Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 230
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Molecules ; 25(3)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028604

RESUMO

To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention. In this study, we focused on, among the altered metabolic processes in cancerous cells, altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance. We hypothesize that the enzymes required for the biosynthesis of UDP-hexoses, glycosyl donors for glycan synthesis, could serve as therapeutic targets for cancers. Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM. The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively. One of GAL-012 derivatives GAL-012-2 also demonstrated the inhibitory activity against GALT and UGP2. Moreover, we showed that GAL-012 suppressed the growth of PC3 cells in a dose-dependent manner with an EC50 of 75 µM with no effects on normal skin fibroblasts at 200 µM. Western blot analysis revealed reduced expression of pAKT (Ser473), pAKT (Thr308) by 77% and 72%, respectively in the treated cells. siRNA experiments against the respective genes encoding the pyrophosphorylases were also performed and the results further validated the proposed roles in cancer growth inhibition. Finally, synergistic relationships between GAL-012 and tunicamycin, as well as bortezomib (BTZ) in killing cultured cancer cells were observed, respectively. With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32048985

RESUMO

Two Gram-stain-negative, aerobic, motile and rod-shaped bacteria, one designated as strain AXBT, capable of degrading estrogens, and another, YL23T, capable of degrading estrogen and bisphenol A, were isolated from activated sludge in Xiamen City, PR China. The optimum temperature and pH of both strains were 25-35 °C and pH 7.0-8.0. While strain AXBT could tolerate 3 % (w/v) NaCl, YL23T could only grow between 0-1 % (w/v) NaCl. They contained ubiquinone-10 as the major quinone, spermidine as the major polyamine, summed feature 8 (comprising C18:1ω6c and/or C18:1ω7c) as the major fatty acids and diphosphatidylglycerol, phosphatidylcholine, phosphatidyldimethylethanolamine, phosphatidylethanolamine, phosphatidylglycerol and sphingoglycolipid as the major polar lipids. The DNA G+C contents of strains AXBT and YL23T were 63.6 and 63.7 mol%, respectively. Based on the results of 16S rRNA gene sequence analysis, strains AXBT and YL23T belonged to the genus Sphingobium. Strain AXBT was most closely related to Sphingobium chlorophenolicum NBRC 16172T (97.5 %) and Sphingobium chungbukense DJ77T (97.2 %), and strain YL23T was most closely related to S. chlorophenolicum NBRC 16172T (97.4 %) and S. quisquiliarum P25T (97.1 %). Average nucleotide identity values between these two strains and S. chlorophenolicum NBRC 16172T, S. chungbukense DJ77T, Sphingobium chinhatense IP26T, Sphingobium quisquiliarum P25T and Sphingobium japonicum UT26ST were from 80.7 to 85.8 %. In conclusion, strains AXBT and YL23T represent novel species of the genus Sphingobium, for which the names Sphingobium estronivorans sp. nov. and Sphingobium bisphenolivorans sp. nov. are proposed, respectively. The type strains of S. estronivorans and S. bisphenolivorans are AXBT (=MCCC 1K01232T=DSM 102173T) and YL23T (=MCCC 1K02300T=DSM 102172T), respectively.

3.
Med Biol Eng Comput ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31950330

RESUMO

Hepatic echinococcosis (HE) is a life-threatening liver disease caused by parasites that requires a precise diagnosis and proper treatments. To assess HE lesions accurately, we propose a novel automatic HE lesion segmentation and classification network that contains lesion region positioning (LRP) and lesion region segmenting (LRS) modules. First, we used the LRP module to obtain the probability map of the lesion distribution and the position of the lesion. Then, based on the result of the LRP module, we used the LRS module to precisely segment the HE lesions within the high-probability region. Finally, we classified the HE lesions and identified the lesion types by a convolutional neural network (CNN). The entire dataset was delineated by the hospital's senior radiologist. We collected CT slices of 160 patients from Qinghai Provincial People's Hospital. The Dice score of the final segmentation result reached 89.89%. The Dice scores, indicating the classification accuracy, for cystic vs. alveolar echinococcosis and calcified vs. noncalcified lesions were 80.32% and 82.45%, the sensitivities were 72.41% and 75.17%, the specificities were 83.72% and 86.04%, the NPVs were 80.01% and 86.96%, the PPVs were 80.45% and 81.74%, and the areas under the ROC curves were 0.8128 and 0.8205, respectively. Graphical abstract.

