The objectives of this study were to propose a clinical prognostic scoring system applicable for intrahepatic cholangiocarcinoma (ICC) and to evaluate the prognostic validity of the American Joint ...Committee on Cancer (AJCC) 7th edition staging system.
Retrospective univariate and multivariate survival analyses were conducted for 344 patients with ICC who underwent hepatectomy. A simple clinical prognostic scoring system (Fudan score) was developed based on the independent predictors. The prognostic validity was assessed in 74 patients with unresected tumors and compared with the AJCC 6th and 7th edition systems.
In the training set, serum alkaline phosphatase level, carbohydrate antigen 19-9 level, tumor boundary type, tumor size, and number of intrahepatic tumors were independent predictive factors of survival in ICC and were incorporated into the Fudan score. Three hundred forty-four patients were categorized into four subsets with 5-year overall survival rates of 48.6%, 25.6%, 10.3%, and 0.0% for low-, intermediate-, high-, and extremely high-risk groups, respectively. The discriminative ability of the Fudan score was better than that of the AJCC staging system and well applied in the unresected patient set.
A Fudan score based on clinical factors may provide a relatively accurate prognostic prediction for ICC patients regardless of resection status.
Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) ...metastasis and chemoresistance have not been fully characterized.
CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1.
CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/β-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients.
CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pure magnesium (Mg) develops a strong basal texture after conventional processing of hot rolling or extrusion. Consequently, it exhibits anisotropic mechanical properties and is difficult to form at ...room temperature. Adding appropriate alloying elements can weaken the basal texture or even change it, but the improvement in formability and mechanical properties is still far from expectations. Over the past 20 years, considerable efforts have been made and significant progress has been made on wrought Mg alloys at the fundamental and technological levels. At the fundamental level, textures formed in sheets and extrusions of different alloy compositions and produced under different strain paths or thermomechanical processing conditions are relatively well established, with the assistance of the advanced characterization technique of electron backscatter diffraction. At the technological level, room temperature formability of sheet has been significantly improved, and tension–compression yield asymmetry of extrusion is also remarkably reduced or eliminated. This paper starts with an overview of dislocations, stacking faults and twins, and deformation of single crystals of pure Mg along different orientations and under different loading conditions, followed by a review of microstructure (texture and grain size) and deformation of polycrystalline pure Mg with different textures, grain sizes, and loading conditions. With this information as a base, texture, grain size, and deformation of polycrystalline Mg alloy sheets and extrusions produced under different processing conditions are systematically examined and compared. Remaining and emerging scientific and technology issues are then highlighted and discussed in the context of texture and grain size. The need for better-resolution diffraction and spectroscopy techniques is also discussed in the relationship between texture change and grain boundary solute segregation.
Summary
Background
Magnetic resonance enterography (MRE) has been proposed as a non‐ionising alternative method to computed tomography enterography (CTE). Some studies have directly compared CTE and ...MRE in patients with small bowel Crohn's disease (CD) with variable results.
Aim
To compare the overall diagnostic accuracy in assessing the activity of small bowel and complications.
Methods
MEDLINE, EMBASE and Cochrane databases were searched for studies on the accuracy of MRE and CTE, as compared with a pre‐defined reference standard. Pooled sensitivity, specificity, the weighted area under the curve (AUC), incremental yield (IY) and other diagnostic indices were evaluated.
Results
A total of 290 CD patients from six different studies were analysed. The pooled sensitivity and specificity for MRE in detecting active small bowel CD was 87.9% 95% confidence interval (CI), 81.8–92.5 and 81.2% (95% CI: 71.9–88.4) respectively. The AUC under the summary receiver‐operating characteristic (sROC) of MRE was 0.905 (SEM 0.03, standard error of the mean). Likewise, the pooled sensitivity and specificity of CTE in detecting active small bowel CD was 85.8% (95% CI: 79.2–90.9) and 83.6% (95% CI: 75.3–90.1) with the AUC of 0.898. The AUC of MRE in detecting fistula, stenosis and abscess was 0.936, 0.931 and 0.996, respectively, compared to 0.963, 0.616 and 0.899 of CTE. No statistically significant IY for MRE vs. CTE was found (fixed model, P > 0.05).
Conclusions
Magnetic resonance enterography has a diagnostic effectiveness comparable to computed tomography enterography, thus may serve as a radiation‐free alternative for evaluation of patients with Crohn's disease.
This paper aims to provide latest research results on consumer attitudes and behaviors about smartphone recycling. In particular, the study considers China as an example and reviews the country's ...recent progress in legislation and business practice in smartphone recycling. The study relies on a national survey to identify the patterns and trends in Chinese consumers' recycling attitudes and behaviors. Our results show that on top of incentive and convenience, information security is the number one requirement for consumers to recycle their smartphones. Additionally, although China has made significant progress in improving social environment and people's consciousness for phone recycling, more people still choose to store their waste smartphones at home. Moreover, the impact of recycling service on the sales of new phones is also discussed in the context of closed-loop supply chain design. As an exploratory attempt to understand smartphone recycling from the consumers' perspectives, this article presents critical factors influencing consumers' attitudes and behaviors in China, and sheds new lights on future academic research directions as well as on managerial applications and policy-making.
