAs (miRNA) in milk fat synthesis in the mammary gland. However, the role of miRNA in bovine mammary epithelial cells (BMEC) remains largely unknown. In this study, we found that the overexpression of miR-130a significantly decreased cellular triacylglycerol (TAG) levels and suppressed lipid droplet formation, whereas the inhibition of miR-130a resulted in greater lipid droplet formation and TAG accumulation in BMEC. MiR-130a also significantly affected mRNA expression related to milk fat metabolism. Specifically, the overexpression of miR-130a reduced the mRNA expression of PPARG, FABP3, PLIN2, and FATP1, whereas the downregulation of miR-130a increased the mRNA expression of PPARG, C/EBPβ, C/EBPα, PLIN2, FABP3, and FATP1. Furthermore, western blot analysis revealed the protein level of PPARG in miR-130a mimic and inhibitor transfection groups to be consistent with the mRNA expression response. Finally, luciferase reporter assays verified that PPARG was the direct target of miR-130a. This study provides the first experimental evidence that miR-130a directly affects TAG synthesis in BMEC by targeting PPARG, suggesting that miR-130a potentially could be used to improve beneficial milk components in dairy cows. [ABSTRACT FROM AUTHOR]

Depletion and dysfunction of dendritic cells in the lung can induce local immunoparalysis, which often leads to multiple organ dysfunction syndrome (MODS)-associated mortality. A therapeutic strategy that reverses this immunoparalysis is required. In the present study, we examined the effects of in vivo Fms-like tyrosine kinase 3 ligand (Flt3L) treatment on zymosan (zym)-induced secondary lung injury and dendritic cell (DC) immunoparalysis. BALBc mice were divided randomly into four groups (20/group): (1) sham [intraperitoneal (i.p.) saline] + vehicle [subcutaneous (s.c.) 0·01% mouse serum albumin]; (2) sham + Flt3L (s.c.); (3) zym (i.p.) + vehicle; and (4) zym + Flt3L. Injections were for 9 consecutive days; 12 days later we examined: survival rate (monitored for 12 days); lung tissue histopathology (haematoxylin and eosin staining); plasma indices of lung function (pH, PaO2, PaCO2, HCO3-); DC subsets in lung tissue; and lung DCs production of interleukin (IL)-12p70 and IL-10. Zym administration resulted in increased mortality associated with significant lung histopathological changes and abnormal blood gas indices; however, these pathological changes were ameliorated by Flt3L treatment. Zym injections also resulted in significant reductions in DC subsets recovered from lungs [CD11c+major histocompatibility complex (MHC)-II/I-Ad+, CD11c+CD11b+ and CD11c+B220+]. Importantly, in-vivo Flt3L treatment reversed these trends for DC immunoparalysis by increasing the percentages of recovered DC subsets concomitant with increased DC production of IL-12 p70 and decreased IL-10 production. These results suggest that Flt3L may have therapeutic potential for reversing DC immunoparalysis and ameliorating lung injury secondary to MODS. [ABSTRACT FROM AUTHOR]

The single-degenerate model is the most widely accepted progenitor model of Type Ia supernovae (SNe Ia), where a carbon–oxygen white dwarf (CO WD) accretes hydrogen-rich material from its companion to increase its mass. The companion may be a main-sequence (MS) star or a subgiant star (WD + MS). When the CO WD approaches the Chandrasekhar mass limit, it explodes as a SN Ia and part of the supernova ejecta collides into the companion envelope. After the impact of the ejecta, the companion survives and may show some special properties. A good way to verify the single-degenerate model is to study the interaction between the supernova ejecta and the companion, and/or search for the companion in the remnant of a SN Ia. Following previous studies, we have carried out a series of binary population synthesis studies exploring the properties of the companions of SNe Ia for different metallicities Z. We present the distributions of the masses , radii of the companions, periods PSN and ratios of separations to radii of WD + MS systems for various Z at the moment of supernova explosion. These parameters can be applied to constrain the numerical simulation of the interaction between the ejecta of a supernova and its companion. We also show the distributions of some integral properties of the companions, i.e. the mass, the space velocity and the surface gravity, for various Z after the interaction. The distributions may help us to search for the companion in a supernova remnant. All the parameters above change significantly with Z. Incorporating the simulation results of the interaction between supernova ejecta and companions from other works into our binary population synthesis study, we found that more than 75 per cent of all supernovae have a strong enough polarization signal to be detected by spectropolarimetric observations. We also found that 13–14 per cent of SNe Ia belong to the class of supernovae like 1991T, which is consistent with observations within the errors. This may indicate that 1991T-like SNe do not have any special physical properties except for the viewing angle of the observer. [ABSTRACT FROM AUTHOR]