4.
Med Sci Monit ; 26: e918174, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31957742

RESUMO

BACKGROUND The aim of this study was to explore the expression of miR-140 and miR-199 in synovia of patients with knee osteoarthritis (KOA) and its correlation with the progression of this disease. We used the Kellgren and Lawrence grading (KLG) system. MATERIAL AND METHODS There were 110 patients with early (KLG <2), middle (KLG=2) and late (KLG >2) stage KOA and 60 healthy individuals (control) included in this study. RESULTS The relative expression levels of miR-140 (1.07±0.091) and miR-199 (1.03±0.110) in synovia of the control group were higher than those of KOA groups (0.511±0.130, 0.298±0.168) and the difference exhibited statistical significance (P<0.01). Expression of miR-140 in the middle and the late stage KOA groups (0.322±0.118 and 0.110±0.088 respectively) were 58.80% and 81.29% lower, respectively, compared to the early stage KOA group (0.588±0.172), which was significant (P<0.05). Expression of miR-199 in the middle and the late stage KOA groups (0.210±0.124 and 0.056±0.068 respectively) were 39.41% (P<0.05) and 83.72% (P<0.01) respectively lower than that in the early KOA group (0.344±0.147). The severity of OA was significantly negatively correlated with the expressions of miR-140 and miR-199 (r=-0.859, P<0.05; r=-0.724, P<0.001 respectively). Matrix metalloproteinase (MMP)-3 levels of the early stage, middle stage and late stage KOA groups were 1.320±0.118, 1.488±0.210, and 1.955±0.023 respectively; and IL-1ß mRNA was 1.401±0.204, 1.522±0.210, and 1.889±0.217 respectively, which were obviously higher than those in the control group (1.020±0.085), (P<0.05). CONCLUSIONS Expression levels of miR-140 and miR-199 in synovia might act as an early diagnostic marker for KOA. These expression levels might also act as indicators of OA progression to some extent.

5.
Eur J Med Chem ; 186: 111893, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31761383

RESUMO

The pyrazolone structural motif is a critical element of drugs aimed at different biological end-points. Medicinal chemistry researches have synthesized drug-like pyrazolone candidates with several medicinal features including antimicrobial, antitumor, CNS (central nervous system) effect, anti-inflammatory activities and so on. Meanwhile, SAR (Structure-Activity Relationship) investigations have drawn attentions among medicinal chemists, along with a plenty of analogues have been derived for multiple targets. In this review, we comprehensively summarize the biological activity and SAR for pyrazolone analogues, wishing to give an overall retrospect and prospect on the pyrazolone derivatives.

6.
Toxicol In Vitro ; 62: 104693, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629899

RESUMO

Acute Myeloid Leukemia (AML) is a cancer of hematopoietic stem cells with a rapid progression. Recent studies indicated that endocrine disruptor chemicals (EDCs) are potential risk factors for AML progression. Our present data showed that an industrial endocrine disrupting chemical, Benzyl butyl phthalate (BBP), can promote the proliferation of AML cells and decrease their sensitivity to daunorubicin (DNR) and cytarabine (Ara-C) treatments. Further, BBP can increase the glucose consumption, lactate generation, and ATP levels of AML cells. Among the measured glycolysis-related genes, BBP can increase the expression of pyruvate dehydrogenase lipoamide kinase isozyme 4 (PDK4), a mitochondrial protein that regulates the tricarboxylic acid cycle (TCA) cycle. The inhibitor of PDK4 or its specific siRNA can attenuate BBP-induced cell proliferation and ATP generation, which suggested the essential roles of PDK4 in BBP-induced glycolysis and proliferation. Further, BBP can increase the mRNA stability of PDK4, while had no effect on its transcription and protein stability. miR-15b-5p can bind with the 3'UTR of PDK4 to decrease its mRNA stability, while BBP can decrease the expression of miR-15b-5p in AML cells. Collectively, our data showed that BBP can trigger the malignancy of AML cells via regulation of miR-15b-5p/PDK4 signals.

