Search

Heart failure (HF) is the end-stage syndrome for most cardiac diseases, and the 5-year morbidity and mortality of HF remain high. Malignant arrhythmia is the main cause of sudden death in the progression of HF. Recently, bridging integrator 1 (BIN1) was discovered as a regulator of transverse tubule function and calcium signalling in cardiomyocytes. BIN1 downregulation is linked to abnormal cardiac contraction, and it increases the possibility of malignant arrhythmias preceding HF. Because of the detectability of cardiac BIN1 in peripheral blood, BIN1 may serve as a predictor of HF and may be useful in therapy development. However, the mechanism of BIN1 downregulation in HF and how BIN1 regulates normal cardiac function under physiological conditions remain unclear. In this review, recent progress in the biological studies of BIN1-related cardiomyocytes and the effect of cardiac dysfunction and malignant arrhythmia will be discussed., (© 2019 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Background: Light conditions significantly influence grape berry ripening and the accumulation of phenolic compounds, but the underlying molecular basis remains partially understood. Here, we applied integrated transcriptomics and pathway-level metabolomics analyses to investigate the effect of cluster bagging during various developmental stages on phenolic metabolism in Cabernet Sauvignon grapes., Results: Bagging treatments had limited effects on berry quality attributes at harvest and did not consistently affect phenolic acid biosynthesis between seasons. Significantly elevated flavan-3-ol and flavonol contents were detected in re-exposed berries after bagging during early-developmental stages, while bagging after véraison markedly inhibited skin anthocyanin accumulation. Several anthocyanin derivatives and flavonol glycosides were identified as marker phenolic metabolites for distinguishing bagged and non-bagged grapes. Coordinated transcriptional changes in the light signaling components CRY2 and HY5/HYHs, transcription regulator MYBA1, and enzymes LAR, ANR, UFGT and FLS4, coincided well with light-responsive biosynthesis of the corresponding flavonoids. The activation of multiple hormone signaling pathways after both light exclusion and re-exposure treatments was inconsistent with the changes in phenolic accumulation, indicating a limited role of plant hormones in mediating light/darkness-regulated phenolic biosynthesis processes. Furthermore, gene-gene and gene-metabolite network analyses discovered that the light-responsive expression of genes encoding bHLH, MYB, WRKY, NAC, and MADS-box transcription factors, and proteins involved in genetic information processing and epigenetic regulation such as nucleosome assembly and histone acetylation, showed a high positive correlation with grape berry phenolic accumulation in response to different light regimes., Conclusions: Altogether, our findings provide novel insights into the understanding of berry phenolic biosynthesis under light/darkness and practical guidance for improving grape features.

When tailing spill accidents occur, the risk of contamination by antimony (Sb) tailings into adjacent rivers, sediments, aquifers and soil environments is high. The Sb concentrations in water and sediment under different stringent control activities were investigated for 60 days in the Jialing River basin after a tailing spill accident. Both reservoir regulation and the construction of a temporary dam with coagulation dosing remarkably reduced the Sb levels in the river water. The increase in dissolved Sb caused by the spill was reduced from ~400 μg/L in the inflow to ~200 μg/L in the outflow by reservoir regulation. Moreover, reservoir regulation led to a high concentration of Sb in the reservoir sediment, which was difficult to remove and may cause subsequent unpredictable long-term ecological and health risks. In contrast, the Sb-enriched deposition inside the temporary dam was convenient to remove. Notably, temperature alternations between day and night in winter resulted in a large fluctuation in coagulation efficiency, which may cause the failure of stringent control projects. The results of this study suggest potential improvements to stringent control activities after mine tailing accidents to mitigate environmental impacts and prevent secondary risks., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The A-kinase anchoring proteins (AKAPs) are a group of structurally diverse proteins identified in various species and tissues. These proteins are able to anchor protein kinase and other signalling proteins to regulate cardiac function. Acting as a scaffold protein, AKAPs ensure specificity in signal transduction by enzymes close to their appropriate effectors and substrates. Over the decades, more than 70 different AKAPs have been discovered. Accumulative evidence indicates that AKAPs play crucial roles in the functional regulation of cardiac diseases, including cardiac hypertrophy, myofibre contractility dysfunction and arrhythmias. By anchoring different partner proteins (PKA, PKC, PKD and LTCCs), AKAPs take part in different regulatory pathways to function as regulators in the heart, and a damaged structure can influence the activities of these complexes. In this review, we highlight recent advances in AKAP-associated protein complexes, focusing on local signalling events that are perturbed in cardiac diseases and their roles in interacting with ion channels and their regulatory molecules. These new findings suggest that AKAPs might have potential therapeutic value in patients with cardiac diseases, particularly malignant rhythm., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: Airborne pollutants have collectively been classified as a known human carcinogen and, more broadly, affect the health of hundreds of millions of people worldwide. Benzene is a frequent component of air pollution, and strategies to protect individuals against unavoidable exposure to this and other airborne carcinogens could improve the public's health. Earlier clinical trials in Qidong, China, demonstrated efficacy in enhancing the detoxication of benzene using a broccoli sprout beverage., Objectives: A randomized, placebo-controlled, multidose trial of a broccoli sprout beverage was designed to determine the lowest effective concentration that enhances benzene detoxication adjudged by enhanced excretion of the urinary biomarker, S-phenylmercapturic acid (SPMA)., Methods: Following informed consent, 170 subjects were randomly assigned in 5 blocks of 34 each to drink either a placebo beverage (n = 55) or 1 of 3 graded concentrations of a broccoli sprout beverage [full (n = 25), one-half (n = 35), and one-fifth (n = 55)] for 10 consecutive days. Concentrations of SPMA arising through induced benzene conjugation with glutathione were quantified by MS in sequential 12-h overnight urine collections during the intervention., Results: MS was also used to quantify urinary sulforaphane metabolites in each dosing regimen that resulted in a median 24-h urinary output of 24.6, 10.3, and 4.3 µmol, respectively, confirming a dose-dependent de-escalation of the inducing principle within the beverage. A statistically significant increase in benzene mercapturic acids in urine was found for the high-dose group (+63.2%) during the 10-d period. The one-half dose (+11.3%) and one-fifth dose groups (-6.4%) were not significantly different from placebo controls., Conclusions: An intervention with a broccoli sprout beverage enhanced the detoxication of benzene, an important airborne pollutant, when dosed at a concentration evoking a urinary elimination of ∼25 µmol sulforaphane metabolites per day, and it portends a practical and frugal population-based strategy to attenuate associated long-term health risks of air pollution. This trial was registered at clinicaltrials.gov as NCT02656420., (Copyright © American Society for Nutrition 2019.)

Coronary heart disease is a serious cardiovascular illness. Percutaneous coronary artery stent implantation has become a routine way to treat coronary heart disease. Although studies have shown how a drug-eluting stent could improve the efficacy of clinical treatment, 10~20% of in-stent restenosis is still an important outcome that restricts the clinical efficacy of drug-eluting stent implantations and causes cardiovascular events such as angina pectoris, acute myocardial infarction, and sudden death. The KCa3.1 channel plays an important role in neoatherosclerosis of in-stent restenosis by regulating macrophage function. Recent studies have shown that the KCa3.1 channel, which belongs to the family of calcium-activated potassium channels, plays an important role in the occurrence and development of various inflammatory diseases by regulating cell membrane potentials and calcium signaling in the processes of macrophage migration and mitogen-stimulated vascular smooth muscle cell and fibroblast proliferation. The KCa3.1 channel is activated by elevated intracellular calcium levels. Inhibition of the KCa3.1 channel can effectively slow the progression of arterial plaque rupture and reduce the degree of vascular restenosis, and so substances that can carry out this inhibition are expected to become targeted drugs for the treatment of in-stent neoatherosclerosis. This article reviews the pathological and physiological roles of the KCa3.1 channel and its roles in the disease prognosis of in-stent neoatherosclerosis.

Alternative splicing (AS) serves as an additional regulatory process for gene expression after transcription, and it generates distinct mRNA species, and even noncoding RNAs (ncRNAs), from one primary transcript. Generally, AS can be coupled with transcription and subjected to epigenetic regulation, such as DNA methylation and histone modifications. In addition, ncRNAs, especially long noncoding RNAs (lncRNAs), can be generated from AS and function as splicing factors ("interactors" or "hijackers") in AS. Recently, RNA modifications, such as the RNA N6-methyladenosine (m6A) modification, have been found to regulate AS. In this review, we summarize recent achievements related to the epigenetic regulation of AS., Competing Interests: None.

