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Background: Phase I/II clinical trials using fetal retinal pigment epithelium (fRPE), human embryonic stem cell (hESC)-derived RPE, or human induced pluripotent stem cell (hiPSC)-derived RPE as potential sources of materials for cell-based therapy to treat degenerative retinal diseases have been carried out during the past decade. Challenges for successful translational cell-based therapy include cell manufacture, cell quality, cell storage, and cell behavior in vivo. In this study, we investigated the culture-induced changes in passaged fetal RPE, hESC-RPE and hiPSC-RPE cells in vitro and explored the differentiation and maturation effect of all-trans retinoic acid (ATRA) on those RPE cells. Methods: A total of 9 fetal RPE cell lines, hESC-RPE and hiPSC-RPE cell lines were set up using previously described methods. The culture-induced changes in subsequent passages caused by manipulating plating density, dissociation method and repeated passaging were studied by microscope, real-time quantitative PCR, western blot and immunofluorescent assays. Gene and protein expression and functional characteristics of fRPE, hESC-RPE and hiPSC-RPE incubated with ATRA at different concentration were also evaluated.Results: Compared with fRPE, hESC-RPE and hiPSC-RPE showed decreased gene and protein expression of RPE markers. Passage 3 RPE of all three types seeded at a density of 6×105 and 9x105 cells/mL in basal medium maintained pigmented polygonal, cobblestone-like morphology. RPE cells underwent mesenchymal changes showing increased expression of mesenchymal markers including a-SMA, N-cadherin, fibronectin and decreased expression of RPE markers including RPE65, E-cadherin and ZO-1, as a subsequence of low plating density, inappropriate dissociated method, and repeated passaging. fRPE, hESC-RPE and iPSC-RPE treated by ATRA at different concentrations showed increased expression of RPE markers such as RPE65, bestrophin (BEST) and CRALBP, and increased expression of negative complement regulatory proteins (CRP) including complement factor H (CFH), CD46, CD55 and CD59, and increased transepithelial resistance (TER) as well.Conclusion: Although hESC and hiPSC-derived RPE are morphologically similar to fRPE, and also have the tendency to undergo epithelial-to-mesenchymal transition (EMT) changes during the culturing and passaging process in vitro, differences in protein and gene expression among three RPE types exist. Moreover, ATRA can increase RPE markers expression, as well as to increase the expression levels of CRPs gene and protein in fRPE and stem cell-derived RPE.

Xuedong Li,1,2,* Xixi Lin,1,2,* Zuoxing Wu,3 Yuangang Su,1,2 Jiamin Liang,1,2 Runfeng Chen,1,2 Xue Yang,1,2 Lei Hou,4 Jinmin Zhao,1,5 Qian Liu,5 Feng Xu1,2,6 1Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 2Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 3School of Medicine, Xiamen University, Xiamen, Fujian 361102, People’s Republic of China; 4Department of Cardiology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 5Research Centre for Regenerative Medicine, Orthopaedic Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 6Department of Subject Planning Shanghai, Ninth People’s Hospital Shanghai, Jiaotong University School of Medicine, Shanghai 200011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng XuDepartment of Subject Planning Shanghai, Ninth People’s Hospital Shanghai, Jiaotong University School of Medicine, Shanghai, People’s Republic of ChinaEmail xufenghhou@163.comQian LiuResearch Centre for Regenerative Medicine, Orthopaedic Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of ChinaEmail luoboqian@hotmail.comIntroduction: Osteoporosis is an osteolytic bone condition characterized by decreased bone strength and increased bone fragility. It is the result of elevated formation or activity of bone-resorbing osteoclasts. Although current therapeutic agents are efficacious against osteoclast-mediated bone loss, detrimental side effects preclude the long-term use of these agents. Pristimerin (PRI) is a naturally occurring quinone-methide triterpenoid that has been revealed to exert anti-inflammatory and anti-tumor effects via regulating various signaling cascades including NF-κB and MAPK activation.Methods: The bone marrow macrophages were used to confirm the anti-osteoclastic and anti-resorptive functions of PRI in vitro. An in vivo ovariectomy (OVX) model was applied to verify the function of PRI protecting bone loss.Results: PRI abolished the early activation of NF-κB and ERK MAPK signal cascades thereby thwarting the downstream expression of c-Fos and NFATc1, which prevented the production of mature osteoclasts. In vivo, PRI protects mice against ovariectomy (OVX)-mediated bone loss by diminishing osteoclast formation and bone resorptive activity.Conclusion: Our study shows that PRI demonstrates therapeutic potential in the effective treatment against osteoclast-induced osteolytic diseases like osteoporosis.Keywords: osteoporosis, osteoclast, pristimerin, ERK, NF-κB

A structure of pn junction with ferroelectric layer (PbTiO3/pn-Si, or PTO/pn cell) was prepared. Instability of open circuit voltage (Voc) was found in this structure. Voc of the cells will decreas...

