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Abstract Background Cardiovascular disease and cancer are the main causes of morbidity and mortality worldwide. Studies have shown that these two diseases may have some common risk factors. Atorvastatin is mainly used for the treatment of atherosclerosis in clinic. A large number of studies show that atorvastatin may produce anti-tumor activities. This study aimed to predict the common targets of atorvastatin against atherosclerosis and non-small cell lung cancer (NSCLC) based on network pharmacology. Methods The target genes of atherosclerosis and NSCLC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The disease–target–component model map and the core network were obtained using Cytoscape 3.7.1. The MTS and wound healing assay were used to detect the effect of atorvastatin on cell viability and migration of A549 cells. The expression of potential common target genes of atorvastatin against atherosclerosis and NSCLC were confirmed in A549 cells and lung cancer tissues of patients. Results We identified 15 identical pathogenic genes, and four of which (MMP9, MMP12, CD36, and FABP4) were considered as the key target genes of atorvastatin in anti-atherosclerosis and NSCLC. The MTS and wound healing assays revealed that atorvastatin decreased A549 cells migration significantly. Atorvastatin markedly decreased the expression of MMP9, MMP12, CD36, and FABP4 in A549 cells and patients were treated with atorvastatin. Conclusions This study demonstrated 15 common pathogenic genes in both atherosclerosis and NSCLC. And verified that MMP 9, MMP 12, CD 36 and FABP 4 might be the common target genes of atorvastatin in anti-atherosclerosis and NSCLC.

Abstract Background Phosphoglycerate mutase 5 (PGAM5), a phosphatase involved in mitochondrial homeostasis, is reported to be closely related to the metabolic stress induced by high-fat diet (HFD) or cold. In this study, we aimed to investigate the effects of PGAM5 on hepatic steatosis, inflammation and fibrosis in nonalcoholic steatohepatitis (NASH). Methods and results We generated PGAM5 global knockout (GKO) mice and their wildtype (WT) littermates using CRISPR/CAS9. The mice were fed with a high fat high fructose (HFHF) diet for 12 weeks or a methionine choline-deficient (MCD) diet (methionine choline supplemented (MCS) as control) for 6 weeks. Hepatic PGAM5 expression was up-regulated in humans with NASH and WT mice fed with HFHF and MCS, and reduced in WT mice fed with MCD diet. In HFHF-fed mice, GKO had reduced body weight, hepatic triglyceride (TG) content and serum transaminase along with decreased hepatic pro-inflammatory and pro-fibrotic responses compared with their WT control. GKO had increased expression of antioxidative gene glutathione peroxidase-6 (GPX6) and activation of mammalian target of rapamycin (mTOR). In mice fed with MCS diet, GKO significantly increased serum TNF-α and IL-6 and decreased hepatic GPX6 mRNA expression. There was no difference in hepatic steatosis, inflammation or fibrosis between GKO and WT mice fed with MCD diet. We investigated the role of PGAM5 deficiency in a variety of cell types. In differentiated THP-1 cells, PGAM5 silencing significantly increased pro-inflammatory cytokine secretion and decreased antioxidative proteins, including nuclear factor erythroid 2- related factors (NRF2), heme oxygenase-1 (HO-1) and GPX6 without affecting mTOR activity. In HepG2 cells with steatosis, PGAM5 knockdown reduced insulin sensitivity, increased mTOR phosphorylation and reduced the expression of NRF2, catalase (CAT), HO-1 and GPX6. Conversely, PGAM5 knockdown reduced TG accumulation, increased insulin sensitivity, and increased antioxidative genes in 3T3-L1 cells, despite the up-regulation in mTOR phosphorylation. Conclusions PGAM5-KO relieved hepatic steatosis and inflammation in HFHF model, promoted inflammation in MCS-fed mice and had no effects on the MCD-fed model. The distinct effects may be owing to the different effects of PGAM5-KO on anti-oxidative pathways in energy-dependent, possible involves mTOR, and/or cell type-dependent manner. Our findings suggest that PGAM5 can be a potential therapeutic target for NASH.

