Carboxymethyl starch as a solid dispersion carrier to enhance the dissolution and bioavailability of piperine and 18ß-glycyrrhetinic acid.

OBJECTIVE: To investigate the applicability of carboxymethyl starch (CMS) as a carrier to prepare solid dispersions (SDs) of piperine (PIP) and 18ß-glycyrrhetinic acid (ß-GA) (PIP-CMS and ß-GA-CMS SDs) and to explore the influence of drug properties on carrier selection. SIGNIFICANCE: The low oral bioavailability of natural therapeutic molecules, including PIP and ß-GA, severely restricts their pharmaceutical applications. Moreover, CMS, a natural polymer, is rarely reported as a carrier for SDs. METHODS: PIP-CMS and ß-GA-CMS SDs were prepared using the solvent evaporation method. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier transform infrared (FT-IR) spectroscopy, and scanning electron microscopy (SEM) were used for formulation characterization. Additionally, drug release characteristics were investigated. RESULTS: In vitro dissolution studies showed that the dissolutions of PIP-CMS and ß-GA-CMS SDs were 1.90-2.04 and 1.97-2.22 times higher than pure PIP and ß-GA, respectively, at a drug:polymer ratio of 1:6. DSC, XRPD, FT-IR, and SEM analyses confirmed the formation of SDs in their amorphous states. Significant improvements in Cmax and AUC0-24 h of PIP-CMS and ß-GA-CMS SDs (17.51 ± 8.15 µg/mL and 210.28 ± 117.13 µg·h/mL, respectively) and (32.17 ± 9.45 µg/mL and 165.36 ± 38.75 µg·h/mL, respectively) were observed in the pharmacokinetic study. Compared with weakly acidic ß-GA, loading weakly basic PIP seemed to have a profound effect on stability through intermolecular forces. CONCLUSIONS: Our findings showed CMS could be a promising carrier for SDs, and loading weakly basic drug may be more suitable, especially in binary SDs system.

Enterovirus A71 capsid protein VP1 increases blood-brain barrier permeability and virus receptor vimentin on the brain endothelial cells.

Enterovirus A71 (EV-A71) is the major cause of severe hand-foot-and-mouth diseases (HFMD), especially encephalitis and other nervous system diseases. EV-A71 capsid protein VP1 mediates virus attachment and is the important virulence factor in the EV-A71pathogenesis. In this study, we explored the roles of VP1 in the permeability of blood-brain barrier (BBB). Sera albumin, Evans blue, and dextran leaked into brain parenchyma of the 1-week-old C57BL/6J mice intracranially injected with VP1 recombinant protein. VP1 also increased the permeability of the brain endothelial cells monolayer, an in vitro BBB model. Tight junction protein claudin-5 was reduced in the brain tissues or brain endothelial cells treated with VP1. In contrast, VP1 increased the expression of virus receptor vimentin, which could be blocked with VP1 neutralization antibody. Vimentin expression in the VP1-treated brain endothelial cells was regulated by TGF-ß/Smad-3 and NF-κB signal pathways. Moreover, vimentin over-expression was accompanied with compromised BBB. From these studies, we conclude that EV-A71 virus capsid protein VP1 disrupted BBB and increased virus receptor vimentin, which both may contribute to the virus entrance into brain and EV-A71 CNS infection.

Polyethylene-glycol-coated gold nanoparticles improve cardiac function after myocardial infarction in mice.

Gold nanoparticles (AuNPs) are widely used for drug delivery because of their unique biological properties, such as their safety and ability to prolong drug action. Some studies have demonstrated that AuNPs accumulate in the heart, especially during pathological processes. Therefore, it is very important to understand the effect of AuNPs on the heart. Myocardial infarction (MI) is a major cause of morbidity and mortality; however, the effect of AuNPs on MI remains unclear. In the present study, we carried out a comprehensive evaluation of AuNPs on acute MI. The results showed that AuNPs accumulated in infarcted hearts, decreased infarction size, improved systolic function, and inhibited cardiac fibrosis and TNF-α accumulation. Our work indicated that AuNPs have cardioprotective effects and can be used in drug delivery systems for the treatment of cardiac diseases.

