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Wiring of cables is very important in the design of electro-mechanical products. Whereas, there is not an effectual virtual wiring method for the moment. Aimed at the problem, a virtual wiring is expatiated in this paper. Virtual layout design is achieved based on human-computer interaction, which is verified by virtual assembling. Geometrical modeling of cables, the precision of which is quite high, is established based on energy-optimized method. The characteristic of virtual assembling to the products, which make up of cables and other parts, is discussed. Especially, the assemble technique programming and transformation simulating of cables are studied. In the end, the wiring is actualized on a product, intention to validate the feasibility of the method.

The essentiality of assembly assessment and assembly optimization in design stage is analyzed, and the existent problems of conventional assembly design method are illuminated. ADMDMU (Assembly Design Method based Digital Mock-Up) is illuminated, and the process of ADMDMU established, and the ADMDMU architecture is given out. The key techniques of ADMDMU are analyzed, and include assembly design based KBE (Knowledge Based Engineering) and virtual assembly based physically attribute. According to physical attribute, physically based modeling, visual object movement control, force simulation method and assembly sequence planning method are emphatically illuminated. Assembly design system based DMU is established in foundation of ADMDMU.

YCP, a novel （1,4）-α-D-glucan, was isolated from the mycelium of the marine filamentous fungus Phoma herbarum YS4108. In this work, we investigated a YCP-binding cellular receptor expressed by macrophages and the intracellular signal transduction pathways involved in YCP-induced macrophage activation. Methods： Fluorescence-labeled YCP （fl-YCP） was prepared using the CDAP-activation method. Fluorescence confocal laser microscopy and fluorescence-activated cell sorting （FACS） were used to analyze the effect of fl-YCP on macrophages. To characterize the properties of the YCP receptor, carbohydrates and antibodies were used to inhibit the binding of fl-YCP to macrophages. Moreover, we investigated the role of membrane receptors Toll-like receptor 2 （TLR2）, Toll-like receptor 4 （TLR4）, Toll-like receptor 6 （TLR6） and complement receptor 3 （CR3）. We also examined the role of the p38 kinase pathway in mediating nitric oxide （NO） production. Results： YCP had an in vitro stimulatory effect on the release of NO in macrophage, and fI-YCP can bind directly to receptors on the surface of macrophages in a time- and dose-dependent manner. Competition studies show that LPS, laminarin, anti-TLR4 antibody and anti-CD11b （CR3） antibody could inhibit fl-YCP binding to macrophages. Conversely, mannose, anti-TLR2 and anti-TLR6 antibody could not. Treatment of RAW264.7 cells with YCP resulted in significant activation of p38 in a time-dependent manner. The specific p38 inhibitor SB203580 abrogated YCP-induced NO generation. Treatment of RAW264.7 cells with anti-TLR4 antibody and anti-CR3 antibody significantly reduced YCP-induced NO production and p38 activation. Conclusion： We have demonstrated that YCP-induced NO production occurs through the TLR4 and CR3 membrane receptors in a p38 kinase-dependent manner in macrophages.

Nomograms for predicting the risk of prostate cancer developed using other populations may introduce sizable bias when applied to a Chinese cohort. In the present study, we sought to develop a nomogram for predicting the probability of a positive initial prostate biopsy in a Chinese population. A total of 535 Chinese men who underwent a prostatic biopsy for the detection of prostate cancer in the past decade with complete biopsy data were included. Stepwise logistic regression was used to determine the independent predictors of a positive initial biopsy. Age, prostate-specific antigen （PSA）, prostate volume （PV）, digital rectal examination （DRE） status, % free PSA and transrectal ultrasound （TRUS） findings were included in the analysis. A nomogram model was developed that was based on these independent predictors to calculate the probability of a positive initial prostate biopsy. A receiver-operating characteristic curve was used to assess the accuracy of using the nomogram and PSA levels alone for predicting positive prostate biopsy. The rate for positive initial prostate biopsy was 41.7% （223/535）. The independent variables used to predict a positive initial prostate biopsy were age, PSA, PV and DRE status. The areas under the receiver-operating characteristic curve for a positive initial prostate biopsy for PSA alone and the nomogram were 79.7% and 84.8%, respectively. Our results indicate that the risk of a positive initial prostate biopsy can be predicted to a satisfactory level in a Chinese population using our nomogram. The nomogram can be used to identify and counsel patients who should consider a prostate biopsy, ultimately enhancing accuracy in diagnosing prostate cancer.

