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A chemical investigation of the arils of Torreya grandis led to the isolation of seven abietane-type diterpenoids (compounds 1–7) including three previously undescribed compounds, one unreported natural product, and three known analogs. The structures of these compounds were determined by means of spectroscopy, single-crystal X-ray diffraction, and ECD spectra. An antibacterial activity assay showed that compounds 5 and 6 had significant inhibitory effects on methicillin-resistant Staphylococcus aureus, with MIC values of 100 μM. Moreover, compounds 1, 3, 4, and 7 exhibited anti-neuroinflammatory activity in LPS-stimulated BV-2 microglia cells, with the IC50 values ranging from 38.4 to 67.9 μM. [ABSTRACT FROM AUTHOR]

ZnO is a promising high‐temperature thermoelectric (TE) material due to its superior stability and earth abundance. However, the coupling relation between Seebeck coefficient and electrical conductivity on carrier concentration limits the optimum TE performance for most TE materials, especially ZnO. Herein, enhancement of TE performance is achieved via a stepwise optimization strategy composed of carrier concentration optimization and carrier filtering effect for fabricating robust ZnO‐based composite ceramics through a self‐developed specific high‐pressure synthesis followed by spark plasma sintering. Specifically, doping SnO2 provide substantial electrons to surge the carrier concentration. The subsequent compositing Si3N4 nanoparticles results in the unique reaction‐generated Zn2SiO4 nanoprecipitates with a larger bandgap and intrinsically low thermal conductivity, which introduce an excellent carrier filtering effect to increase the Seebeck coefficient by 57.7% at 300 K without compromising electrical conductivity much and enhance phonon scattering to cause an ultralow lattice thermal conductivity of 1.39 W m−1 K−1 achieving amorphous limits of ZnO (1.4±0.1 W m−1 K−1). Consequently, a high peak ZT (figure of merit) of 0.691 at 873 K is obtained, which is higher than that of previously reported ZnO‐based TE materials. This work demonstrates a feasible and effective strategy to fabricate high‐performance TE materials, especially those with inferior electrical conductivity. [ABSTRACT FROM AUTHOR]

High capacitance and good rate performance supercapacitors are needed to power sensors and miniaturized electrical devices. Thick electrodes are promising to increase the mass loading of active materials in supercapacitors, but the 3D geometries and microstructures in thick electrodes still hinder the development with high electron and ion exchange rate and accessible active sites. The scaffold 3D electrodes of reduced graphene oxide:manganese oxide/carbon nanotube (rGO:MnOx/CNT) are manufactured by material extrusion 3D printing (ME3DP), where the mass ratio of rGO to MnOx/CNT composites, thickness, and mass loading per unit area are controllable. The increasing amount of MnOx/CNT composites boosts the areal capacitance. Although the rate capability decays fast with the increasing of MnOx/CNT, it remains stable at different thicknesses (1.2, 1.6, and 2 mm). 2 mm thick rGO:MnOx/CNT (weight ratio 5:3) electrode exhibits an area capacitance of 302.13 mF cm−2 at a current density of 0.5 mA cm−2, due to the highly ordered rGO networks. Compared to the casted electrodes, the microstructures in the 3D printed electrode contribute to lower resistances for the charge and ion transportation. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) was defined in 1980 and has the same histological characteristics as alcoholic liver disease except for alcohol consumption. After 40 years, the understanding of this disease is still imperfect. Without specific drugs available for treatment, the number of patients with NAFLD is increasing rapidly, and NAFLD currently affects more than one-quarter of the global population. NAFLD is mostly caused by a sedentary lifestyle and excessive energy intake of fat and sugar. To ameliorate or avoid NAFLD, people commonly replace high-fat foods with high-carbohydrate foods (especially starchy carbohydrates) as a way to reduce caloric intake and reach satiety. However, there are few studies that concentrate on the effect of carbohydrate intake on liver metabolism in patients with NAFLD, much fewer than the studies on fat intake. Besides, most of these studies are not systematic, which has made identification of the mechanism difficult. In this review, we collected and analysed data from studies on human and animal models and, surprisingly, found that carbohydrates and liver steatosis could be linked by inflammation. This review not only describes the effects of carbohydrates on NAFLD and body lipid metabolism but also analyses and predicts possible molecular pathways of carbohydrates in liver lipid synthesis that involve inflammation. Furthermore, the limitations of recent research and possible targets for regulating inflammation and lipogenesis are discussed. This review describes the effects of starchy carbohydrates, a nutrient signal, on NAFLD from the perspective of inflammation. [ABSTRACT FROM AUTHOR]

The zebrafish intestine and liver, as in other vertebrates, are derived from the endoderm. Great effort has been devoted to deciphering the molecular mechanisms controlling the specification and development of the zebrafish intestine and liver; however, genome-wide comparison of the transcriptomes between these two organs at the larval stage remains unexplored. There is a lack of extensive identification of feature genes marking specific cell types in the zebrafish intestine and liver at 5 days post-fertilization, when the larval fish starts food intake. In this report, through RNA sequencing and single-cell RNA sequencing of intestines and livers separately dissected from wild-type zebrafish larvae at 5 days post-fertilization, together with the experimental validation of 47 genes through RNA whole-mount in situ hybridization, we identified not only distinctive transcriptomes for the larval intestine and liver, but also a considerable number of feature genes for marking the intestinal bulb, mid-intestine and hindgut, and for marking hepatocytes and cholangiocytes. Meanwhile, we identified 135 intestine- and 97 liver-enriched transcription factor genes in zebrafish larvae at 5 days post-fertilization. Our findings provide rich molecular and cellular resources for studying cell patterning and specification during the early development of the zebrafish intestine and liver. [ABSTRACT FROM AUTHOR]

Food safety and quality are seriously compromised by the growth of spoilage bacteria in food. Various lactic acid bacteria (LAB) may inhibit the growth of spoilage bacteria in food and animal feed. In our study, the antibacterial activity of Lactobacillus acidophilus NX2‐6 was improved by genome shuffling. The starting populations were obtained via 60Coγ‐ray, diethyl sulfate mutagenesis, and UV mutagenesis of protoplasts. The optimal conditions for protoplast formation and regeneration were found to be 30 mg/ml of lysozyme at 37°C for 40 min. The protoplasts were inactivated by UV irradiation for 110 s or by heating at 58°C for 30 min. After two rounds of genome shuffling, the inhibitory activity of strain F50 was improved by 5.6‐fold compared to the original strain. The shuffled strain has broad‐spectrum antibacterial activity and is a promising candidate for bio‐preservative. The antibacterial substances produced by L. acidophilus NX2‐6 can be applied to the preservation of apple juice. The results showed that the growth of Alicyclobacillus acidoterrestris in apple juice was significantly inhibited by the addition of 0.1% culture supernatant with acidocin NX2‐6 at 28°C and 0.2% culture supernatant with acidocin NX2‐6 at 45°C for 30 days. The sugar−acid ratio, pH value, clarity, and fruit flavor of apple juice were well maintained during storage. This study showed that genome shuffling was an effective strategy to improve the bacterial inhibitory activity of LAB and that the shuffled LAB and their metabolites are expected to be used as bio‐based food protectors for food safety. [ABSTRACT FROM AUTHOR]

African Swine Fever Virus (ASFV) is the cause of an infectious disease in pigs, which is difficult to control. Long viability of ASFV has been shown for several contaminated materials, especially under low temperature. Therefore, when pigs are exposed to a contaminated environment, new infections could occur without the presence of infectious individuals. For example, a contaminated, poorly washed, empty livestock vehicle poses a risk to the next load of pigs. A quantitative stochastic environmental transmission model was applied to simulate the change in environmental contamination levels over time and calculate the epidemic parameters through exposure-based estimation. Due to the lack of experimental data on environmental transmission at low temperatures, we performed a non-linear fit of the decay rate parameter with temperature based on a literature review. Eventually, 16 scenarios were constructed for different temperature (at 20 °C, 10 °C, 0 °C, or −10 °C) and duration of empty periods (1, 3, 5, or 7 days) after the environment had been contaminated. We quantified the variation in the contamination level of the environment over time and the probability of newly added recipients getting infected when exposed to the environment after the empty period. As a result, the transmission rate parameter for ASFV in pigs was estimated to be 1.53 (0.90, 2.45) day-1, the decay rate parameter to be 1.02 (0.73, 1.47) day-1 (at 21 °C), and the excretion rate parameter to be 2.70 (2.51, 3.02) day-1. Without washing and disinfecting, the environment required 9, 14, 24, 54 days to reach a low probability of causing at least one new case (<0.005) at 20 °C, 10 °C, 0 °C, −10 °C, respectively. In addition, the method proposed in this paper enables assessment of the effect of washing and disinfecting on ASFV environmental transmission. We conducted this study to better understand how the viability of ASFV at different temperatures could affect the infectivity in environmental transmission and to improve risk assessment and disease control strategies [ABSTRACT FROM AUTHOR]

