CHIP inhibits odontoblast differentiation through promoting DLX3 polyubiquitylation and degradation.

Dentin is the major hard tissue of teeth formed by differentiated odontoblasts. How odontoblast differentiation is regulated remains enigmatic. Here, we report that the E3 ubiquitin ligase CHIP is highly expressed in undifferentiated dental mesenchymal cells and downregulated after differentiation of odontoblasts. Ectopic expression of CHIP inhibits odontoblastic differentiation of mouse dental papilla cells, whereas knockdown of endogenous CHIP has opposite effects. Chip (Stub1) knockout mice display increased formation of dentin and enhanced expression of odontoblast differentiation markers. Mechanistically, CHIP interacts with and induces K63 polyubiquitylation of the transcription factor DLX3, leading to its proteasomal degradation. Knockdown of DLX3 reverses the enhanced odontoblastic differentiation caused by knockdown of CHIP. These results suggest that CHIP inhibits odontoblast differentiation by targeting its tooth-specific substrate DLX3. Furthermore, our results indicate that CHIP competes with another E3 ubiquitin ligase, MDM2, that promotes odontoblast differentiation by monoubiquitylating DLX3. Our findings suggest that the two E3 ubiquitin ligases CHIP and MDM2 reciprocally regulate DLX3 activity by catalyzing distinct types of ubiquitylation, and reveal an important mechanism by which differentiation of odontoblasts is delicately regulated by divergent post-translational modifications.

Mg2+- or Ca2+-regulated aptamer adsorption on polydopamine-coated magnetic nanoparticles for fluorescence detection of ochratoxin A.

It has been observed that polyvalent metal ions can mediate the adsorption of DNA on polydopamine (PDA) surfaces. Exploiting this, we used two divalent metal ions (Mg2+ or Ca2+) to promote the adsorption of fluorescence-labelled ochratoxin A (OTA) aptamers on PDA-coated magnetic nanoparticles (Fe3O4@PDA). Based on the different adsorption affinities of free aptamers and OTA-bound aptamers, a facile assay method was established for OTA detection. The aptamers adsorbed on Fe3O4@PDA were removed via simple magnetic separation, and the remaining aptamers in the supernatant exhibited a positive correlation with the OTA concentration. The concentrations of Mg2+ and Ca2+ were finely tuned to attain the optimal adsorption affinity and sensitivity for OTA detection. In addition, other factors, including the Fe3O4@PDA dosage, pH, mixing order, and incubation time, were studied. Finally, under optimized conditions, a detection limit (3σ/s) of 1.26 ng/mL was achieved for OTA. Real samples of spiked red wine were analysed with this aptamer-based method. This is the first report of regulating aptamer adsorption on the PDA surface with polyvalent metal ions for OTA detection. By changing the aptamers, the method can be easily extended to other target analytes.

A WWP2-PTEN-KLF5 signaling axis regulates odontoblast differentiation and dentinogenesis in mice.

WW domain-containing E3 Ubiquitin-protein ligase 2 (WWP2) has been found to positively regulate odontoblastic differentiation by monoubiquitinating the transcription factor Kruppel-like factor 5 (KLF5) in a cell culture system. However, the in vivo role of WWP2 in mouse teeth remains unknown. To explore this, here we generated Wwp2 knockout (Wwp2 KO) mice. We found that molars in Wwp2 KO mice exhibited thinner dentin, widened predentin, and reduced numbers of dentinal tubules. In addition, expression of the odontoblast differentiation markers Dspp and Dmp1 was decreased in the odontoblast layers of Wwp2 KO mice. These findings demonstrate that WWP2 may facilitate odontoblast differentiation and dentinogenesis. Furthermore, we show for the first time that phosphatase and tensin homolog (PTEN), a tumor suppressor, is expressed in dental papilla cells and odontoblasts of mouse molars and acts as a negative regulator of odontoblastic differentiation. Further investigation indicated that PTEN is targeted by WWP2 for degradation during odontoblastic differentiation. We demonstrate PTEN physically interacts with and inhibits the transcriptional activity of KLF5 on Dspp and Dmp1. Finally, we found WWP2 was able to suppress the interaction between PTEN and KLF5, which diminished the inhibition effect of PTEN on KLF5. Taken together, this study confirms the essential role of WWP2 and the WWP2-PTEN-KLF5 signaling axis in odontoblast differentiation and dentinogenesis in vivo.

