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Pancreatic cancer is an inflammatory malignancy, and tumor-associated macrophages (TAMs) are the predominant inflammatory cells in tumor tissue. TAMs have complicated interactions with pancreatic cancer cells, however, the details and mechanisms remain largely unknown. In this study, transcriptomics and proteomics analyses were performed to explore the interactions between murine pancreatic cancer cells and TAMs. Dopamine (DA) has been reported to suppress inflammations. However, its roles in TAMs of pancreatic cancer have not been reported. Herein, the roles and mechanisms of DA to affect the chemotherapeutic efficacy for pancreatic cancer were studied. Multi-omics results revealed that there was a tumor-promoting vicious cycle involving murine pancreatic cancer cells and TAMs. DA substantially improved the chemotherapeutic efficacy both in vitro study and in immunocompetent murine pancreatic cancer models by suppression of the M2 characters of TAMs. Further studies found that activation of DRD4 by DA led to the decrease of cAMP, and then inhibited the activation of PKA/p38 signal pathway, which suppressed the tumor-promoting inflammation of TAMs. This study uncovers the reciprocal interactions between TAMs and pancreatic cancer cells using multi-omics techniques and presents that DA has synergistic roles with chemotherapy for pancreatic cancer by suppressing of TAM-derived inflammations. [ABSTRACT FROM AUTHOR]

The interactions between tumor immune microenvironment (TIME) and pancreatic cancer cells can affect chemotherapeutic efficacy; however, the mechanisms still remain largely unknown. Thirty items in TIME were comprehensively screened by using tissue microarray from pancreatic cancer patients. Their expressions, interconnections and predictive roles for survival were analyzed. Twenty-one of 30 items could stratify the survival of the patients; however, multivariate analysis found that only 5 independent risk factors could predict worse survival (M2-polarized tumor-associated macrophages (TAMs), IgG4 positive cells, TGF-β1, GM-CSF and lymphangiogenesis). They had a much higher expression levels in tumoral tissue, compared to peritumoral tissue. The Spearman analysis showed that M2-polarized TAM, TGF-β1 and GM-CSF were positively correlated with pancreatic cancer stem cells (PCSC), angiogenesis and lymphangiogenesis. Both human and murine pancreatic cancer cells could induce M2-polarized TAM, which showed substantial roles to decease chemotherapeutic effects. After treated by gemcitabine, both human and murine pancreatic cancer cell lines expressed higher level of immune check points, PCSC markers and varieties of immunosuppressive factors; however, TGF-β1 and GM-CSF had the highest increase. Based on the above results, TGF-β1 and GM-CSF were proposed to be the optimal potential targets to improve chemotherapeutic effects. In immunocompetent murine models, we demonstrated that combined blockade of TGF-β1 and GM-CSF improved the chemotherapeutic effects by inhibition of M2-polarized TAM and induction of CD8 positive T cells. This study presents a novel promising combined strategy to improve the chemotherapeutic effects for pancreatic cancer. [ABSTRACT FROM AUTHOR]

This paper aimed to restrain the processing defects of aluminum alloy honeycombs using in aerospace with low stiffness and thin-walled, such as burr and collapse edge. The honeycomb material was treated by new method named ice fixation, and a CNC milling machine was used for a series of cryogenic machining. The fixation strength was calculated and machining defect reasons were analyzed. The cryogenic milling mechanism with ice fixation was established at the same time. Results show that compared to the without ice or conventional fixation way, the honeycomb fixation force and strength are all greatly increasing and that can reach 287 N and 19.1 kPa, respectively. Meanwhile, the processing defects are effectively suppressed. Others the cutting depth has greater influence on surface quality, and it makes the milling force improved three times, while the improvement of fixation and milling force and the cryogenic processing are the main reasons of reducing defects. The ice fixation cryogenic processing provides a new and effective method for aluminum alloy honeycomb with low rigidity and thin-wall. [ABSTRACT FROM AUTHOR]

This paper is aimed to restrain the defects such as fluff and ablation, which were often found in machining of the aramid fiber-reinforced composites (AFRP). The cooling method of spray liquid nitrogen was adopted in the orthogonal milling process. The processing parameters including cutting depth, cutting speed, cooling temperature, feed speed, and liquid nitrogen flow were considered in details, and their effects on the processing quality were researched and analyzed. The analysis optimization methods of processing parameter were employed for the influence on the machining surface quality. Meanwhile, the optimal machining surface quality was predicted and verified. The results show that the cryogenic way realizes a bigger improved role on machining quality than the conventional one for AFRP. As well as the influence order of processing parameters on the roughness is cutting depth, cutting speed, cooling temperature, feed speed, and liquid nitrogen flow. And the predicted result Ra = 0.557 μm of minimum surface roughness value is similar with the actual one Ra = 0.572 μm and verifies the feasibility of optimization method. For processing of AFRP, the cooling way of spray liquid nitrogen has a positive role with high quality and efficiency. [ABSTRACT FROM AUTHOR]

This paper presents the first comprehensive investigation on the serious problems of tool wear and service life in conventional milling nickel-based superalloy. A series of machining experiments were conducted at various combinations of cutting parameters in conventional and cryogenic at 77-K milling processes. The morphology and element compositions of tool processing surfaces were analyzed and measured by the scanning electron microscopy and an energy-dispersive spectrometer, respectively. Meanwhile, the carbide tool wear behavior and mechanism in cryogenic cooling condition were also discussed in detail. The new findings indicate that at low cutting speed, the adhesive wear is easily found for the conventional machining, and the oxidation wear is for the high speed. As well as the cutting depth and feed speed are all limited, that is, lower machining efficiency. In liquid nitrogen cryogenic condition, the tool wear is not apparent at low and medium speeds, so that we can choose larger cutting depth and feed speed. At high speed, a part of adhesion and diffusion wears can be found, that is, inconspicuous oxidative wear, and the chip already made the plastic change. Furthermore, the tool service life can be increased four times at high speed and the processing efficiency is also improved obviously. The use of the liquid nitrogen cryogenic processing method can effectively solve the problems of serious tool wear and the lower processing efficiency for the nickel-based superalloy. [ABSTRACT FROM AUTHOR]

This paper presents comprehensive investigation on the nickel-base alloy material used in the aerospace with difficult machining whose cutting tool is worn failure quickly. The reason mainly relates to the high temperature of cutting zone. The cryogenic cooling method was adopted for a series of machining experiments. Based on the entropy production of the cutting system, the entropy productions of diffusion, adhesion, and oxidation wear of tool were calculated under different cutting speeds. And the wear mechanism was explained through the self-organization characteristics of cutting friction and wear system. The results indicate that with the increase of cutting speed, it has the greater entropy production. To traditional cutting, at the 132 m/min speed, the entropy production has not had the decreased stage with time, and the tool self-organizing has not played a role. However, in cryogenic cooling environment, when the speed is 220 m/min, the cutting tool's self-organization is still in effect, and its service life can be significantly extended more than three times. Compared with the traditional processing, the cryogenic one is more likely to form a self-organization dissipative structure and obviously improves the cutting speed which the self-organization can play a role. Furthermore, it also increases the cutting effect with the best processing efficiency. [ABSTRACT FROM AUTHOR]