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Summary Emerging technologies in stem cell engineering have produced sophisticated organoid platforms by controlling stem cell fate via biomaterial instructive cues. By micropatterning and differentiating human induced pluripotent stem cells (hiPSCs), we have engineered spatially organized cardiac organoids with contracting cardiomyocytes in the center surrounded by stromal cells distributed along the pattern perimeter. We investigated how geometric confinement directed the structural morphology and contractile functions of the cardiac organoids and tailored the pattern geometry to optimize organoid production. Using modern data-mining techniques, we found that pattern sizes significantly affected contraction functions, particularly in the parameters related to contraction duration and diastolic functions. We applied cardiac organoids generated from 600 μm diameter circles as a developmental toxicity screening assay and quantified the embryotoxic potential of nine pharmaceutical compounds. These cardiac organoids have potential use as an in vitro platform for studying organoid structure-function relationships, developmental processes, and drug-induced cardiac developmental toxicity., Graphical abstract, Highlights • Micropattern-based geometric confinement directs cardiac organoid development • Cardiac organoid structure-function relationships are guided by organoid size • Cardiac organoids can be used as an in vitro embryotoxicity assessment tool, Advances in organoid engineering have produced sophisticated organoid platforms by controlling stem cell fate via biomaterial instructive cues. Ma and colleagues show that micropatterning is a versatile tool to engineer cardiac organoids with different architectures and cardiac functions. Furthermore, the cardiac organoid development was sensitive to numerous drug compounds and demonstrated potential as an embryotoxicity screening platform.

A k -bisection of a graph G is a partition of its vertex set into two sets V 1 and V 2 such that | | V 1 | − | V 2 | | ≤ 1 and every connected component of G [ V i ] has at most k vertices, where G [ V i ] denotes the subgraph of G induced by V i ( i = 1 , 2 ). A subcubic graph is a graph with maximum degree at most three. In this note, we prove that every subcubic graph G admits a 3-bisection ( V 1 , V 2 ) with an additional property that every connected component of G [ V i ] ( i = 1 , 2 ) is acyclic. This extends a recent result of Esperet, Mazzuoccolo and Tarsi who showed that every cubic graph admits such a 3-bisection.

In recent years, the increasing use of environmental endocrine disruptors has caused serious environmental pollution and hurt aquatic organisms. It is still risky for aquatic species and humans exposed to 17α-methyltestosterone (MT), however, the harmful effect of MT on fish is still poorly understood. The main purpose of this study is to evaluate the influence of MT on Pseudorasbora parva at multi-levels. We analyzed gonadal histology, the sex steroid hormones, steroidogenic genes expression, and transcriptome profiling of gonads in response to MT in adult P. parva. Through this study, we found MT could inhibit the gonadal development of P. parva, and the growth and development of fish could be delayed by exposure to MT at 200 ng/L. MT could produce disruption effects on fish from multiple pathways, while its interference to the HPGL axis happens primarily through the steroidogenic pathway, e.g., disturbing the expression of crucial genes and sex steroids synthesis. Besides, we constructed 4 RNAseq libraries and obtained 7758 and 11,543 DEGs in females and males, respectively. Interestingly, we found MT had more obvious disruption effects on males than the females, mainly reflected in the immune system. Interestingly, we found three common pathways in both sexes after MT exposure, i.e., cell adhesion molecules, cytokine-cytokine receptor interaction, and neuroactive ligand-receptor interaction. These results confirm the suitability of P. parva as a model fish for aquatic toxicological study and provide us a multidimensional sight for the disruption effects of MT on fish.

Hartsfield and Ringel constructed orientable quadrangular embeddings of the complete graph $K_n$ for $n\equiv 5 \pmod 8$, and nonorientable ones for $n \ge 9$ and $n\equiv 1 \pmod 4$. These provide minimal quadrangulations of their underlying surfaces. We extend these results to determine, for every complete graph $K_n$, $n \ge 4$, the minimum genus, both orientable and nonorientable, for the surface in which $K_n$ has an embedding with all faces of degree at least $4$, and also for the surface in which $K_n$ has an embedding with all faces of even degree. These last embeddings provide sharpness examples for a result of Hutchinson bounding the chromatic number of graphs embedded with all faces of even degree, completing the proof of the Even Map Color Theorem. We also show that if a connected simple graph $G$ has a perfect matching and a cycle then the lexicographic product $G[K_4]$ has orientable and nonorientable quadrangular embeddings; this provides new examples of minimal quadrangulations.

Anaerobic degradation is the major pathway for microbial degradation of benzene, toluene, ethylbenzene, and xylenes (BTEX) under electron acceptor lacking conditions. However, how exogenous electron acceptors modulate BTEX degradation through shaping the microbial community structure remains poorly understood. Here, we investigated the effect of various exogenous electron acceptors on BTEX degradation as well as methane production in anaerobic microbiota, which were enriched from the same contaminated soil. It was found that the BTEX degradation capacities of the anaerobic microbiota gradually increased along with the increasing redox potentials of the exogenous electron acceptors supplemented (WE: Without exogenous electron acceptors SS: Sulfate supplement FS: Ferric iron supplement NS: Nitrate supplement), while the complexity of the co-occurring networks (e.g., avgK and links) of the microbiota gradually decreased, showing that microbiota supplemented with higher redox potential electron acceptors were less dependent on the formation of complex microbial interactions to perform BTEX degradation. Microbiota NS showed the highest degrading capacity and the broadest substrate-spectrum for BTEX, and it could metabolize BTEX through multiple modules which not only contained fewer species but also different key microbial taxa (eg. Petrimonas, Achromobacter and Comamonas). Microbiota WE and FS, with the highest methanogenic capacities, shared common core species such as Sedimentibacter, Acetobacterium, Methanobacterium and Smithella/Syntrophus, which cooperated with Geobacter (microbiota WE) or Desulfoprunum (microbiota FS) to perform BTEX degradation and methane production. This study demonstrates that electron acceptors may alter microbial function by reshaping microbial community structure and regulating microbial interactions and provides guidelines for electron acceptor selection for bioremediation of aromatic pollutant-contaminated anaerobic sites.