ATP-sensitive potassium channels (K ATP ) channels are widely distributed in various tissues, including pancreatic beta cells, muscle tissue and brain tissue. K ATP channels play an important role in cardioprotection in physiological/pathological situations. K ATP channels are inhibited by an increase in the intracellular ATP concentration and are stimulated by an increase in the intracellular MgADP concentration. Activation of K ATP channels decreases ischaemia/reperfusion injury, protects cardiomyocytes from heart failure, and reduces the occurrence of arrhythmias. K ATP channels are involved in various signalling pathways, and their participation in protective processes is regulated by endogenous signalling molecules, such as nitric oxide and hydrogen sulphide. K ATP channels may act as a new drug target to fight against cardiovascular disease in the development of related drugs in the future. This review highlights the potential mechanisms correlated with the protective role of K ATP channels and their therapeutic value in cardiovascular diseases., (© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: Previous studies have suggested that exogenous hydrogen sulfide can alleviate the development of diabetic cardiomyopathy (DCM) by inhibiting oxidative stress, inflammation, and apoptosis. However, the underlying mechanism is not fully understood. Nuclear expression and function of the transcription factor Forkhead box protein O (FoxO1) have been associated with cardiovascular diseases, and thus, the importance of FoxO1 in DCM has gained increasing attention. This study was designed to investigate the interactions between hydrogen sulfide (H 2 S) and nuclear FoxO1 in DCM., Methods: Diabetes was induced in adult male C57BL/6J mice by intraperitoneal injection of streptozotocin and was treated with H 2 S donor sodium hydrosulfide for 12 weeks. The H9C2 cardiomyoblast cell line and neonatal rat cardiomyocytes (NRCMs) were treated with the slow-releasing H 2 S donor GYY4137 before high-glucose (HG) exposure with or without pretreatment with the Akt inhibitor MK-2206 2HCl. Changes in FoxO1 protein phosphorylation and subcellular localization were determined in H9C2 cells, NRCMs, and cardiac tissues from normal and diabetic mice. Cardiac structure and function in the diabetic mice were evaluated by echocardiography and histological analysis and compared with those in control animals., Results: The echocardiographic and histopathological data indicated that exogenous H 2 S improved cardiac function and attenuated cardiac hypertrophy and myocardial fibrosis in diabetic mice. H 2 S also improved HG-induced oxidative stress and apoptosis in cardiac tissue and NRCMs. In addition, H 2 S induced FoxO1 phosphorylation and nuclear exclusion in vitro and in vivo, and this function was not inhibited by MK-2206 2HCl. Alanine substitution mutation of three sites in FoxO1-enhanced FoxO1 transcriptional activity, and subsequent treatment with exogenous H 2 S could not prevent HG-induced nuclear retention., Conclusions: Our data indicate that H 2 S is a novel regulator of FoxO1 in cardiac cells and provide evidence supporting the potential of H 2 S in inhibiting the progression of DCM., (© 2018 Wiley Periodicals, Inc., A Wiley Company.)

Objective: This study aimed to explore the relationship between perceived stress, sense of coherence, and depression among older stroke patients., Methods: A demographic questionnaire, the Perceived Stress Scale (PSS), the Sense of Coherence Scale (SOC) and the Center for Epidemiologic Studies Depression Scale (CES-D) were distributed to 3000 older stroke patients from Neurology wards in six large general hospitals, and 2907 individuals completed the survey. Data analysis consisted of correlation, multiple linear regression, and structural equation modeling., Results: The total score of the SOC and perceived stress showed a negative correlation (r = -0.80, P ＜ 0.01), the total SOC of coherence and depression also resulted in a negative correlation (r = -0.77, P ＜ 0.01), and the total score of the perceived stress and depression resulted in a positive correlation (r = 0.82, P ＜ 0.01). The results of multiple regression analyses indicated that SOC mediated the association between perceived stress and depression, and the influence of perceived stress on depression was decreased by 16.0%with in the sense of being out of control dimension and was decreased by 12.3% within the feeling of tension dimension when sense of coherence was added to the model. The structural equation model confirmed that the sense of coherence had a partial mediation effect between perceived stress and depression., Conclusion: SOC is the mediating variable between perceived stress and depression, and can reduce the influence of perceived stress on depression., (Copyright © 2018. Published by Elsevier B.V.)

Xanthone derivatives have shown good α-glucosidase inhibitory activity and have drawn increased attention as potential anti-diabetic compounds. In this study, a series of novel oxazolxanthones were designed, synthesized, and investigated as α-glucosidase inhibitors. Inhibition assays indicated that compounds 4-21 bearing oxazole rings exhibited up to 30-fold greater inhibitory activity compared to their corresponding parent compound 1b. Among them, compounds 5-21 (IC 50  = 6.3 ± 0.4-38.5 ± 4.6 μM) were more active than 1-deoxynojirimycin (IC 50  = 60.2 ± 6.2 μM), a well-known α-glucosidase inhibitor. In addition, the kinetics of enzyme inhibition measured by using Lineweaver-Burk analysis shows that compound 4 is a competitive inhibitor, while compounds 15, 16 and 20 are non-competitive inhibitors. Molecular docking studies showed that compound 4 bound to the active site pocket of the enzyme while compounds 15, 16, and 20 did not. More interestingly, docking simulations reveal that some of the oxazolxanthone derivatives bind to different sites in the enzyme. This prediction was further confirmed by the synergetic inhibition experiment, and the combination of representative compounds 16 and 20 at the optimal ratio of 4:6 led to an IC 50 value of 1.9 ± 0.7 μM, better than the IC 50 value of 7.1 ± 0.9 μM for compound 16 and 8.6 ± 0.9 μM for compound 20., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A new cyprinid gudgeon, Saurogobio punctatus sp. nov., is described based on specimens collected from the Yangtze River, China. The new species can be distinguished from its congeners by differences in both morphology and the cytochrome b (cytb) gene sequence. Numerous minute blackish spots are scattered on dorsal and caudal fins in S. punctatus sp. nov. v. absent in the other seven valid Saurogobio species. The new species can be further distinguished from its congeners by the following unique combination of characters: a dorsal fin with eight branched rays; absence of scales in chest area before pectoral origin; upper and lower lips thick, covered with papillae; and a papillose mental pad approximately triangular. Morphologically, the new species most resembles the Chinese lizard gudgeon Saurogobio dabryi, but the new species lays yellowish adhesive eggs v. white pelagic eggs in S. dabryi. A phylogenetic analysis of all Saurogobio species based on cytb gene sequences indicated that S. punctatus sp. nov was distinctly separated from its congeners, with mean sequence divergence ranging from 12·6 to 21·0%. Therefore, molecular data further supported the distinctiveness of the new species., (© 2018 The Fisheries Society of the British Isles.)

Objective: To evaluate the patients' survival and effectiveness of the live cancer screening for population at high risk for liver cancer in Qidong. Methods: According to the Expert Scheme proposed the Expert Committee of Early Detection and Early Treatment, China Cancer Foundation, diagnostical screening by using combined methods of alpha-fetoprotein and B ultrasound monitoring were carried out biannually in individuals with positive HBsAg who were screened from Qidong area. The evaluation indices of the effectiveness are task completion rate of screening, detection rate of liver cancer, early diagnosis rate, and treatment rate. The deadline of the follow-up for the surviving outcome was March 31, 2016. The life-table method was used to calculate the observed survival, and to make comparison and significant tests between survival rates in Group A (those found via repeated periodic screening) and Group B (those diagnosed without periodic screening). Results: Since 2007, 38 016 target population have been screened, and 3 703(9.74%) individuals with positive HBsAg were found. Except for 29 patients with liver cancer at the initial screening, 3 674 persons in the cohort were followed up; 268 patients with liver cancer were detected from the 33 199 person-times screening, with an annual detection rate of 1.61%. Of them, 186 patients were found in Group A(1.12%), in which 149 patients were the early cases, with an early detection rate of 80.11%; 167 out of 186(89.78%) patients received treatment after diagnosis. The incidence of liver cancer in this HBsAg (+ ) cohort of 25 452 person-years was 1 052.96 per 100 000 annually, 187 cases in males(1 488.45/100 000)and 81 cases in females(628.46/100 000). The 1-, 3-, 5-, and 8-year survival of all patients with liver cancer were 64.55%, 40.50%, 32.54%, and 19.65%, respectively. The 1-, 3-, 5-, and 8-year survival rates were 77.16%, 49.04%, 38.53%, and 24.25% in Group A, and were 36.25%, 21.21%, 21.21%, and 0% in Group B, respectively, with significant differences between two groups ( P <0.05). Conclusion: The findings show that screening of individuals at high-risk of development of liver cancer, with semiannual AFP and B ultrasound, according to the Expert Scheme, is effective not only in increasing detection rate but also in detecting liver cancer at early stage, and in improving patients' survival as well.

