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Senescence of bone marrow mesenchymal stem cells (BMSCs) impairs stemness and osteogenic differentiation, but the key regulators for senescence and the related osteogenesis are not well defined. Herein, we screened the gene expression profiles of human BMSCs from young and old donors and identified that elevation of the nucleosome assembly protein 1-like 2 (NAP1L2) expression was correlated with BMSC senescence and impaired osteogenesis. Elevated NAP1L2 expression was observed in replicative cell senescence and induced cell senescence in vitro, and in age-related senescent human and mouse BMSCs in vivo, concomitant with significantly augmented chromatin accessibility detected by ATAC-seq. Loss-and gain-of-functions of NAP1L2 affected activation of NF-êB pathway, status of histone 3 lysine 14 acetylation (H3K14ac), and chromatin accessibility on osteogenic genes in BMSCs. Mechanistic studies revealed that NAP1L2, a histone chaperone, recruited SIRT1 to deacetylate H3K14ac on promoters of osteogenic genes such as Runx2, Sp7, and Bglap and suppressed the osteogenic differentiation of BMSCs. Importantly, molecular docking analysis showed a possible bond between NAP1L2 and an anti-aging reagent, the nicotinamide mononucleotide (NMN), and indeed, administration of NMN alleviated senescent phenotypes of BMSCs. In vivo and clinical evidence from aging mice and patients with senile osteoporosis also confirmed that elevation of NAP1L2 expression was associated with suppressed osteoblastogenesis. Taken together, our findings suggest that NAP1L2 is a regulator of both BMSC cell senescence and osteogenic differentiation, and provide a new theoretical basis for aging-related disease. [ABSTRACT FROM AUTHOR]

Fast water transport channels are crucial for water‐related membrane separation processes. However, overcoming the trade‐off between flux and selectivity is still a major challenge. To address this, we constructed spherical polyelectrolyte brush (SPB) structures with a highly hydrophilic polyelectrolyte brush layer, and introduced them into GO laminates, which increased both the flux and the separation factor. At 70 °C, the flux reached 5.23 kg m−2 h−1, and the separation factor of butanol/water increased to ≈8000, which places it among the most selective separation membranes reported to date. Interestingly, further studies demonstrated that the enhancement of water transport was not only dependent on the hydrophilicity of the polyelectrolyte chains, but also influenced by their flexibility in the solvent. Quartz crystal microbalance with dissipation and molecular dynamics simulations revealed the structure‐performance correlations between water molecule migration and the flexibility of the ordered polymer chains in the 2D confined space. [ABSTRACT FROM AUTHOR]

Fast water transport channels are crucial for water‐related membrane separation processes. However, overcoming the trade‐off between flux and selectivity is still a major challenge. To address this, we constructed spherical polyelectrolyte brush (SPB) structures with a highly hydrophilic polyelectrolyte brush layer, and introduced them into GO laminates, which increased both the flux and the separation factor. At 70 °C, the flux reached 5.23 kg m−2 h−1, and the separation factor of butanol/water increased to ≈8000, which places it among the most selective separation membranes reported to date. Interestingly, further studies demonstrated that the enhancement of water transport was not only dependent on the hydrophilicity of the polyelectrolyte chains, but also influenced by their flexibility in the solvent. Quartz crystal microbalance with dissipation and molecular dynamics simulations revealed the structure‐performance correlations between water molecule migration and the flexibility of the ordered polymer chains in the 2D confined space. [ABSTRACT FROM AUTHOR]

To efficiently manage water resources in agriculture, the hydrologic model HYDRUS-1D and the crop growth model WOFOST were coupled to improve crop production prediction through accurate simulations of actual transpiration with a root water uptake method and soil moisture profile with the Richards equation during crop growth. An inverse modeling method, the shuffled complex evolution algorithm, was used to identify soil hydraulic parameters for simulating the soil moisture profile. The coupled model was validated by experimental study on irrigated wheat (Triticum aestivum L.) in the middle reaches of the Heihe River, northwest China, in a semiarid and arid region. Good agreement was achieved between the simulated actual evapo-transpiration, soil moisture, and crop production and their respective field measurements under a realistic irrigation scheme. A water stress factor, actual root uptake with potential transpiration, is proposed as an indicator to guide irrigation. Numerical results indicated that the irrigation scheme guided by the water stress factor can save 27% of irrigation water compared with the current irrigation scheme. Based on the calibrated model, uncertainty and sensitivity analysis methods were used to predict the risk of wheat production loss with decreasing irrigation and to study the effects of coupled model parameters and environmental factors on wheat production. The analysis revealed that the most suitable groundwater depth for wheat growth is 1.5 m. These results indicate that the coupled model can be used for analysis of schemes for saving water and study of the interaction between crop growth and the hydrologic cycle. [ABSTRACT FROM AUTHOR]

Spatio-temporal patterns and processes of genetic differentiation in passively dispersing zooplankton are drawing much attention from both ecologists and evolutionary biologists. Two opposite phylogeographical scenarios have already been demonstrated in rotifers, which consist of high levels of genetic differentiation among populations even on small geographical scales on the one hand and the traditionally known cosmopolitanism that is associated with high levels of gene flow and long-distance dispersal via diapausing stages on the other hand. Here, we analysed the population genetic structure and the phylogeography of the Brachionus calyciflorus species complex in eastern China. By screening a total of 318 individuals from ten locations along a 2320-km gradient and analysing samples from two growing seasons, we aimed at focusing on both small- and large-scale patterns. We identified eight cryptic species and verified species status of two of these by sexual reproduction tests. Samples in summer and winter yielded different cryptic species. The distribution patterns of these genetically distinct cryptic species were diverse across eastern China, from full cosmopolitanism to local endemism. The two most abundant cryptic species BcWIII and BcSW showed a pattern of strong genetic differentiation among populations and no significant isolation by distance. Long-distance colonization, secondary contact and recent range expansion are probably responsible for the indistinct pattern of isolation by distance. Our results suggest that geographical distance is more important than temporal segregation across seasons in explaining population differentiation and the occurrence of cryptic species. We explain the current phylogeographical structure in the B. calyciflorus species complex by a combination of recent population expansion, restricted gene flow, priority effects and long-distance colonization. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the biologic links between progressive cellular and structural alterations within knee joint components and the development of symptomatic chronic pain. The study also investigated the molecular basis of alterations in nociceptive pathways caused by osteoarthritis (OA)-induced pain. It utilized Sprague-Dawley rats as animal models of knee joint OA pain. Study authors found structural changes in peripheral knee joint components in relation to central compartment alterations.

