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As an important part of terrestrial carbon cycle research, net primary productivity is an important parameter to evaluate the quality of terrestrial ecosystem and plays an important role in the analysis of global climate change and carbon balance. Anhui Province is in the Yangtze River Delta region in eastern China. Based on the theoretical basis of CASA model, this paper uses MODIS NDVI, vegetation type data, meteorological data, and LUCC to estimate the NPP of Anhui Province during 2001-2020 and analyzes its spatial-temporal pattern. The results showed that the average NPP in Anhui province was 508.95 gC· (m2 ·a) -1, and the spatial heterogeneity of NPP was strong, and the high value areas were mainly distributed in the Jiangnan Mountains and Dabie Mountains. NPP increased in most areas of Anhui Province, but decreased significantly in 17.60% of the area, mainly in the central area affected by urban and rural expansion and the transformation of the Yangtze River. The dynamic change of NPP in Anhui province is the result of climate change and land use change. Meteorological data are positively correlated with NPP. Among them, the correlation between temperature and solar radiation is higher, and the correlation between NPP and precipitation is the lowest among the three. The NPP of all land cover types was more affected by temperature than precipitation, especially forest land and grassland. The decrease of cultivated land and the increase of Artificial Surfaces (AS) may have contributed to the decrease of NPP in Anhui Province. Human activities have weakened the increase in NPP caused by climate change. In conclusion, this study refined the drivers of spatial heterogeneity of NPP changes in Anhui province, which is conducive to rational planning of terrestrial ecosystems and carbon balance measures.

BackgroundPeritoneal fibrosis (PF) is the main complication of peritoneal dialysis (PD) and the most common cause of cessation from PD. There is still no effective therapeutic approach to reserve PF. We aimed to investigate the role of miR-132-3p and underlying potential mechanisms in PF.MethodsA total of 18 Sprague-Dawley (SD) rats were divided randomly into three groups (n = 6): (i)Control group (ii)PF group (iii)PF+Losartan group; Rats in the PF group and PF+Losartan group received daily intraperitoneal injections of 3 mg/kg chlorhexidine for 14 days, and rats in the PF+Losartan group simultaneously received daily intraperitoneal injections of 2 mg/kg losartan for 14 days. The control group was injected with saline in the same volume. Met-5A cells were treated for 24h with TGF-β1 dissolved in recombinant buffered saline at a concentration of 10 ng/ml, meanwhile, PBS solution as a negative control. The human peritoneal solution was collected for the detection of miR-132-3p.ResultsIn vivo, SD rats were infused with chlorhexidine to establish PF model, and we found that miR-132-3p significantly decreased and the expressions of transforming growth factor-β1 (TGF-β1), and Smad2/3 were up-regulated in PF. In vitro, miR-132-3p mimics suppressed TGF-β1/Smad2/3 activity, whereas miR-132-3p inhibition activated the pathway. In human peritoneal solution, we found that the expression of miR-132-3p decreased in a time-dependent model and its effect became more pronounced with longer PD duration.ConclusionMiR-132-3p ameliorated PF by suppressing TGF-β1/Smad2/3 activity, suggesting that miR-132-3p represented a potential therapeutic approach for PF.

Gastric cancer is one of the most frequent causes of cancer-related deaths worldwide. Gastric atrophy (GA) and gastric intestinal metaplasia (IM) of the mucosa of the stomach have been found to increase the risk of gastric cancer and are considered precancerous lesions. Therefore, the early detection of GA and IM may have a valuable role in histopathological risk assessment. However, GA and IM are difficult to confirm endoscopically and, following the Sydney protocol, their diagnosis depends on the analysis of glandular morphology and on the identification of at least one well-defined goblet cell in a set of hematoxylin and eosin (H&E) -stained biopsy samples. To this end, the precise segmentation and classification of glands from the histological images plays an important role in the diagnostic confirmation of GA and IM. In this paper, we propose a digital pathology end-to-end workflow for gastric gland segmentation and classification for the analysis of gastric tissues. The proposed GAGL-VTNet, initially, extracts both global and local features combining multi-scale feature maps for the segmentation of glands and, subsequently, it adopts a vision transformer that exploits the visual dependences of the segmented glands towards their classification. For the analysis of gastric tissues, segmentation of mucosa is performed through an unsupervised model combining energy minimization and a U-Net model. Then, features of the segmented glands and mucosa are extracted and analyzed. To evaluate the efficiency of the proposed methodology we created the GAGL dataset consisting of 85 WSI, collected from 20 patients. The results demonstrate the existence of significant differences of the extracted features between normal, GA and IM cases. The proposed approach for gland and mucosa segmentation achieves an object dice score equal to 0.908 and 0.967 respectively, while for the classification of glands it achieves an F1 score equal to 0.94 showing great potential for the automated quantification and analysis of gastric biopsies.

Protein posttranslational modifications (PTMs) regulate the biological processes of human diseases by genetic code expansion and cellular pathophysiology regulation; however, system-wide changes in PTM levels in the intracerebral hemorrhage (ICH) brain remain poorly understood. Succinylation refers to a major PTM during the regulation of multiple biological processes. In this study, according to the methods of quantitative succinyllysine proteomics based on high-resolution mass spectrometry, we investigated ICH-associated brain protein succinyllysine modifications and obtained 3,680 succinylated sites and quantified around 3,530 sites. Among them, 25 succinyllysine sites on 23 proteins were upregulated (hypersuccinylated), whereas 13 succinyllysine sites on 12 proteins were downregulated (hyposuccinylated) following ICH. The cell component enrichment analysis of these succinylproteins with significant changes showed that 58.3% of the hyposuccinylated proteins were observed in the mitochondria, while the hyper-succinylproteins located in mitochondria decreased in the percentage to about 35% in ICH brains with a concomitant increase in the percentage of cytoplasm to 30.4%. Further bioinformatic analysis showed that the succinylproteins were mostly mitochondria and synapse-related subcellular located and involved in many pathophysiological processes, like metabolism, synapse working, and ferroptosis. Moreover, the integrative analysis of our succinylproteomics data and previously published transcriptome data showed that the mRNAs matched by most differentially succinylated proteins were especially highly expressed in neurons, endothelial cells, and astrocytes. Our study uncovers some succinylation-affected processes and pathways in response to ICH brains and gives us novel insights into understanding pathophysiological processes of brain injury caused by ICH.

Early diagnosis and prevention play a crucial role in the treatment of patients with ARDS. The definition of ARDS requires an arterial blood gas to define the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2 ratio). However, many patients with ARDS do not have a blood gas measured, which may result in under-diagnosis of the condition. Using data from MIMIC-III Database, we propose an algorithm based on patient non-invasive physiological parameters to estimate P/F levels to aid in the diagnosis of ARDS disease. The machine learning algorithm was combined with the filter feature selection method to study the correlation of various noninvasive parameters from patients to identify the ARDS disease. Cross-validation techniques are used to verify the performance of algorithms for different feature subsets. XGBoost using the optimal feature subset had the best performance of ARDS identification with the sensitivity of 84.03%, the specificity of 87.75% and the AUC of 0.9128. For the four machine learning algorithms, reducing a certain number of features, AUC can still above 0.8. Compared to Rice Linear Model, this method has the advantages of high reliability and continually monitoring the development of patients with ARDS.