We investigated the quasi-periodic oscillation (QPO) features in the accretion-powered X-ray pulsar Cen X-3 observed by Insight-HXMT. For two observations in 2020 when Cen X-3 was in an extremely soft state, the power density spectrum revealed the presence of obvious QPO features at ∼40 mHz with an averaged fractional rms amplitude of ∼9 per cent. We study the mHz QPO frequency and rms amplitude over orbital phases, and find that the QPO frequency is ∼33–39 mHz at the orbital phase of 0.1–0.4, increasing to ∼37–43 mHz in the orbital phase of 0.4–0.8, but has no strong dependence on X-ray intensity. We also carried out an energy-dependent QPO analysis, the rms amplitude of the mHz QPOs have a decreasing trend as the energy increases from 2 to 20 keV. In addition, the QPO time-lag analysis shows that the time-delay is ∼20 ms (a hard lag) in the range of ∼5–10 keV, and becomes negative [time-lag of −(20–70) ms] above ∼10 keV. The different QPO theoretical models are summarized and discussed. In the end, we suggest that these energy-dependent timing features as well as the origin of mHz QPOs in Cen X-3 may be ascribed to an instability when the accretion disc is truncated near the corotation radius. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effects of grain (corn vs. wheat) and starch concentrations (low vs. high starch) on ruminal pH, milk production, and inflammatory response in dairy goats. Eight ruminally cannulated lactating goats (34 ± 3.1 kg of BW and 180 ± 8.2 d in milk) were used in a crossover design with a 2 × 2 factorial arrangement. Each period lasted for 27 d. During the first 10 d, goats were fed low-starch (LS) diets (d 8 to 10 for data collection); d 11 to 17, they were transitioned to high-starch (HS) diet; d 18 to 25, the goats were fed the HS diet; and data was collected d 25 to 27. Goats were fed a total mixed diet ad libitum twice daily. Diets were formulated as isonitrogenous (13.6%) and isoenergetic with forage-to-concentrate ratios of 60:40 and 35:65 for LS (24%) and HS (39% starch, DM basis) diets, respectively. Data were analyzed using PROC MIXED of SAS with model including diets as fixed effects and random effect of period and animal. Intake of DM (averaged 1.06 kg/d) was affected neither by grain source nor by starch concentration. However, goats fed the HS diet produced more (P < 0.05) milk (0.82 vs. 0.67 kg/d) and lactose (35.0 vs. 27.3 g/d) than goats fed the LS diet. Ruminal pH (averaged 6.15) did not differ but duration of pH < 5.6 was longer (P < 0.05) with wheat (232 min/d) than with corn (140 min/d). Ruminal pH was greater (6.16 vs. 5.87; P < 0.05) and duration of pH < 5.6 was shorter (33 vs. 339 min) for the HS diet than the LS diet. Concentration of ruminal lipopolysaccharide (LPS) was greater (P < 0.05) with wheat than with corn (35.5 vs. 22.1 ×10³ EU/mL). Goats fed the HS diet also had greater (P < 0.05) LPS concentration in ruminal fluid (40.3 vs. 17.3 × 10³ EU/mL) than goats fed the LS diet. Blood concentration of serum amyloid A (SAA; 75.7 vs. 62.7 μg/mL), haptoglobin (Hp; 96.3 vs. 91.6 μg/mL), and LPS binding protein (LBP; 2.3 vs. 1.6 μg/mL) were not affected by grain source, but goats fed the HS diet had more (P < 0.05) SAA (89.3 vs. 49.1), Hp (116.7 vs. 71.2), and LBP (2.4 vs. 1.5 μg/mL) than goats fed the LS diet. These results indicated that replacing corn with wheat in a lactating goat diet had little impact on ruminal pH and milk production. However, increasing starch concentration in goat diets is beneficial to improve milk production and immune activity by stimulating inflammatory response. [ABSTRACT FROM AUTHOR]

Background: Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is a new determinate syndrome whose exact characteristics remain unclear. Aim: The objective of this study is to find more difference between ACOS and COPD. Design: A retrospective study of ACOS and COPD in Chinese. Methods: Data from 65 patients with ACOS and 65 patients with COPD were retrospectively collected and analyzed. The basis of this study was to compare the two groups while ruling out differences in age, sex and smoking history. Results: Patients with ACOS tended to have earlier ages of onset, longer durations of symptoms, better nutritional status, higher single-breath diffusing capacity of carbon monoxide (DLCO) %predicted and airway resistance %predicted, more exacerbations in the preceding 12 months and shorter lengths of hospitalization. DLCO %predicted, airway resistance %predicted, and length of hospitalization were the variables most significantly associated with the presence of ACOS in patients with COPD. ROC correlating airway resistance %predicted value and current ACOS showed an optimal cutoff of airway resistance %predicted of over 296.6. During follow-up (median: 45 months; interquartile range: 6-82 months), 16 patient deaths were recorded (3 patients with ACOS). The risk remained significantly higher in patients with COPD alone than in patients with ACOS (HR 3.932; 95% CI 1.083-19.755; P=0.046). Conclusion: Patients with ACOS were more likely to have better prognoses and lower mortality than those with COPD alone, though with greater exacerbation frequency. [ABSTRACT FROM AUTHOR]