Binding kinetics and multi-bond: Finding correlations by synthesizing interactions between ligand-coated bionanoparticles and receptor surfaces.

The number of bonds formed between one single bionanoparticle and many surface receptors is an important subject to be studied but is seldom quantitatively investigated. A new evaluation of the correlation between binding kinetics and number of bonds is presented by varying ligand density and receptor density. An experimental system was developed using measurements with surface plasmon resonance spectroscopy. A corresponding multi-site adsorption model elucidated the correlation. The results show that with the increase of the receptor density, the adsorption rate first decreased when the number of bonds was below a maximum value and then increased when the number of bonds stayed at this maximum value. The investigation on ligand density variation suggests that the coating density on top of the bionanoparticle surface may have a particular value below which more ligand will accelerate the adsorption rate. The ratio of ligand amount bound by the receptors to the total ligand amount associated with a single bionanoparticle will remain constant even if one attaches more ligands to a bionanoparticle. We envision that the bionanoparticle desorption will not depend on density changes from either ligand or receptor when the number of bonds reaches a specific efficient value.

Epidemiological Features of Infectious Diseases in Children and Adolescents: A Population-Based Observational Study in Shandong Province, China, 2013-2017.

BACKGROUND: The arrival of the big-data era provides us with a chance to elaborate the spectrum and epidemiological characteristics of infectious diseases in children and adolescents aged 0-18 years in the pre-COVID-19 pandemic era. METHODS: We collected data on infectious diseases in 891,981 participants from the Cheeloo Lifespan Electronic Health Research Data-library. The incidence density of each infection was calculated and stratified by age and region. The annual percentage change (APC) in incidence was estimated by logarithmic linear regression. RESULTS: A total of 18,183 cases of 78 infections were diagnosed, with an overall incidence density of 626.33 per 100,000 person-years (PY). Of these, 6825 cases of 50 non-notifiable infectious diseases were identified. Children aged 1-3 years had the highest incidence of infections. The overall incidence revealed a significant increasing trend from 2013 to 2017 (APC = 36.9%, p < 0.05). Hand, foot, and mouth disease, pneumonia, and influenza were the three most common diseases. The incidence of pneumonia, rubella, scarlet fever, zoster, molluscum contagiosum, and syphilis increased significantly during the study period (all p < 0.05). Taian, Binzhou, and Weihai had the highest incidence of all other cities. The incidence of gastrointestinal infections increased markedly in the eastern coastal regions. CONCLUSIONS: More stress should be placed on a number of non-notifiable infectious diseases with a high burden and a significant increasing trend. Age-based and regional targeting efforts are needed to prevent and contain infectious diseases among children and adolescents.

Determination of low carbon aldehydes and ketones in cigarette smoke by MXene membrane enrichment-liquid chromatography.

Low carbon aldehydes and ketones are typical substances harmful to human body produced during cigarette smoking. Their contents in cigarette smoke are important indicators for evaluating its toxicity and the filtration effect of cigarette filter tips, which provides important guidance for its rational design. In this work, MXene membrane with unique lamellar structure was synthesized and loaded onto glass fiber filters to achieve effective enrichment of low carbon aldehydes and ketones. Compared to commercial Cambridge filters, the MXene-loaded filters exhibited higher extraction efficiency towards low-carbon aldehydes and ketones, making viable the detection of butyraldehyde, which was not detected by that enriched with Cambridge filters. Therefore, a MXene-based membrane enrichment-HPLC method was developed for the determination of low-carbon aldehydes and ketones in cigarette smoke with detection limits ranging from 0.133 µg/mL to 0.285 µg/mL. The applicability of the method was verified by analyzing three different types of filter cigarettes with the concentration in the range of 0.5-140 µg/branch for all the analytes, which were in good agreement with the manufacturer's results. The method is accurate and sensitive, and can be used for the quantitative determination of low carbon aldehydes and ketones in cigarette smoke.