The growing volume of vague information poses interesting challenges and calls for new theories, techniques and tools for analysis of vague data sets. In this paper, we study how to extract knowledge from vague objective information systems (VOISs) based on rough sets theory. We first introduce the basic notion termed rough vague sets by combining rough sets theory and vague sets theory. By using the rough vague lower approximation distribution in the VOIS, the concept of attribute reduction is introduced. Then, we develop an algorithm based on a discernibility matrix to compute all the attribute reductions. Finally, a viable approach for extracting decision rules from the VOIS is proposed. An example is also presented to illustrate the application of the proposed theories and approaches in handling medical diagnosis problems. [ABSTRACT FROM AUTHOR]

The Jiamante Au deposit is one of the important deposits in the Axi ore cluster of the Western Tianshan, Xinjiang. The orebodies occurring mainly as quartz‐sulphide veins are hosted in Late Devonian volcanoclastic rocks and granitic porphyries, and structurally controlled by a group of NNW‐ and NNE‐ trending extensional faults and volcanic breccias. Primary metallic minerals are chalcopyrite, galena, pyrite, sphalerite, and native gold, with minor amounts of bismuthinite and bismuth. Nonmetallic minerals are dominated by quartz, sericite, chlorite, and calcite. Medium to low temperature hydrothermal alterations are well developed and characterized by silicification, beresitization, phyllic alteration, and chloritization. Two hydrothermal stages were identified: (a) the main‐ore quartz‐sulphide stage; and (b) the post‐ore quartz‐calcite stage. Microthermometric measurements indicate that the primary biphase liquid‐rich aqueous fluid inclusions within quartz of the main‐ore stage homogenize at temperatures (Th) of 176 to 251°C and have salinities of 2.1 to 7.4 wt% NaCleqv. A lower range of homogenization temperatures (169 to 212°C) and salinities (1.6 to 5.2 wt% NaCleqv) were obtained in calcite of the post‐ore stage. The fluid characteristics of moderate to low temperatures and salinities imply that the ore‐forming process occurred in an epithermal environment. In addition, there is a positive relationship between Th and salinities consistent with the fluid mixing trend. Together with H–O isotopic data (δDH2O = −118 to −97‰ and δ18OH2O = −5.5 to −1.6‰) and fluid characteristics, it is suggested that the ore‐forming fluids were a mixture of magmatic and meteoric waters. The δ13C values for CO2 in the hydrothermal fluids range from −3.2 to −2.7‰, and the sulphides have δ34S values of −5.2 to 2.9‰ with relatively uniform Pb isotopic compositions (206Pb/204Pb = 18.228 to 18.287, 207Pb/204Pb = 15.574 to 15.617, and 208Pb/204Pb = 38.151 to 38.251), indicating that the ore‐forming materials were magmatic sources that were derived directly from magmatic fluids and/or leached from volcanic‐subvolcanic rocks by hydrothermal fluids. Combined with the evidence from the mineralization and alteration, fluid inclusions, and C–H–O–S–Pb isotopes suggest that the Jiamante deposit is an intermediate‐sulphidation epithermal Au deposit. A combination of fluid mixing and fluid–rock interactions is inferred as the important factors causing ore deposition. According to the close spatial and temporal relationship between intermediate‐epithermal deposits and porphyry deposits, it is further suggested that porphyry‐type mineralization should have a good potential at the deep sites of the Jiamante deposit and its vicinity. [ABSTRACT FROM AUTHOR]

Plant defences require a multitude of tightly regulated resistance responses. In Arabidopsis, the unique gain-of-function mutant suppressor of npr1-1 constitutive 1 ( snc1) carries a point mutation in a Resistance ( R)-gene, resulting in constitutive activation of defence responses without interaction with pathogens. This has allowed us to identify various downstream signalling components essential in multiple defence pathways. One mutant that suppresses snc1-mediated constitutive resistance is modifier of snc1 5 ( mos5), which carries a 15-bp deletion in UBA1, one of two ubiquitin-activating enzyme genes in Arabidopsis. A mutation in UBA2 does not suppress snc1, suggesting that these two genes are not equally required in Arabidopsis disease resistance. On the other hand, a mos5 uba2 double mutant is lethal, implying partial redundancy of the two homologues. Apart from affecting snc1-mediated resistance, mos5 also exhibits enhanced disease susceptibility to a virulent pathogen and is impaired in response to infection with avirulent bacteria carrying the protease elicitor AvrRpt2. The mos5 mutation in the C-terminus of UBA1 might affect binding affinity of the downstream ubiquitin-conjugating enzymes, thus perturbing ubiquitination of target proteins. Furthermore, SGT1b and RAR1, which are necessary for resistance conferred by the SNC1-related R-genes RPP4 and RPP5, are dispensable in snc1-mediated resistance. Our data reveal the definite requirement for the ubiquitination pathway in the activation and downstream signalling of several R-proteins. [ABSTRACT FROM AUTHOR]

A counteracting dither technique is proposed to remedy the bit-weight error issue in pipeline analogue-to-digital converters (ADCs). A capacitor is added to the traditional comparator dither scheme. By switching the added capacitor, the residue swing increment due to comparator dither is counteracted, thereby greatly relaxing the design requirement of the residue amplifier. Behaviour-level simulation results show that the spurious-free-dynamic-range and the signal-tonoise- and-distortion-ratio are improved from 59 and 52.8 dB to 102.7 and 85 dB after calibration in a 14-bit ADC, respectively. [ABSTRACT FROM AUTHOR]

Findings that antioxidant treatment may be beneficial in Alzheimer's disease indicate that oxidative stress is an important factor in its pathogenesis. Studies have also suggested that cholesterol imbalance in the brain might be related to the development of neurological disorders. Previously, we have reported that U18666A, a cholesterol transport-inhibiting agent, leads to apoptosis and intracellular cholesterol accumulation in primary cortical neurons. In this study, we found that neuronal apoptosis mediated by U18666A is associated with oxidative stress in the treated cortical neurons. Cortical neurons treated with U18666A also showed decreased secretion and increased intraneuronal accumulation of β-amyloid. The association of neuronal apoptosis with oxidative stress and Aβ accumulation may provide clues to the pathogenesis of Alzheimer's disease, as well as the role oxidative stress plays in other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

BSTRACT To assess the effect of nutritional composition of cottonseed after introducing Bacillus thuringiensis gene, compositional analyses of Bollgard II cotton event 15985, DPH37B, and 5415 were carried out. Cotton DPH37B contains cry1Ac gene, and Bollgard II 15985 contains cry2Ab and cry1Ac genes. Cotton 5415 was a control. Crude protein, crude fiber, fat, moisture, ash, amino acids level, and selected minerals were measured by chemical analysis. Anti-nutrients including free gossypol, total gossypol, and tannin were also measured. The results showed that the compositional components of the transgenic cottonseed were comparable to those of the nontransgenic cottonseed. The results of numerous qualitative and quantitative analyses revealed that the transgenic cottonseed was compositionally equivalent to the conventional counterpart. [ABSTRACT FROM AUTHOR]

