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Chinese yam polysaccharides (CYP) exhibit superior adjuvant activity and modulate the immune response, but the low bioavailability limits their clinical application. Pickering emulsions have been proven as an efficient vaccine delivery system to enhance the immune response. Here, we used the Chinese yam polysaccharides PLGA-stabilized Pickering emulsion adjuvant system (CYP-PPAS) loaded with Porcine circovirus 2 as a vaccine and focused on investigating its adjuvant activity on humoral and cellular immunity in mice. The CYP-PPAS increased PCV-2 antigen loading efficiency and showed a high antigen uptake efficiency by macrophages in vitro. In vivo, CYP-PPAS significantly facilitated DCs maturation in draining lymph nodes than CYP or PPAS alone group. The CYP-PPAS also induced an increased proliferation index and a CD4

Directional solidification of Ti–46Al–8Nb (at.%) intermetallic in the Y2O3 doped BaZrO3/Al2O3 composite ceramic mould was carried out using Bridgman apparatus. To increase the success rate of Ti–46Al–8Nb single crystals preparation and improve the quality of the ingots, the failure mechanism of the mould in directional solidification experiments was evaluated. Nucleation and propagation of cracks in the moulds were investigated by tracing each key process of the experiment, the effect of pores in the mould on the target alloy was revealed by studying the mould/metal interface. The results show that the macrocracks in the facecoat of the mould would lead to the leakage of the alloy melt. Furthermore, the alloy melt would infiltrate into the mould through large-size pores, which would increase the oxygen content of the target alloy, and also form inclusions containing O, Zr, Si and Y elements in the alloy ingot.

Clinical management of chronic hepatitis B (CHB) virus infection remains a big challenge and urges the development of novel therapeutics to achieve long-term virological control and seroconversion. In this study, we report on the development and evaluation of a highly efficacious therapeutic mRNA vaccine encoding the full-length hepatitis B virus (HBV) surface antigen (HBsAg). In pAAV-HBV1.2 and rAAV8-HBV1.3-transduced CHB mouse models, the HBV mRNA vaccine demonstrated potent therapeutic efficacy indicated by a complete serum viral clearance, a remarkable decline in intrahepatic HBcAg, viral DNA and RNA copies, as well as the induction of robust levels of anti-HBs antibodies, virus-specific T cells and memory B cells. In addition, the HBV mRNA vaccine induced strong innate immune activation, represented by the maturation of CD8α+and CD103+cDC1, CD11b+cDC2, monocytes and neutrophils. Taken together, the HBV mRNA vaccine is a promising therapeutic candidate holding prospect for further development and clinical investigation.

In this study, ramulus mori polysaccharide (RMP) was encapsulated into Poly (lactic-co-glycolicacid) (PLGA) to form PLGA-RMP (PR). The aim of study is to investigate anti-inflammatory effects of PR. The particle size of PR nanoparticles was approximately 205.6 ± 1.86 nm. PR nanoparticles showed significant therapeutic effects on colitis mice model, evidenced by attenuation of the loss of body weight, reduction of the DAI score, and restoration of the colon length. From the histopathological analysis, alleviation of the histopathological damage, less production of IFN-γ and IL-6, and improvement of IL-10 were observed with the treatment of PR. Meanwhile, the treatment of PR not only promoted the expression of ZO-1 and occludin, but also improved the contents of acetate, propionate, and butyrate in the colitis colon. Furthermore, PR extenuated the reduction of the diversity and richness of gut microbiota induced by DSS, and decreased the ratio of Firmicutes to Bacteroidetes while increasing the proportion of Clostridium XIVa, Mucispirillum, and Paraprevotella in the gut microbiota. What's more, PR nanoparticles attenuated the metabolic disorders in the colitis colon induced by DSS. These results indicated that PR nanoparticles could serve as a potent nanomedicine to treat IBD and be used as potential prebiotics.

The purpose of the study was to establish a comprehensive differential gene profile for lung cancer patients treated with cisplatin compared with control patients without any chemotherapy drug treatment. The RNA sequencing data and miRNA sequencing data of 108 lung cancer patients treated with cisplatin only and 232 lung cancer patients treated without any chemotherapeutic drugs, were analyzed using differential expression, protein-protein interaction, and immune cell infiltration ratio analysis. Compared with control patients, the cisplatin-treated patients demonstrated 336 differentially expressed genes, which included 48 upregulated genes and 288 downregulated genes. Meanwhile, 12 differentially expressed miRNAs (DEMs), including 7 upregulated miRNAs and 5 downregulated miRNAs showed a differentially expressed pattern. With further instigation, five miRNAs (hsa-miR-548ah, hsa-miR-466, hsa-miR-552, hsa-miR-371a, and hsa-miR-4445) were suggested to be the key targets in the cisplatin-treated patients. At the same time, we also found a significant correlation between the cisplatin treatment and six immune checkpoints including programmed cell death ligand. This study helped us better understand the potential targets and underline molecular mechanisms for cisplatin treatment and provided references to eliminate existing side effects in the future.

