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High-altitude adaptation of Tibetans represents a remarkable case of natural selection during recent human evolution. Previous genome-wide scans found many non-coding variants under selection, suggesting a pressing need to understand the functional role of non-coding regulatory elements (REs). Here, we generate time courses of paired ATAC-seq and RNA-seq data on cultured HUVECs under hypoxic and normoxic conditions. We further develop a variant interpretation methodology (vPECA) to identify active selected REs (ASREs) and associated regulatory network. We discover three causal SNPs of EPAS1, the key adaptive gene for Tibetans. These SNPs decrease the accessibility of ASREs with weakened binding strength of relevant TFs, and cooperatively down-regulate EPAS1 expression. We further construct the downstream network of EPAS1, elucidating its roles in hypoxic response and angiogenesis. Collectively, we provide a systematic approach to interpret phenotype-associated noncoding variants in proper cell types and relevant dynamic conditions, to model their impact on gene regulation., Tibetan adaptation to the high-altitude environment represents a case of natural selection during recent human evolution. Here the authors investigated the chromatin and transcriptional landscape of umbilical endothelial cells from Tibetan and Han Chinese donors and provide genome-wide characterization of the hypoxia regulatory network associated high-altitude adaptation.

Several chemical compounds can restore pigmentation in vitiligo through mechanisms that vary according to disease etiology. In the present study, we investigated the melanogenic activity of six structurally distinct compounds, namely, scopoletin, kaempferol, chrysin, vitamin D3, piperine, and 6-benzylaminopurine. We determined their effectiveness, toxicity, and mechanism of action for stimulating pigmentation in B16F10 melanoma cells and in a zebrafish model. The melanogenic activity of 6-benzylaminopurine, the compound identified as the most potent, was further verified by measuring green fluorescent protein concentration in tyrp1 a: eGFP (tyrosinase-related protein 1) zebrafish and mitfa: eGFP (microphthalmia associated transcription factor) zebrafish and antioxidative activity. All the tested compounds were found to enhance melanogenesis responses both in vivo and in vitro at their respective optimal concentration by increasing melanin content and expression of TYR and MITF. 6-Benzyamino-purine showed the strongest re-pigmentation action at a concentration of 20 μmol·L-1in vivo and 100 μmol·L-1in vitro, and up-regulated the strong fluorescence expression of green fluorescent protein in tyrp1a: eGFP and mitfa: eGFP zebrafish in vitro. However, its relative anti-oxidative activity was found to be very low. Overall, our results indicated that 6-benzylaminopurine stimulated pigmentation through a direct mechanism, by increasing melanin content via positive regulation of tyrosinase activity in vitro, as well as up-regulating the expression of the green fluorescent protein in transgenic zebrafish in vivo.

By controlling the hydrolysis of titanium butoxide, followed with or without an ethanol washing process, the preparation of nanoscale titania powder was studied in detail. The characteristics of different powders produced by the direct precipitation (without an ethanol wash) and ethanol wash processes were studied by X-ray diffraction, transmission electron microscopy, BET, thermogravimetry and differential thermal analysis techniques. By comparison, it was found that both the direct precipitation and ethanol wash methods can obtain slightly agglomerated nanoscale titania powders of less than 15 nm, but the ethanol wash can further reduce the agglomeration. The particle sizes of titania powders can be modified while still retaining the anatase structure.

A heterogeneous azeotropic distillation process was effectively used to dehydrate hydrous zirconia and therefore prevent the formation of hard agglomerates in the preparation of nanoscale zirconia powder. The mechanism of azeotropic distillation to prevent hard agglomerate from forming was studied by investigating the interaction of hydrous zirconia with n-butanol. The prepared powder was sintered to 99.5% of theoretical density by slow-sintering (average grain size of ∼200 nm), 97.5% by fast-sintering (average grain size of ∼120 nm) at 1250°C.

The preparation of highly pure fine zircon powders (ZrSiO 4 ) was studied using ZrOCl 2 and fumed SiO 2 by the wet chemical method. The gel formation obtained by adding NH 3 ·H 2 O to the slurry consisting of ZrOCl 2 solution and fumed SiO 2 was seeded with zircon sand. The optimum process found to synthesize highly pure fine zircon powder was to calcine the gel at 1400°C for 2h after preheat treatment at 700°C for 2h. The powders obtained are composed of submicrometer particles. The relative density of specimens hot-pressed at 1650°C for 1h under 20 MPa reaches 99·2% and the flexural strength at room temperature is 360 MPa.