7.
BMC Cancer ; 19(1): 1162, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783814

RESUMO

BACKGROUND: To compare the efficacy and safety between conventional transarterial chemoembolization (cTACE) and drug-eluting beads TACE (DEB-TACE) in patients with infiltrative hepatocellular carcinoma (iHCC). METHODS: A total of 89 iHCC patients who were treated with either cTACE (n = 33) or DEB-TACE (n = 56) between April 2013 and September 2017 were included in this retrospective study. Patients with the situations that might have a poor outcome were defined as advanced disease including Child-Pugh class B, bilobar lesions, tumor size greater than 10 cm, ECOG 1-2, tumor burden of 50-70%, and the presence of ascites, arterioportal shunt (APS), and portal venous tumor thrombus (PVTT). The tumor response was measured 1-month and 3-month after the procedure. Progression-free survival (PFS) was calculated. Toxicity was graded by Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0). The differences in tumor response, PFS, and toxicity were compared between the DEB-TACE group and cTACE group. RESULTS: At 1-month and 3-month after the procedure, the objective response rate (ORR) in the overall study population was similar in DEB-TACE group and cTACE group. The disease control rate (DCR), at 1-month after the procedure, was significantly higher in the patients treated with DEB-TACE relative to those treated with cTACE (P = 0.034), while after 3 months, the difference did not differ between two groups. DEB-TACE showed a higher DCR than cTACE in patients with tumor size greater than 10 cm (P = 0.036) or associated with APS (P = 0.030) at 1-month after the procedure, while after 3 months, the difference was only noted in patients with APS (P = 0.036). The median PFS in DEB-TACE group was 96 days, while in cTACE group was 94 days, and there was no difference in PFS between two groups (P = 0.831). In the side effect analysis, abdominal pain (P = 0.034) and fever (P = 0.009) were more frequently present in the cTACE group than DEB-TACE group, but there was no difference in high grade liver toxicity between the two groups. CONCLUSIONS: Compared to cTACE, DEB-TACE offers slightly better DCR and tolerability for iHCC patients, particularly in patients associated with APS and large tumor size. However, DEB-TACE does not provide higher PFS than cTACE.

8.
Cell Syst ; 9(6): 589-599.e7, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31786209

RESUMO

Because of incomplete reference transcriptomes, incomplete sequencing bias models, or other modeling defects, algorithms to infer isoform expression from RNA sequencing (RNA-seq) sometimes do not accurately model expression. We present a computational method to detect instances where a quantification algorithm could not completely explain the input reads. Our approach identifies regions where the read coverage significantly deviates from expectation. We call these regions "expression anomalies." We further present a method to attribute their cause to either the incompleteness of the reference transcriptome or algorithmic mistakes. We detect anomalies for 30 GEUVADIS and 16 Human Body Map samples. By correcting anomalies when possible, we reduce the number of falsely predicted instances of differential expression. Anomalies that cannot be corrected are suspected to indicate the existence of isoforms unannotated by the reference. We detected 88 common anomalies of this type and find that they tend to have a lower-than-expected coverage toward their 3' ends.

9.
Am J Transl Res ; 11(11): 7157-7165, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814918

RESUMO

In this study, we compared different anesthesia and operation methods for modeling VX2 hepatocarcinoma in rabbits. Forty New Zealand white rabbits were randomly divided into three groups: A, B, and C. Group A underwent ultrasound-guided implantation and intravenous anesthesia; Group B underwent ultrasound-guided implantation and inhalation anesthesia; Group C underwent laparotomy implantation and intravenous anesthesia. Anesthesia and operation differences were compared between groups A and B, and A and C, respectively. We used magnetic resonance imaging (MRI) to assess tumor formation and growth, and pathological examination and immunohistochemistry to confirm the biological characteristics of the specimens. The anesthetic preparation and postoperative resuscitation times were shorter in group A compared to group B; there were no significant between-group differences in the intraoperative satisfactory effect rate or mortality rate. The operation time, incision length, hemorrhage volume, and leukocyte counts were lower in group A than group C; there were no significant between-group differences in the postoperative infection rate or mortality rate. MRI revealed that the celiac implantation rate decreased dramatically in groups A and B; there were no significant between-group differences in the largest tumor diameter, tumorigenesis rate, intrahepatic multifocal implantation rate, or abdominal wall invasion rate. Ten samples were confirmed by pathological examination and immunohistochemistry to have VX2 tumors. To conclude, using an inhalation-based anesthetic method is beneficial for improving the efficiency of the VX2 tumor implantation operation. Compared with laparotomy implantation, ultrasound-guided implantation required less operation time, had lower levels of internal damage, and had a lower celiac implantation rate.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31808070

