Cancer tissues consist of cancer cells, surrounding stromal cells and the extracellular matrix. Cancer‐associated fibroblasts (CAF) are one of the key components of stromal cells. CAF have a great ...impact on the behavior of cancer cells, including proliferation, invasion, metastasis and chemoresistance in many ways. However, the underlying mechanism had not been fully elucidated. In this study, we investigated the role of CAF in cisplatin resistance of lung cancer cells. By using conditioned medium from CAF (CAF‐CM), we found that CAF decreased the sensitivity of lung cancer cells to cisplatin. RNA sequencing results showed that CAF expressed a higher level of Annexin A3 (ANXA3) than normal fibroblasts (NF), and CAF‐CM incubation increased the ANXA3 level in lung cancer cells. Overexpression of ANXA3 in lung cancer cells increased cisplatin resistance and activated c‐jun N‐terminal kinase (JNK), whereas knockdown of ANXA3 increased cisplatin sensitivity. Further study showed that CAF‐CM enhanced cisplatin resistance by inhibiting cisplatin‐induced apoptosis, determined by repression of caspase‐3 and caspase‐8, through activation of the ANXA3/JNK pathway. Conversely, suppression of JNK activation by specific inhibitor retarded the effect of CAF‐CM and ANXA3 on cisplatin sensitivity. Taken together, our study demonstrated that CAF potentiated chemoresistance of lung cancer cells through a novel ANXA3/JNK pathway both in vitro and in vivo, suggesting ANXA3 could be a potential therapeutic target for the treatment of chemoresistant cancer.
Cancer‐associated fibroblasts decreased the sensitivity of lung cancer cells to cisplatin. CAF expressed higher level of ANXA3 than normal fibroblasts (NF), and CAF‐CM incubation increased the ANXA3 level in lung cancer cells. CAF potentiated chemoresistance of lung cancer cells through a novel ANXA3/JNK pathway both in vitro and in vivo.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Tumor progression requires the communication between tumor cells and tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are major components of stromal cells. CAFs contribute to ...metastasis process through direct or indirect interaction with tumor cells; however, the underlying mechanism is largely unknown. Here, we reported that autophagy was upregulated in lung cancer-associated CAFs compared to normal fibroblasts (NFs), and autophagy was responsible for the promoting effect of CAFs on non-small cell lung cancer (NSCLC) cell migration and invasion. Inhibition of CAFs autophagy attenuated their regulation on epithelial-mesenchymal transition (EMT) and metastasis-related genes of NSCLC cells. High mobility group box 1 (HMGB1) secreted by CAFs mediated CAFs' effect on lung cancer cell invasion, demonstrated by using recombinant HMGB1, HMGB1 neutralizing antibody, and HMGB1 inhibitor glycyrrhizin (GA). Importantly, the autophagy blockade of CAFs revealed that HMGB1 release was dependent on autophagy. We also found HMGB1 was responsible, at least in part, for autophagy activation of CAFs, suggesting CAFs remain active through an autocrine HMGB1 loop. Further study demonstrated that HMGB1 facilitated lung cancer cell invasion by activating the NFκB pathway. In a mouse xenograft model, the autophagy specific inhibitor chloroquine abolished the stimulating effect of CAFs on tumor growth. These results elucidated an oncogenic function for secretory autophagy in lung cancer-associated CAFs that promotes metastasis potential, and suggested HMGB1 as a novel therapeutic target.