We estimate limits on non-universal coupling of hypothetical hidden fields to standard matter by evaluating the fractional changes in the electron-to-proton mass ratio, μ = m e/ m p, based on observations of Class I methanol masers distributed in the Milky Way disc over the range of the Galactocentric distances |$4 \lesssim R \lesssim 12$| kpc. The velocity offsets Δ V  = V 44 − V 95 measured between the 44- and 95-GHz methanol lines provide, so far, one of the most stringent constraints on the spatial gradient k μ ≡ d(Δμ/μ)/d R < 2 × 10−9 kpc−1 and the upper limit on Δμ/μ <2 × 10−8, where Δμ/μ =  |$(\mu _{\rm \scriptscriptstyle obs}-\mu _{\rm \scriptscriptstyle lab})/\mu _{\rm \scriptscriptstyle lab}$|⁠. We also find that the offsets Δ V are clustered into two groups which are separated by |$\delta _{\scriptscriptstyle \Delta V} = 0.022 \pm 0.003$| km s−1 (1σ confidence level). The grouping is most probably due to the dominance of different hyperfine transitions in the 44- and 95-GHz methanol maser emission. Which transition becomes favoured is determined by an alignment (polarization) of the nuclear spins of the four hydrogen atoms in the methanol molecule. This result confirms that there are preferred hyperfine transitions involved in the methanol maser action. [ABSTRACT FROM AUTHOR]

Study Question: What is the transcriptome signature associated with poor performance of rescue IVM (rIVM) oocytes and how can we rejuvenate them?Summary Answer: The GATA-1/CREB1/WNT signalling axis was repressed in rIVM oocytes, particularly those of poor quality; restoration of this axis may produce more usable rIVM oocytes.What Is Known Already: rIVM aims to produce mature oocytes (MII) for IVF through IVM of immature oocytes collected from stimulated ovaries. It is not popular due to limited success rate in infertility treatment. Genetic aberrations, cellular stress and the absence of cumulus cell support in oocytes could account for the failure of rIVM.Study Design, Size, Duration: We applied single-cell RNA sequencing (scRNA-seq) to capture the transcriptomes of human in vivo oocytes (IVO) (n = 10) from 7 donors and rIVM oocytes (n = 10) from 10 donors. The effects of maternal age and ovarian responses on rIVM oocyte transcriptomes were also studied. In parallel, we studied the effect of gallic acid on the maturation rate of mouse oocytes cultured in IVM medium with (n = 84) and without (n = 85) gallic acid.Participants/materials, Setting, Methods: Human oocytes were collected from donors aged 28-41 years with a body mass index of <30. RNA extraction, cDNA generation, library construction and sequencing were performed in one preparation. scRNA-seq data were then processed and analysed. Selected genes in the rIVM versus IVO comparison were validated by quantitative real-time PCR. For the gallic acid study, we collected immature oocytes from 5-month-old mice and studied the effect of 10-μM gallic acid on their maturation rate.Main Results and the Role Of Chance: The transcriptome profiles of rIVM/IVO oocytes showed distinctive differences. A total of 1559 differentially expressed genes (DEGs, genes with at least 2-fold change and adjusted P < 0.05) were found to be enriched in metabolic processes, biosynthesis and oxidative phosphorylation. Among these DEGs, we identified a repression of WNT/β-catenin signalling in rIVM when compared with IVO oocytes. We found that oestradiol levels exhibited a significant age-independent correlation with the IVO mature oocyte ratio (MII ratio) for each donor. rIVM oocytes from women with a high MII ratio were found to have over-represented cellular processes such as anti-apoptosis. To further identify targets that contribute to the poor clinical outcomes of rIVM, we compared oocytes collected from young donors with a high MII ratio with oocytes from donors of advanced maternal age and lower MII ratio, and revealed that CREB1 is an important regulator. Thus, our study identified that GATA-1/CREB1/WNT signalling was repressed in both rIVM oocytes versus IVO oocytes and in rIVM oocytes of lower versus higher quality. Consequently we investigated gallic acid, as a potential antioxidant substrate in human rIVM medium, and found that it increased the mouse oocyte maturation rate by 31.1%.Large Scale Data: Raw data from this study can be accessed through GSE158539.Limitations, Reasons For Caution: In the rIVM oocytes of the high- and low-quality comparison, the number of samples was limited after data filtering with stringent selection criteria. For the oocyte stage identification, we were unable to predict the presence of oocyte spindle, so polar body extrusion was the only indicator.Wider Implications Of the Findings: This study showed that GATA-1/CREB1/WNT signalling was repressed in rIVM oocytes compared with IVO oocytes and was further downregulated in low-quality rIVM oocytes, providing us the foundation of subsequent follow-up research on human oocytes and raising safety concerns about the clinical use of rescued oocytes.Study Funding/competing Interest(s): This work was supported by the Collaborative Research Fund, Research Grants Council, C4054-16G, and Research Committee Funding (Research Sustainability of Major RGC Funding Schemes), The Chinese University of Hong Kong. The authors have no conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

We analyse five seasons of short-cadence data of a solar-type star of spectral type F: KIC 6225718 observed by Kepler. We obtain the power spectrum of this star by applying the Lomb–Scargle periodogram to the smoothed time series. By applying the autocorrelation technique to the power spectrum, we derive the large-frequency separation Δν = 105.78 ± 0.65 μHz and the frequency of maximum power νmax = 2301 ± 21 μHz. We identify 33 p modes with angular degrees of l = 0–2 in the frequency range 1600–2800 μHz of the power spectrum with Bayesian Markov Chain Monte Carlo algorithms. In order to determine the parameters of the star accurately, we construct a grid of stellar models with core overshooting using the Yale stellar evolution code and then perform preliminary seismological analysis. With both asteroseismic and non-asteroseismic constraints, the following range of stellar parameters is estimated: mass $M=1.10^{+0.04}_{-0.03} \,\mathrm{M}_{{{\odot }}}$, radius $R = 1.22^{+0.01}_{-0.01}\,\mathrm{R}_{{{\odot }}}$ and age $t=3.35^{+0.36}_{-0.75}$ Gyr for this star. In addition, we analyse the effects of overshooting on stellar interiors and find that the upper limit of the overshooting parameter αov is approximately 0.2 for this star. [ABSTRACT FROM AUTHOR]

