Development of shell cross-linked nanoparticles based on boronic acid-related reactions for self-regulated insulin delivery

<p>Shell cross-linked nanoparticles were fabricated by the complexation of poly(3-methacrylamido phenylboronic acid) (PMAPBA) and thiolated chitosan (chitosan-SH) via boronic acid-related reactions. The formation of PMAPBA/chitosan-SH nanoparticles was confirmed by transmission electron microscopy, dynamic light scattering, and UV spectroscopy. The nanoparticles had a narrow size distribution with a relatively high positive charge density, and the size and zeta potential of the nanoparticles correlated with the chitosan-SH concentration. Furthermore, owing to the cross-linking of the nanoparticle shell, insulin was encapsulated in the nanoparticles with a loading capacity of up to 18%. The release of insulin from the nanoparticles slowed down because of the presence of disulfide bonds and increased with increasing glucose level in the medium. The structure of the released insulin was not distorted. More importantly, the nanoparticles had good cytocompatibility, as demonstrated by <i>in vitro</i> experiments. The simplicity of this strategy along with a high loading capacity, glucose sensitivity, and cytocompatibility of the produced nanoparticles should significantly boost their application in self-regulated insulin delivery.</p

Application of Chloride Adduct Ionization Tandem Mass Spectrometry for Characterizing and Sequencing Synthetic Lignin Model Compounds

The need for renewable bioenergy sources has renewed interest in lignin chemistry; however, structural elucidation and characterization of lignin degradation products remain a challenge because of lack of effective analytical methods. The analysis of lignin oligomers has been accomplished by simple deprotonation of weakly acidic phenolic moieties using NaOH and analyzed in a negative ESI mass spectrometry. Although simple deprotonation works to produce excellent results for many types of lignin compounds, others can undergo extensive in-source fragmentation for certain bond types making structural elucidation more complicated. Herein, we present an alternative method for analyzing lignin model compounds using chloride adduct chemistry. In this study, nine β-O-4 dimers, an (4-Ο-α)­(β-Ο-4) trimer, and a (β-O-4)­(β-O-4) trimer were synthesized and analyzed using chloride adduct mass spectrometry in the negative mode using NH₄Cl as the chloride source. Stable chloride adducted molecular ions were observed for all analyzed compounds. Tandem mass spectrometry experiments performed on each precursor ion produced “signature” fragment ions specific to each analyte. The compelling features of this method include the production of stable chloride adduct molecular ions that do not undergo in-source fragmentation, in contrast to simple deprotonation methods that can lead to extensive fragmentation for some structures, the appearance of the chlorine isotope pattern for enhanced recognition of molecular ions, and production of monolignol sequence specific fragment ions using tandem mass spectrometry

Data_Sheet_1_Using AGREE II reporting checklist to evaluate the quality of Tuina clinical practice guidelines.pdf

ObjectiveThe objective of this study is to evaluate the methodological quality of Tuina clinical practice guidelines (CPGs).MethodsComputer searches of China National Knowledge Infrastructure (CNKI), Chinese Technical Periodicals (VIP), Wanfang Data Knowledge Service Platform, PubMed, Cochrane Library, Embase, and other databases were conducted to search for published guidelines on Tuina, with a search time frame from database creation to March 2021. Four evaluators independently used the Appraisal of Guidelines for Research and Evaluation II instrument to evaluate the quality of the included guidelines.ResultsA total of eight guidelines related to Tuina were included in this study. The quality of reporting was low in all included guidelines. The highest quality report had a total score of 404 and was rated as “highly recommended.” The worst guideline had a final score of 241 and was rated as “not recommended.” Overall, 25% of the included guidelines were recommended for clinical use, 37.5% were recommended after revision, and 37.5% were not recommended.ConclusionThe number of existing Tuina clinical practice guidelines is limited. The methodological quality is low, far from the internationally accepted clinical practice guideline development and reporting norms. In the future, reporting specifications of guidelines and the methodology of guideline development, including the rigor of the guideline development process, the clarity, application, and independence of reporting, should be emphasized in the development of the Tuina guidelines. These initiatives could improve the quality and applicability of clinical practice guidelines to guide and standardize the clinical practice of Tuina.</p

Presentation1_Application of RNA processing factors for predicting clinical outcomes in colon cancer.pdf

