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1.
Talanta ; 207: 120298, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594629

RESUMO

The detection of exosomal microRNAs (miRNAs) derived from cancer cells with sensitive and selective methods has stimulated increasing interest due to its potential utility in the application of tumor diagnosis. Here, we developed a ratiometric electrochemical DNA biosensor based on a locked nucleic acid (LNA)-modified "Y" shape-like structure for the detection of exosomal miRNA-21 (miR-21). When miR-21 is present, the LNA-assisted strand displacement reaction on the "Y" shape-like structure is activated, leading to a structure change and augmentation of the signal ratio, which reflects the different distances between the electrode surface and two electroactive molecules labeled on the "Y" shape-like structure. With this dual signal ratiometric method, the biosensor shows high accuracy and sensitivity with a limit of detection as low as 2.3 fM. Moreover, because of the logarithm of the signal ratio displays a linear relationship with the logarithm of the miR-21 concentration, the biosensor is stable enough to be used in the detection of miR-21 in MCF-7 cell-derived exosomes. In addition, the biosensor shows good selectivity even in the detection of even a single base-mismatched target due to the LNA-assisted strand displacement reaction. Notably, the sensor is both regenerative and robust. In brief, the high sensitivity and selectivity, combined with the low cost of the glassy carbon electrode, make this biosensor a promising tool for the development of point-of-care testing in cancer.

2.
IEEE Trans Image Process ; 29: 72-84, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31283505

RESUMO

Single image dehazing is a critical image pre-processing step for subsequent high-level computer vision tasks. However, it remains challenging due to its ill-posed nature. Existing dehazing models tend to suffer from model overcomplexity and computational inefficiency or have limited representation capacity. To tackle these challenges, here, we propose a fast and accurate multi-scale end-to-end dehazing network, called FAMED-Net, which comprises encoders at three scales and a fusion module to efficiently and directly learn the haze-free image. Each encoder consists of cascaded and densely connected point-wise convolutional layers and pooling layers. Since no larger convolutional kernels are used and features are reused layer-by-layer, FAMED-Net is lightweight and computationally efficient. Thorough empirical studies on public synthetic datasets (including RESIDE) and real-world hazy images demonstrate the superiority of FAMED-Net over other representative state-of-the-art models with respect to model complexity, computational efficiency, restoration accuracy, and cross-set generalization. The code will be made publicly available.

3.
IEEE Trans Image Process ; 29: 157-169, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31329119

RESUMO

Many existing non-local means (NLM) methods either use Euclidean distance to measure the similarity between patches, or compute weight ωij only once and keep it unchanged during the subsequent denoising iterations, or use only the structure information of the denoised image to update weight ωij . These may lead to the limited denoising performance. To address these issues, this paper proposes the non-local adaptive means (NLAM) for image denoising. NLAM treats weight ωij as an optimization variable and iteratively updates its value. We then introduce three unbiased distances, namely, pixel-pixel, patch-patch, and coupled unbiased distances. These unbiased distances are more robust to measure the image pixel/patch similarity than Euclidean distance. Using the coupled unbiased distance, we propose the unbiased distance non-local adaptive means (UD-NLAM). Because UD-NLAM uses only a single patch size to compute weight ωij , we introduce multipatch UD-NLAM (MUD-NLAM) to adapt different noise levels. To further improve denoising performance, we then propose a new denoising method called MUD-NLAM with wavelet shrinkage (MUD-NLAM-WS). Experimental results show that the proposed NLAM, UD-NLAM, and MUD-NLAM outperform existing NLM methods, and MUD-NLAM-WS achieves a better performance than the state-of-the-art denoising methods.