Floral nectar usually functions as a pollinator reward, yet it may also attract herbivores. However, the effects of herbivore consumption of nectar or nectaries on pollination have rarely been tested. We investigated Iris bulleyana , an alpine plant that has showy tepals and abundant nectar, in the Hengduan Mountains of SW China. In this region, flowers are visited mainly by pollen-collecting pollinators and nectarivorous herbivores. We tested the hypothesis that, in I. bulleyana , sacrificing nectar and nectaries to herbivores protects tepals and thus enhances pollinator attraction. We compared rates of pollination and herbivory on different floral tissues in plants with flowers protected from nectar and nectary consumption with rates in unprotected control plants. We found that nectar and nectaries suffered more herbivore damage than did tepals in natural conditions. However, the amount of tepal damage was significantly greater in the flowers with protected nectaries than in the controls; this resulted in significant differences in pollinator visitation rates. These results provide the first evidence that floral nectar and nectaries may be 'sacrificed' to herbivores, leading to reduced damage to other floral tissues that are more important for reproduction., (© 2017 The Author(s).)

Pristine LiNi 0.5 Mn 1.5 O 4 and FePO 4 -coated one with Fd-3m space groups were prepared by a sol-gel method. The structure and performance were studied by X-ray diffraction (XRD) rietveld refinement, scanning electron microscopy (SEM), high resolution transmission electron microscopy (HRTEM), energy dispersive spectrometer (EDS) mapping, electrochemical impedance spectroscopy (EIS) and charge-discharge tests, respectively. The lattice parameters of all samples almost remain the same from the Rietveld refinement, revealing that the crystallographic structure has no obvious difference between pristine LiNi 0.5 Mn 1.5 O 4 and FePO 4 -coated one. All materials show similar morphologies with uniform particle distribution with small particle size, and FePO 4 coating does not affect the morphology of LiNi 0.5 Mn 1.5 O 4 material. EDS mapping and HRTEM show that FePO 4 may be successfully wrapped around the surfaces of LiNi 0.5 Mn 1.5 O 4 particles, and provides an effective coating layer between the electrolyte and the surface of LiNi 0.5 Mn 1.5 O 4 particles. FePO 4 (1wt%)-coated LiNi 0.5 Mn 1.5 O 4 cathode shows the highest discharge capacity at high rate (2C) among all samples. After 80 cycles, the reversible discharge capacity of FePO 4 (1wt%) coated LiNi 0.5 Mn 1.5 O 4 is 117mAhg -1 , but the pristine one only has 50mAhg -1 . FePO 4 coating is an effective and controllable way to stabilize the LiNi 0.5 Mn 1.5 O 4 /electrolyte interface, and avoids the direct contact between LiNi 0.5 Mn 1.5 O 4 powders and electrolyte, then suppresses the side reactions and enhances the electrochemical performance of the LiNi 0.5 Mn 1.5 O 4 ., (Copyright © 2017 Science China Press. Published by Elsevier B.V. All rights reserved.)

A facile strategy was developed to prepare Li 5 Cr 7 Ti 6 O 25 @CeO 2 composites as a high-performance anode material. X-ray diffraction (XRD) and Rietveld refinement results show that the CeO 2 coating does not alter the structure of Li 5 Cr 7 Ti 6 O 25 but increases the lattice parameter. Scanning electron microscopy (SEM) indicates that all samples have similar morphologies with a homogeneous particle distribution in the range of 100-500 nm. Energy-dispersive spectroscopy (EDS) mapping and high-resolution transmission electron microscopy (HRTEM) prove that CeO 2 layer successfully formed a coating layer on a surface of Li 5 Cr 7 Ti 6 O 25 particles and supplied a good conductive connection between the Li 5 Cr 7 Ti 6 O 25 particles. The electrochemical characterization reveals that Li 5 Cr 7 Ti 6 O 25 @CeO 2 (3 wt %) electrode shows the highest reversibility of the insertion and deinsertion behavior of Li ion, the smallest electrochemical polarization, the best lithium-ion mobility among all electrodes, and a better electrochemical activity than the pristine one. Therefore, Li 5 Cr 7 Ti 6 O 25 @CeO 2 (3 wt %) electrode indicates the highest delithiation and lithiation capacities at each rate. At 5 C charge-discharge rate, the pristine Li 5 Cr 7 Ti 6 O 25 only delivers an initial delithiation capacity of ∼94.7 mAh g -1 , and the delithiation capacity merely achieves 87.4 mAh g -1 even after 100 cycles. However, Li 5 Cr 7 Ti 6 O 25 @CeO 2 (3 wt %) delivers an initial delithiation capacity of 107.5 mAh·g -1 , and the delithiation capacity also reaches 100.5 mAh g -1 even after 100 cycles. The cerium dioxide modification is a direct and efficient approach to improve the delithiation and lithiation capacities and cycle property of Li 5 Cr 7 Ti 6 O 25 at large current densities.

Abnormal expression of the Recepteur d'Origine Nantais (RON) receptor tyrosine kinase is accompanied by the generation of multiple splice or truncated variants, which mediate many critical cellular functions that contribute to tumor progression and metastasis. Here, we report a new RON splice variant in the human colorectal cancer (CRC) cell line HT29. This variant is a 165 kda protein generated by alternative pre-mRNA splicing that eliminates exon 2, causing an in-frame deletion of 63 amino acids in the extracellular domain of the RON β chain. The deleted transcript was a single chain expressed in the intracellular compartment. Although it lacked tyrosine phosphorylation activity, the RONΔ165E2 variant could phosphorylate phosphatase and tensin homolog (PTEN), thereby activating the PI3K/AKT pathway. In addition, in vitro and in vivo experiments showed that the RONΔ165E2 promoted cell migration and tumor growth. Finally, in an investigation of 67 clinical CRC samples, the variant was highly expressed in about 58% of the samples, and was positively correlated with the invasive depth of the tumor (P < 0.05). These results demonstrate that the novel RONΔ165E2 variant promoted tumor progression while activating the PI3K/AKT pathway via PTEN phosphorylation.

Population-based cancer survival is an improved index for evaluating the overall efficiency of cancer health services in a given region. The current study analysed the observed survival and relative survival of leading cancer sites from a population-based cancer registry between 1972 and 2011 in Qidong, China. A total of 92,780 incident cases with cancer were registered and followed-up for survival status. The main sites of the cancer types, based on the rank order of incidence, were the liver, stomach, lung, colon and rectum, oesophagus, breast, pancreas, leukaemia, brain and central nervous system (B and CNS), bladder, blood [non-Hodgkin's lymphoma (NHL)] and cervix. For all malignancies combined, the 5-year observed survival was 13.18% and the relative survival was 15.80%. Females had higher observed survival and relative survival (19.32 and 22.71%, respectively) compared with males (9.63 and 11.68%, respectively). The cancer sites with the highest five-year relative survival rates were the female breast, bladder, cervix and colon and rectum; followed by NHL, stomach, B and CNS cancer and leukaemia. The poorest survival rates were cancers of oesophagus, lung, pancreas and liver. Higher survival rates were observed in younger patients compared with older patients. Cancers of the oesophagus, female breast and bladder were associated with higher survival in middle-aged groups. Improved survival rates in the most recent two 5-year calendar periods were identified for stomach, lung, colon and rectum, oesophagus, female breast and bladder cancer, as well as leukaemia and NHL. The observations of the current study provide the opportunity for evaluation of the survival outcomes of frequent cancer sites that reflects the changes and improvement in a rural area in China.

