The global carbon emission reduction strongly requires high strength lightweight die-cast aluminium alloys in industry. Here die-cast AlSiMgMn–TiB2 composites with advanced mechanical performance ...were fabricated by the implantation of TiB2 nanoparticles. Super vacuum assisted high pressure die casting was applied to enable the T6 heat treatment of the composites, and the super vacuum of 20 mbar was achieved in the limited evacuation time of 1.6 s. The composites demonstrated good die castability within the addition of 3.5 wt% TiB2, while the composites could not fill into the chill vent with the addition of >3.5 wt% TiB2. The composite with 3.5 wt% TiB2 nanoparticles delivered the high hardness of 150.2 kg/mm2, yield strength of 351 MPa, tensile strength of 410 MPa, and the industrially applicable good ductility of 5.2%, after T6 heat treatment. The strengthening of the T6 heat treated composite was a result of both TiB2 nanoparticles and nanoscale β′′ precipitates that had coherent interfaces with α–Al matrix, i.e., Al(11-1)//TiB2(0001), Al011//TiB211-20, Al320//β″(a-axis), Al1-30//β″(c-axis) and Al(020)//β″(b-axis). The T6 heat treated composite reinforced by 3.5 wt% TiB2 showed ductile fracture.
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•Super vacuum of 20 mbar was achieved in limited evacuation time of 1.6 s during die casting of AlSiMgMn/TiB2 composites.•Heat-treated AlSiMgMn/3.5wt.%TiB2 composite had yield strength of 351MPa, tensile strength of 410MPa and ductility of 5.2%.•Die castability of compsites decreased with increasing of TiB2 nanoparticles due to decrease of die filling ability.•Strengthening of heat-treated AlSiMgMn/TiB2 composites resulted from TiB2 nanoparticles and β′′ precipitates.
Cerebral ischemia is a severe, acute condition, normally caused by cerebrovascular disease, and results in high rates of disability, and death. Phagoptosis is a newly recognized form of cell death ...caused by phagocytosis of viable cells, and has been reported to contribute to neuronal loss in brain tissue after ischemic stroke. Previous data indicated that exposure of phosphatidylserine to viable neurons could induce microglial phagocytosis of such neurons. Phosphatidylserine can be reversibly exposed to viable cells as a result of a calcium-activated phospholipid scramblase named TMEM16F. TMEM16F-mediated phospholipid scrambling on platelet membranes is critical for hemostasis and thrombosis, which plays an important role in Scott syndrome and has been confirmed by much research. However, few studies have investigated the association between TMEM16F and phagocytosis in ischemic stroke. In this study, a middle-cerebral-artery occlusion/reperfusion (MCAO/R) model was used in adult male Sprague-Dawley rats
, and cultured neurons were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate cerebral ischemia-reperfusion (I/R) injury
. We found that the protein level of TMEM16F was significantly increased at 12 h after I-R injury both
and
, and reversible phosphatidylserine exposure was confirmed in neurons undergoing I/R injury
. Additionally, we constructed a LV-TMEM16F-RNAi transfection system to suppress the expression of TMEM16F during and after cerebral ischemia. As a result, TMEM16F knockdown alleviated motor function injury and decreased the microglial phagocytosis of viable neurons in the penumbra through inhibiting the "eat-me" signal phosphatidylserine. Our data indicate that reducing neuronal phosphatidylserine-exposure via deficiency of TMEM16F blocks phagocytosis of neurons and rescues stressed-but-still-viable neurons in the penumbra, which may contribute to reducing infarct volume and improving functional recovering.
The use of PARP inhibitors in combination with radiotherapy is a promising strategy to locally enhance DNA damage in tumors. Loss of XRCC2 compromises DNA damage repairs, and induced DNA damage ...burdens may increase the reliance on PARP-dependent DNA repairs of cancer cells to render cell susceptibility to PARP inhibitor therapy. Here we tested the hypothesis that XRCC2 loss sensitizes colorectal cancer (CRC) to PARP inhibitor in combination with radiotherapy (RT). We show that high levels of XRCC2 or PARP1 in LARC patients were significantly associated with poor overall survival (OS). Co-expression analyses found that low levels of PARP1 and XRCC2 were associated with better OS. Our in vitro experiments indicated that olaparib+IR led to reduced clonogenic survival, more DNA damage, and longer durations of cell cycle arrest and senescence in XRCC2-deficient cells relative to wild-type cells. Furthermore, our mouse xenograft experiments indicated that RT + olaparib had greater anti-tumor effects and led to long-term remission in mice with XRCC2-deficient tumors. These findings suggest that XRCC2-deficient CRC acquires high sensitivity to PARP inhibition after IR treatment and supports the clinical development for the use of olaparib as a radiosensitizer for treatment of XRCC2-deficient CRC.
