Comparison of proteomic landscape of extracellular vesicles in pleural effusions isolated by three strategies

Extracellular vesicles (EVs) derived from pleural effusion (PE) is emerging as disease biomarkers. However, the methods for isolation of EVs from PE (pEVs) were rarely studied. In our study, three methods for isolating pEVs of lung cancer patients were compared, including ultracentrifugation (UC), a combination of UC and size exclusion chromatography (UC-SEC) and a combination of UC and density gradient ultracentrifugation (UC-DGU). The subpopulation of pEVs was identified by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), Western blotting (WB) and nano-flow cytometry (nFCM). Additionally, the proteomic landscape of pEVs was analyzed by Label-free proteomics. The results showed that, compared with UC and UC-DGU, the UC-SEC method separated pEVs with the highest purity. In the proteomic analysis, on average, 1595 proteins were identified in the pEVs isolated by UC-SEC, much more than pEVs isolated by UC (1222) or UC-DGU (807). Furthermore, approximately 90% of identified proteins in each method were found in the EVs public database ExoCarta. Consistent with this, GO annotation indicated that the core proteins identified in each method were mainly enriched in “extracellular exosome.” Many of the top 100 proteins with high expression in each method were suggested as protein markers to validate the presence of EVs in the MISEV2018 guidelines. In addition, combined with lung tissue-specific proteins and vesicular membrane proteins, we screened out and validated several novel protein markers (CD11C, HLA DPA1 and HLA DRB1), which were enriched in pEVs rather than in plasma EVs. In conclusion, our study shows that the method of UC-SEC could significantly improve the purity of EVs and the performance of mass spectrometry-based proteomic profiling in analyzing pEVs. The exosomal proteins CD11C, HLA DPA1 and HLA DRB1 may act as potential markers of pEVs. The proteomic analysis of pEVs provides important information and new ideas for studying diseases complicated with PE

Effect of Hyperglycemia at Presentation on Outcomes in Acute Large Artery Occlusion Patients Treated With Solitaire Stent Thrombectomy

Background: Sporadic data showed hyperglycemia at presentation is associated with poor outcomes in patients with acute ischemic stroke (AIS) under mechanical thrombectomy (MT) treatment.Objective: This study aims to evaluate the relationship of admission hyperglycemia and outcomes in patients treated with solitaire stent thrombectomy.Methods: This multicenter prospective study registered patients with AIS due to anterior circulation large vessel occlusion (LVO) suitable for MT with Solitaire stent retriever. We analyzed the influence of admission hyperglycemia (≥7.8 mmol/L) and serum glucose on functional independence which is defined as modified Rankin Scale score (mRS) of 0–2, symptomatic intracranial hemorrhage (sICH) and several outcomes of interest using univariable and multiple logistic regression analysis.Results: This study involved 17 stroke centers across China and consecutively recruited 149 patients. Patients with hyperglycemia at presentation less frequently exhibited a functional independence at 3 months than patients without hyperglycemia (22.2 vs. 66.4%; odds ratio 0.75, 95% confidence interval 0.61–0.92; P = 0.005). Higher glucose levels were correlated with worse outcome (per 1 mmol/L increase in glucose: odds ratio for mRS score 0–2 at 3 months 0.17, 95% confidence interval 0.06–0.45; P < 0.001) at 3 months and sICH (per 1 mmol/L increase in glucose: odds ratio for sICH was 8.2, 95% confidence interval 1.13–29.57; P < 0.001) after thrombectomy.Conclusions: Higher admission serum glucose and hyperglycemia were independently correlated with lower functional independence at 3 months in patients treated with Solitaire stent thrombectomy of anterior circulation LVO. Higher admission serum glucose was also associated with sICH after thrombectomy

Influence of hydroxypropyl methylcellulose, methylcellulose, gelatin, poloxamer 407 and poloxamer 188 on the formation and stability of soybean oil-in-water emulsions