Light environments have long been known to influence grape ( Vitis vinifera L.) berry development and biosynthesis of phenolic compounds, and ultimately affect wine quality. Here, the accumulation and compositional changes of hydroxycinnamic acids (HCAs) and flavonoids, as well as global gene expression were analyzed in Cabernet Sauvignon grape berries under sunlight exposure treatments at different phenological stages. Sunlight exposure did not consistently affect the accumulation of berry skin flavan-3-ol or anthocyanin among different seasons due to climatic variations, but increased HCA content significantly at véraison and harvest, and enhanced flavonol accumulation dramatically with its timing and severity degree trend. As in sunlight exposed berries, a highly significant correlation was observed between the expression of genes coding phenylalanine ammonia-lyase, 4-coumarate: CoA ligase, flavanone 3-hydroxylase and flavonol synthase family members and corresponding metabolite accumulation in the phenolic biosynthesis pathway, which may positively or negatively be regulated by MYB, bHLH, WRKY, AP2/EREBP, C2C2, NAC, and C2H2 transcription factors (TFs). Furthermore, some candidate genes required for auxin, ethylene and abscisic acid signal transductions were also identified which are probably involved in berry development and flavonoid biosynthesis in response to enhanced sunlight irradiation. Taken together, this study provides a valuable overview of the light-induced phenolic metabolism and transcriptome changes, especially the dynamic responses of TFs and signaling components of phytohormones, and contributes to the further understanding of sunlight-responsive phenolic biosynthesis regulation in grape berries.

Forced-activation of AMP-activated protein kinase (AMPK) can possibly inhibit osteoblastoma cells. Here, we aim to provoke AMPK activation via microRNA silencing its phosphatase Ppm1e (protein phosphatase Mg2+/Mn2+-dependent 1e). We showed that microRNA-135b-5p ("miR-135b-5p"), the anti-Ppm1e microRNA, was significantly downregulated in human osteoblastoma tissues. It was correlated with Ppm1e upregulation and AMPKα1 de-phosphorylation. Forced-expression of miR-135b-5p in human osteoblastoma cells (MG-63 and U2OS lines) silenced Ppm1e, and induced a profound AMPKα1 phosphorylation (at Thr-172). Osteoblastoma cell proliferation was inhibited after miR-135b-5p expression. Intriguingly, Ppm1e shRNA knockdown similarly induced AMPKα1 phosphorylation, causing osteoblastoma cell proliferation. Reversely, AMPKα1 shRNA knockdown or dominant negative mutation almost abolished miR-135b-5p's actions in osteoblastoma cells. Further in vivo studies demonstrated that U2OS tumor growth in mice was dramatically inhibited after expressing miR-135b-5p or Ppm1e shRNA. Together, our results suggest that miR-135b-induced Ppm1e silence induces AMPK activation to inhibit osteoblastoma cell proliferation.

Xanthine oxidase (XOD) and paraoxonase 1 (PON1) are important enzymes in redox reactions in vivo, and are predominantly synthesized by the liver. The aim of the present study was to investigate the redox state in nonalcoholic fatty liver disease, and determine the association between the activities of XOD and PON1 and the severity of NAFLD. Sprague‑Dawley rats were randomly divided into control, model and α‑lipoic acid (high and low dose) groups. The rats in the NAFLD model were induced by feeding a high fat diet for 12 weeks and the in vitro cell model of hepatocyte steatosis was induced by treating L‑02 cells with oleic acid for 24 h. The body weight, liver function, lipid and oxidative stress indices, and histological features of the liver were examined in the rats. Compared with the control group, the rats in the NAFLD model group showed impaired liver function, lipid disorders and damage from oxidative stress. The serum activity of XOD increased significantly from the 4th week and was markedly higher, compared with that in the control group, reaching a peak in the 12th week. The activity of PON1 was negatively correlated with that of XOD. Compared with the control cells, the activity of XOD and levels of free‑fatty acids were significantly higher, and the activity of PON1 was significantly lower in the NAFLD L‑02 cell model. All the above indicators were significantly improved by treatment with the antioxidant, α‑lipoic acid. The activities of XOD and PON1 may be promising as markers in a noninvasive approach for detecting the severity of NAFLD clinically. α‑lipoic acid had protective effects on the NAFLD rats, and the potential mechanism may be associated with the inhibition of oxidative stress and lipid peroxidation.

Layered Li-rich, Co-free, and Mn-based cathode material, Li 1.17 Ni 0.25-x Mn 0.58 Mg x O 2 (0 ≤ x ≤ 0.05), was successfully synthesized by a coprecipitation method. All prepared samples have typical Li-rich layered structure, and Mg has been doped in the Li 1.17 Ni 0.25 Mn 0.58 O 2 material successfully and homogeneously. The morphology and the grain size of all material are not changed by Mg doping. All materials have a estimated size of about 200 nm with a narrow particle size distribution. The electrochemical property results show that Li 1.17 Ni 0.25-x Mn 0.58 Mg x O 2 (x = 0.01 and 0.02) electrodes exhibit higher rate capability than that of the pristine one. Li 1.17 Ni 0.25-x Mn 0.58 Mg x O 2 (x = 0.02) indicates the largest reversible capacity of 148.3 mAh g -1 and best cycling stability (capacity retention of 95.1%) after 100 cycles at 2C charge-discharge rate. Li 1.17 Ni 0.25-x Mn 0.58 Mg x O 2 (x = 0.02) also shows the largest discharge capacity of 149.2 mAh g -1 discharged at 1C rate at elevated temperature (55 °C) after 50 cycles. The improved electrochemical performances may be attributed to the decreased polarization, reduced charge transfer resistance, enhanced the reversibility of Li + ion insertion/extraction, and increased lithium ion diffusion coefficient. This promising result gives a new understanding for designing the structure and improving the electrochemical performance of Li-rich cathode materials for the next-generation lithium-ion battery with high rate cycling performance.

Malignant osteosarcoma (OS) is still a deadly disease for many affected patients. The search for the novel anti-OS agent is extremely urgent and important. Our previous study has proposed that salinomycin is a novel anti-OS agent. Here we characterized DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a primary salinomycin resistance factor in OS cells. DNA-PKcs inhibitors (NU7026, NU7441 and LY294002) or DNA-PKcs shRNA knockdown dramatically potentiated salinomycin-induced death and apoptosis of OS cells (U2OS and MG-63 lines). Further, forced-expression of microRNA-101 ("miR-101") downregulated DNA-PKcs and augmented salinomycin's cytotoxicity against OS cells. Reversely, over-expression of DNA-PKcs in OS cells inhibited salinomycin's lethality. For the mechanism study, we show that DNA-PKcs is required for salinomycin-induced pro-survival autophagy activation. DNA-PKcs inhibition (by NU7441), shRNA knockdown or miR-101 expression inhibited salinomycin-induced Beclin-1 expression and autophagy induction. Meanwhile, knockdown of Beclin-1 by shRNA significantly sensitized salinomycin-induced OS cell lethality. In vivo, salinomycin administration suppressed U2OS xenograft tumor growth in severe combined immuno-deficient (SCID) mice, and its anti-tumor activity was dramatically potentiated with co-administration of the DNA-PKcs inhibitor NU7026. Together, these results suggest that DNA-PKcs could be a primary resistance factor of salinomycin in OS cells. DNA-PKcs inhibition or silence may thus significantly increase salinomycin's sensitivity in OS cells.

Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and mTORC2 are frequently dysregulated in human colon cancers. In the present study, we evaluated the potential anti-colon cancer cell activity by a novel mTORC1/2 dual inhibitor WYE-354. We showed that WYE-354 was anti-survival and anti-proliferative when adding to primary (patient-derived) and established (HCT-116, HT-29, Caco-2, LoVo, and DLD-1 lines) colon cancer cells. In addition, WYE-354 treatment activated caspase-dependent apoptosis in the colon cancer cells. Mechanistically, WYE-354 blocked mTORC1 and mTORC2 activation. Meanwhile, it also induced autophagy activation in the colon cancer cells. Autophagy inhibitors (bafilomycin A1 and 3-methyladenine), or shRNA-mediated knockdown of autophagy elements (Beclin-1 and ATG-5), remarkably sensitized WYE-354-mediated anti-colon cancer cell activity in vitro. Further studies showed that WYE-354 administration inhibited HT-29 xenograft growth in severe combined immunodeficient (SCID) mice. Importantly, its activity in vivo was further potentiated with co-administration of the autophagy inhibitor 3-MA. Phosphorylations of Akt (Ser-473) and S6 were also decreased in WYE-354-treated HT-29 xenografts. Together, these pre-clinical results demonstrate the potent anti-colon cancer cell activity by WYE-354, and its activity may be further augmented with autophagy inhibition.