Three nitrophenol isomer-imprinted polymers were prepared under the same conditions using 4-vinylpyridine as a functional monomer. Different recognition capacities for template molecules were observed for the three polymers. Another imprinting system with stronger acidity than nitrophenol isomers, 2-hydroxybenzoic acid (salicylic acid) and 4-hydroxybenzoic acid, was imprinted using 4-vinylpyridine or acrylamide as functional monomer respectively. Both 4-hydroxybenzoic acid-imprinted polymers using the two monomers showed recognition ability for the template molecule. However, when acrylamide was chosen as functional monomer, the salicylic acid-imprinted polymer showed very weak recognition for the template molecule, whereas strong recognition ability of the resultant polymer for salicylic acid was observed with 4-vinylpyridine as functional monomer. It seems that the structure and acidity of template molecules is responsible for the difference in recognition, by influencing the formation and strength of interaction between template molecule and functional monomer during the imprinting process. An understanding of the mechanism of molecular imprinting and molecular recognition of MIPs will help to predict the selectivity of MIPs on the basis of template molecule properties. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As interleukin‐1β (IL‐1β) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL‐1β‐induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL‐6, inducible nitric oxide synthase, cyclooxygenase‐2, and tumor necrosis factor‐α (TNF‐α) in a concentration‐dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an anti‐inflammatory effect by inactivating the PI3K/AKT/NF‐κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy. [ABSTRACT FROM AUTHOR]

An acid‐free N‐nitrosation/nitration of the N−H bonds in secondary amines with Fe(NO3)3 ⋅ 9H2O as the nitroso/nitro source through an electrocatalyzed radical coupling reaction was developed. Cyclic aliphatic amines and N‐heteroaromatic compounds were N‐nitrosated and N‐nitrated, respectively, under mild conditions. Control and competition experiments, as well as kinetic studies, demonstrate that N‐nitrosation and N‐nitration involve two different radical reaction pathways involving N+ and N. radicals. Moreover, the electrocatalysis method enables the preferential activation of the N−H bond over the electrode and thus provides high selectivity for specific N atoms. Finally, this strategy exhibits a broad scope and provides a green and straightforward approach to generate useful N‐nitroso/nitro compounds in good yields. [ABSTRACT FROM AUTHOR]

Acute peritonitis is an acute inflammatory response of the peritoneal cavity to physical injury and chemical stimulation. Timely resolution of this response is critical to prevent further damage to the body, which can eventually lead to more severe chronic inflammation. Arctigenin (ATG) is the main active ingredient of the Chinese medicine Arctium lappa. In recent years, there have been an increasing number of studies on the anti-inflammatory effect of ATG, but there have been few studies on the effect of ATG on acute inflammation, especially in acute peritonitis, which has not been reported. In this study, a mouse model of experimental acute peritonitis induced by thioglycolate (TG) solution was used to study the protective anti-inflammatory effect of ATG against acute peritonitis and the relevant mechanism. Our results showed that, after 12 hours of TG treatment, ATG significantly reduced inflammatory cell infiltration in mouse tissues and inhibited the secretion and expression of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in mice. ATG significantly reduced the percentage of CD11b+Ly6G+ neutrophils and F4/80+ macrophages in the spleen and peritoneal exudate. In addition, ATG significantly inhibited the expression of the chemokines CCL3 and CCL4 and the adhesion molecule CD62L on the surface of CD11b-positive monocytes. ATG was observed to inhibit the phosphorylation of p65 and p38 in LPS-stimulated RAW264.7 cells. In conclusion, ATG can improve the symptoms of TG-induced acute peritonitis through immune regulation. ATG can reduce the inflammatory response in TG-induced acute peritonitis in mice. [ABSTRACT FROM AUTHOR]

Leaf senescence is an integral part of plant development, during which, nutrients are remobilized from senescent leaves to fast-growing organs. The initiation and progression dynamics of leaf senescence is therefore vital not only to the maximal accumulation of assimilates but also to the efficient remobilization of nutrients. Senescence is a finely tuned process that involves the action of a large number of transcription factors (TFs). The NAC TFs play critical roles in regulating leaf senescence in Arabidopsis, wheat, rice and tomato. Here, we identified a NAC TF, ZmNAC126 that is responsive to leaf senescence in maize. Ectopic overexpression of ZmNAC126 in Arabidopsis and maize enhanced chlorophyll degradation and promoted leaf senescence. Electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that ZmNAC126 could directly bind to the promoters of major chlorophyll catabolic genes in maize. Dual-luciferase assay in maize protoplasts indicated that ZmNAC126 positively regulates these chlorophyll catabolic genes in maize. Moreover, ZmNAC126 could be induced by ethylene, and ZmEIN3, a major TF of ethylene signalling, could bind to its promoter to transactivate its expression. Taken together, ZmNAC126 may play a pivotal role in regulating natural and ethylene-triggered leaf senescence in maize. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have been implicated in the regulation of resistance to radiotherapy in cervical cancer, which is a type of gynecological disease with high mortality in women around the world. Hence, our purpose is to delineate the involvement of LINC00958 in regulating cell sensitivity to radiotherapy in cervical cancer. LINC00958 expression in cervical cancer was assayed, followed by verification of the relationship among LINC00958, microRNA‐5095 (miR‐5095) and ribonucleotide reductase subunit M2 (RRM2). Hela cells were transduced with up‐/downregulation of miR‐5095 or RRM2, or LINC00958 silencing, respectively, and then treated with or without a 6 Gy dose of X‐ray irradiation. Then the cell proliferation, apoptosis, survival fraction rate, as well as sensitivity to radiotherapy, were assessed. Finally, xenograft tumor in nude mice was established by transplanting Hela cells transfected with sh‐LINC00958 and irradiated with 6 Gy of X‐ray. High expression of LINC00958 was revealed in The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis, as well as in radiation‐resistant patients, which was associated with lower sensitivity to radiotherapy in cervical cancer. Moreover, cervical cancer patients with higher LINC00958 expression exhibited a shorter overall survival according to Kaplan–Meier analysis. In addition, LINC00958 could regulate the expression of RRM2 by competing for miR‐5095. A combination of radiotherapy with LINC00958 silencing, RRM2 downregulation or miR‐5095 overexpression was found to inhibit cervical cancer cell proliferation and tumor growth, while promoting cell apoptosis both in vitro and in vivo. Collectively, our results suggest that LINC00958 could regulate RRM2 by competing to miR‐5095, which regulates cell sensitivity to radiotherapy in cervical cancer. [ABSTRACT FROM AUTHOR]

