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Studies on specific cutting energy, damage equivalent stress, and surface roughness were conducted to identify the optimum cutting parameter area in intermittent hard turning. The optimum cutting parameter area was acquired based on finite element simulations, micromechanics, damage mechanics, and intermittent turning tests. It was found that the transient specific cutting energy and the transient damage equivalent stress evolved cyclically with the periodical formation of saw-tooth chip. The average specific cutting energy in the cutting period became larger as tool wear increased. However, the average damage equivalent stress in the cutting period and surface roughness decreased first and then increased when tool wear became higher. The evolution process of these average values and surface roughness with tool wear can be divided into three stages. There were obvious corresponding relationships between these three stages and the tool wear stages. Analysis of the mean values of specific cutting energy, damage equivalent stress, and surface roughness in the steady tool wear stage indicated that when the feed rate was in the range of 0.2 to 0.25 mm/r and cutting speeds ranging from 110 to 125 m/min were adopted, relatively low energy consumption, relatively long tool life, and relatively good surface quality can be obtained at the same time.

Background Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies. Neovascularization during tumorigenesis supplies oxygen and nutrients to proliferative tumor cells, and serves as a conduit for migration. Targeting oncogenes involved in angiogenesis is needed to treat organ-confined and locally advanced ESCC. Although the phospholipase C epsilon-1 (PLCE1) gene was originally identified as a susceptibility gene for ESCC, how PLCE1 is involved in ESCC is unclear. Methods Matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used to measure the methylation status of the PLCE1 promoter region. To validate the underlying mechanism for PLCE1 in constitutive activation of the NF-κB signaling pathway, we performed studies using in vitro and in vivo assays and samples from 368 formalin-fixed esophageal cancer tissues and 215 normal tissues with IHC using tissue microarrays and the Cancer Genome Atlas dataset. Results We report that hypomethylation-associated up-regulation of PLCE1 expression was correlated with tumor angiogenesis and poor prognosis in ESCC cohorts. PLCE1 can activate NF-κB through phosphoinositide-phospholipase C-ε (PI-PLCε) signaling pathway. Furthermore, PLCE1 can bind p65 and IκBα proteins, promoting IκBα-S32 and p65-S536 phosphorylation. Consequently, phosphorylated IκBα promotes nuclear translocation of p50/p65 and p65, as a transcription factor, can bind vascular endothelial growth factor-C and bcl-2 promoters, enhancing angiogenesis and inhibiting apoptosis in vitro. Moreover, xenograft tumors in nude mice proved that PLCE1 can induce angiogenesis, inhibit apoptosis, and increase tumor aggressiveness via the NF-κB signaling pathway in vivo. Conclusions Our findings not only provide evidence that hypomethylation-induced PLCE1 confers angiogenesis and proliferation in ESCC by activating PI-PLCε-NF-κB signaling pathway and VEGF-C/Bcl-2 expression, but also suggest that modulation of PLCE1 by epigenetic modification or a selective inhibitor may be a promising therapeutic approach for the treatment of ESCC.

Vegetable oil–based nanofluid minimum quantity lubrication (VNMQL) and tool surface microstructure can be employed to efficiently improve the cutting process in an environmentally friendly way. Biomimetics-based integration of VNMQL and tool surface microstructure is expected to have beneficial effects on the friction coefficient, the cutting force, the tool temperature, the tool wear, and the surface roughness in intermittent turning process. VNMQL was integrated with tool surface microstructure on the basis of the analysis results of Odontodactylus scyllarus . For the purpose of obtaining better machining results, different combinations of the element area A and the laser angle θ were adopted for the tool surface microstructure to match VNMQL. Biomimetics-based integration of VNMQL and tool surface microstructure led to even lower values of the quantities such as the friction coefficient, the cutting force, the tool temperature, the tool wear, and the surface roughness compared with dry condition and VNMQL condition. The smallest values of these quantities were acquired at the same optimum combination of the microstructure element area A and the laser angle θ. The optimum combination can be described as follows: A was 2.4 × 10 −8 m 2 and θ was 75°. There existed close relationship among the cutting force, the tool temperature, the tool wear, and the surface roughness. Cutting force was found to be more suitable for pre-evaluating tool wear and surface roughness compared with tool temperature.