Well Wutan 1 is a wildcat well deployed in the Dazhou–Kaijiang paleo-uplift, eastern Sichuan Basin and its design depth is 7570 m. The Cambrian and Sinian strata are its main exploration targets, and the strata below the Silurian in this well are geologically uncertain with a high risk. A large section of gypsum-salt layer may be encountered in the Cambrian and the longitudinal pressure system is complex. It is predicted that the bottom hole temperature is up to 175 °C, and the bottom hole liquid column pressure exceeds 140 MPa, and there is hydrogen sulfide. As a result, the casing program design is confronted with great challenges. In this paper, the difficulties and risks of drilling engineering were analyzed. Then, a casing program was designed and optimized referring to the successful drilling experience of subsalt ultra-deep wells at home and abroad, combined with the pressure system characteristics of Well Wutan 1 and the creep performance of gypsum-salt layers. Finally, the casing program was applied on site. And the following research results were obtained. First, in order to prevent lost circulation, blowout and differential pressure induced stuck pipe in the open hole section, it is determined that the casing program shall be in the pattern of six-section casing with 5 setting points. Second, no setting point is needed in the Carboniferous pressure depleted reservoir for it is lithologically tight and differential pressure induced stuck pipe and lost circulation are less risky. Third, to better isolate the salt layer, one section of casing is specially designed for the Cambrian gypsum-salt layer and its collapse strength is 160 MPa to prevent collapse by salt creep. Fourth, Well Wutan 1 is drilled successfully to the expected strata and its total depth is 8060 m. In conclusion, the unconventional six-section casing program with 5 setting points to ensure the subsalt drilling safety in the eastern Sichuan Basin is rational. The successful drilling of Well Wutan 1 provides experiences and references for the follow-up exploration of deep-seated gas in the Dazhou–Kaijiang paleo-uplift. Keywords: Ultra-deep well, Complex pressure system, Gypsum-salt layer, Hydrogen sulfide bearing, Casing program, Sichuan basin, Eastern sichuan basin, Dazhou–kaijiang paleo-uplift, Well wutan 1

MicroRNAs (miRNAs) are small noncoding 20–25 nt RNA molecules that regulate gene expression by posttranscriptional repression of messenger RNA. There have been few investigations on the profiles and functions of miRNAs in ovine subcutaneous fat; their roles in the metabolism and deposition of subcutaneous fat also remain unclear. In this study, small RNA libraries were constructed for 2 important Chinese local sheep breeds, Small-tailed Han Sheep, and Shanxi Meat Sheep Dam Line, and used for high-throughput sequencing. Differentially expressed miRNAs were identified, revealing the effect of miR-124-3p on adipogenic differentiation by targeting C/EBPα. Our results provide both a comprehensive understanding of miRNA expression patterns in sheep subcutaneous fat and an insight into the specific roles of miRNAs in adipogenesis.

Wine grape pomace (WGP) provides a rich source of polyphenols that can act as powerful antioxidants, but their potential as feed ingredients in the lamb industry remains unexploited. The objective of this study was to investigate the effect of dietary WGP supplementation on growth performance, meat quality and antioxidative activity in the longissimus dorsi (LD) muscle of lambs. A total of eighteen lambs (25.0 ± 0.2 kg of body weight, BW) were randomly selected and equally divided into three groups, and offered diet containing different levels of WGP (0%, 5% and 10%). The results showed that supplementation with 10% dietary WGP increased body weight, average daily gain, and reduced the feed to gain ratio (P

The objective of this study was to detect the expression profile of microRNAs (miRNAs) in two breeds of fat-tailed sheep (Guangling Large-tailed sheep and Small-tailed Han sheep), and discover the miRNAs that may play roles in lipid metabolism. Consequently, two small RNA libraries were constructed and high-throughput sequencing was used to identify the miRNAs expressed in the two libraries and to calculate the expression of miRNAs. Bioinformatics methods were used to predict target genes, which were subsequently analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG). Nine miRNAs (miR-10b, miR-29a, miR-30c, miR-155, miR-192, miR-206, novel-miR-102, novel-miR-36, and novel-miR-63) were chosen to verify the sequencing results by detecting their expressions in the two breeds using quantitative real-time PCR. A total of 113 and 131 conserved miRNAs in the two breeds were obtained, of which 40 miRNAs were differentially expressed. KEGG analysis showed that many predicted target genes for these miRNAs are involved in lipid metabolism pathways. By screening the unknown miRNAs using MIREAP, 208 and 215 novel miRNAs were obtained from the two libraries, of which 150 were significantly different. This study represents the comprehensive survey of miRNAs expressed in the tail fat of two breeds of sheep with different tail fat deposition using HiSeq analysis. We conclude that differentially expressed miRNAs may play roles in regulating adipose metabolism, and thus, may contribute to improving the meat quality and fat deposition in sheep.

