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Pancreatic cancer is one of the common malignant tumors of the digestive system, and its clinical treatment is still very challenging. Most of the pancreatic cancer chemotherapeutic drugs have poor plasma stability, low cell uptake efficiency, and are prone to developing drug resistance and toxic side effects. Besides, pancreatic cancer often has a dense extracellular matrix, which consists of collagens, hyaluronic acid, and other proteoglycans. Among them, hyaluronic acid is a key component of the dense matrix, which results in vascular compression and insufficient perfusion, and hinders the delivery of chemotherapeutic drugs. In this study, we explore using hyaluronidase in tumor-bearing mice to eliminate the hyaluronic acid barrier, to reduce blood vessel compression and reshape the tumor microenvironment. In addition, we evaluate using doxorubicin-loaded nanoprobes to improve the stability and local tumor-killing effect of the drug. The nanoprobes have the characteristics of near-infrared optical imaging, which are used to monitor the tumor size in real-time during the treatment process, and dynamically observe the tumor inhibitory effect. The results show that elimination of the hyaluronic acid barrier combined with the doxorubicin-loaded nanoprobes can greatly increase drug penetration into tumor tissue and improve the effectiveness of chemotherapy drugs. This study provides a novel strategy for the treatment of pancreatic cancer.

Pancreatic cancer is one of the most lethal malignancies worldwide. The existing therapeutic regimen in the clinic for advanced inoperable carcinomas are far from satisfactory, thus it is urgent to seek more effective anticancer strategies. In the pursuit of novel, more effective interventions, photothermal therapy (PTT) based on nanomaterials has attracted increased attention. Recent advances in related fields have catalyzed the generation of novel nanoprobes, such as organic dyes, metal nanoparticles. However, organic dyes are poorly stable and easy to quench while metal nanoparticles with potential metal toxicity are difficult to degrade, both of which have low light-to-heat conversion efficiency, broad spectrum of anti-tumor effects, and lack of tumor targeting specificity. Single-walled carbon nanotubes (SWNTs) can remedy the above inadequacies. Herein, we report our water-soluble, bio-stable and low-toxicity SWNTs with excellent photothermal conversion efficiency. Specific modifications can enable visualization of the aggregate characteristics of SWNTs at the macroscopic or microscopic level in tumors. The dye-conjugated SWNTs bound with targeting antibodies that can induce them specifically targeting to pancreatic tumors for purposes of performing dyes imaging-guided cytotoxic PTT. PTT using this method achieves precise and excellent curative effects with minimal adverse effects, thus providing a promising strategy for anticancer therapy.

Recently, invadopodia have been increasingly recognized as important drivers of local invasion and metastasis. Cortactin, as an actin-binding protein, is closely associated with invadopodia through interacting with proteins. Formin-like 2 (FMNL2), a member of diaphanous-related formins which act as nucleation factors, plays an important role in tumor progression. But whether cortactin can interact with FMNL2 to promote invadopodia formation and the role of FMNL2 in invadopodia formation are still unknown. Here we found that cortactin directly bound to FMNL2 and elevated the activities of actin polymerization and recycling endosome motility. FMNL2 was necessary for invadopodia formation and function in CRC cells. The interaction of cortactin and FMNL2 could further promote the invadopodia formation and matrix degradation. The stimulation of EGF/cdc42 enhanced the combination of cortactin and FMNL2 to intensify the numbers of invadopodia and the degrees of matrix degradation. In vivo, induction of invadopodia formation via cortactin is essential for the ability of FMNL2 to promote CRC metastasis. Furthermore, up-regulations of FMNL2 and cortactin were highly linked in CRC tissues. Collectively, our work demonstrates a brand-new mechanism of cortacin and FMNL2 at invadopodia in CRC.