RESUMO

PURPOSE: Knee arthroscopy suffers from a lack of depth information and easy occlusion of the visual field. To solve these limitations, we propose an arthroscopic navigation system based on self-positioning technology, with the guidance of virtual-vision views. This system can work without any external tracking devices or added markers, thus increasing the working range and improving the robustness of the rotating operation. METHODS: The fly-through view and global positioning view for surgical guidance are rendered through virtual-vision rendering in real time. The fly-through view provides surgeons with navigating the arthroscope in the internal anatomical structures using a virtual camera perspective. The global positioning view shows the posture of the arthroscope relative to the preoperative model in a transparent manner. The posture of the arthroscope is estimated from the fusion of visual and inertial data based on the visual-inertial stereo slam. A flexible calibration method that transforms the posture of the arthroscope in the physical world into the virtual-vision rendering framework is proposed for the arthroscopic navigation system with self-positioning information. RESULTS: Quantitative experiments for evaluating self-positioning accuracy were performed. For translation, the acquired mean error was 0.41 ± 0.28 mm; for rotation, it was 0.11° ± 0.07°. The tracking range of the proposed system was approximately 1.4 times that of the traditional external optical tracking system for the rotating operation. Simulated surgical operations were performed on the phantom. The fly-through and global positing views were paired with original arthroscopic images for intuitive surgical guidance. CONCLUSION: The proposed system provides surgeons with both fly-through and global positioning views without a dependence on the traditional external tracking systems for surgical guidance. The feasibility and robustness of the system are evaluated, and it shows promise for medical applications.

11.
Proc Natl Acad Sci U S A ; 116(46): 22931-22937, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31666329

RESUMO

Noisy matrix completion aims at estimating a low-rank matrix given only partial and corrupted entries. Despite remarkable progress in designing efficient estimation algorithms, it remains largely unclear how to assess the uncertainty of the obtained estimates and how to perform efficient statistical inference on the unknown matrix (e.g., constructing a valid and short confidence interval for an unseen entry). This paper takes a substantial step toward addressing such tasks. We develop a simple procedure to compensate for the bias of the widely used convex and nonconvex estimators. The resulting debiased estimators admit nearly precise nonasymptotic distributional characterizations, which in turn enable optimal construction of confidence intervals/regions for, say, the missing entries and the low-rank factors. Our inferential procedures do not require sample splitting, thus avoiding unnecessary loss of data efficiency. As a byproduct, we obtain a sharp characterization of the estimation accuracy of our debiased estimators in both rate and constant. Our debiased estimators are tractable algorithms that provably achieve full statistical efficiency.

12.
Food Funct ; 10(11): 7533-7543, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674605

RESUMO

The development of a new generation antioxidant peptides with high free radical scavenging rates is highly desirable, but remains a great challenge. Herein, a new dual-peptide development strategy based on plant and animal proteins has been proposed to enhance the antioxidant activity of peptides. Sea cucumber peptide and pine nut peptide were selected to assemble the dual-peptides, namely, VTPYKDHCH and VTPYQDHCH. The in vitro antioxidant activity of the dual-peptides was confirmed to be much higher than that of the individual peptides VTPY, KDHCH, and QDHCH according to the DPPH and ABTS radical scavenging and EPR experiments. The antioxidant activity of the dual-peptides was also further confirmed via cell experiments. Moreover, circular dichroism (CD), Raman spectrum and 1H NMR spectrum were recorded to determine the enhancement mechanism, which showed that the enhancement activity was derived from the increase in the random crimp degree of the secondary structure after the two different proteins were bound together. Our findings are expected to establish a new dual-peptide strategy for the enhancement of antioxidant activity based on plant and animal sources and encourage the further exploration of dual-peptides for functional applications.