This study evaluated the effects of berberine on growth performance, immunity, haematological parameters, antioxidant capacity, and the expression of immune response‐related genes in lipopolysaccharide (LPS)‐challenged broilers. We assigned 120 one‐day‐old male broilers (Ross 308) to two treatment groups; each group included two subgroups, each of which included six replicates of five birds per replicate. The experiment used a 2 × 2 factorial arrangement with berberine treatment (0 or 60 mg/kg dietary) and challenge status [injection of saline (9 g/L w/v) or LPS (1.5 mg/kg body weight)] as the main factors. On days 14, 16, 18 and 20, broilers were intraperitoneally injected with LPS or physiological saline. Blood and liver samples were collected on day 21. Dietary berberine supplementation significantly alleviated the compromised average daily gain and average daily feed intake (p < 0.05) caused by LPS. The LPS challenge led to increased lymphocyte and white blood cell (WBC) counts, malondialdehyde (serum and liver) content, and immunoglobulin G and M, tumour necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) expression (p < 0.05) and significantly reduced serum total superoxide dismutase (T‐SOD) activity (p < 0.05). Dietary berberine significantly mitigated the LPS‐induced decreases in the mRNA expression of nuclear factor‐kappa B (NF‐κB), TNF‐α, IL‐1β, inducible nitrite synthase and cyclooxygenase‐2 (p < 0.05) in the liver. In conclusion, berberine supplementation has a positive effect on LPS challenge, which may be related to the increase in antioxidant enzyme activity and inhibition of both NF‐κB signalling and the expression of inflammatory mediators. [ABSTRACT FROM AUTHOR]

Background: Drug resistance and tumor recurrence are the major concerns in clinical practices of gastrointestinal stromal tumor (GIST), with the urgent requirement for exploring undiscovered pathways driving malignancy. To deal with these, recent studies have made many efforts to explore prognosis indicators and establish potential therapeutic targets. Methods: Expression profiles of different risks of GISTs were described and abundant clinical evidences supported our findings in this study. Following exploration in vitro by cell experiments and verification in vivo using tumor microarray were taken to elucidate the underlying mechanism, which drove the malignancy in GIST. Results: Dickkopf 4 (DKK4), as the canonical Wnt pathway antagonist, was unexpectedly and universally upregulated in high‐risk GISTs, and aberrant accumulation of DKK4 was closely correlated with poor prognosis. In addition, tumor‐derived DKK4 could decrease immune cells infiltration and activation in the tumor microenvironment, which decreased the antitumor effects in return. And this phenomenon was recurrent in human tumor specimens. Conclusions: Our findings identified DKK4 as a proper tumor biomarker for prognosis predicting and recurrence monitoring, and suggested a novel immune‐escape mechanism driving malignancy in GIST, which might be a potential therapeutic target to improve the effects of canonical RTK therapy and combined immunotherapy. [ABSTRACT FROM AUTHOR]

Wearing titanium particle‐induced osteoclastogenesis, accompanied by peri‐implant osteolysis, is the main cause of long‐term failure of hip prosthesis. Currently, medications used for the prevention and treatment of peri‐implant osteolysis show serious side effects. Therefore, development for more effective new drugs with less side effects is extremely urgent. Vaccarin is a natural flavonoid extracted from Vaccaria segetalis, with various biological functions, including antioxidantory, anti‐inflammatory, and promotion of angiogenesis. However, the putative role of vaccarin in the inhibition of titanium particle‐induced osteolysis has not been reported. In this study, it was indicated that vaccarin could effectively inhibit RANKL‐induced osteoclastogenesis, fusion of F‐actin rings, bone resorption, and expression of osteoclast marker genes in a dose‐dependent manner in vitro. Moreover, vaccarin could also inhibit RANKL‐induced osteoclastogenesis via the inhibition of NF‐κB and MAPK (p38, ERK, and JNK) signaling pathways, and inhibit the transcription of downstream transcription factors, such as c‐Fos and NFATc1. Consistent with in vitro results, this in vivo study showed that vaccarin exhibited an inhibitory effect on titanium particle‐induced osteolysis by antiosteoclastogenesis. In conclusion, vaccarin could be a promising agent for preventing and treating peri‐implant osteolysis. [ABSTRACT FROM AUTHOR]

Noble-metal free, cost-effective, and highly stable catalysts with efficient activity for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) have attracted tremendous research interest in recent years. Here, a flexible, self-standing hybrid film comprising a N-doped single-wall carbon nanotube (SWCNT) network on which are anchored Ni nanoparticles encapsulated by a monolayer of N-doped carbon (NCNi) is reported. The films are prepared by floating catalyst chemical vapor deposition followed by NH3 treatment. The material obtained at optimum conditions shows excellent bifunctional electrocatalytic activity in alkaline media with low overpotentials of 190 and 270 mV for HER and OER, respectively, to reach a current density of 10 mA cm−2. A current density of 10 mA cm−2 at 1.57 V is achieved when this freestanding and binder-free rod-shaped NCNi/SWCNT assembly is used as cathode and anode in 1 M KOH solution for overall water splitting, presenting one of the best values reported to date. [ABSTRACT FROM AUTHOR]

In this work, the thermoelectric properties of SnTe have been regulated synergistically by introduction of n-type ZnO nanoinclusions. On one hand, the excessive holes in SnTe matrix were compensated properly by n-type ZnO, and the Seebeck coefficient has been improved greatly due to the carrier energy filtering effect by a large quantity of ZnO-SnTe hetero-junction interface barriers; On the other hand, the thermal conductivity gets reduced by the enhanced phonon scattering from multiscale hierarchical architectures. Consequently, a maximum ZT of ~0.9 at 873K has been obtained in the 0.8 wt% sample, which enhances by 112% in comparison with the nanoinclusion-free sample. [ABSTRACT FROM AUTHOR]

Polydatin (PD), a resveratrol glycoside, has been shown to protect renal function in diabetic nephropathy (DN), but the underlying molecular mechanism remains unclear. This study demonstrates that PD stabilize the mitochondrial morphology and attenuate mitochondrial malfunction in both KKAy mice and in hyperglycemia (HG)-induced MPC5 cells. We use Western blot analysis to demonstrate that PD reversed podocyte apoptosis induced by HG via suppressing dynamin-related protein 1 (Drp1). This effect may depend on the ability of PD to inhibit the generation of cellular reactive oxygen species (ROS). In conclusion, we demonstrate that PD may be therapeutically useful in DN, and that, podocyte apoptosis induced by HG can be reversed by PD through suppressing Drp1 expression. [ABSTRACT FROM AUTHOR]

One of the richest reservoirs of antibiotic-resistant bacteria and genes, animal intestinal microbiota contributes to the spread of antibiotic resistance in the environment and, potentially, to human pathogens. Both culture-based genomic technology and culture-independent metagenomics have been developed to investigate the abundance and diversity of antibiotic resistance genes. The characteristics, strengths, limitations, and challenges of these genomic approaches are discussed in this review in the context of antibiotic resistance in animals. We also discuss the advances in single-cell genomics and its potential for surveillance of antibiotic resistance in animals. [ABSTRACT FROM AUTHOR]