Evaluation of toxicity and biocompatibility of a novel Mg-Nd-Gd-Sr alloy in the osteoblastic cell.

BACKGROUND: We investigated the toxicity and biocompatibility of a novel Mg-3Nd-1Gd-0.3Sr-0.2Zn-0.4Zr (abbreviated to Mg-Nd-Gd-Sr) alloy in the osteoblastic cell line MC3T3-E1 as osteoblasts play an important role in bone repair and remodeling. METHODS: We used cytotoxicity tests and apoptosis to investigate the effects of the Mg-Nd-Gd-Sr alloy on osteoblastic cells. Cell bioactivity, cell adhesion, cell proliferation, mineralization, ALP activity, and expression of BMP-2 and OPG by osteoblastic cells were also used to investigate the biocompatibility of Mg-Nd-Gd-Sr alloy. RESULTS: The results showed that the Mg-Nd-Gd-Sr alloy had no obvious cytotoxicity, and did not induce apoptosis to MC3T3-E1 cells. Compared with the control group, the number of adherent cells within 12 h was increased significantly in each experimental group (P < 0.05); the OD value of MC3T3-E1 cells was increased significantly in each experimental group on days 1 and 3 of culture (P < 0.05); the number of mineralized nodules formed in each experimental group was significantly increased (P < 0.05), and ALP activity was significantly increased in each experimental group (P < 0.05). RT-PCR results showed that the mRNA expression of BMP-2 and OPG was significantly higher in each experimental group compared with the control group (P < 0.05). Western blotting showed that the Mg-Nd-Gd-Sr alloy extract significantly increased the protein expression of BMP-2 and OPG compared with the control group (P < 0.05). CONCLUSIONS: Our data indicated that the novel Mg-Nd-Gd-Sr-Zn-Zr alloy had no obvious cytotoxic effects, and did not cause apoptosis to MC3T3-E1 cells; meanwhile it promoted cell adhesion, cell proliferation, mineralization, and ALP activity of osteoblasts. During this process, there was an increase in the expressions of BMP-2 and OPG mRNAs and proteins.

Adapting to the acidic environment of the NP: RADA16-PLGA (TGF-ß3) induces chondrogenic differentiation of BMSCs.

Aim: RADA16-PLGA composite scaffolds constructed with simultaneous loading of BMSCs and TGF-ß3 and explored their ability for chondrogenic differentiation in vitro.Methods: The performance of the composite scaffolds is assessed by rheometer assay, electron microscopic structural observation and ELISA release assay. The biosafety of the composite scaffolds is assessed by cytocompatibility assay and cell migration ability. The chondrogenic differentiation ability of composite scaffolds is evaluated by Alisin blue staining, PCR and immunofluorescence staining.Results: The composite scaffold has a good ECM-like structure, the ability to control the release of TGF-ß3 and good biocompatibility. More importantly, the composite scaffolds can induce the differentiation of BMSCs to chondrocytes.Conclusion: Composite scaffolds are expected to enhance the endogenous NP repair process.

[Box: see text].

Polysaccharides screening for pulmonary mucus penetration by molecular dynamics simulation and in vitro verification.

