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Cubosomes, as biocompatible carriers in drug delivery systems, consist of curved bicontinuous lipid bilayers. With a honeycombed structure divided into two internal aqueous channels, cubosomes could be used for many bioactive ingredients. Achyranthes bidentata polysaccharides (ABPs) are isolated from the roots of Achyranthes bidentata , used in Chinese herbal medicine, and present a noticeable effect as an immunomodulator. This study investigates the optimal preparation of combined cubosome-ABP (Cub-ABP) nanoparticles using response surface methodology and explores their characteristics and stability. The encapsulation efficiency of optimized Cub-ABPs was 72.59%. In-vitro stability studies demonstrated the stability of Cub-ABPs and cubosome nanoparticles without ABPs; both were stable for up to 25 days. Safe concentrations of Cub-ABPs and cubosome nanoparticles without ABPs are 104.06 μg/mL and 208.13 μg/mL with comparatively low cytotoxicity against lymphocytes. Moreover, the feasible immunomodulatory effects of Cub-ABPs were determined by evaluating their proliferation and change of CD4 + /CD8 + ratio on splenic lymphocytes in vitro . Proliferation and flow cytometry studies revealed that, compared with free ABPs and blank cubosomes, Cub-ABPs proved more effective in promoting lymphocyte proliferation and in triggering the transformation of T-lymphocytes into T h -cells. [ABSTRACT FROM AUTHOR]

Wire and arc additive manufacturing (WAAM) is a promising technology for the preparation of refractory metal functional gradient materials (FGMs) due to its high material utilization, high deposition efficiency and ability to create large-sized parts. In the present work, 316L/IN625 FGM with chemical composition gradients of 25 wt% and 100 wt% were fabricated using dual-wire plasma arc additive manufacturing (DW-PAAM) by changing the wire feeding speeds (WFSs) layer by layer. The phase evolution, microstructure, chemical composition and mechanical properties of the FGM were analyzed. The results demonstrated that the microstructure in all regions was predominantly the austenite phase, and no cracks or defects were observed. The microstructure of the 100 wt% 316L zone was composed of the austenite phase (face-centered cubic, FCC) and a small amount of ferrite phase (body-centered cubic, BCC), whereas mainly FCC structure was observed in the other chemical composition regions. There was a certain error between the actual composition gradient and the designed gradient. The microhardness transition of S1 was smoother and wider, while the tensile test results of S2 were better. In addition, the position of the tensile fracture was different for S1 and S2. In conclusion, the DW-PAAM process shows great potential for manufacturing FGM with desirable properties for various industrial applications. Further studies are warranted to optimize process parameters and develop new design strategies to enhance the performance of FGM in various industrial applications. • 316L/IN625 FGM with composition gradients of 25 wt% and 100 wt% were prepared by the DW-PAAM process. • The microstructure in all regions was predominantly the FCC structure, no cracks or defects were observed. • A certain error existed between the chemical composition curve of the actual gradient and the design gradient. • Sample S1 has the lowest microhardness and tensile strength in the zone of 75 wt% 316L. [ABSTRACT FROM AUTHOR]