Interrupted hard turning performance of ceramic tools with varying microscopic geometries on the rake face was analyzed. A new performance index G ma was proposed for the ceramic tools. Both the external loads and the micromechanical properties of the tool material were incorporated in the proposed tool performance index. Quantitative analysis was conducted to reveal the two-dimensional fluid-like characteristics of the chip. Different kinds of microscopic textures such as M A , M B , M C , and M D were created on the rake face for ceramic tools considering the analysis results. Based on the tool performance index, performance of ceramic cutting tools which had varying microscopic textures were pre-evaluated for different groups of cutting speeds and cutting length ratios. Experimental tool lives were acquired to demonstrate the tool performance index and identify the optimum tool surface microscopic geometry. It was found that the tool performance index can be utilized to effectively pre-evaluate tool performance. Microscopic textures M B , M C , and M D were more efficient for tool life extension at relatively small cutting length ratio and relatively large cutting speed. Due to the consideration of the two-dimensional fluid-like characteristics of the chip in the design process, microscopic texture M D exhibited the highest efficiency in the tool performance enhancement.

This paper provides a comprehensive review on copper (Cu) wire bonding. Firstly, it introduces the common types of Cu wire available in the market, including bare Cu wire, coated Cu wire, insulated Cu wire, and alloyed Cu wire. For each type, their characteristics and application areas are discussed. Additionally, we provide detailed insights into the impact of Free Air Ball (FAB) morphology on bonding reliability, including its effect on bond strength and formation mechanisms. Next, the reliability of Cu wire bonding is analyzed, with a focus on the impact of intermetallic compounds and corrosion on bonding reliability. Specifically, the formation, growth, and stability of intermetallic compounds at bonding interfaces are discussed, and their effects on bonding strength and reliability are evaluated. The detrimental mechanisms of corrosion on Cu wire bonding and corrosion inhibition methods are also analyzed. Subsequently, the applications of simulation in Cu wire bonding are presented, including finite element analysis and molecular dynamics simulations, which provide important tools for a deeper understanding of the bonding process and failure mechanisms. Finally, the current development status of Cu wire bonding is summarized, and future research directions are discussed.

In the present study, an attempt is performed to critically review researches on cutting forces, cutting temperature, tool failure mechanisms, and surface roughness in intermittent cutting of hardened steel. Former studies provided much valuable information. However, some limitations can still be identified. For the purpose of having a thorough understanding of intermittent hard cutting, cutting performance of some other suitable tool materials should also be investigated. More researches on high-speed face milling of hardened steel should be conducted. More studies are needed to focus on the characteristics which arise at higher cutting speed in intermittent hard cutting. Development of intensity and area of heat source in milling should be paid attention to, so that accurate analysis of transient cutting temperatures in hard milling can be conducted. Damage mechanics can be considered as a bridge between the analysis of microscopic damage and macroscopic fracture of the tool material in intermittent hard cutting.

Background Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis. Secreted extracellular vesicles (EVs) play a key role in pathogen-host interfaces. Previous studies have shown that S. japonicum adult worms can release microRNA (miRNA)-containing EVs, which can transfer their cargo to mammalian cells and regulate gene expression in recipient cells. Tissue-trapped eggs are generally considered the major contributor to the severe pathology of schistosomiasis; however, the interactions between the host and parasite in this critical stage remain largely unknown. Methods The culture medium for S. japonicum eggs in vitro was used to isolate EVs. Transmission electron microscopy (TEM) analysis was used to confirm that vesicles produced by the eggs were EVs based on size and morphology. Total RNA extracted from EVs was analyzed by Solexa technology to determine the miRNA profile. The in vitro internalization of the EVs by mammalian cells was analyzed by confocal microscopy. The presence of EVs associated miRNAs in the primary hepatocytes of infected mice was determined by quantitative real-time PCR (qRT-PCR). Results EVs were isolated from the culture medium of in vitro cultivated S. japonicum eggs. TEM analysis confirmed that nanosized vesicles were present in the culture medium. RNA-seq analysis showed that the egg-derived EVs contained small non-coding RNA (sncRNA) populations including miRNAs, suggesting a potential role in host manipulation. This study further showed that Hepa1-6, a murine liver cell line, internalized the purified EVs and their cargo miRNAs that were detectable in the primary hepatocytes of mice infected with S. japonicum . Conclusions Schistosoma japonicum eggs can release miRNA-containing EVs, and the EVs can transfer their cargo to recipient cells in vitro. These results demonstrate the regulatory potential of S. japonicum egg EVs at the parasite-host interface.