Mucus penetration is one of the physiologic barriers of inhalation and nanocarriers can effectively facilitate the permeation of drugs. The interactions between the nanocarriers and mucin are crucial for penetration across the mucus layer on the respiratory tract. In this study, we proposed a molecular dynamics (MD) simulation method for the screening of polysaccharides that acted as the surface modification materials for inhalable nano-preparations to facilitate mucus penetration. MD revealed all-atom interactions between the monomers of polysaccharides, including dextran (DEX)/hyaluronic acid (HA)/carboxymethyl chitosan (CMCS) and the human mucin protein MUC5AC (hMUC5AC). The obtained data showed that DEX formed stronger non-covalent bonds with hMUC5AC compared to HA and CMCS, which suggested that HA and CMCS had better mucus permeability than DEX. For the in vitro verification, HA/CMCS-coated liposomes and DEX/PEG-inserted liposomes were prepared. The results of mucin interactions and mucus penetration studies confirmed that HA and CMCS possessed the weakest interactions with mucin and facilitated the mucus penetration, which was in consistent with the data from MD simulation. This work may shed light on the MD simulation-based screening of surface modification materials for inhalable nano-preparations to facilitate mucus penetration.

Liquid-liquid biopolymers aqueous solution segregative phase separation in food: From fundamentals to applications-A review.

As a result of the spontaneous movement of molecules, liquid-liquid biopolymer segregative phase separation takes place in an aqueous solution. The efficacy of this type of separation can be optimized under conditions where variables such as pH, temperature, and molecular concentrations have minimal impact on its dynamics. Recently, interest in the applications of biopolymers and their segregative phase separation-associated molecular stratification has increased, particularly in the food industry, where these methods permit the purification of specific particles and the embedding of microcapsules. The present review offers a comprehensive examination of the theoretical mechanisms that regulate the liquid-liquid biopolymers aqueous solution segregative phase separation, the factors that may exert an impact on this procedure, and the importance of this particular separation method in the context of food science. These discussion points also address existing difficulties and future possibilities related to the use of segregative phase separation in food applications. This highlights the potential for the design of novel functional foods and the enhancement of food properties.

Green, pH-Sensitive, Highly Stretchable, and Hydrogen Bond-Dominated Ionogel for Wound Healing Activity.

Traditional hydrogel dressings generally have poor mechanical properties and stability when subjected to external stress due to the undesirable chain entanglement structure of their single valence bond compositions. Therefore, it is particularly important to develop a type of gel dressing with good mechanical strength, stability, and environment-friendly monitoring. In this work, a transparent, pH-sensitive, highly stretchable, and biocompatible anthocyanidin ionogel dressing was prepared, realizing green and accurate detection. Attributed to the antibacterial activity of the ionic liquid, the biocompatibility of the pectin, and the ability to scavenge free radicals of the anthocyanidin, the ionogel dressing exhibited excellent re-epithelialization in the 14 day wound healing process. Besides, changes in pH values monitoring of the ionogel over 3 days coincided with normal wound exudate. The obtained ionogel also showed good water retention, swelling properties, mechanical stretchability, and 5 week stability, illustrating great potential in wound dressings.

A biomimetic nanocarrier facilitates glucose consumption and reactive oxide species accumulation in enzyme therapy for colorectal cancer.

Glucose oxidase (GOx)-based enzyme therapeutics are potential alternatives for colorectal cancer (CRC) treatment via glucose consumption and accumulation of hydrogen peroxide (H2O2). Given that H2O2 can be eliminated by cytoprotective autophagy, autophagy inhibitors that can interrupt autolysosome-induced H2O2 elimination are promising combination drugs of GOx. Here, we developed a multifunctional biomimetic nanocarrier for effective co-delivery of an autophagy inhibitor-chloroquine phosphate (CQP) and GOx to exert their synergistic effect by irreversibly upregulating intracellular reactive oxygen species (ROS) levels. Poly (D, l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were used to encapsulate both GOx and CQP using a W/O/W multi-emulsion method. Calcium phosphate (CaP) was used to "fix" CQP to GOx in the internal water phase, where it served as a pH-sensitive unit to facilitate intracellular drug release. Folic acid-modified red blood cell membranes (FR) were used to camouflage the GOx/CQP/CaP encapsulated PLGA NPs (referred to as PLGA/GCC@FR). In an AOM/DSS-induced CRC mouse model, PLGA/GCC@FR exhibited improved antitumor effects, in which the number of tumor nodes were only a quarter of that in the free drug combination group. The enhanced therapeutic effects of PLGA/GCC@FR were attributed to the prolonged tumor retention which was verified by both dynamic in vivo imaging and drug biodistribution. This multifunctional biomimetic nanocarrier facilitated combined enzyme therapeutics by depleting glucose and augmenting intracellular ROS levels in tumor cells, which exerted a synergistic inhibitory effect on tumor growth. Therefore, this study proposed a novel strategy for the enhancement of combined enzyme therapeutics, which provided a promising method for effective CRC treatment.

