To construct a prediction model based on peritumoral radiomics signatures from CT images and investigate its efficiency in predicting early recurrence (ER) of hepatocellular carcinoma (HCC) after ...curative treatment.
In total, 156 patients with primary HCC were randomly divided into the training cohort (109 patients) and the validation cohort (47 patients). From the pretreatment CT images, we extracted 3-phase two-dimensional images from the largest cross-sectional area of the tumor. A region of interest (ROI) was manually delineated around the lesion for tumoral radiomics (T-RO) feature extraction, and another ROI was outlined with an additional 2 cm peritumoral area for peritumoral radiomics (PT-RO) feature extraction. The least absolute shrinkage and selection operator (LASSO) logistic regression model was applied for feature selection and model construction. The T-RO and PT-RO models were constructed. In the validation cohort, the prediction efficiencies of the two models and peritumoral enhancement (PT-E) were evaluated qualitatively by receiver operating characteristic (ROC) curves, calibration curves and decision curves and quantitatively by area under the curve (AUC), the category-free net reclassification index (cfNRI) and integrated discrimination improvement values (IDI).
By comparing AUC values, the prediction accuracy in the validation cohort was good for the PT-RO model (0.80 vs. 0.79, P = 0.47) but poor for the T-RO model (0.82 vs. 0.62, P < 0.01), which was significantly overfitted. In the validation cohort, the ROC curves, calibration curves and decision curves indicated that the PT-RO model had better calibration efficiency and provided greater clinical benefits. CfNRI indicated that the PT-RO model correctly reclassified 47% of ER patients and 32% of non-ER patients compared to the T-RO model (P < 0.01); additionally, the PT-RO model correctly reclassified 24% of ER patients and 41% of non-ER patients compared to PT-E (P = 0.02). IDI indicated that the PT-RO model could improve prediction accuracy by 0.22 (P < 0.01) compared to the T-RO model and by 0.20 (P = 0.01) compared to PT-E.
The CT-based PT-RO model can effectively predict the ER of HCC and is more efficient than the T-RO model and the conventional imaging feature PT-E.
Neoadjuvant chemotherapy is a promising treatment option for potential resectable gastric cancer, but patients' responses vary. We aimed to develop and validate a radiomics score (rad_score) to ...predict treatment response to neoadjuvant chemotherapy and to investigate its efficacy in survival stratification.
A total of 106 patients with neoadjuvant chemotherapy before gastrectomy were included (training cohort: n = 74; validation cohort: n = 32). Radiomics features were extracted from the pre-treatment portal venous-phase CT. After feature reduction, a rad_score was established by Randomised Tree algorithm. A rad_clinical_score was constructed by integrating the rad_score with clinical variables, so was a clinical score by clinical variables only. The three scores were validated regarding their discrimination and clinical usefulness. The patients were stratified into two groups according to the score thresholds (updated with post-operative clinical variables), and their survivals were compared.
In the validation cohort, the rad_score demonstrated a good predicting performance in treatment response to the neoadjuvant chemotherapy (AUC 95% CI =0.82 0.67, 0.98), which was better than the clinical score (based on pre-operative clinical variables) without significant difference (0.62 0.42, 0.83, P = 0.09). The rad_clinical_score could not further improve the performance of the rad_score (0.70 0.51, 0.88, P = 0.16). Based on the thresholds of these scores, the high-score groups all achieved better survivals than the low-score groups in the whole cohort (all P < 0.001).
The rad_score that we developed was effective in predicting treatment response to neoadjuvant chemotherapy and in stratifying patients with gastric cancer into different survival groups. Our proposed strategy is useful for individualised treatment planning.
Urine-based cytology is non-invasive and widely used for clinical diagnosis of urothelial carcinoma (UC), but its sensitivity is less than 40% for low-grade UC detection. As such, there is a need for ...new diagnostic and prognostic biomarkers of UC. CUB domain containing protein 1 (CDCP1) is a type I transmembrane glycoprotein highly expressed in various cancers. Using tissue array analysis, we demonstrated that CDCP1 expression in UC patients (n = 133), especially in those with low-grade UC, was significantly higher than in 16 normal persons. In addition, CDCP1 expression in urinary UC cells could also be detected by using immunocytochemistry method (n = 11). Furthermore, in 5637-CD cells, overexpression of CDCP1 affected the expression of epithelial mesenchymal transition-related markers and increased matrix metalloproteinase 2 expression and migration ability. Conversely, the knockdown of CDCP1 in T24 cells had the opposite effects. Using specific inhibitors, we demonstrated the involvement of c-Src/PKCδ signaling in the CDCP1-regulated migration of UC. In conclusion, our data suggest that CDCP1 contributes to the malignant progression of UC and may have the potential as a urine-based biomarker for detecting low-grade UC. However, a cohort study needs to be conducted.