The Mengtuo Basin is proximal to the Bangmai Basin, which holds the world-class coal-hosted Ge deposit and shares the same sediment material provenance as the Lincang batholith. Herein, the mineralogy and geochemistry of Neogene Mengtuo lignite were reanalyzed using supplementary data on major element oxides and minerals. The results indicated that Mengtuo lignite is a medium-ash lignite A. The minerals in lignite are composed of quartz, kaolinite, illite, chamosite, bassanite, and rutile. Compared to common Chinese coals, Mengtuo lignite is significantly enriched in Sb, Cs, and W, enriched in Rb and U, and slightly enriched in Be, As, Cd, Bi, and Th. The rare earth elements plus yttrium (REY) are characterized by significantly positive Ce and Gd anomalies and negative Eu anomalies. A positive Ce anomaly is inherited from the sediment source material. The local Lincang granite around the Mengtuo Basin dominates the mineralogy and geochemistry of lignite and carbonaceous mudstone. Because of the lack of hydrothermal fluids, an indispensable condition for Ge mineralization in the Mengtuo Basin, a large-scale coal-hosted Ge deposit cannot be discovered.

The objective of this study was to investigate the effect of dietary Tartary buckwheat extract (TBE) supplementation on animal growth performance, meat quality and antioxidative activity in the Longissimus thoracis et lumborum muscle of lambs. The results showed that dietary TBE increased body weight, average daily gain, carcass weight, dry matter intake, and digestive organ weight. Dietary TBE had no effect on the pH, color, shear force or intramuscular fat of Longissimus muscle examined, whereas the cooking loss was decreased. The total antioxidative capacity and glutathione peroxidase 4 (GPx4) activity of Longissimus muscle were increased in lambs fed TBE. The mRNA contents of superoxide dismutase, catalase, GPx4 and nuclear factor-like-2 factor (Nrf2) did not vary among the groups, and greater protein levels of GPx4 and Nrf2 were observed. Taken together, these results suggest that TBE can be used as a feed ingredient in lamb production to improve its growth performance, and relieve oxidative stress and increase water holding capacity of meat.

A graph is even cycle decomposable if its edges can be partitioned into cycles of even length. A graph G is strongly even cycle decomposable if every subdivision of G with an even number of edges is even cycle decomposable. Markstrom conjectured that for any simple 2-connected cubic graph G , its line graph L ( G ) is even cycle decomposable. Macajova and Mazak further asked whether L ( G ) is strongly even cycle decomposable. In this paper, we resolve this question (as well as Markstrom’s conjecture) in the affirmative for a class of cubic graphs. We prove that for a (not necessarily simple) 2-connected cubic graph G , if there exists a cycle C in G such that G − V ( C ) is a linear forest (i.e., a forest whose components are paths), then L ( G ) is strongly even cycle decomposable. Our main motivation for considering this class of graphs comes from a conjecture of Ash and Jackson that every cyclically 4-edge-connected cubic graph has a dominating cycle (i.e., a cycle whose deletion results in an independent set of vertices). If this conjecture is true, then our result will imply that the line graph of every cyclically 4-edge-connected cubic graph is strongly even cycle decomposable.

The Notch signaling pathway regulates cell proliferation, differentiation and apoptosis involved in development of the organs and tissues such as nervous system, cartilage, lungs, kidneys and prostate as well as the ovarian follicles. This study aimed to investigate the mRNA expression and localization of NOTCH2, as the key factor in Notch signaling pathway. This was determined by PCR, real-time PCR and immunohistochemistry. Additionally, the effects of inhibiting Notch signaling pathway with different concentrations (5 μM, 10 μM and 20 μM) of N-[N-(3, 5-Difuorophenacetyl)- l -alanyl]- S -phenylglycine t -butyl ester (DAPT), an inhibitor of Notch signaling pathway, on ovine granulosa cells was determined in vitro by detecting estradiol production using enzyme linked immunosorbent assay and expressions of the genes related to the cell cycle and apoptosis using real-time polymerase chain reaction (PCR). NOTCH2, the key member of Notch signaling pathway, was found in ovine follicles, and the expression of NOTCH2 mRNA was highest in the theca cells of the follicles in medium sizes (3–5 mm in diameter) and granulosa cells of the follicles in large sizes (>5 mm in diameter). Immunohistochemical results demonstrated that NOTCH2 protein was expressed in granulosa cells of preantral follicles, in both granulosa cells and theca cells of antral follicles. Compared with DAPT-treated groups, the control group had a higher number of granulosa cells ( P 0.05) and a higher estradiol production ( P 0.05). Compared with the control group, the mRNA abundances of HES1 , MYC , BAX , BCL2 and CYP19A1 in DAPT-treated groups was lower ( P 0.05), respectively; whereas, the expression of CCND2 , CDKN1A and TP53 mRNA showed no remarkable difference compared with control group. Collectively, Notch signaling pathway could be involved in the ovine follicular development by regulating the growth and estradiol production of granulosa cells.

Additive manufacturing of patient-specific biomedical devices from 3D medical scans involves several steps of conversion which can introduce error into the final part. This is particularly critical to the fabrication of minute anatomical features, such as microvasculature. We show a direct conversion of the raw optical coherence tomography (OCT) volumetric data into photomasks in bitmap format, which streamlines the typical process steps used in 3D printing medical scans. OCT scans of rodent retinal microvasculature and projection microstereolithography are used to fabricate a solid vascular replica and a solid volume with hollow embedded microvessels.

