Apoptosis is widely known as programmed cell death eliciting no inflammatory responses. The intricacy of apoptosis has been a focus of an array of researches, accumulating a wealth of knowledge which ...led to not only a better understanding of the fundamental process, but also potent therapies of diseases. The classic intrinsic and extrinsic signaling pathways of apoptosis, along with regulatory factors have been well delineated. Drugs and therapeutic measures designed based on current understanding of apoptosis have long been employed. Small-molecule apoptosis inducers have been clinically used for eliminating morbid cells and therefore treating diseases, such as cancer. Biologics with improved apoptotic efficacy and selectivity, such as recombinant proteins and antibodies, are being extensively researched and some have been approved by the FDA. Apoptosis also produces membrane-bound vesicles derived from disassembly of apoptotic cells, now known as apoptotic bodies (ApoBDs). These little sealed sacs containing information as well as substances from dying cells were previously regarded as garbage bags until they were discovered to be capable of delivering useful materials to healthy recipient cells (e.g., autoantigens). In this review, current understandings and knowledge of apoptosis were summarized and discussed with a focus on apoptosis-related therapeutic applications and ApoBDs.
Multilayer hard coatings of TiCN/TiC/TiN on high speed steel substrates were deposited using a chemical vapor deposition system. Evaluations of microstructure, wear morphology of coatings were ...characterized by scanning electron microscopy, and optical microscopy. Friction coefficient and wear rates of coatings were investigated using ball-on-disk tester sliding against a WC ball at a constant load of 20
N. Tribological behavior of the coatings at room and elevated temperature were discussed. Different changing tendency of friction coefficient were observed from ball-on-disc experiments. Results showed that the friction coefficient of coatings increased gradually to a highest value, then to a relatively constant value at room temperature dry sliding wear. The friction coefficient exhibited a reverse variation tendency at temperature of 550
°C. It got a higher value at the first sliding friction cycles. Then the value of friction coefficient decreased, suffered irregular oscillations and kept a relatively lower value with increasing sliding time. Reasons of the variation of friction coefficient with sliding time and wear mechanism were analyzed and discussed at room and elevated temperatures, respectively.
This study developed a novel and inexpensive method for fabricating size-tunable tapered antireflective nanopillars on a polycarbonate (PC) film using hybrid nano-patterning lithography consisting of ...nanosphere lithography (NSL) and nanoimprint lithography (NIL). The optical properties of the antireflective surfaces can be controlled by the CrN nanomold morphologies resulting from the different reactive ion etching conditions. The nanomold surface of CrN nanohole arrays has a low surface energy at the interface and has an anti-sticking property that can be applied in the problem of the sticking during demolding. A high-performance antireflective tapered nanopillar layer was successfully imprinted on a PC film surface using a contactless gas assisted pressing process along with a CrN nanomold prepared by NSL. The optical properties of antireflective characteristic of the PC tapered nanostructures were analyzed. Such antireflective surfaces are promising for fabrication of high light transmittance and antireflective optical materials to be used in many important fields.
•This study presents a high-throughput strategy and low-cost.•The size-tunable tapered antireflective nanopillars can be controlled by hybrid nano-patterning lithography.•The transmittance of the PC tapered antireflective nanopillars was enhanced in the visible wavelength.
The WNbMoTa-based refractory high entropy alloy (RHEA) is expected to become a new generation of high-temperature materials due to its high thermal stability, which can be used in aerospace, nuclear ...energy and other fields. In this paper, TN10 (TN is the abbreviation of Ti and Ni elements), TN15, TN20 and TN25 non-equimolar WNbMoTa-based RHEAs were designed based on phase engineering and formed by laser powder bed fusion (LPBF) technology. The solidification thermodynamics, microstructure and mechanical properties (compressive strength at 25 °C) of the four alloys were analyzed, and the strengthening mechanism of TN20 alloy was studied. The compressive yield strength of the four alloys exceeds 2050 MPa, the ultimate compressive strength exceeds 2550 MPa, and the elongation exceeds 9%. The compressive yield strength of TN20 alloy is 2513 MPa, the ultimate strength is 3127 MPa, and the elongation is 11.38%. The room temperature (25 °C) compressive yield strength of TN20 alloy is the highest among the high entropy alloys studied so far. TN20 alloy is composed of BCC matrix phase and grain boundary phase containing three different structures, which are B2 TiNi phase, Ni55Nb25Ti15Ta5 phase generating stacking faults and Ni70Ti20Nb10 secondary precipitated phase. The micrometer matrix phase and nanometer grain boundary phase of TN20 alloy show a network distribution in fine crystal region. After the matrix phase cracks due to high thermal stress, the flow TiNi-rich grain boundary phases precipitate to fill the cracks. The grain boundary phase with high proportion in this region is enhanced by the secondary phase and its nanoprecipitated phase. In other regions, stacking faults are generated by the Ni55Nb25Ti15Ta5 phases, which convert the thermal stress that induces crack into lattice defects of the crystal. On the other hand, the content of B2 phase is the highest in grain boundary phase, and the grain boundary between B2 phase and matrix phase is a coherent grain boundary, which realizes the high quality combination of grain boundary phase and matrix phase. The design and strengthening of WNbMoTa-based non-equimolar RHEAs are studied in this paper, which is expected to provide a reference for the design of a new generation of high entropy alloy.