Zwitterionic materials have received great attention because of the non-fouling property. As a result of the electric neutrality of zwitterionic polymers, their layer-by-layer (LBL) assembly is ...generally conducted under specific conditions, such as very low pH values or ionic strength. The formed multilayers are unstable at high pH or in a high ionic strength environment. Therefore, the formation of highly stable multilayers of zwitterionic polymers via the LBL assembly process is still challenging. Here, we report the LBL assembly of poly(sulfobetaine methacrylate) (PSBMA) with a polyphenol, tannic acid (TA), for protein-resistant surfaces. The assembly process was monitored by a quartz crystal microbalance (QCM) and variable-angle spectroscopic ellipsometry (VASE), which confirms the formation of thin multilayer films. We found that the (TA/PSBMA) n multilayers are stable over a wide pH range of 4–10 and in saline, such as 1 M NaCl or urea solution. The surface morphology and chemical composition were characterized by specular reflectance Fourier transform infrared spectroscopy (FTIR/SR), X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). Furthermore, (TA/PSBMA) n multilayers show high hydrophilicity, with a water contact angle lower than 15°. A QCM was used to record the dynamic protein adsorption process. Adsorption amounts of bovine serum albumin (BSA), lysozyme (Lys), and hemoglobin (Hgb) on (TA/PSBMA)20 multilayers decreased to 0.42, 52.9, and 37.9 ng/cm2 from 328, 357, and 509 ng/cm2 on a bare gold chip surface, respectively. In addition, the protein-resistance property depends upon the outmost layer. This work provides new insights into the LBL assembly of zwitterionic polymers.
Krüppel-like factor 10 (KLF10) is a tumor suppressor in multiple cancers. In a murine model of spontaneous pancreatic adenocarcinoma (PDAC), additional KLF10 depletion accelerated distant metastasis. ...However, Klf10 knockout mice, which suffer from metabolic disorders, do not develop malignancy. The mechanisms of KLF10 in PDAC progression deserve further exploration. KLF10-depleted and KLF10-overexpressing PDAC cells were established to measure epithelial-mesenchymal transition (EMT), glycolysis, and migration ability. A murine model was established to evaluate the benefit of genetic or pharmacological manipulation in KLF10-depleted PDAC cells (PDACshKLF10). Correlations of KLF10 deficiency with rapid metastasis, elevated EMT, and glycolysis were demonstrated in resected PDAC tissues, in vitro assays, and murine models. We identified sirtuin 6 (SIRT6) as an essential mediator of KLF10 that modulates EMT and glucose homeostasis. Overexpressing SIRT6 reversed the migratory and glycolytic phenotypes of PDACshKLF10 cells. Linoleic acid, a polyunsaturated essential fatty acid, upregulated SIRT6 and prolonged the survival of mice injected with PDACshKLF10. Modulating HIF1α and NFκB revealed that EMT and glycolysis in PDAC cells were coordinately regulated upstream by KLF10/SIRT6 signaling. Our study demonstrated a novel KLF10/SIRT6 pathway that modulated EMT and glycolysis coordinately via NFκB and HIF1α. Activation of KLF10/SIRT6 signaling ameliorated the distant progression of PDAC.Clinical Trial Registration: ClinicalTrials.gov. identifier: NCT01666184.
The intestinal tract consists of various types of cells, such as epithelial cells, Paneth cells, macrophages, and lymphocytes, which constitute the intestinal immune system and play a significant ...role in maintaining intestinal homeostasis by producing antimicrobial materials and controlling the host-commensal balance. Various studies have found that the dysfunction of intestinal homeostasis contributes to the pathogenesis of inflammatory bowel disease (IBD). As a novel mediator, extracellular vesicles (EVs) have been recognized as effective communicators, not only between cells but also between cells and the organism. In recent years, EVs have been regarded as vital characters for dysregulated homeostasis and IBD in either the etiology or the pathology of intestinal inflammation. Here, we review recent studies on EVs associated with intestinal homeostasis and IBD and discuss their source, cargo, and origin, as well as their therapeutic effects on IBD, which mainly include artificial nanoparticles and EVs derived from microorganisms.