4.
Retina ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31567816

RESUMO

PURPOSE: This study evaluates the efficacy and usefulness of vitrectomy with internal limiting membrane peeling and autologous blood clot covering without gas tamponade in the treatment of macular holes (MHs). METHODS: All patients with a full-thickness MH with a minimum diameter of <600 µm and a base diameter of <1,200 µm underwent pars plana vitrectomy and internal limiting membrane peeling with autologous blood covering the MH at the end of the surgery. No fluid-air exchange or gas tamponade was performed. Postoperatively, all patients were instructed to adopt supine position overnight and thereafter any comfortable posture. RESULTS: A total of 18 eyes of 18 consecutive patients were included. The mean age of the patients (12 women and 6 men) was 59.06 ± 14.31 years (range, 21-81 years). The MHs composed of 13 idiopathic MHs, 2 MHs with high myopia (axial length > 26.5 mm), 2 traumatic MHs, and 1 MH associated with diabetic macular edema. Among them were five large MHs (minimum diameter > 400 µm). Complete MH closure was achieved in all eyes at the end of the follow-up period (range, 3-14 months). Visual acuity was significantly improved from preoperative 0.89 ± 0.41 logarithm of the minimum angle of resolution (20/155 Snellen) to 0.42 ± 0.33 logarithm of the minimum angle of resolution (20/53 Snellen) at the final visit (P < 0.001). CONCLUSION: The novel surgical protocol using vitrectomy, internal limiting membrane peeling, and autologous blood clot covering at the end of the MH surgery with limited diameters achieved highly effective closure and visual improvement and eliminated the gas tamponade and thus the associated adverse effects and the need for postoperative face-down positioning.

5.
Brain Behav ; : e01411, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566916

RESUMO

OBJECTIVE: To investigate the correlation between simplified classification and laboratory indicators in patients with acute ischemic stroke, also provide accurate evidences for simplified classification and guide clinical interventions and treatment. METHODS: Two hundred patients with acute ischemic stroke were classified into four types according to the characteristics of Traditional Chinese Medicine syndrome: phlegm-heat syndrome, phlegm-dampness syndrome, qi deficiency syndrome, and yin deficiency syndrome. The differences between the types of syndromes and the correlation between laboratory indicators and syndromes were analyzed. RESULTS: Among the 200 patients with acute ischemic stroke, there were significant differences in the level of low-density lipoprotein (LDL-C) (p < .05) between patients with phlegm-heat syndrome and other three types. There were significant differences in the levels of homocysteine (HCY) and fibrinogen (Fib) between patients with yin deficiency syndrome and other three types (p < .05). In addition, there were statistically significant differences in blood glucose (Glu), glycosylated hemoglobin (HBA1c), and total cholesterol (CHO) between phlegm-heat syndrome and qi deficiency syndrome (p < .05). There were significant differences in the levels of Glu, HBA1c, D-2 polymer (D-D), and C-reactive protein (CRP)s between patients with phlegm-heat syndrome and phlegm-dampness syndrome (p < .05). There were statistically significant differences in the levels of CRP and urea nitrogen between patients with yin deficiency syndrome and phlegm-dampness syndrome and qi deficiency syndrome (p < .05). CONCLUSIONS: The four-type simplified classification of Integrated TCM and Western medicine in acute ischemic stroke has specific laboratory data to support. Simplified classification with TCM treatment and intervention of different patients improves the survival and treatment, which is an innovative, easy-to-master clinical diagnosis and treatment model.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31597382

RESUMO

The effect of the freeze-thaw process is an important factor in soil nutrient changes and erosion enhancement. Sediments in the middle reaches of the Yarlung Zangbo River are likely affected by the daily freeze-thaw cycles in winter. Examining the freeze-thaw effects of phosphorus from sediments in this area is of great significance for protecting the structure and safety of the ecosystem. The freeze-thaw process of sediments in the middle reaches of the Yarlung Zangbo River was simulated through laboratory experiments, and different phosphorus contents and particle states were synchronously detected and analyzed. The results show that freeze-thaw cycles can accelerate phosphorus migration and release in the sediments, and the total amount of phosphorus release increases by 12%. After being subjected to freeze-thaw cycles, the sediment particles were broken, and the competition between ions for adsorption sites reduced phosphorus adsorption onto the sediments from the middle reaches of the Yarlung Zangbo River. The organic matter on the sediment surface was also broken down, and the energy dispersive spectroscopy (EDS) results showed that the combined ions that were released competed for the adsorption sites on the particle surfaces, thereby promoting phosphorus release. Among the different forms of phosphorus, aluminum-bound phosphorus (Al-P) and iron-bound phosphorus (Fe-P) are the two most released phosphorus forms by the freeze-thaw process. Although the contents of Al-P and Fe-P only account for 2.41% of the total phosphorus content, both phosphorus forms are biologically available, and freeze-thaw cycles may increase the risk of nutrient loss. This research may provide information for the study of phosphorus in river ecosystems in areas subjected to freeze-thaw cycles.

