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Changlin Mao,1 Wei Dong,2 Jiaju Lu,3 Zhao Zhang,4 Hongliang Wu,5 Armin Ghavamian,1 Dongbin Bi,3 Pei Gao,1 Zhao Liu,5 Sentai Ding1,3 1Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People’s Republic of China; 2Department of Urology, Shandong Provincial Hospital West Branch, Jinan, Shandong, 250000, People’s Republic of China; 3Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 4Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China; 5Department of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Zhao LiuDepartment of Urology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaEmail zhao.liu@sdu.edu.cnSentai DingDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of ChinaEmail dingsentai@126.comObjective: Prostate cancer (PCa) ranks as the second common malignancy in males worldwide. Although conspicuous progressions in diagnosis and treatment have been achieved in the past decades, the prognosis expectation of PCa remains unsatisfied yet. To improve the prognosis prediction of PCa, more specific biomarkers are needed. In this retrospective research, we focused on βKlotho and ETS-like transcription factor 4 (ELK4), aiming to identify potential prognostic biomarkers for PCa.Methods: Western blotting was used to determine the expression of βKlotho, ELK4, and PARP in C4-2B and PC3 PCa cell lines. CCK-8 assay and colony formation assay were applied to examine the roles of βKlotho and ELK4 in the proliferation of PCa cells. The expression of βKlotho and ELK4 in PCa tissue samples was determined by immunochemistry. Pearson’s χ 2 test and Fisher’s exact test were performed to investigate the associations among βKlotho, ELK4 and various clinical factors. Kaplan–Meier curves and Cox regression model were established to reveal the correlation among βKlotho, ELK4 expression and the prognosis of patients.Results: βKlotho overexpression down-regulated the ELK4 expression, induced apoptosis and inhibited cell proliferation in both C4-2B and PC3 cells, which were reversed by ELK4 overexpression. βKlotho expression in PCa tissue samples had negative correlation with the ELK4 expression, and higher βKlotho expression was associated with lower Gleason score, absent distant metastasis and lower prostate-specific antigen (PSA) level. On the contrast, higher ELK4 expression was correlated with distant metastasis and higher PSA level. Moreover, βKlotho and ELK4 were both recognized as independent factors for the prognosis of patients with PCa.Conclusion: βKlotho inhibits proliferation of prostate cancer cells by downregulating ELK4. Both βKlotho and ELK4 expressions correlate with the prognosis of PCa, which may serve as potential biomarkers for follow-up surveillance and prognostic assessments.Keywords: FGFR, biomarker, prostate cancer, survival

Shiyu Mao,1 Yuan Wu,2 Ruiliang Wang,1 Yadong Guo,1 Dexi Bi,3 Wenchao Ma,2 Wentao Zhang,1 Junfeng Zhang,1,* Yang Yan,1 Xudong Yao1,* 1Department of Urology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, People’s Republic of China; 2Department of Urology, Shanghai Tenth People’s Hospital, Anhui Medical University, Hefei 230032, People’s Republic of China; 3Department of Pathology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junfeng Zhang; Xudong YaoDepartment of Urology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, People’s Republic of ChinaTel +8613817811836Fax +86-21-66305158Email zjfdipan@126.com; yaoxudong1967@163.comBackground: Growth arrest-specific 6 (GAS6) is a secreted vitamin K-dependent protein abnormally expressed in various human tumor tissues and can activate the receptor Tyro3, Axl, and Mer to promote cancer cell proliferation and invasion. Until now, the role of GAS6 has been poorly understood in bladder cancer (BCa).Materials and Methods: Using bioinformatics analysis, we screened genes significantly associated with overall survival in BCa. The association between GAS6 and survival was evaluated by tissue microarray and IHC staining. We investigated the effect of GAS6 on the development of BCa through in vitro and in vivo experiments.Results: Here, we report that GAS6 is highly expressed in bladder cancer and is significantly associated with tumor grade, T stage, and worse prognosis. We found that GAS6 depletion inhibited proliferation, migration, and invasion of BCa cells. In addition, bioinformatics analysis revealed that GAS6 may be involved in the regulation of PI3K-AKT signaling pathway by binding to receptor TAM and has a significant positive correlation with PI3K family gene expression. Furthermore, Western blot experiments have shown that GAS6 might modulate the PI3K-AKT signaling to regulate proliferation and invasion of BCa cells. Treatment of BCa cells with SC79, an AKT activator, partially restored the effect of GAS6 silencing on cell proliferation and invasion.Conclusion: The present study suggests that GAS6 may play a pivotal role in the development of BCa and may be a potential target for its treatment.Keywords: bladder cancer, GAS6, proliferation, invasion, PI3K/AKT

