Identification of key genes related to heart failure by analysis of expression profiles.

Introduction: To elucidate the candidate biomarkers involved in the pathogenesis process of heart failure (HF) via analysis of differentially expressed genes (DEGs) of the dataset from the Gene Expression Omnibus (GEO). Material and methods: The GSE76701 gene expression profiles regarding the HF and control subjects were respectively analysed. Briefly, DEGs were firstly identified and subjected to Cytoscape plug-in ClueGO + CluePedia and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A protein-protein interaction (PPI) network was then built to analyse the interaction between DEGs, followed by the construction of an interaction network by combining with hub genes with the targeted miRNA genes of DEGs to identify the key molecules of HF. In addition, potential drugs targeting key DEGs were sought using the drug-gene interaction database (DGIdb), and a drug-mRNA-miRNA interaction network was also constructed. Results: A total of 489 DEGs were verified between HF and control, which mainly enriched in type I interferon and leukocyte migration according to molecular function. Significantly increased levels of GAPDH, GALM1, MMP9, CCL5, and GNAL2 were found in the HF setting and were identified as the hub genes based on the PPI network. Furthermore, according to the drug-mRNA-miRNA network, FCGR2B, CCND1, and NF-κb, as well as corresponding miRNA-605-5p, miRNA-147a, and miRNA-671-5p were identified as the drug targets of HF. Conclusions: The hub genes GAPDH, GALM1, MMP9, CCL5, and GNAL2 were significantly increased in HF. miRNA-605-5p, miRNA-147a, and miRNA-671-5p were predicted as the drug target-interacted gene-miRNA of HF.

Assessment of in-situ monitoring and tracking the vertical migration of cyanobacterial blooms using LISST-HAB.

Cyanobacterial harmful algal blooms (cyanoHABs) are becoming increasingly common in aquatic ecosystems worldwide. However, their heterogeneous distributions make it difficult to accurately estimate the total algae biomass and forecast the occurrence of surface cyanoHABs by using traditional monitoring methods. Although various optical instruments and remote sensing methods have been employed to monitor the dynamics of cyanoHABs at the water surface (i.e., bloom area, chlorophyll a), there is no effective in-situ methodology to monitor the dynamic change of cell density and integrated biovolume of algae throughout the water column. In this study, we propose a quantitative protocol for simultaneously measurements of multiple indicators (i.e., biovolume concentration, size distribution, cell density, and column-integrated biovolume) of cyanoHABs in water bodies by using the laser in-situ scattering and transmissometry (LISST) instrument. The accuracy of measurements of the biovolume and colony size of algae was evaluated and exceeded 95% when the water bloom was dominated by cyanobacteria. Furthermore, the cell density of cyanobacteria was well estimated based on total biovolume and mean cell volume measured by the instrument. Therefore, this methodology has the potential to be used for broader applications, not only to monitor the spatial and temporal distribution of algal biovolume concentration but also monitor the vertical distribution of cell density, biomass and their relationship with size distribution patterns. This provides new technical means for the monitoring and analysis of algae migration and early warning of the formation of cyanoHABs in lakes and reservoirs.

Insulin resistance and coronary inflammation in patients with coronary artery disease: a cross-sectional study.

