Magnesium-based biodegradable metals (BMs) as bone implants have better mechanical properties than biodegradable polymers, yet their strength is roughly less than 350 MPa. In this work, binary Zn alloys with alloying elements Mg, Ca, Sr, Li, Mn, Fe, Cu, and Ag respectively, are screened systemically by in vitro and in vivo studies. Li exhibits the most effective strengthening role in Zn, followed by Mg. Alloying leads to accelerated degradation, but adequate mechanical integrity can be expected for Zn alloys when considering bone fracture healing. Adding elements Mg, Ca, Sr and Li into Zn can improve the cytocompatibility, osteogenesis, and osseointegration. Further optimization of the ternary Zn-Li alloy system results in Zn-0.8Li-0.4Mg alloy with the ultimate tensile strength 646.69 ± 12.79 MPa and Zn-0.8Li-0.8Mn alloy with elongation 103.27 ± 20%. In summary, biocompatible Znbased BMs with strength close to pure Ti are promising candidates in orthopedics for loadbearing applications.
AcbstractBackgroundInhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has been intensively studied to lower low-density lipoprotein cholesterol (LDL-C) levels. The purpose of this meta-analysis was to evaluate the safety and efficacy of anti-PCSK9 antibodies in randomized, controlled trials (RCTs).MethodsPubMed, EMBASE, CENTRAL databases, and recent conferences were searched. Safety outcomes were rates of common adverse events. Efficacy outcomes included percentages of LDL-C lowering and other lipid changes compared with placebo and ezetimibe, respectively.ResultsTwenty-five RCTs encompassing 12,200 patients were included. The rates of common adverse events were firstly reported in our study by pooling together all evidence in RCTs, showing largely no significant difference between anti-PCSK9 antibodies and placebo (or ezetimibe), except that alirocumab was associated with reduced rates of death (relative risk (RR): 0.43, 95 % confidence interval (CI): 0.19 to 0.96, P = 0.04) and an increased rate of injection-site reactions (RR: 1.48, 95 % CI: 1.05 to 2.09, P = 0.02); evolocumab reduced the rate of abnormal liver function (RR: 0.43, 95 % CI: 0.20 to 0.93, P = 0.03), both compared with placebo. No significant difference in safety outcomes was detected between monthly 420 mg and biweekly 140 mg evolocumab treatments. Monthly 420 mg evolocumab treatment significantly reduced LDL-C by −54.6 % (95 % CI: −58.7 to −50.5 %) and by absolute −78.9 mg/dl (95 % CI: −88.9 to −68.9 mg/dl) versus placebo, and by −36.3 % (95 % CI: −38.8 to −33.9 %) versus ezetimibe, and increased high-density lipoprotein cholesterol (HDL-C) by 7.6 % (95 % CI: 5.7 to 9.5 %) versus placebo and 6.4 % (95 % CI: 4.3 to 8.4 %) versus ezetimibe. An equal or even greater change was observed following biweekly 140 mg administration. Significant and favorable changes were also detected in other lipids following evolocumab treatment. Biweekly 50 to 150 mg alirocumab lowered LDL-C by −52.6 % (95 % CI: −58.2 to −47.0 %) versus placebo, by −29.9 % (95 % CI: −32.9 to −26.9 %) versus ezetimibe, and increased HDL-C by 8.0 % (95 % CI: 4.2 to 11.7 %) versus placebo.ConclusionsEvolocumab and alirocumab were safe and well-tolerated from our most-powered analyses. Both antibodies substantially reduced the LDL-C level by over 50 %, increased the HDL-C level, and resulted in favorable changes in other lipids.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0358-8) contains supplementary material, which is available to authorized users.
Novel KTiO is successfully fabricated via a facile hydrothermal method combined with a subsequent annealing treatment and further evaluated as an anode material for potassium-ion batteries for the first time. This study may provide a broader vision into developing anode materials for potassium-ion batteries.
Catalases are key regulators of reactive oxygen species homeostasis in plant cells. However, the regulation of catalase activity is not well understood. In this study, we isolated an Arabidopsis thaliana mutant, no catalase activity1-3 (nca1-3) that is hypersensitive to many abiotic stress treatments. The mutated gene was identified by map-based cloning as NCA1, which encodes a protein containing an N-terminal RING-finger domain and a C-terminal tetratricopeptide repeat-like helical domain. NCA1 interacts with and increases catalase activity maximally in a 240-kD complex in planta. In vitro, NCA1 interacts with CATALASE2 (CAT2) in a 1:1 molar ratio, and the NCA1 C terminus is essential for this interaction. CAT2 activity increased 10-fold in the presence of NCA1, and zinc ion binding of the NCA1 N terminus is required for this increase. NCA1 has chaperone protein activity that may maintain the folding of catalase in a functional state. NCA1 is a cytosol-located protein. Expression of NCA1 in the mitochondrion of the nca1-3 mutant does not rescue the abiotic stress phenotypes of the mutant, while expression in the cytosol or peroxisome does. Our results suggest that NCA1 is essential for catalase activity.
Novel KV(PO) and three-dimensional conductive network KV(PO)/C nanocomposites are successfully fabricated and further evaluated as cathode materials for potassium-ion batteries for the first time. The KV(PO)/C nanocomposite exhibits a high-potential platform of 3.6-3.9 V and a good capacity retention of at least 100 cycles. This work may provide new insight into developing cathode materials for potassium-ion batteries.
A hierarchical assembled ITO nanowire array with both horizontal and vertical nanowire branches was fabricated as a new three-dimensional fractal nanobiointerface for efficient cancer cell capture. Comparing with ITO nanowire array without branches, this fractal nanobiointerface exhibited much higher efficiency (89% vs 67%) and specificity in capturing cancer cells and took shorter time (35 vs 45 min) to reach the maximal capture efficiency. As indicated by the immunofluorescent and ESEM images, this enhancement can be attributed to the improvement of topographical interaction between cells and the substrate. The introduction of horizontal and vertical nanowire branches makes the substrate topographically match better with cell filopodia and provides more binding sites for cell capture. The live/dead cell staining and proliferation experiments confirm that this fractal nanobiointerface displays excellent cyto-compatibility with an over 96% cell viability after capture. These results provide new insights and may open up opportunities in designing and engineering new cell-material interfaces for advanced biomedical applications.
A sensitive nucleic acid detection platform based on superhydrophilic microwells spotted on a superhydrophobic substrate is fabricated. Due to the wettability differences, ultratrace DNA molecules are enriched and the fluorescent signals are amplified to allow more sensitive detection. The biosensing interface based on superwettable materials provides a simple and cost-effective way for ultratrace DNA sensing.
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