The reduced solubility of hydrogen in molten aluminium is believed to be a key factor influencing the formation of gas porosity, which adversely affects the mechanical properties. In this study, two ...crucibles of AlSi10MnMg alloy were degassed using conventional rotary degassing and high shear melt conditioning (HSMC) respectively and then cast into tensile specimens using the high-pressure die casting (HPDC) process. An optimal holding time of 10 min was established for both processing techniques corresponding to reduced density index (DI) and reduced variation in tensile performance. After rotary degassing, DI values were found to increase with increasing holding times, rising to 4.1% after 70 min. For HSMC, a quasi-steady state was observed with a maximum DI value of 1.4% after 190 min. The pore size in HPDC cast specimens was observed to be considerably lower after degassing with the HSMC device compared with rotary degassing.
SIRT1 is reported to participate in macrophage differentiation and affect sepsis, and Notch signaling is widely reported to influence inflammation and macrophage activation. However, the specific ...mechanisms through which SIRT1 regulates sepsis and the relationship between SIRT1 and Notch signaling remain poorly elucidated. In this study, we found that SIRT1 levels were decreased in sepsis both
and
and that SIRT1 regulation of Notch signaling affected inflammation. In lipopolysaccharide (LPS)-induced sepsis, the levels of Notch signaling molecules, including Notch1, Notch2, Hes1, and intracellular domain of Notch (NICD), were increased. However, NICD could be deacetylated by SIRT1, and this led to the suppression of Notch signaling. Notably, in macrophages from myeloid-specific
mice, in which Notch signaling is inhibited, pro-inflammatory cytokines were expressed at lower levels than in macrophages from wild-type littermates and in
macrophages, and the NF-κB pathway was also inhibited. Accordingly, in the case of
mice, LPS-induced inflammation and mortality were lower than in wild-type mice. Our results indicate that SIRT1 inhibits Notch signaling through NICD deacetylation and thus ultimately alleviates sepsis.
The Arabidopsis thaliana ASYMMETRIC LEAVES2 (AS2) gene is responsible for the development of flat, symmetric, and extended leaf laminae and their veins. The AS2 gene belongs to the plant-specific ...AS2-LIKE/LATERAL ORGAN BOUNDARIES (LOB)-domain (ASL/LBD), which consists of 42 proteins in Arabidopsis with a conserved amino-terminal domain known as the AS2/LOB domain, and a variable carboxyl-terminal region. AS2/LOB domain consists of an amino-terminal (N-terminal) that contains a cysteine repeat (the C-motif), a conserved glycine residue, and a leucine-zipper-like. AS2/LOB domain has been characterised in plants such as A. thaliana, Zea mays, and Oryza sativum. Nevertheless, it remains uncharacterised in cassava (Manihot esculenta). Characterisation and identification of cassava ASL/LBD genes using the computational algorithms, hidden Markov model profiles (PF03195), determined 55 ASL/LBD genes (MeASLBD1 to MeASLBD55). The gene structure and motif composition were conserved in MeASLBDs, while the expression profiles of these genes were highly diverse, implying that they are associated with diverse functions. Weighted gene co-expression network analysis (WGCNA) of target genes and promoter analysis suggest that these MeASLBDs may be involved in hormone and stress responses. Furthermore, the analysis of cis-regulatory elements in promoter regions suggested that MeASLBDs may be involved in the plant phytohormone signal response. The transcriptome data of cassava under biotic and abiotic stresses revealed that MeASLBD46 and MeASLBD47 greatly respond to disease and drought. The MeASLBD47 gene was selected for functional analysis. The result indicated that MeASLBD47 significantly mitigated the virulence of cassava bacterial blight (XamCHN11) through Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) and Virus-induced gene silencing (VIGS). These findings provided a comprehensive analysis of ASL/LBD genes and laid the groundwork for future research to understand ASL/LBD genes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cysteine-rich receptor-like kinases (CRKs) are transmembrane proteins that bind to the calcium ion to regulate stress-signaling and plant development-related pathways, as indicated by several pieces ...of evidence. However, the CRK gene family hasn’t been inadequately examined in Brassica napus. In our study, 27 members of the CRK gene family were identified in Brassica napus, which are categorized into three phylogenetic groups and display synteny relationship to the Arabidopsis thaliana orthologs. All the CRK genes contain highly conserved N-terminal PKINASE domain; however, the distribution of motifs and gene structure were variable conserved. The functional divergence analysis between BnaCRK groups indicates a shift in evolutionary rate after duplication events, demonstrating that BnaCRKs might direct a specific function. RNA-Seq datasets and quantitative real-time PCR (qRT-PCR) exhibit the complex expression profile of the BnaCRKs in plant tissues under multiple stresses. Nevertheless, BnaA06CRK6-1 and BnaA08CRK8 from group B were perceived to play a predominant role in the Brassica napus stress signaling pathway in response to drought, salinity, and Sclerotinia sclerotiorum infection. Insights gained from this study improve our knowledge about the Brassica napus CRK gene family and provide a basis for enhancing the quality of rapeseed.
