A ternary CrNiTi medium-entropy alloy (MEA) coating with excellent surface performance (hardness and wear resistance) was successfully prepared on pure Ti sheet by pulsed laser cladding. ...Microstructural characteristics of the MEA coating were probed by combined use of multiple characterization techniques and reasons for the formation mechanisms of various phases in the coating were well explored. Results show that fine cellular grains are formed in the MEA coating during the ultrafast non-equilibrium solidification process induced by pulsed laser cladding. These grains have an average size less than 1 μm and correspond to a BCC solid-solution phase. There appears irregular-shaped Cr2Ti Laves phase (C14-type) inside most of the cellular grains, while intergranular structures are demonstrated to be NiTi intermetallics. Hardness tests reveal that the CrNiTi MEA coating has a hardness of 940 ± 35 HV which is ~8 times that of the pure Ti substrate (119 ± 9 HV). Also compared to the pure Ti substrate, a much lower wear rate is noted for the coating demonstrating greatly improved wear resistance. Comprehensive analyses show that the excellent surface performance of the CrNiTi MEA coating can be ascribed to combined contributions from the solid-solution hardening and grain refinement hardening of the BCC phase, as well as second phase hardening produced by Cr2Ti Laves phase and NiTi intermetallics.
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•CrNiTi MEA coating is successfully fabricated on pure Ti sheet using pulsed laser cladding.•The coating is consisted of BCC solid-solution phase, Cr2Ti Laves phase and NiTi intermetallics.•Hardness of the coating is 940 ± 35 HV, ~8 times that of the substrate (119 ± 9 HV).•Specific wear rate of the coating is one order of magnitude lower than that of the substrate.•Such excellent performance can be attributed to joint contribution from specific microstructural characteristics.
Dioecious spinach (Spinacia oleracea L.), a commercial and nutritional vegetable crop, serves as a model for studying the mechanisms of sex determination and differentiation in plants. However, this ...mechanism is still unclear. Herein, based on PacBio Iso-seq and Illumina RNA-seq data, comparative transcriptome analysis of male and female flowers were performed to explore the sex differentiation mechanism in spinach.
Compared with published genome of spinach, 10,800 transcripts were newly annotated; alternative splicing, alternative polyadenylation and lncRNA were analyzed for the first time, increasing the diversity of spinach transcriptome. A total of 2965 differentially expressed genes were identified between female and male flowers at three early development stages. The differential expression of RNA splicing-related genes, polyadenylation-related genes and lncRNAs suggested the involvement of alternative splicing, alternative polyadenylation and lncRNA in sex differentiation. Moreover, 1946 male-biased genes and 961 female-biased genes were found and several candidate genes related to gender development were identified, providing new clues to reveal the mechanism of sex differentiation. In addition, weighted gene co-expression network analysis showed that auxin and gibberellin were the common crucial factors in regulating female or male flower development; however, the closely co-expressed genes of these two factors were different between male and female flower, which may result in spinach sex differentiation.
In this study, 10,800 transcripts were newly annotated, and the alternative splicing, alternative polyadenylation and long-noncoding RNA were comprehensively analyzed for the first time in spinach, providing valuable information for functional genome study. Moreover, candidate genes related to gender development were identified, shedding new insight on studying the mechanism of sex determination and differentiation in plant.
Sex determination and differentiation is an important biological process for unisexual flower development. Spinach is a model plant to study the mechanism of sex determination and differentiation of ...dioecious plant. Till now, little is known about spinach sex determination and differentiation mechanism. MicroRNAs are key factors in flower development. Herein, small RNA sequencing was performed to explore the roles of microRNAs in spinach sex determination and differentiation. As a result, 92 known and 3402 novel microRNAs were identified in 18 spinach female and male flower samples. 74 differentially expressed microRNAs were identified between female and male flowers, including 20 female-biased and 48 male-biased expression microRNAs. Target prediction identified 22 sex-biased microRNA-target pairs, which may be involved in spinach sex determination or differentiation. Among the differentially expressed microRNAs between FNS and M03, 55 microRNAs were found to reside in sex chromosome; one of them,
, was functionally studied via genetic transformation. Silencing of
resulted in abnormal anther while overexpression of
induced early flowering, indicating
was a male-promoting factor and validating the reliability of our small RNA sequencing data. Conclusively, this work can supply valuable information for exploring spinach sex determination and differentiation and provide a new insight in studying unisexual flower development.
Microchromosome maintenance protein 10 (MCM10) is required for DNA replication in all eukaryotes, and it plays a key role in the development of many types of malignancies. However, we currently still ...do not know the relationship between MCM10 and ovarian cancer (OV) prognosis and immune checkpoints.