7.
J Food Biochem ; : e13067, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31599006

RESUMO

Nf-E2-related transcription factor 2 (Nrf2) helps cells fight oxidative stress events in vivo and in vitro by promoting the expression of antioxidants and detoxification enzymes. The necessary factors regulating Nrf2 activity and stability during analgesic nephropathy are not fully understood. Our results suggest that acetaminophen produces nephrotoxicity in HK-2 cells by inhibiting keap1 degradation. APAP subsided Nrf2 nuclear accumulation by inhibition of keap1 degradation, thereby reducing the binding of Nrf2 to ARE, leading to the loss of expression of antioxidant proteins such as HO-1, inducing a series of oxidative stress and apoptosis events. Therefore, Nrf2/keap1/HO-1 signal transduction pathway has a poor prognosis during analgesic nephrotoxicity. Sika deer antler protein (SDAPR) significantly prevented APAP-induced HK-2 cell damage by constitutively stabilized Nrf2 nuclear retention. Excess APAP leads to a decrease in Nrf2 nuclear translocation, leading to severe oxidative stress, increasing the levels of GSH and MDA in HK-2 cells, and reducing the enzyme activities of SOD and CAT in HK-2 cells. Increased biomarker levels of acute kidney injury (AKI) in HK-2 cells, including kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and cystatin C, decrease the mitochondrial membrane potential in HK-2 cells, and cause mitochondrial dysfunction, it also reduced the ratio of mitochondria-associated apoptotic protein Bax/Bcl-2, leading to cell apoptosis. SDAPR dose dependently accorded protection against acetaminophen-induced nephrotoxicity, oxidative damage, and cell apoptosis by its molecular intervention with Nrf2/keap1/HO-1 pathway via keap1 degradation. PRACTICAL APPLICATIONS: In this paper, we investigated the protective effect of SDAPR on APAP-induced AKI in HK-2 cells, and briefly explained its possible mechanism of action, providing a basis for future clinical trials and the development of anti-APAP AKI drugs.

8.
Chem Commun (Camb) ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31599287

RESUMO

A brand new europium(iii) ß-diketonate complex undergoes a single-crystal-to-single-crystal transformation via [2+2] cycloaddition after UV irradiation, triggering strong Eu(iii) red emission turn-on, which is highly photostable even after 50 hours of irradiation. A photo-patterning process is successfully conducted for security printing application in materials science.

9.
J Gen Virol ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31592752

RESUMO

Middle East respiratory syndrome (MERS) is a viral respiratory illness first reported in Saudi Arabia in September 2012 caused by the human coronavirus (CoV), MERS-CoV. Using full-genome sequencing and phylogenetic analysis, scientists have identified three clades and multiple lineages of MERS-CoV in humans and the zoonotic host, dromedary camels. In this study, we have characterized eight MERS-CoV isolates collected from patients in Saudi Arabia in 2015. We have performed full-genome sequencing on the viral isolates, and compared them to the corresponding clinical specimens. All isolates were clade B, lineages 4 and 5. Three of the isolates carry deletions located on three independent regions of the genome in the 5'UTR, ORF1a and ORF3. All novel MERS-CoV strains replicated efficiently in Vero and Huh7 cells. Viruses with deletions in the 5'UTR and ORF1a exhibited impaired viral release in Vero cells. These data emphasize the plasticity of the MERS-CoV genome during human infection.