Prussian blue analogues based polymer monolith with amphiphilic interface to construct highly selective and sensitive imidacloprid chemosensor.

The most widely used assays for pesticides currently rely on the inhibition of natural enzymes, which are particularly sensitive to the surrounding environment, leading to some unreliable results. Up till now, there are few studies explored chemical detection methods for these stable pesticides. Here, we reported a novel chemosensor system and polymer materials for highly sensitive detection of imidacloprid pesticide. The polymer monolith with tunable surface hydrophilicity allows solvent-dependent adsorption of low-abundance target pesticide molecule. Prussian blue particles with Fenton catalytic activity were introduced into the polymeric monolith through Pickering emulsion, which capable of degrading the pesticide adsorbed on the column surface into easily detectable ions (NO3-, Cl-). This all-in-one functional material can minimize the interference of other non-target molecules through dual-channel detection, enabling sensitive detection of imidacloprid pesticide (30 ppb). We believe that the material described in this paper demonstrates for the first time the combination of an active polymer monolith for the enrichment and catalytic degradation with sensitive detection of pesticides, and this protocol can be used to develop a range of pesticides chemical sensing methods in the future.

Expression of FMD virus-like particles in yeast Hansenula polymorpha and immunogenicity of combine with CpG and aluminum adjuvant.

BACKGROUND: Inactivated vaccines are limited in preventing foot-and-mouth disease (FMD) due to safety problems. Recombinant virus-like particles (VLPs) are an excellent candidate for a novel vaccine for preventing FMD, given that VLPs have similar immunogenicity as natural viruses and are replication- and infection-incompetent. OBJECTIVES: The 3C protease and P1 polyprotein of type O FMD virus (FDMV) was expressed in yeast Hansenula polymorpha to generate self-resembling VLPs, and the potential of recombinant VLPs as an FMD vaccine was evaluated. METHODS: BALB/c mice were immunized with recombinant purified VLPs using CpG oligodeoxynucleotide and aluminum hydroxide gel as an adjuvant. Cytokines and lymphocytes from serum and spleen were analyzed by enzyme-linked immunosorbent assay, enzyme-linked immunospot assay, and flow cytometry. RESULTS: The VLPs of FMD were purified successfully from yeast protein with a diameter of approximately 25 nm. The immunization of mice showed that animals produced high levels of FMDV antibodies and a higher level of antibodies for a longer time. In addition, higher levels of interferon-γ and CD4+ T cells were observed in mice immunized with VLPs. CONCLUSIONS: The expression of VLPs of FMD in H. polymorpha provides a novel strategy for the generation of the FMDV vaccine.

Silk fibroin-based biomaterials for disc tissue engineering.

Low back pain is the major cause of disability worldwide, and intervertebral disc degeneration (IVDD) is one of the most important causes of low back pain. Currently, there is no method to treat IVDD that can reverse or regenerate intervertebral disc (IVD) tissue, but the recent development of disc tissue engineering (DTE) offers a new means of addressing these disadvantages. Among numerous biomaterials for tissue engineering, silk fibroin (SF) is widely used due to its easy availability and excellent physical/chemical properties. SF is usually used in combination with other materials to construct biological scaffolds or bioactive substance delivery systems, or it can be used alone. The present article first briefly outlines the anatomical and physiological features of IVD, the associated etiology and current treatment modalities of IVDD, and the current status of DTE. Then, it highlights the characteristics of SF biomaterials and their latest research advances in DTE and discusses the prospects and challenges in the application of SF in DTE, with a view to facilitating the clinical process of developing interventions related to IVD-derived low back pain caused by IVDD.