Recent researches have reported the extensive pharmacological activities of Ginsenoside Rg1 including antioxidant, anti-inflammatory, and anticancer properties. Furthermore Rg1 was also shown to protect various kinds of cells from self-digestion by its anti-autophagy activity. In previous studies, angiotensin II (Ang II), a key mediator of renin-angiotensin system, has been demonstrated to contribute to the progression of renal injury including abnormal autophagy. However, whether Rg1 can relieve Ang II-induced autophagy in podocyte as well as the underlying molecular mechanism remains to be elucidated. Here, we employed Ang II-treated podocyte as a model to investigate the effect of Rg1 on autophagy and the involved signal pathways. In the present study, we found that Ang II strongly promoted autophagy in immortalized mouse podocyte cells by observing the formation of autophagosomes and detecting the expression of autophagic marker, for example, LC3-II. Notably, compared to the Ang II-treated cells, treatment with Rg1 significantly inhibited the formation of autophagosomes and expression of autophagy-related proteins in Ang II pre-treated podocyte. Meanwhile, Rg1 downregulated the activity of AMPK and GSK-3β and upregulated the activity of P70S6K in Ang II-treated podocyte. In conclusion, these findings demonstrate that Ang II promotes autophagy in podocyte, and Rg1 effectively attenuates this process through AMPK/mTOR/PI3K pathway, suggesting that Rg1 may be beneficial to alleviate podocyte injury. [ABSTRACT FROM AUTHOR]

For practical application, the functional piezoelectric film in microelectromechanical systems should meet the requirement of physical properties, as well as the mechanical properties. In this article, 0.5 Ba( Ti0.8 Zr0.2) O3-0.5( Ba0.7 Ca0.3) TiO3 (0.5 BZT-0.5 BCT) thin films with varied properties were prepared on (100) Si substrates via a sol-gel technique at different annealing temperatures. The effects of the annealing temperature on the morphology, piezoelectricity, hardness, and elastic modulus were studied. Particular attention was paid to the surface frictional behavior of films, and the changes in the friction force can be radically explained in terms of differences in the hardness/elastic modulus ratio and the residual stress of films. And, it reveals that the higher ratio of hardness to elastic modulus and tensile residual stress can contribute to a lower friction force for 0.5 BZT-0.5 BCT film during sling friction. [ABSTRACT FROM AUTHOR]

A novel crystal, the mono-protonated metformin acetate (1), was obtained and characterized by elemental analysis, IR spectroscopy and X-ray crystallography. It was found that one of the imino group in the metformin cation was protonated along with the proton transfer from the secondary amino group to the other imino group. Its crystal structure was then compared with the previously reported diprotonated metformin oxalate (2). The difference between them is that the mono-protonated metformin cations can be linked by hydrogen bonding to form dimers while the diprotonated metformin cations cannot. Both of them are stabilized by intermolecular hydrogen bonds to assemble a 3-D supermolecular structure. The four potential tautomer of the monoprotonated metformin cation (tautomers 1a, 1b, 1c and 1d) were optimized and their single point energies were calculated by Density Functional Theory (DFT) B3LYP method based on the Polarized Continuum Model (PCM) in water, which shows that the most likely existed tautomer in human cells is the same in the crystal structure. Based on the optimized structure, their Wiberg bond orders, Natural Population Analysis (NPA) atomic charges, molecular electrostatic potential (MEP) maps were calculated to analyze their electronic structures, which were then compared with the corresponding values of the diprotonated metformin cation (cation 2) and the neutral metformin (compound 3). Finally, the possible tautomeric mechanism of the monoprotonated metformin cation was discussed based on the observed phenomena. [ABSTRACT FROM AUTHOR]

The La2Ce2O7 powder doped with Sr was synthesized by sol-gel method in this study and its dense bulk samples were also prepared by pressureless-sintered at 1600°C for 10 h. Its phase composition, microstructure, and thermophysical property were investigated. Results reveal that pure (La0.95Sr0.05)2Ce2O6.95 with single fluorite structure was successfully synthesized. Microstructure of bulk sample is dense. Its thermal expansion coefficient is higher than that of Y2O3-stabilized ZrO2 ( YSZ) and its thermal conductivity is lower than that of YSZ. These results show that (La0.95Sr0.05)2Ce2O6.95 ceramic can be explored as the candidate material for thermal barrier coatings. [ABSTRACT FROM AUTHOR]

BACKGROUND Xanthoceras sorbifolia Bunge is a valuable oilseed tree that has linoleic acid-rich seed oil. Microsomal oleate desaturase ( FAD2; EC 1.3.1.35) is responsible for the conversion of oleic acid to linoleic acid during fatty acid synthesis. In this study, XsFAD2 was cloned from developing embryos of X. sorbifolia. RESULTS XsFAD2 contained three histidine boxes, a C-terminal endoplasmic reticulum retrieval motif, and five putative transmembrane domains representing the characteristics of membrane-bound fatty acid desaturase. XsFAD2 expression in yeast cells resulted in linoleic acid (18:2) and palmitolinoleic acid (16:2) production, confirming the biological activity of the enzyme encoded by XsFAD2. These fatty acids are not normally present in wild-type yeast. Phylogenetic analysis indicated that XsFAD2 is located in a subgroup of FAD2 enzymes specifically or highly expressed in developing seeds. The expression level of XsFAD2 in seeds was much higher than those in leaves and petals. Furthermore, XsFAD2 expression pattern correlated well with linoleic acid accumulated in seeds. CONCLUSION Results suggested that XsFAD2 is responsible for the high linoleic acid content in X. sorbifolia seed oil. This study provides insight on the regulation mechanism of fatty acid synthesis in X. sorbifolia seeds and a valuable gene for improving the oil quality in oilseed trees. © 2013 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

The genomic amplification of chromosome 1q long arm, the chromosomal region containing Clorf61, is a common event in human cancers. However, the expression pattern of chromosome 1 open reading frame 61 (Clorf61) in hepatocellular carcinoma (HCC) and its effects on HCC progression remain unclear. We have previously reported that Clorf61 is highly up-regulated during human embryogenesis. In this study, we report that Clorf61 expression is associated with the progression of liver disease. We found that Clorf61 is up-regulated in hepatic cirrhosis tissues and is further up-regulated in primary HCC tumors. Moreover, hepatitis B virus (HBV)-positive patients exhibited significantly higher levels of Clorf61 expression than HBV-negative patients. The evaluation of highly malignant HCC cell lines revealed high protein expression levels of Clorf61. Furthermore, the Clorf61 protein was found to be predominantly distributed within the cytoplasm. The ectopic expression of Clorf61 in the nonmalignant L02 cell line promoted cellular proliferation and colony formation in vitro, as well as cell cycle progression via the regulation of the expression of specific cell cycle-related proteins. In addition, the overexpression of Clorf61 in L02 cells facilitated cellular invasion and metastasis. The down-regulation of epithelial markers (E-cadherin and occludin) and the up-regulation of mesenchymal markers (N-cadherin, vimentin, and snail) suggested that the overexpression of Clorf61 induced the epithelial-mesenchymal transition (EMT) that is linked to metastasis. Taken together, our findings demonstrate, for the first time, the roles of Clorf61 in HCC tumorigenesis and metastasis. [ABSTRACT FROM AUTHOR]