BACKGROUND: Insulin resistance (IR) is associated with coronary artery disease (CAD) severity. However, its underlying mechanisms are not fully understood. Therefore, our study aimed to explore the relationship between IR and coronary inflammation and investigate the synergistic and mediating effects of coronary inflammation on the association between IR and CAD severity. METHODS: Consecutive patients with CAD who underwent coronary angiography and coronary computed tomography angiography between April 2018 and March 2023 were enrolled. The triglyceride-glucose index (TyG index) and peri-coronary adipose tissue (PCAT) attenuation around the proximal right coronary artery (RCA) were used to evaluate IR and coronary inflammation, respectively. The correlation between the TyG index and PCAT attenuation was analyzed using linear regression models. Logistic regression models were further used for investigating the correlation of the TyG index and PCAT attenuation with CAD severity. A mediation analysis assessed the correlation between IR and CAD severity mediated by coronary inflammation. RESULTS: A total of 569 participants (mean age, 62 ± 11 years; 67.8% men) were included in the study. PCAT attenuation was positively associated with the TyG index (r = 0.166; P < 0.001). After adjusting for potential confounders, the per standard deviation increment in the TyG index was associated with a 1.791 Hounsfield unit (HU) increase (95% confidence interval [CI], 0.920-2.662 HU; P < 0.001) in the PCAT attenuation. In total, 382 (67.1%) patients had multivessel CAD. The patients in the high-TyG index/high PCAT attenuation group had approximately 3.2 times the odds of multivessel CAD compared with those in the low-TyG index/low PCAT attenuation group (odds ratio, 3.199; 95%CI, 1.826-5.607; P < 0.001). Mediation analysis indicated that PCAT attenuation mediated 31.66% of the correlation between the TyG index and multivessel CAD. CONCLUSIONS: The TyG index positively correlated with PCAT attenuation in patients with CAD. The TyG index and PCAT attenuation showed a synergistic correlation with multivessel CAD. Furthermore, PCAT attenuation partially mediated the relationship between the TyG index and CAD severity. Controlling inflammation in patients with high IR and coronary inflammation may provide additional benefits.

Distribution characteristics of reactive silicon in six water bodies in the Yangtze River Basin in China.

Terrestrial silicon (Si) from biogeochemically weathered rocks and soils into oceans must pass through several water bodies, resulting in some Si immobilized. Hence, the knowledge on Si distribution characteristics in different water bodies at a basin scale is helpful to understand Si immobilization. A total of 65 surface sediments and corresponding overlying water samples were sampled from six water bodies (Dianchi Lake, DL; Dadu River, DR; Tuojiang River, TR; Honghu Lake, HL; Donghu Lake, DhL; Taihu Lake, TL) in the Yangtze River Basin of China, total dissolved Si (TDSi) in overlying water and exchangeable Si (Ex-Si), active non-biogenic Si (NBSi), and total acid dissolved Si (TADSi) in sediments were analyzed. Water chemical parameters (pH, EC, and TDP) and sediment components (LOI, TN, TP, and TADFe) showed that the water environment characteristics of six water bodies differed. TDSi differed among regions and between lakes and rivers, significantly higher in water bodies in the upper reaches and rivers than the middle or lower reaches and lakes (p < 0.05), respectively. Ex-Si in sediments in the upper reaches was significantly higher than in the middle or lower reaches (p < 0.05), except for DhL, whose Ex-Si was the highest. Mean TADSi and active NBSi were significantly higher in lakes than rivers (p < 0.05). Oxidation of sediments significantly increased TDSi in overlying water and active NBSi in sediments (p < 0.01). Si forms in six water bodies significantly depended on components of the sediments (e.g. active Ca2+, Mg2+, Fe, and Al3+) and water chemical parameters (p < 0.05). Our results suggest that immobilization of Si in water bodies in the Yangtze River Basin depends on the types of water bodies and sediments, lakes and Fe-Al dominated sediments have a high potential to immobilize Si, but anthropogenic interference should not be ignored.

Caspase-3/gasdermin-E axis facilitates the progression of coronary artery calcification by inducing the release of high mobility group box protein 1.