: The Gene Expression Profiling Interactive Analysis and Tumor Immunology Estimation Resource (TIMER) databases were used to investigate MCM10 expression in Fan cancer. The Kaplan-Meier Plotter and PrognoScan were used to assess the relationship between MCM10 and OV prognosis. The LinkedOmics database was used to analyze the MCM10 co-expression network and explore GO term annotation and the KEGG pathway. The relationship between MCM10 expression and immune infiltration in OV was investigated using the Tumor Immunology Estimation Resource database. cBioPortal database was used to explore the relationship between MCM10 expression and 25 immune checkpoints. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect MCM10 expression. The prognosis was also analyzed by distinguishing between high and low expression groups based on median expression values.
: The results of the three data sets (220,651_s_at, 222,962_s_at and 223,570_at) in KM Plotter all indicated that the overall survivalof the high MCM10 expression group was lower than that of the low expression group OV, and the results of GSE9891 also reached the same conclusion. The expression level of MCM10 was negatively correlated with B cells and CD8+T cells, and positively correlated with CD4+T Cells and Macrophages. GO term annotation and KEGG pathway analysis showed that the co-expressed genes of MCM10 were mainly enriched in cell cycle and DNA replication. The alterations in MCM10 coexisted statistically with the immune checkpoints CTLA4, TNFSF4, TNFSF18, CD80, ICOSLG, LILRB1 and CD200. PCR results displayed that MCM10 was highly expressed in OV tissues, and the increased expression of MCM10 was significantly associated with poor overall survival.
: These results demonstrated that high expression of MCM10 was associated with poor prognosis in OV and correlated with immune checkpoints.
Hypoxia, a major condition associated with the tumor microenvironment, stimulates the migration of cancer cells. SOX2 is a powerful transcription factor that shows higher expression in several ...cancers, however, its role in hypoxia-induced breast cancer cell migration remains largely elusive.
The human breast cancer cell lines MDA-MB-231 and MDA-MB-468 were cultured under hypoxic conditions. The cell migration rate was determined using the wound-healing and transwell assays. The protein levels of SOX2, NEDD9 and HIF-1α were evaluated via western blotting analysis. The NEDD9 mRNA levels were evaluated using qPCR. The activation of Rac1 was detected with the pulldown assay. The binding of SOX2 to the NEDD9 promoter was checked using the luciferase reporter assay. We also transfected breast cancer cells with specific siRNA for SOX2, NEDD9 or the Rac1 inactive mutant (T17 N) to investigate the role of SOX2, NEDD9 and Rac1 in the response to hypoxia.
Hypoxia markedly increased SOX2 protein levels in a time-dependent manner. SiRNA-mediated disruption of SOX2 inhibited cell migration under hypoxic conditions. Hypoxia also significantly augmented the NEDD9 mRNA and protein levels. Interestingly, SOX2 is a positive transcriptional regulator of NEDD9. Knockdown of SOX2 inhibited hypoxia-induced NEDD9 mRNA and protein expressions. Furthermore, hypoxia-induced upregulation of Rac1 activity and HIF-1α expression was attenuated by SOX2 or NEDD9 silencing, and Rac1-T17 N abolished HIF-1α expression as well as cell migration in cells subjected to hypoxia.
Our results highlight the essential role of SOX2 in breast cancer cell motility. The upregulation of SOX2 under hypoxic conditions may facilitate NEDD9 transcription and expression, and subsequent activation of Rac1 and HIF-1α expression. This could accelerate breast cancer cell migration.
Arsenic trioxide (As₂O₃), a traditional remedy in Chinese medicine, has been used in acute promyelocytic leukemia (APL) research and clinical treatment. Previous studies have shown that As₂O₃ exerts ...its potent antitumor effects in solid tumors by regulating cell proliferation and survival. The aim of this study was to investigate whether As₂O₃ inhibited gastric cancer cell migration and angiogenesis by regulating FOXO3a expression. We found that As₂O₃ reduced gastric cancer cell viability in a dose-dependent manner and also inhibited cell migration and angiogenesis in vitro. Western blotting and immunofluorescence showed that As₂O₃ downregulated the levels of p-AKT, upregulated FOXO3a expression in the nucleus, and attenuated downstream Vascular endothelial growth factor (VEGF) and Matrix metallopeptidase 9 (MMP9) expression. Moreover, we demonstrated that knockdown of FOXO3a significantly reversed the inhibition of As₂O₃ and promoted cell migration and angiogenesis in vitro. Further, As₂O₃ significantly inhibited xenograft tumor growth and angiogenesis by upregulating FOXO3a expression in vivo. However, knockdown of FOXO3a attenuated the inhibitory effect of As₂O₃ in xenograft tumors, and increased microvessel density (MVD) and VEGF expression. Our results demonstrated that As₂O₃ inhibited migration and angiogenesis of gastric cancer cells by enhancing FOXO3a expression.