The BET (bromo and extra-terminal) family proteins are epigenetic readers and master transcription coactivators, which have attracted great interests as cancer therapeutic targets. However, there are few developed labeling toolkits that can be applied for the dynamic studies of BET family proteins in living cells and tissue slices. In order to label and study the distribution of the BET family proteins in tumor cells and tumor tissues, a novel series of environment-sensitive fluorescent probes (6a - 6c) were designed and evaluated for their labeling properties. Interestingly, 6a is capable of identifying tumor tissue slices and making a distinction between the tumor and normal tissues. Moreover, it can localize to the nuclear bodies in tumor slices just like BRD3 antibody. In addition, it also played an anti-tumor role through the induction of apoptosis. All these features render 6a may compatible for immunofluorescent studies and future cancer diagnosis, and guide for the discovery of new anticancer drugs. [Display omitted] • A series of "turn-on" fluorescence probes have been designed and developed for monitoring BET family proteins. • Probe 6a could make a distinction between the tumor-tissue and normal-tissue slices in the imaging study. • In addition to the imaging ability of probe 6a for cells and tissues, it also showed potent anti-tumor activity. • As is easily and affordably prepared, 6a is much more convenient than BRD4/BRD3 antibody in the visualization of tissues. [ABSTRACT FROM AUTHOR]

Abstract To investigate the effects of superheated steam on the quality attributes of oats and oats noodles, the properties of oats flour and noodles prepared with or without superheated steam (200 °C for 2 min) and steam (100 °C for 20 min) processing were characterized. As the results, the residual lipase activity and damaged starch contents in superheated steam processed (SSP) oats were significantly decreased compared with steam processed (SP) oats (P ˂ 0.05). SSP improved morphology and water hydration properties of oat flour and development time of oats dough significantly compared with SP (P ˂ 0.05). Moreover, SSP also improved a part of the texture characteristics and taste quality in sensory evaluations of oat noodles compared with SP (P ˂ 0.05). It indicated that the SSP might provide the protective effects on the characteristics of oats flour, which could be used to produce the better qualities of oats noodles than the SP. Highlights • The superheated steam at 200 °C for 2 min was better than steam at 100°C for 20min on oats flour properties. • The processing improved partly the dough properties of oats compared with the steam processing. • The processing also improved texture characteristics and taste qualities of oat noodles compared with steam processing. [ABSTRACT FROM AUTHOR]

To detect γ-Glutamyl Transpeptidase (GGT) activity in vitro and in vivo, a bioluminescence probe with high sensitivity and specificity was well designed and synthesized. This probe can be recognized by GGT and release strong bioluminescence with its further reaction with luciferase. The performance of this probe was demonstrated in vitro and in cells. Finally, we applied the probe for detection of GGT activity in xenograft model. [ABSTRACT FROM AUTHOR]

Background: Modular tissue engineering (MTE) is a novel "bottom-up" approach that aims to mimic complex tissue microstructural features. The constructed micromodules are assembled into engineered biological tissues with repetitive functional microunits and form cellular networks. This is emerging as a promising strategy for reconstruction of biological tissue. Results: Herein, we constructed a micromodule for MTE and developed engineered osteon-like microunits by inoculating human-derived umbilical cord mesenchymal stem cells (HUMSCs) onto nHA/PLGA microspheres with surface modification of dual growth factors (BMP2/bFGF). By evaluating the results of proliferation and osteogenic differentiation ability of HUMSCs in vitro, the optimal ratio of the dual growth factor (BMP2/bFGF) combination was derived as 5:5. In vivo assessments showed the great importance of HUMSCs for osteogneic differentiation. Ultimately, direct promotion of early osteo-differentiation manifested as upregulation of Runx-2 gene expression. The vascularization capability was evaluated by tube formation assays, demonstrating the importance of HUMSCs in the microunits for angiogenesis. Conclusions: The modification of growth factors and HUMSCs showed ideal biocompatibility and osteogenesis combined with nHA/PLGA scaffolds. The micromodules constructed in the current study provide an efficient stem cell therapy strategy for bone defect repair. [ABSTRACT FROM AUTHOR]

Gallium oxide (Ga 2 O 3) thin films were deposited on c-plane sapphire substrates at low temperature (RT) by magnetron sputtering method using Ga 2 O 3 ceramic target and were post annealed at various temperatures ranging from 500 to 900 ℃. The effect of annealing temperature on the surface morphology, crystalline structure, chemical composition and optical properties of Ga 2 O 3 thin films were investigated. A phase separation is observed at 800 ℃ and α -phase Ga 2 O 3 thin films is obtained at low annealing temperature while β -Ga 2 O 3 at high temperature. With annealing temperature increases, the optical bandgap decreases from 5.47 to 5.00 eV and the surface morphology become more and more smooth. A broad emission band centered at 550 nm is observed for all samples which can be attributed to the donor acceptor pair (DAP) recombination related to the oxygen vacancies. [ABSTRACT FROM AUTHOR]

Abstract: The better adaptation of native Tibetans to hypoxia is thought to be partly due to improved umbilical circulation, which results in reduced pre- and postnatal fatalities. We hypothesized that the difference in umbilical circulation between native Tibetans and other high-altitude inhabitants was due to differences in the expression of hypoxia-induced factor (HIF-1) and its target genes vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS). We tested this hypothesis by examining the effect of hypoxia on the expression of HIF-1α, VEGF, and iNOS in cultured umbilical venous endothelial cells (UVECs) from native Tibetans and immigrant Hans. UVECs were collected and cultured under hypoxic (0.5% oxygen) or normoxic conditions for 2, 4, 12 and 24 h. The mRNA levels of HIF-1α, VEGF, endothelial nitric oxide synthase (eNOS) and iNOS and the protein level of HIF-1α were determined with RT-PCR and Western blot analyses, respectively. In both immigrant Han and Tibetans, HIF-1α mRNA was constitutively expressed under normoxic condition, and remained constant after hypoxic exposure. In contrast, HIF-1α protein was undetectable under normoxic condition, but underwent dynamic changes in response to hypoxia. It was induced at 4 h, peaked at 12 h, and remained elevated at 24 h. Concurrent with the induction of HIF-1α protein, the mRNA levels of VEGF and iNOS were also up-regulated whereas that of eNOS was down-regulated. The lack of a hypoxia-related difference in the expression of HIF-1α and its target genes suggests that HIF-1α does not play a critical role in high altitude adaptation. Alternative mechanisms may be responsible for the better adaptation of native Tibetans. [Copyright &y& Elsevier]

In this paper, based on the deformed cylinder method, the expression of the far-field acoustic scattering form function of a finite-length elastic elliptical cylinder is obtained. The target strength of elastic aluminum and polymethylmethacrylate (PMMA) elliptical cylinders, with different lengths varying with dimensionless frequency k a , is studied for different incident angles. In addition, the change of the target strength of a PMMA elliptical cylinder with incident angle is explored theoretically and experimentally when the frequency range is 20–40 kHz. Simulation results show that there is almost no change in the peak of the curve of the backscattering target strength versus frequency for a finite-length elastic elliptical cylinder with different lengths. As the length decreases, the target strength gradually decreases. When the theoretical simulation results are compared with the experimental results, it is found that the theoretical predictions are in good agreement with the experimental results. Furthermore, the study will provide theoretical and experimental basis for the prediction and recognition of underwater targets. [ABSTRACT FROM AUTHOR]