Highlights • FT-IR has been employed to characterize the Lycium barbarum polysaccharides (LBP). • LBPL enhanced significantly proliferation effects on mouse DC precursor cells. • LBPL induced DCs maturation characterized by up-regulation co-stimulatory molecules. • Enhanced antigen uptake and production of cytokines in DCs after incubation with LBPL. • The mechanism of TLR4 signaling was involved in LBPL-elicited activation of DCs. Abstract Dendritic cells (DCs) are professional antigen-presenting cells (APC) that play a central role in the initiation and regulation of immune responses. We have previously demonstrated that Lycium barbarum polysaccharides liposomes (LBPL) as immune adjuvant elicits strong antigen-specific Th1 immune responses. The purpose of this study was to investigate underlying mechanism of liposomes promoting effect of Lycium barbarum polysaccharides (LBP) on activating DCs. LBP were loaded with high entrapment efficiency (86%) into liposomes using reverse phase evaporation. LBPL activation of phenotypic and functional maturation of DCs was explored through mechanistic studies of the TLR4-MyD88-NF-κB signaling pathway and amount of proinflammatory cytokines released. We found that LBPL indeed activated immature DCs and induced DCs maturation characterized by up-regulation of co-stimulatory molecules (MHCII, CD80, CD86), production of cytokines (IL-12p40, TNF-α), and enhancement of antigen uptake. Additionally, we demonstrated that liposomes could promote LBP up-regulation of TLR4, MyD88, TRAF6, NF-κB gene and protein expression. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Nanoparticles (NPs)-based vaccine delivery systems are widely used for their ability to control the release of antigens and promote immune responses against cancer or infectious diseases. In this study, the immunopotentiator Angelica sinensis polysaccharide (ASP) and model protein antigen ovalbumin (OVA) were encapsulated into Poly(lactic-co-glycolic acid) (PLGA) to formulate the novel NPs-based vaccine delivery system (ASP-PLGA/OVA). These formulations were subcutaneously administered to mice, then the magnitude and kinetics of antibody and cellular immune responses were assessed. The ASP-PLGA/OVA NPs were pherical in shape with smooth surfaces, approximately 225.2 nm in average size, negatively charged (around −11.27 mV), and the encapsulation efficiency of OVA at around 66.28%, respectively. Furthermore, ASP-PLGA/OVA NPs could keep stable at 4 °C over 30 days and provide a sustained and controlled release of OVA from the NPs. The results demonstrated that mice immunized with ASP-PLGA/OVA NPs could significantly enhance lymphocyte proliferation and improve the ratio of CD4+ to CD8+ T cells, thereby ASP-PLGA/OVA NPs could induce a strong cellular immune response. Moreover, the ASP-PLGA/OVA NPs could induce vigorous and long-term IgG immune responses with a mixed Th1 and Th2 responses and up-regulate the levels of Th-associated cytokines. These results suggested that ASP-PLGA/OVA NPs, which stimulated strong and continuous antibody responses and induced cellular immune responses, could potentially serve as an efficient and safe vaccine delivery and adjuvant system against infections and diseases. [ABSTRACT FROM AUTHOR]

Abstract The immunoregulation and immunopotentiation of Polysaccharides of Atractylodes macrocephala Koidz (PAMK) have been widely demonstrated. Nanostructured lipid carriers (NLC) have high drug loading capacity for lipophilic and hydrophilic drugs, and have good biocompatibility and high bioavailability. In this study, the effect of PAKM-NLC on the surface molecule expression of bone marrow-derived dendritic cells (BMDCs) in vitro was investigated by flow cytometry, and the cytokines secreted by dendritic cell supernatants were detected by ELISA. The results showed that compared with other control groups, PAMK-NLC could significantly increase the expression of CD80 and CD86 and promote the secretion of IL-1β, IL-12, TNF-α and IFN-γ, indicating that PAMK-NLC have a more pronounced effect on the maturation and differentiation of BMDCs. In addition, effects of PAMK-NLC nanoparticles on OVA-immunized mice were explored. Compared with other control groups, PAMK-NLC-OVA can significantly promote the production of OVA-specific antibodies in serum, stimulate the secretion of cytokines, increase the proliferation rate of spleen lymphocytes after OVA re-stimulation, and induce stronger activation of CD3+CD4+ and CD3+CD8+ lymphocytes. As an adjuvant of OVA, PAMK-NLC has a better immunological enhancement effect than PAMK or blank NLC, and has good adjuvant activity. [ABSTRACT FROM AUTHOR]