In the present study, we investigated the activity of XL388, a novel mammalian target of rapamycin (mTOR) complex 1/2 (mTORC1/2) dual inhibitor, in preclinical osteosarcoma (OS) models. XL388 was cytotoxic, cytostatic and pro-apoptotic to multiple established OS cell lines and primary human OS cells. XL388 blocked mTORC1/2 activation and downregulated cyclin D1/B1 expressions in OS cells, leaving AKT Thr-308 phosphorylation un-affected. Intriguingly, AKT1 T308A mutation potentiated XL388-induced cytotoxicity in OS cells. XL388 activated cytoprotective autophagy in OS cells. Autophagy inhibition, either pharmacologically or genetically, augmented XL388-induced anti-OS activity. Further, XL388 oral administration inhibited U2OS xenografts growth in severe combined immuno-deficient (SCID) mice. Such activity was enhanced with co-administration of the autophagy inhibitor 3-methyladenine (3-MA). Similarly, Beclin-1-silenced U2OS xenografts were remarkably more sensitive to XL388. Thus, concurrent blockage of mTORC1/2 with XL388 may have therapeutic value for OS., Competing Interests: All listed authors state no conflicts of interest.

We systematically investigated the effects of Al-impurity type on the formation energy, crystal structure, charge density, electronic structure, and optical properties of ZnO by using density functional theory and the Hubbard-U method. Al-related defects, such as those caused by the substitution of Zn and O atoms by Al atoms (Al s(Zn) and Al s(O) , respectively) and the presence of an interstitial Al atom at the center of a tetrahedron (Al i(tet) ) or an octahedron (Al i(oct) ), and various Al concentrations were evaluated. The calculated formation energy follows the order E f (Al s(Zn) ) < E f (Al i(tet) ) < E f (Al i(oct) ) < E f (Al s(O) ). Electronic structure analysis showed that the Al s(Zn) , Al s(O) , Al i(tet) , and Al i(oct) models follow n -type conduction, and the optical band gaps are higher than that of pure ZnO. The calculated carrier concentrations of the Al s(O) and Al i(tet) /Al i(oct) models are higher than that of the Al s(Zn) model. However, according to the curvature of the band structure, the occurrence of interstitial Al atoms or the substitution of O atoms by Al atoms results in a high effective mass, possibly reducing the carrier mobility. The average transmittance levels in the visible light and ultraviolet (UV) regions of the Al s(Zn) model are higher than those of pure ZnO. However, the presence of an interstitial Al atom within the ZnO crystal reduces transmittance in the visible light region; Al s(O) substantially reduces the transmittance in the visible light and UV regions. In addition, the properties of ZnO doped with various Al s(Zn) concentrations were analyzed.

Solid phase immunoassays (SPI) are now routinely used to detect HLA antibodies. However, the flow cytometric crossmatch (FCXM) remains the established method for assessing final donor-recipient compatibility. Since 2005 we have followed a protocol whereby the final allocation decision for renal transplantation is based on SPI (not the FCXM). Here we report long-term graft outcomes for 508 consecutive kidney transplants using this protocol. All recipients were negative for donor-specific antibody by SPI. Primary outcomes are graft survival and incidence of acute rejection within 1 year (AR <1 year) for FCXM+ (n = 54) and FCXM- (n = 454) recipients. Median follow-up is 7.1 years. FCXM+ recipients were significantly different from FCXM- recipients for the following risk factors: living donor (24% vs. 39%, p = 0.03), duration of dialysis (31.0 months vs. 13.5 months, p = 0.008), retransplants (17% vs. 7.3%, p = 0.04), % sensitized (63% vs. 19%, p = 0.001), and PRA >80% (20% vs. 4.8%, p = 0.001). Despite these differences, 5-year actual graft survival rates are 87% and 84%, respectively. AR <1 year occurred in 13% FCXM+ and 12% FCXM- recipients. Crossmatch status was not associated with graft outcomes in any univariate or multivariate model. Renal transplantation can be performed successfully, using SPI as the definitive test for donor-recipient compatibility., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

A new type of N-heterocyclic carbene-PdCl2-(iso)quinoline complexes 3 were successfully achieved in acceptable to good yields from easily available starting materials under mild conditions, and their structures were unambiguously confirmed using X-ray single crystal diffraction. Furthermore, their catalytic activity toward Buchwald-Hartwig arylamination of aryl chlorides with primary and secondary amines was fully tested. Under the optimal reaction conditions, the expected arylated amines can be obtained in high to excellent yields at low catalyst loadings (0.005-0.05 mol%). It may be worth noting here that comparison of these complexes with other well-defined and easily available NHC-Pd(ii) complexes bearing different N-containing ancillary ligands was also carried out, showing their superior catalytic activity over all others.

Genomic imprinting is an epigenetic process that distinguishes parental alleles and results in specific expression of paternal and maternal genes. Imprints are acquired in the process of gametogenesis when genome-wide epigenetic reprogramming occurs and are maintained during early embryonic development. Therefore, the recognition and maintenance of imprints are very important in genome-wide reprogramming. In this review, we summarize the progresses of imprints removal in primordial germ cells (PGCs), imprints acquisition in parental PGCs, and imprints maintenance during early embryonic development. We also discuss the functional mechanisms of epigenetic factors which protect imprinted genes from whole genome DNA methylation.

Novel submicron Li5Cr7Ti6O25, which exhibits excellent rate capability, high cycling stability and fast charge-discharge performance is constructed using a facile sol-gel method. The insights obtained from this study will benefit the design of new negative electrode materials for lithium-ion batteries.

Background: In cardiology, it is controversial whether different therapy strategies influence prognosis after acute coronary syndrome. We examined and compared the long-term outcomes of invasive and conservative strategies in patients with non-ST-segment elevation myocardial infarction (NSTEMI) and characterized the patients selected for an invasive approach., Methods: A total of 976 patients with acute NSTEMI were collected from December 2006 to October 2012 in the First Affiliated Hospital of Dalian Medical University Hospital. They are divided into conservative strategy (586 patients) and invasive strategy (390 patients) group. Unified follow-up questionnaire was performed by telephone contact (cut-off date was November, 2013). The long-term clinical events were analyzed and related to the different treatment strategies., Results: The median follow-up time was 29 months. Mortality was 28.7% (n = 168) in the conservative group and 2.1% (n = 8) in the invasive management at long-term clinical follow-up. The secondary endpoint (the composite endpoint) was 59.0% (n = 346) in the conservative group and 30.3% (n = 118) in the invasive management. Multivariate analysis showed that patients in the conservative group had higher all-cause mortality rates than those who had the invasive management (adjusted risk ratio [RR] = 7.795; 95% confidence interval [CI]: 3.796-16.006, P < 0.001), and the similar result was also seen in the secondary endpoint (adjusted RR = 2.102; 95% CI: 1.694-2.610, P < 0.001). In the subgroup analysis according to each Thrombolysis in Myocardial Infarction risk score (TRS), log-rank analysis showed lower mortality and secondary endpoint rates in the invasive group with the intermediate and high-risk patients (TRS 3-7)., Conclusions: An invasive strategy could improve long-term outcomes for NSTEMI patients, especially for intermediate and high-risk ones (TRS 3-7).