Abstract MRGPRX1, a Mas-related GPCR (MRGPR), is a key receptor for itch perception and targeting MRGPRX1 may have potential to treat both chronic itch and pain. Here we report cryo-EM structures of the MRGPRX1-Gi1 and MRGPRX1-Gq trimers in complex with two peptide ligands, BAM8-22 and CNF-Tx2. These structures reveal a shallow orthosteric pocket and its conformational plasticity for sensing multiple different peptidic itch allergens. Distinct from MRGPRX2, MRGPRX1 contains a unique pocket feature at the extracellular ends of TM3 and TM4 to accommodate the peptide C-terminal “RF/RY” motif, which could serve as key mechanisms for peptidic allergen recognition. Below the ligand binding pocket, the G6.48XP6.50F6.51G6.52X(2)F/W6.55 motif is essential for the inward tilting of the upper end of TM6 to induce receptor activation. Moreover, structural features inside the ligand pocket and on the cytoplasmic side of MRGPRX1 are identified as key elements for both Gi and Gq signaling. Collectively, our studies provide structural insights into understanding itch sensation, MRGPRX1 activation, and downstream G protein signaling.

BackgroundDiabetic kidney disease (DKD), one of the main complications of diabetes mellitus (DM), has become a frequent cause of end-stage renal disease. A clinically convenient, non-invasive approach for monitoring the development of DKD would benefit the overall life quality of patients with DM and contribute to lower medical burdens through promoting preventive interventions.MethodsWe utilized 5hmC-Seal to profile genome-wide 5-hydroxymethylcytosines in plasma cell-free DNA (cfDNA). Candidate genes were identified by intersecting the differentially hydroxymethylated genes and differentially expressed genes from the GSE30528 and GSE30529. Then, a protein interaction network was constructed for the candidate genes, and the hub genes were identified by the MCODE and cytoHubba algorithm. The correlation analysis between the hydroxymethylation level of the hub genes and estimated glomerular filtration rate (eGFR) was carried out. Finally, we demonstrated differences in expression levels of the protein was verified by constructing a mouse model of DKD. In addition, we constructed a network of interactions between drugs and hub genes using the Comparative Toxicogenomics Database.ResultsThis study found that there were significant differences in the overall distribution of 5hmC in plasma of patients with DKD, and an alteration of hydroxymethylation levels in genomic regions involved in inflammatory pathways which participate in the immune response. The final 5 hub genes, including (CTNNB1, MYD88, CD28, VCAM1, CD44) were confirmed. Further analysis indicated that this 5-gene signature showed a good capacity to distinguish between DKD and DM, and was found that protein levels were increased in renal tissue of DKD mice. Correlation analysis indicated that the hydroxymethylation level of 5 hub genes were nagatively correlated with eGFR. Toxicogenomics analysis showed that a variety of drugs for the treatment of DKD can reduce the expression levels of 4 hub genes (CD44, MYD88, VCAM1, CTNNB1).ConclusionsThe 5hmC-Seal assay was successfully applied to the plasma cfDNA samples from a cohort of DM patients with or without DKD. Altered 5hmC signatures indicate that 5hmC-Seal has the potential to be a non-invasive epigenetic tool for monitoring the development of DKD and it provides new insight for the future molecularly targeted anti-inflammation therapeutic strategies of DKD.

Isothiazolinone (IT) biocides are potent antibacterial substances commonly used as preservatives or disinfectants, and 2-n-Octyl-4-isothiazolin-3-one (OIT; octhilinone) is a common IT biocide that is present in leather products, glue, paints, and cleaning products. Although humans are exposed to OIT through personal and industrial use, the potentially deleterious effects of OIT on human health are still unknown. To investigate the effects of OIT on the vascular system, which is continuously exposed to xenobiotics through systemic circulation, we treated brain endothelial cells with OIT. OIT treatment significantly activated caspase-3-mediated apoptosis and reduced the bioenergetic function of mitochondria in a bEnd.3 cell-based in vitro blood–brain barrier (BBB) model. Interestingly, OIT significantly altered the thiol redox status, as evidenced by reduced glutathione levels and protein S-nitrosylation. The endothelial barrier function of bEnd.3 cells was significantly impaired by OIT treatment. OIT affected mitochondrial dynamics through mitophagy and altered mitochondrial morphology in bEnd.3 cells. N-acetyl cysteine significantly reversed the effects of OIT on the metabolic capacity and endothelial function of bEnd.3 cells. Taken together, we demonstrated that the alteration of the thiol redox status and mitochondrial damage contributed to OIT-induced BBB dysfunction, and we hope that our findings will improve our understanding of the potential hazardous health effects of IT biocides.

