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The failure to treat and control the growth of metastases is the main cause of death in breast cancer (BC) patients. Compared to the traditional method of analyzing circulating tumor DNA (ctDNA), capturing intact circulating tumor cells (CTCs) allows us to more accurately characterize mutations and identify suitable targeted therapies. We used CellCollector to collect peripheral CTCs. Thirty metastatic breast cancer (MBC) patients were enrolled, and 17 were analyzed with next-generation sequencing (NGS) methods. Clinical characteristics were analyzed along with the CTCs enumeration and detection rates. Whole-genome amplification (WGA) was used to amplify the CTC genomic DNA of 127 genes. Patients younger than 45 years old, with brain metastasis, with three or more metastatic sites, or with HER2-positive had the highest number of CTCs collected. The CTCs detection rate was also correlated to the number of metastasis sites. Different metastasis sites such as the brain, viscus, bone, and soft tissue contained specific high-frequency gene mutations. AKT3, MYC, and NT5C2 mutations were only found in brain metastases. APC, BCL2L11, ESRP1, FLT3 mutations were only in the visceral metastases. KEAP1, KIT, MET were the specific mutation genes in patients with bone and soft tissue metastases. These findings provide evidence that we can detect gene mutation information for obtaining the biological characteristics by CTCs using CellCollector. Different metastasis sites contain specific high-frequency mutation genes, which provide guidance to the accurate gene therapy.

The effects of trace Sc and Y on the corrosion behaviors of cold-drawn Al-0.2Ce alloys were revealed by scanning Kelvin probe force microscopy (SKPFM), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Electron Probe Micro-analyzer (EPMA), and electrochemical measurements. The results showed that the Al3Sc particles not only enable the increase of subgrain boundaries in the modified alloy after cold drawing but also improve the morphology and size of the Al13Fe3Ce phase. SKPFM analysis showed that the enrichment of Y around the Al13Fe3Ce phase in the modified alloy can decrease its electrochemical inertness and thus reduce the micro-galvanic corrosion susceptibility of the alloy. The results of the electrochemical analysis showed that the individual and composite addition of Sc and Y can improve the corrosion resistance of the cold-drawn Al-0.2Ce alloy. The corrosion potential and current of Al-0.2Ce-0.2Sc alloy are −0.892 V and 0.91 μA·cm−2, while the corrosion potential and current of Al-0.2Ce-0.1Y alloy are −0.918 V and 1.08 μA·cm−2, respectively. It is obvious that Sc element improves the corrosion resistance of Al-0.2Ce alloy more effectively than Y element. The corrosion depth of Al-0.2Ce-0.2Sc-0.1Y alloy was the smallest tested by immersion under the same conditions, and its corrosion potential and corrosion current were −0.842 V and 0.79 μA·cm−2, respectively, corresponding to the best corrosion resistance. The formal mechanism of pitting corrosion in the alloys is also discussed.

Sc-containing Al alloys have excellent mechanical properties, which provide the foundation for their applications. The precipitation of the Al3Sc/Al3(Sc, Zr) is generally considered to be a key factor for the performance boost. However, the performances of the alloy in different production batches often exhibit unstable and fluctuation, which may be related to the heterogeneous of scandium. Herein, we investigated the precipitation behaviors of Al3Sc/Al3(Sc, Zr) phases in the Al-0.5Sc and Al-0.5Sc-0.25Zr alloys at 340 °C. Results shown that the high scandium‑zirconium ratio not only lead to the discontinuous precipitation, but also contribute to the abnormal continuous Al3(Sc, Zr) precipitation in Al-0.5Sc-0.25Zr alloy. The morphology of abnormal Al3(Sc, Zr) is similar to the common secondary Al3(Sc, Zr) phase with a coffee-bean like morphology. With the aid of Three-Dimensional Atomic Probe (3DAP), the core-shell structures of Al3(Sc, Zr) phases are quantitatively analyzed. In the shell layer of abnormal Al3(Sc, Zr) phase, the atomic concentration ratio of Sc to Zr is much higher than the common continuous precipitated Al3(Sc, Zr) phase. The abnormal Al3(Sc, Zr) phase may be one of the key factors for the structure heredity of Sc-containing Al alloys.

