Latest ArticlesPolymerase chain reactions (PCR) are a very important tool for use in cloning, nucleic acid sequencing and diagnostic testing. The storage conditions of PCR reagents are limited to freezing and a lot of mixing steps are needed. In this paper, we report using metal ions to form coordination nanomaterials with the intrinsic components of the PCR reagents including dNTP, DNA primers and DNA polymerase as an integrated PCR reaction system. To complete PCR reactions, users need only to dissolve the coordination nanomaterials with a buffer and add template DNA. A few transition metal ions were screened and Cu2+ was found to be the most effective metal ion for this purpose. Then the encapsulation efficiency of PCR reagents was measured, which can reach close to 100% for the primers and DNA polymerase, but only 10% for dNTP because dNTP was excess. Further study also exhibited this integrated PCR reaction system can be used for DNA detection with a similar detection limit to the normal PCR, and showed good stability of encapsulated PCR nanomaterial after storage for a week.
Available online Immunoglobulins G (IgGs) are Y-shaped globular proteins, however, their high flexibility and heterogeneity pose great challenges to their structure and conformation determinations. Geometric structure of IgG closely correlates to its biofunctions, such as the antibody escape of human immunodeficiency virus (HIV) could attribute to the distance mismatch between the ends of two Fab arms (antigen-binding sites) and envelope glycoprotein spikes on virion surface. Herein, we report the first use of mobility capillary electrophoresis (MCE) and native mass spectrometry (nMS) to resolve the internal geometric structure and conformation of an IgG (trastuzumab) in solution phase. After proteolysis, the ellipsoid dimensions of IgG and its subunits were measured by MCE-nMS experiments. IgG was then reconstructed, in which the sizes and relative positions of these three subunits in three-dimensional space were characterized. It was found that the two Fab arms have an angle of ~102.1° and a distance of ~11.0 nm between the two antigen-binding sites under native condition, and the Fc arm was tilted ~16.0° towards one of the Fab arms. Fc was not on the plane of Fab-Fab, but has an angle of no larger than 103.1°. Under acidic environment (pH 3.0), each subunit of the IgG would unfold into larger dimensions, and the angles between these subunits also change. With great potential for tumor imaging and therapy, the structure of F(ab′)2 fragments was also measured and validated by molecular dynamic simulation. It was found that the electrostatic force among these three subunits and steric hindrance stemming from Fc help maintaining the angle between two Fab arms.
Plasmonic metal nanomaterials with intrinsic surface–enhanced Raman scattering (SERS) and photothermal properties, especially AuAg nanoalloys with both the outstanding merits of Au and Ag nanocrystals, show huge application prospects in bacterial theranostics. However, the direct exposure of AuAg nanoalloys in external conditions probably cause undesirable reactions and poisonous metal ion leakage during SERS detection and photothermal antibacterial therapy process, which severely hinder bacterial theranostics applications. Herein, we report an ultrastable graphene–isolated AuAg nanoalloy (GAA) with AuAg core confined in few–layer graphitic shell as a versatile platform for bacterial detection and therapy. The encapsulation of graphene ensures the good stability of AuAg core, that its superior SERS and photothermal properties are therefore further guaranteed. GAA is used for SERS detection of two vital bacterial biomarkers (including corrosive cyanide and pyocyanin), exhibiting good SERS quantitative and multiplexing ability. GAA is further used for photothermal antibacterial therapy application, and ultrahigh antibacterial efficacies for both Gram–negative Escherichia coli and Gram–positive Staphylococcus aureus are achieved under 808 nm laser irradiation. This work proposes a valuable method to develop robust bacterial theranostic platform.
Therapeutic cancer vaccines have undergone a resurgence in the past decade. Because of the high level of immune cell accumulation and abundant capillary lymphatic system in the dermis, percutaneous vaccination is considered to be an ideal treatment route. For convenient administration, the recent development of microneedles (MNs) provides a safe, painless, and low-cost transdermal delivery strategy, which could bypass the first-pass metabolism of vaccines for enhanced stability and bioavailability. However, the therapeutic effect of MNs-based cancer vaccines is not optimal, which is limited by the complex set of host, tumor, and environmental factors, as well as the limited vaccine loading capacity. Therefore, further improvements are still required to push their clinical translation. In this critical review, we deliberate on how to improve the therapeutic effect of MNs-based vaccines for cancer immunotherapy, summarize the recent advances in MNs-based cancer vaccination, and provide an overview of various design strategies and mechanisms for active or passive targeting delivery, aiming to develop safer, more effective, and more stable MNs-based cancer vaccines. Finally, we briefly describe the potential of vaccine platforms in combination with other therapies, suggest the need to design vaccines according to specific circumstances, and discuss the biosafety of repeated administration for enhancing clinical efficacy.