The objective of this experiment was to investigate the mechanisms through which different levels of dietary energy affect postnatal skeletal muscle development in ewe lambs. Twelve Dorper × Small Thin-Tailed crossbred ewe lambs (100 d of age; 20 ± 0.5 kg BW) were selected randomly and divided into 2 groups in a completely randomized design. Animals were offered identical diets at 100% or 65% of ad libitum intake. Lambs were euthanized when BW in the ad libitum group reached 35 kg and the semitendinosus muscle was sampled. Final BW and skeletal muscle weight were decreased (P0.01) by feed restriction. Both muscle fiber size distribution and myofibril cross-sectional area were altered by feed restriction. Insulin-like growth factor 1 (IGF-1) messenger RNA (mRNA) content was decreased (P0.05) when lambs were underfed, whereas no difference for IGF-2 mRNA expression was observed (P0.05). Feed restriction altered phosphor-Akt protein abundance (P0.01). Moreover, the mammalian target of rapamycin (mTOR) pathway was inhibited by feed restriction, which was associated with decreased phosphor-mTOR, phosphorylated eukaryotic initiation factor 4E binding protein 1 (phosphor-4EBP1), and phosphorylated ribosomal protein S6 kinase (phosphor-S6K). Both mRNA expression of myostatin and its protein content were elevated in feed-restricted ewe lambs (P0.05). In addition, mRNA expression of both muscle RING finger 1 and muscle atrophy F-box was increased when ewe lambs were underfed. In summary, feed restriction in young growing ewe lambs attenuates skeletal muscle hypertrophy by inhibiting protein synthesis and increasing protein degradation, which may act through the Akt-dependent pathway.

Though muscle characteristics in the second half of gestation closely relate to quantity and quality of postnatal muscle, far fewer studies have examined breed differences in prenatal sheep muscle. This study seeks to better understand anatomic prenatal muscle differences and its underpinning mechanisms between two contrasting sheep breeds. A total of 38 sheep fetuses, including 20 Texel with pronounced muscularity and 18 Ujumqin, an indigenous fat-tailed sheep characterized by their hardiness, fetuses aged at up to five time-points from embryonic day (E) 70-135 of gestation were sacrificed and their organs and muscles dissected at 12 anatomical locations from the right side of each animal. Whole Texel fetuses weighed more especially at E70 and E85 (both 1.7-fold, P

Forkhead boxO (FOXO) transcription factors regulate diverse biological processes, including cellular metabolism, cell apoptosis, and the cell cycle. Results from several studies indicate FOXO1 regulates different granulosa cell (GC) pathways involved in proliferation, survival and differentiation. Functions and mechanisms of FOXO1 regulation of sheep GCs remain unclear. This study was conducted to analyze the function of FOXO1 in regulation of sheep GCs. In this study, the 1827 bp sheep FOXO1 coding sequence was cloned from sheep GCs. Multiple sequence alignment and phylogenetic analysis indicated that the FOXO1 protein sequence is highly homologous to FOXO1 protein sequences from other species. The results obtained from using CCK-8 assays indicated sheep GC proliferation increased when there was suppression of FOXO1 gene expression. When there was induced expression of the FOXO1 gene in sheep GCs, there was a resulting increased abundance of P21 and P27 mRNA transcript, whereas suppression of the FOXO1 gene expression had the opposite effect. Furthermore, the relative abundance in vitro of apoptosis-related protein mRNA transcripts (caspase3, caspase8, caspase9, Bax/Bcl-2) was markedly increased or decreased when there was induction or suppression of FOXO1 gene expression, respectively,(P 0.05). Induction of FOXO1 gene expression resulted in an increase in abundance of steroidogenic protein mRNA transcripts (CYP11A1, 3β-HSD), while suppression of FOXO1 gene expresion resulted in a decrease abundance of the CYP11A1, STAR mRNA transcripts. Results from the present study indicated that FOXO1 inhibited the proliferation of sheep GCs and affected mRNA transcript abundance for proteins involved in regulation of apoptosis, the cell cycle and steroidogenesis.

The eye relies on the synergistic cooperation of many different ocular components, including the cornea, crystalline lens, photoreceptors, and retinal neurons, to precisely sense visual information. Complications with a single ocular component can degrade vision and sometimes cause blindness. Immediate treatment and long-term monitoring are paramount to alleviate symptoms, restore vision, and cure ocular diseases. However, successful treatment requires understanding ocular pathological mechanisms, precisely detecting and monitoring the diseases. The investigation and diagnosis of ocular diseases require advanced medical tools. In this mini review, we discuss non-invasive photoacoustic (PA) imaging as a potential research tool and medical screening device. In the research setting, PA imaging can provide valuable information on the disease progression. In the clinical setting, PA imaging can potentially aid in disease detection and treatment monitoring.

Automated visual inspection (AVI) attracts increasing interest in product quality control both academic and industrial communities, particularly on mass production processes, because product qualities of most types can be characterized with their corresponding surface visual attributes. However, many product images in AVI systems are comprised of stochastically accumulative fragmentations (particles) of local homogeneity, without distinctive foregrounds and backgrounds, which brings great challenges in computer analysis, e.g., rice images, fabric images, and consequently, in the intelligent identification of the product qualities. A method of Weibull distribution (WD)-based statistical modeling of image spatial structures (ISSs) to inspect automatically the product quality is presented. The ISS, obtained with multi-scale and omnidirectional Gaussian derivative filters (OGDFs), was demonstrated to be subject to a representative WD model of integral form based on the theory of sequential fragmentation in advance. The WD-model parameters (WD-MPs) of the ISS, with essential human perceptual significance, were extracted as the visual features for product quality identification. The classification performance of the proposed product quality inspection method, namely, the proposed WD-MP features integrated with an introduced spline regression (SR) classifier in this study, was verified on two case studies in the field of the AVI of product quality, namely, automated rice quality classification, and intelligent fabric quality assessment in the corresponding assembly lines of industrial scale. Experimental results indicate that the proposed WD-MP features can effectively characterize the statistical distribution profiles of ISS of complex grain images, piled with a large number of stochastically accumulative fragmentations. The proposed method provides an effective tool for grain image modeling and analysis and consequently lays a foundation for the intelligent perception of product qualities on assembly lines.