Crosstalk between human immunodeficiency virus infection and salivary bacterial function in men who have sex with men.

Background: Engaging in anal sexual intercourse markedly increases the risk of developing HIV among men who have sex with men (MSM); oral sexual activities tend to uniquely introduce gut-derived microbes to salivary microbiota, which, combined with an individual's positive HIV status, may greatly perturb oral microecology. However, till date, only a few published studies have addressed this aspect. Methods: Based on 16S rRNA sequencing data of bacterial taxa, MicroPITA picks representative samples for metagenomic analysis, effectively revealing how the development and progression of the HIV disease influences oral microbiota in MSM. Therefore, we collected samples from 11 HIV-negative and 44 HIV-positive MSM subjects (stage 0 was defined by HIV RNA positivity, but negative or indeterminate antibody status; stages 1, 2, and 3 were defined by CD4+ T lymphocyte counts ≥ 500, 200-499, and ≤ 200 or opportunistic infection) and selected 25 representative saliva samples (5 cases/stage) using MicroPITA. Metagenomic sequencing analysis were performed to explore whether positive HIV status changes salivary bacterial KEGG function and metabolic pathway in MSM. Results: The core functions of oral microbiota were maintained across each of the five groups, including metabolism, genetic and environmental information processing. All HIV-positive groups displayed KEGG functions of abnormal proliferation, most prominently at stage 0, and others related to metabolism. Clustering relationship analysis tentatively identified functional relationships between groups, with bacterial function being more similar between stage 0-control groups and stage 1-2 groups, whereas the stage 3 group exhibited large functional changes. Although we identified most metabolic pathways as being common to all five groups, several unique pathways formed clusters for certain groups; the stage 0 group had several, while the stage 2 and 3 groups had few, such clusters. The abundance of K03046 was positively correlated with CD4 counts. Conclusion: As HIV progresses, salivary bacterial function and metabolic pathways in MSM progressively changes, which may be related to HIV promoting abnormal energy metabolism and exacerbate pathogen virulence. Further, infection and drug resistance of acute stage and immune cell destruction of AIDS stage were abnormally increased, predicting an increased risk for MSM individuals to develop systemic and oral diseases.

Early diagnosis of oral cancer using a hybrid arrangement of deep belief networkand combined group teaching algorithm.

Oral cancer can occur in different parts of the mouth, including the lips, palate, gums, and inside the cheeks. If not treated in time, it can be life-threatening. Incidentally, using CAD-based diagnosis systems can be so helpful for early detection of this disease and curing it. In this study, a new deep learning-based methodology has been proposed for optimal oral cancer diagnosis from the images. In this method, after some preprocessing steps, a new deep belief network (DBN) has been proposed as the main part of the diagnosis system. The main contribution of the proposed DBN is its combination with a developed version of a metaheuristic technique, known as the Combined Group Teaching Optimization algorithm to provide an efficient system of diagnosis. The presented method is then implemented in the "Oral Cancer (Lips and Tongue) images dataset" and a comparison is done between the results and other methods, including ANN, Bayesian, CNN, GSO-NN, and End-to-End NN to show the efficacy of the techniques. The results showed that the DBN-CGTO method achieved a precision rate of 97.71%, sensitivity rate of 92.37%, the Matthews Correlation Coefficient of 94.65%, and 94.65% F1 score, which signifies its ability as the highest efficiency among the others to accurately classify positive samples while remaining the independent correct classification of negative samples.

Microplastics reduced bioavailability and altered toxicity of phenanthrene to maize (Zea mays L.) through modulating rhizosphere microbial community and maize growth.