PurposeTo investigate the relationship between anterior capsule polish and visual function.MethodsData were obtained from Pubmed, Embase, Web of Science, WanFang, VIP and CNKI up to the end of May 2018, without any date or language restrictions for trials. The modified Jadad scale and the newcastle-ottawa scale were used to assess the quality of included studies. Uncorrected visual acuity (UCVA) and posterior capsule opacification (PCO) were used as outcome variables. Data on anterior capsule polish were pooled using weighted, random-effect meta-analysis.ResultsOne randomized controlled trial and 4 observational cohort studies involving 2533 patients were included in the analyses. There was a statistically significant difference of UCVA (OR 1.92, 95% CI 1.41-2.61) between the polish group and the control group, indicating that anterior capsule polish improved UCVA. Further studies with continuous data also suggested that anterior capsule polish was associated with good UCVA (MD 0.11, 95% CI 0.06-0.16). Posterior capsule opacification rate for 1-year or longer follow-up were extracted for 2561 eyes in 3 studies. Posterior capsule opacification rate was lower in the anterior capsule polish group according to summary odds ratio on PCO rate (OR 0.42 95% CI 0.24-0.73).ConclusionsAnterior capsule polish prevents complication of modern cataract surgery and benefits on visual function in short term follow-up period.

Whether cigarette smoking and moderate drinking are associated with non-alcoholic fatty liver disease (NAFLD)has not been fully described. This study investigated the separate and joint effects of smoking and moderate drinking on Chinese men with NAFLD.Across-sectional assay from DFTJ Cohort study was performed with a size of 9432 elderly Chinese men excluding excessive alcohol consumption (

The present study aimed to undertake a review of available evidence assessing whether time-lapse imaging (TLI) has favorable outcomes for embryo incubation and selection compared with conventional methods in clinical in vitro fertilization (IVF).Using PubMed, EMBASE, Cochrane library and ClinicalTrial.gov up to February 2017 to search for randomized controlled trials (RCTs) comparing TLI versus conventional methods. Both studies randomized women and oocytes were included. For studies randomized women, the primary outcomes were live birth and ongoing pregnancy, the secondary outcomes were clinical pregnancy and miscarriage; for studies randomized oocytes, the primary outcome was blastocyst rate, the secondary outcome was good quality embryo on Day 2/3. Subgroup analysis was conducted based on different incubation and embryo selection between groups.Ten RCTs were included, four randomized oocytes and six randomized women. For oocyte-based review, the pool-analysis observed no significant difference between TLI group and control group for blastocyst rate [relative risk (RR) 1.08, 95% CI 0.94-1.25, I2 = 0%, two studies, including 1154 embryos]. The quality of evidence was moderate for all outcomes in oocyte-based review. For woman-based review, only one study provided live birth rate (RR 1,23, 95% CI 1.06-1.44,I2 N/A, one study, including 842 women), the pooled result showed no significant difference in ongoing pregnancy rate (RR 1.04, 95% CI 0.80-1.36, I2 = 59%, four studies, including 1403 women) between two groups. The quality of the evidence was low or very low for all outcomes in woman-based review.Currently there is insufficient evidence to support that TLI is superior to conventional methods for human embryo incubation and selection. In consideration of the limitations and flaws of included studies, more well designed RCTs are still in need to comprehensively evaluate the effectiveness of clinical TLI use.

OBJECTIVES:The aim of this study is to examine the bidirectional association between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). METHODS:The data was derived from the Dongfeng-Tongji cohort study, which was established in 2008 and followed until October 2013. NAFLD was classified as none, mild, moderate/severe based on ultrasound examination. The analysis to examine the association between NAFLD and incident T2DM risk included 18,111 participants free of diabetes at baseline and the duration of follow-up was 4.60 ± 0.60 years. Cox proportional regression model was used to calculate the hazard ratio (HR) for the association. The analysis to investigate the association between T2DM and incident NAFLD risk included 12,435 participants free of NAFLD at baseline. Logistic regression model was used to calculate the odd ratio (OR) of NAFLD. RESULTS:Compared with those without NAFLD, individuals with mild or moderate/severe NAFLD had a monotonic elevated risk of developing T2DM (HR: 1.88 [95% CI: 1.63-2.18] and 2.34 [1.85-2.96], respectively) after adjustment for potential confounders. In a parallel analysis, compared to participants with fasting plasma glucose < 6.1 mmol/L, the ORs of developing NAFLD in subjects with impaired fasting glucose and T2DM were 1.35 (95% CI: 1.16-1.57) and 1.40 (95% CI: 1.22-1.62), respectively. CONCLUSIONS:Our results provide compelling evidence that the NAFLD-T2DM association is bidirectional in Chinese population.

Pigs have played a major role in the economic, social and symbolic systems of China since the Early Neolithic more than 8,000 years ago. However, the interaction between the history of pig domestication and transformations in Chinese society since then, have not been fully explored. In this paper, we investigated the co-evolution from the earliest farming communities through to the new political and economic models of state-like societies, up to the Chinese Empire, using 5,000 years of archaeological records from the Xiawanggang (XWG) and Xinzhai (XZ) sites (Henan Province). To trace the changes of pig populations against husbandry practices, we combined the geometric morphometric analysis of dental traits with a study of the stable carbon and nitrogen isotope ratios from bone collagen. The domestication process intensified during the Neolithic Yangshao, prompted by greater selective pressure and/or better herd control against wild introgression. After that, pig farming, in XWG, relied on local livestock and a gradual change of husbandry practices overtime. This was characterized by a gentle increase in millet foddering and animal protein intake, until a complete change over to household management during the Han dynasty. The only rupture in this steady trend of husbandry occurred during the Longshan period, with the appearance of small sized and idiosyncratic pigs with specific feeding practices (relying on millet and household scraps). From three exploratory hypothesis, we explored the possibility of anti-elite pig production in XWG during the Longshan period, as a means to resist incorporation into a new economic model promoting intensified domestic production. This exploratory hypothesis is the most suitable to our dataset; however, numerous areas need to be explored further in order to adequately document the role of pigs in the rise of China's complex societies.

The ancestor of all modern domestic cats is the wildcat, Felis silvestris lybica, with archaeological evidence indicating it was domesticated as early as 10,000 years ago in South-West Asia. A recent study, however, claims that cat domestication also occurred in China some 5,000 years ago and involved the same wildcat ancestor (F. silvestris). The application of geometric morphometric analyses to ancient small felid bones from China dating between 5,500 to 4,900 BP, instead reveal these and other remains to be that of the leopard cat (Prionailurus bengalensis). These data clearly indicate that the origins of a human-cat 'domestic' relationship in Neolithic China began independently from South-West Asia and involved a different wild felid species altogether. The leopard cat's 'domestic' status, however, appears to have been short-lived--its apparent subsequent replacement shown by the fact that today all domestic cats in China are genetically related to F. silvestris.