Follicular growth is regulated by a complex interaction of pituitary gonadotropins with local regulatory molecules. Previous studies demonstrated an important role for cocaine- and amphetamine-regulated transcript (CART) in regulation of granulosa cell estradiol production associated with dominant follicle selection in cattle. However, intraovarian expression and actions of CART in other species, including sheep, are not known. The objective of this study was to investigate the expression of CART in sheep follicles and determine the effects of CART on indices of ovine granulosa cell function linked to follicular development. Results demonstrated the expression of CART messenger RNA and prominent intraovarian localization of CART peptide in granulosa cells of sheep follicles. Granulosa cell CART messenger RNA was lower, but follicular fluid estradiol concentrations were higher in large (>5 mm) follicles vs smaller 3- to 5-mm follicles harvested from sheep ovaries of abattoir origin. CART treatment inhibited follicle stimulating hormone-induced estradiol production by cultured ovine granulosal cells and also blocked the follicle stimulating hormone-induced increase in granulosa cell numbers. Results demonstrate expression of CART in sheep follicular tissues and suggest potential biological actions of CART, which are inhibitory to ovine follicular growth and development.

In this study, we report on a novel approach for real-time temperature probing using magnetization of magnetic nanoparticles as thermometric property. Differently from the existing approaches, we included diameter distribution function, f ( D ), and temperature dependence of saturation magnetization, M S ( T ), in the model picture herein used to assess temperature. Using simulation as well as experimental data, we found the new approach provides accuracy better than 0.05 K in 1 s measurement. Magnetization data were acquired using low-frequency (25 Hz) and weak triangular-wave applied AC magnetic field (amplitude below 50 Oe), allowing for the use of the first two terms of the Taylor’s expansion of the Langevin function. Experimental conditions reported in the present study are promising for developing new instrumentation to support the upcoming magnetonanothermometry technology and its application in the medical field.

An even cycle decomposition of a graph is a partition of its edges into cycles of even length. In 2012, Markstrom conjectured that the line graph of every 2-connected cubic graph has an even cycle decomposition and proved this conjecture for cubic graphs with oddness at most 2. However, for 2-connected cubic graphs with oddness 2, Markstrom only considered these graphs with a chordless 2-factor. (A chordless 2-factor of a graph is a 2-factor consisting of only induced cycles.) In this paper, we first construct an infinite family of 2-connected cubic graphs with oddness 2 and without chordless 2-factors. We then give a complete proof of Markstrom’s result and further prove this conjecture for cubic graphs with oddness 4.

To investigate the geochemical characteristics of thermally-altered coals formed by igneous intrusion, a series of roof and floor mudstone, thermally-altered coal, and igneous rock samples were collected from a representative borehole profile of the Pansan No. 4-2 coals of the Huainan Coalfield, Anhui Province, Eastern China. Furthermore, seven unaltered coal samples from the same coalbed were collected from seven coal mines of the Huainan Coalfield for comparison. The minerals were analyzed using X-ray diffractometry and optical microscopy. The major element oxides and trace elements were determined by X-ray fluorescence (XRF), inductively coupled plasma mass spectrometry (ICP-MS), ICP-MS with collision/reaction cell technology, an ion-selective electrode (ISE), and a DMA-80 mercury analyzer. The results indicate that kaolinite and quartz are the dominant minerals in the thermally-altered coals, and pyrite is dominant at the contact zone between the thermally-altered coal and igneous rock. The unaltered Huainan No. 4-2 coals were slightly enriched in only Cr, Se, and W compared to the Chinese coals. However, the thermally-altered coals were slightly enriched in F and V and depleted in Co, Ni, Hg, Sb, Zn, and W compared to the Chinese coals. Although the igneous intrusion reached a thickness of 1.97 m, it had a limited effect on the trace elements of terrigenous origin, i.e., Li, F, Sr, Sn, V, Cr, Co, Ni, Cs, Sc, Ga, Rb, Zr, Nb, Ag, Cd, In, Ba, Hf, Ta, W, Th, U, and rare earth elements and Y (REY). Contact metamorphism resulted the devolatilization and redeposition of coal organic matter, which increased the Be and Ge concentrations of the thermally-altered coals adjacent to the intrusion. Copper, As, Sb, Tl, and Bi were transported by the igneous intrusion and redeposited in the thermally-altered coals. The coals were almost completely stripped of Zn, Se, Mo, Pb, and Hg by the igneous intrusion.

The geochemistry of source rock–controlled coals from the Late Triassic Daqiaodi Formation in the Dabaoding Coal Mine of the southwestern Sichuan Province was investigated. A total of 15 coal samples, 6 parting samples, and 4 roof and floor rock samples from the D15–3 and D18 coals were subjected to proximate and ultimate analyses for coal quality, by using LTA-XRD with Siroquant software for minerals, XRF for major element oxides, ICP-MS for trace elements, ICP-CCT-MS for As and Se, ISE for F, and a DMA-80 analyzer for Hg. Results indicate that the Dabaoding D15–3 and D18 coals are classified as low ash and low-volatile bituminous coal. Minerals in coals are dominated by quartz, kaolinite, illite, and dolomite. Most trace elements in the Dabaoding coals are depleted or at normal levels relative to Chinese coals or world hard coals (except for Cr with slight enrichment). The Dabaoding coals and host rocks are characterized by weakly positive Ce and Y anomalies, strongly positive Gd anomalies, and weakly negative Eu anomalies. Based on paleogeographical, mineralogical, and geochemical evidence, the sediment source rocks of the Daqiaodi coal-bearing strata are identified as the Panzhihua trachyte at the top of the Kangdian Upland, which exerted crucial impacts on the Dabaoding coals.

