In cold spray processing of metals, the critical velocity for particle bonding is dependent on both intrinsic material properties, such as density and (spall) strength, and extrinsic process ...parameters, such as the powder particle size. In this work, we specifically isolate and investigate particle size effects on the critical velocity for bonding through laser-induced single particle impact experiments and finite element simulations. We also present a predictive framework to correlate particle size and critical velocity. We show that an increase in particle size leads to an increase in the temperature of the jet formed at the interface of the particle and the substrate. This increased temperature locally decreases the spall strength of the material which, in turn, decreases the critical velocity for larger particles.
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The antifouling properties of poly(vinylidene fluoride) (PVDF) membranes were investigated by blending several types of synthesized amphiphilic poly(poly(ethylene glycol) methyl ether methacrylate- ...methyl methacrylate) P(PEGMA- MMA) copolymers with different initial PEGMA/MMA monomer ratios and PEG side chain lengths. Many types of membranes were prepared using different copolymer/PVDF blend ratios via nonsolvent induced phase separation. The membranes with similar pure water permeabilities and surface pore sizes were prepared by controlling the dope solution composition. Thus, the bovine serum albumin antifouling properties could be assessed under similar hydrodynamic filtration conditions. The membrane hydrophilicity, surface PEGMA coverage, and antifouling properties of the prepared membranes increased with increasing copolymer/PVDF ratio and PEGMA/MMA monomer ratio of the copolymers and PEG length of the copolymer. A molecular dynamics simulation was performed to assess the surface chemical composition, and the results were compared with those of X-ray photoelectron spectroscopy. The antifouling properties depended more strongly on the membrane surface hydrophilicity when the copolymer chemical structures, that is, the PEGMA/MMA monomer ratio and PEG side chain length, were changed, rather than when the copolymer/PVDF blend ratio was changed.
•P(PEGMA-MMA) copolymers with different chemical structures were synthesized.•P(PEGMA-MMA)/PVDF blend membranes with similar water permeability were prepared.•Synthesized copolymer checmical structure effect on the antifouling properties were evalauted.•Molecular dynamic simulation employed to assess the surface chemical composition.
Tumor associated macrophages (TAMs) are important prognostic factors and have been proved to be associated with the invasion and migration of various cancer. However, the relationship between TAMs ...and breast cancer outcomes remains unclear.
Sixteen studies with a total of 4,541 breast cancer patients were included in this meta-analysis. Correlation of TAMs with overall survival (OS), disease-free survival(DFS), relapse-free survival (RFS), breast cancer special survival (BCSS) and clinicopathological features were analyzed. Survival data and clinicopathological value were integrated by analyzing hazard ratio(HR) and odds ratio(OR) separately and using Fixed-effect or Random-effect model according to heterogeneity. All statistical tests were two-sided.
OS and DFS were correlated with high density of TAMs with HR= 1.504(1.200, 1.884)/ 2.228(1.716, 2.892) respectively. And subgroup analysis of location and biomarker in OS and DFS group showed prognosis was associated with TAMs distribution and biomarker selection. Besides, TAMs high infiltration was significantly related to age, size, histologic grade, ER/PR status, basal phenotype and vascular invasion.
High density of TAMs was associated with poor survival rates of breast cancer. TAMs in stroma are associated with worse outcome than that in nest and using CD68 as a biomarker for TAMs to evaluate the risk is better than CD163 or CD206 alone. Moreover, high infiltration of TAMs was significantly associated with negative hormone receptor status and malignant phenotype. TAMs infiltration can serve as a novel prognostic factor in breast cancer patients.