Background: Colon cancer is the fifth most common cause of cancer-related death worldwide, and despite significant advances in related treatment, the prognosis of colon cancer patients remains poor.Objective: This study performs systematic bioinformatics analysis of prognostic-associated RNA processing factor genes in colon cancer using the Cancer Related Genome Atlas database to explore their role in colon carcinogenesis and prognosis and excavate potential therapeutic targets.Methods: Data sets of colon cancer patients were obtained from GEO and TCGA databases. Univariate cox analysis was performed on the GSE39582 training set to identify prognosis-associated RNA processing factor genes and constructed a muticox model. The predictive performance of the model was validated by Correlation curve analysis. Similar results were obtained for the test dataset. Functional analyses were performed to explore the underlying mechanisms of colon carcinogenesis and prognosis.Results: A constructed muticox model consisting of βi and prognosis-related RNA processing factor gene expression levels (Expi) was established to evaluate the risk score of each patient. The subgroup with a higher risk score had lower overall survival (OS), higher risk factor, and mortality. We found that the risk score, age, gender, and TNM Stage were strongly associated with OS, and the 13-gene signature as an independent prognostic factor for colon cancer. The model has good accuracy in predicting patient survival and is superior to traditional pathological staging.Conclusion: This study proposes 13 RNA processing factor genes as a prognostic factor for colon cancer patients, which can independently predict the clinical outcome by risk score. The gene expression profile in this model is closely related to the immune status and prognosis of colon cancer patients. The interaction of the 13 RNA processing factor genes with the immune system during colon carcinogenesis provides new ideas for the molecular mechanisms and targeted therapies for colon cancer.</p

Effect of the Surface Charge of Artificial Chaperones on the Refolding of Thermally Denatured Lysozymes

Artificial chaperones are of great interest in fighting protein misfolding and aggregation for the protection of protein bioactivity. A comprehensive understanding of the interaction between artificial chaperones and proteins is critical for the effective utilization of these materials in biomedicine. In this work, we fabricated three kinds of artificial chaperones with different surface charges based on mixed-shell polymeric micelles (MSPMs), and investigated their protective effect for lysozymes under thermal stress. It was found that MSPMs with different surface charges showed distinct chaperone-like behavior, and the neutral MSPM with PEG shell and PMEO₂MA hydrophobic domain at high temperature is superior to the negatively and positively charged one, because of the excessive electrostatic interactions between the protein and charged MSPMs. The results may benefit to optimize this kind of artificial chaperone with enhanced properties and expand their application in the future

Mean serum sodium concentration in patients according to CD4 count and WHO stage.

<p>Serum sodium concentration decreases with a reduction in CD4 count and an increases with WHO stage (F = 7.004, <i>P</i><0.001).</p

Kaplan–Meier survival curves according to serum sodium concentration.

<p>The serum sodium level affects mainly the 3-year mortality rate of patients. The 3-year cumulative survival rates for patients with moderate/severe and mild hyponatremia were 47.8%±8.5% and 59.8%±5.0%, respectively, and 78.2%±3.8% for normonatremic patients (Log-Rank, <i>P</i><0.001).</p

Basic characteristics of the hyponatremic patients (n = 387).

<p>Basic characteristics of the hyponatremic patients (n = 387).</p

Risk factors for mortality of patients in univariate/multivariate Cox's proportional hazard models.

<p>Risk factors for mortality of patients in univariate/multivariate Cox's proportional hazard models.</p

Targeted Chemo-Photodynamic Combination Platform Based on the DOX Prodrug Nanoparticles for Enhanced Cancer Therapy

Chemo-photodynamic combination therapy has been received widespread attention in cancer treatment due to its excellent characteristics, such as reducing the adverse side effects of chemo-drugs and improving the therapeutic effects for various cancers. In this study, RGD and DOX was conjugated to PEG by thiol–ene addition and Schiff’s base reaction, respectively, to prepare the targeted and pH-sensitive antitumor prodrug nanoparticles (RGD-PEG-DOX NPs, RGD-NPs). Subsequently, the photosensitizer chlorin e6 (Ce6) was encapsulated into RGD-NPs, thus obtaining a simple and efficient chemo-photodynamic combination platform (RGD-PEG-DOX/Ce6 NPs, RGD-NPs/Ce6). This nanoparticle possessed high drug loading property of both the chemo-drug and photosensitizer and could simultaneously release them under the mild acidic microenvironment of cancer cells, which was expected to realize the synchronization therapy of chemotherapy and photodynamic therapy (PDT). Compared with free DOX and Ce6, RGD-NPs/Ce6 could significantly improve the cellular uptake capacities of DOX and Ce6, resulting in the increased contents of ROS in cancer cells and effective cytotoxicity for tumor cells (MDA-MB-231 cells and MCF-7 cells) upon a laser radiation. The in vivo experiment showed that RGD-NPs/Ce6 displayed superior tumor targeting, accumulation, and retention ability than the other groups (free DOX, free Ce6 and NPs/Ce6), and thus significantly enhancing the antitumor effect in vivo with a laser radiation. In addition, the cardiotoxicity induced by DOX was thoroughly wiped out after being loaded and delivered by the nanoparticles according to the pathological analysis. Therefore, the targeted chemo-photodynamic combination therapeutic platform may be a promising candidate for enhanced cancer therapy