10.
Int J Nanomedicine ; 14: 7095-7106, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564867

RESUMO

Background: Norisoboldine (NOR), the main isoquinoline alkaloid constituent in Radix Linderae, was demonstrated to have an outstanding anti-arthritis activity. However, a poor oral bioavailability of NOR creates a barrier for its development and application. Methods: A new self-nanoemulsifying drug delivery system (SNEDDS) loaded with the phospholipid complex (PC) was designed to improve the oral bioavailability of NOR. NOR-PC was prepared by solvent evaporation method with a mixture of phospholipid and NOR at a mass ratio of 3:1. The property of PC is to improve the liposolubility of NOR, and made PC embedded in the drug delivery system. The physicochemical property of NOR-PC was characterized by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). According to the ability to dissolve NOR-PC, the oil and cosurfactant were chosen. The surfactant was selected based on its emulsification efficiency in SNEDDS. Pseudo-ternary phase diagram was created to select the best formulation of NOR-PC-SNEDDS, and the pharmacokinetic parameters were detected in rats. In addition, intestinal lymphatic transport and liver microsome experiment were studied to gain insight into the mechanism for NOR-PC-SNEDDS increasing the oral bioavailability of NOR. Results: Solubility detection showed that the PC significantly improved the liposolubility of NOR. NOR-PC-SNEDDS was prepared using NOR-PC, Ethyl oleate, Labrasol, Cremophor EL and transcutol HP at a weight ratio of 1:2:3.36:2.24:2.4 (w/w/w/w/w). The particle size and zeta potential of NOR-PC-SNEDDS were 36.72±1.47 nm and -4.91±0.49 mV after dilution with distilled water at a ratio of 1:50 (w/w). The absolute bioavailability of NOR in the NOR-PC-SNEDDS group significantly increased and the value was 372% in relative to NOR group. Further studies indicated that NOR-PC-SNEDDS promoted the oral bioavailability of NOR by enhancing intestinal lymphatic absorption and inhibiting Phase II metabolism of NOR. Conclusion: These findings suggested that NOR-PC-SNEDDS was able to promote the oral bioavailability of NOR, which provided a foundation for the further development and application of NOR.

11.
J Cell Mol Med ; 2019 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-31565850

RESUMO

Numerous data show that taraxacum officinale extract (TOE) exerts protective effects on inflammatory diseases. However, the underlying mechanisms by which TOE affects dextran sulphate sodium (DSS)-induced colitis remain unclear. After DSS-induced colitis were treated with different concentrations of TOE for 8 days, the bodyweight, disease activity index (DAI), colon lengths and pathological scoring were assessed, and histopathological examination was confirmed by HE staining. Furthermore, a transcriptome sequencing was performed by using the colon tissues between TOE and DSS groups, and the differentially expressed genes were conducted for the Kyoto Encyclopaedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) and were validated by qRT-PCR and immunohistochemistry analysis. In addition, a 16S rDNA sequencing was carried out to distinguish the differential gut microbiota by using the mouse faecal samples between TOE and DSS groups. We found that TOE attenuated the clinical symptoms, lowered the inflammatory scoring and inhibited the secretion of proinflammatory factors TNF-α, IL-1ß and IL-6 in DSS-induced colitis. KEGG and GSEA analysis demonstrated that fatty acid degradation and cytokine-receptor signalling were predominantly enriched in TOE-treated colitis as compared with the DSS group. Further investigations revealed that TOE increased the expression levels of Adh5, Aldh3a2 and Acox3, but decreased those of CCL20, CCR6 and CXCL1/5 in DSS-induced colitis, where TOE also induced the enrichment of S24-7 and adlercreutzia, but decreased the amount of anaerostipes, enterococcus, enterobacteriaceae and peptostreptococcaceae. In conclusion, TOE ameliorated DSS-induced colitis by regulating fatty acid degradation and microbial dysbiosis.