Due to its large specific surface area and great hydrophobicity, microplastics can adsorb polycyclic aromatic hydrocarbons (PAHs), affecting the bioavailability and the toxicity of PAHs to plants. This study aimed to evaluate the effects of D550 and D250 (with diameters of 550 µm and 250 µm) microplastics on phenanthrene (PHE) removal from soil and PHE accumulation in maize (Zea mays L.). Moreover, the effects of microplastics on rhizosphere microbial community of maize grown in PHE-contaminated soil would also be determined. The results showed that D550 and D250 microplastics decreased the removal of PHE from soil by 6.5% and 2.7% and significantly reduced the accumulation of PHE in maize leaves by 64.9% and 88.5%. Interestingly, D550 microplastics promoted the growth of maize and enhanced the activities of soil protease and alkaline phosphatase, while D250 microplastics significantly inhibited the growth of maize and decreased the activities of soil invertase, alkaline phosphatase and catalase, in comparison with PHE treatment. In addition, microplastics changed the rhizosphere soil microbial community and reduced the relative abundance of PAHs degrading bacteria (Pseudomonas, Massilia, Proteobacteria), which might further inhibit the removal of PHE from soil. This study provided a new perspective for evaluating the role of microplastics on the bioavailability of PHE to plants and revealing the combined toxicity of microplastics and PHE to soil microcosm and plant growth.

Ectopic Expression of BcCUC2 Involved in Sculpting the Leaf Margin Serration in Arabidopsis thaliana.

Leaf margin serration is a morphological characteristic in plants. The CUC2 (CUP-SHAPED COTYLEDON 2) gene plays an important role in the outgrowth of leaf teeth and enhances leaf serration via suppression of growth in the sinus. In this study, we isolated the BcCUC2 gene from Pak-choi (Brassica rapa ssp. chinensis), which contains a 1104 bp coding sequence, encoding 367 amino acid residues. Multiple sequence alignment exhibited that the BcCUC2 gene has a typical conserved NAC domain, and phylogenetic relationship analysis showed that the BcCUC2 protein has high identity with Cruciferae plants (Brassica oleracea, Arabidopsis thaliana, and Cardamine hirsuta). The tissue-specific expression analysis displayed that the BcCUC2 gene has relatively high transcript abundance in floral organs. Meanwhile, the expression profile of BcCUC2 was relatively higher in the '082' lines with serrate leaf margins than the '001' lines with smooth leaf margins in young leaves, roots, and hypocotyls. In addition, the transcript level of BcCUC2 was up-regulated by IAA and GA3 treatment, especially at 1-3 h. The subcellular localization assay demonstrated that BcCUC2 was a nuclear-target protein. Furthermore, leaf serration occurred, and the number of the inflorescence stem was increased in the transgenic Arabidopsis thaliana plants' overexpressed BcCUC2 gene. These data illustrated that BcCUC2 is involved in the development of leaf margin serration, lateral branches, and floral organs, contributing to further uncovering and perfecting the regulation mechanism of leaf serration in Pak-choi.

Effects of nano- and microplastics on kidney: Physicochemical properties, bioaccumulation, oxidative stress and immunoreaction.

The potential toxicity of nanoplastics (NPs) and microplastics (MPs) has raised concerns. However, knowledge of the effects of NPs/MPs on the health of mammals is still limited. Here we investigated the alteration of the physicochemical properties of polystyrene NPs (PS-NPs: 50 nm) and MPs (PS-MPs: 300 nm, 600 nm, 4 µm) in the gastrointestinal tract. Moreover, we investigated the uptake and bioaccumulation and the toxic effects of these plastic particles in the kidneys of mice. The results revealed that their digestion promoted the aggregation of PS-NPs and PS-MPs and increased the Zeta-potential value. Both PS-NPs and PS-MPs bioaccumulated in the kidneys, and the aggregation of 600 nm PS-MPs exacerbated their biotoxicity. The PS-NPs and PS-MPs caused mice weight loss, increased their death rate, significantly alternated several biomarkers, and resulted in histological damage of the kidney. We also found that exposure to PS-NPs and PS-MPs induced oxidative stress and the development of inflammation. These findings provide new insights into the toxic effects of NPs and MPs on mice.