•Four kinds of HEAs were designed through matrix phase mechanical property optimization and defect control.•The compressive yield strength of TN20 alloy is up to 2513 MPa, the ultimate strength is 3127 MPa, and the elongation is 11.38%.•The matrix phase and B2 phase showed a coherent matching relationship, which strengthened the interface.
Hard Cr–N and silicon doped Cr–Si–N nanocomposite coatings were deposited using closed unbalanced magnetron sputtering ion plating system. Coatings doped with various Si contents were synthesized by ...changing the power applied on Si targets. Composition of the films was analyzed using glow discharge optical emission spectrometry (GDOES). Microstructure and properties of the coatings were characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), and nano-indentation. The harnesses and the elastic modulus of Cr–Si–N coatings gradually increased with rising of silicon content and exhibited a maximum at silicon content of 4.1 at.% and 5.5 at.%. The maximum hardness and elastic modulus of the Cr–Si–N nanocomposite coatings were approximately 30 GPa and 352 GPa, respectively. Further increase in the silicon content resulted in a decrease in the hardness and the elastic modulus of the coatings. Results from XRD analyses of CrN coatings indicated that strongly preferred orientations of (111) were detected. The diffraction patterns of Cr–Si–N coatings showed a clear (220) with weak (200) and (311) preferred orientations, but the peak of CrN (111) was decreased with the increase of Si concentration. The XRD data of single-phase Si
3N
4 was free of peak. The peaks of CrN (111) and (220) were shifted slightly and broadened with the increase of silicon content. SEM observations of the sections of Cr–Si–N coatings with different silicon concentrations showed a typical columnar structure. It was evident from TEM observation that nanocomposite Cr–Si–N coatings exhibited nano-scale grain size. Friction coefficient and specific wear rate (SWR) of silicon doped Cr–N coatings from pin-on-disk test were significantly lower in comparison to that of CrN coatings.
In this study, we explored the therapeutic potential of microRNA (miR) analogs against non–small‐cell lung cancer (NSCLC) using lentiviral delivery of short hairpin RNA (shRNA). By using A549 as a ...model cell line, we used analogs and mimics of miR‐4319/miR‐125‐5p to target the tumorigenic RAF1 gene. Lentiviral vectors carrying shRNA of a highly efficient miRNA analog of miR‐4319/miR‐125‐5p, Analog2, were constructed to infect A549 cells. Our results showed that, compared with the noncancerous bronchial epithelial cell line 16HBE, lentivirus delivering Analog2 shRNA induced significant G2/M arrest and subsequent apoptosis in A549 cells, but not in 16HBE cells. Western blot analysis revealed that key factors regulating cell cycle were downregulated following RAF1 inhibition. In vivo xenograft experiments showed that lentivirus carrying Analog2 shRNA markedly decreased tumor size. Therefore, lentiviral delivery of Analog2 shRNA is a valid RNA interference‐based treatment against NSCLC with high potency and specificity.
Lentiviral vectors carrying short hairpin RNA (shRNA) of a highly efficient microRNA (miRNA) analog of miR‐4319/miR‐125‐5p, Analog2, were constructed to infect A549 cells. Our results showed that, compared with the noncancerous bronchial epithelial cell line 16HBE, lentivirus delivering Analog2 shRNA induced significant G2/M arrest and subsequent apoptosis in A549 cells, but not in 16HBE cells.
In this study, we evaluated the efficacy of various mycoplasma removal reagents using nuclear staining, DNA gel electrophoresis, and qPCR-based quantification. Our results showed Plasmocure and ...Plasmocin are two effective anti-mycoplasma reagents whose effects can be observed within a week. However, prolonged treatment with Plasmocin led to development of resistance. Withdrawal of anti-mycoplasma reagents led to reoccurrence of mycoplasma contamination, but addition of prevention reagent, such as Primocin, prevented recontamination. Therefore, sequential treatment by Plasmocure and Primocin is the best course of action against mycoplasma contamination. Lastly, we developed methods based on qPCR to estimate the average number of mycoplasma associated with a single contaminated cell. We have shown, for the first time, that untreated contaminated BEAS-2B cells have approximately 300–400 mycoplasma contaminants per cell in the cytoplasm or attached to the cell membrane. Furthermore, withdrawal of anti-mycoplasma reagents led to reoccurrence of mycoplasma contamination within two days, and therefore continued use of prevention reagent is imperative.