For the purpose of revealing the formation characteristics of the chip and analyzing damage equivalent stress of the cutting tool in high-speed intermittent cutting, cutting tests, and finite element simulation were performed in the present work. Characteristics of chip morphologies acquired in cutting tests were analyzed and compared for different cutting conditions. The effects of cutting parameters on force, temperature, and stress on the shear plane were investigated. On the basis of the concept of damage equivalent stress, the initial damage of the cutting tool and the tool stress were integrated and the influences of cutting parameters on damage equivalent stress were studied. The correlations between damage equivalent stress of the cutting tool and chip formation were analyzed. Analysis results indicated that there existed strong correlations between the evolution of damage equivalent stress of the cutting tool and the chip formation process. Relatively low damage equivalent stress and relatively long tool life appeared at the same time when small values of cutting speed and feed rate were used.

In the present study, cutting conditions in face milling of AISI H13 hardened steel were optimized considering the performance of cemented carbide tool material. The initial microscopic mechanical property of the cemented carbide tool material was analyzed based on damage mechanics and boundary element method. Taking the initial microscopic mechanical property of the tool material, the initial macroscopic mechanical property of the tool material and external loads in the cutting process into account, a new tool life indicator was proposed. On the basis of the characteristics of tool life indicator and specific cutting energy, a theoretical method was established for the optimization of cutting conditions. The optimum cutting conditions were distinguished for different milling conditions. Feed per tooth f z with a value around 0.2 mm/tooth and cutting speed v ranging from 150 to 250 m/min should be used in symmetric milling to acquire a relatively long tool life and relatively low energy consumption. In down milling, feed per tooth f z should be in the range of 0.15 to 0.2 mm/tooth and cutting speed v should be between 100 and 200 m/min. Feed per tooth f z close to 0.2 mm/tooth and cutting speed v between 200 and 300 m/min should be adopted in up milling.

Background Triptolide is a widely utilized natural anti-inflammatory drug in clinical practice. Aim of this study was to evaluate effects of triptolide on hPDLSCs osteogenesis in an inflammatory setting and to investigate underlying mechanisms. Methods Using the tissue block method to obtain hPDLSCs from extracted premolar or third molar. Flow cytometry, osteogenic and adipogenic induction were carried out in order to characterise the features of the cells acquired. hPDLSC proliferative activity was assessed by CCK-8 assay to determine the effect of TNF-α and/or triptolide. The impact of triptolide on the osteogenic differentiation of hPDLSCs was investigated by ALP staining and quantification. Osteogenesis-associated genes and proteins expression level were assessed through PCR and Western blotting assay. Finally, BAY-117,082 was used to study the NF-κB pathway. Results In the group treated with TNF-α, there was an elevation in inflammation levels while osteogenic ability and the expression of both osteogenesis-associated genes and proteins decreased. In the group co-treated with TNF-α and triptolide, inflammation levels were reduced and osteogenic ability as well as the expression of both osteogenesis-associated genes and proteins were enhanced. At the end of the experiment, both triptolide and BAY-117,082 exerted similar inhibitory effects on the NF-κB pathway. Conclusion The osteogenic inhibition of hPDLSCs by TNF-α can be alleviated through triptolide, with the involvement of the p-IκBα/NF-κB pathway in this mechanism.