Serum Metabolic Fingerprints on Bowl-Shaped Submicroreactor Chip for Chemotherapy Monitoring.

Chemotherapy is a primary cancer treatment strategy, the monitoring of which is critical to enhancing the survival rate and quality of life of cancer patients. However, current chemotherapy monitoring mainly relies on imaging tools with inefficient sensitivity and radiation invasiveness. Herein, we develop the bowl-shaped submicroreactor chip of Au-loaded 3-aminophenol formaldehyde resin (denoted as APF-bowl&Au) with a specifically designed structure and Au loading content. The obtained APF-bowl&Au, used as the matrix of laser desorption/ionization mass spectrometry (LDI MS), possesses an enhanced localized electromagnetic field for strengthened small metabolite detection. The APF-bowl&Au enables the extraction of serum metabolic fingerprints (SMFs), and machine learning of the SMFs achieves chemotherapy monitoring of ovarian cancer with area-under-the-curve (AUC) of 0.81-0.98. Furthermore, a serum metabolic biomarker panel is preliminarily identified, exhibiting gradual changes as the chemotherapy cycles proceed. This work provides insights into the development of nanochips and contributes to a universal detection platform for chemotherapy monitoring.

Separation, anti-fouling, and chlorine resistance of the polyamide reverse osmosis membrane: From mechanisms to mitigation strategies.

Membrane technology has been widely used in the wastewater treatment and seawater desalination. In recent years, the reverse osmosis (RO) membrane represented by polyamide (PA) has made great progress because of its excellent properties. However, the conventional PA RO membranes still have some scientific problems, such as membrane fouling, easy degradation after chlorination, and unclear mechanisms of salt retention and water flux, which seriously impede the widespread use of RO membrane technology. This paper reviews the progress in the research and development of the RO membrane, with key focus on the mechanisms and strategies of the contemporary separation, anti-fouling and chlorine resistance of the PA RO membrane. This review seeks to provide state-of-the-art insights into the mitigation strategies and basic mechanisms for some of the key challenges. Under the guidance of the fundamental understanding of each mechanism, operation and modification strategies are discussed, and reasonable analysis is carried out, which can address some key technical challenges. The last section of the review focuses on the technical issues, challenges, and future perspective of these mechanisms and strategies. Advances in synergistic mechanisms and strategies of the PA RO membranes have been rarely reviewed; thus, this review can serve as a guide for new entrants to the field of membrane water treatment and established researchers.

Atmospheric transport and deposition of microplastics in a subtropical urban environment.

As an issue of great concern, microplastics pollution has emerged as a key environmental challenge of our time. The atmosphere is a significant compartment in the global cycle of microplastics, however, studies on the transport and deposition of airborne microplastics is limited. In the present work, atmospheric wet and dry deposition of microplastics were analyzed over one year in an urban environment of megacity Guangzhou, China. The atmospheric deposition fluxes of microplastics ranged from 51 to 178 particles/m2/d (mean: 114 ± 40 particles/m2/d). Fibers, fragments, films and microbeads were observed in the deposition samples, with fibers being the most abundant microplastics, accounting for 77.6 ± 19.1% of the total. The chemical composition of microplastics were identified using micro Fourier transform infrared spectrometer. 78.7% of the fibrous microplastics were derived from petrochemicals and most were polyethylene terephthalate (polyester), suggesting that textiles (e.g., clothes and curtains) were likely the main source. The results of back-trajectory analysis indicated that city rivers may act as secondary sources of airborne microplastics. Though no significant correlation was found between atmospheric microplastic deposition and meteorological factors such as rainfall and wind events, these factors were suggested to be positive drivers for the transport and deposition of airborne microplastic.