Background Increasing evidence has shown that mesenchymal stem cells (MSCs) yield a favorable therapeutic benefit for thermal burn skin wounds. Human amniotic MSCs (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammatory potential which makes them suitable for treating skin wounds. However, the exact effects of hAMSCs on the healing of thermal burn skin wounds and their potential mechanisms are not explored. Methods hAMSCs were isolated from amniotic membrane and characterized by RT-PCR, flow cytometry, immunofluorescence, and tumorigenicity test. We assessed the effects of hAMSCs and hAMSC conditional medium (CM) on wound healing in a deep second-degree burn injury model of mice. We then investigated the biological effects of hAMSCs and hAMSC-CM on the apoptosis and proliferation of heat stress-injured human keratinocytes HaCAT and dermal fibroblasts (DFL) both in vivo and in vitro. Next, we explored the underlying mechanisms by assessing PI3K/AKT and GSK3β/β-catenin signaling pathways in heat injured HaCAT and DFL cells after hAMSCs and hAMSC-CM treatments using PI3K inhibitor LY294002 and β-catenin inhibitor ICG001. Antibody array assay was used to identify the cytokines secreted by hAMSCs that may activate PI3K/AKT signaling pathway. Results Our results showed that hAMSCs expressed various markers of embryonic stem cells and mesenchymal stem cells and have low immunogenicity and no tumorigenicity. hAMSC and hAMSC-CM transplantation significantly promoted thermal burn wound healing by accelerating re-epithelialization with increased expression of CK19 and PCNA in vivo. hAMSCs and hAMSC-CM markedly inhibited heat stress-induced apoptosis in HaCAT and DFL cells in vitro through activation of PI3K/AKT signaling and promoted their proliferation by activating GSK3β/β-catenin signaling. Furthermore, we demonstrated that hAMSC-mediated activation of GSK3β/β-catenin signaling was dependent on PI3K/AKT signaling pathway. Antibody array assay showed that a panel of cytokines including PAI-1, C-GSF, periostin, and TIMP-1 delivered from hAMSCs may contribute to the improvement of the wound healing through activating PI3K/AKT signaling pathway. Conclusion Our results demonstrated that hAMSCs and hAMSC-CM efficiently cure heat stress-induced skin injury by inhibiting apoptosis of skin cells and promoting their proliferation through activating PI3K/AKT signaling pathway, suggesting that hAMSCs and hAMSC-CM may provide an alternative therapeutic approach for the treatment of skin injury.

Hepatocellular carcinoma (HCC) is the third leading cause of the cancer‐related death in the world. Human amniotic mesenchymal stem cells (hAMSCs) have been characterized with a pluripotency, low immunogenicity and no tumorigenicity. Especially, the immunosuppressive and anti‐inflammatory effects of hAMSCs make them suitable for treating HCC. Here, we reported that hAMSCs administrated by intravenous injection significantly inhibited HCC through suppressing cell proliferation and inducing cell apoptosis in tumour‐bearing mice with Hepg2 cells. Cell tracking experiments with GFP‐labelled hAMSCs showed that the stem cells possessed the ability of migrating to the tumorigenic sites for suppressing tumour growth. Importantly, both hAMSCs and the conditional media (hAMSC‐CM) have the similar antitumour effects in vitro, suggesting that hAMSCs‐derived cytokines might be involved in their antitumour effects. Antibody array assay showed that hAMSCs highly expressed dickkopf‐3 (DKK‐3), dickkopf‐1 (DKK‐1) and insulin‐like growth factor‐binding protein 3 (IGFBP‐3). Furthermore, the antitumour effects of hAMSCs were further confirmed by applications of the antibodies or the specific siRNAs of DKK‐3, DKK‐1 and IGFBP‐3 in vitro. Mechanically, hAMSCs‐derived DKK‐3, DKK‐1 and IGFBP‐3 markedly inhibited cell proliferation and promoted apoptosis of Hepg2 cells through suppressing the Wnt/β‐catenin signalling pathway and IGF‐1R‐mediated PI3K/AKT signalling pathway, respectively. Taken together, our study demonstrated that hAMSCs possess significant antitumour effects in vivo and in vitro and might provide a novel strategy for HCC treatment clinically.

The shortage of donors is a major challenge for transplantation; however, organs from genetically modified pigs can serve as ideal supplements 1 , 2 . Until now, porcine hearts and kidneys have been successively transplanted into humans 3 , 4 , 5 , 6 – 7 . In this study, heterotopic auxiliary transplantation was used to donate a six-gene-edited pig liver to a brain-dead recipient. The graft function, haemodynamics, and immune and inflammatory responses of the recipient were monitored over the subsequent 10 days. Two hours after portal vein reperfusion of the xenograft, goldish bile was produced, increasing to 66.5 ml by postoperative day 10. Porcine liver-derived albumin also increased after surgery. Alanine aminotransferase levels remained in the normal range, while aspartate aminotransferase levels increased on postoperative day 1 and then rapidly declined. Blood flow velocity in the porcine hepatic artery and portal and hepatic veins remained at an acceptable level. Although platelet numbers decreased early after surgery, they ultimately returned to normal levels. Histological analyses showed that the porcine liver regenerated capably with no signs of rejection. T cell activity was inhibited by anti-thymocyte globulin administration, and B cell activation increased 3 days after surgery and was then inhibited by rituximab. There were no significant peri-operative changes in immunoglobulin G or immunoglobulin M levels. C-reactive protein and procalcitonin levels were initially elevated and then quickly declined. The xenograft remained functional until study completion. A gene-edited pig liver transplanted into a human recipient remains functional after 10 days and indicates that porcine organs could help meet the growing demand for liver transplants.