The Donglin Coal Mine, an important mine in the Nantong coalfield in southwestern Chongqing, is immediately adjacent to the Songzao coalfield. To investigate the mineralogy and geochemistry of Donglin coals, profile channel samples from the mineable Nos. 4 and 6 coals were collected. The minerals, major element oxides, and trace elements were analyzed by LTA-XRD in combination with Siroquant software, XRF, ICP-MS, ICP-CCT-MS (As and Se), ISE (F), and DMA-80 Hg analyzer (Hg). The results indicate that the Donglin low volatile bituminous coals were characterized by low ash yields and high total sulfur contents. The minerals varied between the Nos. 4 and 6 coals, differentiated by montmorillonite, calcite, ankerite, and pyrite. Despite the low boron concentration, Donglin coals were influenced by brackish water during coal accumulation. Selenium (10.9 mg/kg), F (431 mg/kg), Hg (0.350 mg/kg), Nb (20.7 mg/kg), and Ta (3.68 mg/kg) in the No. 4 coals, and F (425 mg/kg), Be (7.11 mg/kg), Ga (14.5 mg/kg), Ge (22.5 mg/kg), Zr (218 mg/kg), Nb (35.5 mg/kg), and Ta (4.42 mg/kg) in the No. 6 coals are slightly enriched. Four vertical distributions of elements were demonstrated, i.e., roof, floor, roof and floor, and middle enrichments. The slightly enriched trace elements and UCC-normalized REY distribution patterns of the Donglin coals jointly eliminated the impact of various volcanic ashes and terrigenous input from the Kangdian Oldland during the Late Permian. However, the roof rock samples shared the geochemical feature of mafic tonstein (enriched Sc, V, Cr, Co, and Ni), while the floor rock of the No. 6 coals resembles alkali tonsteins (enriched Ga, Zr, Nb, Ta, Hf, and REY). Lithium, Ga, Zr, Ag, Cd, In, Sn, Cs, Hf, Bi, Th, and U occurred in kaolinite and/or montmorillonite in the No. 4 coals, while Li, Nb, Ag, Cd, In, Cs, Ba, and Th occurred in kaolinite in the No. 6 coals. Vanadium, Sr, and Mo in the No. 4 coals, and Sr and Sc in the No. 6 coals were associated with calcite and/or ankerite. Arsenic, Se, Hg, Sb and Tl, and Hg and Mo were associated with pyrite in the Nos. 4 and 6 coals, respectively. Lithium, Be, Ge, and Sb in the No. 4 coals and Be and Ge in the No. 6 coals might be of organic affinity.

The objectives of this study were to investigate the potential effects of 1α,25-(OH)2VD3 (biologically active form of Vitamin D) on basal and LH-induced testosterone production and mitochondrial dehydrogenase activity in Leydig cells from immature and mature rams cultured in vitro. Leydig cells were isolated from testes of immature and mature rams, treated without (control) or with increasing concentrations of LH (1, 10, 100ng/ml) and/or 1α,25-(OH)2VD3 (1, 10, 100nM). After 24h, concentrations of testosterone in culture media were measured. After 96h, mitochondrial dehydrogenase activity in Leydig cells were measured. In immature and mature ram Leydig cells, treatment with 10 and 100ng/ml LH increased testosterone production and mitochondrial dehydrogenase activity. Treatment with 1α,25-(OH)2VD3 in the absence of LH did not increase testosterone production, but 10 and 100nM 1α,25-(OH)2VD3 increased LH induced testosterone production for both immature and mature ram Leydig cells. Treatment with all doses of 1α,25-(OH)2VD3 in the absence of LH and 10 and 100ng/ml LH in the absence of 1α,25-(OH)2VD3 increased mitochondrial dehydrogenase activity for cultured Leydig cells from immature and mature rams and 1 and 10nM 1α,25-(OH)2VD3 treatment enhanced the LH induced increase in mitochondrial dehydrogenase activity. Result demonstrate Vitamin D3 induced regulation of function of Leydig cells from immature and mature rams cultured in the presence or absence of LH and support a potential role for Vitamin D3 in regulation of gonadal function in rams.

Body fat, insulin resistance, and type 2 diabetes are often linked together, but the molecular mechanisms that unify their association are poorly understood. Wnt signaling regulates adipogenesis, and its altered activity has been implicated in the pathogenesis of type 2 diabetes and metabolic syndrome. LRP6(+/-) mice on a high fat diet were protected against diet-induced obesity and hepatic and adipose tissue insulin resistance compared with their wild-type (WT) littermates. Brown adipose tissue insulin sensitivity and reduced adiposity of LRP6(+/-) mice were accounted for by diminished Wnt-dependent mTORC1 activity and enhanced expression of brown adipose tissue PGC1-α and UCP1. LRP6(+/-) mice also exhibited reduced endogenous hepatic glucose output, which was due to diminished FoxO1-dependent expression of the key gluconeogenic enzyme glucose-6-phosphatase (G6pase). In addition, in vivo and in vitro studies showed that loss of LRP6 allele is associated with increased leptin receptor expression, which is a likely cause of hepatic insulin sensitivity in LRP6(+/-) mice. Our study identifies LRP6 as a nutrient-sensitive regulator of body weight and glucose metabolism and as a potential target for pharmacological interventions in obesity and diabetes.