Background: Diaphanous-related formins (DRFs), actin necleator, have been known to participate in the progression of cancer cells. We previously reported that FMNL2 (Formin-like2), a member of DRFs, was a positive regulator in colorectal cancer (CRC) metastasis, yet proteins and pathways required for the function of this pro-invasive DRFs remain to be identified. Methods: The relationship between FMNL2 and COMMD10 was examined using Co-IP, GST pull-down, immunofluorescence and in vitro ubiquitination assay. The in vitro and in vivo function of COMMD10 in CRC was evaluated using CCK-8 proliferation assay, plate colony formation, cell cycle, apoptosis and animal models. The inhibition of NF-κB signalling by COMMD10 was detected using dual-luciferase reporter assay and western blotting. Co-IP, GST pull-down and nuclear protein extraction assay were performed to evaluate the effect on p65 by COMMD10. Real-time PCR and western blotting were performed to detect expressions of FMNL2, COMMD10 and p65 in paired tissues. Results: FMNL2 targets COMMD10 for ubiquitin-mediated proteasome degradation in CRC cells. COMMD10 targets p65 NF-κB (nuclear factor-κB) subunit and reduces its nuclear translocation, thereby leading to the inactivation of NF-κB pathway and suppression of CRC invasion and metastasis. Inhibition of NF-κB signalling by COMMD10 is necessary for FMNL2-mediated CRC cell behaviours. Downregulation of COMMD10 predicts poor prognosis of CRC patients. The expressions of FMNL2, COMMD10 and p65 are highly linked in CRC tissues. Conclusions: These data demonstrate that the FMNL2/COMMD10/p65 axis acts as a critical regulator in the maintenance of metastatic phenotypes and is strongly associated with negative clinical outcomes.

F-box proteins are critical components of the SKP1-CUL1-F-box (SCF) E3 ubiquitin ligases and involved in the ubiquitin-dependent proteolytic pathway. Dysregulation of F-box protein-mediated proteolysis often leads to human malignancies. F-box only protein 8 (FBX8), a novel component of F-box proteins, is down-regulated in several tumors and closely correlates with tumor progression. However, little is known about its function, regulatory mechanisms and substrates in the progression of colorectal carcinoma (CRC). Combining microRNA (miRNA) assay, functional characterization, mechanistic studies with clinical validation, we identify FBX8 as a CRC metastasis suppressor downstream of miR-223, a metastasis promoting miRNA that is transcriptionally regulated by Myocyte enhancer factor (MEF2A). mTOR is a substrate of FBX8 for ubiquitin-mediated degradation and is required for FBX8 induced cell proliferation and invasion in CRC cells. FBX8 is down-regulated in human CRC tissues and correlates with MEF2A, miR-223 and mTOR expression levels. Notably, low FBX8 expression status in CRC tissues was a significant prognostic factor for poor overall survival of patients. These findings illustrate FBX8 as a metastasis suppressor that functions through mTOR signaling pathway and has significant prognostic power.

Background 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. Methods 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. Results 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. Conclusions 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. Electronic supplementary material The online version of this article (10.1186/s12943-019-1019-x) contains supplementary material, which is available to authorized users.

Background: MiR-214 is aberrantly regulated in several tumours, but its underlying mechanisms in colorectal cancer (CRC) metastasis remain largely unknown. This study aimed to demonstrate the function and potential mechanism of miR-214 in regulating invasion and metastasis of CRC. Methods: The transcription factor and targets of miR-214 were predicted by bioinformatics and validated using ChIP and dual-luciferase reporter assay. DNA methylation status was explored using bisulphite sequencing PCR. The in vitro and in vivo function of miR-214 in CRC was evaluated using MTT, plate colony formation, Matrigel invasion and animal models. Real-time PCR or western blotting was performed to detect FOXD3, miR-214 and MED19 expressions in CRC cells and clinical specimens. Results: MiR-214 was downregulated in CRC and was significantly correlated with lymphatic metastasis. Downregulation of miR-214 might due to promoter hypermethylation in CRC. FOXD3 was validated as a transcription factor of miR-214 by ChIP assay. Dual-luciferase assay identified MED19 as a target of miR-214 in CRC. In vitro and in vivo experiments showed that miR-214 mediated the inhibiting effect of FOXD3 on proliferation, invasion and metastasis by targeting MED19. Spearman's correlation analysis showed a positive correlation between FOXD3 and miR-214, and negative correlations between FOXD3 and MED19, miR-214 and MED19 in CRC cells and clinical specimens. Conclusions: FOXD3/miR-214/MED19 axis is important for the regulation of growth, invasion and metastasis of CRC. Targeting the miR-214-mediated axis might be helpful for the treatment of CRC.

Activities of atmospheric aerosols, bulk deposition fluxes, and undisturbed soil inventories of 7Be were investigated in China's East Asian monsoon zone at various latitudes ranging from 23.8°N to 43.5°N. The annual latitudinal distributions of 7Be concentrations in aerosols follow a distribution pattern which looks similar to a normal distribution with the maxima occurring in the mid-latitude region. Simultaneous measurements of 7Be at various latitudes suggest that atmospheric circulation may play an important role in the latitudinal distributions of 7Be in surface air. Latitude and wet precipitation are the main factors controlling the bulk 7Be depositional fluxes. Significant seasonal variations in 7Be depositional fluxes in Beijing, a mid-latitude city, were observed with the highest flux in summer and the lowest in winter, whereas less seasonality were found in the high- and the low-latitude cities. The highest 7Be inventory in undisturbed soils in summer also occurred at a mid-latitudinal area in the East Asian monsoon zone. Precipitation is the main factor controlling the 7Be soil inventory in Qingdao with the highest values occurring in autumn followed by summer.