This paper analyzes the grinding force variation of grind-hardening process and proposes a simulation model to predict the residual stress profile based on the variable grinding forces. ...Time-dependent grinding force is discretized to calculate the heat flux intensity, which is applied on the actual contact length for the grinding temperature field, and the harden layer depth along the workpiece length is predicted. After that, the mechanical and thermal stress field is calculated with the results of variable grinding forces and grinding temperature, respectively. The loading stresses are coupled into an elastic-plastic structural analysis to estimate the residual stresses by defining indicator variables. Experimental results on the residual stress and the harden layer profile have validated the theoretical model.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A magnetorheological shear thickening fluid (MSTF) is prepared through adding carbonyl iron particles and Al
2
O
3
abrasives into the traditional shear thickening fluid (STF) to improve low shear ...stress characteristic of STF in this work. To select the optimal sample as base fluid for MSTF, a series of STFs was pre-prepared and its rheological characteristics were further tested, which contained different concentrations of starch polymer and abrasive. Furthermore, different character parameters of MSTFs, such as magnetic field intensity and carbonyl iron particle’s concentration, were experimentally tested to explore its rheological characteristics. Then, the magnetorheological effect on shear thickening formation of MSTFs was furtherly discussed. Experimental results show that with the same base fluid the viscosity and the shear stress of MSTFs are both higher than of STFs under the action of magnetic field. Moreover, the MSTF exhibits a good shear thickening effect under the weak magnetic field intensity and at low level of iron particle concentration, because the existence of hydrogen bonds and magnetic particle chains makes the shear thickening effect of MSTF enhanced by particle clusters. The results indicate that the MSTFs as polishing fluid contribute to develop a higher efficiency polishing method in the future.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The existing micro-spindle systems equipped with micro-tools compromise micro-machining accuracy and efficiency due to their large error. In this study, the radial error of micro-tool tip was ...classified into static mechanical offset, thermally induced error, and radial motion error. The micro-tool tip, having the smallest stiffness, was the major error source of radial mechanical offset. A stiffness-based error model was proposed to predict the radial mechanical offset of micro-tool tip, and the predictions were well consistent with the measured values. The front bearing, due to its large thermal loss, had lower temperature than the rear bearing at nearly all rotational speeds. The difference of thermal growths between the two ball bearings resulted in the thermally induced error. The thermally induced error increased rapidly with running time within the first hour and then entered into a relative stable state, which was modeled by the least square method. The proposed model of thermally induced error also considered exponential characteristic of spindle thermal growth in nature. It agreed well with the measured values. The radial motion error increased with the over-hang length of micro-tool, but decreased with the rotational speed. It was modeled by the least square method and validated by the measurements. The micro-grinding tests were conducted to further verify the proposed predictive models of static mechanical offset, thermally induced error, and radial motion error. With the error compensation, the micro-grinding thickness was close to the required value, which showed the error predictive models and compensation scheme were effective.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The wear of micro-grinding tools less than 1 mm in diameter is crucial for achieving acceptable surface quality and accurate dimension of the workpiece. To control wear behavior of the micro-grinding ...tools, an investigation through experiments was conducted on the machining and wear performance of various (D-shaped PCD, CVD, electroless plated, and electroplated) diamond micro-grinding tools on monocrystalline silicon workpiece in this study. The experiments showed that a CVD diamond micro-grinding tool had excellent machining performance, but its relatively large diameter limited its application range. An electroplated diamond micro-grinding tool had a good machining performance but displayed severe wear. To comprehensively understand its wear mechanism, a series of grinding experiments were further done. Its mechanism was analyzed through investigating the tool and machining process parameters. In order to accurately evaluate tool wear, the ratio of tool radius loss to average grain diameter (
δ
) and the ratio of the lost grain number to the total grain number (
η
) were proposed. The
δ
-ratio and
η
-ratio related to the wear limit of 600 mesh size micro-grinding tools having a diameter of 0.5 mm were 0.16–0.18 and 11.50–13.88%, respectively.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
An aerostatic journal micro-bearing has advantages of simple structure, almost zero friction and increasable load capacity due to aerodynamic pressure effect, which makes it a possible choice for ...high-speed and precision micro-rotatory machines. This study comprehensively investigates the effects of restriction, structure and operation parameters on the performance of an aerostatic journal micro-bearing using numerical models. The numerical models are verified on a prototype aerostatic journal bearing. Considering both the performance requirement and current machining capacity, the restriction parameters of 8–12 μm in average bearing clearance and 0.08–0.14 mm in orifice diameter are recommended. Another focus of this study is the aerodynamic pressure effect on the performance of micro-bearing, which is thoroughly investigated from the aspects of restriction, structure and operation parameters. The aerodynamic pressure effect is outstanding only at ultra-high speeds and large eccentricities. Two prototypical high-speed precision micro-spindles are developed and their micro-tools with a diameter of 3.175 mm are directly supported by the micro-bearing. The aerodynamic pressure effect resulting from the ultra-high rotational speeds can improve the performance of micro-spindles under loading. However, the low rotational accuracy and balance quality compromise their performance.