Abstract For quantitative assaying tylerdipine hydrochloride, and its two primary metabolites (M2 and M4) in human urine, two sensitive and accurate LC-MS/MS methods were firstly developed and validated, where multiple reaction monitoring (MRM) was applied under positive electrospray ionization mode for tylerdipine and negative electrospray ionization mode for M2/M4, respectively. Urinary proteins were precipitated using acetonitrile, and deuterated isotopes of tylerdipine and M4 ([D5]‑tylerdipine and [D6]-M4) were used as internal standards. Triton X-100, a good surfactant, was used to prevent the adsorption. An Agilent Poroshell 120 column was employed for chromatographic separation of the analytes with the mobile phases of 2 mM ammonium formate solution (containing 0.1% formic acid) and acetonitrile (45:55 for tylerdipine and 75:25 for the M2/M4, v/v). Flow rate was 0.3 mL/min. Calibration curves for tylerdipine, M2 and M4 in urine were linear over the ranges of 0.02–10 ng/mL, 2–1500 ng/mL and 0.5–200 ng/mL, respectively. The precision, accuracy, specificity and stability of two methods all evaluated and achieved the acceptable criteria. The LC-MS/MS methods were successfully applied to assay urinary excretion of tylerdipine and the metabolites in healthy Chinese subjects who orally received a single dose of 20 mg tylerdipine tablet. Generally, the urinary excretion of the two primary metabolites accounted for 11.7% of the total dose of tylerdipine in healthy Chinese subjects, while little tylerdipine was recovered in urine. Highlights • LC-MS/MS methods were firstly developed and validated for assaying urinary tylerdipine and its two metabolites in human. • The methods were applied to evaluate urinary excretion of tylerdipine and its two metabolites in healthy Chinese subjects. • The urinary excretion of the two metabolites accounted for 11.7%, while little tylerdipine was recovered in human urine. [ABSTRACT FROM AUTHOR]

In this study, angelica sinensis polysaccharide (ASP) was encapsulated into the Poly (lactic-co-glycolicacid) (PLGA) to constitute the ASP-PLGA. The aim of the study is to obtain optimal encapsulation efficiency of ASP-PLGA by optimizing the preparation conditions and investigate the immunological enhancement activity of ASP-PLGA. To obtain the optimal processing parameters, the parameters, such as the ratio of organic phase (o) to internal water phase (w 1 ), the ratio of external water phase (w 2 ) to organic phase (o) and the concentration of Pluronic F68 (F68) (w/v) were examined through response surface methodology (RSM). The optimum preparation conditions of ASP-PLGA for maximizing encapsulation efficiency (EE) was as follows:ratio of organic phase (o) to internal water phase (w 1 ) at 10:1, ratio of external water phase (w 2 ) to organic phase (o) at 11:1, the concentration of F68 at 0.8% and the experimental EE 67.89 ± 0.48% was achieved. In addition, the results showed that ASP-PLGA could significantly promote the lymphocytes proliferation and increase the ratio of CD4 + to CD8 + T cells compared with ASP and blank PLGA. This study provided strong evidence that the immunological enhancement of ASP was significantly improved through establishing a drug delivery system with PLGA. [ABSTRACT FROM AUTHOR]

Powder plasma arc additive manufacturing (PPA-AM) is a promising method for the preparation of high-entropy alloys (HEAs), and has the advantages of low cost, high efficiency, and high quality. In this study, the CoCrFeNiW x (x = 0, 0.2, 0.5, 0.7, and 1.0) HEAs were successfully prepared via the PPA-AM technique. Microstructure and mechanical properties of alloys with different W content were investigated. The results showed that the microstructure changed from a single FCC phase (x = 0) to the dual-phase FCC + µ (x = 0.2 and 0.5), and then to a three-phase combination of FCC + µ + BCC (x = 0.7 and 1.0) with the addition of W. The volume fraction of the µ phase and BCC phase increases with the increase in W content, while the size of FCC columnar grain is significantly reduced. The solid-solution strengthening of the FCC phase and the second phase strengthening were mainly responsible for the increase in the microhardness (136–413 HV) and yield strength (187–567 MPa) while the brittleness of the μ phase contributes to the expansion of the crack, which leads to a decrease in the ductility (50.8% to 0.3%). These results can provide a systematic understanding of the phase transformation of PPA-AM HEAs with different W content and its effects on the mechanical properties. • Powder plasma arc additive manufacturing (PPA-AM) of CoCrFeNiWx high-entropy alloys. • PPA-AM can produce high-entropy alloys with lower cost and high efficiency. • The microstructure and mechanical properties of the CoCrFeNiWx HEAs were investigated. • W element can promote the phase transformation from FCC phase to µ and BCC phase. • The strength of the HEAs was significantly improved with addition of W. [ABSTRACT FROM AUTHOR]