In many clinical studies, prebiotics have been used as adjuvant therapy for inflammatory bowel disease (IBD). Phellinus igniarius polysaccharide (PIP) possesses great anti-inflammatory and prebiotic activities. Herein, we developed an orally deliverable PIP-loaded chitosan-modified PLGA nanomedicine (CS-PIPP) to investigate its anti-inflammatory effect in vitro and in vivo. Dextran sodium sulfate (DSS)-induced colitis model was established to evaluate the preventive effect of CS-PIPP on IBD. This study characterized that CS-PIPP had a size of 288.7 ± 5.49 nm, positive zeta potential, and showed good stability over four weeks. The in-vitro study suggested that CS-PIPP had enhanced phagocytosis by macrophages, which could further significantly inhibit M1-like macrophages phenotype and regulate lipopolysaccharide (LPS)-induced inflammatory cytokines. The in-vivo study revealed that CS-PIPP prominently prevented intestinal inflammatory damage and protected the integrity of the intestinal barrier. Moreover, CS-PIPP increased the contents of short-chain fatty acids (SCFAs) and positively regulated the gut microbiota. Specifically, CS-PIPP reduced enteropathogenic microorganisms while increasing the beneficial microbiota, including Lactobacillus and Akkermansia, which revealed the potential of CS-PIPP as prebiotics. Generally, CS-PIPP promoted the anti-inflammatory effect of PIP, so it could be regarded as a novel and potent nanoformulation to treat IBD.

The Chinese yam polysaccharides PLGA nanoparticles were applied as stabilizers in this study to prepare O/W Pickering emulsion. The optimized preparation conditions were PLGA concentration of 5 mg/mL, ultrasonic power of 50 %, and ultrasonic time of 2 min. The CYP-PPAS emulsion exhibits a raspberry-like morphology with a large number of nanoparticles surrounding the oil droplets. The CYP-PPAS emulsion exhibited outstanding stability at 4 °C and 37 °C for 28 days with high antigen loading efficiency and provided a controlled and sustained release of Chinese yam polysaccharides and OVA antigen in vitro. CYP-PPAS/OVA elicited robust antigen-specific immune response and induced a mixed Th1/Th2 immune response after immunization. Furthermore, CYP-PPAS/OVA caused a high CD4+/CD8+ ratio leading in increased activation of splenic T lymphocytes subpopulations. Moreover, CYP-PPAS is a safe vaccination adjuvant with high safety profile in vivo. Thus, the novel designed Pickering emulsion CYP-PPAS was a safe and effective adjuvant for inducing the strong and long-term immune response.

Pickering emulsion has great potential as a vaccine adjuvant due to its unique advantages such as its high antigen loading efficiency, great stability, etc. Among several adjuvants on the market, aluminum adjuvant (Alum) is the most widely used at present. However, problems such as the inability to effectively induce cellular immunity and the poor effect on subunit vaccines limit the application of Alum. As an immunopotentiator, Lycium barbarum polysaccharides (LBP) have been proven to have the ability to regulate humoral and cellular immunity. To overcome the insufficiency of Alum, we explored a new adjuvant delivery system. The Lycium barbarum polysaccharides-loaded Particulate Alum via Pickering emulsion (LBPPE) was prepared by loading Alum on the squalene/water interphase following LBP was adsorbed on the Alum surface (Fig. 10). Similar to squalene, LBPPE possesses a good biosafety profile. LBPPE was spherical with uneven surface, which increased the possibility of efficient antigen adsorption on the surface and crack of LBPPE. And the result shown that the LBPPE had high antigen loading rate at approximately 90 %. In vivo experiments, LBPPE showed an excellent ability to recruit antigen-presenting cells (APCs) at the injection sites, activate dendritic cells in the lymph nodes. Then, in the evaluation of humoral immunity, LBPPE was able to effectively induce the production of IgG, IgG1, and IgG2a. Moreover, LBPPE significantly enhanced the expression and activation of T lymphocytes, and induced a strong immune memory T cells response. All the results above suggested that LBPPE is likely to provide promising insights toward a safe and efficient adjuvant platform for vaccines.

