Short-chain fatty acids and their corresponding acyl-CoAs sit at the crossroads of metabolic pathways and play important roles in diverse cellular processes. They are also precursors for protein ...post-translational lysine acylation modifications. A noteworthy example is the newly identified lysine 2-hydroxyisobutyrylation （Khib） that is derived from 2-hydroxyisobutyrate and 2-hydroxyisobutyryl-CoA. Histone Khib has been shown to be associated with active gene expression in spermatogenic cells. However, the key elements that regulate this post-translational lysine acyla- tion pathway remain unknown. This has hindered characterization of the mechanisms by which this modification exerts its biological functions. Here we show that Esalp in budding yeast and its homologue Tip60 in human could add Khib to substrate proteins both in vitro and in vivo. In addition, we have identified HDAC2 and HDAC3 as the major enzymes to remove Khmb. Moreover, we report the first global profiling of Khib proteome in mammalian cells, identifying 6 548 Khb sites on 1 725 substrate proteins. Our study has thus discovered both the ＂writers＂ and ＂erasers＂ for histone Kh~b marks, and major Khib protein substrates. These results not only illustrate the landscape of this new lysine acylation pathway, but also open new avenues for studying diverse functions of cellular metabolites associated with this pathway.
BACKGROUNDThe drug interaction between warfarin and rifampicin is widely known, but there are still some difficulties in managing the combination of the two drugs. CASE SUMMARYA patient with ...brucellosis received strict monitoring from a Chinese pharmacist team during combination of warfarin and rifampicin. The dose of warfarin was increased to 350% in 3 mo before reaching the lower international normalized ratio treatment window. No obvious adverse reaction occurred during the drug-adjustment period. This is the first case report of long-term combined use of rifampicin and warfarin in patients with brucellosis and valve replacement in China based on the Chinese lower warfarin dose and international normalized ratio range. CONCLUSIONAnticoagulation for valve replacement in Chinese patients differs from that in other races. Establishment of a pharmacist clinic provides vital assistance in warfarin dose adjustment.
AIM： To use the tyrosinase minigene as a visual marker to perform microinjection training and improve the techniques related with transgene to greatly elevate the effidency of gene transfer. METHODS： ...A mouse tyrosinase minigene, i.e., TyBS, in which the 2.25-kb authentic genomic 5＇ non-coding flanking sequence of mouse tyrosinase was fused to a mouse tyrosinase cDNA, was introduced into the fertilized eggs of outbred Kunming albino mice. RESULTS： Of the 11 animals that developed from the injected eggs, two mice （P1 and #8） exhibited pigmented hair （P1） and eyes （P1 and #8）, as confirmed by PCR analysis for the tyrosinase minigene integrated into the genome. When founder P1 was bred to Kunming male mouse, six progeny out of 11 offspring inherited the transgene and the pigmented-eye phenotype. CONCLUSION： Taken together, these results suggest that this minigene encodes the active tyrosinase protein and that its 5＇ flanking region contains the sequences regulating the expression of mouse tyrosinase gene as expected. We have rescued the albino phenotype by introduction and expression of a functional tyrosinase minigene in the Kunming albino mouse and the transgene can be passed to subsequent generation. These findings also indicate that TyBS can be a useful visual marker gene in the co-transgenic experiments.
2D/3D registration of preoperative computed tomography angiography with intra-operative X-ray angiography improves image guidance in percutaneous coronary intervention. However, previous registration ...methods are inaccurate and time-consuming due to simple deformation and iterative optimization, respectively. In this paper, we propose a novel method for non-rigid registration of coronary arteries based on a point set registration network, which predicts the complex deformation field directly without iterative optimization. In order to maintain the structure of coronary arteries, we advance the classical point set registration network with a loss function containing global and local topological constraints. The method was evaluated on ten clinical data, and it achieved a median chamfer distance of 73.60 pixels with a run time of less than 1s on CPU. Experimental results demonstrate that the proposed method is highly accurate and efficient.
The research on sea ice resources is the academic base of sea ice exploitation in the Bohai Sea. According to the ice-water spectrum differences and the correlation between ice thickness and albedo, ...this paper comes up with a sea ice thickness inversion model based on the NOAA/AVHRR data. And then a sea ice resources quantity （SIQ） time series of Bohai Sea is established from 1987 to 2009. The results indicate that the average error of inversion sea ice thickness is below 30%. The maximum sea ice resources quantity is about 6×109 m3 and the minimum is 1.3×109 m3. And a preliminary analysis has been made on the errors of the estimate of sea ice resources quantity （SIQ）.