13.
BMC Med Genet ; 20(1): 169, 2019 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694554

RESUMO

BACKGROUND: Proximal symphalangism is a rare disease with multiple phenotypes including reduced proximal interphalangeal joint space, symphalangism of the 4th and/or 5th finger, as well as hearing loss. At present, at least two types of proximal symphalangism have been identified in the clinic. One is proximal symphalangism-1A (SYM1A), which is caused by genetic variants in Noggin (NOG), another is proximal symphalangism-1B (SYM1B), which is resulted from Growth Differentiation Factor 5 (GDF5) mutations. CASE PRESENTATION: Here, we reported a Chinese family with symphalangism of the 4th and/or 5th finger and moderate deafness. The proband was a 13-year-old girl with normal intelligence but symphalangism of the 4th finger in the left hand and moderate deafness. Hearing testing and inner ear CT scan suggested that the proband suffered from structural deafness. Family history investigation found that her father (II-3) and grandmother (I-2) also suffered from hearing loss and symphalangism. Target sequencing identified a novel heterozygous NOG mutation, c.690C > G/p.C230W, which was the genetic lesion of the affected family. Bioinformatics analysis and public databases filtering further confirmed the pathogenicity of the novel mutation. Furthermore, we assisted the family to deliver a baby girl who did not carry the mutation by genetic counseling and prenatal diagnosis using amniotic fluid DNA sequencing. CONCLUSION: In this study, we identified a novel NOG mutation (c.690C > G/p.C230W) by target sequencing and helped the family to deliver a baby who did not carry the mutation. Our study expanded the spectrum of NOG mutations and contributed to genetic diagnosis and counseling of families with SYM1A.

14.
Methods Appl Fluoresc ; 8(1): 015002, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31622961

RESUMO

The effect of aminopyridines substituted at different positions on the fluorescence properties deserves to be studied. Since 2-aminopyridyl-based probes have been reported, the effects of 3-aminopyridine and 4-aminopyridine on the performance of fluorescein probes were discussed in here. Two Schiff base fluorescein probes FN-1, FN-2 were designed and synthesized. Among them, since the ligand shows a highly selective and sensitive response to metal charge transfer (LMCT), the fluorescence of FN-1 can be quenched by Ce3+ ions in PBS buffer. At the same time, a specific precipitation reaction between Ce3+ and F- releases the free probe to restore the fluorescence of FN-1. Therefore, FN-1 can be used for the recyclable 'ON-OFF-ON' detection of Ce3+and F-. The detection limits for Ce3+and F- are 4.48 µM and 11.58 µM in concentration range of 0-50 µM and 0-150 µM. However, due to the para position of N and amino groups on 4-aminopyridine, the spatial structure of FN-2 cannot be complexed with ions, resulting in poor selectivity. Polyvinylidene fluoride (PVDF) membrane containing FN-1 were prepared for the real-time qualitative detection of Ce3+and F- in real water samples. FN-1 exhibits high water solubility and biocompatibility and has been successfully applied to biological imaging in vascular smooth muscle cells (VSMCs).

15.
Proc Natl Acad Sci U S A ; 116(45): 22598-22608, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31624125

RESUMO

Pontocerebellar hypoplasia (PCH) is a group of neurological disorders that affect the development of the brain, in particular, the pons and cerebellum. Homozygous mutations of TBC1D23 have been found recently to lead to PCH; however, the underlying molecular mechanisms remain unclear. Here, we show that the crystal structure of the TBC1D23 C-terminal domain adopts a Pleckstrin homology domain fold and selectively binds to phosphoinositides, in particular, PtdIns(4)P, through one surface while binding FAM21 via the opposite surface. Mutation of key residues of TBC1D23 or FAM21 selectively disrupts the endosomal vesicular trafficking toward the Trans-Golgi Network. Finally, using the zebrafish model, we show that PCH patient-derived mutants, impacting either phosphoinositide binding or FAM21 binding, lead to abnormal neuronal growth and brain development. Taken together, our data provide a molecular basis for the interaction between TBC1D23 and FAM21, and suggest a plausible role for PtdIns(4)P in the TBC1D23-mediating endosome-to-TGN trafficking pathway. Defects in this trafficking pathway are, at least partially, responsible for the pathogenesis of certain types of PCH.