Background/Aims: Acute kidney injury (AKI) is a major complication of kidney transplantation, resulting in early graft dysfunction. Since diuretic acetazolamide (AZA) has been shown to improve contrast induced AKI, we hypothesized that AZA also protected against ischemia-reperfusion (I/R) caused AKI. Methods: An in vivo mouse renal I/R injury model and an in vitro H2O2 stimulated HK-2 cell injury model were utilized to examine the renoprotective effect of AZA. Renal injury and blood flow were measured. Nitric oxide synthase (eNOS)/Nitric oxide (NO), cell apoptosis and hypoxia-inducible factor-1α (HIF-1α) changes were analyzed. Results: AZA reduced kidney injury scores and improved renal function by decreasing serum creatinine and BUN levels after I/R. Impaired renal blood flow was restored by increasing eNOS activities and NO production, as indicated by Laser Doppler imaging. TUNEL staining presented that AZA reduced apoptotic cells due to attenuated caspase activation and increased Bcl-2/Bax ratio. Furthermore, HIF-1α induction by AZA was demonstrated. AZA also enhanced in vitro NO production, reduced cell apoptosis and increased HIF-1α expression. Knockdown of HIF-1α by RNAi confirmed that AZA exerted its protective role depending on HIF-1α. AZA's effects were significantly reduced by Akt inhibitor LY294002. Conclusions: The present study demonstrated that AZA exerted a renoprotective role against I/R induced AKI through activating HIF-1α and downstream pathways.

Brain-pancreas relative protein (BPRP) is a novel protein that we found in our laboratory. Previously we demonstrated that it is involved in ischemia and depression. In light of the putative association between diabetes and clinical depression, and the selective expression of BPRP in brain and pancreas, the present study examined whether BPRP levels are affected by induction of diabetes by alloxan injection in rats and exposure to high glucose levels in PC12 cells. Western blot and immunohistochemical analyses revealed that BPRP levels were decreased in the hippocampal CA1 neurons of diabetic rats 4 and 8 weeks post-alloxan injection and in PC12 cells 48 h after exposure to high concentrations of glucose. BPRP protein levels were not affected by osmolarity control treatments with mannitol. Follow-up pharmacological experiments in PC12 cells revealed that glucose-induced BPRP down-regulation was markedly attenuated by the calpain inhibitors N-acetyl-Leu-Leu-norleucinal (ALLN) or calpeptin, but not the proteasome-specific inhibitor carbobenzoxy-Leu-Leu-leucinal (MG132). The ability of calpain inhibitors to specifically counter the effects of high glucose exposure on BPRP levels further suggests that BPRP and calpain activity may contribute to diabetes complications in the central nervous system. Keywords:: brain-pancreas relative protein, diabetes, high glucose, proteasome inhibitor, calpeptin

BACKGROUND: Ulcerative colitis (UC) was the most frequently diagnosed inflammatory bowel disease (IBD) and closely linked to colorectal carcinogenesis. By far, the underlying mechanisms associated with the disease are still unclear. With the increasing accumulation of microarray gene expression profiles, it is profitable to gain a systematic perspective based on gene regulatory networks to better elucidate the roles of genes associated with disorders. However, a major challenge for microarray data analysis is the integration of multiple-studies generated by different groups. METHODOLOGY/PRINCIPAL FINDINGS: In this study, firstly, we modeled a signaling regulatory network associated with colorectal cancer (CRC) initiation via integration of cross-study microarray expression data sets using Empirical Bayes (EB) algorithm. Secondly, a manually curated human cancer signaling map was established via comprehensive retrieval of the publicly available repositories. Finally, the co-differently-expressed genes were manually curated to portray the layered signaling regulatory networks. RESULTS: Overall, the remodeled signaling regulatory networks were separated into four major layers including extracellular, membrane, cytoplasm and nucleus, which led to the identification of five core biological processes and four signaling pathways associated with colorectal carcinogenesis. As a result, our biological interpretation highlighted the importance of EGF/EGFR signaling pathway, EPO signaling pathway, T cell signal transduction and members of the BCR signaling pathway, which were responsible for the malignant transition of CRC from the benign UC to the aggressive one. CONCLUSIONS: The present study illustrated a standardized normalization approach for cross-study microarray expression data sets. Our model for signaling networks construction was based on the experimentally-supported interaction and microarray co-expression modeling. Pathway-based signaling regulatory networks analysis sketched a directive insight into colorectal carcinogenesis, which was of significant importance to monitor disease progression and improve therapeutic interventions.