Gangfeng Hu,1,2 Hui Wang,1 Xiaocong Yao,1 Dawei Bi,1 Gang Zhu,1 Songchao Tang,2 Jie Wei,2 Lili Yang,3 Peijian Tong,4 Luwei Xiao4 1The First People’s Hospital of Xiaoshang, Hangzhou, People’s Republic of China; 2Key Laboratory of Ultra-fine Materials, Ministry of Education, East China University of Science and Technology, Shanghai, People’s Republic of China; 3Department of Orthopedic Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai, People’s Republic of China; 4Zhejiang Traditional Chinese Medical University, Hangzhou, People’s Republic of China Abstract: Fluorapatite with low solubility is a promising biomaterial due to its structure, which is similar to hydroxyapatite. In this study a bioactive composite of nanofluorapatite (n-FA) and polyamide 12 (PA12) was fabricated. The results revealed that the mechanical properties (such as compressive strength and elastic modulus), hydrophilicity, and antibacterial properties of n-FA/PA12 composite were obviously improved by adding n-FA into PA12 as compared with PA12. In addition, cell proliferation of MC3T3-E1 cells cultured on n-FA/PA12 composite was significantly higher than with PA12, and alkaline phosphatase activity of MC3T3-E1 cells on the n-FA/PA12 composite was expressed at obviously higher levels as compared with PA12. The results suggest that n-FA/PA12 composite could support cell proliferation and differentiation, showing good cytocompatibility. Histological evaluation indicates that n-FA/PA12 composite enhances the efficiency of new bone formation with the introduction of n-FA into PA12, and the quantity of the newly formed bone for n-FA/PA12 composite is significantly higher than with PA12. In conclusion, n-FA/PA12 composite exhibits good biocompatibility and osteogenesis, which might be used for various orthopedic prostheses and dental implants. Keywords: nanofluorapatite, bioactive composites, cell behavior, orthopedic implants

Gangfeng Hu,1 Luwei Xiao,2 Peijian Tong,2 Dawei Bi,1 Hui Wang,1 Haitao Ma,1 Gang Zhu,1 Hui Liu21The First People’s Hospital of Xiaoshan, Hangzhou, China; 2Zhejiang Traditional Chinese Medical University, Hangzhou, ChinaAbstract: Nanoporous bioglass containing silver (n-BGS) was fabricated using the sol-gel method, with cetyltrimethyl ammonium bromide as template. The results showed that n-BGS with nanoporous structure had a surface area of 467 m2/g and a pore size of around 6 nm, and exhibited a significantly higher water absorption rate compared with BGS without nanopores. The n-BGS containing small amounts of silver (Ag) had a slight effect on its surface area. The n-BGS containing 0.02 wt% Ag, without cytotoxicity, had a good antibacterial effect on Escherichia coli, and its antibacterial rate reached 99% in 12 hours. The n-BGS’s clotting ability significantly decreased prothrombin time (PT) and activated partial thromboplastin time (APTT), indicating n-BGS with a higher surface area could significantly promote blood clotting (by decreasing clotting time) compared with BGS without nanopores. Effective hemostasis was achieved in skin injury models, and bleeding time was reduced. It is suggested that n-BGS could be a good dressing, with antibacterial and hemostatic properties, which might shorten wound bleeding time and control hemorrhage.Keywords: antibacterial, bioglass, cytotoxicity, dressing, hemostasis, nanopore, silver

BRM is an ATPase component of the SWI/SNF complex that regulates chromatin remodeling and cell proliferation and is considered a tumor suppressor. In this study we characterized transcripts from the Smarca2 gene that encodes the BRM protein. We found that the human Smarca2 gene (hSmarca2), like its mouse counterpart (mSmarca2), also initiated a short transcript from intron 27 of the long transcript. We name the long and short transcripts as Smarca2-a and Smarca2-b, respectively. Like its human counterpart, mSmarca2-a also underwent alternative splicing at the 54-bp exon 29. The hSmarca2-b had two alternative initiation sites and underwent alternative splicing at three different 3' sites of exon 1 and at exons 2, 3 and/or 5. We identified nine hSmarca2-b mRNA variants that might produce five different proteins. mSmarca2-b also underwent alternative splicing at exon 3 and/or exon 5, besides alternatively retaining part of intron 1 in exon 1. Smarca2-b was expressed more abundantly than Smarca2-a in many cell lines and was more sensitive to serum starvation. Moreover, cyclin D1 also regulated the expression of both Smarca2-a and Smarca2-b in a complex manner. These data suggest that the functions of the Smarca2 gene may be very complex, not just simply inhibiting cell proliferation, and in certain situations may be elicited mainly by expressing the much less known Smarca2-b, not the better studied Smarca2-a and its products BRM proteins.

The objective of this study was to compare the indications and outcomes of the total inferior border ostectomy and T-shape genioplasty. A retrospective study was conducted using the clinical notes and records of patients who underwent total inferior border ostectomy (group 1, n = 42) and T-shape genioplasty (group 2, n = 60). The outcomes were evaluated by assessment of computed tomography images combined with medical records and photographs. Lower facial height, chin width, chin symmetry, and facial proportions, as well as patient satisfaction and complications were investigated. The data were collected preoperatively and 6–24 months postoperatively. All 102 patients showed an improved lower facial contour. No severe complications were observed during the follow-up period. Although the postoperative lower to midfacial height ratios were similar in the two groups (P = 0.080), both the preoperative and postoperative chin width to lower facial height ratios were lower in group 1 (both P < 0.001). A larger amount of chin narrowing, as well as better chin symmetry were observed in group 1 (P < 0.001). In conclusion, compared to the T-shape genioplasty, the total inferior border ostectomy is well suited for a longer, wider, and more asymmetrical chin. The surgical options should be considered and chosen quantitatively to achieve aesthetically pleasing results. [ABSTRACT FROM AUTHOR]

As the presence of friction in a haptic display device seriously affects its performance, proper compensation of the frictional effects in such a device is of practical importance for advanced virtual reality applications where haptic display plays a critical role. This paper addresses the issue of friction modeling and compensation for haptic control system designs. A new method based on the Support Vector Machine (SVM) is developed in a controller design based on a two-port network to achieve accurate haptic display. The approximation model of friction is established offline through SVM learning and is used for online feed forward friction compensation. The advantages of this novel method are demonstrated through the experiments performed. Index Terms--Friction modeling and compensation, haptic display, Support Vector Machine (SVM), two-port-network-based controller.