16.
Mar Pollut Bull ; 145: 370-376, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31590799

RESUMO

In the present study, 13 endocrine disrupting compounds (EDCs) and their transformation products (TPs) were monitored in Jiulong River and its estuary, China in different seasons. The analytes included antimicrobials [triclosan (TCS) and triclocarbon (TCC)]; estrogens [estrone (E1), estradiol (E2), estriol (E3) and ethinylestradiol (EE2)]; alkylphenol ethoxylates [4-n-nonylphenol (NP) and 4-n-octylphenol (OP)] and the TPs [methyl triclosan (MeTCS), carbanilide (NCC), dichlorocarbanilide, 4-hydroxy estrone (4-OH E1) and 4-hydroxy estradiol (4-OH E2)]. A significant seasonal variation was observed for most EDCs. Approximately, 79% of the total E2 residues were detected in the normal season in comparison with the wet season to indicate recalcitrant behavior of E2 during the normal season. Risk assessment revealed that E2 was most potent among the EDCs to cause highest risk to both vertebrate and invertebrate aquatic species, whereas, E1, EE2, MeTCS and TCS also showed relatively high risk for some surface water aquatic species.


Assuntos
Disruptores Endócrinos/toxicidade , Monitoramento Ambiental , Rios , Poluentes Químicos da Água/toxicidade , China , Disruptores Endócrinos/análise , Disruptores Endócrinos/química , Estuários , Rios/química , Estações do Ano , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química
17.
Ann Stat ; 47(4): 2204-2235, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31598016

RESUMO

This paper is concerned with the problem of top-K ranking from pairwise comparisons. Given a collection of n items and a few pairwise comparisons across them, one wishes to identify the set of K items that receive the highest ranks. To tackle this problem, we adopt the logistic parametric model - the Bradley-Terry-Luce model, where each item is assigned a latent preference score, and where the outcome of each pairwise comparison depends solely on the relative scores of the two items involved. Recent works have made significant progress towards characterizing the performance (e.g. the mean square error for estimating the scores) of several classical methods, including the spectral method and the maximum likelihood estimator (MLE). However, where they stand regarding top-K ranking remains unsettled. We demonstrate that under a natural random sampling model, the spectral method alone, or the regularized MLE alone, is minimax optimal in terms of the sample complexity - the number of paired comparisons needed to ensure exact top-K identification, for the fixed dynamic range regime. This is accomplished via optimal control of the entrywise error of the score estimates. We complement our theoretical studies by numerical experiments, confirming that both methods yield low entrywise errors for estimating the underlying scores. Our theory is established via a novel leave-one-out trick, which proves effective for analyzing both iterative and non-iterative procedures. Along the way, we derive an elementary eigenvector perturbation bound for probability transition matrices, which parallels the Davis-Kahan Θ theorem for symmetric matrices. This also allows us to close the gap between the l 2 error upper bound for the spectral method and the minimax lower limit.