Kelch proteins are implicated in the pathogenesis of many human diseases, including cancer. Nasopharyngeal carcinoma (NPC) is a rare malignancy in most countries, but prevalent in southern China and certain areas of Southeast Asia. In this study, we identified Kelch Domain Containing 4 (KLHDC4), an orphan member of the kelch repeat superfamily, as a prognosis marker for NPC. We examined the expression of KLHDC4 in 168 NPC cases by immunohistochemical staining and found a substantially higher level of KLHDC4 in NPC biopsies compared to adjacent normal nasopharyngeal mucosa. KLHDC4 expression was significantly related to the T classification (P

BACKGROUND:Several metals have been reported to be associated with childhood asthma. However, the results on relationships between metals and risk of childhood asthma are inconclusive, and the research on adult asthma in the Chinese general population is rare. OBJECTIVES:To investigate potential associations between levels of urinary metals and adult asthma. METHODS:A case-control study of 551 adult asthma cases and 551 gender- and age-matched controls was conducted in Wuhan, China. Demographic information was obtained, and lung function was assessed. The urinary concentrations of 22 metals were measured by inductively coupled plasma mass spectrometry. RESULTS:After adjusting for other metalsand other covariates, urinary cadmium, molybdenum, chromium, copper, uranium and selenium were positively associated with asthma, with odds ratios (95% CI) of 1.69 (1.00, 2.85), 3.76 (2.30, 6.16), 4.89 (3.04, 7.89), 6.06 (3.27, 11.21), 6.99 (4.37, 11.19) and 9.17 (4.16, 20.21), respectively. By contrast, urinary lead, barium, iron, zinc, nickel, manganese and rubidium were negatively associated with asthma, with odds ratios (95% CI) of 0.48 (0.29, 0.80), 0.44 (0.27, 0.71), 0.41 (0.26, 0.64), 0.40 (0.24, 0.66), 0.30 (0.22, 0.41), 0.23 (0.14, 0.39) and 0.07 (0.03, 0.15), respectively. When comparing urinary metals in different subgroups of cases with those in matched controls, the associations of above 13 metals with asthma prevalence were nearly the same. CONCLUSIONS:Our results suggested that asthma prevalence in the Chinese adults was positively associated with urinary chromium, chromium, selenium, molybdenum, cadmium, and uranium, and negatively associated with urinary manganese, iron, nickel, zinc, rubidium, barium and lead. Additional research with larger populations in different regions is required to support our findings.

In our previous study, we found significant differences in the mRNA and microRNA (miRNA) levels among hypertensive patients with different degrees of vascular endothelial cells damage. These differences were closely associated with endoplasmic reticulum stress (ERS)-related proteins. Moreover, compared to the control group, the expression of transcription factor activating factor 4 (ATF4) was also found to be significantly different in the hypertensive patients with different degrees of vascular endothelial cells damage groups. These results were confirmed using gene prediction software, which showed synergistic effects between ATF4 and miR-1283. ATF4 is a key molecule in ERS. Three ERS pathways exist:protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6) and inositol-requiring enzyme-1 (IRE-1)-induced apoptosis. The PERK pathway is the most important and also includes the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) and ATF4. In this report, we studied the regulatory effects of miR-1283 and ATF4 on the PERK-eIF2α-ATF4 signaling pathway using human umbilical vein endothelial cells (HUVECs) and mice.We verified the relationship between miR-1283 and ATF4 using a luciferase activity assay and observed the regulatory effects of miR-1283 and ATF4 on the PERK-eIF2α-ATF4 signaling pathway in vivo and in vitro.ATF4 is a target gene of miR-1283, which regulates the PERK-eIF2α-ATF4 signaling pathway by inhibiting ATF4, and it plays a critical role in inducing injury in HUVECs and mouse heart tissue.

Freshwater fisheries are central to food security in China and this remains one of the most important priorities for the growing human population. Thus, combining ecosystem restoration with economics is pivotal in setting successful conservation in China. Here, we have developed a practical management model that combines fishery improvement with conservation. For six years, a ban on fertilizer and a reduction of planktivorous fish stocking along with the introduction of both mandarin fish Siniperca chuatsi and Chinese mitten crab Eriocheir sinensis was apparent in Wuhu Lake, a highly eutrophic lake located in the middle reaches of the Yangtze River. Annual fish yield decreased slightly after the change in management, whereas fisheries income increased 2.6 times. Mandarin fish and Chinese mitten crab accounted for only 16% of total fisheries production but for 48% of total fisheries income. During this six year period, water clarity increased significantly from 61 cm to 111 cm. Total nitrogen, total phosphorus and chlorophyll decreased significantly from 1.14 to 0.84 mg/L, 0.077 to 0.045 mg/L, and 21.45 to 11.59 μg/L respectively, and macrophyte coverage increased by about 30%. Our results showed that the ecological status of shallow lakes could be rapidly reversed from eutrophic to oligotrophic using simple biomanipulation, whilst maintaining fisheries economic value. It also offers a better approach to shallow fisheries lake management in Asia where traditionally the stocking of Chinese carp and use of fertilizers is still popular.

Leucocytozoon parasites infect a large number of avian hosts, including domestic chicken, and cause significant economical loss to the poultry industry. Although the transmission stages of the parasites were observed in avian blood cells more than a century ago, the specific host cell type(s) that the gametocytes infect remain uncertain. Because all the avian blood cells, including red blood cells (RBCs), are nucleated, and the developing parasites dramatically change the morphology of the infected host cells, it has been difficult to identify Leucocytozoon infected host cell(s). Here we use cell-type specific antibodies to investigate the identities of the host cells infected by Leucocytozoon sabrazesi gametocytes. Anti-RBC antibodies stained RBCs membrane strongly, but not the parasite-infected cells, ruling out the possibility of RBCs being the infected host cells. Antibodies recognizing various leukocytes including heterophils, monocytes, lymphocytes, and macrophages did not stain the infected cells either. Antisera raised against a peptide of the parasite cytochrome B (CYTB) stained parasite-infected cells and some leukocytes, particularly cells with a single round nucleus as well as clear/pale cytoplasm suggestive of thrombocytes. Finally, a monoclonal antibody known to specifically bind chicken thrombocytes also stained the infected cells, confirming that L. sabrazesi gametocytes develop within chicken thrombocytes. The identification of L. sabrazesi infected host cell solves a long unresolved puzzle and provides important information for studying parasite invasion of host cells and for developing reagents to interrupt parasite transmission.

