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1.
Z Gastroenterol ; 58(2): 137-145, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32050284

RESUMO

PURPOSE: Rectal neuroendocrine tumors are rare with good prognosis. Several endoscopic methods such as endoscopic polypectomy, endoscopic submucosal dissection (ESD), endoscopic mucosal resection (EMR), and modified endoscopic mucosal resection (m-EMR) are used in the treatment of rectal neuroendocrine tumors. Although m-EMR is derived from traditional EMR, it has not been widely used in clinical practice. In this study, we compared the efficacy and safety of EMR and m-EMR in the treatment of rectal neuroendocrine tumors by performing a meta-analysis. MATERIALS AND METHODS: We searched PubMed, Web of Science, and EMBASE index up to the end of January 2017 for all published literature about EMR and m-EMR in the treatment of rectal neuroendocrine tumors. RESULTS: A total of 11 studies involving 811 patients were included. The pooled data suggested that there was a significantly higher rate of histologic complete resection and endoscopic complete resection among patients treated with m-EMR than those treated with EMR (histologic complete resection: OR = 0.23, 95 % CI = 0.10-0.51, p < 0.01; endoscopic complete resection: OR = 0.13, 95 % CI = 0.02-0.74, p = 0.02). The procedure time of EMR was longer than m-EMR (MD = 2.40, 95 % CI = 0.33-4.46, p = 0.02). There was a significantly higher rate of vertical margin involvement among patients treated with EMR than those treated with m-EMR; whereas, there was no significant difference of lateral margin involvement between the m-EMR and EMR groups (vertical margin involvement: OR = 5.00, 95 % CI = 2.67-9.33, p < 0.01; lateral margin involvement: OR = 1.44, 95 % CI = 0.48-4.37, p = 0.52). There was no significant difference in mean tumor size among patients treated with m-EMR versus those treated with EMR (MD = -0.30, 95 % CI = -0.75-0.14, p = 0.18); further, there was no significant difference in endoscopic mean sizes of the tumor and pathological mean sizes of the tumor between the m-EMR and EMR groups (endoscopic mean sizes of the tumor: MD = 0.20, 95 % CI = -0.44-0.84, p = 0.43; pathological mean sizes of the tumor: MD = 0.62, 95 % CI = -0.68-1.92, p = 0.05). No significant differences were detected among the treatment groups with regard to complications (bleeding: OR = 0.87, 95 % CI = 0.39-1.95, p = 0.73; complications (bleeding and perforation): OR = 0.87, 95 % CI = 0.40-1.88, p = 0.73). CONCLUSION: The efficacy of m-EMR are better than EMR among patients undergoing endoscopic treatment of rectal neuroendocrine tumors, and the safety of m-EMR is equivalent to EMR treatment.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32052346

RESUMO

People's parallel-processing ability is limited, as demonstrated by the psychological refractory period (PRP) effect: The reaction time to the second stimulus (RT2) increases as the stimulus onset asynchrony (SOA) between two stimuli decreases. Most theoretical models of PRP are independent of modalities. Previous research on PRP mainly focused on vision and audition as input modalities; tactile stimuli have not been fully explored. Research using other paradigms and involving tactile stimuli, however, found that dual-task performance depended on input modalities. This study explored PRP with all the combinations of input modalities. Thirty participants judged the magnitude (small or large) of two stimuli presented in different modalities with an SOA of 75-1,200 ms. PRP effect was observed, i.e., RT2 increased with a decreasing SOA, in all the modalities. Only in the auditory-tactile condition did the accuracy of Task 2 decrease with a decreasing SOA. In the auditory-tactile and tactile-visual conditions, RT to the first stimulus also increased with a decreasing SOA. Current models could only explain part of the results, and modality characteristics help to explain the overall data pattern better. Limitations and directions for future studies regarding reaction time, task difficulty, and response modalities are discussed.

