Mechanical properties and wear resistance of medium entropy Fe40Mn40Cr10Co10/TiC composites

The Fe40Mn40Cr10Co10/TiC (volume fraction of TiC, 10%) composites were synthesized in combination of ball milling and spark plasma sintering (SPS) in the present work. Mechanical properties and wear resistance of the Fe40Mn40Cr10Co10/TiC composites were individually investigated. It was found that TiC particles homogenously distributed in the Fe40Mn40Cr10Co10/TiC composite after being sintered at 1373 K for 15 min. Meanwhile, grain refinement was observed in the as-sintered composite. Compared with the pure Fe40Mn40Cr10Co10 medium entropy alloy (MEA) matrix grain, addition of 10% TiC particles resulted in an increase in the compressive strength from 1.571 to 2.174 GPa, and the hardness from HV 320 to HV 872. Wear resistance results demonstrated that the friction coefficient, wear depth and width of the composite decreased in comparison with the Fe40Mn40Cr10Co10 MEA matrix. Excellent mechanical properties and wear resistance could offer the Fe40Mn40Cr10Co10/TiC composite a very promising candidate for engineering applications.

PINK1 gene mutation by pair truncated sgRNA/Cas9-D10A in cynomolgus monkeys

Mutations of PTEN-induced kinase I(PINK1)cause early-onset Parkinson’s disease(PD)with selective neurodegeneration in humans.However,current PINK1 knockout mouse and pig models are unable to recapitulate the typical neurodegenerative phenotypes observed in PD patients.This suggests that generating PINK1 disease models in non-human primates(NHPs)that are close to humans is essential to investigate the unique function of PINK1 in primate brains.Paired single guide RNA(sgRNA)/Cas9-D10A nickases and truncated sgRNA/Cas9,both of which can reduce off-target effects without compromising on-target editing,are two optimized strategies in the CRISPR/Cas9 system for establishing disease animal models.Here,we combined the two strategies and injected Cas9-D10A mRNA and two truncated sgRNAs into one-cell-stage cynomolgus zygotes to target the PINK1 gene.We achieved precise and efficient gene editing of the target site in three newborn cynomolgus monkeys.The frame shift mutations of PINK1 in mutant fibroblasts led to a reduction in mRNA.However,western blotting and immunofluorescence staining confirmed the PINK1 protein levels were comparable to that in wild-type fibroblasts.We further reprogramed mutant fibroblasts into induced pluripotent stem cells(iPSCs),which showed similar ability to differentiate into dopamine(DA)neurons.Taken together,our results showed that co-injection of Cas9-D10A nickase mRNA and sgRNA into one-cell-stage cynomolgus embryos enabled the generation of human disease models in NHPs and target editing by pair truncated sgRNA/Cas9-D10A in PINK1 gene exon 2 did not impact protein expression.

Anti-inflammatory effects of Eucommia ulmoides Oliv. male flower extract on lipopolysaccharide-induced inflammation