BACKGROUND:Elevated heavy metals and fasting plasma glucose (FPG) levels were both associated with increased risk of cardiovascular diseases. However, studies on the associations of heavy metals and essential elements with altered FPG and diabetes risk were limited or conflicting. The objective of this study was to evaluate the potential associations of heavy metals and essential trace elements with FPG and diabetes risk among general Chinese population. METHODS:We conducted a cross-sectional study to investigate the associations of urinary concentrations of 23 metals with FPG, impaired fasting glucose (IFG) and diabetes among 2242 community-based Chinese adults in Wuhan. We used the false discovery rate (FDR) method to correct for multiple hypothesis tests. RESULTS:After adjusting for potential confounders, urinary aluminum, titanium, cobalt, nickel, copper, zinc, selenium, rubidium, strontium, molybdenum, cadmium, antimony, barium, tungsten and lead were associated with altered FPG, IFG or diabetes risk (all P< 0.05); arsenic was only dose-dependently related to diabetes (P< 0.05). After additional adjustment for multiple testing, titanium, copper, zinc, selenium, rubidium, tungsten and lead were still significantly associated with one or more outcomes (all FDR-adjusted P< 0.05). CONCLUSIONS:Our results suggest that multiple metals in urine are associated with FPG, IFG or diabetes risk. Because the cross-sectional design precludes inferences about causality, further prospective studies are warranted to validate our findings.

BACKGROUND AND PURPOSE:It is important to identify patients with head and neck squamous cell carcinoma (SCC) who fail to respond to chemoradiotherapy so that they can undergo post-treatment salvage surgery while the disease is still operable. This study aimed to determine the diagnostic performance of dynamic contrast enhanced (DCE)-MRI using a pharmacokinetic model for pre-treatment predictive imaging, as well as post-treatment diagnosis, of residual SCC at primary and nodal sites in the head and neck. MATERIAL AND METHODS:Forty-nine patients with 83 SCC sites (primary and/or nodal) underwent pre-treatment DCE-MRI, and 43 patients underwent post-treatment DCE-MRI, of which 33 SCC sites had a residual mass amenable to analysis. Pre-treatment, post-treatment and % change in the mean Ktrans, kep, ve and AUGC were obtained from SCC sites. Logistic regression was used to correlate DCE parameters at each SCC site with treatment response at the same site, based on clinical outcome at that site at a minimum of two years. RESULTS:None of the pre-treatment DCE-MRI parameters showed significant correlations with SCC site failure (SF) (29/83 sites) or site control (SC) (54/83 sites). Post-treatment residual masses with SF (14/33) had significantly higher kep (p = 0.05), higher AUGC (p = 0.02), and lower % reduction in AUGC (p = 0.02), than residual masses with SC (19/33), with the % change in AUGC remaining significant on multivariate analysis. CONCLUSION:Pre-treatment DCE-MRI did not predict which SCC sites would fail treatment, but post-treatment DCE-MRI showed potential for identifying residual masses that had failed treatment.

Hypoxia is a prominent characteristic of inflammatory tissue lesions. It can affect platelet function. While mean platelet volume (MPV) and platelet distribution width (PDW) are sample platelet indices, they may reflect subcinical platelet activation. To investigated associations between adiposity indices and platelet indices, 17327 eligible individuals (7677 males and 9650 females) from the Dongfeng-Tongji Cohort Study (DFTJ-Cohort Study, n=27009) were included in this study, except for 9682 individuals with missing data on demographical, lifestyle, physical indicators and diseases relative to PDW and MPV. Associations between adiposity indices including waist circumstance (WC), waist-to-height ratio (WHtR), body mass index (BMI), and MPV or PDW in the participants were analyzed using multiple logistic regressions. There were significantly negative associations between abnormal PDW and WC or WHtR for both sexes (ptrend

A total of 13 phosphate transporters in rice (Oryza sative) have been identified as belonging to the Pht1 family, which mediates inorganic phosphate (Pi) uptake and transport. We report the biological property and physiological role of OsPht1;4 (OsPT4). Overexpressing OsPT4 resulted in significant higher Pi accumulation in roots, straw and brown rice, and suppression of OsPT4 caused decreased Pi concentration in straw and brown rice. Expression of the β-glucuronidase reporter gene driven by the OsPT4 promoter showed that OsPT4 is expressed in roots, leaves, ligules, stamens, and caryopses under sufficient Pi conditions, consistent with the expression profile showing that OsPT4 has high expression in roots and flag leaves. The transcript level of OsPT4 increased significantly both in shoots and roots with a long time Pi starvation. OsPT4 encoded a plasma membrane-localized protein and was able to complement the function of the Pi transporter gene PHO84 in yeast. We concluded that OsPT4 is a functional Pi-influx transporter involved in Pi absorption in rice that might play a role in Pi translocation. This study will enrich our understanding about the physiological function of rice Pht1 family genes.

Autoinducer-2 (AI-2) molecules are one class of signalling molecules involved in gene regulation dependent on population density in a mechanism commonly referred to as quorum sensing (QS). AI-2 is produced by the methylthioadenosine/S-adenosyl-homocysteine nucleosidase LuxS. In the present study, we characterise the function of bifidobacterial LuxS proteins to address the question whether these economically important bacteria are able to perform QS communication. All publically available genome sequences of bifidobacteria harbour putative luxS genes. The deduced amino acid sequences are well conserved in the genus and show good homology to the LuxS protein of the prototypical AI-2 producer Vibrio harveyi. The luxS genes of three bifidobacterial strains were successfully expressed in AI-2-negative Escherichia coli DH5α. Supernatants of these recombinant E. coli strains contained significant AI-2 activity. In initial experiments, we failed to detect AI-2 activity in supernatants of bifidobacteria grown in MRSc. High concentration of glucose as well as acidic pH had strong inhibitory effects on AI-2 activity. AI-2 activity could be detected when lower volumes of supernatants were used in the assay. Homologous overexpression of luxS in Bifidobacterium longum NCC2705 increased AI-2 levels in the supernatant. Furthermore, over-expression of luxS or supplementation with AI-2-containing supernatants enhanced biofilm formation of B. longum NCC2705. Collectively, these results suggest that bifidobacteria indeed harbour functional luxS genes that are involved in the production of AI-2-like molecules. To the best of our knowledge, this represents the first report on AI-2 activity produced by bifidobacteria. Self-produced AI-2 activity as well as AI-2-like molecules of other bacteria of the intestinal tract may have a regulatory function in biofilm formation and host colonization by bifidobacteria.