A betaine-free reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed and optimised for detecting tomato chlorosis virus (ToCV), one of the most important viruses that infect tomato crops worldwide. A set of four specific primers was designed against the RNA-dependent RNA polymerase (RdRp) gene. The betaine-free RT-LAMP procedure could be completed within 40 min under isothermal conditions at 60 °C without a thermal cycler, and no cross-reactivity was seen with other tomato viral pathogens. Sensitivity analysis showed that RT-LAMP could detect viral dilutions up to 2.0×10(-7)ng, which is 100-times more sensitive than reverse transcription-polymerase chain reaction (RT-PCR). In addition, naked-eye observation after staining in-tube RT-LAMP products with SYBR Green I facilitated detection of ToCV by avoiding the requirement for ethidium staining following gel electrophoresis. These results suggest that ToCV RT-LAMP is a rapid, sensitive, and affordable diagnostic tool that is more suitable than RT-PCR for the detection and surveillance of ToCV in field samples., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Chemosensor (CS1) was designed and synthesized by simple green chemistry procedure. CS1 exhibited both colorimetric and fluorescence turn-off responses for cyanide (CN(-)) ion in aqueous solution. The probe showed an immediate visible color changes from yellow to colorless and green fluorescence disappearance when CN(-) was added. The mechanism of chemosensor reaction with CN(-) was studied using (1)HH NMR and (13)C NMR spectroscopies and mass spectrometry. Moreover, test strips based on the sensor were fabricated, which served as convenient and efficient CN(-) test kits., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Recent studies have identified that constitutively active phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling is an important feature of osteosarcoma, where it promotes cell proliferation, survival, and chemo-resistance. Here, we studied the therapeutic potential of NVP-BEZ235, a novel dual PI3K/mTOR dual inhibitor, on osteosarcoma cells in vivo and in vitro. NVP-BEZ235 was cytotoxic and cytostatic to a panel of osteosarcoma lines (MG-63, U2OS and SaOs-2), where it induce apoptosis and cell-cycle arrest. At the molecular level, NVP-BEZ235 inhibited PI3K-AKT-mTORC1 activation and downregulated cyclin D1/cyclin B1 expressions, while increasing MEK/Erk phosphorylation in osteosarcoma cells. MEK/Erk inhibitors PD98059 and MEK-162 increased NVP-BEZ235 activity on osteosarcoma cells. In vivo, oral NVP-BEZ235 inhibited U2OS xenograft in SCID mice, and its anti-tumor efficiency was further enhanced by MEK-162 co-administration. Taken together, our findings indicate that dual inhibition of PI3K and mTOR with NVP-BEZ235, either alone or in combination with MEK/Erk inhibitors, may be an efficient treatment for osteosarcoma.

Traditional Chinese medicine (TCM) plays a systemic role in disease treatment, targeting multiple etiological factors simultaneously. Based on clinical experience, rhubarb and Salvia miltiorrhiza are commonly prescribed together for the treatment of chronic kidney disease (CKD) and have been proven to be very effective. However, the rationale of the combination remains unclear. The major active ingredients of these two herbs are rhein (RH) and danshensu (DSS), respectively. The aim of this paper is to investigate the renoprotective effects of RH and DSS in vitro and in vivo, and the underlying mechanism. A total of 5/6 nephrectomy rats and HK-2 cells were subjected to chronic renal injury. The combination of RH and DSS conferred a protective effect, as shown by a significant improvement in the renal function, blood supply, and fibrotic degree. Proinflammatory cytokines and adhesion molecules were suppressed by RH and DSS through NK-κB signaling. The combination also inhibited apoptosis by up-regulating Bcl-2 and down-regulating Bax. Inhibiting the TGF-β/Smad3 pathway was at least in part involved in the antifibrotic mechanism of the combination treatment of RH and DSS. This study demonstrates for the first time the renoprotective effect and the mechanism of RH and DSS combination on chronic renal injury. It could provide experimental evidence to support the rationality of the combinatorial use of TCM in clinical practices.

Well-defined Li4Ti5O12-TiO2 nanosheet and nanotube composites have been synthesized by a solvothermal process. The combination of in situ generated rutile-TiO2 in Li4Ti5O12 nanosheets or nanotubes is favorable for reducing the electrode polarization, and Li4Ti5O12-TiO2 nanocomposites show faster lithium insertion/extraction kinetics than that of pristine Li4Ti5O12 during cycling. Li4Ti5O12-TiO2 electrodes also display lower charge-transfer resistance and higher lithium diffusion coefficients than pristine Li4Ti5O12. Therefore, Li4Ti5O12-TiO2 electrodes display lower charge-transfer resistance and higher lithium diffusion coefficients. This reveals that the in situ TiO2 modification improves the electronic conductivity and electrochemical activity of the electrode in the local environment, resulting in its relatively higher capacity at high charge-discharge rate. Li4Ti5O12-TiO2 nanocomposite with a Li/Ti ratio of 3.8:5 exhibits the lowest charge-transfer resistance and the highest lithium diffusion coefficient among all samples, and it shows a much improved rate capability and specific capacity in comparison with pristine Li4Ti5O12 when charging and discharging at a 10 C rate. The improved high-rate capability, cycling stability, and fast charge-discharge performance of Li4Ti5O12-TiO2 nanocomposites can be ascribed to the improvement of electrochemical reversibility, lithium ion diffusion, and conductivity by in situ TiO2 modification.

The search for novel and more efficient chemo-agents against malignant osteoblastoma is important. In this study, we examined the potential anti-osteoblastoma function of bufotalin, and studied the underlying mechanisms. Our results showed that bufotalin induced osteoblastoma cell death and apoptosis in dose- and time-dependent manners. Further, bufotalin induced endoplasmic reticulum (ER) stress activation in osteoblastoma cells, the latter was detected by the induction of C/EBP homologous protein (CHOP), phosphorylation of inositol-requiring enzyme 1 (IRE1) and PKR-like endoplasmic reticulum kinase (PERK), as well as caspase-12 activation. Conversely, the ER stress inhibitor salubrinal, the caspase-12 inhibitor z-ATAD-fmk as well as CHOP depletion by shRNA significantly inhibited bufotalin-induced osteoblastoma cell death and apoptosis. Finally, by using a mice xenograft model, we demonstrated that bufotalin inhibited U2OS osteoblastoma cell growth in vivo. In summary, our results suggest that ER stress contributes to bufotalin-induced apoptosis in osteoblastoma cells. Bufotalin might be investigated as a novel anti-osteoblastoma agent., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: As a well-known traditional Chinese medicine the root bark of Aralia taibaiensis has multiple pharmacological activities, including relieving rheumatism, promoting blood circulation to arrest pain, inducing diuresis to reduce edema, and antidiabetic action. It has long been used as a folk medicine for the treatment of traumatic injury, rheumatic arthralgia, nephritis, edema, hepatitis and diabetes mellitus in China., Aim of Study: To evaluate the antihyperglycemic, hypolipidemic and antioxidant activities of total saponins extracted from Aralia taibaiensis (SAT) in experimental type 2 diabetic mellitus (T2DM) rats., Materials and Methods: Acute toxicity was studied in rats to determine the safe oral dose of SAT. Then, SAT was given orally to normal and streptozotocin-nicotinamide induced T2DM rats at 80, 160 and 320 mg/kg doses for a series of 28 days to determine the antihyperglycemic activity. Glibenclamide (600 μg/kg), a standard antidiabetic drug, was used as a positive control drug. At the end of treatment, biochemical parameters and antioxidant levels were measured to evaluate the hypolipidemic and antioxidant activities of SAT., Results: Oral administration of SAT did not exhibit toxicity and death at a dose not more than 2000 mg/kg. SAT dose-dependently improved the symptoms of polydipsia, polyuria, polyphagia and weight loss in diabetic rats. Compared with diabetic control group, administration of 320 mg/kg SAT resulted in significant (P<0.05) fall in the levels of fasting blood glucose, glycosylated hemoglobin, creatinine, urea, alanine transarninase, aspartate aminotransferase, total cholesterol, triglycerides, low density lipoprotein cholesterol and malondialdehyde, but significant (P<0.05) increase in the levels of serum insulin, superoxide dismutase and reduced glutathione. However, SAT did not have any effect on the normal rats., Conclusions: SAT had excellent antihyperglycemic, hypolipidemic and antioxidant activities in T2DM rats and might be a promising drug in the therapy of diabetes mellitus and its complications., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

To elucidate the microscopic origin of the difference behaviors, first-principles calculations were performed to investigate the thermal and mechanical stabilities of LixFePO4 and LixMnPO4. The calculated free energies suggested that LiFePO4 and LiMnPO4 are thermal stable with respect to relevant oxides both in their pristine and fully delithiated states. According to the calculations, it can be identified that the shear deformations are more easier to occur with respect to the volume compressions in LixFePO4 and LixMnPO4, and this phenomenon is related to M-O(I) and M-O(II) bonds. Typically for MnPO4, Li(+) extraction from the host structures further weakens the Mn-O(I) bonds by about 33%, and it thus becomes very brittle. The shear anisotropy (AG) of MnPO4 is abnormally large and has already reached 19.05 %, which is about 6 times as large as that of FePO4. Therefore, shear deformations and dislocations occur easily in MnPO4. Moreover, as the Mn-O(I) bonds in MnPO4 are mainly spread within the {101} and {1̅01} crystal planes, the relevant slip systems thus allow the recombination of bonds at the interfaces, leading to the experimentally observed phase transformation. It can be concluded that mechanical reason will play an important role for the poor cycling performance of MnPO4.