Background:Eucommia ulmoides Oliv. is a medicinal plant native to China, with its bark (Eucommiae Cortex) traditionally being used for medicinal purposes. Previous research has shown that Eucommia male flowers can exert anti-inflammatory, analgesic, antibacterial, and other pharmacological effects, including immune regulation. This study explored the anti-inflammatory effects of the 70% ethanol extract of male flowers (EF) of E. ulmoides in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and LPS-administered mice.Methods:Cytotoxicity of EF for RAW 264.7 cells was investigated using Cell Counting Kit-8. The production of proinflammatory mediators, nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 was determined using enzyme-linked immunosorbent assays. IL-17, IL-23, and IL-10 mRNA levels were determined using quantitative real-time polymerase chain reaction. Activation of the nuclear factor (NF)-κB pathway in RAW 264.7 cells was investigated via Western blotting. In vivo antiinflammatory effects of EF were studied in an LPS-induced acute inflammation mouse model by analyzing lung tissue histopathology, serum TNF-α and IL-6 levels, and myeloperoxidase (MPO) activity in lung tissue.Results:EF showed no significant cytotoxicity at concentrations from 10 to 60 μg/mL (cell viability > 80%) in the CCK-8 cell viability assay. EF inhibited the RAW 264.7 cell proliferation (EF 60 μg/mL, 120 μg/mL, and 250 μg/mL vs. negative control: 87.31±2.39% vs. 100.00±2.50%, P=0.001;79.01±2.56 vs. 100.00±2.50%, P<0.001;and 64.83±2.50 vs. 100.00±2.50%, P<0.001), suppressed NO (EF 20 μg/mL and 30 μg/mL vs. LPS only, 288.81±38.01 vs. 447.68±19.07 μmol/L, P=0.004;and 158.80±45.14 vs. 447.68±19.07 μmol/L, P<0.001), TNF-α (LPS+EF vs. LPS only, 210.20±13.85 vs. 577.70±5.35 pg/mL, P<0.001), IL-1β (LPS+EF vs. LPS only, 193.30±10.80 vs. 411.03±42.28 pg/mL, P<0.001), and IL-6 (LPS+EF vs. LPS only, 149.67±11.60 vs. 524.80±6.24 pg/mL, P<0.001) secretion, and downregulated the mRNA expression of IL-17 (LPS+EF vs. LPS only, 0.23±0.02 vs. 0.43±0.12, P<0.001), IL-23 (LPS+EF vs. LPS only, 0.29±0.01 vs. 0.42±0.06, P=0.002), and IL-10 (LPS+EF vs. LPS only, 0.30±0.01 vs. 0.47±0.01, P=0.008) in LPS-stimulated RAW 264.7 cells. EF inhibited the LPS-induced NF-κB p65 (LPS+EF 20 μg/mL and 30 μg/mL vs. LPS only: 0.78±0.06 vs. 1.17±0.08, P<0.001;and 0.90±0.06 vs. 1.17±0.08, P=0.002) and inhibitor of kappa B (IκBα) phosphorylation (LPS+EF 20 μg/mL and 30 μg/mL vs. LPS only: 0.25±0.01 vs. 0.63±0.03, P<0.001;and 0.31±0.01 vs. 0.63±0.03, P<0.001), LPS+EF 30 μg/mL inhibited IκB kinase (IKKα/β) phosphorylation (LPS+EF 30 μg/mL vs. LPS only, 1.12±0.14 vs. 1.71±0.25, P=0.002) in RAW 264.7 cells. Furthermore, EF 10 mg/kg and EF 20 mg/kg inhibited lung tissue inflammation in vivo and suppressed the serum TNF-α (LPS+EF 10 mg/kg and 20 mg/kg vs. LPS only, 199.99±186.49 vs. 527.90±263.93 pg/mL, P=0.001;and 260.56±175.83 vs. 527.90±263.93 pg/mL, P=0.005), and IL-6 (LPS+EF 10 mg/kg and 20 mg/kg vs. LPS only, 41.26±30.42 vs. 79.45±14.16 pg/ml, P=0.011;and 42.01±26.26 vs. 79.45±14.16 pg/mL, P=0.012) levels and MPO (LPS+EF 10 mg/kg and 20 mg/kg vs. LPS only, 3.19±1.78 vs. 5.39±1.51 U/g, P=0.004;and 3.32±1.57 vs. 5.39±1.51 U/g, P=0.006) activity in lung tissue.Conclusions:EF could effectively inhibit the expression of inflammatory factors and overactivation of neutrophils. Further investigation is needed to evaluate its potential for anti-inflammation therapy.

Optimization of mechanical and antibacterial properties of Ti-3wt%Cu alloy through cold rolling and annealing

In this work,a process of cold rolling with 70%thickness reduction and different annealing temperatures was selected to regulate the microstructure of Ti-3wt%Cu alloy.Microstructural evolution,mechanical properties and antibacterial properties of the Ti-3wt%Cu alloy under different conditions were systematically investigated in terms of X-ray diffraction(XRD),scanning electron microscope(SEM),transmission electron microscope(TEM),tensile and antibacterial test.The results indicated that cold rolling could dramatically increase the ultimate tensile stress(UTS)from 520 to 928 MPa,but reduce the fracture strain from 15.3%to 3.8%.With the annealing temperature increasing from 400 to 800C for 1 h,the UTS decreased from 744 to 506 MPa and the fracture strain increased from12.7%to 24.4%.Moreover,the antibacterial properties of the Ti-3wt%Cu alloy under different conditions showed excellent antibacterial rate(>96.69%).The results also indicated that the excellent combination of strength and ductility of the Ti-3wt%Cu alloy with cold rolling and following annealing could be achieved in a trade-off by tuning the size and distribution of Ti2Cu phase,which could increase the applicability of the alloy in clinical practice.More importantly,the antibacterial properties maintained a good stability for the Ti-3wt%Cu alloy under different conditions.The excellent combination of mechanical properties and antibacterial properties could make the Ti-3wt%Cu alloy a good candidate for long-term orthopaedic implant application.