3.
Cell Death Dis ; 11(2): 81, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015336

RESUMO

Glioblastoma is the most common and malignant form of primary central nervous tumor in adults. Long noncoding RNAs (lncRNAs) have been reported to play a pivotal role in modulating gene expression and regulating human tumor's malignant behaviors. In this study, we confirmed that lncRNA brain-derived neurotrophic factor antisense (BDNF-AS) was downregulated in glioblastoma tissues and cells, interacted and stabilized by polyadenylate-binding protein cytoplasmic 1 (PABPC1). Overexpression of BDNF-AS inhibited the proliferation, migration, and invasion, as well as induced the apoptosis of glioblastoma cells. In the in vivo study, PABPC1 overexpression combined with BDNF-AS overexpression produced the smallest tumor and the longest survival. Moreover, BDNF-AS could elicit retina and anterior neural fold homeobox 2 (RAX2) mRNA decay through STAU1-mediated decay (SMD), and thereby regulated the malignant behaviors glioblastoma cells. Knockdown of RAX2 produced tumor-suppressive function in glioblastoma cells and increased the expression of discs large homolog 5 (DLG5), leading to the activation of the Hippo pathway. In general, this study elucidated that the PABPC1-BDNF-AS-RAX2-DLG5 mechanism may contribute to the anticancer potential of glioma cells and may provide potential therapeutic targets for human glioma.

4.
J Magn Reson Imaging ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32061014

RESUMO

BACKGROUND: MRI-based radiomics has been used to diagnose breast lesions; however, little research combining quantitative pharmacokinetic parameters of dynamic contrast-enhanced MRI (DCE-MRI) and diffusion kurtosis imaging (DKI) exists. PURPOSE: To develop and validate a multimodal MRI-based radiomics model for the differential diagnosis of benign and malignant breast lesions and analyze the discriminative abilities of different MR sequences. STUDY TYPE: Retrospective. POPULATION: In all, 207 female patients with 207 histopathology-confirmed breast lesions (95 benign and 112 malignant) were included in the study. Then 159 patients were assigned to the training group, and 48 patients comprised the validation group. FIELD STRENGTH/SEQUENCE: T2 -weighted (T2 W), T1 -weighted (T1 W), diffusion-weighted MR imaging (b-values = 0, 500, 800, and 2000 seconds/mm2 ) and quantitative DCE-MRI were performed on a 3.0T MR scanner. ASSESSMENT: Radiomics features were extracted from T2 WI, T1 WI, DKI, apparent diffusion coefficient (ADC) maps, and DCE pharmacokinetic parameter maps in the training set. Models based on each sequence or combinations of sequences were built using a support vector machine (SVM) classifier and used to differentiate benign and malignant breast lesions in the validation set. STATISTICAL TESTS: Optimal feature selection was performed by Spearman's rank correlation coefficients and the least absolute shrinkage and selection operator algorithm (LASSO). Receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of the radiomics models in the validation set. RESULTS: The area under the ROC curve (AUC) of the optimal radiomics model, including T2 WI, DKI, and quantitative DCE-MRI parameter maps was 0.921, with an accuracy of 0.833. The AUCs of the models based on T1 WI, T2 WI, ADC map, DKI, and DCE pharmacokinetic parameter maps were 0.730, 0.791, 0.770, 0.788, and 0.836, respectively. DATA CONCLUSION: The model based on radiomics features from T2 WI, DKI, and quantitative DCE pharmacokinetic parameter maps has a high discriminatory ability for benign and malignant breast lesions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

5.
Chemistry ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32053247

RESUMO

C-N bond formation is regarded as a very useful and fundamental reaction, which is important for the synthesis of nitrogen-containing molecules in both organic and pharmaceutical chemistry. Noble metal and homogeneous catalysts have been used for C-N bond formation frequently, however, there are still some problems for these catalysts such as high cost, serious pollution and low atom economy. Herein the low-toxic and cheaper iron complex was loaded on CNTs and the heterogenous single-atom catalyst (SAC) named Fe-N x /CNTs was prepared. We applied this SAC to the synthesis of C-N bonds for the first time. It was found that Fe-N x /CNTs was an efficient catalyst for the synthesis of C-N bonds from aromatic amines and ketones. The catalytic performance is markedly excellent with the yield up to 96%, 6-fold higher than that of noble metal catalysts such as AuCl 3 /CNTs and RhCl 3 /CNTs. It was suitable for up to 13 aromatic amine substrates with no additives and 17 enaminones were obtained. By using high-angle annular darkfield scanning transmission electron microscopy (HAADF-STEM) in combination with X-ray adsorption spectroscopy (XAS), we have observed iron species of Fe-N x /CNTs were in good dispersion as single atoms and Fe-N x might be the catalytic active site. This Fe-N x /CNTs catalyst has potential industrial application for its seven runs without any significant loss of activity.