Coronary artery calcification (CAC) is commonly observed in atherosclerotic plaques, which is a pathogenic factor for severe coronary artery disease (CAD). The phenotype changes of vascular smooth muscle cells (VSMCs) are found to participate in CAC progression, which is mainly induced by vascular inflammation and oxidative stress (OS). HMGB1, a critical inflammatory cytokine, is recently reported to induce arterial calcification, which is regulated by the Caspase-3/gasdermin-E (GSDME) axis. However, the function of the Caspase-3/GSDME axis in CAC is unknown. Herein, the involvement of the Caspase-3/GSDME axis in CAC was studied to explore the possible targets for CAC. CAC model was constructed in mice, which was verified by red cytoplasm in coronary artery tissues, increased macrophage infiltration, aggravated inflammation, and enhanced RAGE signaling, accompanied by an increased release of HMGB1 and an activated Caspase-3/ GSDME axis. In ß-GP-treated MOVAS-1 cells, calcification, the ROS accumulation, enhanced LDH and HMGB1 release, enlarged macrophage production, aggravated inflammation, and activated RAGE signaling were observed, which were markedly abolished by the transfection of si-HMGB1 and si-GSDME. Moreover, the calcification deposition, the activity of Caspase-3/ GSDME axis, release of HMGB1, macrophage infiltration, cytokine production, and RAGE signaling in CAC mice were notably alleviated by VSMCs-specific GSDME knockdown, not by hematopoietic stem cells (HSCs)-specific GSDME knockdown. Collectively, Caspase-3/GSDME axis facilitated the progression of CAC by inducing the release of HMGB1.

Evaluation of sediment phosphorus dynamics in cascade reservoir systems: A case study of Weiyuan River, China.

Reservoirs tend to accumulate phosphorus (P) originating from agriculture, industry, and other upstream sources in sediment, with this stored P later released. However, the spatiotemporal dynamics of sediment P release in reservoirs remains unclear. This study investigated the spatiotemporal dynamics in P of the sediment and water of three cascade reservoirs in the Weiyuan River (Tuojiang tributary). The results showed elevated P in sediment [total P (TP): 1208.93 mg kg-1] and water (TP: 0.23 mg L-1) during the low-water season (LWS), which could be attributed to notably higher organic matter content (9.65%), finer particle size (20.95 µm), and extended hydraulic retention time (HRT: 13.13 days) downstream of the cascade reservoirs. Further study employing static in-situ diffusive gradient in thin films (DGT) and dynamic ex-situ adsorption kinetic experiments confirmed that the downstream release of P from sediments [diffusion flux (Fd): 1.67 mg m-2 d-1, equilibrium P concentrations (EPC0): 0.22 ± 0.10 mg L-1] greatly exceeded those upstream (-0.66 ± 0.17 mg m-2 d-1, 0.07 ± 0.001 mg L-1), Fe (II) was a critical factor in regulating sedimentary P release. The combined effects of high P in overlying water and sediment significantly stimulated downstream phytoplankton growth, particularly among cyanobacteria (26.48%) and green algae (8.33%). Further regulatory steps are needed to regulate LWS algal blooms downstream of cascade reservoirs.

Applications of Carbon Dots for the Treatment of Alzheimer's Disease.

There are currently approximately 50 million victims of Alzheimer's disease (AD) worldwide. The exact cause of the disease is unknown at this time, but amyloid plaques and neurofibrillary tangles in the brain are hallmarks of the disease. Current drug treatments for AD may slow the progression of the disease and improve the quality of life of patients, but they are often only minimally effective and are not cures. A major obstacle to developing and delivering more effective drug therapies is the presence of the blood-brain barrier (BBB), which prevents many compounds with therapeutic potential from reaching the central nervous system. Nanotechnology may provide a solution to this problem. Among the medical nanomaterials currently being studied, carbon dots (CDs) have attracted widespread attention because of their ability to cross the BBB, non-toxicity, and potential for drug/gene delivery.

Numerical Investigations of Urban Pollutant Dispersion and Building Intake Fraction with Various 3D Building Configurations and Tree Plantings.