Application of microwave energy for materials processing is emerging as an innovative technology with many advantages over the conventional processing, and the rapid progress in this field suggests that microwave material processing (e.g., microwave and microwave-hydrothermal process) will play an outstanding role in the broad field of nanoscience and nanotechnology. This review article gives an up-to-date overview of the current microscopical and physical characterization of the products synthesized by microwave and microwave-hydrothermal process, particularly for oxide nanomaterials because they are indispensable for nanotechnological innovations due to their combinations of infinite variety of structural motifs and properties with manifold morphological features. Basic principles, advantages, and limitations of microwave and microwave-hydrothermal processes are first introduced, and then their recent applications in the synthesis of different classes of functional materials especially for oxide nanomaterials are critically reviewed. Next, the recent progress on the structural and physical characterizations is summarized and discussed. Finally, prospects for future researches within this field are elaborated.

Epitaxial gradient barium strontium titanate (Ba/sub x/Sr/sub 1-x/)TiO/sub 3/ (x=0.75, 0.8, 0.9, 1.0) thin films were prepared by the pulsed laser deposition method on the (La/sub 0.7/Sr/sub 0.3/)MnO/sub 3/ (LSMO)/LaAlO/sub 3/ (LAO) substrate. Their epitaxial structure was characterized via x-ray diffraction (XRD). The gradient change of composition is determined by the energy dispersive X-ray analysis (EDAX). P-E loops were obtained. The dielectric properties in the frequency ranging from 100 Hz to 100 kHz were measured using an impedance analyzer. Results indicated that the epitaxial structure has good dielectric properties.

In Part 1 of this article the authors presented theoretical results pertaining to the yield behavior of pressure-sensitive plastic materials with emphasis on shear band width and orientation. These results are applied here to model the experimental data obtained for compression and tension tests of ultra fine grained Fe-10% Cu alloys. As will be reported in detail elsewhere these alloys exhibit almost perfectly plastic behavior and deform by intense shear banding as the only mode of plastic deformation. Due to the fine grain structure, it may be speculated that grain rotation and void formation can contribute significantly to the aforementioned shear band mechanism for plastic flow, in addition to the traditional dislocation motion. It follows that the pressure-sensitive plastic models elaborated upon in Part 1 may be suitable candidates for the description of the shear band behavior for these alloys. In fact, it is shown in Part 2 that the mechanical property data obtained for the strengths in tension and compression, the shear band angles and the shear band widths verify the theoretical expressions derived in Part 1 for the yield condition, the shear band orientation, and the shear band width.

The purpose of this two-part article is to theoretically establish and experimentally support a simple method for calculating shear band angles and shear band widths in tension or compression samples commonly used to investigate mechanical properties. The method is illustrated in conjunction with experimental results on the yielding behavior and shear band formation in tension and compression of an ultra fine grained Fe-10% Cu alloy, properly milled and consolidated. The experimental techniques for preparing the samples, their microstructural characteristics and the details of the performed mechanical tests will be reported elsewhere, but a brief summary is contained in Part 2 of the present article. In Part 2 comparisons are made between theoretical predictions for pressure-sensitive plastic materials established in Part 1 and experiments on the yield behavior of an ultra fine grained Fe-10% Cu alloy along with observations on shear band orientations and widths.

Liver transplantation for liver carcinoma with cirrhosis is a treatment still in dispute. The objectives were to summarize the survival and cost of 50 liver transplant cases performed for liver carcinoma over nearly 3 years. Methods We performed 138 liver transplants from January 1999 to February 2002. There were 50 cases (36.2%) of liver carcinoma with HBV cirrhosis, which were divided into three stages based on the tumor pathology: Stage 1 cases showed a single mass (≤5 cm), 4 cases; Stage 2, a single mass >5 cm or intrahepatic multiple masses without PV cancer embolus, 32 cases; and Stage 3: tumor invasion of the PV or perihepatic lymph nodes or organs, 14 cases. All patients received three to six courses of chemotherapy postoperatively. Results All four cases of stage 1 survived >1 year; one of them is at 3 years with good liver function and tumor free. The mean half-year medical cost was $27.100 ± 108 in stage 1. The half-year survival and medical costs were 62.5% and $31,500 ± 260 in stage 2 and 15.0% and $35,500 ± 134 in stage 3. Conclusion Liver transplantation is an effective treatment for early-stage liver carcinoma, that achieves good medical and economic results, but should be limited to advanced liver cancer.