12.
J Cell Physiol ; 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31587299

RESUMO

Apoptosis is the major cause of cardiomyocyte death in myocardial ischemia/reperfusion injury (MI/RI). Increasing evidence suggests that microRNAs (miRNAs) can contribute to the regulation of cardiomyocytes apoptosis by posttranscriptional modulation of gene expression networks. However, the effects of miR-327 in regulating MI/RI-induced cardiomyocytes apoptosis have not been extensively investigated. This study was performed to test whether miR-327 participate in cardiomyocytes apoptosis both in vitro and in vivo, and reveal the potential molecular mechanism of miR-327 regulated MI/RI through targeting apoptosis repressor with caspase recruitment domain (ARC). Sprague-Dawley (SD) rats were subjected to MI/RI by left anterior descending coronary artery occlusion for 30 min and reperfusion for 3 hr. H9c2 cells were exposed to hypoxia for 4 hr and reoxygenation for 12 hr to mimic I/R injury. miRNA-327 recombinant adenovirus vectors were transfected into H9c2 cells for 48 hr and rats for 72 hr before H/R and MI/RI treatment, respectively. The apoptosis rate, downstream molecules of apoptotic pathway, and the target reaction between miRNA-327 and ARC were evaluated. Our results showed that miR-327 was upregulated and ARC was downregulated in the myocardial tissues of MI/RI rats and in H9c2 cells with H/R treatment. Inhibition of miR-327 decreased the expression levels of proapoptotic proteins Fas, FasL, caspase-8, Bax, cleaved caspase-9, cleaved caspase-3, and the release of cytochrome-C, as well as increasing the expression levels of antiapoptotic protein Bcl-2 via negative regulation of ARC both in vivo or vitro. In contrast, overexpression miR-327 showed the reverse effect. Moreover, the results of luciferase reporter assay indicated miR-327 targets ARC directly at the posttranscriptional level. Taken together, inhibition of miR-327 could attenuate cardiomyocyte apoptosis and alleviate I/R-induced myocardial injury via targeting ARC, which offers a new therapeutic strategy for MI/RI.

13.
Int J Med Sci ; 16(9): 1199-1206, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588184

RESUMO

Background: Oxidative stress plays key roles in the progression of lung adenocarcinoma. Recently, we reported that peroxiredoxin 4 (PRDX4), an antioxidant enzyme, can be a prognostic marker of lung adenocarcinoma (LUAD). In the present study, we aimed to further investigate the relationship among the PRDX4 expression, epidermal growth factor receptor (EGFR) mutations and cell proliferation in LUAD. Methods: The expression of PRDX4 was immunohistochemically analyzed and the EGFR mutation status was examined in 127 paraffin-embedded human surgical specimens from patients with stage I LUAD. The PRDX4 expression was considered to be high when >40% of the adenocarcinoma cells were positively stained. In vitro, using plasmid transfection methods, PRDX4 plasmid DNAs were transfected into human lung adenocarcinoma cell lines, A549 (EGFR-wild) or PC-9 (EGFR mutant). The viability of these cells was analyzed using a Cell Counting Kit-8 kit. Results: The number of cases with high PRDX4 expression levels among patients with LUAD with EGFR mutations was significantly larger than that in patients with EGFR wild-type. The combination of the PRDX4 expression level with the EGFR mutation status was closely associated with the prognosis of patients with stage I LUAD. Viability assays showed that the proliferation of A549 cells was significantly suppressed after PRDX4 plasmid transfection, while the overexpression of PRDX4 had no effect on the proliferation of EGFR-mutant PC-9 cells. Conclusions: The PRDX4 expression and EGFR mutation status were significantly associated with the prognosis of patients with stage I LUAD, and EGFR mutations affected the role of PRDX4 in the proliferation of LUAD cells.

14.
Chem Commun (Camb) ; 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31588447

RESUMO

A novel series of emissive o-carborane derivatives, which showed multicolor, highly solid-state emission (ΦF ≥ 43%) and ideal photochemical stability, were synthesized. Inspired by the powerful mammalian olfactory system, we, for the first time, successfully obtained a fluorescent sensor array, which exhibits superior detection capability for nicotine in the gaseous phase (down to 3 ppb). Furthermore, the sensor array can be extended to detect nicotine in aqueous solution at the nano-gram level (∼0.1 ng cm-2) and determine the smoke of cigarette and electronic cigarette.

15.
Adv Mater ; : e1904548, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31588630

RESUMO

Exploring highly efficient electrocatalysts for the oxygen evolution reaction (OER) and unveiling their activity origin are pivotal for energy conversion technologies. Herein, atomically distributed Ni sites over a N-doped hollow carbon matrix are reported as a promising electrocatalyst for OER in alkaline conditions. Significantly boosted activity is observed after the decoration of the active Ni sites with well-controlled coordination geometry. Results of X-ray absorption spectroscopy investigation and density functional theory (DFT) calculation reveal that the effective electronic coupling via the Ni-N coordination can move down the Fermi level and lower the adsorption energy of intermediates, thus resulting in the facilitated OER kinetics.

