Effect of Strain Rate on Tensile Properties of Carbon Fiber-Reinforced Epoxy Laminates with Different Stacking Sequences and Ply Orientations

In practical application situations, a carbon fiber-reinforced polymer (CFRP) is often subjected to complex dynamic loadings. The effect of the strain rate on mechanical properties is very important for the CFRP design and product development. In this work, static and dynamic tensile properties of CFRP with different stacking sequences and ply orientations were investigated. The results showed that the tensile strengths of CFRP laminates were sensitive to the strain rate, while Young’s modulus was independent of the strain rate. Moreover, the strain rate effect was related to the stacking sequences and ply orientations. The experimental results showed that the strain rate effects of the cross-ply laminates and quasi-isotropic-ply laminates were lower than that of the unidirectional-ply laminates. Finally, the failure modes of CFRP laminates were investigated. Failure morphology demonstrated that the differences in strain rate effects among cross-ply laminates, quasi-isotropic-ply laminates, and unidirectional-ply laminates were caused by the mismatch between the fiber and the matrix when the strain rate increased

Identification and validation of poor prognosis immunoevasive subtype of muscle-invasive bladder cancer with tumor-infiltrating podoplanin+ cell abundance

The choice of chemo- or immuno-therapy for muscle-invasive bladder cancer (MIBC) patients remains contentious. Podoplanin is newly identified as an immune checkpoint which intrigues us to explore the clinical significance and immunoregulatory role of tumor-infiltrating podoplanin+ cells (PDPN+ cells) in MIBC. A retrospective analysis of 259 MIBC patients from Zhongshan Hospital (n = 141) and Shanghai Cancer Center (n = 118) was conducted. A total of 406 MIBC patients from TCGA database were enrolled to investigate the relationship between PDPN and molecular characterization. We found that tumor-infiltrating PDPN+ cell abundance indicated an inferior overall survival and recurrence-free survival. pT2 MIBC patients with PDPN+ cell low infiltration could benefit more from adjuvant chemotherapy (ACT). Increased PDPN+ cell infiltration was associated with diminished GZMB and TNF-α expression while correlated with expanded PD-1, PD-L1, LAG-3 and TIM-3 expression and tumor-promoting regulatory T cell and M2 macrophage infiltration. Tumors with high PDPN mRNA expression mainly presented luminal-infiltrated and basal-squamous subtypes (2017 TCGA classification) or stroma-rich and Ba/Sq subtypes (consensus classification). Elevated PDPN mRNA expression was associated with less FGFR3 activation signature and more T-cell-inflamed signature and EGFR activation signature. In conclusion, tumor-infiltrating PDPN+ cells could be applied as an independent prognosticator for clinical outcome and a predictive biomarker for suboptimal ACT responsiveness, which was also associated with immunosuppressive contexture infiltration. Intratumoral PDPN expression had a correlation with MIBC molecular classification and therapy-related signatures. The novel immune checkpoint PDPN should be considered as a possible immunotherapeutic target for MIBC

CCR5 blockade inflames antitumor immunity in BAP1-mutant clear cell renal cell carcinoma

Background Patients with BRCA1-associated protein 1 (BAP1)-mutant clear cell renal cell carcinoma (ccRCC) have worse prognosis. C-C chemokine receptor 5 (CCR5) plays an important role in ccRCC development and its expression is elevated in BAP1-mutant tumors.Methods 533 patients with ccRCC from The Cancer Genome Atlas cohort and 797 patients with ccRCC from the Shanghai cohort were enrolled. In vitro and in vivo studies were conducted with human ccRCC tumors and murine tumor models. The association between BAP1 and CCR5 or its ligands was assessed by immunohistochemistry, flow cytometry, real-time PCR and ELISA. Survival was compared between different subpopulations of patients using Kaplan-Meier curve. Therapeutic effect of CCR5 blockade was validated using human ccRCC tumors and murine models.Results Expression of CCR5 and its ligands were elevated in BAP1-mutant patients with ccRCC. High CCR5 expression was indicative of poor prognosis in BAP1-low group of patients. CCR5 blockade prolonged the survival of tumor-bearing mice, resulting in enhanced cytotoxicity of T cells and antigen presentation of dendritic cells but repressed immune checkpoint expression. CCR5 ligands could recruit CCR5+ regulatory T cells to the tumor microenvironment. Additionally, BAP1-mutant ccRCC tumor cells secreted CCR5 ligands, which increased programmed cell death ligand 1 expression. However, both processes could be inhibited by CCR5 blockade. Study limitations include the unclear impact of CCR5 expressed by other cell populations.Conclusions CCR5 in BAP1-mutant ccRCC results in an immune-suppressive microenvironment. Targeting CCR5 could provide a potential therapeutic benefit for patients.Trial registration number NCT01358721, CA209-009

Tumor-infiltrating IL-17A+ cells determine favorable prognosis and adjuvant chemotherapeutic response in muscle-invasive bladder cancer

The role of IL-17A+ cells remains controversial among various cancer types. This study aimed to investigate the effects of IL-17A+ cells on tumor immune contexture and clinical outcome in muscle-invasive bladder cancer (MIBC). In this study, we enrolled 141 patients from Zhongshan Hospital, 118 patients from Shanghai Cancer Center and 403 patients from TCGA cohort. In vitro studies were conducted in 32 freshly resected tumors. Survival analysis was conducted using Kaplan–Meier and Cox regression analysis. The results suggested that patients with high levels of IL-17A+ cells had prolonged overall survival and recurrence-free survival (HR = 0.268, P < .001; and HR = 0.433, P < .001). Moreover, these patients tended to be at lower risk of death and recurrence after adjuvant chemotherapy (P = .012 and P = .004). An increased number of IL-17A+ cells correlated with the infiltration of several anti-tumor immune cells into tumors. In addition, IL-17A+ cells had an influence on the recruitment, proliferation, and activation of CD8+ cells, and were positively associated with the expression of several anti-tumor effector cytokines. In conclusion, tumor-infiltrating IL17A+ cells were correlated with an elevated anti-tumor immunity in MIBC. Besides, high infiltration of IL17A+ cells can predict benefit from ACT for MIBC patients