Research on Low-Velocity Impact Response of Novel Short-Fiber-Reinforced Composite Laminates.

Short-fiber-reinforced polymers (SFRPs) based on unidirectionally arrayed chopped strands (UACSs) have excellent formability and outstanding mechanical response. The low-velocity impact response, such as the delamination, damage tolerance and energy absorption of UACS composites, are essential to guarantee the stability and safety of composite components in service. The current study investigates the low-velocity impact response of continuous carbon-fiber-reinforced polymer (CFRP) and UACS laminates with vertical slits under drop-weight impact with various impact energies (4, 7 and 11 J). The in-plane size of the studied samples is 100 mm × 100 mm, and the stacking sequence is [0/90]4s. The time-history curves of load and energy are examined during low-velocity impact experiments, as well as the nonvisible damages are obtained by ultrasound C-scan imaging technique. A user-defined subroutine VUMAT, including the Johnson-Cook material and failure model, which is used to simulate the elastic-plastic property of the slits filled with resin, is coded in ABAQUS/Explicit. According to C-scan inspections of the impact-damaged laminates, UACS specimens show more severe delamination as impact energy increases. The damaged area of continuous CFRP laminates under impact energy of 11 J is 311 mm2, while that of UACS laminates is 1230 mm2. The slits have a negative effect on the load-bearing capacity but increase the energy absorption of UACS laminates by approximately 80% compared to the continuous CFRP laminates at 7 J. According to the variables of different damage modes in numerical simulation, cracks appear at the slits and then expand along the direction perpendicular to the slits, leading to the fracture of fiber. Nevertheless, as the damage expands to the slits, the delamination confines the damage propagation. The existence of slits could guide the path of damage propagation.

A simple LC-MS/MS method for the simultaneous quantification of drug metabolic enzymes.

OBJECTIVE: The aim of this study is to develop a LC-MS/MS method for the quantitation of seven cytochrome P450 (CYP450) enzymes. METHODS: A high-performance liquid chromatography-tandem mass spectrometry method was developed using multiple reaction monitoring mode with positive electrospray ionization. The method was validated with selectivity, linearity, stability, accuracy and precious. In addition, the abundance of seven CYP450 enzymes in human liver microsomes and CYP3A4 in placenta were determined using the current method. RESULTS: The linear range for CYP1A2, CYP2B6 and CYP2C8 was 0.036-3.6 nM and for CYP2C9, CYP2C19, CYP2D6 and CYP3A4 was 0.090-9.0 nM. No interference was found between the blank matrix and each specific peptides. The accuracy and precious results were in accord with the requirement of analytical methods for biological samples in Chinese Pharmacopoeia. In addition, the peptides were stable under current stability conditions. The content of CYP3A4 in placenta and the seven CYP450 enzymes in human liver microsomes were accurately quantified. CONCLUSION: The developed method is sensitive and specific and can be applied to the quantification of enzymes abundance in different human derived samples like placenta and liver microsomes.

Stitching Repair for Delaminated Carbon Fiber/Bismaleimide Composite Laminates.

Due to the excellent mechanical properties and heat resistance, bismaleimide matrix composite materials have been widely used in aircraft. However, they are susceptible to low-energy impacts, such as bird hits, gravel, tools falling, etc., which can easily result in delamination. The delamination can significantly reduce the compression performance of composites and become a potential hazard for aircraft in service. In this paper, a stitching method developed from the Z-pin manufacturing process was proposed to repair delaminated laminates. Firstly, the delaminated area was stitched by fiber bundles that were pre-impregnated with glue. Then, the fiber bundles threading through the laminate become the pins after the curing process, thus producing the bridging effect between delaminated layers. As a result, the in-plane compressive properties of the laminate are enhanced. The parameters, including the size, number, and position of the stitching hole, for the stitching repair were optimized, and the factors affecting the repair effect were discussed through both finite element analysis and experiments. The results showed that for a carbon fiber/bismaleimide composite plate with a circular delamination roughly 30 mm in diameter, the in-plane compressive strength can be recovered from 54.45% to 84.23% of the pristine plate, and the modulus was fully recovered.