In this paper, the role of material chemistry for the synthesis and processing of advanced materials is addressed. Advanced nitride materials, essentially those that may be generated within the complex Si-Al-Y-N-0 system have been chosen to illustrate the two issues that material chemistry studies are important. These are: (1) the phase compositional design of materials guided by a detailed knowledge of the phase relationships of these complex systems; and (2) the kinetics related with the processing of silicon nitride solid solution - Sialon composites and its influence on microstructure development. It is aimed to explore the potential of these material chemistry approaches by some examples studied in this Lab. It is also relevant to note that significant advancements can be expected through close collaboration between chemists, physicists, and materials scientists and that is what is called for in the Age of Materials.

To study the effects of placement of double cannula using trocar puncture for intra-abdominal abscess drainage.A retrospective study was performed to investigate the clinical data of 32 patients undergoing intra-abdominal abscess drainage with double cannula placed using trocar puncture between June 2010 and December 2010.the location and size of the abscess was evaluated by ultrasound and CT. Placement of double cannula using trocar puncture was performed under CT or ultrasound guidance.Trocar puncture was successful in all the patients. One patient died of liver metastasis and multiple organ failure after surgery for pancreatic cancer. One patient required laparotomy and drainage because non-localization of sepsis from intestinal fistula. The remaining 30 patients experienced alleviation of septic symptoms after drainage and eventually cured. The mean healing time was(7±3) days. Two patients developed subcutaneous bleeding and were management by local compression.Placement of double cannula using trocar puncture for intra- abdominal abscess drainage results in satisfactory outcomes. This technique is especially suitable for abscesses with viscous drainage, those with the presence of phlegmon or necrotic debris, and those with multiple large cavities.

To investigate the effects of microRNA-144 (miR-144) expression on H9C2 (2-1) myocytes.MiR-144 was up-regulated in primary cultured H9C2 (2-1) myocytes through transfection. Cells transfected with Lipofectamine(TM) 2000 and its mixture with miRNA synthesized randomly as blank control and negative control respectively. The up-regulation of miR-144 was confirmed by real-time PCR. Cell apoptosis was evaluated by means of CCK-8, Caspase-3 and flow cytometry.Real-time PCR results showed that the miR-144 expression was obviously increased in miR-144 up-regulation group (2178.84 ± 838.52) compared with negative (2.06 ± 0.73) and blank (1.00 ± 0.00) control group (all P0.01). The proliferation was lower, the activity of Caspase-3 was elevated and the apoptosis rates were significantly increased in miR-144 up-regulation group compared with negative and blank control group, while no significant difference was found between the latter 2 groups.MiR-144 mimics may selectively up-regulate the expression of miR-144 in myocardial cells and consequently promote apoptosis and inhibit proliferation in myocardial cells.

In this paper, the role of material chemistry for the synthesis and processing of advanced materials is addressed. Advanced nitride materials, essentially those that may be generated within the complex Si-Al-Y-N-0 system have been chosen to illustrate the two issues that material chemistry studies are important. These are: (1) the phase compositional design of materials guided by a detailed knowledge of the phase relationships of these complex systems; and (2) the kinetics related with the processing of silicon nitride solid solution - Sialon composites and its influence on microstructure development. It is aimed to explore the potential of these material chemistry approaches by some examples studied in this Lab. It is also relevant to note that significant advancements can be expected through close collaboration between chemists, physicists, and materials scientists and that is what is called for in the Age of Materials.

Phase relationships in Si3N4-AIN-MxOy systems involving α′-sialon, where M represents lithium, magnesium, calcium, yttrium, neodymium, samarium, gadolinium, dysprosium, erbium and ytterbium are outlined. Their implications for the formation and fabrication of single-phase α′-sialon and two-phase β:α′ sialon ceramics are discussed.

The aim of this study was to identify the presence of dopamine receptor D2 and adenosine receptor A2A in human retinal pigment epithelium (RPE) in order to determine whether the RPE is a potential site of action for these two receptors.RPE Cells were isolated and cultured. Reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry were performed to detect the expression of D2 and A2A receptors in the RPE.RT-PCR analysis showed that mRNA of D2 and A2A receptors were expressed in the RPE. D2 and A2A receptors were distributed in the RPE by immunocytochemistry.This study demonstrated the presence of D2 and A2A receptors in human RPE at both mRNA and protein levels. D2 and A2A receptors may play an important role in the maintenance of the function of human retinal pigment epithelium. Furthermore, their cooperation appeared to be important in the development of axial myopia and retinal and choroidal neovascularization.

