Thermo-Viscoelastic Response of 3D Braided Composites Based on a Novel FsMsFE Method

A homogenization-based five-step multi-scale finite element (FsMsFE) simulation framework is developed to describe the time-temperature-dependent viscoelastic behavior of 3D braided four-directional composites. The current analysis was performed via three-scale finite element models, the fiber/matrix (microscopic) representative unit cell (RUC) model, the yarn/matrix (mesoscopic) representative unit cell model, and the macroscopic solid model with homogeneous property. Coupling the time-temperature equivalence principle, multi-phase finite element approach, Laplace transformation and Prony series fitting technology, the character of the stress relaxation behaviors at three scales subject to variation in temperature is investigated, and the equivalent time-dependent thermal expansion coefficients (TTEC), the equivalent time-dependent thermal relaxation modulus (TTRM) under micro-scale and meso-scale were predicted. Furthermore, the impacts of temperature, structural parameters and relaxation time on the time-dependent thermo-viscoelastic properties of 3D braided four-directional composites were studied.     

Cold‐inducible RNA‐binding protein (CIRP) in inflammatory diseases: Molecular insights of its associated signalling pathways

Cold‐inducible RNA‐binding protein (CIRP) was previously identified as an intracellular stress‐response protein, which can respond to a variety of stress conditions by changing its expression and regulating mRNA stability through its binding site on the 3′‐UTR of its targeted mRNAs. Recently, extracellular CIRP (eCIRP) was discovered to be present in various inflammatory conditions and could act as a pro‐inflammatory factor. Genetic studies have demonstrated a key role for eCIRP in inflammatory conditions that led to the importance of targeting eCIRP in these diseases. Currently, the underlying mechanism of eCIRP‐induced inflammation is under intensive investigation and several signalling pathways are being explored. Here, we epitomized various signalling pathways that mediate the pro‐inflammatory effects of CIRP and also recapitulated all the CIRP‐derived peptides that can block the interaction between CIRP and its receptors in inflammatory setting.     

Time-dependent ROC analysis for censored biomarker data due to limit of detection

Receiver operating characteristic (ROC) curve is a well-established analysis method to evaluate biomarker’s discrimination accuracy for binary outcomes. When the endpoint of interest is time to event outcome such as time to cancer recurrence, a biomarker’s time-varying discriminatory performance is often assessed by time-dependent ROC analysis. In practice, biomarkers are often imprecisely measured due to the limitation of assay sensitivity. The values below the limit of detection are not detectable. Ignorance of such data characteristic may lead to inaccurate estimation of marker’s potential discriminatory power. The objective of this article is to extend time-dependent ROC method to censored biomarker data by using parameter estimates from the Cox regression model that accommodates censored biomarker measurements. In the simulation study, the proposed methods are shown to outperform the simple substitution method that has been conventionally adopted for handling censored data. Application data are also given to illustrate our methods.     

Global patent landscape of programmed cell death 1: implications of the rapid expansion

Introduction: Inhibitors of programmed cell death 1 (PD-1) and its ligands are producing a paradigm shift in cancer treatment. The promising clinical outcomes and a multi-billion dollar market have prompted active research and development and resulted in relentless patent protection. However, the global patent landscape in this field remains unclear.

Areas covered: The patent landscape encompassing global patenting activities and developing trends in the field is discussed based on a data set of 1287 patent families. Patenting activities have expanded rapidly in the past three years. Specific trends in relevant aspects are presented, including patent filing countries, patent ownership, co-patents, technical areas, and technological connections in terms of patent citation relationships.

Expert opinion: Together with patenting momentum in recent years, fragmented ownership and dense technological connections of PD-1-related inventions raise the possibility of a patent thicket. The explosion of patent applications and complex citation relationships could also lead to considerable patent conflicts and disputes on overlapping intellectual property rights, in addition to existing legal uncertainties. Patent applicants in this field are encouraged to be aware of these concerns when developing valid patent strategies.     

A visible fluorescent nanovaccine based on functional genipin crosslinked ovalbumin protein nanoparticles

Accurate and efficient antigen delivery is crucial for inducing a strong and long-term immune response. A visible protein nanovaccine made from antigen could provide a novel and promising technology for secure and efficient delivery of the antigen with imaging visualization. In this study, a functional nanovaccine based on genipin crosslinked ovalbumin (OVA) fluorescent nanoparticles with chitosan (CS-OVA-NPs) was developed. The nanovaccine can carry abundant antigens by self-crosslinking without additional carriers. The fluorescence imaging technique was applied to monitor and reveal the process of antigen delivery in vivo based on the fluorescence of genipin with a non-invasive and real-time manner. This functional OVA nanovaccine can enhance the uptake of OVA in Dendritic Cells (DCs) and further promote DCs to maturate in vitro. In vivo study further indicated CS-OVA-NPs could trigger antigen-specific immune responses, which demonstrated that this fluorescent nanovaccine provided a novel design approach for accurate and efficient vaccine delivery.     