MicroRNAs play important roles in various biological processes by regulating their corresponding target genes. However, the function and regulatory mechanism of fungal microRNA‐like RNAs (milRNAs) are still largely unknown. In this study, a milRNA (Vm‐milR37) was isolated and identified from Valsa mali, which causes the most serious disease on the trunk of apple trees in China. Based on the results of deep sequencing and quantitative reverse transcription PCR, Vm‐milR37 was found to be expressed in the mycelium, while it was not expressed during the V. mali infection process. Overexpression of Vm‐milR37 did not affect vegetative growth, but significantly decreased pathogenicity. Based on degradome sequencing, the target of Vm‐milR37 was identified as VmGP, a glutathione peroxidase. The expression of Vm‐milR37 and VmGP showed a divergent trend in V. mali–apple interaction samples and Vm‐milR37 overexpression transformants. The expression of VmGP could be suppressed significantly by Vm‐milR37 when coexpressed in tobacco leaves. Deletion of VmGP showed significantly reduced pathogenicity compared with the wild type. VmGP deletion mutants showed more sensitivity to hydrogen peroxide. Apple leaves inoculated with Vm‐milR37 overexpression transformants and VmGP deletion mutant displayed increased accumulation of reactive oxygen species compared with the wild type. Thus, Vm‐milR37 plays a critical role in pathogenicity by regulating VmGP, which contributes to the oxidative stress response during V. mali infection. These results provide important evidence to define the roles of milRNAs and their corresponding target genes in pathogenicity. [ABSTRACT FROM AUTHOR]

The specification of endoderm cells to prospective hepatoblasts is the starting point for hepatogenesis. However, how a prospective hepatoblast gains the hepatic fate remains elusive. Previous studies have shown that loss-of-function of either hhex or prox1a alone causes a small liver phenotype but without abolishing the hepatocyte differentiation, suggesting that absence of either Hhex or Prox1a alone is not sufficient to block the hepatoblast differentiation. Here, via genetic studies of the zebrafish two single (hhex −/− and prox1a −/− ) and one double (hhex −/− prox1a −/− ) mutants, we show that simultaneous loss-of-function of the hhex and prox1a two genes does not block the endoderm cells to gain the hepatoblast potency but abolishes the hepatic differentiation from the prospective hepatoblast. Consequently, the hhex −/− prox1a −/− double mutant displays a liverless phenotype that cannot be rescued by the injection of bmp2a mRNA. Taken together, we provide strong evidences showing that Hhex teams with Prox1a to act as a master control of the differentiation of the prospective hepatoblasts towards hepatocytes. • Hhex and Prox1 are two transcription factors essential for hepatogenesis. • Depletion of either hhex or prox1a causes a small liver phenotype with differentiated hepatocytes. • The hhex and prox1a double mutant does not block the endoderm cells to gain the hepatoblast potency. • The hhex and prox1a double mutant abolishes the hepatic differentiation from the prospective hepatoblast. • The liverless phenotype in the hhex −/− prox1a −/− double mutant cannot be rescued by the injection of bmp2a mRNA. [ABSTRACT FROM AUTHOR]

SUMMARY: Effectors play important roles in facilitating the infection of plant pathogenic fungi. However, the gene expression regulatory mechanism of effector genes, in particular at the post‐transcriptional level, is largely unknown. In this study, we uncovered the post‐transcriptional regulation of an effector gene VmSP1 by a miRNA‐like RNA (Vm‐milR16) facilitating the infection of the apple tree Valsa canker pathogen Valsa mali. Genetic and molecular biological assays indicated that the expression of VmSP1 could be suppressed by Vm‐milR16‐mediated mRNA cleavage in a sequence‐specific manner. During V. mali infection, Vm‐milR16 was downregulated, whereas VmSP1 was upregulated, which further indicated the regulation relationship. VmSP1 was further demonstrated to be a secreted protein and could suppress plant immunity. Deletion of VmSP1 did not affect the vegetative growth but significantly reduced the virulence of V. mali. Further study indicated that VmSP1 could interact with the transcription factor MdbHLH189 of apple. Transiently overexpression of MdbHLH189 enhanced host resistance to V. mali by enhancing the expression of apple defense‐related genes, together with the increased callose deposition. Silencing of MdbHLH189 compromised host resistance to V. mali. Our findings uncovered the novel epigenetic regulation mechanism of a virulence‐associated effector gene mediated by a fungal milRNA at the post‐transcriptional level, and the results enriched the understanding of the function and action mechanism of effectors in tree pathogenic fungi. Significance Statement: Fungal effectors are proposed as major contributors to plant disease development. However, the regulation mechanism of the effector gene is largely unknown. Combining bioinformatics, molecular biology, genetic, and biochemistry methods, we report a new strategy that post‐transcriptional regulation of the virulence‐related effector gene VmSP1 by the milRNA‐mediated sequence‐specific cleavage, and the action mechanism of VmSP1 by targeting an apple resistance‐related transcription factor, which enhances the survival and host adaption of plant pathogenic fungi. [ABSTRACT FROM AUTHOR]

Background: The prognosis of patients with colorectal cancer is related to early detection. However, commonly used screening markers lack sensitivity and specificity. In this study, we identified diagnostic methylation sites for colorectal cancer. Methods: After screening the colorectal cancer methylation dataset, diagnostic sites were identified via survival analysis, difference analysis, and ridge regression dimensionality reduction. The correlation between the selected methylation sites and the estimation of immune cell infiltration was analyzed. The accuracy of the diagnosis was verified using different datasets and the 10-fold crossover method. Results: According to Gene Ontology, the main enrichment pathways of genes with hypermethylation sites are axon development, axonogenesis, and pattern specification processes. However, the Kyoto Encyclopedia of Genes and Genomes (KEGG) suggests the following main enrichment pathways: neuroactive ligand–receptor interaction, calcium signaling, and cAMP signaling. In The Cancer Genome Atlas (TCGA) and GSE131013 datasets, the area under the curve of cg07628404 was > 0.95. For the NaiveBayes machine model of cg02604524, cg07628404, and cg27364741, the accuracies of 10-fold cross-validation in the GSE131013 and TCGA datasets were 95% and 99.4%, respectively. The survival prognosis of the hypomethylated group (cg02604524, cg07628404, and cg27364741) was better than that of the hypermethylated group. The mutation risk did not differ between the hypermethylated and hypomethylated groups. The correlation coefficient between the three loci and CD4 central memory T cells, hematological stem cells, and other immune cells was not high (p < 0.05). Conclusion: In cases of colorectal cancer, the main enrichment pathway of genes with hypermethylated sites was axon and nerve development. In the biopsy tissues, the hypermethylation sites were diagnostic for colorectal cancer, and the NaiveBayes machine model of the three loci showed good diagnostic performance. Site (cg02604524, cg07628404, and cg27364741) hypermethylation predicts poor survival for colorectal cancer. Three methylation sites were weakly correlated with individual immune cell infiltration. Hypermethylation sites may be a useful repository for diagnosing colorectal cancer. [ABSTRACT FROM AUTHOR]

Accurately estimating aboveground dry biomass (ADB) is crucial. The ADB of rice has primarily been estimated using vegetation indices with several discrete bands; nevertheless, these indices cannot take advantage of continuous bands available with hyperspectral remote sensing. This study analyzed the quantitative relationship between canopy hyperspectral characteristic parameters (HCPs) and the ADB of rice. Twenty HCPs were used, including red edge area (SDr), blue edge area (SDb), and others. The variable-screening methods involved stepwise regression (SR), a regression coefficient (RC), variable importance in projection (vip), and random forest (RF). Stepwise and partial least squares regression methods were employed with traditional linear regression as well as machine learning methods including random forest (RF), a support vector machine (SVM), a BP artificial neural network (BPNN), and an extreme learning machine. Whole- and screening-variable models were constructed to estimate rice ADB at jointing, booting, heading, and maturing stages and across growth stages. Screening-variable models include SVM models based on SR (SVM-sr), RF models based on vip (RF-vip), and others. The results show that the HCPs had a significant correlation with ADB containing elements in the red edge region, namely SDr, SDr/SDb, and (SDr − SDb)/(SDr + SDb) at each growth stage. In addition, the screening performance of vip and SR was better than that of RC and RF, and fewer variables were screened. Moreover, the HCPs of the red edge region were screened using different screening methods at each growth stage. Among them, SDr/SDb and (SDr − SDb)/(SDr + SDb) appeared frequently, indicating they are important. Furthermore, at each growth stage, ADB could be well-estimated using diverse models with the RF modeling method based on vip screening variables found to be the best modeling method for ADB estimation; the independent variables of the RF-vip model involved the (SDr − SDb)/(SDr + SDb) at each growth stage. [ABSTRACT FROM AUTHOR]