The effect of Sc content on microstructure and properties of Al-Zn-Mg-Cu-Zr alloy was studied by transmission electron microscopy (TEM), scanning electron microscopy (SEM), optical microscopy (OM), tensile tests, hardness measurements and corrosion evaluation. It is revealed that the increase in the volume fraction of the η' phase and the precipitation of Al3(Sc, Zr) particles within the alloy contribute to the significant grain refinement within the Al-7.0Zn-3.0 Mg-0.3Cu-0.15Sc-0.12 Zr (wt.%) alloy. The strength and hardness of the alloy have also been improved. Due to the addition of Sc element, the precipitates at the grain boundaries of the alloy become discontinuous, and the size of such precipitates is reduced. The population density is also decreased. Consequently, the alloy has excellent resistance to intergranular corrosion and exfoliation corrosion. Electrochemical data also shows that the alloys have a smaller tendency to corrode and slower corrosion rates.

One of the most complex systems in the human body is the nervous system, which is divided into the central and peripheral nervous systems. The regeneration of the CNS is a complex and challenging biological phenomenon hindered by the low regenerative capacity of neurons and the prohibition factors in response to nerve injuries. To date, no effective approach can achieve complete recovery and fully restore the functions of the nervous system once it has been damaged. Developments in neuroscience have identified properties of the local environment with a critical role in nerve regeneration. Advances in biomaterials and biomedical engineering have explored new approaches of constructing permissive environments for nerve regeneration, thereby enabling optimism with regard to nerve-injury treatment. This article reviews recent progress in nanoengineered environments for aiding nerveinjury repair and regeneration, including nanofibrous scaffolds, functional molecules, and stem cells.

Self-assembling peptide (SAP) RADA16-I (Ac-(RADA)4-CONH2) has been suffering from a main drawback associated with low pH, which damages cells and host tissues upon direct exposure. In this study, we presented a strategy to prepare nanofiber hydrogels from two designer SAPs at neutral pH. RADA16-I was appended with functional motifs containing cell adhesion peptide RGD and neurite outgrowth peptide IKVAV. The two SAPs were specially designed to have opposite net charges at neutral pH, the combination of which created a nanofiber hydrogel (-IKVAV/-RGD) characterized by significantly higher G' than G″ in a viscoelasticity examination. Circular dichroism, Fourier transform infrared spectroscopy, and Raman measurements were performed to investigate the secondary structure of the designer SAPs, indicating that both the hydrophobic/hydrophilic properties and electrostatic interactions of the functional motifs play an important role in the self-assembling behavior of the designer SAPs. The neural progenitor cells (NPCs)/stem cells (NSCs) fully embedded in the 3D-IKVAV/-RGD nanofiber hydrogel survived, whereas those embedded within the RADA 16-I hydrogel hardly survived. Moreover, the -IKVAV/-RGD nanofiber hydrogel supported NPC/NSC neuron and astrocyte differentiation in a 3D environment without adding extra growth factors. Studies of three nerve injury models, including sciatic nerve defect, intracerebral hemorrhage, and spinal cord transection, indicated that the designer -IKVAV/-RGD nanofiber hydrogel provided a more permissive environment for nerve regeneration than the RADA 16-I hydrogel. Therefore, we reported a new mechanism that might be beneficial for the synthesis of SAPs for in vitro 3D cell culture and nerve regeneration.

The morphology of primary Al3Sc phase in Al-2.2Sc(wt%) was found to be influenced by melting condition. Some representative morphology appeared in large quantities at specific melting temperatures, holding times, and cooling rates. Crystallography of primary phases with various morphologies was researched, and the growth processes of the primary phase were investigated. Deformed cubes and dendrite can be developed from cubes, the butterfly-like particles had multiple layers inside, and repeated eutectic reactions were the main reason for the formation of multilayer structures. Al-2.2Sc(wt%) master alloys with different morphologies of primary Al3Sc phase can lead to different refining effects, and the mechanical properties of alloys were consequently influenced. The structure heredity of Al Sc master alloy was proved to be existed, and not influenced by prolonging insulation time and sufficient stirring.