Macromolecules of polysaccharides, proteins and poloxamers have a hydrophobic portion and a hydrophilic one that can be used as emulsifiers. Parts of these emulsifiers are safe pharmaceutical excipients, which can replace the irritant low molecular weight surfactants to formulate emulsions for the pharmaceutical field. This project focused on preparing O/W emulsions stabilized with polymers for pharmaceuticals such as polysaccharides, proteins and poloxamers, including hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), gelatin, poloxamer 407 (F127) and poloxamer 188 (F68). Emulsion physical stability was assessed by centrifugation, autoclaving sterilization and droplet size measurements. The stabilization mechanisms of emulsions were determined by interfacial tension and rheological measurements. Results stated that the efficacy of these polymers for pharmaceuticals stabilized emulsions was sorted in the order: F127 > F68 > HPMC > MC > Gelatin

Fabrication and Mechanical Properties of High-Durability Polypropylene Composites via Reutilization of SiO2 In-Situ-Synthesized Waste Printed Circuit Board Powder

This paper focuses on the characterization of the physico-chemical properties, surface modification, residual copper content and in situ hybrid inorganic particle modification of polypropylene (PP) composites reinforced by waste printed circuit board powder (WPCBP). A series of WPCBP/SiO2 hybrids (TSW) were prepared by a sol–gel method at different pH values. Characterization results revealed the in situ generation of SiO2 on the surface of WPCBP, and showed that with an increase in pH value, the size of SiO2 particles increased gradually and the copper content decreased in the TSW powder. The mechanical properties, oxidation induction time (OIT) and thermal properties of PP composites were improved by reinforcement with TSW, which might be ascribed to the formation of serrated interfaces. This work not only develops a powerful method to enhance the properties of PP/WPCBP composites, but also provides an environmentally sustainable approach to the high-added-value reutilization of WPCBP

The Geological History of the Chang’e-5 Sample Return Region

Chang’e-5 (CE-5), China’s first sample-return mission, has successfully landed in Oceanus Procellarum near Mons Rümker. It is important to have a detailed study of the geological evolution of the CE-5 sample return region. This work aims to study the geological background, topography, geomorphology, major chemical composition, mineralogy, and chronology of the landing site region. First, we used the map of topography obtained by the Kaguya TC merged Digital Terrain Model (DTM) to analyze the topographic characteristics. Then, we used the Kaguya Multiband Imager (MI) reflectance data to derive FeO and TiO2 abundance and the hyperspectral data of the Moon Mineralogy Mapper (M3) onboard the Chandrayaan-1 spacecraft to study the mineralogy of the landing site region. Later, we defined and dated the geological units of the landing area using the crater size–frequency distribution (CSFD) method. Finally, we conducted a detailed analysis of the volcanism and tectonism that occurred in the CE-5 landing area. The study region has experienced multi-stage magmatic activities (~3.36 Ga to ~1.22 Ga) and formed multiple mare units with different chemical and mineral compositions. The relationship between the wrinkle ridges cut by small impact craters suggests that the U7/Em5 has experienced Copernican aged tectonism recently ~320 Ma. The U7/Em5 unit where the Chang’e-5 sample return mission landed is dominantly composed of mature pyroxene and the basalts are mainly high-iron and mid-titanium basalts. Additionally, the analysis of pure basalt in the U7/Em5 suggests that the samples returned by the CE-5 mission may contain the ejecta and ray materials of young craters, including sharp B, Harding, Copernicus, and Aristarchus

TNF-α Regulates Mast Cell Functions by Inhibiting Cell Degranulation

Background/Aims: The aim of this study was to investigate the involvement of inducible co-stimulatory ligand (ICOSL) expression in stimulation of mast cells (MCs) by TNF-α and the ability of TNF-α stimulation of MCs to influence CD4+ T cell differentiation and function. The mechanisms underlying TNF-α stimulation of MCs were also explored. Methods: Mast cells and CD4+ T cells were prepared from C57BL/6 mice (aged 6–8 weeks). ICOSL expression by MCs was measured by real-time PCR and flow cytometry, and levels of IL-4, IL-10 and IFN-γ were measured by ELISA. Results: ICOSL expression by MCs was increased by TNF-α stimulation, and resulted in interaction with CD4+ T cells. The IL-4 and IL-10 levels in the co-culture system increased, while IFN-γ levels decreased. Furthermore, CD4+CD25+Foxp3+ T cell proliferation was induced by co-culture with TNF-α-stimulated MCs. The mechanism by which TNF-α stimulated MCs was dependent on the activation of the MAPK signaling pathway. Conclusion: TNF-α upregulated the expression of ICOSL on mast cells via a mechanism that is dependent on MAPK phosphorylation. TNF-α-treated MCs promoted the differentiation of regulatory T cells and induced a shift in cytokine expression from a Th1 to a Th2 profile by up-regulation ICOSL expression and inhibition of MC degranulation. Our study reveals a novel mechanism by which mast cells regulate T cell function