Rapid urbanisation and rising vehicular emissions aggravate urban air pollution. Outdoor pollutants could diffuse indoors through infiltration or ventilation, leading to residents' exposure. This study performed CFD simulations with a standard k-ε model to investigate the impacts of building configurations and tree planting on airflows, pollutant (CO) dispersion, and personal exposure in 3D urban micro-environments (aspect ratio = H/W = 30 m, building packing density λp = λf = 0.25) under neutral atmospheric conditions. The numerical models are well validated by wind tunnel data. The impacts of open space, central high-rise building and tree planting (leaf area density LAD= 1 m2/m3) with four approaching wind directions (parallel 0° and non-parallel 15°, 30°, 45°) are explored. Building intake fraction is adopted for exposure assessment. The change rates of demonstrate the impacts of different urban layouts on the traffic exhaust exposure on residents. The results show that open space increases the spatially-averaged velocity ratio (VR) for the whole area by 0.40−2.27%. Central high-rise building (2H) can increase wind speed by 4.73−23.36% and decrease the CO concentration by 4.39−23.00%. Central open space and high-rise building decrease under all four wind directions, by 6.56−16.08% and 9.59−24.70%, respectively. Tree planting reduces wind speed in all cases, raising by 14.89−50.19%. This work could provide helpful scientific references for public health and sustainable urban planning.

Impact of river dams on phosphorus migration: a case of the Pubugou Reservoir on the Dadu River in China.

Reservoirs in agricultural catchments retain large proportions of inflowing phosphorus (P). However, the effects of reservoirs on the P cycle and related biogeochemical processes remain unclear. Therefore, this study investigated the degree to which a typical river-transition-reservoir in Southwest China retains both inflowing particulate phosphorus (PP) and dissolved total phosphorus (DTP) and various forms of P in sediments over different water seasons [normal-water season (NWS), low-water season (LWS), and high-water season (HWS)]. The proportions of inflowing PP and DTP retained were 37% and 27%, respectively. This result could be attributed to the absorption of DTP by the large load of intercepted sediment in the dam and the interception of PP itself. The rank of water seasons in terms of the proportion and load of inflowing TP retained was LWS (79%, 336 t P yr-1) > NWS (21%, 43 t P yr-1) > HWS (4%, 27 t P yr-1), which might be due to the high P concentration 0.78 mg L-1 and long hydraulic retention time (HRT) 780 d during the LWS. In the long-term, there was a high rate of retention of bioavailable phosphorus (BAP) in sediments (63%). This result could be attributed to the combined effect of fine sediment particles and organic matter (OM). In addition, HRT (R2 = 0.89, p < 0.05) affected the retention of P more significantly than P concentration (R2 = 0.56, p < 0.05). Dam interception during the LWS resulted in high BAP contents (280 mg kg-1) in sediments, high P concentrations (0.78 mg L-1), and weak hydrodynamics (HRT: 780 d) in overlying water. Therefore, further regulatory measures are urgently demanded during the LWS to prevent reservoir algal blooms.

Histone deacetylase HDAC4 participates in the pathological process of myocardial ischemia-reperfusion injury via MEKK1/JNK pathway by binding to miR-206.

Histone deacetylases (HDACs) and microRNAs (miRs) have been reported to exert pivotal roles on the pathogenesis of myocardial ischemia-reperfusion injury (MIRI). Therefore, the present study was performed to define the underlying role of HDAC4 and miR-206 in the pathological process of MIRI. An IRI rat model was established. The interaction between HDAC4 and the promoter region of miR-206 was determined using ChIP, and that between miR-206 and mitogen-activated protein kinase kinase kinase 1 (MEKK1) was determined using dual luciferase reporter gene assay. After the loss- or gain-of-function assay in cardiomyocytes, western blot analysis, RT-qPCR, TUNEL, and ELISA assay were performed to define the roles of HDAC4, miR-206, and MEKK1. Up-regulation of HDAC4 and down-regulation of miR-206 occurred in rat myocardial tissues and cardiomyocytes in MIRI. HDAC4 down-regulation or miR-206 up-regulation contributed to reduced cell apoptosis and the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and malondialdehyde (MDA), while elevating the superoxide dismutase (SOD) and glutathione (GSH) contents. Meanwhile, HDAC4 silencing promoted the expression of miR-206, which targeted and negatively regulated MEKK1. Then inhibition of JNK phosphorylation reduced the cardiomyocyte apoptosis to alleviate MIRI. Coherently, HDAC4 silencing could up-regulate the expression of miR-206 to reduce cardiomyocyte apoptosis and inhibit oxidative stress, and exerting a protective effect on MIRI via the MEKK1/JNK pathway.