Powder plasma arc additive manufacturing (PPA-AM) is a promising method for fabricating high-entropy alloys (HEAs). However, the characteristics of thermal cycling during the PPA-AM process and the mechanism of subsequent heat treatment on the microstructure and mechanical properties are unclear. In this study, an Al 1.2 CoCrFeNi 2.1 HEA with dual-phase (FCC + B2) was fabricated via PPA-AM. The microstructure and mechanical properties of the as-built and heat-treated samples were explored. The crystallographic orientations of the FCC and B2 phases were also determined. Because the alloy in the bottom region was affected by thermal cycling, B2 particles precipitated in the FCC phase, and FCC particles precipitated in the B2 phase. During the tensile test, the phase boundary between B2 matrix and FCC particles produced cracks preferentially. These cracks reduced the strength and elongation of the alloy. After heat treatment at 1200 °C, the FCC and B2 precipitates formed globular shapes inside the B2 and FCC grain matrix, respectively. The alloy showed a uniform structure and the ductility of the alloy was improved significantly. This work elucidates the mechanisms of thermal cycling and heat treatment on the microstructure and mechanical properties of the alloy. [ABSTRACT FROM AUTHOR]

• AlCoCrFeNi 2.1 high-entropy alloy was fabricated by PPA-AM method. • The B2 phase precipitates at the bottom region of the HEA due to thermal cycling. • The ductility of the HEA increases and the strength decreases due to thermal cycling. High-entropy alloys (HEAs) are a novel class of materials. In this study, the AlCoCrFeNi 2.1 HEA was prepared using powder plasma arc additive manufacturing (PPA-AM). The influence of thermal cycling in the PPA-AM process on AlCoCrFeNi 2.1 HEA was investigated. The AlNi elements in the FCC phase in the bottom region were aggregated by thermal cycling to form the acicular B2 particles. This weakened the solid solution strengthening effect of the FCC phase, reduced its yield strength (421 to 389 MPa), and improved its ultimate tensile strength (929 to 981 MPa) and elongation (15.6 % to 21.0 %). The results of this study might have reference significance for the AlCoCrFeNi alloy system. [ABSTRACT FROM AUTHOR]

High-entropy alloys (HEAs) are promising coating materials for wear resistance applications. However, the preparation of HEA coatings with powder has the disadvantages of high cost and low efficiency. In this study, an innovative triple-wire plasma arc cladding (TW-PAC) method was used to prepare HEA coatings. Nonequiatomic Cr-Fe-Ni-Ti x (x is Ti wire feeding speed, x = 0, 0.5, 0.8 and 1.0 m/min, denoted as Ti 0 , Ti 0.5 , Ti 0.8 and Ti 1.0) HEA coatings were successfully prepared by using three commercial wires (ERTi-2, ER304L and Cr 20 Ni 80 wire). With increasing Ti content, the structure of the Cr-Fe-Ni-Ti x HEA coatings changed from the single FCC phase to the FCC + γ′ (Ni 3 Ti) + Laves (Fe 2 Ti) phase, and the microhardness of the coatings increased from 137 HV to 873 HV. Due to the addition of Ti, Ni 3 Ti and Fe 2 Ti phases with high hardness precipitated in the alloy coating, accompanied by the solid solution strengthening effect of the FCC phase, the wear resistance of the coatings was significantly improved (from 9.67 × 10−4 to 1.49 × 10−4 mm3/N·m). The results of this study contribute to the preparation of thick HEA coatings overlarge areas at low cost and with high efficiency and provide new insights into Cr-Fe-Ni-Ti x HEA coatings. • Triple-wire plasma arc cladding (TW-PAC) of Cr-Fe-Ni-Tix high-entropy alloy coatings. • High-entropy alloy coatings were prepared using three commercial wires. • The phase of the coatings changed from FCC to FCC + Ni 3 Ti + Fe 2 Ti with the addition of Ti. • The wear resistance of the coatings was significantly improved with addition of Ti. [ABSTRACT FROM AUTHOR]