Climatic variations are known to engender life-history diversification of species and populations at large spatial scales. However, the extent to which microgeographic variations in climate (e.g., those occurring within a single large ecosystem) can also drive life-history divergence is generally poorly documented. We exploited a spatial gradient in water temperatures at three sites across a large montane lake in southwest China (Lake Erhai) to examine the extent to which life histories of a short-lived fish species (icefish, Neosalanx taihuensis) diversified in response to thermal regime following introduction 25 y prior. In general, warmwater icefish variants grew faster, had larger adult body size and higher condition and fecundity, but matured at smaller sizes. Conversely, coldwater variants had smaller adult body size and lower condition, but matured at larger sizes and had larger eggs. These life-history differences strongly suggest that key ecological trade-offs exist for icefish populations exposed to different thermal regimes, and these trade-offs have driven relatively rapid diversification in the life histories of icefish within Lake Erhai. Results are surprisingly concordant with current knowledge on life-history evolution at macroecological scales, and suggest that improved conservation management might be possible by focusing on patterns operating at microgeographical, including, within-ecosystem scales.

Overall, gastric cancer prognosis remains poor. Detailed characterization of molecular markers that govern gastric cancer pathogenesis is warranted to establish innovative therapeutic options. HIF-1α overexpression has been linked to poor gastric cancer prognosis. However, though researched for years, the prognostic role of HIF-1α in gastric cancer is still controversial. Hence, the objective of the present study was to analyze the prognostic values of HIF-1α, TGF-β, VEGF and pERK1/2 in gastric cancer patients following gastrectomy.This study included 446 patients with confirmed gastric cancer who underwent gastrectomy in a single Chinese Cancer Center between 2005 and 2006. Clinicopathologic features, as well as immunohistochemical analysis of TGF-β, HIF-1α, VEGF and pERK1/2 were determined. Long-term survival of these patients was analyzed using univariate and multivariate analyses.HIF-1α overexpression was more frequent in patients with hepatic metastases (71.6% versus 43.0% in those without hepatic metastases, P = 0.000, χ2 = 23.086) and more frequent in patients with peritoneum cavity metastasis (62.3% versus 43.0% in those without such metastasis, P = 0.000, χ2 = 13.691). In univariate analysis, patients with HIF-1α overexpression had a shorter disease-free survival (DFS) and overall survival (OS) than patients with weak-expression (DFS: NA VS. 16.8 m, P = 0.000, χ2 = 74.937; OS: NA VS. 25.5 m, P = 0.000, χ2 = 90.594). Importantly, HIF-1α overexpression was a promising prognostic marker for poor survival by multivariate analysis (DFS: HR 2.766, 95%CI 2.136-2.583, P = 0.000; OS: HR 3.529, 95%CI 2.663-4.667, P = 0.000).HIF-1α overexpression could be considered a useful independent prognostic biomarker in gastric cancer after gastrectomy, and is correlated to both a poor overall survival and disease-free survival in these patients. HIF-1α expression can be used to stratify patients at higher risk for poor prognosis, and is potentially an important therapeutic target in gastric cancer patients.

Long-term adherence to a high-fat, high-calorie diet influences human health and causes obesity, metabolic syndrome and nonalcoholic steatohepatitis (NASH). Inflammation plays a key role in the development of NASH; however, the mechanism of inflammation induced by over-nutrition remains largely unknown. In this study, we fed Bama minipigs a high-fat, high-sucrose diet (HFHSD) for 23 months. The pigs exhibited characteristics of metabolic syndrome and developed steatohepatitis with greatly increased numbers of inflammatory cells, such as lymphocytes (2.27-fold, P

PURPOSE: This study was aimed to determine whether pure molecular-based diffusion coefficient (D) and perfusion-related diffusion parameters (perfusion fraction f, perfusion-related diffusion coefficient D*) differ in healthy livers and fibrotic livers through intra-voxel incoherent motion (IVIM) MR imaging. MATERIAL AND METHODS: 17 healthy volunteers and 34 patients with histopathologically confirmed liver fibrosis patients (stage 1 = 14, stage 2 = 8, stage 3 & 4 = 12, METAVIR grading) were included. Liver MR imaging was performed at 1.5-T. IVIM diffusion weighted imaging sequence was based on standard single-shot DW spin echo-planar imaging, with ten b values of 10, 20, 40, 60, 80, 100, 150, 200, 400, 800 sec/mm2 respectively. Pixel-wise realization and regions-of-interest based quantification of IVIM parameters were performed. RESULTS: D, f, and D* in healthy volunteer livers and patient livers were 1.096±0.155 vs 0.917±0.152 (10(-3) mm2/s, p = 0.0015), 0.164±0.021 vs 0.123±0.029 (p

OBJECTIVE: Our purpose was to validate an early enhancement time point for accurately measuring the myocardial contrast partition coefficient (lambda) using dynamic-equilibrium magnetic resonance imaging. MATERIALS AND METHODS: The pre- and post-contrast longitudinal relaxation rates (reciprocal of T1) of the interventricular septum (R1(m)) and blood pool (R1(b)) were obtained from fifteen healthy volunteers and three diabetic patients with hypertension using two optimized T1 mapping sequences (modified Look-Locker inversion recovery) on a 3-Tesla magnetic resonance scanner. Reference lambda values were calculated as the slope of the regression line of R1(m) versus R1(b) at dynamic equilibrium (multi-point regression method). The simplified pre-/post-enhancement two-acquisition method (two-point method) was used to calculate lambda by relating the change in R1(m) and R1(b) using different protocols according to the acquisition stage of the post-enhancement data point. The agreement with the referential method was tested by calculating Pearson's correlation coefficient and the intra-class correlation coefficient. RESULTS: The lambda values measured by the two-point method increased (from 0.479 ± 0.041 to 0.534 ± 0.043) over time from 6 to 45 minutes after contrast and exhibited good correlation with the reference at each time point (r ≥ 0.875, p

As a member of the polymerase delta-interacting protein 1 (PDIP1) gene family, potassium channel tetramerisation domain-containing 10 (KCTD10) interacts with proliferating cell nuclear antigen (PCNA) and polymerase δ, participates in DNA repair, DNA replication and cell-cycle control. In order to further investigate the physiological functions of KCTD10, we generated the KCTD10 knockout mice. The heterozygous KCTD10(+/-) mice were viable and fertile, while the homozygous KCTD10(-/-) mice showed delayed growth from E9.0, and died at approximately E10.5, which displayed severe defects in angiogenesis and heart development. Further study showed that VEGF induced the expression of KCTD10 in a time- and dose-dependent manner. Quantitative real-time PCR and western blotting results revealed that several key members in Notch signaling were up-regulated either in KCTD10-deficient embryos or in KCTD10-silenced HUVECs. Meanwhile, the endogenous immunoprecipitation (IP) analysis showed that KCTD10 interacted with Cullin3 and Notch1 simultaneously, by which mediating Notch1 proteolytic degradation. Our studies suggest that KCTD10 plays crucial roles in embryonic angiogenesis and heart development in mammalians by negatively regulating the Notch signaling pathway.