6.
Rev Sci Instrum ; 91(1): 014703, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32012643

RESUMO

A pulsed intense magnetic field device was developed for the Shanghai Shenguang-II (SG-II) laser facility. The device using a double-turn coil with 12 mm diameter is capable of producing a peak current of 42 kA with 280 ns rising edge and 200 ns flat top width. A peak magnetic field of 8.8 T is achieved at the center of the coil. A two-section transmission line composed by a flexible section and a rigid section is designed to meet the target chamber environment of SG-II laser facility. The flexible section realizes the soft-connection between the capacitor bank and the target chamber, which facilitates the installation of the magnetic field device and the adjustment of the coil. The rigid section is as small as possible so that it can be inserted into the target chamber from any smallest flange, realizing elastic magnetic field configuration. The magnetic coil inside the chamber can be adjusted finely through a mechanical component on the rigid transmission line outside the target chamber. The adjustment range is up to 5 cm in both radial and axial directions with ∼50 µm precision. The device has been successfully operated on SG-II laser facility.

7.
BMC Cancer ; 20(1): 106, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041568

RESUMO

OBJECTIVE: Solitary pulmonary nodules (SPNs) is a common radiographic finding and require further evaluation because of the possibility of lung cancer. This study aimed to determine the sensitivity and specificity of circulating tumour cells (CTCs) as a marker for the diagnosis of SPNs and the integration of CTCs, carcinoembryonic antigen (CEA) and imaging findings to improve the sensitivity and specificity of diagnosis in patients with SPNs suspected of being lung cancer. METHOD: For the serum biomarker assay, the concentration of CEA was measured by an automated electrochemiluminescence analyzer. CTCs were collected from 6 ml of blood by the SE i-FISH method, which detects the gene copy number in eight chromosomes and the tumour-associated antigen CK18. RESULTS: With a threshold of 6 CTC units, the method showed a sensitivity of 67.1% and a specificity of 56.5% in the diagnosis of NSCLC, especially in the upper lobe, in which the diagnostic strength was the highest (P < 0.01). CTCs, CEA and nodule type had the highest diagnostic efficacy (area under the curve, 0.827; 95% confidence interval, 0.752-0.901) in patients with SPNs being suspected lung cancer. Combining CTCs (cut-off value 12 units) with CEA (1.78 ng/ml), the method showed a sensitivity of 77.8% and a specificity of 90% in the diagnosis of NSCLC, especially in the upper lobe, subsolid nodules and nodules ≥8 mm. CONCLUSIONS: Our results demonstrated that CTCs are feasible diagnostic biomarkers in patients with SPNs, especially in the upper lobe. Furthermore, CTCs combined with CEA showed higher diagnostic efficacy in the upper lobe, subsolid nodules and nodules ≥8 mm.