The aim of this study was to identify the presence of retinoid acid receptors in cultured human scleral fibroblasts and the effect of retinoic acid (RA) on the regulation of cell growth.Human scleral fibroblasts from three donors were isolated and cultured in Dulbecco Modified Ealge's Medium. Cells from the third or fifth generation were used in the present study. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used to detect the expression of retinoid acid receptor subtypes in the fibroblasts. RA was added to the culture medium at concentrations of 0.01, 0.10, 1.00, 10.00 and 100.00 nmol/L, separately. Cells were counted and statistically analyzed six days after being treated with RA. Each strain of the cells was examined three times.Cultured fibroblasts mainly showed a bipolar or spindle-shaped morphology with an average time of 2 to 3 days for each division. RT-PCR showed mRNA expression of six subtypes of RA receptors (RAR alpha, RAR beta, RAR gamma, RXR alpha, RXR beta, and RXR gamma). The proliferation of scleral fibroblasts was inhibited by 2.2%, 17.6%, 37.6%, 43.8% and 63.2% following the treatment with 0.01, 0.10, 1.00, 10.00 and 100.00 nmol/L of RA, respectively. Cell proliferation in RA-treated samples reduced significantly as compared to the control samples (P0.05) when the RA concentration exceeded 0.10 nmol/L.Six retinoid acid receptor subtypes are present in cultured human scleral fibroblasts and the growth of scleral fibroblasts was inhibited significantly by retinoic acid. These findings indicate that the sclera is a potential site of action for the retinoid acid during progression of myopia.

The aim of this study was to identify the presence of muscarinic acetylcholine receptors-I (M1 receptor) in human retinal pigment epithelium (RPE) in order to determine the role of M1 receptor in the maintenance of function of RPE and its role in the occurrence and development of myopia.The 3rd-5th passages of RPE cells established in our laboratory were used in the present study. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect mRNA expression of M1 receptor in cultured RPE. Immunocytochemistry was used to detect M1 receptor protein in the RPE cells.Cultured RPE demonstrated mRNA expression of M1 receptor in RT-PCR. Protein of M1 receptor was presented in the RPE under immunocytochemistry.This study demonstrated the presence of M1 receptor in human RPE at both mRNA and protein levels. M1 receptor plays an important role in the maintenance of function of RPE. Injection of M1 receptor antagonist into the vitreous can delay the occurrence and inhibit the development of myopia, which is possibly related to the inhibition of RPE cells function.

In this paper, the following frontier RD (2) Processing, microstructure and properties of advanced ceramics; (3) Strengthening and toughening of advanced ceramics; and (4) Bioceramics and their superfine microstructure studies. The major intention of this overview is to attract comments and discussions with an aim to stimulate new ideas for the advancement of this important branch of materials science and engineering.

The present work is concerned with the thermal shock behavior of a ceramic matrix composite consisting of an alumina base containing 5vol% of copper particles. The composite, hot-pressed at 1550°C, exhibited increased flexural strength, enhanced toughness and higher resistance to thermal shock compared with monolithic alumina. Some mechanical and thermal properties relevant to thermal shock were discussed which gave plausible explanations for the differences between the composite and the monolithic alumina.

The processing of silicon nitride reinforced with carbon fibre was studied. The problems of physical and chemical incompatibility between carbon fibre and the silicon nitride matrix were solved by addition of a small amount of zirconia to the matrix and by low-temperature hot-pressing. The composite material possesses a much higher toughness than hot-pressed silicon nitride. Its work of fracture increased from 19.3 J m−2 for unreinforced Si3N4, to 4770 J m−2; its fracture toughness,K lc , increased from 3.7 MN m−3/2 for unreinforced material, to 15.6 MN m−3/2. The strength remains about the same as unreinforced Si3N4 and the thermal expansion coefficient is only 2.51×10−6 ° C−1 (RT to 1000° C). It is anticipated that this composite may be promising because of its mechanical and good thermal shock-resistance properties.