The quench sensitivity of Al–Mg–Si–Mn–Cr alloy was studied through time-temperature-transformation (TTT) and time-temperature-property (TTP) curves. The high quench sensitive region ranges from 250 °C to 430 °C with nose temperature at about 350 °C, where the quenching rate is required to higher than 9 °C/s for avoiding the formation of quench-induced precipitates. B′(Al3Mg9Si7) precipitates from the supersaturated solid solution, and gradually transforms to equilibrium β (Mg2Si) and excess Si phase with increasing isothermal time at 350 °C. The loss of the solute atoms in matrix results in the reduction of the aging hardening precipitation and the formation of the precipitate-free zones (PFZs) during artificial aging. The nucleation rate of the quench-induced precipitation is studied by nucleation theory, and the phase transformation kinetics is analyzed through Avrami equation. The Al(MnCrFe)Si dispersoids, (sub)grain boundaries and dislocations are the preferential heterogeneous nucleation sites for quench-induced precipitation.

The hardening behavior of Al-0.25Sc and Al-0.25–0.12 (wt.%) alloys during isothermal annealing were studied by transmission electron microscopy (TEM), scanning electron microscopy (SEM), optical microscopy (OM), and hardness measurements. The results show that Sc-containing aluminum alloy contained fine dispersion of spherical secondary Al3Sc particles, which developed during the annealing process. Al3(Sc, Zr) precipitates in the Al-0.25Sc-0.12Zr alloys are core-shell structure. Different isothermal annealing temperatures can lead to different strengthening effects on the alloys. Al-0.25Sc and Al-0.25Sc-0.12Zr alloys both exhibit obvious annealing hardening behavior, and the ternary Al-0.25Sc-0.12Zr alloy shows better thermal stability than Al-0.25Sc alloy.

The effect of Scandium (Sc) and Copper (Cu) on the microstructure and mechanical properties of the 3003 alloy were investigated. The results showed that the addition of Cu can promote the precipitation of α-Al(Mn,Fe)Si dispersoids during brazing. With the addition of Sc and Cu, the average grain size of 3003 alloy was significantly refined. The recrystallization resistance of the simulated brazing alloy was improved by Sc, which was mainly due to the precipitation of Al3Sc particles. The α-Al(Mn,Fe)Si dispersoids and Al3Sc particles exist simultaneously after annealing, which can improve the strength of Sc-containing 3003 alloy. The 3003 alloy added with Sc and Cu has the best mechanical performance among the three experimental alloys.

Aim: To investigate the influence of ion pairing of carboxylated multiwalled carbon nanotubes (MWCNT-COOH) and polycations on the layer-by-layer assembly of nanocomposites and their biocompatibility for biomedical applications. Materials & methods: Strong polycation poly(dimethyldiallylammonium chloride), and weak polycations chitosan and polyethyleneimine were selected to assembly with MWCNT-COOH. The MWCNT-COOH/polycation nanocomposites were analyzed by their physicochemical, electrical properties and biocompatibility. Results: The ion pairing of CNTs/polyelectrocytes played a critical role in the layer-by-layer assembly. Strong interactions between MWCNTs and poly(dimethyldiallylammonium chloride) produced thicker nanocomposites with rougher surfaces, higher MWCNT mass and better conductance. All the MWCNT multilayered nanocomposites were of good biocompatibility. Conclusion: The MWCNT multilayered nanocomposites hold high potential for biomedical applications.

As novel, promising, man-made nanomaterials with extraordinary properties, carbon nanotubes have been attracting massive attention in regenerative medicine. However, published reports on their potential cytotoxic effects are not concordant and are even conflicting. In the current study, the cytotoxic effects of carboxyl-modified multi-walled carbon nanotubes (COOH-MWCNTs), as well as their influences on the cell adhesion of NIH-3T3 fibroblasts, were thoroughly investigated. Live/dead cell viability assay and cell counting kit-8 assay both indicated that the viability of the NIH-3T3 cells exposed to COOH-MWCNTs in the culture medium was dependent on the latter's concentration. Cell viability increased at COOH-MWCNT concentrations below 50 μg ml(-1) and then decreased with increasing concentration. Scanning electron microscopy and immunofluorescent staining of the NIH-3T3 cells revealed that the cells were well adherent to the substrate after exposure to the COOH-MWCNTs for 48 h. Western blot demonstrated that COOH-MWCNT exposure enhanced the expression of adhesion-associated proteins compared with normal cells, peaking at an intermediate concentration. Our study showed that the cytotoxicity of COOH-MWCNTs, as well as their effects on NIH-3T3 fibroblast adhesion, was dose dependent. Therefore, COOH-MWCNT concentrations in the cell culture medium should be considered in the biomedical application of COOH-MWCNTs.

