Skin stem cells can regenerate epidermal appendages; however, hair follicles (HF) lost as a result of injury are barely regenerated. Here we show that macrophages in wounds activate HF stem cells, leading to telogen–anagen transition (TAT) around the wound and de novo HF regeneration, mostly through TNF signalling. Both TNF knockout and overexpression attenuate HF neogenesis in wounds, suggesting dose-dependent induction of HF neogenesis by TNF, which is consistent with TNF-induced AKT signalling in epidermal stem cells in vitro. TNF-induced β-catenin accumulation is dependent on AKT but not Wnt signalling. Inhibition of PI3K/AKT blocks depilation-induced HF TAT. Notably, Pten loss in Lgr5+ HF stem cells results in HF TAT independent of injury and promotes HF neogenesis after wounding. Thus, our results suggest that macrophage-TNF-induced AKT/β-catenin signalling in Lgr5+ HF stem cells has a crucial role in promoting HF cycling and neogenesis after wounding.

Xenotransplantation of human cells into immunodeficiency mice has been frequently used to study stem cells in tissue repair and regeneration and cancer cell metastasis. However, a sensitive and reproducible method to quantify cell engraftment lacks. Here, we developed a Real-Time PCR-based method which facilitated consistent detection and quantification of small amounts of human cells distributed in mouse organs after infusion. The principle of the method was to directly detect a humans-specific sequence in the human-murine genomic DNA mixture. In a mouse myocardial infarction model, the Real-Time PCR-based method consistently determined the amounts of human mesenchymal stem cells (hMSCs) engrafted into the heart and other organs 7 days after infusion of as little as 2.5 × 10(5) cells, indicating a high sensitivity, and the amounts of hMSCs detected in mice highly correlated to the numbers of hMSCs transplanted. Importantly, different from previous PCR-based methods, our method produced highly consistent and reproducible results. The reliability of the method was further proven by parallel analyses of DiI-labeled hMSCs in tissue sections and in single cell suspensions of mice. Our data show that the present human genomic DNA-specific primers-based Real-Time PCR method is sensitive and highly reproducible in determining the amount of xenotransplanted human cells in murine tissues.

Cyclooxygenase-2 (COX-2) inhibitors have been shown to enhance antitumor activity of therapeutic agents in a variety of solid tumor cells. However, this has not been well established in hematopoietic tumors, especially in acute myeloid leukemia (AML). This study was designed to investigate the effects of the combination of celecoxib, a specific COX-2 inhibitor, and doxorubicin on cell growth and apoptosis in human leukemia cells. Co-treatment with celecoxib and doxorubicin significantly inhibited cell growth and induced cell apoptosis in the acute leukemia cell line HL60 and primary AML cells. The growth inhibition effect was accompanied by down-regulation of the expression of cyclin E and cyclin-dependent kinase 2 (CDK2), the key regulators of cell cycle progression, which was associated with arrest of cells at G0/G1 phase. The pro-apoptotic effect was accompanied by down-regulation of the expression of survivin, an inhibitor of apoptosis protein, which mediated anti-apoptosis in AML cells. These results provide the first evidence that the growth inhibitory and pro-apoptotic effects of celecoxib and doxorubicin on AML cells are synergistic.

Vehicle platoon is one of the innovations in the automated highway systems, which has the potential to reduce fuel consumption, alleviate traffic congestion and lighten the driver’s burden. How to control the vehicle effectively to ensure the stability of the queue is a challenge. Aiming to overcome the shortcomings of the platoon control method based on traditional sliding mode control, a non-singular terminal sliding mode control method optimized by the extreme learning machine is proposed in this paper. Firstly, the vehicle longitudinal dynamics are derived from the analysis of the forces acting on the vehicle in the longitudinal direction. A constant time headway policy is taken as the spacing policy. The modified non-singular terminal sliding mode control method has outstanding performance, simulation results demonstrate that the following vehicles can rapidly track the trajectory of the leading vehicle in the platoon with less spacing error and guarantee string stability. In this study, several experiments are set up to consider the disturbance and other uncertain practical factors. The performance of the proposed method is superior to the traditional sliding mode control method. Experimental results show that the proposed method can significantly reduce chattering and has good robustness under the circumstances of the disturbance.

Introduction Accurately assessing axillary lymph node (ALN) status in breast cancer is vital for clinical decision making and prognosis. The purpose of this study was to evaluate the predictive value of sentinel lymph node (SLN) mapped by multidetector-row computed tomography lymphography (MDCT-LG) for ALN metastasis in breast cancer patients. Methods 112 patients with breast cancer who underwent preoperative MDCT-LG examination were included in the study. Long-axis diameter, short-axis diameter, ratio of long-/short-axis and cortical thickness were measured. Logistic regression analysis was performed to evaluate independent predictors associated with ALN metastasis. The prediction of ALN metastasis was determined with related variables of SLN using receiver operating characteristic (ROC) curve analysis. Results Among the 112 cases, 35 (30.8%) cases had ALN metastasis. The cortical thickness in metastatic ALN group was significantly thicker than that in non-metastatic ALN group (4.0 ± 1.2 mm vs. 2.4 ± 0.7 mm, P < 0.001). Multi-logistic regression analysis indicated that cortical thickness of > 3.3 mm (OR 24.53, 95% CI 6.58–91.48, P < 0.001) had higher risk for ALN metastasis. The best sensitivity, specificity, negative predictive value(NPV) and AUC of MDCT-LG for ALN metastasis prediction based on the single variable of cortical thickness were 76.2%, 88.5%, 90.2% and 0.872 (95% CI 0.773–0.939, P < 0.001), respectively. Conclusion ALN status can be predicted using the imaging features of SLN which was mapped on MDCT-LG in breast cancer patients. Besides, it may be helpful to select true negative lymph nodes in patients with early breast cancer, and SLN biopsy can be avoided in clinically and radiographically negative axilla.