Optimized extraction of astaxanthin from shrimp shells treated by biological enzyme and its separation and purification using macroporous resin.

The best enzymatic protease treatment of shrimp shells was identified by comparing the enzymatic hydrolysis effects of many different types of biological enzymes using fresh Arctic sweet shrimp as raw materials. The optimal enzymolysis conditions were determined using neutral protease as the best enzymatic protease. Among multiple macroporous adsorption resins, XDA-8 macroporous adsorption resin was preferable due to its static adsorption rate and desorption rate. The yield of astaxanthin (134.20 µg/g) after treatment with neutral protease was 3.7 times higher than that of the control group (36.03 µg/g). The yield of astaxanthin was obviously improved after enzymolysis of the shrimp shells. The purity of the astaxanthin was up to 87.34%, approximately 6508 times higher than that of the raw material. The production cost of astaxanthin would be greatly reduced by use of XDA-8 resin to obtain high-purity astaxanthin. This technique offers a high value-added utilization of shrimp shells.

Microplastic pollution research methodologies, abundance, characteristics and risk assessments for aquatic biota in China.

The widespread presence of microplastics in global aquatic ecosystems has aroused growing concern about the potential impacts of microplastics on aquatic biota. In marine and freshwater environments, microplastics are distributed pervasively within water bodies from the upper water column to the bottom layer, making them available to a large variety of aquatic organisms that inhabit different locations. The ingestion of microplastic particles may cause harm to aquatic organisms. Although China's aquatic environments have been seriously polluted by microplastics, the impacts of microplastics on aquatic biota remain to be elucidated. This review summarizes the current state of knowledge about microplastic pollution in aquatic biota in China; specifically, the concentration and characteristics of microplastic particles in aquatic organisms from both seawater and freshwater environments are discussed. The results showed that various aquatic organisms in China have been found to consume microplastics. The average number of microplastic pieces discovered in biota ranged from 0.07 particles to 164 particles per individual in different organisms. The most frequently observed colors of microplastics detected in biota were blue and transparent, and the detected microplastics mainly consisted of fibers. In addition, the impacts of microplastics on aquatic organisms, including physical impacts, chemical impacts, the trophic transfer of microplastics and the potential risks to humans, were discussed. Finally, knowledge gaps were identified in order to guide future studies.

Adsorptive recovery of Au(III) from aqueous solution using crosslinked polyethyleneimine resins.

Resin adsorption is considered as a promising method to recover gold ions from wastewater, but further reduction reaction is required to convert gold ions into particles. In this study, a crosslinked polyethyleneimine resin (CPEIR) was developed via a suspension polymerization of polyethyleneimine (PEI) and ethylene glycol diglycidyl ether (EGDE) for gold recovery. The Au(III) adsorption capacities of CPEIR were significantly impacted by solution pH and initial Au(III) concentrations but unaffected by co-existing metal ions. Compared with commercial anion-exchange resin IRA400, the CPEIR exhibited higher sorption amount and selectivity for Au(III) due to its high density of amine and hydroxyl groups on the surfaces. The adsorption isotherm of Au(III) on CPEIR was well described by the Langmuir equation, and the maximum uptake amount of Au(III) was high up to 943.5 mg/g, much higher than the reported sorbents. The adsorption kinetic data on the CPEIR were fitted well by the Pseudo-second-order equation, and the intraparticle diffusion was found to be the rate-controlling process of Au(III) adsorption. X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) analysis confirmed that Au(III) ions were adsorbed on the CPEIR via electrostatic attraction and chelating interaction, and subsequently the partial loaded Au(III) ions were reduced to elemental gold whereas the hydroxyl groups of CPEIR were oxidized to carbonyl groups.

High-efficiency Ni2+-NTA/PAA magnetic beads with specific separation on His-tagged protein.