A pH-Sensitive, Stretchable, Antibacterial Artificial Tongue Based on MXene Cross-Linked Ionogel.

Dehydration has always been a confusing problem for a hydrogel exposed to air, which restricts its application in practical detection. While an ionogel with unique properties can lock water molecules efficiently due to its low vapor pressure, the design and development of an ionogel with excellent water-locking properties and stability to achieve satisfactory detection are thus highly desirable. In this work, a pH-sensitive, stretchable, antibacterial, and stable ionogel artificial tongue was fabricated through dual cross-linking. The artificial tongue consisted of MXene as a cross-linking agent, phenol red as an indicator, gelatin, N-(2-hydroxyethyl) acrylamide, and 1-butyl-3-methylimidazolium chloride as the three-dimensional polymer network. A small quantity of MXene was used as a cross-linker the first time to promote the initiator in the system to generate free radicals, accelerating the reaction process and the multilevel linkage among the polymers. Meanwhile, the indicator phenol red was introduced into the ionogel successfully for the first time, showing great stability in 5 weeks. After evaluation by the Brand-Altman analysis, it was found that the method of pH measurement using ionogels had good consistency with the pH meter measurement method. Additionally, the prepared ionogel presented excellent water retention, mechanical stretchability, antibacterial property, and stability, as well as good test results in the test of artificial simulated saliva, demonstrating great potential in clinical applications.

Effect and mechanism of a novel Mg-Nd-Gd-Sr alloy on osteogenic differentiation of bone marrow mesenchymal stem cells.

We investigated the effect and mechanism of a novel Mg-3Nd-1Gd-0.3Sr-0.2Zn-0.4Zr (abbreviated to Mg-Nd-Gd-Sr) alloy on the osteogenic differentiation of bone marrow mesenchymal stem cells extracted from Sprague-Dawley rats. Cultured cells were divided into five groups: a control group cultured in osteogenic induction medium alone without Mg-Nd-Gd-Sr alloy extract, and four experimental groups cultured in the same medium with 25%, 50%, 75%, and 100% Mg-Nd-Gd-Sr alloy extracts, respectively. After 14 days of culture, ALP activity was determined and expressions of osteogenesis-related factors Runx2, OCN, and OPN at the mRNA level and Runx2, OCN, and OPN at the protein level were detected by RT-PCR and western blot, respectively. After 21 days of culture, mineralized nodules were detected by alizarin red staining. The results showed that bone marrow mesenchymal stem cells from Sprague-Dawley rats were successfully isolated in vitro using the whole bone marrow adherence method. Flow cytometry revealed that the cells expressed high levels of CD44 and CD90, but low levels of CD31 and CD45. Alizarin red staining indicated the formation of mineralized nodules in all five groups. Compared with the control group, the number of mineralized nodules was increased significantly in the four experimental groups (p < 0.05). The ALP activity in each group was significantly higher on day 14 than on day 7, and was significantly higher in the four experimental groups compared with the control group (p < 0.05). Moreover, the ALP activity was highest when the concentration of Mg-Nd-Gd-Sr alloy extract was 75% (p < 0.05). RT-PCR results showed that, compared with the control group, the mRNA expression of Runx2, OPN, and OCN was significantly higher in the four experimental groups (p < 0.05), and the highest mRNA expression of Runx2, OPN, and OCN was observed in the 75% experimental group (p < 0.05). Western blotting showed that Mg-Nd-Gd-Sr alloy extract significantly increased the protein expression of Runx2, OCN, and OPN compared with the control group (p < 0.05). Our data indicate that the novel Mg-Nd-Gd-Sr alloy can promotes the osteogenic differentiation of bone marrow mesenchymal stem cells isolated from Sprague-Dawley rats. During this process, there is an increase in the expressions of Runx2, OPN, and OCN mRNAs and Runx2, OCN, and OPN proteins.

Self-assembled micelle responsive to quick NIR light irradiation for fast drug release and highly efficient cancer therapy.