Available acid consumption capacity of sediments in six water bodies in the Yangtze River Basin in China.

Acid-base reactivity is a fundamental property of sediments and is responsible for sediments' multiple roles in aquatic ecosystems. However, little information currently exists about the composition, magnitude, and change of the available acid consumption capacity (AACC) of sediments. To optimize reaction conditions, we developed operational procedures to determine AACC using base titration to recover surplus acid in suspensions. We characterized the sediment AACC of Dianchi Lake (DL), Daduhe River (DR), Tuojiang River (TR), Honghu Lake (HL), Wuhan Donghu Lake (DhL), and Taihu Lake (TL) in the Yangtze River Basin, China. The procedure demonstrated that reacting 40 mL 0.1 M HCl with fresh sediments equivalent to 1.0 g dry weight for 4 h and recovering surplus acid in the suspension by NaOH titration to an endpoint pH of 3.0 could determine sediment AACC. Sediment AACC in the Yangtze River Basin had high regional variability. The mean magnitude of AACC among sites was ranked DL > DR > DhL > TR > HL > TL, which is extremely similar to their geographical location from the upper to lower reaches of the Yangtze River Basin. Qualitative results from acid titration curves showed that more components contributed to AACC in DL, DR, TR, and DhL sediments than to those in HL and TL sediments. The correlation between AACC and the total amount of multivalent cations released indicated that AACC depended significantly on labile acid-soluble minerals that contain multivalent cations (Fe3+, Fe2+, Ca2+, Al3+, Mg2+, and Mn2+) (p < 0.01). Based on the contribution percentages of multivalent cations to AACC, sediment AACC of six water bodies were divided into two types: Ca-Mg dominated (DL, DR, and TR) and Fe-Al dominated (HL, DhL, and TL). We suggest that sediment AACC complexing with pH can contribute to a better description of the acid-base characteristics of sediments.

MMP9, CXCR1, TLR6, and MPO participant in the progression of coronary artery disease.

Coronary artery disease (CAD) is the most frequent cardiovascular disease, which is induced by the decreased myocardial blood supply. The present study is conducted to understand the mechanisms of CAD. The GSE98583, GSE69587, and GSE71226 datasets from the Gene Expression Omnibus database were obtained. The differentially expressed genes (DEGs) were analyzed by the limma package, then the DEGs appeared in two or three datasets were selected as the coregulated genes using the VENNY tool, followed by enrichment analysis using DAVID tool. Protein-protein interaction (PPI) network, microRNA-transcription factor-target regulatory network, and drug-gene network were visualized. Finally, quantitative PCR and dual-luciferase reporter assay were conducted to validate the expression of key genes and the target relationship. There were 221 coregulated genes in GSE98583, GSE69587, and GSE71226. Besides, four pathways and 23 functional terms for co-upregulated genes, and 11 functional terms for co-downregulated genes were enriched. The degrees of PPI network nodes matrix metallopeptidase 9 (MMP9), C-X-C motif chemokine receptor 1 (CXCR1), toll-like receptor 6 (TLR6), and myeloperoxidase (MPO) were relatively higher. Moreover, MPO could interact with MMP9, CXCR1, and TLR6 in the PPI network. In the regulatory network, TLR6 and MMP9 separately were targeted by miR-3960 and v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA). Additionally, MMP9, CXCR1, and MPO were involved in the drug-gene network. The expression of MMP9, CXCR1, TLR6, and MPO were significantly upregulated in CAD samples than control, and miR-3960 could bind to TLR6 to inhibit its expression. CXCR1 and MPO might be involved in the progression of CAD. Besides, miR-3960 might function in the pathogenesis of CAD through targeting TLR6, and RELA might exert its role in CAD via targeting MMP9.