BACKGROUND: Anti-angiogenic activity is considered to play a key role in the statin-induced anti-tumor effects. We aimed to identify new targets underlying this pleiotropic effect of lovastatin. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the inhibitory effects of lovastatin on endothelial cell biology and angiogenesis in vitro. Lovastatin at high doses inhibited endothelial cell migration and tube formation. Using two-dimensional gel electrophoresis followed by mass spectrometry, we identified the up-regulation of the actin-binding protein transgelin 2 in endothelial cells following treatment with lovastatin. Changes in transgelin 2 levels were confirmed by Western blot and confocal microscopy. We further demonstrated that the Rho signaling inactivation and actin depolymerization contributed to the up-regulation of transgelin 2. The knockdown of transgelin 2 by siRNA dramatically enhanced endothelial migration and tube formation, and meanwhile attenuated the inhibitory effects of lovastatin on cell motility. Moreover, the lovastatin-induced inhibition of myosin light chain phosphorylation was also reversed by transgelin 2 knockdown. The activation of Rho GTPase in the absence of transgelin 2 may represent a mechanism underlying the regulation of phosphorylated myosin light chain by transgelin 2. CONCLUSIONS/SIGNIFICANCE: These results strongly imply a novel role for transgelin 2 in the angiostatic activities of lovastatin.

BACKGROUND: Diuretic agents are widely used on the treatment of water retention related diseases, among which acetazolamide (AZA) acts originally as a carbonic anhydrase (CA) inhibitor. Aquaporin-1 (AQP1) being located in renal proximal tubules is required for urine concentration. Previously our lab has reported AZA putatively modulated AQP1. Aim of this study is to testify our hypothesis that regulating AQP1 may mediate diuretic effect of AZA. METHODOLOGY/PRINCIPAL FINDINGS: For in vivo study, we utilized Sprague Dawley rats, as well as AQP1 knock-out (AQP1(-/-)) mice to examine urine volume, and human kidney-2 (HK-2) cell line was used for in vitro mechanism study. In our present study we found that AZA decreased CAs activity initially but the activity gradually recovered. Contrarily, diuretic effect was consistently significant. AQP1 protein expression was significantly decreased on day 7 and 14. By utilizing AQP1(-/-) mice, we found diuretic effect of AZA was cancelled on day 14, while urine volume continuously increased in wild-type mice. Surface plasmon resonance (SPR) results indicated AQP1 was physiologically bound by myosin heavy chain (MHC), immunoprecipitation and immunofluorescence results confirmed this protein interaction. In vitro study results proved AZA facilitated AQP1 translocation onto cell membrane by promoting interaction with MHC, dependent on ERK/ myosin light chain kinase (MLCK) pathway activation. MHC inhibitor BDM and ERK inhibitor U0126 both abolished above effect of AZA. Eventually AZA induced AQP1 ubiquitination, while proteasome inhibitor MG132 reversed AZA's down-regulating effect upon AQP1. CONCLUSIONS/SIGNIFICANCE: Our results identified AZA exerted diuretic effect through an innovative mechanism by regulating AQP1 and verified its inhibitory mechanism was via promoting MHC-dependent translocation onto cell membrane and then ubiquitin mediated degradation, implicating a novel mechanism and target for diuretic agent discovering.