Upconversion nanoparticles (UCNPs) have been used for designing near infrared (NIR) light-responsive nanocarriers and controllable drug release. However, the need for long-term NIR light irradiation over hours impaired their application efficiency. Here we develop a self-assembled micelle of amphipathic polymer P-DASA which degrades via quick NIR light irradiation. UCNPs and DOX are also encapsulated in the micelle for quick drug release. P-DASA is composed of hydrophilic polyethylene glycol segment and photo-responsive hydrophobic donor-acceptor Stenhouse adduct (DASA). Only 5-min NIR irradiation causes the hydrophilicity conversion of P-DASA and the complete disruption of micelle with DOX fast release of 83.7% in 30 min to achieve highly efficient therapy. Moreover, the P-glycoprotein mediated DOX efflux is also diminished by concomitantly producing NO intracellularly. This micelle demonstrates impressive in vivo therapeutic effect, and thus provides an avenue for highly efficient cancer therapy.

Intraocular Lens with Mussel-Inspired Coating for Preventing Posterior Capsule Opacification via Photothermal Effect.

Phacoemulsification with implantation of intraocular lens (IOLs) has been widely applied as a standard treatment for cataract, which is the leading cause of vision impairment. However, it still remains a critical challenge to prevent posterior capsule opacification (PCO) in terms of postoperative visual quality. Herein, we report IOLs with mussel-inspired coatings for inhibiting lens epithelial cells and then preventing PCO through photothermal conversion effect. The mussel-inspired coatings are deposited on the nonoptical surface areas of IOLs, endowing the modified IOLs with efficient photothermal conversion property. The temperature can be facilely raised to 50-60 °C for the photothermal IOLs (PT-IOLs) by near-infrared (NIR) laser irradiation at a safe intensity of 0.3 W/cm2. These PT-IOLs display high capability of inhibiting lens epithelial cells (LECs) in vitro. Therefore, under routine NIR laser irradiation, New Zealand white rabbits implanted with the PT-IOLs demonstrate significantly lower evaluation of PCO (EPCO) scores than the control groups. The overall results indicate that our PT-IOLs provide a promising choice for the clinical prevention of PCO, thus opening a way to maintain the postoperative visual qualities for cataract patients.

Corrosion behavior and mechanical degradation of as-extruded Mg-Gd-Zn-Zr alloys for orthopedic application.

The microstructures, corrosion behavior, and mechanical degradation of the as-extruded Mg-6.0Gd-0.5Zn-0.4Zr (wt %, GZ60K) and Mg-6.0Gd-1.0Zn-0.4Zr (wt %, GZ61K) alloys were investigated. In both alloys, stacking faults and precipitates are formed in the recrystallized microstructures. The corrosion rate of GZ61K calculated by the hydrogen evolution in simulated body fluid is 0.34 ± 0.13 mm/year, which is lower than that of GZ60K (0.45 ± 0.09 mm/year); and the current density of GZ61K (5.23 ± 1.41 µA cm-2 ) is much lower than that of GZ60K (11.95 ± 3.37 µA cm-2 ). The corrosion results indicate GZ61K is more resistant to corrosion than GZ60K, but GZ60K presents more uniform corrosion mode as compared to GZ61K. After immersion in simulated body fluid for 7, 14, and 21 days, a slight decrease in the strength of both alloys is observed. The yield strength half-life is assessed for mechanical degradation and determined to be 125 and 85 days for GZ60K and GZ61K, respectively. The as-extruded GZ60K alloy with more uniform corrosion and longer mechanical integrity shows promising potential for orthopedic application.

Photo-tearable tape close-wrapped upconversion nanocapsules for near-infrared modulated efficient siRNA delivery and therapy.

