Nanocarriers are of paramount significance for drug delivery and nanomedicine technology. Given the imperfect systems and nonideal therapeutic effects, there are works to be done in synthesis as much as in biological studies, if not more so. Building the foundation of synthesis would offer more tools and deeper insights for exploring the biological systems with extreme complexity. This review aims at a broad‐scope summary and classification of nanocarriers for drug delivery, with focus on the synthetic strategy and structural implications. The nanocarriers are divided into four categories according to the loading principle: molecular‐level loading, surface loading, matrix loading, and cavity loading systems. Making comparisons across diverse nanocarrier systems would make it easier to see the fundamental characteristics, from where the weakness can be addressed and the strengths combined. The systematic comparisons may also inspire new ideas and methods.
High thermal conductivity graphite nanoplatelets/ultra high molecular weight polyethylene (GNPs/UHMWPE) nanocomposites are fabricated via mechanical ball milling followed by a hot-pressing method.
Middle East respiratory syndrome coronavirus (MERS-CoV) has continued spreading since its emergence in 2012 with a mortality rate of 35.6%, and is a potential pandemic threat. Prophylactics and therapies are urgently needed to address this public health problem. We report here the efficacy of a vaccine consisting of chimeric virus-like particles (VLP) expressing the receptor binding domain (RBD) of MERS-CoV. In this study, a fusion of the canine parvovirus (CPV) VP2 structural protein gene with the RBD of MERS-CoV can self-assemble into chimeric, spherical VLP (sVLP). sVLP retained certain parvovirus characteristics, such as the ability to agglutinate pig erythrocytes, and structural morphology similar to CPV virions. Immunization with sVLP induced RBD-specific humoral and cellular immune responses in mice. sVLP-specific antisera from these animals were able to prevent pseudotyped MERS-CoV entry into susceptible cells, with neutralizing antibody titers reaching 1: 320. IFN-γ, IL-4 and IL-2 secreting cells induced by the RBD were detected in the splenocytes of vaccinated mice by ELISpot. Furthermore, mice inoculated with sVLP or an adjuvanted sVLP vaccine elicited T-helper 1 (Th1) and T-helper 2 (Th2) cell-mediated immunity. Our study demonstrates that sVLP displaying the RBD of MERS-CoV are promising prophylactic candidates against MERS-CoV in a potential outbreak situation.
African swine fever virus (ASFV), the etiological agent of African swine fever (ASF), a hemorrhagic fever of domestic pigs, has devastating consequences for the pig farming industry. More than 1,000,000 pigs have been slaughtered since 3 August 2018 in China. However, vaccines or drugs for ASF have yet to be developed. As such, a rapid test that can accurately detect ASFV on-site is important to the timely implementation of control measures. In this study, we developed a rapid test that combines recombinase polymerase amplification (RPA) of the ASFV p72 gene with lateral flow detection (LFD). Results showed that the sensitivity of recombinase polymerase amplification with lateral flow dipstick (RPA-LFD) for ASFV was 150 copies per reaction within 10 min at 38°C. The assay was highly specific to ASFV and had no cross-reactions with other porcine viruses, including classical swine fever virus (CSFV). A total of 145 field samples were examined using our method, and the agreement of the positive rate between RPA-LFD (10/145) and real-time PCR (10/145) was 100%. Overall, RPA-LFD provides a novel alternative for the simple, sensitive, and specific identification of ASFV and showed potential for on-site ASFV detection.
A study was made on the antibacterial mechanism of copper-bearing austenitic antibacterial stainless steel by a series of methods such as atomic force microscopy (AFM) observation, force-distance curves and inductively coupled plasma mass spectrometer test. It was observed by AFM that the structure of the outer cell membrane responsible for the cell permeability was substantially changed for the bacteria after contacting with the antibacterial stainless steel, showing that cell walls were seriously damaged and a lot of contents in the cells leaked. It was also found that the adhesion force of bacteria to antibacterial stainless steel was considerably greater than that to the contrast steel, indicating that the electrostatic forces by Cu(2+ )being an important factor for killing bacteria.