Crosswell seismic data recorded at 620–650 m offsets in an oil-bearing sand/shale reservoir formation at the Liaohe Oil Field, northeast China, provide robust evidence for waveguide action by low-velocity reservoir layers. Crosswell-section velocity models derived from survey-well sonic logs and further constrained by observed waveguide seismic wavegroup amplitudes and phases yield plausible evidence for interwell reservoir–sand continuity and discontinuity. A pair of back-to-back Liaohe crosswell vector-seismic surveys were conducted using a source well between two sensor wells at 650 and 620 m offsets along a 200-m-thick reservoir formation dipping 7° down-to-east between depths of 2.5 and 3 km. A downhole orbital vibrator generated seismic correlation wavelets with frequency range 50–350 Hz and signal/noise ratio up to 5:1 over local downhole ambient noise. The sensor wells were instrumented with a mobile 12- to 16-level string of clamped vector-motion sensor modules at 5 m intervals. Using 5 m source depth increments, crosswell Surveys 1 and 2 cover source/sensor well intervals above and through the reservoir of, respectively, 600 m/600 m (13 000 vector traces in 9 common sensor fans) and 300 m/560 m (7000 vector traces in 7 common sensor fans). Survey 1 common sensor gathers show clear, consistent high-amplitude 20 ms waveletgroup lags behind the first-arrival traveltime envelope. Such arrivals are diagnostic of seismic low-velocity waveguides connecting the source and sensor wells. Observed Survey 1 retarded wavegroup depths tally with source and sensor depths in low-velocity layers identified in sonic well logs. Finite-difference acoustic model wavefields computed for waveguide acoustic layers constrained by well-log sonic velocity data match the observed waveguide traveltime and amplitude systematics. Model waveforms duplicate the observed m-scale and ms-scale sensitivity of waveguide spatio-temporal energy localization. Survey 2 crosswell data, in contrast, provide no comparable evidence for waveguide action despite a sensor-well sonic well log similar to that of Survey 1. Instead, acoustic wavefield modelling of Survey 2 data clearly favours an interpreted waveguide model with 10° downdip interrupted by a 75–100 m throw down-fault near the sensor well. The absence of clear waveguide arrivals is adequately explained by dispersal of waveguide energy at the fault discontinuity. Auxiliary well sonic velocity and lithologic logs confirm the model-implied 75–100 m of down-throw faulting near the sensor well. [ABSTRACT FROM AUTHOR]

Brain and spinal arteriovenous malformations are congenital lesions causing intracranial haemorrhage or permanent disability especially in young people. We investigated whether the vast majority or all brain and spinal arteriovenous malformations are associated with detectable tumour-related somatic mutations. In a cohort of 31 patients (21 with brain and 10 with spinal arteriovenous malformations), tissue and paired blood samples were analysed with ultradeep next generation sequencing of a panel of 422 common tumour genes to identify the somatic mutations. We used droplet digital polymerase chain reaction to confirm the panel sequenced mutations and identify the additional low variant frequency mutations. The association of mutation variant frequencies and clinical features were analysed. The average sequencing depth was 1077 ± 298×. High prevalence (87.1%) of KRAS/BRAF somatic mutations was found in brain and spinal arteriovenous malformations with no other replicated tumour-related mutations. The prevalence of KRAS/BRAF mutation was 81.0% (17 of 21) in brain and 100% (10 of 10) in spinal arteriovenous malformations. We detected activating BRAF mutations and two novel mutations in KRAS (p.G12A and p.S65_A66insDS) in CNS arteriovenous malformations for the first time. The mutation variant frequencies were negatively correlated with nidus volumes of brain (P = 0.038) and spinal (P = 0.028) arteriovenous malformations but not ages. Our findings support a causative role of somatic tumour-related mutations of KRAS/BRAF in the overwhelming majority of brain and spinal arteriovenous malformations. This pathway homogeneity and high prevalence implies the development of targeted therapies with RAS/RAF pathway inhibitors without the necessity of tissue genetic diagnosis.10.1093/brain/awy307_video1awy307media15978667388001. [ABSTRACT FROM AUTHOR]