The specificity of nucleic acids’ binders is crucial for developing this kind of drug, especially for novel G-quadruplexes’ binders. Quindoline derivatives have been developed as G-quadruplex ...stabilizers with good interactive activities. In order to improve the selectivity and binding affinity of quindoline derivatives as c-myc G-quadruplex binding ligands, novel triazole containing benzofuroquinoline derivatives (T-BFQs) were designed and synthesized by using the 1,3-dipolar cycloaddition of a series of alkyne and azide building blocks. The selectivity toward c-myc G-quadruplex DNA of these novel T-BFQs was significantly improved, together with an obvious increase on binding affinity. Further cellular and in vivo experiments indicated that the T-BFQs showed inhibitory activity on tumor cells’ proliferation, presumably through the down-regulation of transcription of c-myc gene. Our findings broadened the modification strategies of specific G-quadruplex stabilizers.
Zn–iodine (I2) battery, as a promising energy storage device, especially under high I2 loading, is harassed by the shuttle effect of the soluble polyiodide intermediates. Herein, the bifunctional ...role of 2D carbon nanosponge with rich P‐dopant (4.2 at%) and large specific surface area (1966 m2 g−1) in anchoring I2/Ix− (x = 1, 3 or 5) and catalyzing their mutual conversion is reported. Both experiment and computational results reveal the transfer of electrons from the P‐doped site to iodine species, showing strong interfacial interaction. When being used as a host, it possesses high specific capture capacity for I2 (3.34 giodine g−1 or 1.6 mgiodine m−2) and Ix− (6.12 gtriiodide g−1 or 3.1 mgtriiodide m−2), which thus effectively suppresses the shuttle effect, supported by in situ UV–vis and Raman spectra. In addition to the strong interfacial interaction that favors iodine conversion, the P‐doped sites can also catalyze the conversion of I5− to I2, which is the rate‐determining step. Consequently, Zn–I2 batteries under a high I2 content (70 wt%) deliver high specific capacity (220.3 mAh g−1), superior Coulombic efficiency (>99%), and low self‐discharge rate; moreover, they can also operate steadily at 2 A g−1 with ignorable capacity decay for 10 000 cycles.
An on-line cyclodextrin assisted sweeping-micellar electrokinetic chromatography (CD assisted sweeping-MEKC) was developed for the simultaneous separation and concentration of four neutral analytes ...(erianin, dendrophenol, naringenin and scoparone) in Dendrobium officinale Kimura et Migo (D. officinale). The D. officinale was directly determined by this on-line stacking method after simple extraction and dilution. The optimized background solution (BGS) was 50 mM phosphoric acid (PA) containing 100 mM SDS and 30% (v/v) methanol. The best separation and concentration performance of analytes dissolved in 90 mM CD and 100 mM PA was achieved in a short analysis time when injected at 50 mbar for 100 s. Compared with conventional sweeping-MEKC and MEKC method, significant improvement in enrichment efficiency was achieved by using this proposed method. A series of validation studies of the present method was performed under the optimal conditions. Good linearities were obtained with the correlation coefficients in the range of 0.994–0.999, the detection limits were ranged from 13 to 40 ng/mL. Sensitivity enhancement factors (SEFs) were in the range of 28.5–46.8 compared with traditional injection (injection time 3 s). Therefore, the proposed method was successfully applied for the separation and concentration of neutral analytes in real samples.
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•An on-line CD assisted sweeping-MEKC method is developed for separation and concentration of neutral analytes.•Satisfactory resolution and enrichment efficiency are achieved in a short analysis time.•Compared with conventional sweeping-MEKC and MEKC method, the proposed method shows higher enrichment efficiency.
•A facile and green protocol has been developed to hydrophilize membrane surfaces.•The co-deposited coatings of tannic acid and diethlyenetriamine are almost colorless.•The protocol is suitable for ...various hydrophobic membranes.
We report a novel approach toward the surface modification of commercial polymer membranes via co-deposition of tannic acid (TA) and diethlyenetriamine (DETA). Particle-free, superhydrophilic, and almost colorless coatings are fabricated on the surfaces of polypropylene, poly(vinylidene fluoride), and poly(tetrafluoroethlene) microfiltration membranes. Cross-linking between TA and DETA plays a crucial role during the co-deposition process, as well as the adhesion of TA on the hydrophobic membrane surfaces. Both the surface wettability and water permeation flux are dramatically improved for the studied membranes after the co-deposition. The results indicate that co-deposition of TA and DETA is great potential for the surface modification of hydrophobic membranes.
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