Genetic variations in LRP6 gene are associated with high serum LDL cholesterol levels. We have previously shown that LDL clearance in peripheral B-lymphocytes of the LRP6(R611C) mutation carriers is significantly impaired. In this study we have examined the role of wild type LRP6 (LRP6(WT)) and LRP6(R611C) in LDL receptor (LDLR)-mediated LDL uptake. LDL binding and uptake were increased when LRP6(WT) was overexpressed and modestly reduced when it was knocked down in LDLR-deficient CHO (ldlA7) cells. These findings implicated LRP6 in LDLR-independent cellular LDL binding and uptake. However, LRP6 knockdown in wild type CHO cells resulted in a much greater decline in LDL binding and uptake compared with CHO-ldlA7 cells, suggesting impaired function of the LDLR. LDLR internalization was severely diminished when LRP6 was knocked down and was restored after LRP6 was reintroduced. Further analysis revealed that LRP6(WT) forms a complex with LDLR, clathrin, and ARH and undergoes a clathrin-mediated internalization after stimulation with LDL. LDLR and LRP6 internalizations as well as LDL uptake were all impaired in CHO-k1 cells expressing LRP6(R611C). These studies identify LRP6 as a critical modulator of receptor-mediated LDL endocytosis and introduce a mechanism by which variation in LRP6 may contribute to high serum LDL levels.

Covariance functions have been proposed as an alternative to model longitudinal data in animal breeding because of their various merits in comparison to the classical analytical methods. In practical estimation, different models and polynomial orders fitted can influence the estimates of covariance functions and thus genetic parameters. The objective of this study was to select model for estimation of covariance functions for body weights of Angora goats at 7 time points. Covariance functions were estimated by fitting 6 random regression models with birth year, birth month, sex, age of dam, birth type, and relative birth date as fixed effects. Random effects involved were direct and maternal additive genetic, and animal and maternal permanent environmental effects with different orders of fit. Selection of model and orders of fit were carried out by likelihood ratio test and 4 types of information criteria. The results showed that model with 6 orders of polynomial fit for direct additive genetic and animal permanent environmental effects and 4 and 5 orders for maternal genetic and permanent environmental effects, respectively, were preferable for estimation of covariance functions. Models with and without maternal effects influenced the estimates of covariance functions greatly. Maternal permanent environmental effect does not explain the variation of all permanent environments, well suggesting different sources of permanent environmental effects also has large influence on covariance function estimates.

Gastric cancer causes nearly one million deaths worldwide per year. Although Helicobacter pylori infection is the main risk factor, in about 80% or more of gastric cancers, the molecular pathway underlying H. pylori infection leading to the development of gastric cancers remains unclear. Recently accumulating evidence suggests that microRNAs (miRNAs) may regulate diverse biological processes and may be important in tumorigenesis. miR-21 has been frequently observed to be aberrantly overexpressed in various tumors. Using TaqMan quantitative real-time PCR, we confirmed that miR-21 was significantly overexpressed in human gastric cancer tissues and cell lines. Remarkably, miR-21 was also significantly overexpressed in H. pylori-infected gastric mucosa, implying that overexpression of miR-21 in gastric cancer may be due in part to H. pylori infection. More importantly, we showed that forced expression of miR-21 significantly enhanced cell proliferation and invasion in AGS cells, a human gastric cancer cell line, whereas knockdown of miR-21 by inhibitor caused a significant reduction in cell proliferation and a significant increase in apoptosis. Furthermore, we demonstrated that knockdown of miR-21 significantly decreased cell invasion and migration of AGS cells. Finally, we showed that RECK, a known tumor suppressor in gastric cancer, is a bona fide target of miR-21. Taken together, miR-21 may be important in the initiation and progression of gastric cancers as an oncomiR, likely through regulating RECK. Our findings suggest a potential regulatory pathway in which H. pylori infection upregulates expression of miR-21, which in turn downregulates RECK, and then leads to the development of gastric cancer.

In this paper, boundary cubic rooted planar maps are investigated and exact enumerative formulae are given. First, an enumerative formula for boundary cubic inner-forest maps with the size (number of edges) as a parameter is derived. For the special case of boundary cubic inner-tree maps, a simple formula with two parameters is presented. Further, according to the duality, a corresponding result for outer-planar maps is obtained. Finally, some results for boundary cubic planar maps and general planar maps are obtained. Furthermore, two known Tutte's formulae are easily deduced in the paper.

Data on 864 Angora goats, collected from 1988 to 2000, were used to study non-genetic effects on body weight and daily gain from birth to 24 months of age and body size at different ages. Non-genetic factors included birth year, birth month, sex, age of kids, age of dam, type of birth and rearing. Birth year, sex and type of birth and rearing were the major factors affecting growth of Angora goats. Age of dam influenced body weights at birth and weaning, early growth rate and height at withers. The unfavorable effects of young dams on their kids suggested that it was essential to strengthen the feeding and management of kids, especially in maintaining the body weight during mating and pregnancy. Growth rate of kids born from November to February was relatively slower during sucking period but more rapid after weaning than those born between March and July. This can result from seasonal change and suggests that it is necessary to plan the kidding season rationally by controlling the estrus and mating time. The kids born as twin had lower birth weight and slower early growth rate than those born as single, but had a higher post-weaning growth rate. The general trend was the differences between singles and twins decreased as the kids became older, possibly due to a decreasing maternal effect and a growth compensation of twin kids. Additive and multiplicative adjustment factors for body weights and growth rates were derived from least squares means of subclasses for birth month, sex, age of dam, type of birth and rearing. Subclass variances were tested for heterogeneity with Levene's test. The results were used to determine appropriate adjustment for non-genetic effects.