• Haihe River is a sluice-controlled coastal plain river showing both salinity and trophic gradients. • TSI posed a greater influence than salinity on the CDOM abundance. • TSI affected the CDOM abundance more than the fluorescence intensity. • Salinity affected the abundance of CDOM but rarely affected FDOM. Due to the combined effect of sluices and sea tide, the sluice-controlled coastal plain river would be characterized by both trophic state and salinity gradients, affecting the spatiotemporal optical properties of dissolved organic matter (DOM). In this study, we investigated the spatiotemporal variation of water quality parameters and optical properties of DOM in the Haihe River, a representative sluice-controlled coastal plain river in Tianjin, China. A significant salinity gradient and four trophic states were observed in the water body of the Haihe River. Two humic- and one protein-like substances were identified from the DOM by the three-dimensional fluorescence spectra combined with the parallel factor (PARAFAC) analysis. Pearson's correlation analysis and redundancy analysis (RDA) showed that the salinity significantly affected the abundance of chromophoric DOM (CDOM) but did not cause significant changes in the fluorescence optical characteristics. In addition, the effect of Trophic state index (TSI) on the CDOM abundance was greater than that on the fluorescence intensity of fluorescent dissolved organic matter (FDOM). In the water body with both salinity and trophic state gradients, TSI posed a greater influence than salinity on the CDOM abundance. Our results fill the research gap in spatiotemporal DOM characteristics and water quality variation in water bodies with both salinity and trophic state gradients. These results are beneficial for clarifying the joint influence of saline intrusion and sluices on the DOM characteristics and water quality in sluice-controlled coastal plain rivers. [Display omitted] [ABSTRACT FROM AUTHOR]

In the rice–rapeseed rotation system, straw incorporation plays an important role in achieving the rational utilization of resources and maintaining crop production. However, in the study of rice–rapeseed rotation, there was no study on the effect of straw and nitrogen (N) fertilizer in the rice season on the dry matter accumulation (DMA) and nutrient accumulation of subsequent rapeseed. So, this study relied on the localization experiment of rice–rapeseed rotation and annual straw incorporation (full straw returning to the field, SR; the control is full straw removal from the field, CK) with different N fertilizer application rates (N1: 0 kg ha−1, N2: 75 kg ha−1, N3: 150 kg ha−1, and N4: 225 kg ha−1) in the rice season. Based on the fourth year of experiment implementation, the effects of annual straw incorporation combined with the N fertilizer application rate in the rice season on the leaf area index (LAI), photosynthetic potential (PP), DMA and its distribution proportion and rate, and nutrient uptake and its allocation proportion in rapeseed were discussed. At the bolting stage (BS), initial flowering stage (IFS), terminal flowering stage (TFS), and mature stage (MS), the DMA of rapeseed in SR was significantly higher than that in CK by 69.90, 64.27, 62.90, and 41.27%, respectively. The accumulation of N, phosphorus (P), and potassium (K) in SR was significantly higher than that in CK at the BS, IFS, TFS, and MS. Straw treatment had a significant impact on the apparent surplus of N, P, and K in the rice, rapeseed, and annual seasons, while the application of N fertilizer in the rice season had a significant or extremely significant impact on the apparent surplus (AS) of N in the rice, rapeseed, and annual seasons, indicating that fertilization of previous crops had a certain aftereffect. Therefore, straw incorporation is a sustainable farmland management measure. [ABSTRACT FROM AUTHOR]

Sirtuin 6 (SIRT6) is a nuclear silencing information regulator that is widely expressed in brain. Inhibition of SIRT6 in the brain induced antidepressant effects in rodents. However, SIRT6 knockout in neurons induced developmental retardation and cognitive impairments. In this study, a mouse strain of astrocyte conditional knockout SIRT6 (AKO) was constructed. Unlike whole brain SIRT6 knockout mice, AKO mice did not show growth retardation. We showed that SIRT6 knockout in astrocytes did not impair the learning and memory ability of mice. Chronic unpredictable mild stress (CUMS) was used to evaluate the anti-depression and anti-anxiety effects in mice. In tail suspension test and forced swimming test, AKO mice did not show depression like phenotype induced by CUMS. In addition, knockout of SIRT6 in astrocytes alleviated the high anxiety level induced by CUMS in light and dark box test, open field test and elevated cross maze test. Three box social test showed that the deletion of SIRT6 in astrocytes changed the social preference of mice. Re-expression of SIRT6 in astrocytes mediated by adeno-associated virus reversed the social preference of AKO mice, but the re-expression also eliminated the anti-depression and anti-anxiety effects in AKO mice. Deletion of SIRT6 in astrocytes change the purine metabolic homeostasis of medial prefrontal cortex in mice. The results of transcriptomics and metabolomics analysis showed that the deletion of SIRT6 would change the purine metabolic pathway of cultured astrocytes and increase the contents of inosine and the second messenger cyclic adenosine monophosphate in astrocytes. In conclusion, knockout of SIRT6 in astrocytes induced anti-depression and anti-anxiety effects in mice without impairing the development and cognitive ability of mice. • SIRT6 deletion in astrocytes did not induce developmental retardation or cognitive impairment • SIRT6 deletion in astrocytes induced anti-depressive and anti-anxiety effects in mice • The behavioral phenotype induced by SIRT6 deletion was reversed by re-expression of SIRT6 in astrocytes • SIRT6 regulates purine metabolism in astrocytes [ABSTRACT FROM AUTHOR]

Bisphosphoglycerate mutase (BPGM) is expressed in human erythrocytes and responsible for the production of 2,3-bisphosphoglycerate (2,3-DPG). However, the expression and role of BPGM in other cells have not been reported. In this work, we found that BPGM was significantly upregulated in astrocytes upon acute hypoxia, and the role of this phenomenon will be clarified in the following report. The mRNA and protein expression levels of BPGM and the content of 2,3-DPG with hypoxia treatment were determined in vitro and in vivo. Furthermore, glycolysis was evaluated upon in hypoxic astrocytes with BPGM knockdown and in normoxic astrocytes with BPGM overexpression or 2,3-DPG treatment. To investigate the mechanism by which BPGM/2,3-DPG regulated glycolysis in hypoxic astrocytes, we detected the expression of HIF-1α, FIH-1 and TET2 with silencing or overexpression of BPGM and 2,3-DPG treatment. The expression of glycolytic genes and the capacity of lactate markedly increased with 6 h, 12 h, 24 h, 36 h and 48 h 1 % O 2 hypoxic treatment in astrocytes. The expression of BPGM was upregulated, and the production of 2,3-DPG was accelerated upon hypoxia. Moreover, when BPGM expression was knocked down, glycolysis was promoted in HEB cells. However, overexpression of BPGM and addition of 2,3-DPG to the cellular medium in normoxic cells could downregulate glycolytic genes. Furthermore, HIF-1α and TET2 exhibited higher expression levels and FIH-1 showed a lower expression level upon BPGM silencing, while these changes were reversed under BPGM overexpression and 2,3-DPG treatment. Our study revealed that the BPGM/2,3-DPG pathway presented a suppressive effect on glycolysis in hypoxic astrocytes by negatively regulating HIF-1α and TET2. • Hypoxia enhanced BPGM/2,3-DPG pathway activity in hypoxic astrocytes. • BPGM/2,3-DPG pathway suppressed glycolytic process in hypoxic astrocytes. • BPGM/2,3-DPG regulated glycolysis in hypoxic astrocytes by FIH-1/HIF-1α and TET2/5-hmC pathway. [ABSTRACT FROM AUTHOR]

Summary: Small RNAs (sRNAs) play important roles in various biological processes by silencing their corresponding target genes in most eukaryotes. However, cross‐kingdom regulation mediated by fungal microRNA‐like RNAs (milRNAs) in plant–pathogen interactions is still largely unknown.Using molecular, genetic, histological, and biochemical approaches, we found that the apple tree Valsa canker pathogen Valsa mali milRNA Vm‐milR1 could suppress the host immunity by silencing two host receptor‐like kinase genes, MdRLKT1 and MdRLKT2.Vm‐milR1 was highly induced during V. mali infection. Deletion of Vm‐milR1 precursor abolished the generation of Vm‐milR1 and reduced the virulence of V. mali. Inoculation of Vm‐milR1 deletion mutants induced the host defence responses, including reactive oxygen species (ROS) accumulation, callose deposition, and high expression of defence‐related genes. Furthermore, Vm‐milR1 was confirmed to be able to suppress the expression of MdRLKT1 and MdRLKT2 in a sequence‐specific manner. Moreover, overexpression of either MdRLKT1 or MdRLKT2 enhanced apple resistance to V. mali by activating the host defence responses. Furthermore, knockdown of MdRLKT1 or MdRLKT2 compromised the host resistance to V. mali.Our study revealed that V. mali was equipped with Vm‐milR1 as an sRNA effector to silence host receptor‐like kinase genes, suppress the host defence responses, and facilitate pathogen infection. [ABSTRACT FROM AUTHOR]