MicroRNA-2861 and microRNA-5115 regulates myocardial ischemia-reperfusion injury through the GPR30/mTOR signaling pathway by binding to GPR30.

Myocardial ischemia-reperfusion (I/R) injury, a major contributor to morbidity and mortality, represents a combination of intrinsic cellular response to ischemia and the extrinsic acute inflammatory response. In the present study, microarray analysis of GSE67308 and GSE50885 identified differentially expressed GPR30 and upstream regulatory miR-2861 and miR-5115 in myocardial I/R. Furthermore, GPR30 was confirmed as a common target gene of miR-2861 and miR-5115, and miR-2861 and miR-5115 inhibited GPR30 expression. Poor expression of GPR30 was identified in the myocardial I/R injury mouse model. Overexpressed GPR30 led to alleviated the pathological conditions, diminished myocardial infarct size and apoptosis of myocardial tissue in mice. Moreover, miR-2861 and miR-5115 were found to be highly expressed in the myocardial I/R injury mouse model and to subsequently accelerate the disease progression. Notably, PR30 curtailed the development of myocardial I/R injury through activation of the mTOR signaling pathway. The key findings suggested that miR-2861 and miR-5115 blocked the activation of the GPR30/mTOR signaling pathway by targeting GPR30, thereby accelerating myocardial I/R injury in mice.

Effects of sediment oxidation on phosphorus transformation in three large shallow eutrophic lakes in China.

Oxidation of surface sediments is an important means for altering phosphorus (P) exchanges across sediment-water interface (SWI) in shallow lakes. In this study, the potential and composition of regenerated oxidation capacity (OC) of surface sediments were evaluated in three large shallow lakes (Tai Lake, Chao Lake, and Dianchi Lake) in China; the transformation of sedimentary P was quantified through P fractionation scheme. The composition of the regenerated OC differed among these three lakes, with Fe(III) and SO42- dominant in Dianchi Lake, Mn(IV) and Fe(III) in Chao Lake and Tai Lake. Oxidation of sediments enhanced the transformation of sedimentary P and altered P exchanges across the SWI. In Chao Lake, the HCl-P was transformed to BD-P; in Tai Lake, the NaOH-P was involved too, and transformed to BD-P; whereas in Dianchi Lake, an increase in NH4Cl-P was also observed except for the transformation from HCl-P to BD-P. The sediment-to-water flux of P was enhanced with 0.17 mg/g DW in Dianchi Lake and 0.08 mg/g DW in Chao Lake, while a contrary water-to-sediment flux of P was observed in Tai Lake, reaching 0.01 mg/g DW. This study advances our knowledge on the impacts of sediment oxidation on P cycles in lakes, which will be beneficial to eutrophication control.

Atherosclerosis-associated endothelial cell apoptosis by miRNA let7-b-mediated downregulation of HAS-2.

MicroRNAs (miRNAs) play essential roles in the regulation and pathophysiology of various types of human diseases including atherosclerosis. Increasing numbers of miRNAs have been identified to be important regulators in the progression of atherosclerosis by regulating gene expression. However, functional miRNAs and the underlying mechanisms involved in atherosclerosis need fully elucidation. In the present study, the function of miRNA let-7b was investigated in human aortic endothelial cells (HAECs). The results showed that downregulation of let-7b in the high-fat diet mice and HAECs was inversely correlated with the expression level of HAS-2. upregulation of let-7b significantly reduced apoptosis of HAECs. The results also revealed that HAS-2 was a target gene of let-7b and HAS-2 reduction reversed the antiapoptotic effect of let-7b through regulation of the P13K/Akt pathway. These results together suggest the potential of regulating the let-7b expression and endothelial apoptosis against development and progression of atherosclerosis.