Impact of Dose Reduction of Afatinib Used in Patients With Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Background and Aim: As one of the second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors, afatinib brings survival benefits to patients with common and rare EGFR mutations. This study aimed to compare the effectiveness and safety of 30 and 40 mg of afatinib in patients with non-small cell lung cancer (NSCLC) using qualitative and quantitative analysis methods so as to provide reference for clinical medication. Methods: The PubMed, Embase, ClinicalTrials.gov, Cochrane Library, China National Knowledge Infrastructure, and WanFang databases were thoroughly searched from inception to February 26, 2021. Two researchers independently screened the literature, extracted data, and evaluated the quality. RevMan and Stata 15.0 were used for meta-analysis. Results: Twelve cohort studies including 1290 patients for final analysis were selected; of which, 1129 patients were analyzed to measure the effectiveness outcomes and 470 patients were analyzed for safety outcomes. In patients with non-brain metastasis, the progression-free survival of the first- or second-line treatment with reduced-dose afatinib was equivalent to the conventional dose. In terms of safety, the reduced dose could significantly lower the incidence of severe diarrhea and severe rash, but not the total incidence of diarrhea, rash, and all levels of paronychia. Conclusions: The incidence of common serious adverse reactions was significantly lower with 30 mg of afatinib than with 40 mg of afatinib in patients with NSCLC. The effectiveness appeared to be similar to that in patients with non-brain metastasis. This study provides a reference for clinical dose reduction of afatinib. Systematic Review Registration: [PROSPERO], identifier [CRD42021238043].

Prognostic value of endogenous and exogenous metabolites in liver transplantation.

Liver transplantation has been widely accepted as an effective intervention for end-stage liver diseases and early hepatocellular carcinomas. However, a variety of postoperative complications and adverse reactions have baffled medical staff and patients. Currently, transplantation monitoring relies primarily on nonspecific biochemical tests, whereas diagnosis of multiple complications depends on invasive pathological examination. Therefore, a noninvasive monitoring method with high selectivity and specificity is desperately needed. This review summarized the potential of endogenous small-molecule metabolites as biomarkers for assessing graft function, ischemia-reperfusion injury and liver rejection. Exogenous metabolites, mainly those immunosuppressive agents with high intra- and inter-individual variability, were also discussed for transplantation monitoring.

3D dense connectivity network with atrous convolutional feature pyramid for brain tumor segmentation in magnetic resonance imaging of human heads.

The existing deep convolutional neural networks (DCNNs) based methods have achieved significant progress regarding automatic glioma segmentation in magnetic resonance imaging (MRI) data. However, there are two main problems affecting the performance of traditional DCNNs constructed by simply stacking convolutional layers, namely, exploding/vanishing gradients and limitations to the feature computations. To address these challenges, we propose a novel framework to automatically segment brain tumors. First, a three-dimensional (3D) dense connectivity architecture is used to build the backbone for feature reuse. Second, we design a new feature pyramid module using 3D atrous convolutional layers and add this module to the end of the backbone to fuse multiscale contexts. Finally, a 3D deep supervision mechanism is equipped with the network to promote training. On the multimodal brain tumor image segmentation benchmark (BRATS) datasets, our method achieves Dice similarity coefficient values of 0.87, 0.72, and 0.70 on the BRATS 2013 Challenge, 0.84, 0.70, and 0.61 on the BRATS 2013 LeaderBoard, 0.83, 0.70, and 0.62 on the BRATS 2015 Testing, 0.8642, 0.7738, and 0.7525 on the BRATS 2018 Validation in terms of whole tumors, tumor cores, and enhancing cores, respectively. Compared to the published state-of-the-art methods, the proposed method achieves promising accuracy and fast processing, demonstrating good potential for clinical medicine.

Failure Mechanisms and Reinforcing Modes of Ply Splice Fiber-Reinforced Composite Laminates under Tensile Load.