Abstract: Approximately 26.8% of China's land area has an elevation of 3000m above sea level or higher. Because of recent demands for economic development and new construction in highland areas, many people have relocated from the plains to high plateau regions and have to face the possibility of contracting acute mountain sickness. Therefore, prevention and treatment strategies are necessary to reduce the incidence of acute mountain sickness in people who rapidly ascend to plateau areas. This paper describes the Chinese experience when large numbers of people moved to the plateau and the steps that were taken to deal with this illness. These steps included implementing basic prevention measures, increasing medical awareness among populations ascending to high altitudes, and installing standardized medical management systems to prevent and treat acute mountain sickness before, during, and after ascent. The incidence of acute mountain sickness can be reduced by improving prevention and treatment and by implementing the recommendations described in this manuscript. [Copyright &y& Elsevier]

Mitochondria are the energy metabolism centers of the cell. More than 95% of cellular energy is produced by mitochondrial oxidative phosphorylation. Hypoxia affects a wide range of energy generation and consumption processes in animals. The most important mechanisms limiting ATP consumption increase the efficiency of ATP production and accommodate the reduced production of ATP by the body. All of these mechanisms relate to changes in mitochondrial function. Mitochondrial function can be affected by variations in mitochondrial DNA, including polymorphisms, content changes, and deletions. These variations play an important role in acclimatization or adaptation to hypoxia. In this paper, the association between mitochondrial genome sequences and high-altitude adaptation is reviewed. [ABSTRACT FROM AUTHOR]

Our previous studies revealed that the expression of stanniocalcin-1 (STC1) in astrocytes increased under hypoxic conditions. However, the role of STC1 in hypoxic astrocytes is not well understood. In this work, we first showed the increased expression of STC1 in astrocyte cell line and astrocytes in the brain tissues of mice after exposure to hypoxia. Then, we found that knockdown of STC1 inhibited cell viability and increased apoptosis. These effects were mediated by decreasing the levels of SIRT3, UCP2, and glycolytic genes and increasing the levels of ROS. Further studies suggested that STC1 silencing promoted oxidative stress and suppressed glycolysis by downregulating AMPKα1. Moreover, HIF-1α knockdown in hypoxic astrocytes led to decreased expression of STC1 and AMPKα1, indicating that the expression of STC1 was regulated by HIF-1α. In conclusion, our study showed that HIF-1α-induced STC1 could protect astrocytes from hypoxic damage by regulating glycolysis and redox homeostasis in an AMPKα1-dependent manner. [ABSTRACT FROM AUTHOR]

High-altitude pulmonary edema (HAPE) is a severe disease caused by high-altitude hypoxia. Since some individuals are more susceptible to high altitude than others, the incidence is variable and cannot be predicted. Furthermore, multiple genes can contribute to the occurrence of HAPE, making it even more difficult to predict. The genes associated with HAPE include those in the renin-angiotensin-aldosterone system pathway, the nitric oxide pathway and the hypoxia-inducible factor pathway. Other genes associated with HAPE include tyrosine hydroxylase (TH), vascular endothelial growth factor (VEGF), pulmonary surfactant proteins and β2-adrenergic receptor. The association of the polymorphisms of these genes with HAPE susceptibility has previously been investigated. Among the genes evaluated, polymorphisms of NOS3, ACE, CYP11B2, Hsp70 and endothelin-1 and pulmonary surfactant proteins A1 and A2 were shown to be associated with HAPE incidence, while associations between TH, VEGF and HAPE remain to be fully elucidated. Novel technological approaches, including genome-wide association studies and next-generation sequencing, are currently being used to identify new HAPE susceptibility genes. The goal of this review article is to summarize the current literature and to define the outstanding areas of research that need to be explored to advance our ability to predict when HAPE will occur. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Quercetin is an active constituent of Hippophae rhamnoides L. and Ginkgo Biloba, which are commonly taken for high altitude sickness. The preventive effect of quercetin on hypobaric hypoxic rats was investigated. Male Wistar rats (180–220g) were placed into six groups: normoxic group (normal control), a hypoxic group (model control), three quercetin-treated groups (5, 10, 20mg/kg, i.g.), and acetazolamide-treated group (22.5mg/kg, i.g., positive control), 10 animals in each group. Hypoxic rats were raised in a hypobaric hypoxia chamber simulating a high altitude of 5000m for 23h per day after a five-day pretreatment. Normoxic control rats were raised at an altitude of 300m. After the five-day treatment, hemodynamic, arterial blood gas and electrolyte parameters, antioxidants and nitric oxide metabolism were measured. Hypobaric hypoxia enhanced the right ventricular systolic pressure, right ventricular end-diastolic pressure and left ventricular end-diastolic pressure, which were reversed by quercetin. Quercetin increased the declined pH, PO2, SpO2, PCO2 levels in arterial blood induced by hypobaric hypoxia, and increased Na+, HCO3 −, Cl−, but decreased K+ concentrations. Quercetin increased superoxide dismutase, catalase, glutathione peroxidase activities, glutathione levels, and it decreased malondialdehyde levels in serum. Furthermore, quercetin increased nitric oxide levels and inducible nitric oxide synthase activity in serum. Rats failed to gain body weight under hypobaric hypoxia and quercetin had no effect on it. These results suggest that the activities of quercetin on cardiac function, arterial blood gas, antioxidants and nitric oxide metabolism may be related to its protective potential on hypobaric hypoxia-induced damage. [Copyright &y& Elsevier]

Abstract: Pikas originated in Asia and are small lagomorphs native to cold climates. The plateau pika, Ochotona curzoniae is a keystone species on the Qinghai–Tibet Plateau and an ideal animal model for hypoxic adaptation studies. Altered mitochondrial function, especially cytochrome c oxidase activity, is an important factor in modulation of energy generation and expenditure during cold and hypoxia adaptation. In this study, we determined the complete nucleotide sequence of the O. curzoniae mitochondrial genome. The plateau pika mitochondrial DNA is 17,131bp long and encodes the complete set of 37 proteins typical for vertebrates. Phylogenetic analysis based on concatenated heavy-strand encoded protein-coding genes revealed that pikas are closer to rabbit and hare than to rat. This suggests that rabbit or hare would be a good control animal for pikas in cold and hypoxia adaptation studies. Fifteen novel mitochondrial DNA-encoded amino acid changes were identified in the pikas, including three in the subunits of cytochrome c oxidase. These amino acid substitutions potentially function in modulation of mitochondrial complexes and electron transport efficiency during cold and hypoxia adaptation. [Copyright &y& Elsevier]

• Spatio-temporal variations of water quality parameters in the Yongding New River were jointly caused by different pollutant sources and climatic factors. • Combined weighting based on game theory was firstly put forward to improve the comprehensive water quality identification index. • Improved comprehensive water quality identification index (ICWQII) based on entropy weight and variation coefficient underestimated the assessment result, while ICWQII based on superstandard multiple overvalued the assessment result. • ICWQII based on game theory is a relatively reasonable tool for water quality assessment. The Yongding New River is essential for the water supplies of Tianjin. To date, there is no comprehensive report that assesses the year-round water quality of the Yongding New River Main stream. Moreover, little attention has been given to determining a combined weight for improving the traditional comprehensive water quality identification index (ICWQII) by the game theory. Seven water quality parameters were investigated monthly along the main stream of the Yongding New River from May 2018 to April 2019. Organic contaminants and nitrogen pollution were mainly caused by point sources pollution, and the total phosphorus mainly by non-point source pollution. Dramatic spatio-temporal variations of water quality parameters were jointly caused by different pollutant sources and hydrometeorological factors. In terms of this study, an improved comprehensive water quality identification index (ICWQII) based on entropy weight or variation coefficient and traditional CWQII underestimated the water qualities, and an ICWQII based on the superstandard multiple method overvalued the assessments. By contrast, water qualities assessments done with an ICWQII based on the game theory matched perfectly with the practical situation. The ICWQII based on game theory proposed in this study takes into account not only the degree of disorder and variation of water quality data, but also the influence of standard-exceeded pollution indicators, whose results are relatively reasonable. All findings and the ICWQII based on game theory can provide scientific support for decisions related to the water environment management of the Yongding New River and other waters. Water quality characteristics and assessment of Yongding New River by improved comprehensive water quality identification index based on game theory [Display omitted] [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) is a major cause of heart failure and is associated with insufficient myocardial oxygen supply. However, the molecular mechanisms underlying hypoxia-induced cardiomyocyte apoptosis are not completely understood. In the present study, the role of human coilin interacting nuclear ATPase protein (hCINAP) in cardiomyocytes was investigated. AC16 cells were divided into the following four groups: i) Small interfering (si)RNA-control (Ctrl); (ii) siRNA-hCINAP; (iii) empty vector; and (iv) hCINAP-Flag. Protein expression was assessed using western blotting. MTT and apoptosis assays were conducted to detect cell viability and apoptosis, respectively. CCK8 assays and apoptosis assays were used to detect cell viability and apoptosis, respectively. hCINAP promoter activity was examined by luciferase reporter assay. hCINAP expression was induced in a hypoxia-inducible factor-1α-dependent manner under hypoxic conditions. Compared with the siRNA-Ctrl group, hCINAP knockdown inhibited apoptosis, whereas compared with the vector group, hCINAP overexpression increased apoptosis under hypoxic conditions. Mechanistically, compared with the siRNA-Ctrl group, hCINAP knockdown decreased hypoxia-induced lactate accumulation via regulating lactate dehydrogenase A activity. Moreover, the results indicated that hCINAP was associated with mitochondrial-mediated apoptosis via Caspase signaling. Collectively, the present study suggested that hCINAP was an important regulator in hypoxia-induced apoptosis and may serve as a promising therapeutic target for AMI. [ABSTRACT FROM AUTHOR]