8.
Ecotoxicol Environ Saf ; 192: 110265, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32045784

RESUMO

Diarrheic shellfish poisoning (DSP) toxins are produced by harmful microalgae and accumulate in bivalve mollusks, causing various toxicity. These toxic effects appear to abate with increasing DSP concentration and longer exposure time, however, the underlying mechanisms remain unclear. To explore the underlying molecular mechanisms, de novo transcriptome analysis of the digestive gland of Perna viridis was performed after Prorocentrum lima exposure. RNA-seq analysis showed that 1886 and 237 genes were up- and down-regulated, respectively after 6 h exposure to P. lima, while 265 genes were up-regulated and 217 genes were down-regulated after 96 h compared to the control. These differentially expressed genes mainly involved in Nrf2 signing pathways, immune stress, apoptosis and cytoskeleton, etc. Combined with qPCR results, we speculated that the mussel P. viridis might mainly rely on glutathione S-transferase (GST) and ABC transporters to counteract DSP toxins during short-term exposure. However, longer exposure of P. lima could activate the Nrf2 signaling pathway and inhibitors of apoptosis protein (IAP), which in turn reduced the damage of DSP toxins to the mussel. DSP toxins could induce cytoskeleton destabilization and had some negative impact on the immune system of bivalves. Collectively, our findings uncovered the crucial molecular mechanisms and the regulatory metabolic nodes that underpin the defense mechanism of bivalves against DSP toxins and also advanced our current understanding of bivalve defense mechanisms.

9.
Crit Rev Biotechnol ; 40(2): 265-281, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31928250

RESUMO

As a host for therapeutic protein expression, Chinese hamster ovary (CHO) cells are widely utilized in the mainstream biopharmaceutical industry. Cell culture process development plays an important role in transitioning laboratory research to manufacturing. Among different mathematic tools, kinetic modeling is commonly achieved through analyzing cell culture data to design process parameters, optimize media, and scale up bioreactors. In this review, we examine key factors for upstream process development, and summarize currently used kinetic modeling strategies. In addition, two original examples of kinetic modeling application optimizing cell culture performance are presented. A comprehensive understanding is provided for the kinetic modeling and its applications in cell culture process development.

10.
Biotechnol Prog ; : e2959, 2020 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-31930722

RESUMO

Temperature shifts to lower culture temperatures are frequently employed in the manufacturing of protein therapeutics in mammalian cells to improve productivity, viability, or quality attributes. The direction and extent to which a temperature shift affects productivity and quality may vary depending on the expression host and characteristics of the expressed protein. We demonstrated here that two Chinese hamster ovary (CHO) clones expressing different human monoclonal antibodies responded differently to a temperature shift despite sharing a common parental CHO cell line. Within a single CHO line, we observed a nonlinear response to temperature shift. A moderate shift to 35°C significantly decreased final titer relative to the unshifted control while a larger shift to 32°C significantly increased final titer by 25%. Therefore, we proposed a systematic empirical approach to assess the utility of a temperature shift for faster implementation during process development. By testing multiple shift parameters, we identified optimum shift conditions in shake flasks and successfully translated findings to benchtop bioreactors and 1,000-L bioreactor scale. Significant differences in final antibody titer and charge variants were observed with temperature shift increments as small as Δ1.5°C. Acidic charge variants decreased monotonically with decreasing shift temperature in both cell lines; however, final antibody titer required simultaneous optimization of shift day and temperature. Overall, we were able to show that a systematic approach to identify temperature shift parameters at small scales is useful to optimize protein production and quality for efficient and confident translation to large-scale production.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31940514

RESUMO

Due to the complicated thoracic movements which contain both sliding motion occurring at lung surfaces and smooth motion within individual organs, respiratory estimation is still an intrinsically challenging task. In this paper, we propose a novel regularization term called locally adaptive total p-variation (LaTpV) and embed it into a parametric registration framework to accurately recover lung motion. LaTpV originates from a modified Lp -norm constraint ([Formula: see text]), where a prior distribution of modeled by the Dirac-shaped function is constructed to specifically assign different values to voxels. LaTpV adaptively balances the smoothness and discontinuity of the displacement field to encourage an expected sliding interface. Additionally, we also analytically deduce the gradient of the cost function with respect to transformation parameters. To validate the performance of LaTpV, we not only test it on two mono-modal databases including synthetic images and pulmonary computed tomography (CT) images, but also on a more difficult thoracic CT and positron emission tomography (PET) dataset for the first time. For all experiments, both the quantitative and qualitative results indicate that LaTpV significantly surpasses some existing regularizers such as bending energy and parametric total variation. The proposed LaTpV based registration scheme might be more superior for sliding motion correction and more potential for clinical applications such as the diagnosis of pleural mesothelioma and the adjustment of radiotherapy plans.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31995490