Farnesyltransferase inhibitors have been tested in clinical trials for the treatment of tumours. In sepsis, the binding of programmed death 1 (PD-1) to programmed death ligand 1 (PD-L1) promotes lymphocyte apoptosis and decreases cytokine expression, thus affecting survival rates. The PD-1/PD-L1 pathway plays an important role in chronic viral infection, bacterial infection and sepsis. However, the precise immunosuppressive and anti-inflammatory functions of this pathway remain poorly understood. In our previous study, the induction of sepsis by caecal ligation and puncture (CLP) resulted in increased farnesyltransferase activity and farnesylated protein levels in the spleen relative to sham treatment. However, the effect of inhibition of farnesyltransferase activity on overall survival rates in patients with sepsis and the specific signalling pathway involved remain to be investigated. In this study, mice with CLP-induced sepsis were treated with farnesyltransferase inhibitor (FTI-277), and PD-L1 expression on septic spleen lymphocytes was examined. Flow cytometric analysis revealed that PD-L1 is expressed constitutively on lymphocytes and that PD-L1 protein expression was up-regulated strongly following CLP. FTI-277 down-regulated PD-L1 mRNA and protein expression on septic spleen lymphocytes in a dose-dependent manner. This effect was associated closely with nuclear factor kappa B (NF-κB). In addition, the significant damping effect of FTI-277 on the PD-L1 signal promoted interferon (IFN)-γ secretion, interleukin (IL)-2 production and splenocyte proliferation in response to anti-CD3+CD28+ antibodies in mice. Furthermore, FTI-277 reduced spleen lymphocyte apoptosis in septic mice. Therefore, FTI-277 regulates spleen lymphocyte activity via the PD-L1 signalling pathway, with significant anti-inflammatory effects attributable to suppression of the NF-κB pathway. Farnesyltransferase represents a valuable therapeutic target for the treatment of sepsis. [ABSTRACT FROM AUTHOR]

We intend to use stellar models with and without α-enhancement, as well as asteroseismic analysis, to study two α-enhanced stars, KIC 7976303 and KIC 8694723. For the α-enhanced models, we adopt [α/Fe] = 0.2 and 0.4. For the evolved subgiant KIC 7976303 with mixed modes, the α-enhanced models fit the observations better than the models without α-enhancement, and point to a star with M = 1.20 ± 0.02M⊙, t = 4.88 ± 0.08Gyr, R = 2.04 ± 0.01 R⊙ and L = 5.07 ± 0.05 L⊙. For the post turn-off star KIC 8694723, we find that the models fit the observations well in all three cases ([α/Fe] = 0.0, 0.2 and 0.4). According to the observed metal abundances, only α-enhanced models are used to estimate the stellar parameters, which are M = 1.13 ± 0.06M⊙, t = 5.47 ± 0.43Gyr, R = 1.55 ± 0.13 R⊙ and L = 3.18 ± 0.26 L⊙. Our α-enhanced models indicate that KIC 7976303 has a larger mass and younger age than in previous works based on standard models. Furthermore, the differences of estimated mass and age between the three cases are~0.1M⊙ and ~0.5-1.3Gyr. These results suggest that we include α-enhancement in the modelling of α-enhanced stars, such as members of globular clusters and metal-poor stars in the disc and in the halo. [ABSTRACT FROM AUTHOR]

Objective: Hypersplenism is a common disease. The conventional treatment is splenectomy and partial splenic embolization; however, both of them have high complication rates and technical defects. Therefore, safer and more effective techniques should be considered for the treatment of hypersplenism. High-intensity focused ultrasound (HIFU) may provide an effective and safe way for treatment of hypersplenism. Therefore, we conducted this study to assess the safety and efficacy of HIFU in treatment of secondary hypersplenism. Methods: A to ta l of 28 patients who suffered from secondary hypersplenism were treated w ith HIFU ablation. All patients who underwent HIFU were closely followe dup over a year. MRI scan was performed, and the spleens were observed. Blood counts and liver function tests were also carried out. Results: In the follow-up process, the levels of white blood cells and platelets in the blood after HIFU were significantly higher than those before HIFU, liver function also improved after HIFU treatment. In addition, the symptoms were ameliorated significantly or even disappeared. The MRI showed that the ablation area had turned into a non-perfused volume, and after 12 months of HIFU ablation, the ablated area shrank evidently; the sunken spleen formed a lobulated shape and the splenic volume decreased. Conclusion: HIFU ablation is a safe, effective and noninvasive approach for secondary hypersplenism. Advances in knowledge: For the first time we used HIFU ablation to treat secondary hypersplenism. It not only expands indications of HIFU but also provides better choice for the treatment of secondary hypersplenism. [ABSTRACT FROM AUTHOR]

Hereditary angioedema ( HAE) is characterized by potentially life-threatening recurrent episodes of oedema. The open-label extension ( OLE) phase of the For Angioedema Subcutaneous Treatment ( FAST)-1 trial ( NCT00097695) evaluated the efficacy and safety of repeated icatibant exposure in adults with multiple HAE attacks. Following completion of the randomized, controlled phase, patients could receive open-label icatibant (30 mg subcutaneously) for subsequent attacks. The primary end-point was time to onset of primary symptom relief, as assessed by visual analogue scale ( VAS). Descriptive statistics were reported for cutaneous/abdominal attacks 1-10 treated in the OLE phase and individual laryngeal attacks. Post-hoc analyses were conducted in patients with ≥ 5 attacks across the controlled and OLE phases. Safety was evaluated throughout. During the OLE phase, 72 patients received icatibant for 340 attacks. For cutaneous/abdominal attacks 1-10, the median time to onset of primary symptom relief was 1·0-2·0 h. For laryngeal attacks 1-12, patient-assessed median time to initial symptom improvement was 0·3-1·2 h. Post-hoc analyses showed the time to onset of symptom relief based on composite VAS was consistent across repeated treatments with icatibant. One injection of icatibant was sufficient to treat 88·2% of attacks; rescue medication was required in 5·3% of attacks. No icatibant-related serious adverse events were reported. Icatibant provided consistent efficacy and was well tolerated for repeated treatment of HAE attacks. [ABSTRACT FROM AUTHOR]