PbTiO3 (PTO) thin film was deposited on a Si-based pn-junction to form a ferroelectric-pn junction structure (PTO/pn cell). It exhibits a coupling photovoltaic property. Voc of the PTO/pn cell is a...

This is the first study that empirically investigates the contribution that an expansion in China's emerging services sector may make to China's per capita economic growth. In addition, the study examines the spillover effects of growth in China's services sector on growth in the manufacturing sector and vice versa. The framework consists of a single structural growth equation and a simultaneous equation to measure the spillover effects. Multiple regression analysis is used to analyse data from 1994 to 2011. The empirical results indicate that an increase in exports and government spending will positively affect value-added in the services sector. The findings also indicate that the services sector has a positive influence on the growth of per capita GDP. Finally, as published studies on the contribution of the services sector to China's per capita growth are sparse, the study presents policy implications.

0.9Pb(Sc0.5Ta0.5)O3-0.1PbTiO3 (PSTT10) thin films were deposited on Si(1 0 0) substrate with a LaNiO3 buffer layer by RF magnetron sputtering technique and post annealed by a two-steps rapid thermal annealing method. Dielectric, ferroelectric behaviors and surface morphology of the films were analyzed. The films show good ferroelectric and dielectric properties which is similar to the PSTT5 thin films. The leakage current behavior of the films is according with Ohm law in a low electric field region, while it satisfies a space-charge limited conduction in a medium electric field region. With the increasing of frequency, the dielectric constant decrease and the dielectric loss increase, which shows a typical relaxor behavior. The dielectric constant of the films in low frequency band can be explained as Rayleigh law. The films exhibits crack free and uniform surface, with roughness of about 17 nm.

The 0.95Pb(Sc 0.5 Ta 0.5 )O 3 -0.05%PbTiO 3 (PSTT5) thin films were deposited on LSCO/Pt/SiO 2 /Si(110) substrate by magnetron sputtering. The samples were annealed at 650°C∼ 850°C in a rapid thermal annealing (RTA) furnace from 1∼ 6 minutes. The x-ray diffraction patterns show that the PSTT5 films were (220) preferred orientation after annealing at 850°C for 1 min. This films possess dielectric constant ϵ r = 450 with loss tgδ = 0.118 at 1kHz. Ferroelectric hysteresis loop of this films showed the remanent polarization 2P r and the coercive field 2E c were 40 μ C/cm 2 , 85 kV/cm, respectively. The leakage currents of the films at ± 80 kV/cm were in the order of 10−5A/cm 2 .

Wenji Zhang,1,3,* Xuedong Li,2,* Tiantian Ye,3 Fen Chen,3 Shihui Yu,3 Jianting Chen,3 Xinggang Yang,3 Na Yang,2 Jinsong Zhang,2 Jinlu Liu,2 Weisan Pan,3 Jun Kong2 1Department of Pharmaceutics, School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Department of Ophthalmology, The Fourth Affiliated Hospital of China Medical University, Eye Hospital of China Medical University, Key Lens Research Laboratory of Liaoning Province, Shenyang, People’s Republic of China; 3Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China *These authors contributed equally to this work Abstract: This study was carried out to evaluate the ocular performance of a cationic Eudragit (EDU) RS 100-coated nanostructured lipid carrier (NLC). The genistein encapsulated NLC (GEN-NLC) was produced using the melt-emulsification technique followed by surface absorption of EDU RS 100. The EDU RS 100 increased the surface zeta potential from −7.46 mV to +13.60 mV, by uniformly forming a spherical coating outside the NLC surface, as shown by transmission electron microscopy images. The EDU RS 100 on the NLC surface effectively improved the NLC stability by inhibiting particle size growth. The obtained EDU RS 100-GEN-NLC showed extended precorneal clearance and a 1.22-fold increase in AUC (area under the curve) compared with the bare NLC in a Gamma scintigraphic evaluation. The EDU RS 100 modification also significantly increased corneal penetration producing a 3.3-fold increase in apparent permeability coefficients (Papp) compared with references. Draize and cytotoxicity testing confirmed that the developed EDU RS 100-GEN-NLC was nonirritant to ocular tissues and nontoxic to corneal cells. These results indicate that the NLC surface modified by EDU RS 100 significantly improves the NLC properties and exhibits many advantages for ocular use. Keywords: genistein, precorneal retention, cytotoxicity