Thin-layer fine-sand capping of polluted sediments decreases nutrients in overlying water of Wuhan Donghu Lake in China.

Capping water body sediments with a thin layer of sand is an effective technique to decrease nutrient concentrations in the water column and accelerate ecological restoration of eutrophic water bodies. However, long-term effects of thin-layer sand capping in shallow lakes are reported less often. Using clean fine sand and geotextile mats as capping materials for sediments collected from Wuhan Donghu Lake in China, we designed a 290-day tank experiment with 3 cm of sand capping at four percentages of sediment coverage from 25 to 100% and a control (no capping). We monitored total nitrogen (TN), total phosphorus (TP), nitrate (NO3-), ammonia (NH4+), and soluble reactive phosphorus (SRP) in the overlying water every 7 days. Mean TN and NO3- concentrations were significantly the lowest (P < 0.05) at 50% coverage. Further increase in coverage kept them slightly fluctuating. NH4+ concentration was significantly lowest (P < 0.05) at 75% coverage. The relation between coverage and mean TP and SRP concentrations indicated that 75% coverage significantly decreased (P < 0.05) them, and increasing coverage to 100% decreased them even more. The fluxes of TN and TP estimated between sediments and overlying water showed that the thin fine-sand layer significantly increased the function of sediments as a sink of TN from overlying water and the potential of a sand layer to block release of TP from sediments (P < 0.05). Our results suggested that if thin-layer sand capping were applied to Wuhan Donghu Lake, more than 50% coverage is required to decrease nutrients in the lake's water.

FGF23 promotes myocardial fibrosis in mice through activation of ß-catenin.

Fibroblast growth factor 23 (FGF23) has been reported to induce left ventricular hypertrophy, but it remains unclear whether FGF23 plays a role in cardiac fibrosis. This study is attempted to investigate the role of FGF23 in post-infarct myocardial fibrosis in mice. We noted that myocardial and plasma FGF23 and FGF receptor 4 were increased in mice with heart failure as well as in cultured adult mouse cardiac fibroblasts (AMCFs) exposed to angiotensin II, phenylephrine, soluble fractalkine. Recombinant FGF23 protein increased active ß-catenin , procollagen I and procollagen III expression in cultured AMCFs. Furthermore, intra-myocardial injection of adeno-associated virus-FGF23 in mice significantly increased left ventricular end-diastolic pressure and myocardial fibrosis, and markedly upregulated active ß-catenin, transforming growth factor ß (TGF-ß), procollagen I and procollagen III in both myocardial infarction (MI) and ischemia/reperfusion (IR) mice, while ß-catenin inhibitor or silencing of ß-catenin antagonized the FGF23-promoted myocardial fibrosis in vitro and in vivo. These findings indicate that FGF23 promotes myocardial fibrosis and exacerbates diastolic dysfunction induced by MI or IR, which is associated with the upregulation of active ß-catenin and TGF-ß.

An innovative approach for sequential extraction of phosphorus in sediments: Ferrous iron P as an independent P fraction.