The genetic association between a variant in the Toll-like receptor 3 (TLR3) gene (C1234T in mRNA, L412F in protein, Reference SNP Cluster Report rs3775291) and geographic atrophy (GA; also called advanced "dry" age-related macular degeneration) was controversial in previous studies. We performed a meta-analysis by pooling the current evidence in literature and found that the T allele of the TLR3 C1234T variant showed a summary odds ratio of 0.753 (95% confidence interval: 0.612-0.927; P=0.007). Further experiments were performed to analyze how this mutant influences the function of TLR3. We found that this SNP did not affect mRNA, protein, or surface expression of TLR3. However, the binding capacity of L412F mutation of TLR3 for double-stranded RNA in the TLR3 protein was only 51.12 ± 3.96% (P<0.001) of the wild-type level. There was a consistently reduced TLR3-mediated NF-κB activation. Therefore, TLR3 C1234T (L412F in the protein) may protect against GA by reduced binding capacity of TLR3 to dsRNA. This study may provide a better understanding of the genetic architecture underlying disease susceptibility and may advance the potential for preclinical prediction in future genetic testing. [ABSTRACT FROM AUTHOR]

The posttranscriptional regulation of miRNAs is important for organism development. To investigate the role of miRNAs in angiogenesis, we performed a loss-of-function screening assay in human umbilical vein endothelial cells (HUVECs) and found that knockdown of 7 miRNAs (miR-95a, miR-126, miR-129, miR-137, miR-139, miR-200a, and miR-335) significantly suppressed cell viability. As miR-200a was highly expressed in HUVECs, blocking endogenous miR-200a using 2′-OMe antisense oligonucleotide (ASOs) resulted in a decrease of cell viability and migration. Bioinformatics analysis indicates the 3′ untranslated region (UTR) of thrombospondin-1 (THBS1) has a putative binding site for miR-200a. MiR-200a can directly bind to THBS1 3′UTR and negatively regulate THBS1 expression. The identification of endothelial cells (ECs) related miRNA and its target gene may gain new insight into the mechanism of angiogenesis. © 2011 IUBMB IUBMB Life, 63(7): 553-559, 2011 [ABSTRACT FROM AUTHOR]

MicroRNAs are small noncoding RNAs that negatively regulate target mRNAs at the posttranscription level. Here, we show that miR-16 is upregulated in human laryngeal carcinoma tissues. Inhibition of miR-16 in HEp-2 laryngeal cancer cell line could suppress cell migration and enhance cell-cell adhesion. Subsequently, zyxin, whose expression is negatively regulated by miR-16, is confirmed to be a direct target gene of miR-16. Furthermore, overexpression of zyxin could also restrain cell movement and enhance cell-cell adhesion. The study of miR-16 and its target zyxin will shed light on diagnosis and therapy of laryngeal cancer. © 2011 IUBMB IUBMB Life, 63(2): 101-108, 2011 [ABSTRACT FROM AUTHOR]

Li X, Li J, Du W, Zhang J, Liu W, Chen X, Li H, Huang S, Li X. Relevance of immunophenotypes to prognostic subgroups of age, WBC, platelet count, and cytogenetics in de novo acute myeloid leukemia. APMIS 2010. Immunophenotyping is one of the independent prognostic factors in acute myeloid leukemia (AML). Relevance of immunophenotypes to prognostic subgroups of age, white blood cells (WBC), platelet count, and cytogenetics in de novo AML was comprehensively investigated in this study for the first time. Human leukocyte antigen (HLA)-DR and CD14 expression associated with the elderly, highest WBC count, and unfavorable-risk cytogenetics; CD4, CD7, and CD11b expression correlated with highest WBC count and unfavorable-risk cytogenetics; CD64 expression was associated with higher WBC count while that of CD13 was associated with lower platelet count; CD22, CD34, CD123, and terminal deoxynucleotidyl transferase (TdT) expression correlated with unfavorable-risk cytogenetics; CD5 expression was associated with normal platelet count while that of CD19 was associated with children and favorable-risk cytogenetics; CD117 expression was associated with low WBC and lower platelet counts; myeloperoxidase (MPO) expression correlated with lower platelet count; and MPO and glycophorin A (Gly-A) expression was associated with lower WBC count and favorable-risk cytogenetics. The results of the relevance analysis revealed the distribution characteristics of antigen expression in different AML prognostic subgroups. The majority of antigens associated with good or poor prognostic subgroups were in accordance with the previous reports of correlation of expression of these antigens with prognosis. Antigens associated with good (or poor) prognostic subgroups were defined as good (or poor)-risk antigens. [ABSTRACT FROM AUTHOR]

Earlier studies identified testes-specific protease 50 ( TSP50), which encodes a threonine protease, and showed that it was abnormally reactivated in many breast cancer biopsies. Further, it was shown to be negatively regulated by the p53 gene. However, little is known about the biological function of TSP50. In this study, we applied RNA interference to knockdown TSP50 gene expression in P19 murine embryonal carcinoma stem cells and tested whether this modulated the cell phenotype. The results showed that downregulation of TSP50 expression not only reduced cell proliferation, colony formation, and migration but also induced cell apoptosis. Further investigation revealed that knockdown of TSP50 resulted in greater sensitivity to doxorubicin-induced apoptosis and that activation of caspase-3 was involved in this process. © 2010 IUBMB IUBMB Life, 2010 [ABSTRACT FROM AUTHOR]

Sequence stratigraphical analysis was applied to the Upper Carboniferous-Lower Permian sedimentary succession of the northeastern Ordos Basin, north China based on data acquired from ten entire logging curves and eight outcrops. The facies framework of the lithostratigraphical unit, the Taiyuan Formation comprises seven facies in two facies associations, varying from fluvio-delta to shelf-barrier islands. The facies are presented within a chronostratigraphical framework, linked by systems tract, which in turn are limited by flooding surfaces and sequence boundaries. Six third-order depositional sequences are recognised, bounded by six type 2 unconformities. An upwards-shallowing epicontinental sea sedimentary model is created, which consists of a sandstone, coal seam and carbonate succession. [ABSTRACT FROM AUTHOR]

MicroRNAs are an evolutionarily conserved class of endogenous noncoding RNAs that modulate gene expression at the post-transcriptional level. Recently, microRNA-23a (miR-23a) has been found to function as a growth-promoting and antiapoptotic factor in hepatocellular carcinoma cells. Our previous study showed that miR-23a was significantly upregulated in gastric adenocarcinoma tissues. In this study, we found that miR-23a promoted the proliferative potential of gastric adenocarcinoma cell line MGC803. We also identified IL6R as a direct target gene for miR-23a using a fluorescent reporter assay. The mRNA and protein levels of IL6R were both inversely correlated with the miR-23a expression level. Our results demonstrate that miR-23a can target IL6R and promote the growth activity of gastric adenocarcinoma cells in vitro. The downregulation of IL6R by miR-23a may explain why the suppression of miR-23a can inhibit gastric cancer cell proliferation. [ABSTRACT FROM AUTHOR]