Ramulus mori polysaccharide (RMP), one of the most important active components of R. mori, has been attracting increasing interest because of its potent bioactive properties, including anti-inflammatory, antitumor, and antidiabetic effects. Despite the great therapeutic potential of RMP, its inherent properties of low bioavailability and brief biological half-life have limited its applications to the clinic. Thus, RMP was packaged by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to develop a novel anti-inflammatory nanomedicine (PLGA-RMP) in this study. The nanoparticles were synthesized via a double-emulsion solvent evaporation technique, and the average diameter of PLGA-RMP was about 202 nm. PLGA-RMP nanoparticles reduced the expression of inflammatory cytokines while promoting the production of IL-10, and boosted the phenotypic shift in macrophages in vitro. Furthermore, lipopolysaccharide (LPS)-induced inflammatory bowel disease (IBD) in mouse was used to examine the anti-inflammatory effect of PLGA-RMP in vivo. Oral administration of PLGA-RMP in LPS-induced IBD mice substantially mitigated the intestinal inflammation compared to treatment with LPS alone, as evidenced by attenuation of disease activity index scores and inflammatory damage in the intestine. Meanwhile, PLGA-RMP suppressed the expression and secretion of specific inflammatory cytokines including TNF-α, IL-6, IL-1β, and PGE2 in the inflamed intestine while inhibiting the activation of CD3+CD8+ T-cells and increasing the number of activated Tregs in the intestine. These results indicated that PLGA-RMP deserves further consideration as a potential therapeutic nanomedicine to treat various inflammatory diseases, including IBD.

Graphite crucible is widely used in high temperature viscosity measurement due to its low cost. However, it may cause measurement errors because of contamination with fine graphite particles, non-wetting conditions, or chemical reactions between melt and graphite. In order to clarify the effect of graphite crucible on viscosity measurement, in this work, more than 800 compositions and 3300 viscosity measurements within CaO-MgO-Al2O3-SiO2 systems were collected and analyzed, using a statistical and modeling-based way. It is found the viscosity data obtained in graphite crucible show much larger scatter than those obtained in metal crucibles. Averagely, viscosity obtained in graphite crucible is 24% higher. The chemical reaction SiO2(l) + 3C(s) = SiC(s) + 2CO(g) is the primary error source for viscosity measurement in graphite crucible. It is suggested that the viscosity data obtained in graphite crucible can be used only with great caution.

BACKGROUND This work aimed to screen key biomarkers related to sepsis progression by bioinformatics analyses. MATERIAL AND METHODS The microarray datasets of blood and neutrophils from patients with sepsis or septic shock were downloaded from Gene Expression Omnibus database. Then, differentially expressed genes (DEGs) from 4 groups (sepsis versus normal blood samples; septic shock versus normal blood samples; sepsis neutrophils versus normal controls and septic shock neutrophils versus controls) were respectively identified followed by functional analyses. Subsequently, protein-protein network was constructed, and key functional sub-modules were extracted. Finally, receiver operating characteristic analysis was conducted to evaluate diagnostic values of key genes. RESULTS There were 2082 DEGs between blood samples of sepsis patients and controls, 2079 DEGs between blood samples of septic shock patients and healthy individuals, 6590 DEGs between neutrophils from sepsis and controls, and 1056 DEGs between neutrophils from septic shock patients and normal controls. Functional analysis showed that numerous DEGs were significantly enriched in ribosome-related pathway, cell cycle, and neutrophil activation involved in immune response. In addition, TRIM25 and MYC acted as hub genes in protein-protein interaction (PPI) analyses of DEGs from microarray datasets of blood samples. Moreover, MYC (AUC=0.912) and TRIM25 (AUC=0.843) had great diagnostic values for discriminating septic shock blood samples and normal controls. RNF4 was a hub gene from PPI analyses based on datasets from neutrophils and RNF4 (AUC=0.909) was capable of distinguishing neutrophil samples from septic shock samples and controls. CONCLUSIONS Our findings identified several key genes and pathways related to sepsis development.

Recently, the recycle of TiAl scrap becomes an important issue; however, its high oxygen content, which deteriorates mechanical properties, should be deoxidized. In this study, the scrap of TiAl alloy is melted using the water-cooling copper crucible, then the metallic yttrium and calcium fluoride slag are added on this melt. The deoxidation behavior of scrap is investigated, and the change of oxygen concentration is measured to evaluate the performance of this novel deoxidation technology. The results showed that the oxygen content of TiAl alloys under atmospheric pressure varied between 0.169 and 0.182 wt%. When the sample cell was vacuumed, the oxygen content varied between 0.131 and 0.167 wt%. In addition, the TiAl alloy contains a certain amount of element Y after deoxidation. This fact shows that the metallic yttrium and calcium fluoride slag exhibit a good deoxidation for the TiAl alloy melts. It may be one of the promising deoxidation processes of scrap of TiAl alloy.