OBJECTIVE: Irritable bowel syndrome (IBS) is a common clinical gastrointestinal dysfunction disorders. 5-sertonon (5-hydroxytryptamine, 5-HT) is a very important neurotransmitter, which is involved in gastrointestinal motion and sensation. Solute carrier family 6 member 4 (SLC6A4) gene encode serotonin transporter (SERT) which function is to rapidly reuptake the most of 5-HT. Therefore, it is needed to explore the association between SLC6A4 gene polymorphisms and IBS. METHODS: 119 patients and 238 healthy controls were administrated to detect the SLC6A4 gene polymorphisms including 5-HT-transporter-gene-linked polymorphic region (5-HTTLPR), variable number of tandem repeats (VNTRs) and three selected tag Single Nucleotide Polymorphisms (SNPs) rs1042173, rs3794808, rs2020936 by using polymerase chain reaction (PCR) and TaqMan® SNP Genotyping. RESULTS: There were significant difference for 5-HTTLPR between IBS and control groups (X2 = 106.168, P

Little is known about the long-term health impact of pregnancy on women. The objective of this study was to examine the association between parity and the risk of diabetes among a population of Chinese women.A total of 14,196 women (aged ≥ 45 years) from the Dongfeng-Tongji Cohort study who had experienced at least one live birth completed baseline questionnaires, medical examinations, and provided baseline blood samples. Participants were categorized into four groups according to parity (one, two, three, or four or more live births). Logistic regression models were used to investigate the association between parity and the risk of diabetes after controlling potential confounders.The prevalence of diabetes in the study population was 18.0% (2,552/14,196). Fasting plasma glucose levels increased with the increasing number of live births (P

Bacterial laccases are ideal alternatives of fungal laccases for specific industrial applications due to specific characteristics such as alkalescence dependence and high chloride tolerance. However, some bacterial laccases presented as inclusion bodies when expressing in Escherichia coli and showed thermal instability. In this study, rational design was employed to enhance the solubility and the thermostablity of the bacterial laccase Lac15-His6 based on the crystal structure obtained previously. After deletion of His-tag and residues323-332, the obtained Lac15D was completely expressed in soluble form even at a higher temperature of 28°C, compared to only 50% of Lac15-His6 expressed solubly at 16°C. It showed a two-time higher activity at temperatures lower than 35°C and a half-life increasing from 72 min to 150 min at 45°C. When used in chromogenic reactions, Lac15D showed constant activity toward dye precursors and their combinations under alkaline conditions, demonstrating its application potential in hair coloring biotechnology.

PURPOSE:To technically investigate the non-Gaussian diffusion of head and neck diffusion weighted imaging (DWI) at 3 Tesla and compare advanced non-Gaussian diffusion models, including diffusion kurtosis imaging (DKI), stretched-exponential model (SEM), intravoxel incoherent motion (IVIM) and statistical model in the patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS:After ethics approval was granted, 16 patients with NPC were examined using DWI performed at 3T employing an extended b-value range from 0 to 1500 s/mm(2). DWI signals were fitted to the mono-exponential and non-Gaussian diffusion models on primary tumor, metastatic node, spinal cord and muscle. Non-Gaussian parameter maps were generated and compared to apparent diffusion coefficient (ADC) maps in NPC. RESULTS:Diffusion in NPC exhibited non-Gaussian behavior at the extended b-value range. Non-Gaussian models achieved significantly better fitting of DWI signal than the mono-exponential model. Non-Gaussian diffusion coefficients were substantially different from mono-exponential ADC both in magnitude and histogram distribution. CONCLUSION:Non-Gaussian diffusivity in head and neck tissues and NPC lesions could be assessed by using non-Gaussian diffusion models. Non-Gaussian DWI analysis may reveal additional tissue properties beyond ADC and holds potentials to be used as a complementary tool for NPC characterization.

BackgroundThe prevalence of metabolic syndrome (MetS) is growing rapidly in China. Tai chi and dancing are common types of exercise among middle-aged and elderly Chinese. It remains unclear whether these activities are associated with a lower risk of MetS.Methodology/principal findingsA total of 15,514 individuals (6,952 men, 8,562 women) aged 50 to 70 years from the Dongfeng-Tongji Cohort in Shiyan, China participated in a cross-sectional study. Physical activity and other lifestyle factors were assessed with semi-structured questionnaires during face-to-face interviews. MetS was defined by the current National Cholesterol Education Program/Adult treatment Panel III criteria for Asian Americans. The prevalence of MetS was 33.2% in the study population. In the multivariable-adjusted logistic regression analyses, total physical activity levels were monotonically associated with a lower odds of MetS [OR 0.75 comparing extreme quintiles, 95% confidence interval (CI) 0.66-0.86, PConclusions/significanceJogging, tai chi and dancing are associated with a significantly lower risk of having MetS in middle-aged and older Chinese. Future intervention studies should consider the role of jogging, tai chi and dancing in preventing MetS.

BackgroundShift work has been associated with adverse health effects by disturbing circadian rhythms. However,its potential long-term health effects and the persistent effects after leaving shifts have not been well established.Methods and resultsWe studied 26,463 workers from Tongji-Dongfeng Cohort in China. All the participants are retired employees of Dongfeng Motor Company. Information on demographics, occupational history and medical history were gathered through questionnaires. After adjusting potential confounders in the logistic regression models, shift work was associated with poor sleeping quality, diabetes and hypertension independently. We observed significant effects of shift work on poor sleeping quality, diabetes and hypertension; the ORs (95%CI) are 1.18 (1.09-1.27), 1.10 (1.03-1.17) and 1.05 (1.01-1.09) respectively. In the further analysis, we found elevated ORs (95%CI) for participants with poor sleeping quality, the ORs (95%CI) are 1.34 (1.08-1.60), 1.13 (1.05-1.21), 1.05 (1.03-1.07) and 1.05 (1.01-1.09) for 1-4, 5-9, 10-19, ≥20 years of shift work respectively. However, with the extension of leaving shift work duration, the effects of shift work on sleep quality gradually reduced.ConclusionsShift work may be an independent risk factor for sleeping quality, diabetes and hypertension even in retired workers. Applicable intervention strategies are needed for prevention of sleep loss, diabetes, and hypertension for shift workers.

Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS) have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome wide association studies on four common lipid traits including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) in a Han Chinese population totaling 3,451 healthy subjects. Replication was performed in an additional 8,830 subjects of Han Chinese ethnicity. We replicated eight loci associated with lipid levels previously reported in a European population. The loci genome wide significantly associated with TC were near DOCK7, HMGCR and ABO; those genome wide significantly associated with TG were near APOA1/C3/A4/A5 and LPL; those genome wide significantly associated with LDL were near HMGCR, ABO and TOMM40; and those genome wide significantly associated with HDL were near LPL, LIPC and CETP. In addition, an additive genotype score of eight SNPs representing the eight loci that were found to be associated with lipid levels was associated with higher TC, TG and LDL levels (P = 5.52 × 10(-16), 1.38 × 10(-6) and 5.59 × 10(-9), respectively). These findings suggest the cumulative effects of multiple genetic loci on plasma lipid levels. Comparisons with previous GWAS of lipids highlight heterogeneity in allele frequency and in effect size for some loci between Chinese and European populations. The results from our GWAS provided comprehensive and convincing evidence of the genetic determinants of plasma lipid levels in a Chinese population.