•This study establishes the numerical models for the performance calculation of aerostatic journal micro-bearings. Dynamic pressure effect of the bearing is investigated with different rotational speeds and eccentricities. The presented graphs of performance change with restriction, structure and operation parameters provide a comprehensive understanding and design reference for engineers.•The numerical models are verified on a prototype aerostatic journal bearing. Considering both the performance requirement and current machining capacity, the restriction parameters of 8–12 µm in average bearing clearance and 0.08–0.14 mm in orifice diameter are recommended.•According to the theoretical analysis, a prototype micro-spindle is developed and a micro-bearing with a diameter of 3.175 mm is applied to support the micro-tool. Due to the accommodation of a monolithic flexible coupling, the static load capacity of the micro-tool can be regard as the performance of the micro-bearing. However, the poor machining precision is badly affected its performance. Therefore, another improved prototype micro-spindle is developed. Its maximum speed exceeds 240,000 rpm and the radial run-out of the tool shaft decreases to 2.79 μm, whose performance is greatly improved.•The load capacity of the micro tool at high-speeds is measured. It follows that the aerodynamic pressure effect resulting from rotational speeds has little improvement on the load capacity and stiffness of the micro-tool unless the speed and eccentricity are greatly increased. The static performance mainly depends on the aerostatic pressure effect. But the aerodynamic pressure effect plays an important role at high speeds as eccentricities are more than 3 μm, which is benefit to the dynamic stability of ultra-precision micro-spindles. Moreover, the low accuracy of miniature parts and poor balance quality of micro-shaft also compromise its performance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Mechanical micro-machining has significant advantages in compassion with other machining techniques in terms of workpiece complexity, material diversity, energy consumption, and cost. The existing ...micro-spindles, as the key fundamental equipment, cannot simultaneously guarantee ultra-high rotational speed, high rotational accuracy, and compact structure. This study discussed the details in designing of high-speed precision micro-spindles, and a new micro-spindle was proposed, which is driven by an air turbine. To enhance its stiffness and rotational accuracy, the porous ceramic aerostatic bearings are used. The key structural parameters were selected based on theoretical calculation and simulation analysis. More importantly, the theoretical models for its static error and dynamic response predictions were established and combined to optimize the size of micro-spindle. The prototype micro-spindle has a radial motion error of approximately 6.0 μm and no heating problem. The micro-grinding experiment of micro-channel shows its good feasibility and potential application in mechanical micro-machining. And it has very simple and compact structure (28 mm in diameter × 45 mm in length) and low manufacturing difficulty and cost.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The machining quality of the blade tip has a great influence on the service performance and life of the aero-engine blade. The recent paper investigates the effect of vibration during the grinding ...process of the GH4169 nickel-based superalloy blade tip. Moreover, this paper proposes a theoretical model to link the unbalance of the grinding wheel, the vibration, and the surface topography characteristics of the blade. The results show that the blade vibration during grinding and the resulting non-linear change of the grinding depth could reduce the surface quality of the blade tip and lead to differences in the surface quality of the blade tip in different areas, where the surface roughness in the entry area zone I is the largest, in the exit area zone III is the second largest, and the intermediate area zone III is the smallest. Grinding depth has a greater impact on the difference of the surface quality in the blade tip grinding process, especially when the grinding depth is greater than 4 μm, the difference of surface roughness increases significantly. On the other hand, the feed rate has little effect on the difference in surface quality. Adding damping block can reduce the surface roughness of the blade tip; however, it does not reduce the difference in surface quality.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Adiponectin (APN), also known as apM1, Acrp30, GBP28 and adipoQ, is a circulating hormone that is predominantly produced by adipose tissue. Many pharmacological studies have demonstrated that this ...protein possesses potent anti-diabetic, anti-atherogenic and anti-inflammatory properties. Although several studies have demonstrated the antioxidative activity of this protein, the regulatory mechanisms have not yet been defined in skeletal muscles. The aim of the present study was to examine the cytoprotective effects of APN against damage induced by oxidative stress in mouse-derived C2C12 myoblasts. APN attenuated H
O
-induced growth inhibition and exhibited scavenging activity against intracellular reactive oxygen species that were induced by H
O
. Furthermore, treating C2C12 cells with APN significantly induced heme oxygenase-1 (HO-1) and nuclear factor-erythroid 2 related factor 2 (Nrf2). APN also suppressed H
O
-induced mitophagy and partially inhibited the colocalization of mitochondria with autophagosomes/lysosomes, correlating with the expression of Pink1 and Parkin and mtDNA. Moreover, APN protected C2C12 myoblasts against oxidative stress-induced apoptosis. Furthermore, APN significantly reduced the mRNA and protein expression levels of Bax. These data suggest that APN has a moderate regulatory role in oxidative stress-induced mitophagy and suppresses apoptosis. These findings demonstrate the antioxidant potential of APN in oxidative stress-associated skeletal muscle diseases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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