Background Methanesulfonic acid sodium salt （Dipyrone）, an antipyretic and analgesic drug, has been demonstrated to improve cerebral ischemia through the inhibition of mitochondrial cell death ...cascades. The aim of this study was to evaluate the potential photoprotective activity of methanesulfonic acid sodium salt in a model of light-induced retinopathy. Methods One hundred mice were assigned randomly into vehicle （V）, methanesulfonic acid sodium salt （D）, light damage model plus vehicle （MV） and light damage model plus methanesulfonic acid sodium salt （MD） groups （n=25 each）. In the MD group, methanesulfonic acid sodium salt （100 mg/kg） was administered by intraperitoneal injection 30 minutes before light exposure. Twenty-four hours after light exposure, hematoxylin and eosin staining and transmission electron microscopy （TEM） were used for histological evaluation. The thickness of the outer plus inner-segment and outer nuclear layer was measured on sections parallel to the vertical meridian of the eye at a distance of 1000 I~m from the optic nerve. Electroretinography （ERG） test was performed to assess the functional change. The morphology of mitochondria was also revealed by TEM. Finally, the expression of cytochrome c （CytC） and the relative apoptotic proteins were detected by Western blotting, and the interaction between mitochondrial proteins was investigated by co-immunoprecipitation. Results The photoreceptor inner and outer segments of the MV group were significantly disorganized than the MD group. The thicknesses of the outer plus inner-segment layers and the outer nuclear layer, and the amplitudes of the a and b waves of the scotopic ERG response markedly decreased in the MV group compared to those in the MD group （P 〈0.05）. TEM examination revealed that the mitochondria of the MV group were distinctly swollen and contained disrupted cristae. In contrast, the morphology of mitochondria in the MD group was unaffected. Western blotting analysis showed that CytC, apoptosis proteinase activating factor-1 （Apaf-1）, caspase 3, p53, p53-upregulated modulator of apoptosis （PUMA）, Bax, and Bad were increased, whereas the anti-apoptotic proteins Bcl-2 and Bcl-XL were significantly decreased in the MV group than the MD group. Co-immunoprecipitation detection revealed that PUMA immunoreactivity precipitated by Bcl-XL decreased, whereas Bax immunoreactivity precipitated by Bcl-XL increased in the MD group compared to those in the MV group. Conclusion Methanesulfonic acid sodium salt is an effective photoprotective agent against light-induced retinopathy through the inhibition of CytC-mediated mitochondrial impairment.
In this study, the residual strain of a thin conductive metal wire on a polymer substrate after electrical failure is measured with SEM moir′e. Focused ion beam(FIB) milling is applied to fabricate ...micron moir′e gratings on the surfaces of constantan wires and the random phase shifting technique is used to process moir′e fringes. The virtual strain method is briefly introduced and used to calculate the real strain of specimens. In order to study the influence of a defect on the electrical failure of the constantan wire, experiments were conducted on two specimens, one with a crack, while the other one without any crack. By comparing the results, we found that the defect makes the critical beam current of electrical failure decrease. In addition, the specimens were subjected to compression after electrical failure, in agreement with the observed crack closure of the specimen. The successful results demonstrate that the moir′e method is effective to characterize the full-field deformation of constantan wires on the polymer membrane, and has a good potential for further application to the deformation measurement of thin films.
OBJECTIVE： To investigate the tumor inhibition effect of Yangfei Kongliu Formula （YKF）, a compound Chinese herbal medicine, combined with cisplatin （DDP） and its action mechanisms. METHODS： C57BL/6 ...mice with Lewis lung carcinoma were divided into six groups： control group （C）, DDP group （2 mg/kg, DDP）, low-dose YKF group （2.43 g/kg, L）, high-dose YKF group （24.3 g/kg, H）, low- dose YKF combined with DDP group （L ＋ DDP） and high-dose YKF combined with DDP group （H ＋ DDP）. Transforming growth factor-β1 （TGF-β1）, mothers against decapentaplegic homolog 3 （Smad3） and Smad7 levels were measured with quantitative real-time polymerase chain reaction （qPCR）, Western blotting and immunohistochemistry. An enzyme-linked immunosorbent assay was used to analyze the expressions of interleukin-2 （IL-2） and tumor necrosis factor-α （TNF-α）. RESULTS： YKF combined with DDP significantly inhibited the growth and metastasis of tumors relative to the control group, and YKF groups （P 〈 0.05）. There was no significant difference between high-dose YKF group and low-dose YKF group （P 〉 0.05）. We also found that the expression levels of TGF-β1 and Smad3 were both significantly decreased by YKF relative to the control group （P 〈 0.05）. Furthermore, after treatment with YKF combined with DDP, the expression levels of TGF-β1 and Smad3 were decreased but the expression level of Smad7 was increased relative to the DDP group （P 〈 0.05）. Compared to the DDP group, the combination of YKF and DDP enhanced the effect of tumor inhibition （P 〈 0.05）, showing obvious synergy between YKF and DDP. Treatment with DDP or YKF decreased serum levels of IL-2 and TNF-α relative to the control group （P 〈 0.05）. Furthermore, the expression levels of IL-2 and TNF-α were significantly decreased when treated with YKF in combination with DDP. Co-treatment with YKF and DDP significantly inhibited tumor growth, decreased the expressions of TGF-β1, Smad3, IL-2 and TNF-α and increased the expression of Smad7; these differences were significant relative to both YKF groups and the control group （P 〈 0.05）. CONCLUSION： YKF can inhibit tumor growth synergistically with DDP, mainly through the TGF-β1 signaling pathway.
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