Purpose: To investigate the clinical value in lung cancer of a combination of four serum tumor markers, haptoglobin (Hp), carcinoembryonic antigen (CEA), neuron specific enolase (NSE) as well as the cytokeratin 19 fragment (CYFRA21-1)., Materials and Methods: Serum Hp (with immune-turbidimetric method), CEA, NSE, CYFRA21-1 (with chemiluminescence method) level were assessed in 193 patients with lung cancer, 87 patients with benign lung disease and 150 healthy controls. Differences of expression were compared among groups, and joint effects of these tumor markers for the diagnosis of lung cancer were analyzed., Results: Serum tumor marker levels in patients with lung cancer were obviously higher than those with benign lung disease and normal controls (p<0.01). The sensitivities of Hp, CEA, NSE and CYFRA21-1 were 43.5%, 40.9%, 23.3% and 41.5%, with specificities of 90.7%, 99.2%, 97.9% and 97.9%. Four tumor markers combined together could produce a positive detection rate of 85.0%, significantly higher than that of any single test. With squamous carcinomas, the positive detection rates with Hp and CYFRA21-1 were higher than that of other markers. In the adenocarcinoma case , the positive detection rate of CEA was higher than that of other markers. For small cell carcinomas, the positive detection rate of NSE was highest. The area under receiver operating characteristic curve (AUCROC) of Hp in squamous carcinoma (0.805) was higher than in adenocarcinoma (0.664) and small cell carcinoma (0.665)., Conclusions: Hp can be used as a new serum tumor marker for lung cancer. Combination detection of Hp, CEA, NSE and CYFRA21-1 could significantly improve the sensitivity and specificity in diagnosis of lung cancer, and could be useful for pathological typing.

Objective: To explore the relationship between glycated haemoglobin A1C (HbA1C) and subclinical atherosclerosis as assessed by carotid intima-media thickness (cIMT) in Chinese Han obese children and adolescents without diabetes., Methods: A total of 524 obese children and adolescents without diabetes were analysed. All participants underwent HbA1C measurements, oral glucose tolerance tests and ultrasound measurements of cIMT. The logistic regression models were implemented to evaluate the adjusted OR of HbA1C for increased cIMT., Results: In obese boys, HbA1C was associated with increased cIMT independently of age, measurements of anthropometry, blood pressure, plasma lipid and lipoprotein, fasting plasma glucose, 2 h postchallenge glucose, uric acid and hepatic function. After adjustment for all these risk factors, the OR of increased cIMT for every 1% (11 mmol/mol) increase in HbA1C was 2.702 (95% CI 1.640 to 4.452). However, in girls, the major risk factor independently associated with cIMT was measurement of abdominal obesity instead of HbA1C., Conclusions: Our research suggests that the adoption of HbA1C as a diagnostic criterion of prediabetes and diabetes in obese boys may help to identify early macrovascular complications.

Primary liver cancer (PLC) is the third leading cause of cancer mortality globally. In endemic areas of sub-Saharan Africa and Asia, PLC largely arises from chronic infection with hepatitis B virus (HBV) and ingestion of aflatoxins. Although synergistic interactions between these two risk factors have been observed in cohort studies in China, here we determined the impact of agricultural reforms in the 1980s leading to diminished maize consumption and implementation of subsidized universal vaccination against HBV in the 2000s on PLC primary prevention. A population-based cancer registry was used to track PLC mortality in Qidong, China and was compared with the timeline of HBV immunization. Randomly selected serum samples from archived cohort collections from the 1980s to present were analyzed for aflatoxin biomarkers. More than 50% reductions in PLC mortality rates occurred across birth cohorts from the 1960s to the 1980s for Qidongese less than 35 years of age although all were born before universal vaccination of newborns. Median levels of the aflatoxin biomarker decreased from 19.3 pg/mg albumin in 1989 to undetectable (<0.5 pg/mg) by 2009. A population attributable benefit of 65% for reduced PLC mortality was estimated from a government-facilitated switch of dietary staple from maize to rice; 83% of this benefit was in those infected with HBV. Food policy reforms in China resulted in a dramatic decrease in aflatoxin exposure, which, independent of HBV vaccination, reduced liver cancer risk. The extensive HBV vaccine coverage now in place augurs even greater risk reductions in the future.

Objective: To study the correlation of azoospermia and severe oligozoospermia with Y chromosome microdeletions, chromosome karyotype and reproductive hormones in male infertility patients., Methods: We collected semen samples from 63 patients with azoospermia, 49 with severe oligozoospermia and 60 men with normal semen parameters, and determined the incidence of Y chromosome microdeletions, chromosome karyotypes and the levels of reproductive hormones., Results: The incidence rate of Y chromosome microdeletions was 11.11% in the azoospermia and 8.16% in the severe oligozoospermia patients, as compared with 0 in the normal controls (P<0.05). The rate of chromosome abnormalities was 9.52% in the azoospermia group, with statistically significant differences from the severe oligozoospermia and normal control men (both 0) (P<0.05). The levels of FSH and LH were significantly higher in the azoospermia ([20.41 +/- 19.34] IU/L and [11.44 +/- 9.48] IU/L) and the severe oligozoospermia patients ([8.88 +/- 7.04] IU/L and [6.78 +/- 3.85] IU/L) than in the normal males ([3.88 +/- 2.21] IU/L and [4.63 +/- 1.51] IU/L) (P<0.05)., Conclusion: Examinations of genetics and reproductive hormones are necessary for infertile males with azoospermia and severe oligozoospermia, which may contribute to early diagnosis and treatment.

Study Question: How does the frequency of trinucleotide repeat dynamic mutations in offspring conceived through assisted reproductive technology (ART) compare with the frequency of these mutations in control offspring conceived from spontaneous pregnancies?, Summary Answer: There is a slight increase in dynamic mutation instability in offspring conceived through ART compared with the naturally conceived offspring., What Is Known Already: There is evidence to suggest that ART can increase the risk of birth defects and karyotypic abnormalities. However, the accumulating evidence of an association between ART and de novo genetic aberrations is controversial., Study Design, Size, Duration: A prospective clinical observational study was performed on 246 families recruited from an in vitro fertilisation (IVF) centre at a tertiary-care, university-affiliated teaching hospital from 2008 to 2012. The study included 147 ART families [75 IVF and 72 intracytoplasmic sperm injection (ICSI)] in the study group and 99 natural-conception families in the control group., Participants, Setting, Methods: Parental, umbilical cord and infant peripheral blood samples were collected, and the trinucleotide repeats of the ATN1, AR, ATXN1, ATXN3, Huntington, DMPK and FMR-1 genes were investigated between the generations; these genes were chosen due to their ability to undergo dynamic mutation. The frequencies and sizes of the mutational repeats, as well as the intergenerational instability, were measured., Main Results and the Role of Chance: In 2466 transmissions identified in the ART offspring, 2.11% (n = 52/2466) of the alleles were unstable upon transmission, while in the control group offspring, the frequency of dynamic mutation was 0.77% (n = 10/1300); this difference was statistically significant (P < 0.01). The unstable transmission alleles were detected in 32 (2.48%) of the 1288 alleles from the IVF offspring and in 20 (1.70%) of the 1178 alleles from the ICSI offspring; both of these frequencies were significantly different from that of naturally conceived offspring (0.77%) (P < 0.01 and P < 0.05, respectively). However, there were no significant differences in the sizes of the mutational repeats or in the rates of expansion or contraction among the three groups (P > 0.05). The repeat copy numbers of the examined genes were found to be within the normal ranges in all parents and infants., Limitations, Reasons for Caution: One strength of our study is the relatively large sample size; we were able to detect mutations in seven common dynamic genes, and this large sample size allowed us to detect unstable alleles. Although we observed a clear alteration in the frequency of dynamic mutation in the ART offspring compared with controls, further studies are urgently needed to confirm this observation and determine the cause of this phenomenon., Wider Implications of the Findings: DNA microsatellite analysis provides an important tool to assess genomic instability. In this study, we report an association between ART and the frequency of dynamic mutation. The instability could be a reflection of the core infertility problem, the controlled ovarian hyperstimulation and/or the in vitro culture conditions.