Isothermal annealing induced nanocrystallization of a Fe 74.5 Cu 1 Si 13.5 B 9 Al 2 amorphous alloy and the impact of the nanocrystallization on mechanical properties were investigated. Annealing at 831 K results in the formation of body-centered cubic α-Fe(Si) nanocrystals in the amorphous matrix. Increasing the annealing time increases both the grain sizes and lattice parameter of the nanocrystalline α-Fe(Si) phase. The latter is caused by the separation of the Si from the α-Fe(Si) phase. Al in the alloy does not effectively inhibit the grain growth of α-Fe(Si) nanocrystals during the annealing process. Isothermal annealing effectively increases the hardness and Young's modulus of the alloy. In the testing range of the present study, the highest hardness (14.0 GPa) and Young's modulus (193.4 GPa) are achieved after annealing for 60 min and 120 min, respectively.

Fe 76.5 Cu 1 Si 13.5 B 9 alloy rods with a diameter of 3 mm were fabricated using the copper mold suction casting method. Structural characterization revealed that different parts of the rods have different microstructures that comprise a complete amorphous structure, an amorphous-crystalline composite structure and a complete crystalline structure. Compression and nanoindentation testing showed that the hardness, strength and elastic modulus of the alloy increase with the crystalline component. High crack propagation rate and narrow shear bands contribute to the local melting and softening for the complete amorphous structure although it exhibits the lowest calculated value of the static elastic energy density.

To summarize the disposal methods and the reasons of complications in operation of totally implantable central venous port (TICVP).A total of 2 007 patients were enrolled in this observational, single-center study between December 2008 and March 2013. TICVP implantation was performed with one small skin incision and subcutaneous puncture of subclavian or jugular vein. Patient's profiles, indications of port system, early and delayed complications, and disposal methods were evaluated. There were 38 male and 1 969 female patients, aged from 21 to 85 years, with a mean of 47.6 years.The mean duration of the TICVP system was (242 ± 12) days, ranging from 9 to 1 243 days. The achievement rate of puncture in the right jugular vein (99.76%) was the highest. Sonographic approach using the internal jugular vein were better than the external landmark-guided technique (99.80% vs. 96.34%, χ² = 29.905, P = 0.000). The rate of immediate complication was 0.80%, which included pneumothorax, hemothorax, lymphatic fistula and thrombosis. Early complications rate was 0.10%, which included pocket hematoma, catheter migration, venous thrombosis, port pocket infection, fibrin sheath formation. Late complications rate was 7.87%, which included catheter fracture, pinch-off syndrome, catheter-related bloodstream infection, fibrin sheath formation, catheter migration, extravasation, port inversion and port reveal. The rate of removal due to complications was 1.34% (27/2 007), and the early complication was higher (χ² = 8.053, P = 0.011).The low incidence of complications suggests that TICVP is safe and reliable for long term intermittent venous access. The results support the use of TICVP in the oncology patients and patients requiring long-term intravenous therapy.

In the current study, we present three designer self-assembling peptides (SAPs) by appending RADA 16-I with epitopes IKVAV, RGD, and YIGSR, which have different net charges and amphiphilic properties at neutral pH. The self-assembly of the designer SAPs is intensively investigated as a function of pH, canion type, and assembly time. The morphologies of the designer SAPs were studied by atomic force microscope. The secondary structure was investigated by circular dichroism. The dynamic viscoelasticity of designer SAP solutions was examined during titration with different alkaline reagents. Our study indicated that both electrostatic and hydrophilic/hydrophobic interactions of the motifs exhibited influences on the self-assembly, consequentially affecting the fiber morphologies and rheological properties. Moreover, NaOH induced a quicker assembly/reassembly of the designer SAPs than Tris because of its strong ionic strength. Therefore, our study gained comprehensive insight into the self-assembling mechanism as references for developing RADA 16-I-based functional SAPs.