Background: Reovirus is a naturally occurring oncolytic virus that usurps activated Ras-signaling pathways of tumor cells for its replication. Ras pathways are activated in most malignant gliomas via upstream signaling by receptor tyrosine kinases. The purpose of this study was to determine the effectiveness of reovirus as an experimental treatment for malignant gliomas.Methods: We investigated whether reovirus would infect and lyse human glioma cell lines in vitro. We also tested the effect of injecting live reovirus in vivo on human gliomas grown subcutaneously or orthotopically (i.e., intracerebrally) in mice. Finally, reovirus was tested ex vivo against low-passage cell lines derived from human glioma specimens. All P values were two-sided.Results: Reovirus killed 20 (83%) of 24 established malignant glioma cell lines tested. It caused a dramatic and often complete tumor regression in vivo in two subcutaneous (P =.0002 for both U251N and U87) and in two intracerebral (P =.0004 for U251N and P =.0009 for U87) human malignant glioma mouse models. As expected, serious toxic effects were found in these severely immunocompromised hosts. In a less immunocompromised mouse model, a single intratumoral inoculation of live reovirus led to a dramatic prolongation of survival (compared with control mice treated with dead virus; log-rank test, P<.0001 for both U251N and U87 cell lines). The animals treated with live virus also appeared to be healthier and gained body weight (P =.0001). We then tested the ability of reovirus to infect and kill primary cultures of brain tumors removed from patients and found that it killed nine (100%) of nine glioma specimens but none of the cultured meningiomas.Conclusions: Reovirus has potent activity against human malignant gliomas in vitro, in vivo, and ex vivo. Oncolysis with reovirus may be a potentially useful treatment for a broad range of human cancers. [ABSTRACT FROM AUTHOR]

Background: Human cancer cell lines grown in the presence of the cytotoxic agent mitoxantrone frequently develop resistance associated with a reduction in intracellular drug accumulation without increased expression of the known drug resistance transporters P-glycoprotein and multidrug resistance protein (also known as multidrug resistance-associated protein). Breast cancer resistance protein (BCRP) is a recently described adenosine triphosphate-binding cassette transporter associated with resistance to mitoxantrone and anthracyclines. This study was undertaken to test the prevalence of BCRP overexpression in cell lines selected for growth in the presence of mitoxantrone.Methods: Total cellular RNA or poly A+ RNA and genomic DNA were isolated from parental and drug-selected cell lines. Expression of BCRP messenger RNA (mRNA) and amplification of the BCRP gene were analyzed by northern and Southern blot hybridization, respectively.Results: A variety of drug-resistant human cancer cell lines derived by selection with mitoxantrone markedly overexpressed BCRP mRNA; these cell lines included sublines of human breast carcinoma (MCF-7), colon carcinoma (S1 and HT29), gastric carcinoma (EPG85-257), fibrosarcoma (EPF86-079), and myeloma (8226) origins. Analysis of genomic DNA from BCRP-overexpressing MCF-7/MX cells demonstrated that the BCRP gene was also amplified in these cells.Conclusions: Overexpression of BCRP mRNA is frequently observed in multidrug-resistant cell lines selected with mitoxantrone, suggesting that BCRP is likely to be a major cellular defense mechanism elicited in response to exposure to this drug. It is likely that BCRP is the putative "mitoxantrone transporter" hypothesized to be present in these cell lines. [ABSTRACT FROM AUTHOR]

We hypothesize that supplementation of live yeast or feed enzyme (FE) may improve intestinal digestion and gut health, but with ruminants, the challenge is to deliver additive with high activity post-ruminally due to the highly proteolytic environment of the rumen. The objective of this study was to develop a micro-encapsulation method by measuring ruminal stability of encapsulated yeast and FE, and its release in the intestine. Live yeast and liquid FE were encapsulated using barley protein hordein and glutelin as capsule material. The barley protein powders were hydrated at pH 11.0 to form a 15% (w/v) solution. The pH was then adjusted to 7.0 followed by an immediate mixing with yeast or FE to form a coarse emulsion using a homogenizer. Microcapsules were then formed by passing the premixed emulsion through a microfluidizer system. The mixtures were spray-dried using a laboratory scale spray dryer. The ratio of capsule to additive was 1:1. The stability of encapsulated products in the rumen was measured as DM disappearance (DMD) in batch culture. Briefly, the encapsulated products (100 mg) were weighed into Ankom bags and placed in 100-mL serum bottles. Rumen inoculant (15 mL) from beef heifer and buffer solution (45 mL) was added to each bottle and incubated at 39oC for 0, 3, 6, 12 or 24 h. The residues in bags were digested in 1% pancreatin solution for 1 h to remove the encapsulation protection. Number of yeast colonies (cfu/g) was enumerated by spread plate method. Enzyme activity (EC 3.2.1.1) was assayed and expressed as μmol glucose equivalents/min/g FE. The DMD of encapsulated yeast were 3.1, 7.8, 9.1, 12.0 or 16.0%, and the cfu were 9.5, 2.2, 1.3, 1.1 and 0.6 (× 109), respectively, for residues after 0, 3, 6, 12, and 24 h of incubation. The DMD of encapsulated FE were 5.1, 31.4, 33.8, 40.6 or 43.6%, and the enzyme activity in residue were 41.9, 33.8, 19.7, 12.7 and 10.2 µmol/min/g, respectively, at 0, 3, 6, 12 and 24 h of incubation. The results showed that the encapsulated yeast products were stable in the rumen. Subsequently, the encapsulated yeast was released by digesting in pancreatin solution and cfu counts demonstrated over 90% survival rates. It suggests that this encapsulation technique is applicable as a novel method for delivering active yeast to the intestine. However, this technique may be not efficacy to protect liquid enzyme from rumen degradation. [ABSTRACT FROM AUTHOR]