Exosomal microRNAs (miRNAs/miRs) are potential biomarkers for the diagnosis and treatment of cardiovascular disease, and hyperglycemia serves an important role in the development of atherosclerosis. The present study aimed to investigate the expression profile of serum-derived exosomal miRNAs in coronary heart disease (CHD) with hyperglycemia, and to identify effective biomarkers for predicting coronary artery lesions. Serum samples were collected from eight patients with CHD and hyperglycemia and eight patients with CHD and normoglycemia, exosomes were isolated and differentially expressed miRNAs (DEMIs) were filtered using a human miRNA microarray. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using standard enrichment computational methods for the target genes of DEMIs. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the values of the selected DEMIs in predicting the severity of coronary stenosis. A total of 10 DEMIs, including four upregulated miRNAs (hsa-let-7b-5p, hsa-miR-4313, hsa-miR-4665-3p and hsa-miR-940) and six downregulated miRNAs (hsa-miR-4459, hsa-miR-4687-3p, hsa-miR-6087, hsa-miR-6089, hsa-miR-6740-5p and hsa-miR-6800-5p), were screened in patients with CHD and hyperglycemia. GO analysis showed that the 'cellular process', 'single-organism process' and 'biological regulation' were significantly enriched. KEGG pathway analysis revealed that the 'mTOR signaling pathway', 'FoxO signaling pathway' and 'neurotrophin signaling pathway' were significantly enriched. Among these DEMIs, only hsa-let-7b-5p expression was positively correlated with both hemoglobin A1C levels and Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery score. ROC curves showed that hsa-let-7b-5p could serve as an effective biomarker for differentiating the severity of coronary stenosis. In conclusion, the present study demonstrated that serum-derived exosomal hsa-let-7b-5p is upregulated in patients with CHD and hyperglycemia, and may serve as a noninvasive biomarker for the severity of coronary stenosis. [ABSTRACT FROM AUTHOR]

Mammalian sirtuin 6 (SIRT6) is involved in the regulation of many essential processes, especially metabolic homeostasis. SIRT6 knockout mice undergo premature aging and die at age ~4 weeks. Severe glycometabolic disorders have been found in SIRT6 knockout mice, and whether a dietary intervention can rescue SIRT6 knockout mice remains unknown. In our study, we found that at the same calorie intake, a high‐fat diet dramatically increased the lifespan of SIRT6 knockout mice to 26 weeks (males) and 37 weeks (females), reversed multi‐organ atrophy, and reduced body weight, hypoglycemia, and premature aging. Furthermore, the high‐fat diet partially but significantly normalized the global gene expression profile in SIRT6 knockout mice. Regarding the mechanism, excessive glucose uptake and glycolysis induced by the SIRT6 deficiency were attenuated in skeletal muscle through inhibition of insulin and IGF1 signaling by the high‐fat diet. Similarly, fatty acids but not ketone bodies inhibited glucose uptake, glycolysis, and senescence in SIRT6 knockout fibroblasts, whereas PI3K inhibition antagonized the effects of a high‐fatty‐acid medium in vitro. Overall, the high‐fat diet dramatically reverses numerous consequences of SIRT6 deficiency through modulation of insulin and IGF1 signaling, providing a new basis for elucidation of SIRT6 and fatty‐acid functions and supporting novel therapeutic approaches against metabolic disorders and aging‐related diseases. [ABSTRACT FROM AUTHOR]

In the design of super-long-span suspension bridges, the floating system is commonly adopted. However, this system may lead to the excessive earthquake-excited longitudinal displacement (LD) at the end of the main girder, which in return could result in pounding damage at expansion joints. In this paper, Taizhou Bridge, the triple-tower suspension bridge with the longest main span in the world, is taken as an example to demonstrate the effectiveness of three different approaches (elastic links, viscous dampers, and their combination) of mitigating the possible excessive LD. The finite element code ABAQUS is used to build the numerical model of the bridge and calculate the dynamic characteristics as well as the seismic responses. Then, 24 cases with different parameters of elastic links and viscous dampers are investigated and it is observed that the mitigation effect of the 24 cases varies significantly with different parameters. To obtain the optimized mitigation effect for seismic responses, including the LD of the girder, the LD and shear force of all towers, in the 24 cases, the modified analytic hierarchy process (AHP) method is introduced to realize the compositive optimal control of the triple-tower suspension bridge. Results show that the 24th case is the optimal one in which the LD of the girder is reduced significantly while the inner force of towers does not get excessive increase. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is characterized by persistent pulmonary vasoconstriction and pulmonary vascular remodeling. The pathogenic mechanisms of PAH remain to be fully clarified and measures of effective prevention are lacking. Recent studies; however, have indicated that epigenetic processes may exert pivotal influences on PAH pathogenesis. In this review, we summarize the latest research findings regarding epigenetic regulation in PAH, focusing on the roles of non-coding RNAs, histone modifications, ATP-dependent chromatin remodeling and DNA methylation, and discuss the potential of epigenetic-based therapies for PAH. [ABSTRACT FROM AUTHOR]

This study aimed to use long-term diazoxide treatment to establish a loss-of-cardioprotection model and then perform proteomics analysis to explore which proteins of mitochondrial inner membrane (MIM) are potentially involved in delayed cardioprotection. Rats received 1 to 8 weeks of diazoxide treatments (20 mg•kg–1•d–1) to establish a loss-of-cardioprotection model in different groups. Detection of serum cTnI levels and cell apoptosis assays in heart tissue were performed. Then, rats MIM after 0, 4 and 6 weeks of diazoxide treatment was isolated and proteomics analysis was performed. An invitro model of H9C2 cells was performed to explore the effects of targeted protein on delayed cardioprotection. The effect of delayed cardioprotection by diazoxide preconditioning disappeared when diazoxide treatments were given for six weeks or longer. Ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) was identified in the proteomics analysis. UQCRC1 expression was upregulated by diazoxide treatment in H9C2 cells, and UQCRC1 down-regulation could increase the lactate dehydrogenase release and apoptosis rate after injury induced by oxygen glucose deprivation. These results showed that UQCRC1 might contribute to the loss-of-cardioprotection model induced by long-term diazoxide treatment and play a role in delayed cardioprotection. [ABSTRACT FROM AUTHOR]

Exploring effective microwave absorption materials is always a challenge especially in the relatively low frequency range of 2–8 GHz and broad absorption band. Here we developed a Fe 3 C/helical carbon nanotube (HCNT) hybrid structures synthesized via catalytic chemical vapor deposition (CCVD) using Fe 3 O 4 nanoparticles as catalyst. The microwave-absorbing characteristics of such hybrid nanomaterials were investigated based on the transmission line theory through the evaluation of the experimental data including complex permittivity and permeability. Considering the reaction temperature range of 400–750 °C, the as-prepared hybrid synthesized at 700 °C can be adjusted to have effective performance of RL value less than −10 dB in the relatively lower frequency ranged from 2.9 GHz to 9.9 GHz at the thickness range of 2–5 mm. Furthermore, the hybrid in case of 750 °C bears bandwidths with RL lower than −10 dB from 7.3 GHz to 18 GHz and the minimum RL is about −21 dB. The observed advantageous reflection loss was attributed to the pronounced impedance match owing to the reasonable synergistic effect between magnetic nanoparticles and HCNTs. [ABSTRACT FROM AUTHOR]