This research focuses onmacrofungi in Baotianman Biosphere Reserve and their relationships with plant ecosystems. The findings demonstrate the reserve’s macrofungal resources. The study collected 832 specimens, among which 351 macrofungi species were identified, belonging to six classes, 19 orders, 54 familiae, and 124 genera, and one new species of Abortiporus was found. Among them, 11 familiae with a total of 231 species were dominated, accounting for 20.37% of the total number of familiae and 65.81% of the total number of species; 14 genera with a total of 147 species were dominated, accounting for about 11.38% the total number of genera and 41.88% of the total number of species. The richness of macrofungi at the species level was considerably different across the four vegetation types in the reserve, showing that the vegetation types had a bigger influence on macrofungi. In the evaluation of macrofungal resources, a total of 196 species of edible fungi, 121 species of medicinal fungi, 52 species of poisonous fungi, and 37 species of macrofungi with unclear economic value were counted. Abortiporus baotianmanensis is a new species of podoscyphaceae in the genus Abortiporus. The new species display the reserve’s richness. Next, the project seeks to generate and conserve macrofungal resources. [ABSTRACT FROM AUTHOR]

The analysis of transient voltage and current characteristics of DPFC （distributed power flow controller） under lightning strikes is an essential consideration in its design and operational management. Firstly， the structure and operational principles of DPFC are introduced， and simulation models are respectively constructed for two scenarios： a centralized arrangement of DPFC sub-modules in substations and a decentralized arrangement along transmission lines. Subsequently， the electromagnetic transient characteristics of DPFC are simulated and analyzed in the case of back strikes on the conductors and circling strikes on the transmission line， and the overvoltage and overcurrent levels at critical positions of DPFC during lightning strikes are thereby obtained. Finally， the differences in overvoltage and overcurrent between the centralized and decentralized arrangement of DPFC sub-modules are compared and analyzed in the case of back strikes and circling strikes. It is concluded that when lightning strikes the lightning conductor， the overvoltage to earth and the overvoltage at the submodule port of the centrally arranged DPFC are larger than the results of the decentralized arrangement； the overcurrents of the submodule of the centrally arranged DPFC and the arrester are smaller than the results of the decentralized arrangement.

Folding wings are flight device structural components that require small space for ammunition seeking, facilitating the storage and transportation of launch boxes (barrels), greatly saving ammunition storage and transportation space, and increasing the delivery and combat capabilities of weapon systems. This article studies the aeroelastic characteristics of longitudinal secondary folding wings during deployment, establishes the dynamic equations of secon-dary folding wings during deformation, calculates the generalized unsteady aerodynamic forces of folding wings during deformation, and conducts aeroelastic flutter analysis of folding wings. The results indicate that due to the uncertainty of the atmospheric environment and the changes in missile flight speed and folding wing opening speed, the folding wing aeroelastic system exhibits an unstable state. During the deformation process, the displacement amplitude and angular degree of freedom changes during the folding wing unfolding process are key factors to ensure the flight stability of missiles and rockets.

Leaf angle is one of the most important agronomic traits in rice, and changes in leaf angle can alter plant architecture to affect photosynthetic efficiency and thus determine grain yield. Therefore, it is important to identify key genes controlling leaf angle and elucidate the molecular mechanisms to improve rice yield. We obtained a mutant rela (regulator of leaf angle) with reduced leaf angle in rice by EMS mutagenesis, and map-based cloning revealed that OsRELA encodes a protein of unknown function. Coincidentally, DENSE AND ERECT PANICLE 2 (DEP2) was reported in a previous study with the same gene locus. RNA-seq analysis revealed that OsRELA is involved in regulating the expression of ILI and Expansin family genes. Biochemical and genetic analyses revealed that OsRELA is able to interact with OsLIC, a negative regulator of BR signaling, through its conserved C-terminal domain, which is essential for OsRELA function in rice. The binding of OsRELA can activate the expression of downstream genes repressed by OsLIC, such as OsILI1 , a positive regulator of leaf inclination in rice. Therefore, our results suggest that OsRELA can act as a transcriptional regulator and is involved in the regulation of leaf inclination by regulating the transcriptional activity of OsLIC. [ABSTRACT FROM AUTHOR]

Distributed power flow controller （DPFC） can improve power flow distribution in the power grid and solve the problem of power flow section excess. Based on the topology structure and operation principle of DPFC and with the backing of the world’s first 220 kV DPFC demonstration project， a distributed power flow control simulation model is established. The cases of distributed power flow controllers centrally installed in substations and dispersedly installed in transmission lines are considered， respectively. The overvoltage and overcurrent levels of DPFC key nodes in the case of short-circuit faults on the transmission lines are simulated. Moreover， it is analyzed how fault location influences the DPFC's overvoltage and overcurrent. The calculation results in this paper can provide a reference for DPFC insulation coordination in engineering practice.