RESUMO

Medical image registration can be used for studying longitudinal and cross-sectional data, quantitatively monitoring disease progression and guiding computer assisted diagnosis and treatments. However, deformable registration which enables more precise and quantitative comparison has not been well developed for retinal optical coherence tomography (OCT) images. This paper proposes a new 3D registration approach for retinal OCT data called OCTRexpert. To the best of our knowledge, the proposed algorithm is the first full 3D registration approach for retinal OCT images which can be applied to longitudinal OCT images for both normal and serious pathological subjects. In this approach, a pre-processing method is first performed to remove eye motion artifact and then a novel design-detection-deformation strategy is applied for the registration. In the design step, a couple of features are designed for each voxel in the image. In the detection step, active voxels are selected and the point-to-point correspondences between the subject and template images are established. In the deformation step, the image is hierarchically deformed according to the detected correspondences in multi-resolution. The proposed method is evaluated on a dataset with longitudinal OCT images from 20 healthy subjects and 4 subjects diagnosed with serious Choroidal Neovascularization (CNV). Experimental results show that the proposed registration algorithm consistently yields statistically significant improvements in both Dice similarity coefficient and the average unsigned surface error compared with the other registration methods.

13.
Biomed Pharmacother ; 124: 109852, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31972357

RESUMO

BACKGROUND: Breast cancer is the most common malignant tumor in women. Due to limited treatment outcome and high rate of metastasis, the prognosis is especially poor for triple-negative breast cancer. It is urgent to discover and develop novel agents for treatment of breast cancer. Herein, we investigated the potential mechanisms of Oleandrin's (a cardiac glycoside) cytotoxic activity against breast cancer cells. METHODS: Cell proliferation was assessed by xCELLigence Real-Time Cell Analyzer (RTCA)-MP system. Apoptotic cells were detected by using Annexin V/PI staining and nuclear fragments observation. The effect of oleandrin on ATP1B3 expression and markers of ER stress were determined by western blot. A primary cell sensitivity assay was performed via a collagen gel droplet-embedded culture drug sensitivity method (CD-DST). RESULTS: Oleandrin suppressed cell proliferation and colony formation in the three breast cancer cell lines but did not affect normal mammary epithelial cells. Additionally, the expression of ATP1B3 was higher in the three breast cancer cell lines compared to MCF10A cells. Treatment with oleandrin increased the number of apoptotic cells and led to nuclear pyknosis, fragmentation, and apoptotic body formation in breast cancer cells. Furthermore, oleandrin treatment increased expression of Bax and Bim but decreased that of Bcl-2. Treatment with oleandrin also upregulated the expression of endoplasmic reticulum stress associated proteins, including eIF2α, ATF4, and CHOP, but not PERK. oleandrin treatment also induced the phosphorylation of PERK and eIF2α. Of note, oleandrin exhibited antitumor effects on patient-derived breast cancer cells under three-dimensional culture conditions. CONCLUSIONS: Taken together, our results suggest that oleandrin induces mitochondrial-mediated apoptosis by activating endoplasmic reticulum stress in breast cancer. Moreover, oleandrin may be an effective strategy for the treatment of breast cancer.

14.
J Am Chem Soc ; 142(6): 3002-3012, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31968934

RESUMO

The rapid growth in the global energy demand for space cooling requires the development of more efficient environmental chillers for which adsorption-based cooling systems can be utilized. Here, in this contribution, we explore sorbents for chiller use via a pore-engineering concept to construct analogs of the 1-dimensional pore metal-organic framework MOF-74 by using elongated organic linkers and stereochemistry control. The prepared pore-engineered MOFs show remarkable equilibrium adsorption of the selected fluorocarbon refrigerant that is translated to a modeled adsorption-based refrigeration cycle. To probe molecular level interactions at the origin of these unique adsorption properties for this series of Ni-MOFs, we combined in situ synchrotron X-ray powder diffraction, neutron powder diffraction, X-ray absorption spectroscopy, calorimetry, Fourier transform infrared techniques, and molecular simulations. Our results reveal the coordination of fluorine (of CH2F in R134a) to the nickel(II) open metal centers at low pressures for each Ni-MOF analog and provide insight into the pore filling mechanism for the full range of the adsorption isotherms. The newly designed Ni-TPM demonstrates exceptional R134a adsorption uptake compared to its parent microporous Ni-MOF-74 due to larger engineered pore size/volume. The application of this adsorption performance toward established chiller conditions yields a working capacity increase for Ni-TPM of about 400% from that of Ni-MOF-74, which combined with kinetics directly correlates to both a higher coefficient of performance and a higher average cooling capacity generated in a modeled chiller.