High altitude polycythemia (HAPC) is a serious public health problem among Han Chinese immigrants to the Qinghai–Tibetan Plateau. This study aims to explore the genetic basis of HAPC in the Han Chinese population. 484 male subjects (234 patients and 250 controls) were enrolled in this study. Genotyping was performed for polymorphisms of I/D in ACE, C1772T and G1790A in exon 12 of HIF-1α, rs2567206 in CYP1B1, rs726354 in SENP1, rs3025033 in VEGFA, rs7251432 in HAMP, rs2075800 in HSPA1L and rs8065364 in CARD14. Gene–gene interaction was assessed by multifactor dimensionality reduction. A significant association was seen between CARD14 polymorphism rs8065364 and risk of HAPC development in male Han Chinese, and the C allele of rs8065364 was a risk factor (odds ratio (OR) = 1.59, 95% confidence interval (95% CI) = 1.21–2.08). Gene–gene interaction analysis indicated that a synergistic relationship existed between rs3025033 and rs8065364 (1.00%), rs3025033 and rs726354 (0.18%), and rs726354 and rs8065364 (0.17%). The combination of rs8065364 in CARD14, rs3025033 in VEGFA and rs726354 in SENP1 was the best model to predict HAPC development in this study (testing accuracy = 0.6183, p = 0.0010, cross-validated consistency = 10/10). Genetic interactions of SNPs in CARD14, SENP1 and VEGFA might represent a functional mechanism in the pathogenesis of HAPC. [ABSTRACT FROM AUTHOR]

Angiotensin II (Ang II) stimulates endothelin (ET-1) transcription, which contributes to cardiac hypertrophy and fibrosis. We have previously reported that myocardin related transcription factor A (MRTF-A) is indispensable for ET-1 transcription in vascular endothelial cells under hypoxic conditions, indicating that MRTF-A might mediate Ang II-induced pathological hypertrophy. Here we report that Ang II augmented the expression of MRTF-A in cultured endothelial cells and in the lungs of mice with cardiac hypertrophy. Over-expression of MRTF-A enhanced, whereas depletion of MRTF-A attenuated, transcriptional activation of ET-1 gene by Ang II. MRTF-A deficiency ameliorated Ang II induced cardiac hypertrophy and fibrosis in mice paralleling diminished synthesis and release of ET-1. Mechanistically, MRTF-A was recruited to the ET-1 promoter by c-Jun/c-Fos (AP-1) in response to Ang II treatment. Once bound, MRTF-A altered the chromatin structure by modulating histone acetylation and H3K4 methylation on the ET-1 promoter. More importantly, mice with endothelial-specific MRTF-A silencing by lentiviral particles phenocopied mice with systemic MRTF-A deletion in terms of Ang II-induced pathological hypertrophy. In conclusion, we data have unveiled a MRTF-A-containing complex that links ET-1 transactivation in endothelial cells to cardiac hypertrophy and fibrosis by Ang II. [ABSTRACT FROM AUTHOR]

Hypoxia induced pulmonary hypertension (HPH) represents a complex pathology that involves active vascular remodeling, loss of vascular tone, enhanced pulmonary inflammation, and increased deposition of extracellular matrix proteins. Megakaryocytic leukemia 1 (MKL1) is a transcriptional regulator known to influence cellular response to stress signals in the vasculature. We report here that in response to chronic hypobaric hypoxia, MKL1 expression was up-regulated in the lungs in rats. Short hairpin RNA (shRNA) mediated depletion of MKL1 significantly ameliorated the elevation of pulmonary arterial pressure in vivo with a marked alleviation of vascular remodeling. MKL1 silencing also restored the expression of NO, a key vasoactive molecule necessary for the maintenance of vascular tone. In addition, hypoxia induced pulmonary inflammation was dampened in the absence of MKL1 as evidenced by normalized levels of pro-inflammatory cytokines and chemokines as well as reduced infiltration of pro-inflammatory immune cells in the lungs. Of note, MKL1 knockdown attenuated fibrogenesis in the lungs as indicated by picrosirius red staining. Finally, we demonstrate that MKL1 mediated transcriptional activation of type I collagen genes in smooth muscle cells under hypoxic conditions. In conclusion, we data highlight a previously unidentified role for MKL1 in the pathogenesis of HPH and as such lay down groundwork for future investigation and drug development. [ABSTRACT FROM AUTHOR]

Hypobaric hypoxia is the primary cause of high altitude polycythemia (HAPC). Mitochondria are critical organelles that consume high levels of oxygen and generate ATP. We hypothesize that the mitochondrion may be at the center of HAPC, and mitochondrial DNA (mtDNA) SNPs may be involved in its development. First, we conducted a case-control study to investigate the association of mtDNA variants with HAPC in Han Chinese migrating to the Qinghai-Tibetan Plateau. Pearson’s chi-square tests revealed that mtDNA 8414T (MU) frequency (19.5%) in the HAPC group was significantly higher than that of the control (13.0%, P = 0.04, OR = 1.615, 95%CI: 1.020–2.555). The multivariate logistic regression analysis, after adjustment for environmental factors, revealed that mtDNA 10609T (WT) was significantly associated with an increased risk of HAPC (P<0.01, OR = 2.558, 95%CI: 1.250–5.236). Second, to verify the association, in vitro experiments of transmitochondrial cybrids was performed and revealed that the mtDNA 10609 variant promoted hypoxia-induced increase of intracellular ROS, but the mtDNA 8414 variant did not. Our findings provide evidence that, in Han Chinese, mtDNA 10609T promotes hypoxia-induced increase of intracellular ROS and is a HAPC risk factor. [ABSTRACT FROM AUTHOR]

Aims Establishment of an inflammatory milieu following elevated leukocyte adhesion to the vascular endothelium, which is mediated by transcriptional activation of cell adhesion molecules (CAMs), contributes to the pathogenesis of chronic hypoxia-induced pulmonary hypertension (HPH). The epigenetic switch that dictates CAM transactivation in response to hypoxia in endothelial cells leading up to HPH is not fully appreciated. Methods and results We report here that brahma-related gene 1 (Brg1) and brahma (Brm), two catalytic components of the mammalian chromatin remodelling complex, were induced in cultured endothelial cells challenged with hypoxia in vitro as well as in pulmonary arteries in an animal model of HPH. Over-expression of Brg1/Brm enhanced, while the depletion of Brg1/Brm attenuated, CAM transactivation and adhesion of leukocytes. Endothelial-specific deletion of Brg1/Brm ameliorated vascular inflammation and HPH in mice. Chromatin immunoprecipitation (ChIP) and re-ChIP assays revealed that hypoxia up-regulated the occupancies of Brg1 and Brm on CAM promoters in a nuclear factor κB (NF-κB) -dependent manner. Finally, Brg1 and Brm activated CAM transcription by altering the chromatin structure surrounding the CAM promoters. Conclusion Our data suggest that Brg1 provides the crucial epigenetic link to hypoxia-induced CAM induction and leukocyte adhesion that engenders endothelial malfunction and pathogenesis of HPH. As such, targeting Brg1 in endothelial cells may yield promising strategies in the intervention and/or prevention of HPH. [ABSTRACT FROM PUBLISHER]

A nucleolus as a prominent sub-nuclear, membraneless organelle plays a crucial role in ribosome biogenesis, which is in the major metabolic demand in a proliferating cell, especially in aggressive malignancies. We develop a γ -glutamyltranspeptidase (GGT)-activatable indole-quinolinium (QI) based cyanine consisting of a novel tripeptide fragment (Pro-Gly-Glu), namely QI-PG-Glu as a turn-on red fluorescent probe for the rapid detection of GGT-overexpressed A549 cancer cells in vivo. QI-PG-Glu can be triggered by GGT to rapidly release an activated fluorophore, namely HQI , in two steps including the cleavage of the γ -glutamyl group recognized by GGT and the rapid self-driven cyclization of the Pro-Gly linker. HQI exhibits dramatically red fluorescence upon binding to rRNA for imaging of nucleolus in live A549 cells. HQI also intervenes in rRNA biogenesis by declining the RNA Polymerase I transcription, thus resulting in cell apoptosis via a p53 dependent signaling pathway. Our findings may provide an alternative avenue to develop multifunctional cancer cell-specific nucleolus-targeting fluorescent probes with potential anti-cancer effects. [Display omitted] • A turn-on fluorescent probe (QI-PG-Glu) can be triggered by the γ-glutamyltranspeptidase (GGT) for A549 cell detection. • The activated probe shows dramatic red fluorescence responds upon binding to rRNA in the nucleolus. • A fast tissue penetration allows probes to respond to the GGT-enriched subcutaneous tumor in vivo. • The probe induces cancer cell apoptosis via a p53 signaling pathway by declining the RNA Polymerase I transcription. [ABSTRACT FROM AUTHOR]