To fabricate large-scale or unusually shaped composite structures, pieces of fabric plies can be spliced to match size and shape requirements, forming ply splice structures. The junction of different plies can be considered as a defect in the resulting composite material, affecting the overall mechanical properties. In this paper, unidirectional carbon fiber-reinforced plastic (CFRP) with ply splices was used as a research object to study these potential material defects. The effects of ply splices at different positions on the tensile properties of CFRP and the coupling between position of ply splicing were analyzed. Simultaneously, a finite element model was established to analyze the damage evolution, in which a continuous damage model and a cohesive zone model were used to describe the damage of the composite and interface layers, respectively. The model results were in good agreement with observed experimental results. Our results showed that there were three main factors for this failure mechanism: boundary effects, whether the ply splices were independent, or whether they were close to each other. In short, when two ply splices were located at the edge or independent of each other, the failure mode was first delamination and then fiber fracture, and the tensile strength was high. However, when the two ply splices were close to the edge or close to each other, the failure mode was first local fiber fracture and then delamination damage, and the resulting tensile strength was low. Finally, different reinforcement methods to improve the tensile properties of composites were adopted for the splicing layers at different positions through the analysis via model simulation. The two-side patch repair method was used to reinforce the ply splices on or near the edge. Additionally, increasing the toughness of the adhesive layer was used to reinforce the ply splices that were inside the material. These results showed that the tensile strength was enhanced by these two methods of reinforcement, and the initial damage load was especially increased.

A responsive porous hydrogel particle-based delivery system for oncotherapy.

Liver cancer is one of the malignant cancers that seriously threatens human health. Although some common treatments including chemotherapy have been applied in oncotherapy, there are often serious shortcomings such as frequent and uncontrollable drug infusion. To overcome these limitations, here, we introduced responsive porous hydrogel microparticles loaded with 5-fluorouracil and metformin for oncotherapy. Because of the interconnected porous structures, various forms of active molecules could be loaded into the particles. In addition, the relatively higher temperature of the tumor site and the temperature-responsive shape transition of pNIPAM hydrogel enabled controllable drug release. The porous pNIPAM particles not only exhibited large loading efficiency and sustained release for the 5-fluorouracil and metformin co-delivery, but also protected drugs from being resolved. Thus, it can be anticipated that the porous microparticles will have great potential in oncotherapy.

A novel approach to devise the therapy for ventricular fibrillation by epicardial delivery of lidocaine using active hydraulic ventricular attaching support system: An experimental study in rats.

Active hydraulic ventricular attaching support system (ASD) placed around the heart is not only a novel, nontransplant surgical device used for epicardial administration of drugs like lidocaine, but also a promising treatment option for ventricular fibrillation (VF) and arrhythmias. We hypothesize that lidocaine in 5 mg/kg dose released by ASD significantly improves the VF in the rat model. Sprague-Dawley (SD) rats were selected and were divided into four groups, intravenous injection (IV), epicardial infusion (EI), ASD, and control. ASD group was further divided into four subgroups for different lidocaine doses (i) ASD+A group (10 mg/kg), (ii) ASD+B group (5 mg/kg), (iii) ASD+C group (1 mg/kg), and (iv) ASD+D group (0.1 mg/kg). VF was induced with calcium chloride injection and was confirmed by electrocardiogram (ECG) in all the groups. VF was treated with different doses of lidocaine using different modes of administration. Data were analyzed using the SPSS 19.0 Chi-square tests and one-way analysis of variance (ANOVA). The Kaplan-Meier curve for OS was compared to the Logrank test based on the survival time. P < 0.05 was considered as statistically significant. ASD + B group (5 mg/kg) showed significantly reduced sgroup. The time of first sinus rhythm recovered (15.96 ± 21.77 min) and ▵T-SOD in plasma (-42.02 ± 26.99 U/mL) was significantly different than that of control, IV, and EI groups. ▵T-SOD in plasma for all ASD-treated groups was smaller than the control and IV groups. This study proves that ASD with 5 mg/kg lidocaine dose appears as a promising therapeutic platform for treating VF in rats. Furthermore, ASD may also have potential for treating VF or other cardiovascular disease with different therapeutic agents. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1722-1731, 2019.

The epigenetic modification during the induction of Foxp3 with sodium butyrate.