Lentinan (LNT), a β-1,3-linked-d-glucan with β-1,6 glucose branches, is the main bioactive component extracted from Lentinus edodes. As a carbohydrate polymer, it has attracted increasingly attention because of immune enhancement effect. Pickering emulsion has been widely used in biomedicine due to its great stability, high loading capacity, and appreciable biocompatibility. The aim of this study is to construct an adjuvant delivery system (LNTPP/OVA) (Lentinan PLGA-stabilized Pickering emulsion loading OVA antigen) which can enhance the immune activity of LNT and can together deliver model protein antigen ovalbumin (OVA) into the organism. The characterization of the LNTPP/OVA was demonstrated that the size of LNTPP/OVA was around 1050.68 nm and was stable to store at least 28 days. Pickering emulsion was spherical shape like the raspberry with the high antigen load rate at around 82.53%. Moreover, the adjuvant effect of LNTPP/OVA formulation was detected. Compared with LNT/OVA formulation, our experimental results showed that LNTPP/OVA could promote the uptake of the OVA-antigen by macrophages in vitro. In vivo experiments, LNTPP/OVA facilitated the activation of dendritic cells (DCs) and induced strong humoral and cellular immune responses carrying a Th1 and Th2 immune responses. Therefore, LNTPP/OVA formulation have the latent capacity as a vaccine transmission system.

Processes that control the distribution and natural attenuation (NA) of petroleum hydrocarbons dissolved from the released diesel fuel in a bench-scale model aquifer were evaluated. The experimental results obtained in two-dimensional aqueous-phase petroleum hydrocarbon concentrations indicated that the total petroleum hydrocarbon (TPH) in the aquifer migrated in longitudinal and lateral directions. The TPH plume of 2 mg L−1 spread to the entire area of the aquifer, and the maximum concentration at the center of the plume was 44.15 mg L−1 after 90 days of release. After diesel fuel release, the NA of TPH was evaluated and quantified. Experimental data indicated that the NA of TPH was immediately implemented to prevent migration of the plume into the downgradient of the aquifer, but controlling the TPH plumes using NA mechanisms requires a long time.

To analyze and evaluate the distribution network failure interruption, this paper establishes the comprehensive evaluation index power distribution network failure interruption. By using the normal cloud model, this paper also realizes the risk evaluation of power distribution network fault. First, fault risk sources are classified and divided into internal risk sources and external risk sources. Based on this, key risk sources are identified. Then, risk indices of the distribution network fault are analyzed, and the comprehensive evaluation index system is established. By using the characteristics of the normal cloud model, this paper proposes a risk evaluation method based on the normal cloud model for the distribution network. This paper takes a city in the southeast of China as a sample. This method is verified, and some advices for distribution network operation maintenance are proposed. Practice proved that the normal cloud model failure risk evaluation overcomes uncertainty, random and fuzzy problems of the indicators value. This method can carry on the reasonable evaluation of distribution network power failure interruption.

Near-field subwavelength imaging has been realized at visible and mid-infrared frequencies, but it has not been achieved at near-infrared (NIR). In this work, the transparent conducting oxides (TCO)-based near-field superlenses working at NIR frequencies were proposed. As one of easily available TCO materials, Al-doped ZnO (AZO) was considered in both stratified ZnO-AZO-ZnO and single-layered AZO structures, which had the subwavelength resolution of better than λ/25 at a wavelength of 2.57μm andλ/20 at 2.01μm, respectively. These findings reveal that the TCO can find the applications not only in liquid-crystal displays, photovoltaic devices, and electromagnetic interface shielding, but also in superresolution and subsurface imaging at NIR frequencies.

Based on the first-principles density functional theory with plane wave ultrasoft and norm-conserving pseudo- potential methods, the elasticity and hardness of the three selected bc-B n CN ( n =1, 2, 4) are investigated in details using LDA and GGA potential field. In addition, we pay close attention to their otherness of elastic and plastic anisotropies. The calculated results prove that these three kinds of structures are all stable in thermodynamics. Among these three structures, bc-BCN, which has the maximum absolute values of formation enthalpy and cohesive energy, is the most stable one with the lowest rate of atom B. And the reason why bc-BCN is the most resisting structure and has the largest absolute value of energy is that it owns large number of relatively low energy bonds such as B—N, B—C, C—N bonds and the fewest of B—B bond. The analysis of elasticity and hardness results shows that the values of elastic modulus and hardness decrease accordingly with the increasing ratio of atom B in the system. Then in line with the universal elastic anisotropic index A U, percent elastic anisotropy A B and A G, and shear anisotropic factors A 1, A 2 and A 3 of bc-B n CN ( n =1, 2, 4), it is revealed that all of the three structures show different extent of anisotropy. Among these, bc-BCN displays better anisotropic property than c-BN as a whole. Finally, the ideal stress-strain curves of bc-B n CN ( n =1, 2, 4) are fitted through the simulation of stepped tensile and shear deformation, and it indicates the anisotropy during deformation process. What’s more, the matched curves reveal their respective yield surfaces, which are the easiest to slide. Additionally, the most effortless slip directions of different structures are deduced explicitly. In general, bc-BCN is the most easily to synthesize and most suitable for applications among these three compounds.