16.
Spine (Phila Pa 1976) ; 44(20): 1412-1417, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31589199

RESUMO

STUDY DESIGN: A retrospective clinical study. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of fluoroscopy-guided atlantoaxial pedicle screw fixation in patients younger than 12 years. SUMMARY OF BACKGROUND DATA: C1-C2 pedicle screw fixation is a widely accepted treatment method for atlantoaxial dislocation (AAD). However, data regarding its use for atlantoaxial fusion (AAF) in children are limited. METHODS: Thirty-six consecutive patients younger than 12 years underwent C1-C2 pedicle screw fixation for AAD between 2007 and 2017. Anatomical parameters of the C1 pedicle were measured on preoperative computed tomography (CT). Accuracy of pedicle screw fixation was assessed on postoperative CT using the following definitions: Type I, screw threads completely within the bone; Type II, less than half the diameter of the screw violating the surrounding cortex; and Type III, clear violation of the transverse foramen or spinal canal. Demographic, surgical, radiation dose, and clinical data were recorded. RESULTS: Patients underwent 144 screw fixations (67 C1 pedicle screws, 68 C2 pedicle screws, 5 C1 lateral mass screws, and 4 C-2 laminar screws) for a variety of pediatric AADs, with 36.5 ±â€Š8.5 months of follow-up. Among the 135 pedicle screws, 96.3% were deemed "safe" (Type I or II) and 80.7% (109/135) of the screws were rated as being ideal (Type I); five screws (3.7%) were identified as unacceptable (Type III). Average estimated blood loss (EBL) was 92 mL, and the average total radiation exposure during the operation was 6.2 mGy (in the final 26 cases). There were no neurovascular injuries. All patients showed radiographic stability and symptom resolution. CONCLUSION: C1-C2 pedicle screw fixation under fluoroscopy is safe and effective for the treatment of AAD in children younger than 12 years. However, it may be technically challenging owing to the special anatomical features of children and should be performed by experienced surgeons. LEVEL OF EVIDENCE: 3.

17.
Rev Sci Instrum ; 90(9): 093702, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31575269

RESUMO

We present a continuous flow cryostat scanning tunneling microscope (STM) which can be operated at temperatures between 4.9 K and 300 K. A variable temperature insert with 20 mm aperture is installed in the cryostat. A base temperature of 4.9 K at the STM head was achieved with helium exchange gas cooling. By using a novel design of zirconia structure, the size of the STM head was minimized to 9.2 mm in outer diameter. The high compactness and rigidity of the STM head make it less sensitive to vibrations, contributing to the high stability of the tip-sample junction. The drifting rates of the STM at 4.9 K in the X-Y plane and Z direction are 1.96 and 3.05 pm/min, respectively. The performance of the STM was demonstrated by atomically resolved imaging of graphite and NbSe2 without using external vibrational isolation. Furthermore, the dI/dV spectra of NbSe2 were resolved near its critical temperature, illustrating the formation process of the superconducting gap as a function of temperature. This STM is ultrahigh vacuum and strong magnetic field compatible, making it promising for direct application in the extreme conditions involving water-cooled magnets and hybrid magnets.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31577560