CONTEXT: CD4 + CD25+ regulatory T (Treg) lymphocytes are critical for immune homeostasis. Foxp3 (Forkhead Box protein P3) is always considered as a marker of function and identities determination of Treg cells because of special occurring in Treg cell. People who lack Treg cells or have a low expression of Foxp3 gene will suffer fatal autoimmunity. Scientists are trying to use Treg cells as a treatment for autoimmune disease, such as systemic lupus erythematosus. OBJECTIVE: Our objective was to induce Foxp3 + CD4+ T cells from naïve CD4 + T cells isolated from C57 mice spleen in vitro using stimuli that include the short chain fatty acid sodium butyrate. Furthermore, to explore the relationship between Foxp3+ T cells induction and epigenetic modification, by observing the changes of Foxp3, Ezh2 (Enhancer of Zeste Homolog 2) and phosphorylated Ezh2 in the induced Treg cells. MATERIALS AND METHODS: The naïve CD4+ T cells were separated from C57 mice spleen by immunomagnetic separation. Anti-CD28, anti-CD3, IL-2, TGF-ß1, and sodium butyrate were added with proper concentration to induce Foxp3 expression during 72 hours. Then, we observed the effect of GSK126 (Ezh2 inhibitor) on the induction within the same over 72 hours duration. Then, western blot and Q-PCR were used to see the changes in gene/protein expression of Foxp3, Ezh2, and phosphorylated Ezh2. RESULTS: According to our results, group 3 that received full stimulus had a significant higher level of Foxp3 and Ezh2 expression (p < .05, comparing with group 1,2) and adding 5 mM sodium butyrate to the full stimulus (group 5) increased significantly the induction of Foxp3 and Ezh2 than control group and higher concentration group (p < .05, comparing with group 3,4, 6). The gene and protein expression of Foxp3 and Ezh2 both were enhanced in group 5 (p < .05 comparing with group 3). However, phosphorylated Ezh2 decreased in group 5 (p < .05 comparing with group3). Sodium butyrate removed part inhibition of GSK126, result in Foxp3 and Ezh2 expression (p < .05, p < .01, comparing with group7). CONCLUSION: In this study, we were able to transform CD4 + T cells into CD4 + Foxp3 + T cell by using stimulus like antibodies (anti-CD28, anti-CD3) and cytokines (IL-2, TGF-ß1). Sodium butyrate contributes to CD4 + Foxp3 + T cell induction in vitro and at an optimum concentration of 5 mM. Sodium butyrate promotes expression of Ezh2 and Fxop3 of T cells in vitro; in addition, to lowering relative expression of phosphorylated Ezh2 probably be influencing some pathways like PI3K-Akt. Epigenetic modification is also thought to take essential part into the upregulation of Foxp3 from naïve CD4 + Tcells.

Cardiac support device (ASD) delivers bone marrow stem cells repetitively to epicardium has promising curative effects in advanced heart failure.

Ventricular restraint therapy is a non-transplant surgical option for the management of advanced heart failure (HF). To augment the therapeutic applications, it is hypothesized that ASD shows remarkable capabilities not only in delivering stem cells but also in dilated ventricles. Male SD rats were divided into four groups (n = 6): normal, HF, HF + ASD, and HF + ASD-BMSCs respectively. HF was developed by left anterior descending (LAD) coronary artery ligation in all groups except normal group. Post-infarcted electrocardiography (ECG) and brain natriuretic peptide (BNP) showed abnormal heart function in all model groups and HF + ASD-BMSCs group showed significant improvement as compared to other HF, HF + ASD groups on day 30. Masson's trichrome staining was used to study the histology, and a large blue fibrotic area has been observed in HF and HF + ASD groups and quantification of fibrosis was assessed. ASD-treated rats showed normal heart rhythm, demonstrated by smooth -ST and asymmetrical T-wave. The mechanical function of the heart such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and heart rate was brought to normal when treated with ASD-BMSCs. This effect was more prominent than that of ASD therapy alone. In comparison to HF group, the SD rats in HF + ASD-BMBCs group showed a significant decline in BNP levels. So ASD can deliver BMSCs to the cardiomyocytes successfully and broaden the therapeutic efficacy, in comparison to the restraint device alone. An effective methodology to manage the end-stage HF has been proved.