The objective of this study was to screen for the effects of live yeast (LY) or yeast derivative (YD) on DM disappearance (DMD), fermentation characteristics and microbial profiles in batch culture. The study was a 2 × 7 factorial arrangement including low (5.8) and high media pH (6.5); treatments were: control (no additives), three LY (LY1, LY2, LY3, 8 × 106 cfu/bottle for each LY), two YD (YD4, YD5, 30 mg/bottle for each YD), and monensin (positive control; 0.17 mg monensin/bottle). Substrate was a high-forage diet containing 60% barley silage and 40% concentrate (DM basis). Inoculum was obtained from two ruminally fistulated beef heifers fed the same diets to the substrate. Substrate (0.75 g) ground through a 1-mm sieve was weighed into a filter bag and incubated for 24 h in a gas-tight culture bottle in three replications by each combination of treatments. The culture was repeated at different day. Data were analyzed using mixed procedure of SAS with a model that includes fixed effects of yeast, pH level and their interactions, and the random effect of day. There was no interaction of yeast products with media pH on DMD. Increased media pH from 5.8 to 6.5 improved (P < 0.01) DMD (averaged 47 vs 54%). Supplementation of LY1 (48.2%) or YD5 (47.8%) had greater (P < 0.05) DMD than control (45.6%) or monensin (46.1%) at pH 5.8; and at pH 6.5, the DMD was greater (P < 0.05) with all 5 yeasts (averaged 54.8%) than control (52.8%) or monensin (52.7%). An interaction between pH and treatment was noticed (P < 0.02) for total VFA concentration (mM) which was greater (P < 0.05) with LY1, LY3, YD4 and YD5 (averaged 62.5) than control (57.0) and monensin (57.8) at pH 5.8. Ratio of acetate to propionate was less with monensin at either pH 5.8 (1.89) or pH 6.5 (2.22), whereas no differences were found between yeast and control. Overall, microbial profiles that were measured based on copy number of 16s rRNA gene (log10) were not affected by yeast supplementation except that the copy number of Fibrobacter succinogenes was less (P < 0.01) with monensin (7.16) than yeasts (7.95). These results suggest that in vitro DMD of high-forage diet varied with source of yeast and media pH. The improved DMD at pH 5.8 with LY1 and YD5 and at pH 6.5 with all five yeast products would be beneficial to high-forage fed cattle. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the effect of adding ruminal protected versus non-protected live yeast (LY) on DM intake, omasal flows, site and extent of feed digestion in the digestive tract of beef heifers. The LY was encapsulated using barley protein (mainly hordein and glutelin) extracted from barley grain. Five rumen cannulated beef heifers (BW = 650 ± 48.8 kg) were used in a 5 × 5 Latin square design. Heifers were fed ad libitum total mixed diet containing 10% barley silage and 90% barley-based concentrate (DM basis). Five treatments were: 1) control (no additives); 2) antibiotics (28 mg monensin + 11 mg tylosin/kg dietary DM); 3) 1.5 g LY/d; 4) 3.5 g encapsulated LY/d (ELY); and 5) combination of treatments #3 and 4 (MLY). The encapsulated LY consisted of 1.5 g LY and 2 g capsule. Number of yeast colonies was 1.71 × 1010 cfu/g. Digesta and rumen microbes were labeled with Yb and 15N, respectively. Data were analysed using the MIXED procedure of SAS with model including fixed effect of treatment and random effects of heifer and period. Intake of DM (averaged 11.8 kg/d) was not affected by treatment. No treatment effects on flows (kg/d) of OM (5.4) and starch (0.75) to the omasum were observed, whereas flows of NDF were greater (P < 0.02) with antibiotics (1.9) than ELY (1.7). Ruminal digestibility of OM tended (P < 0.09) to be less with ELY (62.4%) or MLY (62.9) than control (66.4%) or antibiotics (68.1%), but no differences in ruminal digestibility of NDF (averaged 44.1%) and starch (averaged 83.0%) were observed among treatments. In contrast, greater (P < 0.03) postruminal digestibility (% of intake) of OM (30.9 vs 22.9%) and NDF (17.9 vs 7.9%) was observed with ELY and MLY than control and antibiotic groups. As a result, digestibility of OM (81.1 vs 77.0%) and NDF (64.1 vs 49.9%) in the total digestive tract was greater (P < 0.01) with ELY or MLY than control. No treatment effect was observed on the flows of N to omasum (averaged 292 g/d) and microbial protein synthesis (averaged 147 g/d). Digestibility of N in the total digestive tract was greater (P < 0.02) with ELY or MLY than control (79.2 vs 75.4%). These results indicate the potential postruminal activity of LY, and benefits to feeding protected LY on improving intestinal digestibility of nutrients in beef heifers fed high-grain diet. [ABSTRACT FROM AUTHOR]