Background Liver fibrosis is an outcome of restoring process in chronic liver injury. Human amniotic mesenchymal stem cells (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammatory potential which makes them suitable for treating liver fibrosis. This study aimed to explore the effect and mechanism of hAMSCs on liver fibrosis. Methods hAMSCs were transplanted into carbon tetrachloride (CCl 4 )-induced liver fibrosis mice via tail vein, and the effects of hAMSCs on hepatic fibrosis were assessed. The effects of hAMSCs and hAMSCs conditional medium (CM) on the activation of hepatic stellate cells (HSCs) were investigated in vivo and in vitro. Antibody array assay was used to identify the cytokines secreted by hAMSCs that may inhibit the activation of HSCs. Finally, the underlying mechanisms were explored by assessing IGF-1R/PI3K/AKT and GSK3β/β-catenin signaling pathways in the activated HSCs (LX-2) with hAMSCs and hAMSCs transfected with corresponding siRNAs. Results Our results showed that hAMSCs possessed the characterizations of mesenchymal stem cells. hAMSCs significantly reduced liver fibrosis and improved liver function in mice by inhibiting HSCs activation in vivo. Both hAMSCs and hAMSC-CM remarkably inhibited the collagen deposition and activation of LX-2 cells in vitro. Antibody array assay showed that insulin-like growth factor binding protein-3 (IGFBP-3), Dickkopf-3 (DKK-3), and Dickkopf-1 (DKK-1) were highly expressed in the co-culture group and hAMSC-CM group compared with LX-2 group. Western blot assay demonstrated that IGFBP-3, DKK-3, and DKK-1 derived from hAMSCs inhibit LX-2 cell activation through blocking canonical Wnt signaling pathway. Conclusions Our results demonstrated that IGFBP-3, Dkk3, and DKK-1 secreted by hAMSCs attenuated liver fibrosis in mice through inhibiting HSCs activation via depression of Wnt/β-catenin signaling pathway, suggesting that hAMSCs or hAMSC-CM provides an alternative therapeutic approach for the treatment of liver fibrosis.

Three-dimensional (3D) artificial metacrystals host rich topological phases, such as Weyl points, nodal rings, and 3D photonic topological insulators. These topological states enable a wide range of applications, including 3D robust waveguides, one-way fiber, and negative refraction of the surface wave. However, these carefully designed metacrystals are usually very complex, hindering their extension to nanoscale photonic systems. Here, we theoretically proposed and experimentally realized an ideal nodal ring in the visible region using a simple 1D photonic crystal. The π-Berry phase around the ring is manifested by a 2π reflection phase’s winding and the resultant drumhead surface states. By breaking the inversion symmetry, the nodal ring can be gapped and the π-Berry phase would diffuse into a toroidal-shaped Berry flux, resulting in photonic ridge states (the 3D extension of quantum valley Hall states). Our results provide a simple and feasible platform for exploring 3D topological physics and its potential applications in nanophotonics.

Cell division cycle protein 42 (Cdc42) is a member of the Rho GTPase subfamily that serves as a signal mediating factor in cell cycle division, cytoskeleton arrangement, cell polarization, membrane trafficking and signal transduction. However, the role of Cdc42 in cardiac remodeling, including hypertrophy and fibrosis, remains controversial. This study aimed to clarify the role and underlying mechanism of Cdc42 in cardiac remodeling. Cardiac Cdc42 knockout (Cdc42 CKO ) mice were generated by crossing Cdc42 loxP/loxP mice with MLC2v-Cre mice. Mouse cardiac remodeling models were induced by subcutaneous administration of AngII (1500 ng/kg/min) for 7 days or transverse aortic constriction (TAC) for 2 or 8 weeks. Our results showed that cardiac Cdc42 deletion significantly suppressed AngII- or TAC-induced cardiac hypertrophy and fibrosis and improved cardiac function in mice. Cdc42 CKO or specific inhibition of Cdc42, markedly inhibited Ang II-mediated activation of the MKK3/6-p38 cascade in the heart and in isolated newborn/adult mouse cardiomyocytes or H9c2 cells. Furthermore, Cdc42 overexpression increased the surface area and hypertrophic gene expression in myocytes, whereas ML141 (a Cdc42 inhibitor) and SB203580 (a p38 inhibitor) specifically decreased p38 activation and hypertrophy in Cdc42-overexpressing or AngII-induced hypertrophic cardiomyocytes, indicating that p38 is a downstream effector of Cdc42 in cardiac hypertrophy. Taken together, our results demonstrated that Cdc42 is a key driver of cardiac remodeling via activation of the p38 signaling pathway. Graphical abstract Highlights Cell division cycle protein 42 (Cdc42) participates in cell cycle division, cytoskeleton arrangement, cell polarization, membrane trafficking and signal transduction. Cardiac deletion of Cdc42 protects against multiple mouse models of cardiac remodeling, including hypertrophy and fibrosis, both in vivo and in vitro . Cardiac Cdc42 deficiency attenuates cardiac remodeling by suppressing hypertrophy, apoptosis and inflammation via inhibiting MKK3/6-p38 signaling pathway in myocardium.