Disease-directed design of biodegradable polymers: Reactive oxygen species and pH-responsive micellar nanoparticles for anticancer drug delivery

Herein, we report reactive oxygen species (ROS)- and pH-responsive biodegradable polyethylene glycol (PEG)-block-polycarbonate by installing thioether groups onto the polycarbonate and its self-assembled core/shell structured micelles for anticancer drug delivery. Oxidation of thioethers to sulfoxide and subsequently sulfone induces an increase in hydrophilicity, resulting in more hydrophilic micellar core. This phase-change caused the micelles to swell and enhance cargo release. Carboxylic acid groups have also been installed onto thioether-containing polycarbonate to promote loading of amine-containing anticancer doxorubicin through electrostatic interaction. Urea-functionalized thioether-containing PEG-block-polycarbonates were synthesized to mix with the acid-functionalized PEG-block-polycarbonate for stabilizing micelle structure through hydrogen-bonding interaction. The mixed micelles were 50?nm in diameter and had a 25?wt% loading capacity for doxorubicin. Enhanced drug release from the micelles was triggered by low pH and high content of ROS. Drug-encapsulated micelles accumulated in tumors through leaky tumor vasculature in PC-3 human prostate cancer xenograft mouse model.     

瘦素与肿瘤坏死因子在妊娠高血压综合征发病中的关系

目的探讨瘦素和肿瘤坏死因子(TNF-α)在妊娠高血压综合征(妊高征)发病中相互关系。方法采用放射免疫法测定34例妊高征患者(妊高征组)的外周血清瘦素及TNF-α水平,并以20例正常晚期妊娠妇女(正常妊娠组)为对照。将血清瘦素水平与TNF-α、肌酐、尿酸水平进行相关分析。结果(1)妊高征组血清瘦素水平为32.85±11.46ng/ml,明显高于正常妊娠组(18.92±3.03ng/ml,P<0.05);轻度妊高征组血清瘦素水平为21.98±4.83ng/ml,与正常妊娠组比较,差异无显著性(P>0.05);中、重度妊高征患者血清瘦素水平分别31.13±5.18ng/ml,41.84±10.90ng/ml,与轻度妊高征及妊娠正常组比较,差异显著(P均<0.05);轻、中、重度妊高征患者之间血清瘦素水平差异明显(P均<0.05)。妊高征患者的血清瘦素水平与肌酐、尿酸正相关(r分别为0.46、0.59,P均<0.01)。(2)妊高征组血清TNF-α水平为22.65±11.48fmol/ml,明显高于正常妊娠组(9.21±2.14fmol/ml,P<0.05);轻度妊高征患者血清TNF-α水平为11.51±4.12fmol/ml,与正常妊娠组比较,差异无显著性(P>0.05);中、重度妊高征患者血清TNF-α水平分别为19.46±7.41fmol/ml和32.89±8.31fmol/ml,与轻度妊高征及正常妊娠组比较,差异均有显著性(P均<0.05);轻、中、重度妊高征患者之间血清TNF-α水平差异明显(P均<0.05)。(3)妊高征组血清瘦素水平与TNF-α水平呈正相关(r=0.56,P<0.01)。结论妊高征患者血清TNF-α水平增高可能是导致血清瘦素水平升高的原因之一。     

Genomic characterisation of breast fibroepithelial lesions in an international cohort

Fibroepithelial lesions (FELs) are a heterogeneous group of tumours comprising fibroadenomas (FAs) and phyllodes tumours (PTs). Here we used a 16-gene panel that was previously discovered to be implicated in pathogenesis and progression, to characterise a large international cohort of FELs via targeted sequencing. The study comprised 303 (38%) FAs and 493 (62%) PTs which were contributed by the International Fibroepithelial Consortium. There were 659 (83%) Asian and 109 (14%) non-Asian FELs, while the ethnicity of the rest was unknown. Genetic aberrations were significantly associated with increasing grade of PTs, and were detected more in PTs than FAs for MED12, TERT promoter, RARA, FLNA, SETD2, TP53, RB1, EGFR, and IGF1R. Most borderline and malignant PTs possessed ≥ 2 mutations, while there were more cases of FAs with ≤ 1 mutation compared to PTs. FELs with MED12 mutations had significantly higher rates of TERT promoter, RARA, SETD2, EGFR, ERBB4, MAP3K1, and IGF1R aberrations. However, FELs with wild-type MED12 were more likely to express TP53 and PIK3CA mutations. There were no significant differences observed between the mutational profiles of recurrent FAs, FAs with a history of subsequent ipsilateral recurrence or contralateral occurrence, and FAs without a history of subsequent events. We identified recurrent mutations which were more frequent in PTs than FAs, with borderline and malignant PTs harbouring cancer driver gene and multiple mutations. This study affirms the role of a set of genes in FELs, including its potential utility in classification based on mutational profiles. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.