RNA interference (RNAi) has become an appealing therapeutic approach for cancer and other diseases. One key challenge is the effective protection of these small fragile biomolecules against complicated physiological environments as well as efficient on-demand release. Here we design a photo-tearable polymer tape close-wrapped nanocapsule for efficient NIR modulated siRNA delivery. The photo-tearable nanocapsules comprise core-shell upconversion nanoparticles (UCNPs) coated with mesoporous silica layer for loading of photosensitizer hypocrellin A (HA) and small interfering RNA (siRNA) against polo-like kinase 1 (PLK1), and covalently bound thin membranes of polyethylene glycol (PEG) via a synthesized photocleavable linker (PhL). Upon irradiation at 980 nm, the UCNPs produce UV emissions to break PhL and tear out PEG membrane for siRNA release, and blue emissions to activate HA for generating reactive oxygen species (ROS). The close PEG membrane wrapping not only guarantees the efficient intracellular photocleavage, but also extends the circulation time and protects the loaded cargos from leakage and degradation. The ROS assists endosomal escape of the loaded cargos, therefore effectively improves the gene silencing efficiency and the suppressions of cell proliferation in vitro and tumor growth in vivo. The proposed photo-tearable tape-wrapped nanocapsules have promising potential application in precision medicine.

Sandwich-type electrochemical immunosensor based on Au@Ag supported on functionalized phenolic resin microporous carbon spheres for ultrasensitive analysis of α-fetoprotein.

Signal amplification is crucial for obtaining low detection limits in electrochemical immunosensor. In this work, we developed a novel signal amplification strategy using Au@Ag nanoparticles loaded by polydopamine functionalized phenolic resin microporous carbon spheres (Au@Ag/PDA-PR-MCS). Phenolic resin microporous carbon spheres (PR-MCS) possesses uniform size and a large surface area (1656.8 m2 g-1). Polydopamine (PDA) functionalized phenolic resin microporous carbon spheres (PDA-PR-MCS) retains the advantages of PR-MCS and possesses strong adsorption ability. With the unique structure of PDA-PR-MCS, it not only improves the loading capacity and dispersity of Au@Ag nanoparticles (Au@Ag NPs), but also enhances the stability for the combination of the Au@Ag NPs by chemical absorption between Au@Ag NPs and -NH2 of PDA. The Au@Ag/PDA-PR-MCS exhibits extraordinary electrocatalytic activity towards reduction of hydrogen peroxide (H2O2) to make the electrochemical response more sensitive. Furthermore, Au NPs with good biocompatibility and excellent conductivity were electrodeposited on the surface of electrode, which was used as a sensing platform to immobilize primary antibody (Ab1) and accelerate the electron transfer on the electrode interface. Herein, the designed immunosensor provided a broad linear range from 20 fg/mL to 100 ng/mL for alpha fetoprotein (AFP) detection and a low detection limit of 6.7 fg/mL (signal-to-noise ratio of 3) under optimal experimental conditions. Moreover, the excellent performance in detection of human serum samples indicated that the proposed immunosensor will provide promising applications in clinical monitoring of AFP.

A promising biodegradable magnesium alloy suitable for clinical vascular stent application.

We report a Mg alloy Mg-2.2Nd-0.1Zn-0.4Zr (wt.%, denoted as JDBM-2) showing great potential in clinical vascular stent application by integrating the advantages of traditional medical stainless steel and polymer. This alloy exhibits high yield strength and elongation of 276 ± 6 MPa and 34.3 ± 3.4% respectively. The JDBM-2 with a stable degradation surface results in a highly homogeneous degradation mechanism and long-term structural and mechanical durability. In vitro cytotoxicity test of the Mg extract via human vascular endothelial cells (HUVECs) indicates that the corrosion products are well tolerated by the tested cells and potentially negligible toxic effect on arterial vessel walls. This alloy also exhibits compromised foreign body response (FBR) determined by human peripheral blood derived macrophage adhesion, foreign body giant cell (FBGC) formation and inflammatory cytokine and chemokine secretion. Finally, vascular stents manufactured from the JDBM-2 were implanted into rabbits for long-term evaluation. The results confirm excellent tissue compatibility and up to 6-month structural and mechanical integrity of the stent in vivo. Thus, the JDBM-2 stent with up to 6-month structural and mechanical integrity and excellent tissue compatibility represents a major breakthrough in this field and a promising alternative to traditional medical stainless steel and polymer for the clinical application.