The Weibull strength distributions and fracture characteristics of three abrasive grains, brown corundum, white corundum and green silicon carbide, are investigated. The effects of the surface defects from crushing and the inherent microcracks from processing prior to crushing on fracture strengths and characteristics of the abrasive grains are discussed together with SEM observations. A novel proof-testing has been carried out in terms of low energy ball milling so that survived abrasive grains have improved strength characteristics. Strength distributions before and after the proof-testing have been compared. It is concluded that the strength of larger grains is strongly influenced by surface defects due to crushing, and the strength of smaller grains is more relevant to the inherent processing microcracks and pores formed during the manufacturing process prior to crushing. The influence of processing conditions, such as fusing and sintering, on strength distributions of the brown corundum is also discussed.

In this paper, both rigid-plastic FEM simulation and experimental methods are used to systematically analyze axisymmetric deep-drawing process, summarize material flow law in deep-drawing process. The relation between punch force and drawing depth is measured with transducer and other equipment. Contrasting to the experimental result, it shows that this method is successfully applied to simulate deep-drawing process. The method of dealing with boundary conditions raised in this paper precisely simulate the material warping in the center and the cavity in the flange, and investigate the influence of friction and other parameters on the limit depth of deep-drawing. Although the program shown in this paper deals merely with the axisymmetric deep-drawing deformation, it could be applied to upsetting and forging process either.

Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant cutaneous disorder, characterized by a mixture of hyperpigmented and hypopigmented macules mostly on the dorsal portions of the extremities. Pathogenic mutations have been identified in the double-stranded RNA-specific adenosine deaminase (DSRAD) gene. We studied a Chinese family that included four affected individuals with DSH phenotypes. PCR and direct sequencing were carried out to detect the entire coding region and exon-intron boundaries of the DSRAD gene. A novel nucleotide c.3002G>T missense mutation in the exon 11 of the DSRAD gene was detected in the proband and his father. This information expands the database on DSRAD gene mutations associated with DSH.

THE CLASSIC orthotopic liver transplantation with venovenous bypass has both advantages and disadvantages. Advantages include maintaining the balance of the internal environment, relieving gastrointestinal congestion, decreasing blood loss, and protecting of bypass renal function during the anhepatic period. Disadvantages include the amount of time consumed, expensive cost, blood cell destruction, and complications to the blood vessels used for bypass. This article reviews the experience in 45 cases of classic orthotopic liver transplantation without venovenous bypass.

First-principles electronic-structure and total-energy calculations have been performed for NbH in the \ensuremath{\beta}- and \ensuremath{\gamma}-phase structures. Lattice constants, bulk moduli, and heats of formation have been calculated and found to be in excellent agreement with measured values. We have made detailed ``frozen-phonon'' calculations investigating the effect of anharmonic couplings on the optical vibrations of hydrogen and its isotopes in NbH.

In this study, the Fe41Co7Cr15Mo14C15B6Y2 bulk amorphous alloy with high glass-forming ability was prepared using the arc- melting copper mold casting technique, and corresponding amorphous coating was obtained using the laser melt amorphous powders on the surface of carbon steel. The corrosion resistance performance of the laser cladding coating in hydrochloric acid was analyzed and tested in experiments under the conditions of different laser cladding speeds. The amorphous alloy coating with different fabrication parameters have the difference internal structure, which lead to the difference corrosion resistance in the same environment to some extent. The nature of amorphous alloy and the corrosion morphology were investigated using XRD and SEM method, respectively. The corrosion experiments showed that: when the laser power was 3300W, the corrosion resistance of four kinds of samples in hydrochloric acid from strong to weak as follows: as-cast sample > the coating with laser cladding speed 110 mm/min > the coating with laser cladding speed 120 mm/min > the coating with laser cladding speed 130 mm/min. The free corrosion current density of casting sample, sample 1, sample 2 and sample 3 is 3.304 × 10-6 A/cm2, 2.600×10-3 A/cm2, 2.030×10-3 A/cm2 and 3.396×10-4 A/cm2, respectively.