16.
Cancer Sci ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31943575

RESUMO

Upstream ORF (uORF) is a translational initiation element located in the 5'UTR of eukaryotic mRNAs. Studies have found that uORFs play an important regulatory role in many diseases. Based on The Cancer Genome Atlas database, the results of our experiments and previous research evidence, we investigated transcription factor AP-4 (TFAP4) and its uORF, LIM and SH3 protein 1 (LASP1), long noncoding RNA 00520 (LINC00520), and microRNA (miR)-520f-3p as candidates involved in glioma malignancy, which is a poorly understood process. Both TFAP4-66aa-uORF and miR-520f-3p were downregulated, and TFAP4, LASP1, and LINC00520 were highly expressed in glioma tissues and cells. TFAP4-66aa-uORF or miR-520f-3p overexpression or TFAP4, LASP1, or LINC00520 knockdown inhibited glioma cell proliferation, migration, and invasion, but promoted apoptosis. TFAP4-66aa-uORF inhibited the translation of TFAP4 by binding to the TFAP4 mRNA. MicroRNA-520f-3p inhibited TFAP4 expression by binding to its 3'UTR. However, LINC00520 could promote the expression of TFAP4 by competitively binding to miR-520f-3p. In addition, TFAP4 transcriptionally activated LASP1 and LINC00520 expression by binding to their promoter regions, forming a positive feedback loop of TFAP4/LINC00520/miR-520f-3p. Our findings together indicated that TFAP4-66aa-uORF inhibited the TFAP4/LINC00520/miR-520f-3p feedback loop by directly inhibiting TFAP4 expression, subsequently leading to inhibition of glioma malignancy. This provides a basis for developing new therapeutic approaches for glioma treatment.

17.
Eur Radiol ; 30(2): 1096-1104, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31673836

RESUMO

OBJECTIVES: To evaluate the impact of intrahepatic cholestasis on liver fibrosis staging using liver stiffness measurements (LSM). METHODS: Between July 2011 and September 2016, a total of 1197 patients with chronic hepatitis B (CHB) infection were enrolled to collect clinical, biological, 2D shear wave elastography (SWE), and histological (METAVIR scoring system) data. LSM was compared in patients with normal total bilirubin (TB) versus abnormal TB for each group of fibrosis stage, alanine aminotransferase (ALT) levels, and inflammation grade. Logistic regression and ROC analyses were performed to assess the benefit of adding TB and to LSM for fibrosis staging. RESULTS: Nine hundred and seventy-three patients were analyzed. Within the same fibrosis stage, LSMs showed significantly higher value in patients with abnormal TB than those with normal TB. Increased LSM for abnormal TB was generally found within different sub-groups of patients (≤ F2 or ≥ F3; ALT < 2 × upper limit of normal (ULN) or ALT ≥ 2 × ULN; METAVIR activity grade ≤ 1 or ≥ 2). Patients with abnormal TB level showed higher optimal cutoff values: 10.46 kPa for ≥ F2, 10.94 kPa for ≥ F3, and 15.88 kPa for F4, than those with normal TB (7.62 kPa, 8.26 kPa, and 11.01 kPa, respectively). LSM assessed fibrosis stage (≥ F2, ≥ F3, F4) showed higher false positive rate in patients with abnormal TB level (44.6%, 45.1%, 39.6%) than those with normal TB (20.7%, 17.1%, 14.4%). However, the area under the ROC curve did not change appreciably when adding TB to LSM for fibrosis stage. CONCLUSION: Intrahepatic cholestasis showed slight effect on LSM in patients with CHB, also leading to overestimation of liver fibrosis stages. But adding TB level to LSM did not improve the overall diagnostic performance of liver fibrosis stage. KEY POINTS: • Intrahepatic cholestasis showed slight effect on liver stiffness measurements (LSMs) in chronic HBV patients. • Patients with abnormal total bilirubin (TB) level showed higher optimal cutoff values and false positive rate. • When taking into account intrahepatic cholestasis, the diagnostic performance of LSM for liver fibrosis staging in patients with chronic HBV infection will not improve.