RESUMO

INTRODUCTION: Adverse histopathological status (AHS) decreases outcomes of gastric cancer (GC). With the lack of a single factor with great reliability to preoperatively predict AHS, we developed a computational approach by integrating large-scale imaging factors, especially radiomic features at contrast-enhanced computed tomography, to predict AHS and clinical outcomes of patients with GC. METHODS: Five hundred fifty-four patients with GC (370 training and 184 test) undergoing gastrectomy were retrospectively included. Six radiomic scores (R-scores) related to pT stage, pN stage, Lauren & Borrmann (L&B) classification, World Health Organization grade, lymphatic vascular infiltration, and an overall histopathologic score (H-score) were, respectively, built from 7,000+ radiomic features. R-scores and radiographic factors were then integrated into prediction models to assess AHS. The developed AHS-based Cox model was compared with the American Joint Committee on Cancer (AJCC) eighth stage model for predicting survival outcomes. RESULTS: Radiomics related to tumor gray-level intensity, size, and inhomogeneity were top-ranked features for AHS. R-scores constructed from those features reflected significant difference between AHS-absent and AHS-present groups (P < 0.001). Regression analysis identified 5 independent predictors for pT and pN stages, 2 predictors for Lauren & Borrmann classification, World Health Organization grade, and lymphatic vascular infiltration, and 3 predictors for H-score, respectively. Area under the curve of models using those predictors was training/test 0.93/0.94, 0.85/0.83, 0.63/0.59, 0.66/0.63, 0.71/0.69, and 0.84/0.77, respectively. The AHS-based Cox model produced higher area under the curve than the eighth AJCC staging model for predicting survival outcomes. Furthermore, adding AHS-based scores to the eighth AJCC staging model enabled better net benefits for disease outcome stratification. DISCUSSION: The developed computational approach demonstrates good performance for successfully decoding AHS of GC and preoperatively predicting disease clinical outcomes.

19.
J Clin Microbiol ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578261

RESUMO

Vaccination with inactivated vaccines is still the main measure to control foot-and-mouth disease (FMD) in endemic areas, and the level of neutralizing antibody in vaccinated animals is directly related to their protection against virus challenge. Currently, neutralizing antibody is mainly detected using virus neutralization test (VNT) based on cell culture, which is laborious, time-consuming and requiring restrictive biocontainment facilities. In this study, two broadly neutralizing antibodies (bnAbs) E46 and F128 were successfully produced using single B cell isolation techniques from peripheral blood mononuclear cells (PBMCs) of bovine sequentially immunized with three topotypes of foot-and-mouth disease virus (FMDV) serotype O. Based on these bnAbs, a blocking ELISA for detecting neutralizing antibodies (NA-ELISA) against FMDV serotype O was developed. The specificity and sensitivity of the test were estimated as 99.21% and 100%, respectively. A significant correlation (P<0.01) was observed between the NA-ELISA titers and the VNT titers for all sera from vaccinated animals and for all tested strains, suggesting that NA-ELISA could detect neutralizing antibodies against FMDV serotype O strains of wide antigenic and molecular diversity, and could be used for the evaluation of protective immunity.

20.
Oncol Rep ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31578585

RESUMO

Platinum­containing doublet chemotherapy is the cornerstone of lung cancer treatment; however, cisplatin resistance is a major obstacle in the treatment of lung cancer. However, the mechanism underlying this resistance has not been fully elucidated. Previous studies have shown that serum apurinic/apyrimidinic endonuclease 1 (APE1) levels in patients with NSCLC are inversely associated with progression­free survival after platinum­containing doublet chemotherapy, and can serve as a biomarker for predicting disease prognosis and treatment efficacy. The present study was designed to investigate the role played by APE1 in the resistance of lung cancer to cisplatin. The levels of mitochondrial apurinic endonuclease 1 (m­APE1) and total APE1 (t­APE1) protein in a cisplatin­resistant A549 cell line (A549/DDP) and cisplatin­sensitive A549 cells were analyzed by western blotting. Mitochondrial membrane potential was detected by using the JC­1 staining method. The cisplatin­resistance of APE1­overexpressing A549 cells and APE1­silenced A549/DDP cells was assessed by cell apoptosis and colony formation assays. The results revealed that cisplatin­resistant A549 cells contained high levels of APE1, and exhibited elevated levels of autophagy. The levels of m­APE1 and t­APE1 protein were increased in the A549/DDP cells when compared with these levels in the A549 cells. Overexpression of APE1 and Mia40 enhanced the cisplatin resistance and autophagy of the A549 cells. APE1 knockdown restored the cisplatin sensitivity and reduced the levels of LC3II and Parkin in the A549/DDP cells, but promoted the release of cytochrome c. Furthermore, Parkin silencing or treatment with 3­methyladenine (3­MA, an autophagy inhibitor) promoted the apoptosis of APE1­overexpressing A549 cells, indicating that Parkin­mediated mitophagy plays an important role in the APE1­induced cisplatin resistance of A549 cells. In conclusion, APE1 promotes the cisplatin resistance of lung cancer cells by inducing Parkin­mediated mitophagy.

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