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In this study, a comprehensive experimental and theoretical work was conducted on the bending performance of hybrid carbon-polyethylene terephthalate (C-PET) fiber-reinforced polymer (FRP) strengthened reinforced concrete (RC) beams with U-strip anchorages. Eleven RC beams were tested under a four-point bending load to investigate the influence of stacking sequence and U-strip anchorages. The bending performance of strengthened beams was carefully examined and discussed with regard to failure mode, flexural strength, ductility coefficient, and FRP strain development. The hybrid strengthened beams with U-strip anchorages exhibited 10.54 %−21.97 % higher flexural strength and 4.30 %−206.27 % higher ductility factors than the corresponding strengthened beams without U-strip anchorages. In addition, a theoretical analysis model with high accuracy was proposed to simulate the load-deflection curves of the strengthened beams based on the section analysis and plastic hinge model. Finally, this paper evaluated the accuracy of design guidelines (including GB 50608, ACI 440.2 R, and CNR DT 200 R1) in calculating the load-bearing capacities of strengthened beams. • Flexural performance was studied for hybrid carbon-PET FRP-strengthened RC beams with U-strip anchorages. • Effect of U-strip anchorages on flexure performance was investigated and discussed. • A simple but accurate theoretical model for load-deflection curves was proposed. • The design guidelines were evaluated in calculating the load-bearing capacities of the strengthened beams. [ABSTRACT FROM AUTHOR]

This paper presents an experimental study of the flexural performance of reinforced concrete (RC) beams externally bonded with hybrid fiber-reinforced polymer (FRP) laminates made of carbon and polyethylene terephthalate (PET) fibers. Ten beam specimens were subjected to four-point bending tests, with a focus on assessing the effects of the stacking sequence and the elastic modulus of hybrid carbon-PET FRP laminates on the flexural performance of the strengthened beams. The failure modes, load-bearing capacities, displacement ductility of the specimens and strain distributions in the FRP laminates were examined and discussed. The experimental results showed that the load-carrying capacities of the FRP-strengthened specimens were significantly increased by 10.18∼27.98%, while the displacement ductility decreased by 51.36∼77.85%. The peak load and ductility of the beam specimens strengthened with PC (i.e., PET-C FRP) and CPC (i.e., C-PET-C FRP) stacking sequences were higher than those of their counterparts strengthened with two or three layers of hybrid FRP laminates. The accuracy and reliability of the calculation methods specified in ACI 440.2R-17, CNR DT 200 R1/2014 and GB 50608–2020 for estimating the flexural strengths of the strengthened RC beams were evaluated through a comparison of theoretical predictions with experimental results. The average predicted-to-tested ratios for the flexural strengths of the strengthened beams using ACI 440.2R-17, CNR-DT 200 R1/2014 (based on PE debonding failure), CNR-DT 200 R1/2014 (based on IC debonding failure), and GB 50608–2020 are 0.994, 0.704, 0.946, and 0.930, respectively. • Flexural behavior of RC beams strengthened with hybrid carbon-PET FRP laminates was studied. • Effects of the stacking sequence and the elastic modulus of hybrid FRP laminates were examined and compared. • The hybrid FRPs achieved a significant increase in load-carrying capacity accompanying with a displacement ductility reduction. • The design methods specified in current guidelines reasonably predicted the flexural strengths of the tested specimens. [ABSTRACT FROM AUTHOR]

Highlights • CYP17A1 was significantly higher in the glioma tissues than the normal brain tissues. • The expression of CYP17A1 gene was positively correlative with glioma pathological grades. • CYP17A1 gene silence inhibited the proliferation and invasion of glioma cells and promoted the apoptosis in glioma cells. • We firstly poses a hypothesis to explain why incidence of glioma is lower in females than in males. Abstract Gliomas are the most common malignant primary brain tumors with poor prognosis. We attempted to explore the role of CYP17A1 in glioma progression. We demonstrated that the expression of CYP17A1 was significantly higher in the glioma tissues than the normal brain tissues, especially in malignant glioma. Moreover, the expression of CYP17A1 gene was positively correlative with glioma pathological grades. In vitro, CYP17A1 gene silence inhibited the proliferation and invasion of glioma cells and promoted the apoptosis in glioma cells. Also, the subcutaneously transplanted tumour in BALB/C–nu showed that CYP17A1 gene silence inhibited glioma growth. These results reveal that CYP17A1 plays a major role in the progress of glioma. [ABSTRACT FROM AUTHOR]

To investigate the role and mechanisms of HAUSP (Herpesvirus Associated Ubiquitin Specific Protease) and NANOG in pathogenesis of malignant human gliomas progression. Lentivirus-mediated HAUSP over-expression and RNAiHAUSP mediated HAUSP down-regulation were established in the glioma cells (U87 and U251 cell lines). Firstly, Real-time qPCR, western-blot (WB) and immunofluorescence staining were performed to detect mRNA levels, protein expressions and deposition of HAUSP and NANOG in the glioma cells, respectively. Then cell proliferation, invasion, apoptosis and xenograft tumor growth in nude mice were assessed by using cell counting kit-8 (CCK-8) assay, transwell assay, flow cytometry (FCM) and Hematoxylin-Eosin (HE) staining. We first demonstrated HAUSP was significantly increased in lentivirus- mediated HAUSP over-expression cells compared to the Control group. HAUSP over-expression could upregulate genes involved in proliferation and invasion such as NANOG. However, the mRNA of NANOG had no significant changes. Similarly, in RNAiHAUSP mediated HAUSP down-regulation group, HAUSP were significantly decreased compared to the Control group. Simultaneously, NANOG protein were decreased significantly, which decreased the proliferation and invasion, increased the apoptosis rate of glioma cells. Finally, low expression of HAUSP could suppress xenograft tumors growth in nude mice in different periods. This study revealed that HAUSP-NANOG pathway is a key target to inhibit glioma cells proliferation, and NANOG play important role in the formation and evolution of glioma cells. The regulation of HAUSP could change the biological activity of glioma cells through regulate NANOG expression. [ABSTRACT FROM AUTHOR]