Objective: To evaluate the safety and efficacy of interventional care in pediatric hemoptysis for anomalous bronchial arteries (BAs) and to identify the potential factors resulting in hemoptysis recurrence.Methods: 20 children complained of hemoptysis were diagnosed with anomalous BAs. All patients received transcatheter plug occlusion in Department of Cardiology, Children's Hospital of Chongqing Medical University. The safety and efficacy were evaluated according to clinical symptoms and images monitoring of enrolled subjects grouped as recurrence group and nonrecurrence group. The potential factors causing hemoptysis recurrence were reviewed and summarized.Results: No deaths were recorded in a follow-up. Otherwise, hemoptysis recurrence was found in 8 subjects for 14 times, accounting for about 40%. Compared with nonrecurrence group, it indicated a statistical significance in hemoglobin levels (P=0.049), mycoplasma pneumonia particle assays (MP-PA) titers (P=0.030), and number of anomalous BAs (P=0.020). Meanwhile, 50% recurrent scenarios were associated with a respiratory infection by microbiological assessment before transcatheter plug occlusion. The repeat occlusion was applied for unclosed BAs leading to visual recurrent hemoptysis, the average interval time of which was 5.4 ± 3.6 mon.Conclusion: The data from this retrospective study have shown that transcatheter plug occlusion is a relatively safe procedure with a low mortality. The number of abnormal BAs has been identified as a highly significant predictor of recurrence, and the role of MP and other potential factors should be verified in a multicenter, larger sample size, and randomized controlled trial. [ABSTRACT FROM AUTHOR]

We propose a straightforward and effective approach to design, by pattern-tunable strain-engineering, photonic topological insulators supporting high quality factors edge states. Chiral strain-engineering creates opposite synthetic gauge fields in two domains resulting in Landau levels with the same energy spacing but different topological numbers. The boundary of the two topological domains hosts robust time-reversal and spin-momentum-locked edge states, exhibiting high quality factors due to continuous strain modulation. By shaping the synthetic gauge field, we obtain remarkable field confinement and tunability, with the strain strongly affecting the degree of localization of the edge states. Notably, the two-domain design stabilizes the strain-induced topological edge state. The large potential bandwidth of the strain-engineering and the opportunity to induce the mechanical stress at the fabrication stage enables large scalability for many potential applications in photonics, such as tunable microcavities, new lasers, and information processing devices, including the quantum regime.

Deformed wing mechanism is a developed system of aircraft for miniaturization, which is convenient for box (cylinder) storage, transportation and launch, thus can save the storage and transportation space of aircraft and can improve the space utilization performance of flight system. In order to study wing dynamic opening motion characteristics during aircraft flight, based on gas theory and structural dynamics, this paper studies the dynamic process of the rotary opening movement of deformed wing system caused by the pressure acting on the piston because of propellant combustion with different charge amounts in the chamber, and analyzes relationship between the opening angle of inner and outer wings, angular velocity with time under different gas pressure. The results show that the opening motion of the deformed wing is sensitive to the initial conditions, and different motion characteristics is reflected at different gas pressures.

Leucocalocybe mongolica (S. Imai) X.D. Yu &Y.J. Yao is an endemic mushroom with a distribution in Mongolian Plateau. It is an important edible and medicinal mushroom which is often collected unscrupulously. Wild L. mongolica is facing an unprecedented threat and is in a critically endangered state. Exploration of the genetic diversity and population structure of L. mongolica is important for conservation biology. The main distribution areas were investigated. In total, 402 alleles of 223 individuals from 17 wild geographical populations were obtained based on the eight simple sequence repeat loci. The total number of alleles from each population ranged from 11 to 31 with an average of 24 per population. The average observed heterozygosity (HO) and expected heterozygosity (HE) ranged from 0.300 to 0.875 and from 0.188 to 0.621, respectively. Analysis of molecular variance (AMOVA) indicated that 14.19% of the total molecular variance could be attributed to differences between populations (p <.001), whereas 85.81% to differences within populations. The mean genetic distance (FST) value of 0.171 suggested low genetic differentiation among populations. The UPGMA dendrogram generated from the SSR data suggested that the 17 populations separated into three main sister clusters on the Nei's genetic identity coefficient 0.8. The 223 L. mongolica individuals were divided into three groups by STRUCTURE analysis. Keeping and enriching the population diversity is crucial for the conservation of L. mongolica. The data about the population structure and genetic diversity obtained in this study will facilitate the establishment of conservation measures. Abbreviations AMOVA: analysis of molecular variance; Dest: estimator of actual differentiation; EST-SSR: Expressed sequence tag- simple sequence repeats; Fis: Inbreeding coefficient; Fit: total inbreeding coefficient; Fst: fixation index; GST coefficient of gene differentiation; G'ST: standardized measure of genetic differentiation; HE: expected Heterozygosity; H0: observed heterozygosity; HS: mean genetic diversity within populations; HT: total genetic diversity for species; I: Shannon's diversity index; km: kilometer; L. mongolica: Leucocalocybe mongolica; N: sample size; NA: number of average alleles; NE: number of effective alleles; Nm: gene flow; NP: number of private alleles; NR: allelic richness; NT: number of total alleles; PCoA: principal coordinate analysis; PIC: polymorphism information content; PPB: Percentage of polymorphic loci; TP-M13-SSR: tailed primer M13; UHE: unbiased expected Heterozygosity [ABSTRACT FROM AUTHOR]