PIK3CA (phosphoinositide-3-kinase, catalytic, alpha polypeptide) mutations can help predict the antitumor activity of phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway inhibitors in both preclinical and clinical settings. In light of the recent discovery of tumor-initiating cancer stem cells (CSCs) in various tumor types, we developed an in vitro CSC model from xenograft tumors established in mice from a colorectal cancer patient tumor in which the CD133+/EpCAM+ population represented tumor-initiating cells. CD133+/EpCAM+ CSCs were enriched under stem cell culture conditions and formed 3-dimensional tumor spheroids. Tumor spheroid cells exhibited CSC properties, including the capability for differentiation and self-renewal, higher tumorigenic potential and chemo-resistance. Genetic analysis using an OncoCarta™ panel revealed a PIK3CA (H1047R) mutation in these cells. Using a dual PI3K/mTOR inhibitor, PF-04691502, we then showed that blockage of the PI3K/mTOR pathway inhibited the in vitro proliferation of CSCs and in vivo xenograft tumor growth with manageable toxicity. Tumor growth inhibition in mice was accompanied by a significant reduction of phosphorylated Akt (pAKT) (S473), a well-established surrogate biomarker of PI3K/mTOR signaling pathway inhibition. Collectively, our data suggest that PF-04691502 exhibits potent anticancer activity in colorectal cancer by targeting both PIK3CA (H1047R) mutant CSCs and their derivatives. These results may assist in the clinical development of PF-04691502 for the treatment of a subpopulation of colorectal cancer patients with poor outcomes.

Four pairs of XX and XY gonads from Nile tilapia were sequenced at four developmental stages, 5, 30, 90, and 180 days after hatching (dah) using Illumina Hiseq(TM) technology. This produced 28 Gb sequences, which were mapped to 21,334 genes. Of these, 259 genes were found to be specifically expressed in XY gonads, and 69 were found to be specific to XX gonads. Totally, 187 XX- and 1,358 XY-enhanced genes were identified, and 2,978 genes were found to be co-expressed in XX and XY gonads. Almost all steroidogenic enzymes, including cyp19a1a, were up-regulated in XX gonads at 5 dah; but in XY gonads these enzymes, including cyp11b2, were significantly up-regulated at 90 dah, indicating that, at a time critical to sex determination, the XX fish produced estrogen and the XY fish did not produce androgens. The most pronounced expression of steroidogenic enzyme genes was observed at 30 and 90 dah for XX and XY gonads, corresponding to the initiation of germ cell meiosis in the female and male gonads, respectively. Both estrogen and androgen receptors were found to be expressed in XX gonads, but only estrogen receptors were expressed in XY gonads at 5 dah. This could explain why exogenous steroid treatment induced XX and XY sex reversal. The XX-enhanced expression of cyp19a1a and cyp19a1b at all stages suggests an important role for estrogen in female sex determination and maintenance of phenotypic sex. This work is the largest collection of gonadal transcriptome data in tilapia and lays the foundation for future studies into the molecular mechanisms of sex determination and maintenance of phenotypic sex in non-model teleosts.

The published antibodies (Abs) against CD22 on B cells including Epratuzumab could inhibit B cell activation mainly through binding to C2-set Ig domain of CD22, but they are rarely reported to modulate the pathogenic CD4(+) T cell function in systemic lupus erythematosus (SLE). Recently, it was proved that the extracellular amino-terminal V-set Ig domain of CD22 might mediate the interaction of B and T cells, but for now the exact effect of this domain on CD4(+) T cell biology have not been identified. Thus, in this study, we screened out a peptide termed B2285 from this V-set Ig domain, developed the novel specific anti-B2285 Abs in rabbits, and investigated their effects in MRL/lpr mice with spontaneous SLE. The results showed that anti-B2285 Abs could ameliorate the disease severity obviously in spontaneous SLE mice with the decreased differentiations of Th1 and Th17 cells and no changes of Th2 and Treg cells. In co-cultured B cells and CD4(+) T cells, this specific anti-CD22 Abs was observed to inhibit the anti-dsDNA Abs production, CD4(+) T cells proliferation, the protein levels of T-bet and RORγt, and the mRNA levels of TNF-α, IFN-γ, IL-6 and IL-17 in CD4(+) T cells. Moreover, the expression of CD45RO on CD4(+) T cells could be also apparently diminished by this novel Abs. The data suggested that anti-B2285 Abs could slow SLE progression significantly by regulating Th1 and Th17 cells function via B-T cell interaction and the cytokine network regulation. The treatment against V-set Ig domain of CD22 would be a valuable therapeutic method for SLE and other autoimmune diseases.

BACKGROUND:High carbohydrate antigen 125 (CA-125) level was reported to be associated with some cardiac dysfunctions, such as chronic heart failure, but the relationship between CA-125 level and coronary heart disease (CHD) risk remains unclear. The aim of this study was to explore the potential association in a Chinese older population. METHODS:In a population-based case-control study conducted in a Chinese older population, serum CA-125 levels were measured in 1177 diagnosed CHD patients and 3531 age and sex matched control subjects without CHD. RESULTS:Serum CA-125 level was significantly higher in CHD patients than controls (P < 0.001) with adjustment for age, gender, smoking, drinking, BMI, physical activity, hypertension, dyslipidemia, diabetes mellitus, medication history and family history of CHD and myocardial infarction. CHD risk was doubled (OR: 2.10, 95%CI: 1.69-2.60) among subjects in the highest quartile compared to those in the lowest quartile of CA-125 level (P trend < 0.001). Furthermore, CA-125 levels were associated with CHD risks in subjects with age over 60 years (OR: 2.19, 95%CI: 1.75-2.73), current smokers (OR: 2.29, 95%CI: 1.50-3.49), current drinkers (OR: 2.35, 95%CI: 1.57-3.53) and subjects with hypertension (OR: 2.04, 95%CI: 1.71-2.43). CONCLUSIONS:Elevated serum CA-125 level might be associated with increased risk of coronary heart disease in the Chinese older population. Further investigations are needed to identify the possible biological role of CA-125 in CHD development in the future.

Cellular retinoic acid binding protein 2 (CRABP2), a member of a family of specific carrier proteins for Vitamin A, belongs to a family of small cytosolic lipid binding proteins. Our previous study suggested that CRABP2 was involved in skeletal muscle development; however, the molecular function and regulatory mechanism of CRABP2 in myogenesis remained unclear. In this study, we found that the expression of the CRABP2 gene was upregulated during C2C12 differentiation. An over-expression assay revealed that CRABP2 promotes myogenic transformation by regulating the cell cycle during C2C12 differentiation. The region from -459 to -4 bp was identified as the core promoter and contains a TATA box, a GC box and binding sites for the transcription factors MyoD and Sp1. Over-expression, site-directed mutagenesis and EMSA assays indicated that the transcription factors MyoD and Sp1 regulate CRABP2 expression and promote myoblast differentiation in C2C12 cells.