Red osier dogwood (ROD; Cornus sericea) is an abundant native shrub plant across Canada and it is rich in bioactive compounds with total phenolic concentration varying between 40 to 220 mg/g depending on the season. The phenolics include anthocyanins, gallic acid, ellagic acid, quercetin, and cyanin have both antioxidant and antimicrobial properties. Studies demonstrated that feeding ROD may reduce the use of antibiotics in livestock animals. It is hypothesized a greater feed value than barley silage in beef cattle diet. The objective was to determine the effect of increasing substitution of ROD for barley silage in high-grain diet on ruminal pH and fermentation, feed digestion in the total digestive tract in beef heifers. Five rumen cannulated Angus heifers (BW = 660 ± 40.8 kg) were used in a 5 × 5 Latin square design. Treatments were control diet containing 15% barley silage and 85% barley concentrate (DM basis), diet that substituted with 3%, 7% or 15% of ROD for equal barley silage, or diet supplemented with monensin (28 mg/kg diet DM). Ruminal pH was monitored continuously for 4 days using wireless pH probe of each period. Fermentation characteristics were measured for two consecutive days at 1, 3, 5, and 7 h of each day after the morning feeding. Apparent digestibility was determined using Cr2O3 as external marker by sampling feces from the rectum. Data were analysed using the MIXED procedure of SAS with model including fixed effect of diets and random effects of heifer and period. Intake of DM quadratically (P < 0.02) increased with increasing the replacement of silage by ROD from 0, 3, 7, to 10% (11.5, 12.1, 12.4, and 11.8 kg/d). Mean ruminal pH ranged from 5.95 to 6.14 and were not affected by diets, and no effects of diets on total VFA concentration (averaged 138 mM) were observed. However, ruminal NH3-N concentration linearly (P < 0.01) decreased with increasing ROD (10.7, 9.0, 9.8, and 8.0 mM). Digestibility of DM quadratically (P < 0.01) increased with increasing ROD from 0, 3, 7 to 10% (72.9, 74.8, 77.2, and 75.0%). Furthermore, feeding ROD vs monensin increased DM intake (12.1 vs 11.2 kg/d; P < 0.01), DM digestibility (75.8 vs 72.1%; P < 0.01), and VFA concentration (141 vs 130 mM; P < 0.05). These results indicate greater feed value of ROD vs barley silage or monensin but it was dose-dependant. It suggests that ROD could be fed potentially as an alternative to silage or monensin in beef cattle. [ABSTRACT FROM AUTHOR]

This study was carried out to evaluate the effects of processing method (grinding vs steam-flaking) on DM intake (DMI), ruminal pH and fermentation characteristics, total digestibility of DM, and milk production of dairy cows fed blended barley and corn-based diets. Eight multiparous mid-lactation Holstein cows (88 ± 12 DIM and 44.0 ± 1.5 kg milk/d) were used in a replicated 4 × 4 Latin square design with 21-d long of each period. Cows were fed ad libitum total mixed diet consisting of 25% corn silage, 15% alfalfa hay, and 60% concentrate with equal portion of barley and corn (DM basis). Treatments were: 1) ground barley and corn (GBGC), 2) steam-flaked barley and corn (SBSC), 3) ground barley and steam-flaked corn (GBSC), and 4) steam-flaked barley and ground corn (SBGC). Data were analysed using the MIXED procedure of SAS with model including treatment as fixed effect and the random effects of square, period within square and cow within square. The PDIFF option adjusted by the Tukey method was included in the LSMEANS statement to account for multiple comparisons among treatments. Intake of DM (kg/d) tended (P < 0.06) to be less with SBSC (23.1) than other treatments (averaged 24.2). Digestibility of DM (% of intake) in the total digestive tract was greater (P < 0.04) with SBSC (73.9) and GBSC (73.4) than GBGC (70.3) and tended (P < 0.10) to be greater than SBGC (71.5). However, yield of actual milk (averaged 44.7 kg/d) and 3.5% fat corrected milk (FCM; 39.9 kg/d) as well as milk composition did not differ among treatments. Milk efficiency (milk yield/DMI) tended (P < 0.09) to be improved with SBSC (1.93) vs GBGC (1.85) or SBGC (1.84). Ruminal pH (averaged 6.45), total VFA (averaged 125 mM), and molar proportions of individual VFA were not affected except that molar proportion of acetate tended (P < 0.06) to be greater with SBGC (58.8%) than other treatments (averaged 56.0%). Cows fed GBGC diet had sorting index below 100 for the particles retained on 19- and 8-mm sieves, indicated that cows sorted for these particles. In contrast, cows fed SBSC diet had sorting index superior to 100 for the particles retained on 19 and 8-mm sieves, thus, cows sorted against these particles. These results suggest that feeding cows with blend of steam-flaked barley and corn is beneficial to improve DM digestibility and milk efficiency. [ABSTRACT FROM AUTHOR]