Human embryogenesis is believed to involve an integrated set of complex yet coordinated development of different organs and tissues mediated by the changes in the spatiotemporal expression of many genes. Here, we report a genome-wide expression analysis during wk 4-9 of human embryogenesis, a critical period when most organs develop. About half of all human genes are expressed, and 18.6% of the expressed genes were significantly regulated during this important period. We further identified >5000 regulated genes, most of which previously were not known to be associated with animal development. Our study fills an important gap in mammalian developmental studies by identifying functional pathways involved in this critical but previously not studied period. Our study also revealed that the genes involved here are distinct from those during early embryogenesis, which include three groups of maternal genes. Furthermore, we discovered that genes in a given developmental process are regulated coordinately. This led us to develop an easily searchable database of this entire collection of gene expression profiles, allowing for the identification new genes important for a particular developmental process/pathway and deducing the potential function of a novel gene. The validity of the predictions from the database was demonstrated with two examples through spatiotemporal analyses of the two novel genes. Such a database should serve as a highly valuable resource for the molecular analysis of human development and pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Cerebral oedema leading to cerebral herniation is a major cause of death during acute liver failure (ALF), but the underlying mechanism is not clear. Aims: We investigated the role of tumour necrosis factor (TNF)-α in changing the permeability of the blood–brain barrier (BBB) during ALF. Methods: ALF animal models were generated by administeringd-galactosamine (GalN) and lipopolysaccharide, or GalN and TNF-α. ALF induction was blocked by first administering anti-TNF-α–IgG or anti-TNF-α-R1. We investigated the BBB permeability with Evans blue staining, and the structure with electron microscopy. Results: BBB permeability increased in ALF mice and correlated with elevated serum TNF-α levels. No vascular endothelial cell (EC) apoptosis was detected, but electron microscopy of cells from human and mouse ALF tissues revealed tight junction (TJ) disruptions and EC shrinkage, as well as increased vesicles and vacuoles. In addition, the expression of the TJ-associated protein occludin was significantly decreased in both ALF mice and patients, although the expression of occludin mRNA did not change. Changes in BBB permeability, brain tissue ultrastructure and occludin expression in ALF-induced mice could be prevented by prophylaxis treatment with either antibody to TNF-α–IgG or antibody to TNF-α-R1. Conclusions: Our results suggest that TNF-α plays a critical role in the development of brain oedema in ALF, and that both vasogenic and cytotoxic mechanisms may be involved. Increased BBB permeability may be because of the disruption of TJs, and loss of the TJ-associated protein occludin. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the function and number of Treg cells in patients with antibiotic-refractory Lyme arthritis. According to the authors, Treg cells were functional in patients with antibiotic-refractory arthritis while in some patients, higher number of Treg cells in synovial fluid appeared to be involved in the treatment of arthritis. In a mouse model, the authors explain that antibiotic-refractory arthritis and lower number of Treg cells were unable to achieve the treatment of synovial disease.

Background and objective: Sequential three-step empirical therapy is useful for the management of chronic cough. The purpose of this study was to evaluate the efficacy and safety of modified sequential three-step empirical therapy. Methods: Consecutive patients ( n = 240) with chronic cough were recruited and randomly assigned to receive modified (modified group) or primary (primary group) sequential three-step empirical therapy. The primary end-point was the overall rate of control of chronic cough. Secondary end-points were the rate of control of chronic cough at each step of therapy, the duration of treatment required, changes in cough symptom score, health-related quality of life and possible adverse effects. Results: The study was completed by 106 patients in the modified group and 108 patients in the primary group. The overall rate of control of chronic cough was 88.7% in the modified group and 91.7% in the primary group (χ2 = 0.54, P > 0.05). There were no obvious differences in the rate of control of cough at each step of therapy, the duration of treatment required, patterns of cough symptom scores or improvements in the health-related quality of life between the modified and primary groups. However, the incidence of drowsiness was significantly lower in the modified group than in the primary group (11.7% vs 21.7%, χ2 = 4.32, P = 0.04). Conclusions: Modified three-step empirical therapy was as efficacious as primary three-step therapy for chronic cough, but was preferable because it had fewer side-effects. [ABSTRACT FROM AUTHOR]

MicroRNAs are a group of endogenously expressed, single-stranded, 18–24 nt RNAs that regulate diverse cellular pathways. Although documented evidence indicates that some microRNAs can function as oncogenes or tumor-suppressors, the role of miR-214 in regulating human cervical cancer cells remains unexplored. We determined the expression level of miR-214 and found it is downregulated in cervical cancer compared with normal tissue. Overexpression of miR-214 in HeLa cells, a human cervical cancer cell line, significantly inhibited cell proliferation according to the MTT and colony forming assays. HeLa cells that stably overexpress miR-214 downregulate the expression of MEK3 and JNK1 at both mRNA and protein levels. Further investigation revealed that miR-214 regulates the expression of MEK3 and JNK1 by targeting the 3′UTRs of these genes. Collectively, these results suggest that miR-214 negatively regulates HeLa cell proliferation by targeting the noncoding regions of MEK3 and JNK1 mRNAs. © 2009 IUBMB IUBMB Life, 61(11): 1075–1082, 2009 [ABSTRACT FROM AUTHOR]

The vacuolar NHX-type Na+/H+ exchangers play a key role in salt tolerance in plants. However, little is known about the Na+/H+ exchangers in the salt-resistant tree, Populus euphratica. In this study, we identified six putative vacuolar Na+/H+ exchanger genes from P. euphratica, designated as PeNHX1–6. Real-time polymerase chain reaction indicated that the PeNHX1/3/6 transcripts were abundant compared with the other three PeNHX genes in the three tissues (roots, stems and leaves) examined. After NaCl treatment for 6 h, the transcript levels of PeNHX1–6 were upregulated in the roots. To address the function of PeNHX1–6, complementation studies were performed with the salt-sensitive yeast mutant strain R100, which lacks activity of the endosomal Na+/H+ antiporter NHX1. The results showed that PeNHX1–6 compensates, at least in part, for the function of yeast NHX1. Moreover, PeNHX3 was targeted to the tonoplast when transiently expressed in onion. Together, these results suggest that PeNHX1–6 function as vacuolar Na+/H+ exchangers and that PeNHX products play an important role in the salt resistance of P. euphratica. [ABSTRACT FROM AUTHOR]