The magnitude of drug-drug interaction between tacrolimus and voriconazole is highly variable, and individually tailoring the tacrolimus dose when concomitantly administered with voriconazole remains difficult. This study aimed to develop a semiphysiologically based population pharmacokinetic (semi-PBPK) model and a web-based dashboard to identify the dynamic inhibition of tacrolimus metabolism caused by voriconazole and provide individual tacrolimus regimens for Chinese adult liver transplant recipients. A total of 264 tacrolimus concentrations and 146 voriconazole concentrations were prospectively collected from 32 transplant recipients. A semi-PBPK model with physiological compartments including the gut wall, portal vein, and liver was developed using the nonlinear mixed-effects modeling software NONMEM (version 7.4). A web-based dashboard was established in R software (version 3.6.1) to recommend the individual tacrolimus regimens when concomitantly administered with voriconazole. The reversible inhibition of tacrolimus metabolism caused by voriconazole was investigated in both the liver and the gut wall. Moreover, voriconazole could highly inhibit the CYP3A activity in the gut wall more than in the liver. BMI and postoperative days were identified as significant covariates on intrinsic intestinal and hepatic clearance of tacrolimus, respectively. Age and postoperative days were identified as significant covariates on the volume of distribution of voriconazole. The individual tacrolimus regimens when concomitantly administered with voriconazole could be recommended in the dashboard (https://tac-vor-ddi.shinyapps.io/shinyapp3/). In conclusion, the semi-PBPK model successfully described the dynamic inhibition process between tacrolimus and voriconazole, and the web-based dashboard could provide individual tacrolimus regimens when concomitantly administered with voriconazole. [Display omitted] [ABSTRACT FROM AUTHOR]

• A population pharmacokinetic model of efavirenz (EFV) was developed to quantitatively explore the influence of CYP2B6 functional variants and albumin (ALB) on EFV PK in HIV-infected han chinese patients. • The SNPs of rs2099361 in CYP2B6 , along with ALB were identified as important covariates for EFV PK for the first time. • The CYP2B6 phenotype and ALB levels of patients could be used in prescribing optimal EFV doses. Efavirenz is a vital component used to treat HIV-1 infection. Nevertheless, it shows large between-subject variability, which affects both its therapeutic response and adverse effects. To investigate the impact of gene polymorphisms and non-genetic factors on the variability of efavirenz pharmacokinetics and to propose the optimal dose regimens. A total of 769 plasma samples from 376 HIV-infected Han Chinese outpatients were collected to develop a population pharmacokinetic model using NONMEM software. The impact of patient demographics, laboratory tests, concomitant medication, and genetic polymorphisms of CYP2B6 and ABCB1 on efavirenz pharmacokinetics were explored. According to the final model, the model-informed dose optimization was conducted. The pharmacokinetics of efavirenz was characterized by a one-compartment model with first-order absorption and elimination. The typical values of the estimated apparent oral clearance, volume of distribution, and absorption rate constant in the final model were 9.44 L/h, 200 L, and 0.727 h −1, respectively. Efavirenz clearance was significantly influenced by CYP2B6 variants, including rs2099361, rs3745274, and rs2279343, along with albumin and weight. The volume of distribution was affected by albumin and weight. Based on the CYP2B6 polymorphisms of patients, the recommended daily doses of efavirenz were 100 mg for CYP2B6 slow metabolizers, 400 or 600 mg for intermediate metabolizers, and 800 or 1000 mg for extensive metabolizers. Polymorphisms of CYP2B6 , along with albumin and weight, resulted as the predictors of efavirenz pharmacokinetic variability, which could be used in prescribing optimal efavirenz doses. [Display omitted] [ABSTRACT FROM AUTHOR]

Tissue engineering is a promising strategy to repair spinal cord injury (SCI). However, a bioscaffold with mechanical properties that match those of the pathological spinal cord tissue and a pro-regenerative matrix that allows robust neurogenesis for overcoming post-SCI scar formation has yet to be developed. Here, we report that a mechanically enhanced decellularized spinal cord (DSC) scaffold with a thin poly (lactic-co-glycolic acid) (PLGA) outer shell may fulfill the requirements for effective in situ neuroengineering after SCI. Using chemical extraction and electrospinning methods, we successfully constructed PLGA thin shell-ensheathed DSC scaffolds (PLGA-DSC scaffolds) in a way that removed major inhibitory components while preserving the permissive matrix. The DSCs exhibited good cytocompatibility with neural stem cells (NSCs) and significantly enhanced their differentiation toward neurons in vitro. Due to the mechanical reinforcement, the implanted PLGA-DSC scaffolds showed markedly increased resilience to infiltration by myofibroblasts and the deposition of dense collagen matrix, thereby creating a neurogenic niche favorable for the targeted migration, residence and neuronal differentiation of endogenous NSCs after SCI. Furthermore, PLGA-DSC presented a mild immunogenic property but prominent ability to polarize macrophages from the M1 phenotype to the M2 phenotype, leading to significant tissue regeneration and functional restoration after SCI. Taken together, the results demonstrate that the mechanically matched PLGA-DSC scaffolds show promise for effective tissue repair after SCI. [ABSTRACT FROM AUTHOR]