Radiotherapy is the standard adjuvant treatment for glioma patients; however, the efficacy is limited by radioresistance. The function of Interleukin-1 receptor associated kinase 1 (IRAK1) in ...tumorigenesis and radioresistance remains to be elucidated. IRAK1 expression and its correlation with prognosis were analyzed in glioma tissues. We found that glioma patients with overexpressed IRAK1 show a poor prognosis. Notably, ionizing radiation (IR) remarkably induces IRAK1 expression, which was decreased by STING antagonist H-151 treatment. JASPAR prediction, ChIP assays, and dual luciferase reporter assays indicated that transcription factor FOXA2, suppressed by STING inhibition, directly binds to the IRAK1 promoter region and activates its transcription. IRAK1 knockdown inhibits malignancy and enhances the radiosensitivity of glioma in vitro and in vivo. To explore the potential IRAK1 interacting targets mediating the radioresistance of glioma cells, IP/Co-IP, LC-MS/MS, GST pull-down, and ubiquitination analyses were conducted. Mechanistically, IRAK1 bound to PRDX1, a major member of antioxidant enzymes, and further prevents ubiquitination and degradation of PRDX1 mediated by E3 ubiquitin ligase HECTD3; Both the DOC and HECT domains of HECTD3 directly interacted with PRDX1 protein. Overexpression of PRDX1 reverses the radiotherapy sensitization effect of IRAK1 depletion by diminishing autophagic cell death. These results suggest the IRAK1-PRDX1 axis provides a potential therapeutic target for glioma patients.
Lipidomics is an omics approach to comprehensively study lipid profiles in biological samples, such as plasma, serum, urine, and tissue specimens. Moreover, lipidomic analyses are useful for ...identifying novel lipid biomarkers, especially for various metabolic and malignant diseases in humans. Extracellular vesicles (EVs) are lipid bilayer-encapsulated nanoparticles secreted from various cells into the extracellular space. In particular, circulating EVs in the blood stream have attracted considerable research interest as they are considered the fingerprint of the cells from which they are secreted and are a promising source for less-invasive biomarker screening. Here, we describe the entire workflow for the lipidomic analysis of circulating EVs, including the methods for their purification from human plasma and serum, liquid chromatography coupled with high-resolution mass spectrometry-based lipid measurement, and data analyses for profiling EV lipids. Using this methodological workflow, over 260 lipid molecules belonging to the glycerophospholipid and sphingolipid groups can be detected.
Radioresistance, a poorly understood phenomenon, results in the failure of radiotherapy and subsequent local recurrence, threatening a large proportion of patients with ESCC. To date, lncRNAs have ...been reported to be involved in diverse biological processes, including radioresistance.
FISH and qRT-PCR were adopted to examine the expression and localization of lncRNA-NORAD, pri-miR-199a1 and miR-199a-5p. Electron microscopy and nanoparticle tracking analysis (NTA) were conducted to observe and identify exosomes. High-throughput microRNAs sequencing and TMT mass spectrometry were performed to identify the functional miRNA and proteins. A series of in vitro and in vivo experiments were performed to investigate the biological effect of NORAD. ChIP, RIP-qPCR, co-IP and dual-luciferase reporter assays were conducted to explore the interaction of related RNAs and proteins.
We show here that DNA damage activates the noncoding RNA NORAD, which is critical for ESCC radioresistance. NORAD was expressed at high levels in radioresistant ESCC cells. Radiation treatment promotes NORAD expression by enhancing H3K4me2 enrichment in its sequence. NORAD knockdown cells exhibit significant hypersensitivity to radiation in vivo and in vitro. NORAD is required to initiate the repair and restart of stalled forks, G2 cycle arrest and homologous recombination repair upon radiation treatment. Mechanistically, NORAD inhibits miR-199a-5p expression by competitively binding PUM1 from pri-miR-199a1, inhibiting the processing of pri-miR-199a1. Mature miR-199a-5p in NORAD knockdown cells is packaged into exosomes; miR-199a-5p restores the radiosensitivity of radioresistant cells by targeting EEPD1 and then inhibiting the ATR/Chk1 signalling pathway. Simultaneously, NORAD knockdown inhibits the ubiquitination of PD-L1, leading to a better response to radiation and anti-PD-1 treatment in a mouse model.
Based on the findings of this study, lncRNA-NORAD represents a potential treatment target for improving the efficiency of immunotherapy in combination with radiation in ESCC.