To effective capture and universal enrichment of His-tagged protein, polyacrylic acid (PAA) brushes were used to encapsulate Fe3O4 nanoparticles, connect NTA, and Ni2+ to prepare magnetic beads. These materials provide many advantages, such as excellent stability, tuneable particle size, and a surface for further functionalisation with biomolecules. His-tagged green fluorescence protein (GFP) was separated efficiently, and the binding capacity of Fe3O4/MPS@PAA/NTA-Ni2+ was 93.4 mg/g. Compared with High-Affinity Ni-NTA Resin and Ni-NTA Magnetic Agarose Beads, Fe3O4/MPS@PAA/NTA-Ni2+ nanocomposites exhibited higher separation efficiency and binding capacity towards His-tagged GFP. Moreover, the selectivity and recyclability of them for the target proteins were maintained well after six cycles. This study would widen the application of PAA in constructing multifunctional nanocomposites for biomedical fields.

PI3K-AKT-mTOR pathway alterations in advanced NSCLC patients after progression on EGFR-TKI and clinical response to EGFR-TKI plus everolimus combination therapy.

BACKGROUND: Several mechanisms including abnormal activation of PI3K-AKT-mTOR pathway have been proved to generate acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). In this study, we investigated the genomic characteristics of PI3K pathway activated in NSCLC patients after progression on EGFR-TKIs and whether both targeting EGFR and PI3K pathway could overcome resistance. METHODS: A total of 605 NSCLC cases with a history of EGFR TKI treatment were reviewed, in which 324 patients harboring EGFR mutations were confirmed progression on at least one EGFR TKI and finally enrolled. Tumor tissues or blood samples were collected at the onset of TKI progression for next generation sequencing (NGS). Six EGFR mutant patients with co-occurring mutations in PI3K pathway were retrospectively collected to assess the effect of EGFR TKI plus everolimus, a mTOR inhibitor. RESULTS: Forty-nine (14.9%) patients resistant to EGFR TKIs have at least one genetic variation in PI3K pathway. PIK3CA, PTEN and AKT1 variations were detected in 31 (9.5%), 18 (5.5%) and 3 (0.9%) of patients, respectively. No significant differences were observed in distribution of PI3K pathway alterations among patients with different EGFR mutations (EGFR exon19 deletion mutations/EGFR L858R/uncommon EGFR mutations) and among patients resistant to different EGFR TKIs. For patients treated with everolimus and EGFR-TKI, five (5/6, 83.3%) achieved stable disease (SD) and one (1/6, 16.7%) didn't receive disease control. The median progression-free survival (PFS) was 2.1 months (95% confidence interval, 1.35-4.3 months, range, 0.9-4.4 months). The most common adverse events were dental ulcer (6/6), rash (1/6). CONCLUSIONS: Our study revealed that PI3K pathway was activated in at least 14.9% in EGFR-TKI resistant patients. EGFR-TKIs plus everolimus showed limited antitumor activity in EGFR mutant NSCLC patients with PI3K pathway aberrations.

Silver triethanolamine-loaded PVB/CO films for a potential liquid bandage application.

Many studies have reported that silver has excellent antibacterial properties. However, silver ions can easily react with oxygen to form Ag2O, thus leading to a color change and a reduction in its anti-microbial characteristics. In this study, silver triethanolamine- (ST) loaded PVB/CO solution was prepared as a potential candidate liquid bandage. PVB/CO/ST retained high transparency after exposure to light for 12 months, which allowed convenient inspection of the wound bed without removal of the dressing. The PVB/CO/ST film exhibited favorable properties, such as speed of drying, excellent tensile strength and elongation characteristics and water vapor transmission rate (WVTR). It was comfortable and waterproof, and therefore effective at preventing bacterial invasion, providing effective biosafety. PVB/CO/ST solution-treated wounds exhibited accelerated healing and reduced inflammation in a nude mouse mode. Our data suggested that PVB/CO/ST solution could serve as a promising liquid bandage for treatment of minor trauma.