Study on the Expression Differences and the Correlation with H2BE Gene of Th Related Cytokines in SSDHS and LDSDS TCM-Syndromes of CHB Patients

Although our previous studies revealed that H2BE exhibited significantly differential expression between two CHB TCM-syndromes: Spleen-stomach dampness-heat syndrome, SSDHS and liver-depression spleen-deficiency syndrome, LDSDS, the underlying mechanisms remain largely unknown. Recent studies showed that dynamic expression fluctuation of Th related cytokines in CHB TCM-syndromes, and furthermore, their expression levels were largely regulated by H2BE. This study aims to detect the expression level differences of Th related cytokines between these two TCM-syndromes and further investigate the underlying regulatory mechanisms. The expression levels of the four Th related cytokines and H2BE were analyzed and the protein-protein interaction networks between H2BE and the four cytokines were constructed. Our results suggested that almost all the cytokines were significantly upregulated compared with the healthy group P<0.05. Interestingly, among the four cytokines, only IL-4 and INF-γ showed statistical significance between these two syndromes. The protein-protein interaction networks demonstrated that H2BE was indirectly associated with IL-4 and IL-10, and H2BE may regulate the expression levels of cytokines through GATA3. Taken together, our results indicated that IL-4 and INF-γ are two representative cytokines that may serve as two potential biochemical indicators of SSDHS and LDSDS in CHB patients; except what has been reported, our study found that one possible way for H2BE to regulate the expression of cytokines is to interact with GATA3 directly or indirectly

Cost-effectiveness acceptability curve.

BackgroundTo evaluate the cost-effectiveness of Tislelizumab vs Sorafenib as the first-line treatment of unresectable hepatocellular carcinoma (HCC) from the perspective of the Chinese health service system.MethodsA lifetime partitioned survival model (PSM) was developed to cost-effectively analyze Tislelizumab vs Sorafenib as the first-line treatment of unresectable HCC. The clinical and safety data were derived from a recently randomized clinical trial (RATIONALE-301). Utilities were collected from the published literature. Costs were obtained from an open-access database (http://www.yaozh.com) and previous studies. The model cycle was 21 days, according to the RATIONALE-301 study, and the simulation period was patients’ lifetime. Long-term direct medical costs and quality-adjusted life-years (QALYs) were determined. The incremental cost-effectiveness ratio (ICER) was used as the evaluation index. one-way sensitivity analysis (OSWA) and probabilistic sensitivity analysis (PSA) were used to analyze the uncertainty of parameters and to adjust and verify the stability of the baseline results.ResultsThe Tislelizumab group generated a cost of $39,746.34 and brought health benefits to 2.146 QALYs, while the cost and utility of the Sorafenib group were$26750.95 and 1.578 QALYs, respectively. The Tislelizumab group increased QALYs by 0.568, the incremental cost was $12995.39, and the ICER was$22869.64/QALY, lower than the willingness to pay threshold (WTP). OSWA results showed that the utility of progressed disease (PD), cost of Camrelizumab, and cost of Tislelizumab were the main factors affecting the ICER. PSA results showed that, within 1000 times the Monte Carlo simulation, the cost of the Tislelizumab group was lower than three times the per capita gross domestic product (GDP) of China ($37653/QALY). The cost-effectiveness acceptability curves (CEAC) revealed that when WTP was no less than$12251.00, the Tislelizumab group was the dominant scheme, and the economic advantage grew with an increasing WTP. When WTP ≥ $19000.00, the Tislelizumab group became the absolute economic advantage.ConclusionUnder the current economic conditions in China, the Tislelizumab therapeutic scheme is more cost-effective than the Sorafenib therapeutic scheme for treating patients with unresectable HCC.</div

Model parameters: Baseline values, ranges, and distributions for sensitivity analysis.

Model parameters: Baseline values, ranges, and distributions for sensitivity analysis.</p