Branched-chain amino acids (BCAA) showed multiple functions in glycolipid metabolism and protein synthesis. However, the impacts on the metabolic health of low or high dietary BCAA remain ...controversial due to the various experimental conditions. Gradient levels of BCAA were supplemented in lean mice for four weeks: 0BCAA (without BCAA), 1/2BCAA (half BCAA), 1BCAA (regular BCAA), and 2BCAA (double BCAA). The results showed that the diet without BCAA caused energy metabolic disorders, immune defects, weight loss, hyperinsulinemia, and hyperleptinemia. 1/2BCAA and 2BCAA diets reduced body fat percentage, but 1/2 BCAA also decreased muscle mass. 1/2BCAA and 2BCAA groups improved lipid and glucose metabolism by affecting metabolic genes. Meanwhile, significant differences between low and high dietary BCAA were observed. The results of this study provide evidence and reference for the controversy about dietary BCAA levels, which indicates that the main difference between low and high BCAA dietary levels may present in the longer term.
Preparation route of positively charged PVI/PSF composite NF membranes.
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Developing nanofiltration (NF) membranes with highly efficient and precise separation ability is of great ...significance for the molecular and ionic separations. In this work, positively charged composite NF membranes were engineered via soaking of polysulfone (PSF) ultrafiltration membranes in poly(N-vinyl imidazole) (PVI) solutions followed by a quaternization crosslinking step. The PVI was firmly attached to the PSF membrane by this method and acted as an active separation layer of the composite NF membrane. The obtained composite NF membrane featured a high rejection (83%) to vitamin B12 (molecular radius: 0.74 nm) but a low rejection (24.6%) to vitamin B2 (molecular radius: 0.47 nm), exhibiting a great potential in precisely molecular separation. Furthermore, the ionic separation ability of the composite NF membrane was confirmed with a rejection order of Na2SO4 < MgSO4 < NaCl < MgCl2 and the MgCl2 rejection reached up to 90.1%. Compared to conventional polyamide NF membranes, the developed PVI/PSF composite NF membranes were characterized with high separation precision to organic molecules, higher rejection over cationic ions than over anionic ones, better chlorine resistance and stability in long-term operation. In addition, the membrane fabrication process is convenient and easily scaled up in industry. This work offers a novel alternative of NF membranes for high precision in molecular and ionic separations.
In practical applications, the signals received by a hydrophone array include coherent and incoherent signals, while estimating the direction of arrival (DOA) of coherent or incoherent signals has ...been studied for simplicity with poor performance for a mixed signal. The present study proposes a novel approach for estimating the DOA of mixed broadband signals to solve this problem, namely the oblique method. The unitary oblique method is simultaneously proposed to improve operational efficiency with the complex matrix shifted into a real valued matrix through a unitary transform. For independent signals, the incoherent signal subspace method (ISSM) is used to estimate the DOA. Matrix difference and oblique projection methods are adopted for multi-group coherent signals in order to eliminate the influence of incoherent signals and other groups of coherent signals. For broadband signals, the Tasseled Cap Transformation focusing transform is utilized to convert the broadband signal to the focusing frequency, and then the high-resolution Multiple Signal Classification algorithm method is employed to solve the problem. Simulation results indicate that the oblique method reconciles DOA estimation performance and computational efficiency and can be extended to other types of arrays.
Emerging evidence have illustrated the vital roles of long noncoding RNAs (lncRNAs) in glioma. Nevertheless, the majority of their roles and mechanisms in gliomagenesis are still largely unclear. In ...this study, we investigate the roles of lncRNA CASC9 on glioma tumourigenesis and authenticate its potential mechanisms. Results manifested that CASC9 was highly expressed in glioma specimens and cells, moreover, the ectopic overexpression was correlated with glioma patients’ clinic. Functional studies found that siRNA‐mediated CASC9 silencing inhibited the proliferative ability, invasion in vitro, and impaired the tumour growth in vivo. Mechanical studies revealed that miR‐519d both targeted the 3′‐UTR of CASC9 and STAT3 mRNA, which was identified by luciferase reporter assay and RNA immunoprecipitation (RIP). Moreover, chromatin immunoprecipitation (ChIP) and luciferase reporter assay revealed that STAT3, an oncogenic transcription factor, could bind with the promoter of CASC9 and activate its transcriptional level. In conclusion, our results concluded that CASC9 promotes STAT3 expression via sponging miR‐519d, in return, STAT3 activate CASC9 transcription, forming a positive feedback loop of CASC9/miR‐519d/STAT3. The novel finding provides a potential therapeutic target for glioma.
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