Leucocalocybe mongolicais a prestigious rare wild edible mushroom in Northeast Asia. It is the unique species of the genus and the studying of its phynotype and genome is crucial to genus and species classification. Beyond that, it has high application and ecological value in the industry of food and atmosphere investigation. On account of the fact that transcriptomic and genomic data ofL. mongolicalacked in the biological information database, that is a limitation to further study. The transcriptome data were obtained by virtue of Illumina paired-end sequencing technology: 42,622,958 clean reads were achieved and 37,302 contigs were generated. These contigs were subsequently assembled into 13,821 unigenes. These unigenes were annotated within 7 public databases. The 3914 unigenes were associated with a COG classification. Throughout all of the unigenes, 6642 were classified as three functional groups; 3110 unigenes were selected from KEGG pathways, and taken to further clustering analysis for 5 main categories; 57 genes, potentially involved in terpenoid, steroid, and unsaturated fatty acids biosynthesis were identified and selected for further research. The total number of carbohydrate-active enzymes ofL. mongolicais 446 and the number of carbohydrate binding module (CBM) is relatively low. CE11, GT19, GT51, GT56, GH131, GH133, GH135 constitute the characteristic carbohydrate-active enzymes subfamily compared to other edible mushrooms. The characteristic carbohydrate enzymes relative to other mushrooms could play a vital role on the metabolism of nutrients. In these generated sequences, 1860 SSRs were identified and characterized as molecular candidate markers existingL. mongolica. [ABSTRACT FROM PUBLISHER]

Objectives. This study collected and evaluated data on the costs of outpatient medical care and family burden associated with osteoporosis-related fracture rehabilitation following hospital discharge in China. Materials and Methods. Data were collected using a patient questionnaire from osteoporosis-related fracture patients (N = 123) who aged 50 years and older who were discharged between January 2011 and January 2013 from 3 large hospitals in China. The survey captured posthospital discharge direct medical costs, indirect medical costs, lost work time for caregivers, and patient ambulatory status. Results. Hip fracture was the most frequent fracture site (62.6%), followed by vertebral fracture (34.2%). The mean direct medical care costs per patient totaled 3,910¥, while mean indirect medical costs totaled 743¥. Lost work time for unpaid family caregivers was 16.4 days, resulting in an average lost income of 3,233¥. The average posthospital direct medical cost, indirect medical cost, and caregiver lost income associated with a fracture patient totaled 7,886¥. Patients’ ambulatory status was negatively impacted following fracture. Conclusions. Significant time and cost of care are placed on patients and caregivers during rehabilitation after discharge for osteoporotic fracture. It is important to evaluate the role and responsibility for creating the growing and inequitable burden placed on patients and caregivers following osteoporotic fracture. [ABSTRACT FROM AUTHOR]