Structure and properties of silk fibroin grafted carboxylic cotton fabric via amide covalent modification.

A novel eco-friendly production of silk fibroin-grafted carboxylic cotton fabrics without using any crosslinking agents was developed via the reaction of silk fibroin with oxidized cotton. The effect of reaction parameters on mechanical properties of oxidized fabrics and graft add-on of silk fibroin in grafted fabrics was examined. The results showed that appropriate oxidation time of HNO3/H3PO4-NaNO2 mixture and grafting time of fibroin were 45min and 2h respectively. FTIR analysis of grafted sample indicated that the CN amido bond was generated through the reaction between primary amines in silk fibroin and carboxyl groups in oxidized cotton, which was further confirmed by XPS spectra. The grafted fabrics were also evaluated for physical properties like tensile strength, wrinkle recovery angle, moisture regain and yellowness index. Cactus flavonoid coated on grafted fabric through treatment with flavonoid extract of cactus, such treated fabric exhibited a highly inhibitory effect against both Staphylococcus aureus and Escherichia coli bacteria.

Gingerol activates noxious cold ion channel TRPA1 in gastrointestinal tract.

TRPA1 channels are non-selective cation channels that could be activated by plant-derived pungent products, including gingerol, a main active constituent of ginger. Ginger could improve the digestive function; however whether ginger improves the digestive function through activating TRPA1 receptor in gastrointestinal tract has not been investigated. In the present study, gingerol was used to stimulate cell lines (RIN14B or STC-1) while depletion of extracellular calcium. TRPA1 inhibitor (rethenium red) and TRPA1 gene silencing via TRPA1-specific siRNA were also used for mechanistic studies. The intracellular calcium and secretion of serotonin or cholecystokinin were measured by fura-2/AM and ELISA. Stimulation of those cells with gingerol increased intracellular calcium levels and the serotonin or cholecystokinin secretion. The gingerol-induced intracellular calcium increase and secretion (serotonin or cholecystokinin) release were completely blocked by ruthenium red, EGTA, and TRPA1-specific siRNA. In summary, our results suggested that gingerol derived from ginger might improve the digestive function through secretion releasing from endocrine cells of the gut by inducing TRPA1-mediated calcium influx.

Evaluation of change in the skin concentration of tazarotene and betamethasone dipropionate based on drug-drug interaction for transdermal drug delivery in miniature pig.

1. The present study was designed to investigate drug-drug interaction in a new combination cream which contains both tazarotene (TZRT) and betamethasone dipropionate (BTMSDP) by comparing the pharmacokinetic (PK) behaviors of TZRT, BTMSDP, and their major metabolites, tazarotenic acid (TZRTAC) and betamethasone (BTMS) with those in the commonly prescribed TZRT gel and BTMSDP cream. 2. The trial was performed on six Bama mini-pigs. The different regions on the back side of each pig were randomly assigned to one of three treatment groups: TZRT 0.05% gel, BTMSDP 0.05% cream, and combination cream. The stratum corneum and epidermis-dermis samples were collected at various times after drug administration and analyzed for TZRT, TZRTAC, BTMSDP, and BTMS by LC-MS/MS. Compared with TZRT gel alone, TZRT + BTMSDP did not significantly change the PK profiles of TZRT; neither did BTMSDP + TZRT significantly change the PK profiles of BTMSDP, compared with the BTMSDP cream alone. In addition, the concentrations of TZRTAC and BTMS in most samples were below the lower limit of quantitation (LLOQ). 3. The results suggest that there was no significant drug-drug interaction trend between TZRT and BTMSDP in the process of transdermal permeation of combination cream into the stratum corneum and epidermis-dermis of mini-pigs.

Comparison of pharmacokinetics, tissue distribution and pharmacodynamics of liposomal and free doxorubicin in tumour-bearing mice following intratumoral injection.