18.
Atherosclerosis ; 290: 9-18, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31539718

RESUMO

BACKGROUND AND AIMS: The process of endothelial repair in diabetic patients after stent implantation was significantly delayed compared with that in non-diabetic patients, and oxidative stress is increasingly considered to be relevant to the pathogenesis of diabetic endothelial repair. However, the mechanisms linking diabetes and reendothelialization after vascular injury have not been fully elucidated. The aim of this study was to evaluate the effect of microRNA-24 (miR-24) up-regulation in delayed endothelial repair caused by oxidative stress after balloon injury in diabetic rats. METHODS: In vitro, vascular smooth muscle cells (VSMCs) isolated from the thoracic aorta were stimulated with high glucose (HG) after miR-24 recombinant adenovirus (Ad-miR-24-GFP) transfection for 3 days. In vivo, diabetic rats induced using high-fat diet (HFD) and low-dose streptozotocin (30 mg/kg) underwent carotid artery balloon injury followed by Ad-miR-24-GFP transfection for 20 min. RESULTS: The expression of miR-24 was decreased in HG-stimulated VSMCs and balloon-injured carotid arteries of diabetic rats, which was accompanied by increased expression of Ogt and Keap1 and decreased expression of Nrf2 and Ho-1. Up-regulation of miR-24 suppressed VSMC oxidative stress induced by HG in vitro, and miR-24 up-regulation promoted reendothelialization in balloon-injured diabetic rats. The underlying mechanism was related to the activation of the Nrf2/Ho-1 signaling pathway, which subsequently suppressed intracellular reactive oxidative species (ROS) production and malondialdehyde (MDA) and NADPH oxidase (Nox) activity, and to the restoration of Sod and Gsh-px activation. CONCLUSIONS: The up-regulation of miR-24 significantly promoted endothelial repair after balloon injury through inhibition of oxidative stress by activating the Nrf2/Ho-1 signaling pathway.

19.
Can J Microbiol ; 65(12): 913-921, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31491332

RESUMO

This study reports the use of reverse transcription - loop-mediated isothermal amplification (RT-LAMP) to detect Listeria monocytogenes in meat. The assay was designed to target the iap gene of L. monocytogenes, to which four primers, recognizing six distinct iap sites, were designed. We optimized the RT-LAMP conditions and established the following optimal systems: 60 min, 63 °C, 2.0 mmol/L MgSO4, 1.0 mol/L betaine, 2.0 mmol/L dNTPs, 320 U/mL Bst DNA polymerase, 0.4 µmol/L outer primers, and 0.8 µmol/L inner primers. The RT-LAMP amplification products were identified by a visible white Mg2P2O7 precipitate or electrophoresis on a 2% agarose gel. RT-LAMP has a sensitivity of 7.3 × 101 CFU/mL, which is 2-fold higher than that of LAMP. When commercially available raw meat samples (including beef, pork, mutton, and rabbit) were analyzed simultaneously with RT-LAMP and the Chinese National Standard GB 4789.30-2016, their abilities to detect L. monocytogenes were the same. Samples containing L. monocytogenes killed by 15 psi at 121 °C for 15 min were used to confirm the specificity of RT-LAMP for live microorganisms. Thus, we used RT-LAMP to efficiently detect L. monocytogenes in meat products.


Assuntos
Microbiologia de Alimentos/métodos , Listeria monocytogenes/isolamento & purificação , Produtos da Carne/microbiologia , Técnicas de Amplificação de Ácido Nucleico , Animais , Proteínas de Bactérias/genética , Lipoproteínas/genética , Listeria monocytogenes/genética , Carne/microbiologia , Sensibilidade e Especificidade
20.
Vascul Pharmacol ; 122-123: 106597, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31479752

RESUMO

SUMOylation of peroxisome proliferator-activated receptor gamma (PPAR γ) plays important regulatory role in its transcriptional activity. Our recent studies in vitro found that over-SUMOylation of PPARγ, like high glucose and high fat (HG/HF), induced endothelial insulin resistance (IR). However, whether such an event occurs in rats remains unclear. Therefore, our study aimed at investigating whether PPARγ over-SUMOylation could mimic high sucrose/fat diet (HFD) to induce endothelial IR and dysfunction and explored its underlying mechanisms. Normal chow-fed rats were intravenously infected with adenoviruses carrying the wild type cDNAs encoding PPARγ, SUMO1 and PIAS1 (protein inhibitor of activated STAT1). HFD-fed rats were regarded as a positive control. Body physical and biochemical parameters, glucose tolerance and vessel function were detected. The expression and SUMOylation levels of PPARγ were measured by western blotting and co-immunoprecipitation. Our results showed that like HFD, PPARγ over-SUMOylation induced endothelial IR and dysfunction via a negative regulation of eNOS-NO pathway. More importantly, we found that PPARγ over-SUMOylation induced endogenous SUMOylation cascade and exacerbated endothelial IR and dysfunction.The findings will deepen the understanding on PPARγ SUMOylation-regulating insulin signaling network and offer a potential target for prevention and cure of diabetic vascular complications.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA