360 research outputs found
GW26-e5430 Serum CTRP5 is associated with in-stent restenosis after percutaneous coronary intervention
Proof of a conjecture on the ϵ-spectral radius of trees
The ϵ-spectral radius of a connected graph is the largest eigenvalue of its eccentricity matrix. In this paper, we identify the unique n-vertex tree with diameter 4 and matching number 5 that minimizes the ϵ-spectral radius, and thus resolve a conjecture proposed in [W. Wei, S. Li, L. Zhang, Characterizing the extremal graphs with respect to the eccentricity spectral radius, and beyond, Discrete Math. 345 (2022) 112686]
The M-T hook structure increases the potency of HIV-1 fusion inhibitor sifuvirtide and overcomes drug resistance
Objectives Peptides derived from the C-terminal heptad repeat (CHR) of HIV-1 gp41 are potent fusion inhibitors. We have recently demonstrated that the unique M-T hook structure preceding the pocket-binding motif of CHR peptide-based inhibitors can greatly improve their antiviral activity. In this study, we applied the M-T hook structure to optimize sifuvirtide (SFT), a potent CHR-derived inhibitor currently under Phase III clinical trials in China. Methods The peptide MT-SFT was generated by incorporating two M-T hook residues (Met-Thr) into the N-terminus of sifuvirtide. Multiple structural and functional approaches were used to determine the biophysical properties and antiviral activity of MT-SFT. Results The high-resolution crystal structure of MT-SFT reveals a highly conserved M-T hook conformation. Compared with sifuvirtide, MT-SFT exhibited a significant improvement in the ability to bind to the N-terminal heptad repeat, to block the formation of the six helix bundle and to inhibit HIV-1 Env-mediated cell fusion, viral entry and infection. Importantly, MT-SFT was fully active against sifuvirtide- and enfuvirtide (T20)-resistant HIV-1 variants and displayed a high genetic barrier to developing drug resistance. Conclusions Our studies have verified that the M-T hook structure offers a general strategy for designing novel HIV-1 fusion inhibitors and provide new insights into viral entry and inhibitio
Identification of MACC1 as a novel prognostic marker in hepatocellular carcinoma
<p>Abstract</p> <p>Background</p> <p>Metastasis-associated in colon cancer-1 (<it>MACC1</it>) is a newly identified gene that plays a role in colon cancer metastasis through upregulation of c-MET proto-oncogene (c-MET). However, the value of <it>MACC1 </it>as a potential biomarker for hepatocellular carcinoma (HCC) remains unknown.</p> <p>Methods</p> <p><it>MACC1 </it>mRNA expression in 128 HCC tissues was examined by quantitative polymerase chain reaction. To show the potential correlation of <it>MACC1 </it>and c-MET, c-MET was also analysed.</p> <p>Results</p> <p><it>MACC1 </it>was more highly expressed in HCC than in non-HCC tissues (<it>P </it>= 0.009). High <it>MACC1 </it>expression was significantly increased in cases with high alpha fetoprotein (AFP) (<it>P </it>= 0.025). A positive correlation was found between <it>MACC1 </it>and c-MET mRNAs (r = 0.235, <it>P </it>= 0.009). Both univariate and multivariate analyses revealed that <it>MACC1 </it>expression was associated with overall survival (OS) and disease-free survival (DFS). Moreover, stratified analysis showed that tumour-node-metastasis (TNM) stage I patients with high <it>MACC1 </it>levels had shorter OS and DFS than those with low <it>MACC1</it>.</p> <p>Conclusions</p> <p><it>MACC1 </it>may identify low- and high-risk individuals with HCC and be a valuable indicator for stratifying the prognosis of TNM stage I patients. <it>MACC1 </it>may serve as a novel biomarker for HCC.</p
Reducing Crosstalk of Silicon-based Optical Switch with All-optical Multi-wavelength Regenerator
Improving crosstalk performance of Mach–Zehnder-interferometer-type optical switches is experimentally investigated by use of an all-optical multi-wavelength regenerator. Extinction ratio and bit error rate of WDM signals are simultaneously improved in proposed regenerative optical switching
Chemometrics-assisted identification of anti-inflammatory compounds from the green alga klebsormidium flaccidum var. Zivo
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). The green alga Klebsormidium flaccidum var. zivo is a rich source of proteins, polyphenols, and bioactive small-molecule compounds. An approach involving chromatographic fractionation, anti-inflammatory activity testing, ultrahigh performance liquid chromatography-mass spectrometry profiling, chemometric analysis, and subsequent MS-oriented isolation was employed to rapidly identify its small-molecule anti-inflammatory compounds including hydroxylated fatty acids, chlorophyll-derived pheophorbides, carotenoids, and glycoglycerolipids. Pheophorbide a, which decreased intracellular nitric oxide production by inhibiting inducible nitric oxide synthase, was the most potent compound identified with an IC50 value of 0.24 µM in lipopolysaccharides-induced macrophages. It also inhibited nuclear factor kappaB activation with an IC50 value of 32.1 µM in phorbol 12-myristate 13-acetate-induced chondrocytes. Compared to conventional bioassay-guided fractionation, this approach is more efficient for rapid identification of multiple chemical classes of bioactive compounds from a complex natural product mixture
Efficient gene editing in adult mouse livers via adenoviral delivery of CRISPR/Cas9
AbstractWe developed an adenovirus-based CRISPR/Cas9 system for gene editing in vivo. In the liver, we demonstrated that the system could reach the level of tissue-specific gene knockout, resulting in phenotypic changes. Given the wide spectrum of cell types susceptible to adenoviral infection, and the fact that adenoviral genome rarely integrates into its host cell genome, we believe the adenovirus-based CRISPR/Cas9 system will find applications in a variety of experimental settings
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Pilot Study on Image Quality and Radiation Dose of CT Colonography with Adaptive Iterative Dose Reduction Three-Dimensional
Objective: To investigate image quality and radiation dose of CT colonography (CTC) with adaptive iterative dose reduction three-dimensional (AIDR3D). Methods: Ten segments of porcine colon phantom were collected, and 30 pedunculate polyps with diameters ranging from 1 to 15 mm were simulated on each segment. Image data were acquired with tube voltage of 120 kVp, and current doses of 10 mAs, 20 mAs, 30 mAs, 40 mAs, 50 mAs, respectively. CTC images were reconstructed using filtered back projection (FBP) and AIDR3D. Two radiologists blindly evaluated image quality. Quantitative evaluation of image quality included image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). Qualitative image quality was evaluated with a five-score scale. Radiation dose was calculated based on dose-length product. Ten volunteers were examined supine 50 mAs with FBP and prone 20 mAs with AIDR3D, and image qualities were assessed. Paired t test was performed for statistical analysis. Results: For 20 mAs with AIDR3D and 50 mAs with FBP, image noise, SNRs and CNRs were (16.4 ± 1.6) HU vs. (16.8 ± 2.6) HU, 1.9 ± 0.2 vs. 1.9 ± 0.4, and 62.3 ± 6.8 vs. 62.0 ± 6.2, respectively; qualitative image quality scores were 4.1 and 4.3, respectively; their differences were all not statistically significant. Compared with 50 mAs with FBP, radiation dose (1.62 mSv) of 20 mAs with AIDR3D was decreased by 60.0%. There was no statistically significant difference in image noise, SNRs, CNRs and qualitative image quality scores between prone 20 mAs with AIDR3D and supine 50 mAs with FBP in 10 volunteers, the former reduced radiation dose by 61.1%. Conclusion: Image quality of CTC using 20 mAs with AIDR3D could be comparable to standard 50 mAs with FBP, radiation dose of the former reduced by about 60.0% and was only 1.62 mSv
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