OBJECTIVES: The clinical application of doxorubicin (DOX) is limited by severe systemic side effects. The aim of this study was to develop a strategy that combined the liposomal DOX (LipDOX) and intratumoral injection to reduce the toxicity and enhance the antitumor efficiency. METHODS: The pharmacokinetics, tissue distribution and pharmacodynamics of LipDOX compared with free DOX were investigated by intratumoral injection in murine H22 hepatoma-bearing mice at a dose of 20 mg/kg body weight. A sensitive HPLC-tandem mass spectrometry method was used to determine the DOX levels in plasma and tissues. The tumour volume and body weight of mice were measured every 3 days. KEY FINDINGS: LipDOX administration resulted in 1.3-fold longer mean residence time (MRT) and 2.4-fold higher area under concentration (AUC)-time curve compared with free DOX administration in tumour. Free DOX caused higher peak plasma concentration (Cmax ) than LipDOX in plasma and major organs, which may result in significant mortality for acute cardiac toxicity. After successive 21 days treatment, the final volume of tumour treated by normal saline, free DOX and LipDOX was 5.0-, 1.3-fold higher and 1.6-fold lower than the initial tumour volume, respectively. CONCLUSIONS: Our results indicated that the intratumoral injection of LipDOX is a promising approach with higher therapeutic efficacy and lower systemic toxicity than free DOX.

Prostate extract with aluminum hydroxide injection as a novel animal model for chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVES: To establish a new animal model to mimic the clinical condition of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). CP/CPPS is a highly prevalent condition with detrimental effect on the quality of life, but the etiology, pathogenesis, and optimal treatment of CP/CPPS remain unknown. This new animal model would greatly contribute to the understanding and treatment of CP/CPPS. METHODS: Forty Wistar rats were averagely and randomly divided into 5 groups (3 experimental groups, a normal control group, and a positive group) of 8 rats each. Experimental groups were subcutaneously injected with the mixture of prostate extract and aluminum hydroxide, the positive control group with prostate extract and complete Freund adjuvant (CFA), and the normal control group with 0.01 mol/L phosphate-buffered saline (0.01 M PBS). Hematoxylin and eosin stain and immunohistochemistry were respectively used to investigate the inflammatory lesion and the expression of tumor necrosis factor-alpha (TNF)-α in the prostate. In addition, the serum IgG was also evaluated. The t test was used to compare the statistical differences among groups. RESULTS: Histopathological analyses indicated that prostate lesions in the group immunized with high concentrations of aluminum hydroxide in the presence of prostate extract 3 times was most severe, in addition there was also the highest expression of TNF-α and IgG in this group. CONCLUSIONS: Prostate extract with aluminum hydroxide injection could successfully induce CP/CPPS in Wistar rats, which was in a dose-dependent and injection number-dependent fashion. This animal model might greatly benefit with further understanding of the etiology, pathogenesis, and optimal treatment of CP/CPPS.

[Comparison of pretreatment methods for the simultaneous determination of diclazuril and toltrazuril residues in chicken tissues].

The effects of four pretreatment methods (acetonitrile extraction-evaporation concentration, acetonitrile extraction-solid phase extraction (SPE), matrix solid-phase dispersion (MSPD) extraction and MSPD-SPE) for the simultaneous analysis of diclazuril and toltrazuril residues in chicken tissues were compared. The average recovery of 70% for the former three methods as achieved. In comparison with other methods, the MSPD method saved more than 60% in time and solvent. So, MSPD as the sample pretreatment method, an MSPD-high performance liquid chromatography with ultraviolet detection (MSPD-HPLC/UV) method was established for the analysis. Under the optimal chromatographic conditions, the linear range was between 50 and 1,000 microg/kg. At the added levels of 50, 500, 1,000 ng/g, the recoveries of diclazuril and toltrazuril in chicken tissues ranged from 71.13% - 84.02% with the relative standard deviations (RSD) in the range of 3.76% - 12.11%, and the RSDs of intra- and interday analyses ranged from 3.70% - 6.77%. The detection limits of diclazuril and toltrazuril were less than 10 microg/kg. The quantitative limits of diclazuril and toltrazuril were less than 20 microg/kg. The method meet the requirements of the residue analysis on accuracy and precision.