Now stimulation of AMPA receptor as well as its downstream pathways is considered as potential central mediators in antidepressant mechanisms. As a signal integrator which binds to AMPA receptor, A-kin ase anchoring protein 79-(AKAP79-) PKA complex is regarded as a potential drug target to exert neuroprotective effects. A well-tolerated and multitarget drug curcumin has been confirmed to exert antidepressant-like effects. To explore whether AKAP79-PKA complex is involved in curcumin-mediated antiexcitotoxicity, we detected calcium signaling, subcellular location of AKAP79-PKA complex, phosphorylation of glutamate receptor, and ERK and AKT cascades. In this study, we found that curcumin protected neurons from glutamate insult by reducing Ca2+ influx and blocking the translocation of AKAP79 from cytomembrane to cytoplasm. In parallel, curcumin enhanced the phosphorylation of AMPA receptor and its downstream pathways in PKA-dependent manner. If we pretreated cells with PKA anchoring inhibitor Ht31 to disassociate PKA from AKAP79, no neuroprotective effects were observed. In conclusion, our results show that AKAP79-anchored PKA facilitated the signal relay from AMPA receptor to AKT and ERK cascades, which may be crucial for curcumin-mediated antiexcitotoxicity. [ABSTRACT FROM AUTHOR]

Ethylene and abscisic acid (ABA) have a complicated interplay in many developmental processes. Their interaction in rice is largely unclear. Here, we characterized a rice ethylene-response mutant mhz4, which exhibited reduced ethylene-response in roots but enhanced ethylene-response in coleoptiles of etiolated seedlings. MHZ4 was identified through map-based cloning and encoded a chloroplast-localized membrane protein homologous to Arabidopsis thaliana (Arabidopsis) ABA4, which is responsible for a branch of ABA biosynthesis. MHZ4 mutation reduced ABA level, but promoted ethylene production. Ethylene induced MHZ4 expression and promoted ABA accumulation in roots. MHZ4 overexpression resulted in enhanced and reduced ethylene response in roots and coleoptiles, respectively. In root, MHZ4-dependent ABA pathway acts at or downstream of ethylene receptors and positively regulates root ethylene response. This ethylene-ABA interaction mode is different from that reported in Arabidopsis, where ethylene-mediated root inhibition is independent of ABA function. In coleoptile, MHZ4-dependent ABA pathway acts at or upstream of OsEIN2 to negatively regulate coleoptile ethylene response, possibly by affecting OsEIN2 expression. At mature stage, mhz4 mutation affects branching and adventitious root formation on stem nodes of higher positions, as well as yield-related traits. Together, our findings reveal a novel mode of interplay between ethylene and ABA in control of rice growth and development. [ABSTRACT FROM AUTHOR]

Endothelial progenitor cell (EPC) dysfunction is a key contributor to diabetic refractory wounds. Endothelial nitric oxide synthase (eNOS), which critically regulates the mobilization and function of EPCs, is uncoupled in diabetes due to decreased cofactor tetrahydrobiopterin (BH4). We tested whether GTP cyclohydrolase I (GTPCH I), the rate-limiting enzyme of BH4 synthesis, preserves EPC function in type 1 diabetic mice. Type 1 diabetes was induced in wild-type (WT) and GTPCH I transgenic (Tg-GCH) mice by intraperitoneal injection of streptozotocin (STZ). EPCs were isolated from the peripheral blood and bone marrow of WT, Tg-GCH, and GTPCH I-deficient hph-1 mice. The number of EPCs was significantly lower in STZ-WT mice and hph-1 mice and was rescued in STZ Tg-GCH mice. Furthermore, GTPCH I overexpression improved impaired diabetic EPC migration and tube formation. EPCs from WT, Tg-GCH, and STZ-Tg-GCH mice were administered to diabetic excisional wounds and accelerated wound healing significantly, with a concomitant augmentation of angiogenesis. Flow cytometry measurements showed that intracellular nitric oxide (NO) levels were reduced significantly in STZ-WT and hph-1 mice, paralleled by increased superoxide anion levels; both were rescued in STZ-Tg-GCH mice. Western blot analysis revealed that thrombospondin-1 (TSP-1) was significantly upregulated in the EPCs of STZ-WT mice and hph-1 mice and suppressed in STZ-treated Tg-GCH mice. Our results demonstrate that the GTPCH I/BH4 pathway is critical to preserve EPC quantity, function, and regenerative capacity during wound healing in type 1 diabetic mice at least partly through the attenuation of superoxide and TSP-1 levels and augmentation of NO level. [ABSTRACT FROM AUTHOR]