The loss of the SOST gene product sclerostin leads to sclerosteosis characterized by high bone mass. In this report, we found that sclerostin could antagonize canonical Wnt signaling in human embryonic kidney A293T cells and mouse osteoblastic MC3T3 cells. This sclerostin-mediated antagonism could be reversed by overexpression of Wnt co-receptor low density lipoprotein receptor-related protein (LRP) 5. In addition, we found that sclerostin bound to LRP5 as well as LRP6 and identified the first two YWTD-EGF repeat domains of LRP5 as being responsible for the binding. Although these two repeat domains are required for transduction of canonical Wnt signals, canonical Wnt did not appear to compete with sclerostin for binding to LRP5. Examination of the expression of sclerostin and Wnt7b, an autocrine canonical Wnt, during primary calvarial osteoblast differentiation revealed that sclerostin is expressed at late stages of osteoblast differentiation coinciding with the expression of osteogenic marker osteocalcin and trailing after the expression of Wnt7b. Given the plethora of evidence indicating that canonical Wnt signaling stimulates osteogenesis, we believe that the high bone mass phenotype associated with the loss of sclerostin may be attributed, at least in part, to an increase in canonical Wnt signaling resulting from the reduction in sclerostin-mediated Wnt antagonism.

Commissioning for a UTSP plant has been started for commercial production at Tangshan Iron & Steel Company Ltd in China. The plant was constructed by an international consortium from Japan, Italy and the USA, and production of hot coils has been begun in only 25 months. The annual production capacity for the first stage is 1.5 million tons and strip thickness ranges from 0.8 to 4.0 mm. The plant is featured by a high-performance PLC system and advanced process control technologies, with which semi-endless rolling operation was introduced for the first time in China. This paper describes these features and functions in detail.

Similar to other herpesviruses, human cytomegalovirus remains in the infected host following resolution of the primary infection. The ability to persist in the host after primary infection is believed to be strongly influenced by the ability of HCMV to down-regulate immune recognition of infected cells. One of the genes contributing to immune evasion is the US3 gene. The US3 gene has been shown to retain major histocompatibility complex type I molecules in the endoplasmic reticulum. The US3 gene gives rise to three alternatively spliced RNAs which encode distinct but related proteins. Each of the alternatively spliced transcripts is present early in viral infection, suggesting that the encoded proteins play a role in the viral life cycle. We demonstrate that only the protein encoded by the unspliced US3 transcript is able to retain MHC class I heavy chains in the endoplasmic reticulum. The protein encoded by the singly spliced US3 transcript appears to be processed through the secretory pathway while the protein encoded by the doubly spliced transcript becomes localized to the Golgi apparatus. These experiments raise interesting questions about the functions of the smaller US3 proteins during viral infection in the host.

Light emitted by Ag atoms following the bombardment of a Ag target with Ar ions has been studied. Light yields that include contributions from both displaced surface and sputtered atoms have been obtained as a function of incident ion beam kinetic energy and with different Ar ion charge states. No change in the light yield was observed as the incident ion charge state was varied. The light yield was found to increase by nearly a factor of 10 as the ion beam kinetic energy changed from 8 to 100 keV.

Background & Aims We assessed the efficacy and safety of 4 bismuth-containing quadruple regimens as empiric therapies for Helicobacter pylori infections in patients who did not respond to previous treatment. Methods We performed a prospective single-center study of 424 patients with H pylori infection that was not eradicated by previous therapies. Patients were assigned randomly to groups given lansoprazole (30 mg twice daily) and bismuth potassium citrate (220 mg twice daily), along with 500 mg tetracycline and 400 mg metronidazole 4 times daily (LBTM), 500 mg tetracycline and 100 mg furazolidone 3 times daily (LBTF), 1000 mg amoxicillin 3 times and 500 mg tetracycline 4 times daily (LBAT), or 1000 mg amoxicillin and 100 mg furazolidone 3 times daily (LBAF). Eradication was assessed by a 13C-urea breath test. Antimicrobial susceptibility was assessed in 188 patients by the agar dilution method. Results Per-protocol rates of H pylori eradication were greater than 90% for all regimens: 93.1% for LBTM (95% confidence interval [CI], 88.1%–98.0%), 96.1% for LBTF (95% CI, 92.4%–99.8%), 94.6% for LBAT (95% CI, 90.0%–99.2%), and 99.0% for LBAF (95% CI, 97.0%–100%). The intention-to-treat response rates were 87.9% for LBTM (95% CI, 81.7%–94.0%), 91.7% for LBTF (95% CI, 87.1%–96.3%), 83.8% for LBAT (95% CI, 76.8%–90.9%), and 95.2% for LBAF (95% CI, 91.1%–99.3%). Significantly more patients had infections eradicated by furazolidone-containing regimens than nonfurazolidone regimens (P = .01). Side effects occurred in 33.6% of subjects and occurred significantly more frequently in the LBTM group than the other 3 groups (vs LBTF, P = .006; vs LBAT, P = .003; vs LBAF, P = .02). Metronidazole resistance was 96.8%; no isolates were resistant to amoxicillin, tetracycline, or furazolidone. Conclusions Four bismuth-containing quadruple therapies achieved greater than 90% eradication of H pylori in patients who did not respond to previous treatment, including patients with metronidazole resistance. For patients allergic to penicillin, tetracycline and either metronidazole- or furazolidone-containing regimens are recommended. ClincialTrials.gov number, NCT01668927.