•Employed DNA gel electrophoresis and nuclear staining to preliminarily determine the level of mycoplasma contamination in cultured cells.•Assayed for five anti-mycoplasma reagents using DNA gel electrophoresis and nuclear staining and discovered an efficient and effective treatment using Plasmocure and Primocin.•Prolonged treatment with reagent containing single antibiotic, i.e. Plasmocin in this study, led to development of bacterial resistance and therefore should be avoided. Reagents containing more than one antibiotic or peptides are recommended.•Recontamination of mycoplasma is highly likely following withdrawal of reagents. Therefore, use of prevention reagent is mandatory.•qPCR-based quantification of mycoplasma in contaminated cultured cells was able to determine the number of mycoplasma in a single contaminated cell.
Microfibril-associated glycoprotein 2 (MAGP2) plays an important role in regulating cell signaling and acts as a biomarker to predict the prognostic effect of tumor therapy. However, research on ...MAGP2 mostly focuses on its extracellular signal transmission features, and its potential intracellular function is rarely reported. Here, we reported that intracellular MAGP2 increased the stability of urokinase-type plasminogen activator receptor (uPAR) in the cell by direct interaction which inhibits the lysosomal-mediated degradation of uPAR. Furthermore, with the detection of protein content changes and proteomics analysis, we found that highly expressed MAGP2 promoted the proliferation of tumor cells through uPAR-mediated p38-NF-ĸB signaling axis activation, enhancement of DNA damage repair and reduction of cell stagnation in the S phase of the cell cycle. In the nude mouse xenograft model of colorectal cancer, the upregulation of MAGP2 in tumor cells significantly promoted tumor progression, while the downregulation of uPAR significantly attenuated tumor progression. These studies elucidate the role of MAGP2 inside the cell and provide a new explanation for why patients with higher MAGP2 expression in tumors are associated with a worse prognosis. In addition, we also determined a mechanism for the stable existence of uPAR in the cell, providing information for the development of tumor drugs targeting uPAR.
•MAGP2 interacts directly with uPAR to improve the protein stability of uPAR.•MAGP2 promotes uPAR-mediated cell proliferation by regulating the p38/NF-κB axis, DNA damage and cell cycle.•MAGP2 promotes uPAR-mediated tumor growth in vivo.
The optimization of the powder bed fusion (PBF) parameters is always an important part of a new alloy forming process, especially in the field of high-entropy alloys (HEAs). In this work, based on ...the extraction of molten pool feature, a kind of efficient process design method for pores suppression is proposed and eliminates the pores generated during the PBF process for a new Nb30Mo10Ta30Ti20Ni10 HEA whose tensile strength and elongation can reach 1.46 GPa and 5.5 %, respectively, after the optimization process. The high strength of this HEA is not only due to the high Archimedes' density but also the high grain boundary density ρ, which causes a proportion of the heat transfer interface of the molten pool. Therefore, as a guide for the PBF process, the proposed pores suppression process design method is benefit for finding the performance limits of HEAs, which are always hidden by non-optimal processes.
The Fas-associated death domain (FADD) has long been regarded as a crucial adaptor protein in the extrinsic apoptotic pathway. Despite the non-apoptotic function of FADD is gradually being discovered ...and confirmed, its corresponding physiological and pathological significance is still unclear. Based on the database of GWAS catalog and GTEx Portal, 17 SNPs associated with leukemia susceptibility were found to be linked to FADD expression. We then investigated a regulatory role of FADD in T-acute lymphoblastic leukemia (T-ALL) using Jurkat cells as a model. Jurkat cells stably depleted of FADD (FADD
Jurkat) expression exhibited dampened proliferation, hypersensitivity to Etoposide-induced intrinsic apoptosis whereas near total resistance to TRAIL-induced extrinsic apoptosis. Comparison between wild type and FADD
Jurkat cells using iTRAQ-based proteomics revealed considerably altered expression spectrum of genes, and led us to focus on metabolic pathways. Investigation of glycolytic and mitochondrial pathways and relevant enzymes revealed that FADD knockout triggered a metabolic shift from glycolysis to mitochondrial respiration in Jurkat cells. Re-expression of FADD in FADD
Jurkat cells partially rescued glycolytic capacity. FADD loss triggers global metabolic reprogramming in Jurkat cells and therefore remains as a potential druggable target for ALL treatment.
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