ABSTRACT
Special economic zones (SEZs) have been used by many developing countries as a policy tool to promote industrialization and economic transformation. Since the initiation of the first modern ...zone in Shannon, Ireland, special economic zones have evolved in many ways, from an initial ‘enclave’ nature towards today’s ‘Economic Zone 5.0’, which is built on emerging digital technologies and well integrated with urban development. The special economic zones represents a new unilateral compromise between the state and market, while still contributing to economic globalization, by presenting itself as a complementary or as an alternative approach to integrate with the global market in addition to the international economic law instruments. Despite the prevalence of special economic zones worldwide, their performance and impact on the economy and structural transformation are quite mixed. Among the many lessons learned from successful special economic zone programmes, the key elements include a strategic location, integration of zone strategy with the overall development strategy, understanding the market and leveraging comparative advantage, and, most importantly, ensuring that zones are ‘special’ in terms of a business-friendly environment—especially a sound legal and regulatory framework and an embodiment of sustainability and resiliency towards various external shocks like today’s COVID-19 pandemic.
Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme that generates NADPH to maintain reduced glutathione (GSH), which scavenges reactive oxygen species (ROS) to protect cancer cell from ...oxidative damage. In this study, we mainly investigate the potential roles of G6PD in colorectal cancer (CRC) development and chemoresistance. We discover that G6PD is overexpressed in CRC cells and patient specimens. High expression of G6PD predicts poor prognosis and correlated with poor outcome of oxaliplatin-based first-line chemotherapy in patients with CRC. Suppressing G6PD decreases NADPH production, lowers GSH levels, impairs the ability to scavenge ROS levels, and enhances oxaliplatin-induced apoptosis in CRC via ROS-mediated damage in vitro. In vivo experiments further shows that silencing G6PD with lentivirus or non-viral gene delivery vector enhances oxaliplatin anti-tumor effects in cell based xenografts and PDX models. In summary, our finding indicated that disrupting G6PD-mediated NADPH homeostasis enhances oxaliplatin-induced apoptosis in CRC through redox modulation. Thus, this study indicates that G6PD is a potential prognostic biomarker and a promising target for CRC therapy.
Cell lines are widely-used models to study metastatic cancer although the extent to which they recapitulate the disease in patients remains unknown. The recent accumulation of genomic data provides ...an unprecedented opportunity to evaluate the utility of them for metastatic cancer research. Here, we reveal substantial genomic differences between breast cancer cell lines and metastatic breast cancer patient samples. We also identify cell lines that more closely resemble the different subtypes of metastatic breast cancer seen in the clinic and show that surprisingly, MDA-MB-231 cells bear little genomic similarities to basal-like metastatic breast cancer patient samples. Further comparison suggests that organoids more closely resemble the transcriptome of metastatic breast cancer samples compared to cell lines. Our work provides a guide for cell line selection in the context of breast cancer metastasis and highlights the potential of organoids in these studies.
Joining NiTi to Ti6Al4V is of great interest for applications in the biomedical and aerospace fields. Despite the importance, no joining techniques have been developed that avoid the formation of ...brittle intermetallics to produce high strength joints. In this work, Niobium was used as an interlayer to prevent the formation of these brittle phases when joining NiTi to Ti6Al4V. The presence of this interlayer ensured that crack free welds were obtained and no brittle intermetallic compounds were observed. The Niobium interlayer was of a much higher melting temperature than the base materials so the bulk Niobium did not melt during the joining process, acting as a diffusion barrier between the NiTi and Ti6Al4V. The laser was focused on the Ti6Al4V side of the joint, which joined the Ti6Al4V and Niobium by fusion welding. At this interface a (Ti, Nb) region was formed due to dilution of the Niobium and mixing with the Ti6Al4V. At the NiTi–Nb interface a eutectic reaction was responsible for joining. Mechanical testing of the joints revealed that the minimum tensile strength matched the ultimate tensile strength of the weakest material, Niobium. These results highlight new possibilities for the use of high melting point filler materials when joining NiTi to dissimilar materials, so that the formation of undesired phases can be avoided.
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Texture evolution in cold-rolled Mg-0.3Zn-0.1Ca, Mg-0.4Zn and Mg-0.1Ca (at.%) alloys during static recrystallization is monitored using a quasi-in-situ electron backscatter diffraction (EBSD) method. ...The quasi-in-situ EBSD results show that most of recrystallized grains formed in the early stage of recrystallization have randomised orientations in the ternary alloy and they grow uniformly during the recrystallization process. The formation and uniform growth of these recrystallized grains with randomised orientations give rise to a weak texture in fully recrystallized samples of the ternary alloy. A weak recrystallization texture also forms in the early stage of recrystallization in the two binary alloys, but it is gradually replaced by a strong basal texture via the preferential growth of recrystallized grains with specific orientations. The grain size in the ternary alloy is smaller than those in the two binary alloys at each stage of recrystallization, and the grain size distribution in the ternary alloy is significantly narrower than those in the two binary alloys after full recrystallization. Solute segregation to grain boundaries is observed in all three alloys in the fully recrystallized state. It is hypothesised that Zn and Ca atoms in the ternary alloy segregate strongly to high-energy boundaries of the recrystallized grains that would otherwise grow preferentially in the counterpart binary alloys, and that this co-segregation would significantly reduce the boundary mobility, by reducing grain boundary energy and enhancing solute dragging effect, and therefore lead to a more uniform growth of recrystallized grains with randomised orientations.
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