Accurate identification of phosphorus (P) forms is crucially important for understanding the geochemical cycle of P; however, until now the role of ferrous iron P (Fe(II)-P) buried in sediments has been completely ignored in nearly all sequential extraction procedures developed. Using sediment cores sampled from Donghu Lake in Wuhan, China, this study explored a modified version of widely used sequential P extraction method (SEDEX; Ruttenberg, 1992) in which Fe(II)-P was identified as an independent fraction. Based on the high selectivity of the extractant (0.2% 2,2'-bipyridine+0.1 M KCl) and the dissolution equilibrium of P, procedures for extracting Fe(II)-P were optimized using a 1:100 solid:liquid ratio and extraction at 50 ± 1 °C for 24 h. The sedimentary P extracted was divided into five fractions: loosely-bound P, Fe(II)-P, CDB-P, Ca-P and O-P. Fe(II)-P was the predominant fraction in fresh sediments in Donghu Lake, accounting for 15.7-49.9% of TP, with a mean of 31.6%. The mean values of Ca-P, O-P, CDB-P and loosely-bound P were 28.4%, 22.7%, 17.1% and 4.3%, respectively. Combined with component analysis of extracts and recovery experiments of standard reference minerals (vivianite, Fe3(PO4)2·8H2O) in natural sediments, extraction of Fe(II)-P with 0.2% 2,2-bipridine and 0.1 M KCl was robust, with a good recovery rate (88.7-100.6%) and little of the Ca-P dissolved. It is possible to use this innovative SEDEX not only to distinguish the contribution of different P matrices in fresh sediments, but also to investigate the transformation of sedimentary P under different redox conditions. Therefore, greater focus on Fe(II)-P is necessary, because it is a major sink for the geochemical process of sedimentary P.

Inhibition of microRNA-497 ameliorates anoxia/reoxygenation injury in cardiomyocytes by suppressing cell apoptosis and enhancing autophagy.

MiR-497 is predicted to target anti-apoptosis gene Bcl2 and autophagy gene microtubule-associated protein 1 light chain 3 B (LC3B), but the functional consequence of miR-497 in response to anoxia/reoxygenation (AR) or ischemia/reperfusion (IR) remains unknown. This study was designed to investigate the influences of miR-497 on myocardial AR or IR injury. We noted that miR-497 was enriched in cardiac tissues, while its expression was dynamically changed in murine hearts subjected to myocardial infarction and in neonatal rat cardiomyocytes (NRCs) subjected to AR. Forced expression of miR-497 (miR-497 mimic) induced apoptosis in NRCs as determined by Hoechst staining and TUNEL assay. In response to AR, silencing of miR-497 using a miR-497 sponge significantly reduced cell apoptosis and enhanced autophagic flux. Furthermore, the infarct size induced by IR in adenovirus (Ad)-miR-497 sponge infected mice was significantly smaller than in mice receiving Ad-vector or vehicle treatment, while Ad-miR-497 increased infarct size. The expression of Bcl-2 and LC3B-II in NRCs or in murine heart was significantly decreased by miR-497 mimic and enhanced by miR-497 sponge. These findings demonstrate that inhibition of miR-497 holds promise for limiting myocardial IR injury.

Ablation of C/EBP homologous protein increases the acute phase mortality and doesn't attenuate cardiac remodeling in mice with myocardial infarction.

Endoplasmic reticulum stress is a proapoptotic and profibrotic stimulus. Ablation of C/EBP homologous protein (CHOP) is reported to reverse cardiac dysfunction by attenuating cardiac endoplasmic reticulum stress in mice with pressure overload or ischemia/reperfusion, but it is unclear whether loss of CHOP also inhibits cardiac remodeling induced by permanent-infarction. In mice with permanent ligation of left coronary artery, we found that ablation of CHOP increased the acute phase mortality. For the mice survived to 4 weeks, left ventricular anterior (LV) wall thickness was larger in CHOP knockout mice than in the wildtype littermates, while no difference was noted on posterior wall thickness, LV dimensions, LV fractional shortening and ejection fraction. Similarly, invasive assessment of LV hemodynamics, morphological analysis of heart and lung weight indexes, myocardial fibrosis and TUNEL-assessed apoptosis showed no significant differences between CHOP knockout mice and their wildtype ones, while in mice with ischemia for 45 min and reperfusion for 1 week, myocardial fibrosis and apoptosis in the infarct area were significantly attenuated in CHOP knockout mice. These findings indicate that ablation of CHOP doesn't ameliorate cardiac remodeling induced by permanent-myocardial infarction, which implicates that early reperfusion is a prerequisite for ischemic myocardium to benefit from CHOP inhibition.