Sitafloxacin is a new fluoroquinolone antimicrobial agent with high activity. In this article, we reported a simple, rapid and specific LC–MS/MS method for accurate determination of sitafloxacin concentrations in human urine from healthy volunteers in detail. A two-step dilution method for the analysis of sitafloxacin in human urine using LC coupled to positive MS/MS has been developed and validated according to US FDA guidelines and Chinese State Food and Drug Administration (CFDA) guidelines for the validation of bioanalytical methods. The method uses 50 μL of urine and covers a working range from 0.025 to 20 μg/mL with a LLOQ of 0.025 μg/mL. This new LC–MS/MS assay is sensitive and specific. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to develop a rapid and sensitive method for the simultaneous quantification of metronidazole (MEZ), tinidazole (TNZ), ornidazole (ONZ) and morinidazole (MNZ) in human saliva. A reversed-phase high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection at 318nm was carried out on a C18 column, using a mixture of potassium dihydrogen phosphate buffer, acetonitrile, and methanol (55:15:30, v/v/v) as a mobile phase with a flow rate of 1.0ml/min. The saliva samples (100μl) were firstly deproteinized by precipitation with methanol (400μl), after which they were centrifuged and the supernatants were directly injected into the HPLC system. This method produced linear responses in the concentration ranges of 25.2–5040.0, 23.9–4790.0, 25.4–5080.0, 25.0–5000.0ng/ml with detection limits of 6.0, 17.6, 10.0 and 11.3ng/ml for MEZ, TNZ, ONZ and MNZ (S/N=3), respectively. The methods were validated in terms of intra- and inter-batch precision (within 7.3% and 9.1%, respectively), accuracy, linearity, recovery and stability. The study proved that HPLC is both sensitive and selective for the simultaneous quantification of MEZ, TNZ, ONZ and MNZ in human saliva using a single mobile phase. [Copyright &y& Elsevier]

Abstract: A specific and sensitive liquid chromatography electrospray ionization tandem mass spectrometric (LC–ESI-MS/MS) method for quantitative determination of sertaconazole in human plasma was developed. The analysis was performed and validated in positive ion multiple reactions monitoring mode using loratadine as an internal standard (IS). Sample preparation involved one-step liquid–liquid extraction using ether–dichloromethane (80/20, v/v). Sertaconazole and IS was separated on a C18 column using isocratic elution with a mobile phase of methanol: 0.2% formic acid aqueous solution (70:30, v/v,) at the flow rate of 0.2mL/min. The transition monitored were m/z 439 [M+H]+ → m/z 181 for sertaconazole and m/z 383[M+H]+ → m/z 337 for IS. The lower limit of quantification was 0.1ng/mL based on 500μL of plasma, and no interferences were detected in chromatograms. Calibration curve was linear over the range of 0.1–10ng/mL, and correlation coefficients were 0.999. Intra- and inter-day assay variations were <10%, and the accuracy values were between −0.4% and 9.0% relative error (RE). The extraction recoveries ranged from 60% to 70% across the calibration curve range. The described method provides a sensitive analytical tool to determine sertaconazole in plasma, and was successfully applied to a pharmacokinetic study in 10 healthy human subjects after administration of 300mg vaginal suppository formulation of sertaconazole nitrate. [Copyright &y& Elsevier]