Ground dry leaves of two emerged macrophytes Zinania Caduciflora and Phragmites australis from Lake Dianchi were soaked in distilled water in laboratory to track their DOM release process. The results showed that: (1) during soaking, concentration of DOM which was released to the overlying water by the two species increased at first, then decreased and increased again at last. Concentrations of DOC, DON, and DOP released by both species reached their peaks at the 8th, 8th, and 24th hour, respectively; (2) the two species showed the same DOM release trend, i.e., release rates and intensities of DOC, DON, and DOP by both species reached the peaks at the 8th hour, and for both of them, the release rates and intensities of DOC, DON, and DOP at the 8th hour followed the order of DOC > DON > DOP; (3) the SUVA254 value obtained by the UV-visible spectroscopy increased at first and then decreased; (4) Fourier transform infrared (FT-IR) spectroscopy showed that the characteristic peak -OH disappeared during the decomposition process; (5) intensity of the humic-acid fluorescence peak as showed by the 3D-EEM fluorescence intensity (F/DOC) increased along with degradation.

Objective: To observe the dynamic levels of serum Golgi protein 73(GP73) in patients prior to and after the onset of liver cancer, and to explore the related factors., Methods: From 2007 to 2012, a periodical screening program was carried out in a group of high risk population with positive Hepatitis B surface antigens (HBsAg) , twice a year. Their serum specimens from every screening time point were kept in Qidong Biobank until liver cancer was diagnosed. Thirty-nine patients with liver cancer were recruited for the study, each of them at least had three times of specimens collected as well as B ultrasound scan (BUS) exam results at onset of disease and within 30 months before diagnosed, amongst 6 time points. In total, there were 162 specimens collected to test GP73 by double-antibody sandwich enzyme-linked immuno-sorbent assay (ELISA). Statistical analyses of time series and differences among groups were performed by stata software 10., Results: The average value of 39 patient's GP73 at the time point of liver cancer onset was (126.77 ± 73.73) µg/L, while the values at the other five time points prior to the onset were (128.32 ± 81.18) , (129.97 ± 83.62) , (127.38 ± 80.10) , (135.52 ± 97.88) and (138.24 ± 93.58) µg/L, respectively, with no significant difference (F = 0.07, P = 0.997). No obvious changing trends of GP73 were observed among the 39 liver cancer cases at the 6 time points. All 162 samples were divided into two groups: without hepatic cirrhosis (63 samples) and with cirrhosis (99 samples) according to findings of B-ultrasonic wave; whose average GP73 values were separately (97.16 ± 51.39) and (151.20 ± 91.68) µg/L. The difference showed statistical significance (F = 18.22, P < 0.01). Furthermore, if we grouped the samples by the average value of GP73 at 130.19 µg/L, then there were only 1/14 of the subjects without hepatic cirrhosis having higher GP73 values, but 12 of the 25 subjects with hepatic cirrhosis having higher GP73 values. The difference showed statistical significance (P = 0.013). The results of Linear regression model also showed that there was no correlation between GP73 and time series (t = 0.75, P = 0.455), but significant correlation between GP73 and hepatic cirrhosis (t = 4.30, P < 0.01)., Conclusion: No significant changes of the dynamic levels of GP73 could be found among the liver cancer patients within 30 months prior to the onset of disease. GP73 values of the patients with liver cancer may depend on their background of hepatic diseases; and hepatic cirrhosis might be one of the main influencing factors or confounding factors.

Adsorption of alkaline phosphatase (APase) on minerals (goethite, montmorillonite) and sediments from Taihu Lake was studied. However, the concentration of alkaline phosphatase in the supernatant cannot be analyzed by the adsorption at 280 nm due to that the UV spectroscopy was changed. Quantitative analysis of alkaline phosphatase in the supernatant by the absorption peak (252-305 nm) integration method of UV spectroscopy was developed. This method determined the concentrations of alkaline phosphatase well. Compared to the results of Bradford, the absorption peak integration method can determine the concentrations of supernatant fast, conveniently, and accurately. This method can also be applied to other protein solution analysis and similar experiments. The drawbacks of traditional single wavelength method (280nm) were overcome to some extent based on the method of absorption peak integration.

Aim: To investigate the effects of safflor yellow A (SYA), a flavonoid extracted from Carthamus tinctorius L, on cultured rat cardiomyocytes exposed to anoxia/reoxygenation (A/R)., Methods: Primary cultured neonatal rat cardiomyocytes were exposed to anoxia for 3 h followed by reoxygenation for 6 h. The cell viability was measured using MTT assay. The releases of lactate dehydrogenase (LDH) and creatine kinase (CK), level of malondialdehyde (MDA), and activities of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were analyzed. Hoechst 33258 staining and changes in Bcl-2/Bax ratio and caspase 3 activity were used to examine A/R-induced apoptosis., Results: The A/R exposure markedly decreased the viability of cardiomyocytes, suppressed the activities of SOD, GSH, CAT and GSH-Px, and Bcl-2 protein expression. Meanwhile, the A/R exposure markedly increased the release of LDH and CK, and MDA production in the cardiomyocytes, and increased the rate of apoptosis, caspase 3 activity, Bax protein expression. Pretreatment with SYA (40, 60 and 80 nmol/L) concentration-dependently blocked the A/R-induced changes in the cardiomyocytes. Pretreatment of the cardiomyocytes with the antioxidant N-acetylcysteine (NAC, 200 μmol/L) produced protective effects that were comparable to those caused by SYA (80 nmol/L)., Conclusion: SYA protects cultured rat cardiomyocytes against A/R injury, maybe via inhibiting cellular oxidative stress and apoptosis.

Traditional Chinese medicine uses a systemic treatment approach, targeting multiple etiological factors simultaneously. Danhong injection (DHI), a very popular Chinese medicine injection, is reported to be effective for many cardiovascular conditions. The primary active ingredients of DHI, and their systemic and interrelated mechanism have not been evaluated in an established myocardial ischemia/reperfusion (MI/R) model. We identified the main active constituents in DHI, including hydroxysafflor yellow A (A), salvianolic acid B (B), and danshensu (C), by HPLC fingerprint analysis and assessed their effect on MI/R rats and cardiomyocytes. These 3 compounds and DHI all decreased the levels of IL-1, TNF- α , and MDA, increased those of IL-10 and SOD activity in vivo and in vitro, and had antiapoptotic effects, as shown by flow cytometric analysis and TUNEL assay. Moreover, these compounds increased phosphorylation of Akt and ERK1/2 in cardiomyocytes. Interestingly, we found compound A exerted a more prominent anti-inflammatory effect than B and C, by decreasing NF- κ B levels; compound B had more powerful antioxidative capacity than A and C, by increasing Nrf2 expression; compound C had stronger antiapoptotic ability than A and B, by lowering caspase-3 activity. Our results elucidate the mechanisms by which DHI protects against MI/R induced injury.

Background: BK viremia can lead to nephritis, which can progress to irreversible kidney transplant failure. Our prospective study provides management and outcome of BK viremia in renal transplant recipients., Methods: Two hundred forty de novo kidney-only recipients were enrolled from July 2007 to July 2010 and followed for 1 year. Standard immunosuppression with Thymoglobulin/interleukin 2 receptor blocker and mycophenolate mofetil/tacrolimus (Tac)/prednisone was employed. Quantitative BK virus (BKV) DNA surveillance in plasma/urine was performed at 1, 3, 6, 12, and 24 months after transplantation. Patients with significant viremia (defined as ≥10,000 viral copies/mL) underwent renal biopsy and treated with 30% to 50% reduction in doses of both mycophenolate mofetil and Tac without antiviral therapy. The target 12-hr Tac trough levels were lowered to 4 to 6 ng/mL in the significant viremia group, whereas the target levels remained unchanged at 5 to 8 ng/mL for all other groups., Results: Sixty-five patients (27%) developed BK viremia; 28 (12%) of whom had significant viremia. A total of five (21%) of the 23 (of 28) patients who underwent biopsy presented with subclinical BKV nephritis. The mean plasma BKV DNA declined by 98% (range, 76%-100%) at 1 year after peak viremia. Acute cellular rejection seen in four (14%) of 28 patients, responded to bolus steroids. There was no decline in estimated glomerular filtration rate over time from 1 month after transplantation to 1 year after peak viremia (P=0.57)., Conclusion: Reduction in immunosuppression alone resulted in the successful resolution of viremia with preservation of renal function and prevention of clinical BKV nephritis and graft loss.