Rheumatoid arthritis (RA) is a persistent autoimmune condition with no identified cure currently. Recently, scientists have applied metabolomics to investigate altered metabolic profiles and unique ...diseases-associated metabolic signatures. Herein, we applied metabolomics approach to analyze serum samples of 41 RA patients and 42 healthy controls (HC) with the aim to characterize RA patients' metabolic profile, investigate related underlying pathological processes, and identify target metabolites. By utilizing ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry, we found 168 proposed metabolites and 45 vital metabolic pathways. Our analysis revealed that deoxyinosine (DI), a metabolite of the purine metabolic pathway, was the most significant reduced metabolite in RA patients. Furthermore, through targeted detection, we confirmed lower concentration of DI in RA patients' peripheral blood. Moreover, DI inhibited lipopolysaccharide-induced inflammation both in vitro and in vivo. We further assessed DI's therapeutic potential in a collagen-induced arthritis (CIA) murine model. The results revealed that DI attenuated CIA, as evidenced by significantly lowered clinical scores of arthritis, alleviated joint swelling, and mitigated bone destruction. Moreover, we elucidated the underlying mechanism by which DI increased the population of myeloid-derived suppressor cells (MDSCs) and suppressed the proliferation of induced T cells. Collectively, these findings suggested that DI potentially ameliorated RA by inducing immunosuppressive MDSCs. The study provides key observations on RA pathogenesis and may contribute to developing novel therapeutic strategies for this debilitating condition.
Gastric cancer is a common and lethal human malignancy worldwide and cancer cell metastasis is the leading cause of cancer-related mortality. MICAL2, a flavoprotein monooxygenase, is an important ...regulator of epithelial-to-mesenchymal transition. The aim of this study was to explore the effects of MICAL2 on gastric cancer cell migration and determine the underlying molecular mechanisms.
Cell migration was examined by wound healing and transwell assays. Changes in E-cadherin/β-catenin signaling were determined by qPCR and analysis of cytoplasmic and nuclear protein fractions. E-cadherin/β-catenin binding was determined by co-immunoprecipitation assays. Cdc42 activity was examined by pulldown assay.
MICAL2 was highly expressed in gastric cancer tissues. The knockdown of MICAL2 significantly attenuated migratory ability and β-catenin nuclear translocation in gastric cancer cells while LiCl treatment, an inhibitor of GSK3β, reversed these MICAL2 knockdown-induced effects. Meanwhile, E-cadherin expression was markedly enhanced in MICAL2-depleted cells. MICAL2 knockdown led to a significant attenuation of E-cadherin ubiquitination and degradation in a Cdc42-dependent manner, then enhanced E-cadherin/β-catenin binding, and reduced β-catenin nuclear translocation.
Together, our results indicated that MICAL2 promotes E-cadherin ubiquitination and degradation, leading to enhanced β-catenin signaling via the disruption of the E-cadherin/β-catenin complex and, consequently, the promotion of gastric cell migration. Video Abstract.
Enhanced migration potential is a common characteristic of cancer cells induced by mechanisms that are incompletely defined. The present study was designed to investigate relationship of a new ...discovered cytoskeleton regulator MICAL‐L2 and the endogenous epidermal growth factor receptor (EGFR) signalling pathways in gastric cancer cell migration. Increased expression of MICAL‐L2 in gastric cancer cells up‐regulated EGFR protein level, accompanied by the increase of cell migration, whereas silencing MICAL‐L2 down‐regulated EGFR and inhibited cell migration. Expression of MICAL‐L2 was also shown positively correlated with the activation of HSP27/cytoskeleton and HSP27/β‐catenin signalling pathways that provide key mechanisms controlling cell migration. The up‐regulating effect of MICAL‐L2 on EGFR is mediated through a transcription‐independent mechanism that involves inhibiting EGFR protein degradation in lysosome. Further analysis indicated that Cdc42 activation contributed in maintaining the effect of MICAL‐L2 on EGFR stability. Furthermore analysis of clinic specimens revealed increased expression of MICAL‐L2 in carcinoma tissues and a positive correlation between MICAL‐L2 and EGFR expression levels. The above results indicate that MICAL‐L2 potentiates gastric cell migration via inhibiting EGFR degradation in lysosome via a Cdc42‐dependent manner that leads to the activation of EGFR/HSP27 signalling pathways.
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