105 research outputs found
Mulberry biomass-derived nanomedicines mitigate colitis through improved inflamed mucosa accumulation and intestinal microenvironment modulation
The therapeutic outcomes of conventional oral medications against ulcerative colitis (UC) are restricted by inefficient drug delivery to the colitis mucosa and weak capacity to modulate the inflammatory microenvironment. Herein, a fluorinated pluronic (FP127) was synthesized and employed to functionalize the surface of mulberry leaf-derived nanoparticles (MLNs) loading with resveratrol nanocrystals (RNs). The obtained FP127@RN-MLNs possessed exosome-like morphologies, desirable particle sizes (around 171.4 nm), and negatively charged surfaces (â 14.8 mV). The introduction of FP127 to RN-MLNs greatly improved their stability in the colon and promoted their mucus infiltration and mucosal penetration capacities due to the unique fluorine effect. These MLNs could efficiently be internalized by colon epithelial cells and macrophages, reconstruct disrupted epithelial barriers, alleviate oxidative stress, provoke macrophage polarization to M2 phenotype, and down-regulate inflammatory responses. Importantly, in vivo studies based on chronic and acute UC mouse models demonstrated that oral administration of chitosan/alginate hydrogel-embedding FP127@RN-MLNs achieved substantially improved therapeutic efficacies compared with nonfluorinated MLNs and a first-line UC drug (dexamethasone), as evidenced by decreased colonic and systemic inflammation, integrated colonic tight junctions, and intestinal microbiota balance. This study brings new insights into the facile construction of a natural, versatile nanoplatform for oral treatment of UC without adverse effects.We are grateful to Dr. J. Sun from University of Oxford for his corrections and improvement of this manuscript. Funding: This study was supported by the National Natural Science Foundation of China (82072060 and 22008201), the Fundamental Research Funds for the Central Universities (SWU-XDPY22006), the Venture & Innovation Support Program for Chongqing Overseas Returnees (2205012980212766), the Natural Science Foundation Project of Chongqing (cstc2020jcyj-msxmX0292), and the Natural Science Foundation Project of Chongqing for Distinguished Young Scholar. Author contributions: W.Y., M.W., X.S., and B.X. designed experiments, supervised the project, and wrote the manuscript draft. W.Y., Y.M., H.X., Z.Z., J.W., C.X., W.S., and E.Z. performed the experiments. R.L.R., S.C.K., M.W., X.S., and B.X. edited and revised the manuscript. All authors have approved the final version of the manuscript. Competing interests: The authors declare that there is no con flict of interest regarding the publication of this article
Investigation of systemic immune-inflammation index, neutrophil/high-density lipoprotein ratio, lymphocyte/high-density lipoprotein ratio, and monocyte/high-density lipoprotein ratio as indicators of inflammation in patients with schizophrenia and bipolar disorder
BackgroundThe systemic immune-inflammation index (SII), system inflammation response index (SIRI), neutrophil/high-density lipoprotein (HDL) ratio (NHR), lymphocyte/HDL ratio (LHR), monocyte/HDL ratio (MHR), and platelet/HDL ratio (PHR) have been recently investigated as new markers for inflammation. The purpose of this research is to use large-scale clinical data to discuss and compare the predictive ability of the SII, SIRI, NHR, LHR, MHR, and PHR in patients with schizophrenia (SCZ) and bipolar disorder (BD), to investigate potential biomarkers.Materials and methodsIn this retrospective, naturalistic, cross-sectional study, we collected the hematological parameter data of 13,329 patients with SCZ, 4,061 patients with BD manic episodes (BD-M), and 1,944 patients with BD depressive episodes (BD-D), and 5,810 healthy subjects served as the healthy control (HC) group. The differences in the SII, SIRI, NHR, LHR, MHR, and PHR were analyzed, and a receiver operating characteristic (ROC) curve was used to analyze the diagnostic potential of these parameters.ResultsCompared with the HC group, the values of the SII, SIRI, NHR, LHR, MHR, and PHR and the levels of neutrophils, monocytes, and triglycerides (TG) were higher in SCZ and BD groups, and levels of platelets, cholesterol (CHO), HDL, low-density lipoprotein (LDL), and apoprotein B (Apo B) were lower in SCZ and BD groups. Compared to the BD group, the values of the SIRI, lymphocytes, monocytes, and HDL were lower and the values of the SII, NHR, PHR, and platelet were higher in the SCZ group. In contrast to the BD-D group, the values of the SII; SIRI; NHR; and MHR; and levels of neutrophils, monocytes, and platelets were higher in the BD-M group, and the levels of CHO, TG, LDL, and Apo B were lower in the BD-M group. The MHR and NHR were predictors for differentiating the SCZ group from the HC group; the SIRI, NHR, and MHR were predictors for differentiating the BD-M group from the HC group; and the MHR was a predictor for differentiating the BD-D group from the HC group. The combination model of the indicators improved diagnostic effectiveness.ConclusionOur study highlights the role of systemic inflammation in the pathophysiology of SCZ, BD-M, and BD-D, the association between inflammation and lipid metabolism, and these inflammation and lipid metabolism indicators showed different variation patterns in SCZ, BD-D, and BD-M