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•BLM increased the pro-fibrosis factor TGF-β level in bronchoalveolar lavage fluid of BLM-Treated mice.•ISE decreases TGF-β production in the lung of BLM-treated mice.•ISE attenuates ...lung cell infiltration and fibrosis in vivo and inhibits the EMT process via interfering TGF-β signal.•ISE may be a critical phytochemical to attenuate pulmonary fibrosis.
Mushroom Inonotus sanghuang has been characterized as a traditional medicine in China and has pharmacological activities to treat inflammation, gastroenteric dysfunction, and cancer. Recently, we reported the impact of Inonotus sanghuang extract (ISE) from ethyl acetate fraction on bleomycin (BLM)-induced acute lung injury in mice. Here, we aimed to investigate ISE's impact on pulmonary fibrosis using in vivo and in vitro models and the underlying mechanisms. To evaluate pulmonary fibrosis, female C57BL/6 mice fed ISE (0% or 0.6% in diet) for 4 weeks were instilled intratracheally with BLM and then continued the same diet before the end of the experiment. A549 cells were used to evaluate the epithelial-mesenchymal transition (EMT). Feeding ISE improved BLM-treated mice's survival via decreasing lung infiltrating cells and fibrosis, followed by reducing hydroxyproline content, collagen deposition, and mesenchymal markers (α-SMA and vimentin) while increasing epithelial marker E-cadherin. ISE also suppressed the TGF-β expression, Smad2/3 phosphorylation, and EMT-related transcription factor Snail upon BLM instillation. Iin vitro study demonstrated that ISE inhibited TGF-β-induced EMT-like phenotype and cell behaviors, the expression of α-SMA and vimentin, and prevented E-cadherin reduction of A549 cells. Consistent with in vivo study, ISE abrogated p-Smad2/3, and Snail expression. Finally, the influence of ISE on EMT was not due to ISE toxicity. Our findings indicated that ISE effectively attenuated BLM-induced lung fibrosis. These ISE properties were thought to be involved in interfering TGF-β, Smad2/3 phosphorylation, and EMT process, suggesting that the material has the potential health benefits to improve lung fibrosis.
Hepatocellular carcinoma (HCC) represents a malignant tumor predominantly arising in the setting of cirrhosis and is the third most common cause of cancer-associated death on a global scale. The ...heterogeneous nature of HCC and limited well-recognized biomarkers may contribute to poor patient prognosis and treatment failure. In this study, we identified expression pattern of microRNA-202-3p (miR-202-3p) in HCC and characterized its functional role as well as related mechanisms. First, we collected 50 HCC tissues and 38 normal liver tissues, and after bioinformatics prediction, the expression of miR-202-3p and KDM3A was determined in the tissues. We found lowly expressed miR-202-3p and overexpressed KDM3A in HCC tissues. Then, dual-luciferase reporter gene assay was employed to test the presence of miR-202-3p binding sites in the 3'UTR of KDM3A and chromatin immunoprecipitation (ChIP) assay to homeobox A1 (HOXA1) interaction with KDM3A and MEIS3. It has been confirmed that miR-202-3p negatively regulated KDM3A responsible for increasing the expression of HOXA1 by eliminating the histone H3 lysine 9 (H3K9)me2 in HCC cells. HOXA1 could evidently increase H3K4me1 and H3K27ac enrichment in the MEIS3 enhancer region and enhance the expression of MEIS3. Functional assays were also performed with the results showing that upregulated miR-202-3p or downregulated KDM3A retarded HCC cell viability, migration, and invasion. In addition, HepG2 cells were xenografted into nude mice, and we demonstrated that upregulated miR-202-3p reduced the growth of human HCC cells
. Taken together, the present study elicits a novel miR-202-3p/KDM3A/HOXA1/MEIS3 pathway in HCC, potentiating an exquisite therapeutic target for HCC.
MicroRNAs (miRNAs) are implicated in various cancer-relevant cellular processes, including cell proliferation, migration, invasion, and angiogenesis. However, the function of miRNAs in hepatocellular ...cancer (HCC) has not been fully clarified. This study aimed to investigate the role of miR-1178-3p in HCC metastasis and try to reveal the potential mechanism. In the present study, we found that miR-1178-3p was down-regulated, while TBL1XR1 was up-regulated in HCC cancer tissues by bioinformatics analysis and RT-PCR. We further confirmed the connection of miR-1178-3p and TBL1XR1 using dual-luciferase reporter (DLR) assay. Moreover, gain- and loss-of-function experiments demonstrated that overexpress miR-1178-3p inhibited cell proliferation, migration, and invasion in HCC cells and reduced the xenograft tumor growth and angiogenesis by regulating the TBL1XR1/PI3K/Akt axis. Our results indicated that the novel identified miR-1178-3p functions as a tumor suppressor in HCC through regulating TBL1XR1/PI3K/Akt pathway, and these findings could be a valid molecular target for liver cancer therapy.
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