Cholesterol oxides in fish products popular in Japan, including salted and dried, boiled and dried and smoked products, were qualitatively and quantitatively determined as trimethylsilyl ether derivatives by gas‐liquid chromatography and mass spectrometry. The level of total cholesterol oxides ranged widely between 8.3 ppm in boiled and dried shrimp and 188.0 ppm in boiled and dried anchovy. 7β‐Hydroxycholesterol and 7‐ketocholesterol were the most prominent oxidative decomposition products of cholesterol. The levels of epimeric epoxides, cholestane triol and 25‐hydroxycholesterol were relatively low. To elucidate a mechanism of cholesterol oxidation proceeding during fish processing and subsequent preservation, four model systems, consisting of a mixture of purified cod liver triglycerides plus cholesterol, of a mixture of authentic triolein plus cholesterol, of triolein alone and of cholesterol alone, were stored separately at 25°C in dry air for up to 104 d. The residual fatty acids of the triglycerides, and the cholesterol oxides produced, were recovered and determined. Oxygen uptake remained almost unchanged for the mixture of triolein plus cholesterol. No detectable amount of cholesterol oxides was produced, and the fatty acid content of the residual oleic acid, measured by an internal standard, remained almost unchanged. For the mixture of cod liver triglycerides plus cholesterol, a remarkable increase in oxygen uptake was observed. A continuous increase in the amount of cholesterol oxides was observed, accompanied by a remarkable concurrent decrease in polyunsaturated fatty acid residues, as well as of the oleic acid naturally present. These results strongly suggest that cholesterol oxidation in fish products proceeds in conjunction with oxidative decomposition of the coexisting polyunsaturated fatty acids of fish oils.
Most of the magnesium (Mg) alloys possess excellent biocompatibility, mechanical property and biodegradability in orthopedic applications. However, these alloys may suffer from bacterial infections due to their insufficient antibacterial capability. In order to reduce the post-surgical infections, a series of biocompatible Mg–1Ca-0.5Sr-xZn (x=0, 2, 4, 6) alloys were fabricated with the addition of antibacterial Zn with variable content and evaluated in terms of their biocompatibility and antibacterial property. The in vitro corrosion study showed that Mg-1Ca-0.5Sr-6Zn alloys exhibited a higher hydrogen evolution volume after 100 h immersion and resulted in a higher pH value of the immersion solution. Our work indicated that Zn-containing Mg alloys exhibited good biocompatibility with high cell viability. The antibacterial studies reveal that the number of bacteria adhered on all of these Mg alloy samples diminished remarkably compared to the Ti-6Al-4V control group. We also found that the proliferation of the bacteria was inhibited by these Mg alloys extracts. Among the prepared alloys, Mg-1Ca-0.5Sr-6Zn alloy not only exhibited a strong antibacterial effect, but also promoted the proliferation of MC3T3-E1 osteoblasts, suggesting that it is a promising alloy with both good antibacterial property and good biocompatibility for use as an orthopedic implant.
SummaryPorphyromonas gingivalis is an obligately anaerobic bacterium recognized as an aetiological agent of adult periodontitis. P. gingivalis produces cysteine proteinases, the gingipains. The crystal structure of a domain within the haemagglutinin region of the lysine gingipain (Kgp) is reported here. The domain was named K2 as it is the second of three homologous structural modules in Kgp. The K2 domain structure is a 'jellyroll' fold with two anti-parallel b-sheets. This fold topology is shared with adhesive domains from functionally diverse receptors such as MAM domains, ephrin receptor ligand binding domains and a number of carbohydrate binding modules. Possible functions of K2 were investigated. K2 induced haemolysis of erythrocytes in a dose-dependent manner that was augmented by the blocking of anion transport. Further, cysteine-activated arginine gingipain RgpB, which degrades glycophorin A, sensitized erythrocytes to the haemolytic effect of K2. Cleaved K2, similar to that found in extracted Kgp, lacks the haemolytic activity indicating that autolysis of Kgp may be a staged process which is artificially enhanced by extraction of the protein. The data indicate a functional role for K2 in the integrated capacity conferred by Kgp to enable the porphyrin auxotroph P. gingivalis to capture essential haem from erythrocytes.
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