Expression and purification of soluble single-chain Fv against human fibroblast growth factor receptor 3 fused with Sumo tag in Escherichia coli
Background: Overexpression or mutated activation of Fibroblast growth
factor receptor 3 (FGFR3) is involved in the pathogenesis of many
tumors. More and more studies focus on the potential usage of
therapeutic antibodies against FGFR3. Results: In this study, a novel
single-chain Fv (ScFv) against FGFR3 was prepared and characterized. To
achieve the soluble expression, ScFv was fused with Sumo (Small
ubiquitin-related modifier) by polymerase chain reaction (PCR), and
cloned into pET-20b. The recombinant bacteria were induced by 0.5 mM
Isopropyl-\u3b2-D-thiogalactopyranoside (IPTG) for 16 h at 20\ub0C,
and the supernatant liquid of Sumo-ScFv was harvested and purified by
Ni-NTA chromatography. After being cleaved by the Sumo protease, the
recombinant ScFv was released from the fusion protein, and further
purified by Ni-NTA chromatography. The purity of ScFv was shown to be
higher than 95% and their yield reached 4 mg per liter of bacterial
culture. In vitro data showed that ScFv can significantly attenuate
FGF9-induced phosphorylation of FGFR3. Conclusion: We provide a novel
method to produce soluble expression and bioactive functions of ScFv in
Escherichia coli
Search for CP violation using T-odd correlations in D-0 -> K+K-pi(+)pi(-) decays
A search for violation using -odd correlations is performed using the four-body decay, selected from semileptonic decays. The data sample corresponds to integrated luminosities of and recorded at the centre-of-mass energies of 7 TeV and 8 TeV, respectively. The -violating asymmetry is measured to be . Searches for violation in different regions of phase space of the four-body decay, and as a function of the decay time, are also presented. No significant deviation from the conservation hypothesis is found
Measurement of CP asymmetry in B-s(0) -> D-s(-/+) K--/+ decays
We report on measurements of the time-dependent CP violating observables in decays using a dataset corresponding to 1.0 fb of pp collisions recorded with the LHCb detector. We find the CP violating observables , , , , , where the uncertainties are statistical and systematic, respectively. We use these observables to make the first measurement of the CKM angle in decays, finding = (115) modulo 180 at 68% CL, where the error contains both statistical and systematic uncertainties.We report on measurements of the time-dependent CP violating observables in B  → D K decays using a dataset corresponding to 1.0 fb of pp collisions recorded with the LHCb detector. We find the CP violating observables C = 0.53±0.25±0.04, A  = 0.37 ± 0.42 ± 0.20, , S = −1.09±0.33±0.08, , where the uncertainties are statistical and systematic, respectively. Using these observables together with a recent measurement of the B mixing phase −2β leads to the first extraction of the CKM angle γ from B  → D K decays, finding γ = (115 )° modulo 180° at 68% CL, where the error contains both statistical and systematic uncertainties.We report on measurements of the time-dependent CP violating observables in decays using a dataset corresponding to 1.0 fb of pp collisions recorded with the LHCb detector. We find the CP violating observables , , , , , where the uncertainties are statistical and systematic, respectively. Using these observables together with a recent measurement of the mixing phase leads to the first extraction of the CKM angle from decays, finding = (115) modulo 180 at 68% CL, where the error contains both statistical and systematic uncertainties
AppFA: A Novel Approach to Detect Malicious Android Applications on the Network
We propose AppFA, an Application Flow Analysis approach, to detect malicious Android applications (simply apps) on the network. Unlike most of the existing work, AppFA does not need to install programs on mobile devices or modify mobile operating systems to extract detection features. Besides, it is able to handle encrypted network traffic. Specifically, we propose a constrained clustering algorithm to classify apps network traffic, and use Kernel Principal Component Analysis to build their network behavior profiles. After that, peer group analysis is explored to detect malicious apps by comparing apps’ network behavior profiles with the historical data and the profiles of their selected peer groups. These steps can be repeated every several minutes to meet the requirement of online detection. We have implemented AppFA and tested it with a public dataset. The experimental results show that AppFA can cluster apps network traffic efficiently and detect malicious Android apps with high accuracy and low false positive rate. We have also tested the performance of AppFA from the computational time standpoint
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