BACKGROUND: Head and neck Magnetic Resonance (MR) Images are vulnerable to the arterial blood in-flow effect. To compensate for this effect and enhance accuracy and reproducibility, dynamic tracer concentration in veins was proposed and investigated for quantitative dynamic contrast-enhanced (DCE) MRI analysis in head and neck. METHODOLOGY: 21 patients with head and neck tumors underwent DCE-MRI at 3T. An automated method was developed for blood vessel selection and separation. Dynamic concentration-time-curves (CTCs) in arteries and veins were used for the Tofts model parameter estimations. The estimation differences by using CTCs in arteries and veins were compared. Artery and vein voxels were accurately separated by the automated method. Remarkable inter-slice tracer concentration differences were found in arteries while the inter-slice concentration differences in veins were moderate. Tofts model fitting by using the CTCs in arteries and veins produced significantly different parameter estimations. The individual artery CTCs resulted in large (>50% generally) inter-slice parameter estimation variations. Better inter-slice consistency was achieved by using the vein CTCs. CONCLUSIONS: The use of vein CTCs helps to compensate for arterial in-flow effect and reduce kinetic parameter estimation error and inconsistency for head and neck DCE-MRI.

Brucella melitensis is a facultative intracellular bacterium that replicates within macrophages. The ability of brucellae to survive and multiply in the hostile environment of host macrophages is essential to its virulence. The RNA-binding protein Hfq is a global regulator that is involved in stress resistance and pathogenicity. Here we demonstrate that Hfq is essential for stress adaptation and intracellular survival in B. melitensis. A B. melitensis hfq deletion mutant exhibits reduced survival under environmental stresses and is attenuated in cultured macrophages and mice. Microarray-based transcriptome analyses revealed that 359 genes involved in numerous cellular processes were dysregulated in the hfq mutant. From these same samples the proteins were also prepared for proteomic analysis to directly identify Hfq-regulated proteins. Fifty-five proteins with significantly affected expression were identified in the hfq mutant. Our results demonstrate that Hfq regulates many genes and/or proteins involved in metabolism, virulence, and stress responses, including those potentially involved in the adaptation of Brucella to the oxidative, acid, heat stress, and antibacterial peptides encountered within the host. The dysregulation of such genes and/or proteins could contribute to the attenuated hfq mutant phenotype. These findings highlight the involvement of Hfq as a key regulator of Brucella gene expression and facilitate our understanding of the role of Hfq in environmental stress adaptation and intracellular survival of B. melitensis.

BACKGROUND: Platelet aggregation mediated by inflammation played a critical role in the development of coronary heart diseases (CHD). Our previous clinical researches showed that Th17 cells and their characteristic cytokine IL-17A were associated with the plaque destabilization in patients with acute coronary syndrome (ACS). However, the potent effect of IL-17A on platelets-induced atherothrombosis remains unknown. METHODS AND RESULTS: In this study, we detected the plasma IL-17A levels and platelet aggregation in patients with stable angina (SA), unstable angina (UA), acute myocardial infarction (AMI) and chest pain syndrome (CPS). In addition, the markers of platelet activation (CD62P/PAC-1) and the mitogen-activated protein kinases (MAPKs) pathway were detected in platelets from ACS patients. We found that plasma IL-17A levels and platelet aggregation in patients with ACS (UA and AMI) were significantly higher than patients with SA and CPS, and the plasma IL-17A levels were positively correlated with the platelet aggregation (R = 0.47, P

Parabasalia are single-celled eukaryotes (protists) that are mainly comprised of endosymbionts of termites and wood roaches, intestinal commensals, human or veterinary parasites, and free-living species. Phylogenetic comparisons of parabasalids are typically based upon morphological characters and 18S ribosomal RNA gene sequence data (rDNA), while biochemical or molecular studies of parabasalids are limited to a few axenically cultivable parasites. These previous analyses and other studies based on PCR amplification of duplicated protein-coding genes are unable to fully resolve the evolutionary relationships of parabasalids. As a result, genetic studies of Parabasalia lag behind other organisms.Comparing parabasalid EF1α, α-tubulin, enolase and MDH protein-coding genes with information from the Trichomonas vaginalis genome reveals difficulty in resolving the history of species or isolates apart from duplicated genes. A conserved single-copy gene encodes the largest subunit of RNA polymerase II (Rpb1) in T. vaginalis and other eukaryotes. Here we directly sequenced Rpb1 degenerate PCR products from 10 parabasalid genera, including several T. vaginalis isolates and avian isolates, and compared these data by phylogenetic analyses. Rpb1 genes from parabasalids, diplomonads, Parabodo, Diplonema and Percolomonas were all intronless, unlike intron-rich homologs in Naegleria, Jakoba and Malawimonas.The phylogeny of Rpb1 from parasitic and free-living parabasalids, and conserved Rpb1 insertions, support Trichomonadea, Tritrichomonadea, and Hypotrichomonadea as monophyletic groups. These results are consistent with prior analyses of rDNA and GAPDH sequences and ultrastructural data. The Rpb1 phylogenetic tree also resolves species- and isolate-level relationships. These findings, together with the relative ease of Rpb1 isolation, make it an attractive tool for evaluating more extensive relationships within Parabasalia.

BACKGROUND: Brucella melitensis is a facultative, intracellular, pathogenic bacterium that replicates within macrophages. The type IV secretion system encoded by the virB operon (virB) is involved in Brucella intracellular survival. However, the underlying molecular mechanisms, especially the target proteins affected by the virB, remain largely unclear. METHODOLOGY/PRINCIPAL FINDINGS: In order to define the proteins affected by virB, the proteomes of wild-type and the virB mutant were compared under in vitro conditions where virB was highly activated. The differentially expressed proteins were identified by MALDI-TOF-MS. Forty-four down-regulated and eighteen up-regulated proteins which exhibited a 2-fold or greater change were identified. These proteins included those involved in amino acid transport and metabolism, lipid metabolism, energy production, cell membrane biogenesis, translation, post-translational modifications and protein turnover, as well as unknown proteins. Interestingly, several important virulence related proteins involved in intracellular survival, including VjbR, DnaK, HtrA, Omp25, and GntR, were down-regulated in the virB mutant. Transcription analysis of virB and vjbR at different growth phase showed that virB positively affect transcription of vjbR in a growth phase dependent manner. Quantitative RT-PCR showed that transcription of these genes was also affected by virB during macrophage cell infection, consistent with the observed decreased survival of the virB mutant in macrophage. CONCLUSIONS/SIGNIFICANCE: These data indicated that the virB operon may control the intracellular survival of Brucella by affecting the expression of relevant proteins.