Electrochemical nitrate reduction reaction (NITRR) is regarded as a “two birds-one stone” method for the treatment of nitrate contaminant in polluted water and the synthesis of valuable ammonia, which is retarded by the lack of highly reactive and selective electrocatalysts. Herein, for the first time, nickel foam supported Co4N was designed as a high-performance NITRR catalyst by an in-situ nonmetal leaching-induced strategy. At the optimal potential, the Co4N/NF catalyst achieves ultra-high Faraday efficiency and NH3 selectivity of 95.4% and 99.4%, respectively. Ex situ X-ray absorption spectroscopy (XAS), together with other experiments powerfully reveal that the nitrogen vacancies produced by nitrogen leaching are stable and play a key role in boosting nitrate reduction to ammonia. Theoretical calculations confirm that Co4N with abundant nitrogen vacancies can optimize the adsorption energies of NO3- and intermediates, lower the free energy (ΔG) of the potential-determining step (*NH3 to NH3) and inhibit the formation of N-containing byproducts. In addition, we also conclude that the nitrogen vacancies can stabilize the adsorbed hydrogen, making H2 quite difficult to produce, and lowering ΔG from *NO to *NOH, which facilitates the selective reduction of nitrate. This study reveals significant insights about the in-situ nonmetal leaching to enhance the NITRR activity.
Photodynamic therapy (PDT) is an effective treatment method for tumors. But the specifically accumulated of photosensitizer was very difficult in the tumor site, which greatly limited the efficacy of PDT. Here, mitochondria-targeted Janus mesoporous nanoplatform (JPMO-Pt-CTPP-ZnPc) for PDT was prepared, the nanoplatform has uniform size (275 nm) and good dispersion and biocompatibility. The confocal laser scanning microscopy (CLSM) revealed the signal of ZnPc of JPMO-Pt-CTPP-ZnPc were higher than JPMO-Pt-ZnPc in tumor cells, and flow cytometry results showed the cell uptake efficiency of JPMO-Pt-CTPP-ZnPc was 2.5-fold higher than that of JPMO-Pt-ZnPc. This revealed the modification of CTPP significantly improves the targeting ability of the nanoplatform. In vitro anti-tumor experiment showed the JPMO-Pt-CTPP-ZnPc significantly inhibited the growth of tumor cells upon the irradiation of low-power laser, and the survival rate of cells incubated with 60 µg/mL JPMO-Pt-CTPP-ZnPc was only 3%. Simultaneously, compared with JPMO-Pt-ZnPc (not modified with mitochondria targeting molecules CTPP), the PDT efficacy of JPMO-Pt-CTPP-ZnPc was significantly better, as it has targeted mitochondria in cells.
In order to solve the contradiction between the rapidly growing energy demand and the excessive exploitation of fossil fuels, it is urgent to research and develops more environmentally friendly and efficient energy storage technologies. Therefore, the development of high-performance cathode materials to enhance the energy density of SIB is currently one of the most important topics of scientific research. Advanced high-voltage and low-cost cathode material for SIBs, a composite of carbon-coated Na4MnCr(PO4)3 (NASICON-type), polyvinylpyrrolidone (PVP), and modified carbon nanotubes (CNTs) is prepared by sol-gel and freeze-drying method. Due to the high conductivity of CNTs, the conductivity of the composite is significantly improved, and its initial capacity is increased to 114 mAh/g at 0.5 C and 96 mAh/g at 5 C (Mn2+/Mn4+ conversion for voltage windows 1.4-4.3 V). Moreover, the multi-electrons transfer of Cr3+/Cr4+ and Mn2+/Mn4+ can provide a high capacity of 165 mAh/g at 0.1 C and 102 mAh/g at 5 C in the high voltage window of 1.4-4.6 V. Furthermore, PVP can effectively inhibit the Jahn-Teller effect caused by Mn ion, making the composite have more excellent high-rate performance and stability. In addition, GITT, EIS and CV curves were drawn to better reveal the excellent kinetic properties of Na4MnCr(PO4)3@C@PVP@CNT cathode, and the mechanism of its performance improvement is deeply studied and discussed. Accordingly, the co-doping of CNTs and PVP is a simple way to high conductivity and fast charging of cathode materials for SIBs.
Although it has been developed for many years, nucleic acid aptamer screening technology still fails to be widely used, a considerable part of it is due to the variability of tumor cell morphology, which leads to the use of immortalized cell lines in the laboratory to screen nucleic acid aptamers for recognition ability of tumor cells in the diseased body. To address this, primary cells that can be stably passaged were isolated and extracted from spontaneous tumors of genetically engineered pancreatic ductal adenocarcinoma model mice in this study. Next, an automated screening instrument for nucleic acid aptamers developed autonomously by our group was used to perform efficient aptamer screening using a limited number of cells, and the obtained nucleic acid aptamers were affinity verified at the cellular level. Finally, to answer the question of the cell growth environment difference on the recognition ability of nucleic acid aptamers, we verified its targeting ability to tumors in vivo on a nude mice xenograft tumor model, and further used a common antitumor drug doxorubicin combined with nucleic acid aptamers to verify the drug loading ability of this aptamer combined with the targeting therapeutic ability.
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