18.
J Cell Mol Med ; 24(1): 342-355, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31654502

RESUMO

Recent studies indicate circular RNAs are related to dysregulation of vascular endothelial cell function, yet the underlying mechanisms have remained elusive. Here, we characterized the functional role of circular RNA USP1 (circ-USP1) in the regulation of the blood-tumour barrier (BTB) permeability and the potential mechanisms. In the current study, the circ-USP1 expressing level was up-regulated in glioma cerebral microvascular endothelial cells (GECs) of the BTB model in vitro. Knockdown of circ-USP1 disrupted the barrier integrity, increased its permeability as well as reduced tight junction-related protein claudin-5, occludin and ZO-1 expressions in GECs. Bioinformatic prediction and luciferase assay indicated that circ-USP1 bound to miR-194-5p and suppressed its activity. MiR-194-5p contributed to circ-USP1 knockdown-induced increase of BTB permeability via targeting and down-regulating transcription factor FLI1. Furthermore, FLI1 regulated the expressions of claudin-5, occludin and ZO-1 in GECs through binding to their promoter regions. Single or combined treatment of circ-USP1 and miR-194-5p effectively promoted anti-tumour drug doxorubicin across BTB to induce apoptosis of glioma cells. Overall, this present study identified the crucial regulation of circ-USP1 on BTB permeability via miR-194-5p/FLI1 axis-mediated regulation of tight junction proteins, which might facilitate the development of therapeutics against human gliomas.

19.
Nat Mater ; 19(1): 49-55, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31611669

RESUMO

Epitaxially fused colloidal quantum dot (QD) superlattices (epi-SLs) may enable a new class of semiconductors that combine the size-tunable photophysics of QDs with bulk-like electronic performance, but progress is hindered by a poor understanding of epi-SL formation and surface chemistry. Here we use X-ray scattering and correlative electron imaging and diffraction of individual SL grains to determine the formation mechanism of three-dimensional PbSe QD epi-SL films. We show that the epi-SL forms from a rhombohedrally distorted body centred cubic parent SL via a phase transition in which the QDs translate with minimal rotation (~10°) and epitaxially fuse across their {100} facets in three dimensions. This collective epitaxial transformation is atomically topotactic across the 103-105 QDs in each SL grain. Infilling the epi-SLs with alumina by atomic layer deposition greatly changes their electrical properties without affecting the superlattice structure. Our work establishes the formation mechanism of three-dimensional QD epi-SLs and illustrates the critical importance of surface chemistry to charge transport in these materials.

20.
Hepatology ; 71(1): 112-129, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31148184

RESUMO

To identify hepatocellular carcinoma (HCC)-implicated long noncoding RNAs (lncRNAs), we performed an integrative omics analysis by integrating mRNA and lncRNA expression profiles in HCC tissues. We identified a collection of candidate HCC-implicated lncRNAs. Among them, we demonstrated that an lncRNA, which is named as p53-stabilizing and activating RNA (PSTAR), inhibits HCC cell proliferation and tumorigenicity through inducing p53-mediated cell cycle arrest. We further revealed that PSTAR can bind to heterogeneous nuclear ribonucleoprotein K (hnRNP K) and enhance its SUMOylation and thereby strengthen the interaction between hnRNP K and p53, which ultimately leads to the accumulation and transactivation of p53. PSTAR is down-regulated in HCC tissues, and the low PSTAR expression predicts poor prognosis in patients with HCC, especially those with wild-type p53. Conclusion: This study sheds light on the tumor suppressor role of lncRNA PSTAR, a modulator of the p53 pathway, in HCC.

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