The mitochondrion is an important cellular component responsible for regulating energy, oxidative metabolism, and acclimatization to high altitude. This study is aimed at investigating the impact of long-term exposure to hypoxia on the amount of mitochondrial DNA (mtDNA) in rat livers. Male Sprague-Dawley rats were randomized and exposed to normoxia (group I), or 5,000 m (barometric pressure about 405.35 mmHg) above the sea level (a hypoxic condition) for 23 and 1 h normoxia daily for five consecutive days (group II), 15 days (group III), and 30 days (group IV), respectively. The levels of plasma malondialdehyde (MDA), homocysteine (Hcy), superoxide dismutase (SOD), and alanine aminotransferase (ALT), the contents of liver mtDNA, mitochondrial transcription factor A (mtTFA), cytochrome oxidase 1 (COX1), COX2, and COX3 mRNA transcripts, and mitochondrial respiratory activity were examined immediately after the last cycle. In comparison with that in control rats, 5-15 cycles of hypoxia/normoxia significantly increased the levels of plasma MDA and ALT, but reduced the levels of Hcy and SOD, accompanied by impairing liver respiratory function in rats. Long-term (30) cycles of hypoxia/normoxia reduced the levels of plasma MDA and ALT, but increased the levels of SOD and Hcy, accompanied by decreased mtTFA expression and mtDNA amount, improved mitochondrial respiratory function in rat liver, when compared that of 5-15 cycles of hypoxia/normoxia. Our data indicate that long-term cycles of hypoxia/normoxia increases the amount of mtDNA and up-regulates COX expression, contributing to acclimatization to very high altitude in rats. [ABSTRACT FROM AUTHOR]

AbstractLuo, Yongjun, Yu Chen, Yao Zhang, and Yuqi Gao. The Association of Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphisms with Acute Mountain Sickness Susceptibility: A Meta-Analysis. High Alt Med Biol13:252–257, 2012.—Altitude exposure in nonacclimatized subjects may lead to acute mountain sickness (AMS). AMS is defined as headache upon recent arrival to altitude and may be accompanied by loss of appetite, nausea or vomiting, dizziness, fatigue, and poor sleep. Susceptibility for AMS varies and has been linked to angiotensin-converting enzyme (ACE) gene polymorphisms. We performed a meta-analysis of studies to assess the association between the ACEdeletion (D) and insertion (I) alleles and AMS from published data. A fixed effects model was applied and study quality was assessed in duplicate. Five studies with a total of 333 AMS cases and 373 healthy controls were assessed. Our results revealed no significant differences in risk for AMS between carriers of ACE deletion and insertion polymorphism alleles. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Oral epidemiologic investigations in China western territory have showed that the immigrants in the plateau have a higher morbidity with periodontitis. To find the possible relationship between the pathogenesis of periodontitis and altitude hypoxia, we designed a periodontitis rat model via housed in low pressure oxygen chamber and investigated the bacterial diversity in the gingival crevicular fluid (GCF). Design: Eighty Sprague-Dawley rats were divided into CON-normal, CON-hypoxia, EXP-normal and EXP-hypoxia group, without or with periodontal induce, breeding in normal environment or altitude hypoxia environment. Periodontal parameters (including gingival index, GI, and tooth mobility, TM) were measured after 2, 4, 6 and 8 weeks; periodontal samples were collected for histological analysis after rats were sacrificed at the 8th week. The 16S rDNA of bacteria in GCF was amplified by PCR at the 8th week, and separated by the denaturing gradient gel electrophoresis (DGGE) approach. Results: EXP-hypoxia group''s GI and TM showed later and more severe periodontal tissue damage than EXP-normal (p <0.05 or 0.01). The histologic analyses did not find any pathologic difference between EXP-hypoxia and EXP-normal groups except for a slight difference on the lesion degree. By the DGGE analyses, the bacteria of five samples in the same group showed high concordance, but the bacteria in the different groups showed a great diversity. Conclusion: The course of periodontitis in altitude hypoxia environment is later than normal, but the degree of periodontal lesion was more severe and microbial community in GCF can be affected by the altitude hypoxia environment. [Copyright &y& Elsevier]

Objective: Mitochondria are factories for energy production and genetic alterations in mtDNA will directly impact OXPHOS function. The copy number of mtDNA (i.e., the number of mtDNA per spermatozoon) is one of the major mitochondrial genetic features. Besides mtDNA copy number, the change of either mtDNA or nDNA integrity is another important factor causing asthenospermia, or poor sperm motility in infertile men. In this study, we investigated the mtDNA copy number and the integrities of mtDNA and nDNA respectively in semen samples from different donors at 5,300 m altitudes. Methods: Total DNA was extracted from semen samples from donors in two different altitudes. Quantitative PCR was performed to evaluate the mtDNA copy number. PCR amplification was used to examine the integrity of sperm mtDNA. Flow cytometry was carried out to investigate sperm nDNA integrity. All data were analyzed to show the statistical significance. Results: Sperm mtDNA copy number for those living at high altitude (5,300 m) for one month was significantly higher ( P < 0.05) than for those at the lower altitude (1,400 m) or in donors who had been living at the 5,300 m altitude for 1 year. In addition, sperm mtDNA copy numbers were remarkably decreased ( P < 0.05) in those who had lived at the greater altitude for 1 year compared to those who had lived there for one month. The ratio of nDNA integrity among the 10,000 sperms at high altitude for one month was significantly lower ( P < 0.05) than that at the lower altitude (1,400 m) or at 5,300 m for 1 year, and the ratio of nDNA integrity sperms at high altitude for 1 year was increased, and higher than that for at the lower altitude ( P < 0.05). Conclusion: High altitude can alter the mtDNA copy number and nDNA integrity in the sperms. [ABSTRACT FROM AUTHOR]

Tibetans are well adapted to living and thriving in high-altitude environments. Mitochondria are central links to oxygen consumption, and variations in mitochondrial DNA (mtDNA) could play a role in high-altitude adaptation. Alleles at several polymorphic sites in mtDNA define common haplotypes, or haplogroups, including some that have been implicated in the risk of developing certain diseases. However, few reports have determined whether relationships exist between haplogroups and high-altitude adaptation in the Tibetan population. The D4 haplogroup is a major haplogroup of the Han Chinese. In the present study, genotypes of 12 polymorphisms were determined in members of a Tibetan population ( n == 72), low altitude-Han (la-Han, n == 144), and high altitude-Han (ha-Han, n == 227) populations using polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction-ligase detection reaction assays. The mitochondrial haplogroup D4 was negatively associated with high-altitude adaptation in Tibetans ( P == 0.001 vs. la-Han, OR == 0.166, 95% CI == 0.048-0.567; P == 0.009 vs. ha-Han OR == 0.232, 95% CI == 0.069-0.778). The frequency of the nt3010G-nt3970C haplotype was significantly higher in Tibetans than in la-Han ( P == 0.000) and ha-Han ( P == 0.001) subjects. Findings in the present study suggest that unique mitochondrial variations determine a genetic background that is associated with high-altitude adaptation in the Tibetan population. [ABSTRACT FROM AUTHOR]

Background: The identification of human mitochondrial DNA (mtDNA) sequence variations, especially single nucleotide polymorphisms (SNPs), is important for many applications. The PCR-ligase detection reaction (LDR) method can reduce false-positives and eliminate the need for both post-PCR and post-ligation purifications in SNP analyses. In addition, it has been successfully employed to detect point mutations in various nuclear genes. In this study, we used the PCR-LDR platform to characterize mtDNA SNPs. Methods: Multiplex PCR-LDRs were used to genotype 19 mtDNA single nucleotide polymorphic sites from 812 samples. Performance of the method was assessed by direct sequencing of 44 samples. Results: We established an overall 97.4% success rate with 99.2% accuracy using the multiplex PCR-LDR methodology. Conclusions: The PCR-LDR mtDNA genotyping technique is simple, highly accurate, has high-throughput, and is cost-effective. Therefore, this method is applicable to mtDNA haplotyping in various applications. Clin Chem Lab Med 2010;48:475–83. [ABSTRACT FROM AUTHOR]