MicroRNAs are emerging as important regulators of cancer-related processes. Our studies show that microRNA-9 (miR-9) is downregulated in human ovarian cancer relative to normal ovary, and overexpression of miR-9 suppresses cell growth in vitro. Furthermore, the 3′-UTR of NF-κB1 mRNA is found to be regulated directly by miR-9, demonstrating that NF-κB1 is a functionally important target of miR-9 in ovarian cancer cells. When miR-9 is overexpressed in ovarian cancer cells, the mRNA and protein levels of NF-κB1 are both suppressed, whereas inhibition of miR-9 results in an increase in the NF-κB1 expression level. Ovarian cancer tissues display significantly low expression of miR-9 and a high level of NF-κB1 compared with normal tissues, indicating that regulation of NF-κB1 by miR-9 is an important mechanism for miR-9 to inhibit ovarian cancer proliferation. [ABSTRACT FROM AUTHOR]

Aim: Fluorofenidone (1-(3-fluorophenyl)-5-methyl-2-(1H)-pyridone) is a novel pyridone agent. The aim of the present study is to investigate the effects of fluorofenidone on angiotensin (Ang)II-induced fibrosis and the involved molecular mechanism in rat proximal tubular epithelial cells. Methods: NRK-52E cells, a rat proximal tubular epithelial cell line, were incubated with medium containing AngII, with or without nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenylene iodonium (DPI), losartan, fluorofenidone (2, 4 and 8 mmol/L) and pirfenidone (8 mmol/L) for 24 h. Cells in the serum-free medium were controls. The expression of three subunits of NADPH oxidase, including p47phox, Nox-4 and p22phox, were determined by real-time reverse transcription polymerase chain reaction (RT–PCR) and western blot. NADPH oxidase activity was measured directly by superoxide dismutase (SOD) inhibitable cytochrome C reduction assay. The generation of reactive oxygen species (ROS) was measured by dichlorofluorescein fluorescence analysis. The mRNA and protein expression of collagen I and transforming growth factor (TGF)-β1 were determined by real-time RT–PCR and enzyme-linked immunosorbent assay. Results: Fluorofenidone significantly inhibited TGF-β1 and collagen I expression upregulation induced by AngII or TGF-β1 respectively. Moreover, fluorofenidone greatly reduced the elevation of expression and activity of NADPH oxidase and inhibited ROS generation induced by AngII in rat proximal tubular epithelial cells. These responses were also attenuated by DPI, losartan, and pirfenidone. Conclusion: Fluorofenidone acted as an anti-oxidative and anti-fibrotic agent through the mechanisms of blocking NADPH oxidase-dependent oxidative stress and inhibiting TGF-β1 expression in rat proximal tubular epithelial cells. [ABSTRACT FROM AUTHOR]

A total of 67 eyes of 67 patients that have undergone vitrectomy and silicone oil tamponade for rhegmatogenous retinal detachment were included in this prospective clinical study. We measured the axial length (AL) and the anterior chamber depth (ACD) with A-mode ultrasonography and IOL Master before and after removal of silicone oil. Phase refractive indices of silicone oil at different wavelengths from 400 nm to 1000 nm were measured with an Abbe refractometer and a series of equations were derived to adjust the AL values obtained with the IOL Master in silicone-filled eyes. The instruments showed good agreement between the AL values measured before and after removal of silicone oil. The ACD values obtained with A-mode ultrasonography were lower than the values obtained with the IOL Master ( p < 0.01). The AL values obtained with the IOL Master after removal of silicone oil were lower than the values obtained preoperatively ( p < 0.01). The AL values obtained with the IOL Master after adjustment are more accurate than A-mode ultrasonography in silicone-filled eyes. [ABSTRACT FROM AUTHOR]

This paper demonstrates that fine-grained (2–3 μm), transparent Nd:YAG can be achieved at SiO2 doping levels as low as 0.02 wt% by the sinter plus hot isostatic pressing (HIP) approach. Fine grain size is assured by sintering to 98% density, in order to limit grain growth, followed by HIP. Unlike dry-pressed samples, tape-cast samples were free of large, agglomerate-related pores after sintering, and thus high transparency (i.e., >80% transmission at 1064 nm) could be achieved by HIP at <1750°C along with lower silica levels, thereby avoiding conditions shown to cause exaggerated grain growth. Grain growth was substantially limited at lower SiO2 levels because silica is soluble in the YAG lattice up to ∼0.02–0.1 wt% at 1750°C, thus allowing sintering and grain growth to occur by solid-state diffusional processes. In contrast, liquid phase enhanced densification and grain growth occur at ∼0.08–0.14 wt% SiO2, especially at higher temperatures, because the SiO2 solubility limit is exceeded. [ABSTRACT FROM AUTHOR]

Accumulation of neurotoxic amyloid-β (Aβ) is central to the pathology of Alzheimer’s disease (AD). Elucidating the mechanisms of Aβ accumulation will therefore expedite the development of Aβ-targeting AD therapeutics. We examined activity of an Aβ-degrading protease (matrix metalloprotease 2) to investigate whether biochemical factors consistent with conditions in the AD brain contribute to Aβ accumulation by altering Aβ sensitivity to proteolytic degradation. An Aβ amino acid mutation found in familial AD, Aβ interactions with zinc (Zn), and increased Aβ hydrophobicity all strongly prevented Aβ degradation. Consistent to all of these factors is the promotion of specific Aβ aggregates where the protease cleavage site, confirmed by mass spectrometry, is inaccessible within an amyloid structure. These data indicate decreased degradation due to amyloid formation initiates Aβ accumulation by preventing normal protease activity. Zn also prevented Aβ degradation by the proteases neprilysin and insulin degrading enzyme. Treating Zn-induced Aβ amyloid with the metal-protein attenuating compound clioquinol reversed amyloid formation and restored the peptide’s sensitivity to degradation by matrix metalloprotease 2. This provides new data indicating that therapeutic compounds designed to modulate Aβ-metal interactions can inhibit Aβ accumulation by restoring the catalytic potential of Aβ-degrading proteases. [ABSTRACT FROM AUTHOR]

Yttria-stabilized zirconia (YSZ) deposits were prepared by an atmospheric plasma spray (APS) on a stainless-steel substrate preheated to different temperatures from room temperature to 1100°C. The microstructure of the deposits was characterized from polished and fractured cross sections by scanning electron microscopy (SEM). The ionic conductivity of the deposits was measured using both DC and AC methods, and the relationship between ionic conductivity and microstructure of deposits was examined. SEM observation revealed that the YSZ deposits exhibit different microstructures with different deposition temperatures. With the increase of the deposition temperature, the columnar grain growth across lamellar interfaces was enhanced and subsequently the intersplat bonding ratio in the deposit was improved. The ionic conductivity of YSZ deposits at the direction perpendicular to the deposit surface was significantly increased through the microstructure development on increasing the deposition temperature. However, it was found that the intergrain resistance changed little despite a remarkable change of the deposition temperature. A microstructure model is proposed to correlate the relative conductivity to the mean lamellar interface bonding ratio. The increase in ionic conductivity of the YSZ deposit with the deposition temperature can be attributed to the increase in the lamellar interface bonding ratio. [ABSTRACT FROM AUTHOR]