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ProposeTo review published Physical Activity (PA) on the Mental Health of Children and Adolescents aged 5 to 18 years during COVID-19 pandemic-induced school closures.MethodsFrom the database creation to April 2022, 10 databases are retrieved, with 4427 records filtered, 14 included in this research. The research takes Agency for Healthcare Research and Quality (AHRQ) evaluation standards.ResultsThe thesis selects 14 studies from 6 countries, involving 400009 children and adolescents. These studies happened during the lockdown of COVID-19 (from December 2019 to April 2021). During the lockdown of COVID-19, schools were closed, which was considered part of a more extensive lockdown. Schools were closed for 1 to 4 weeks. There were 10 high quality studies (71.4%) and 4 medium quality studies (28.6%). 4 studies report that the pandemic reduces the time of PA but increases the time of watching screen and sitting. 10 studies (71.4%) identify that PA is positive for the mental health, because it helps reduce mental symptoms to a certain extent, especially anxiety, depression, and emotional disorders. 5 studies show that PA may not improve the mental health of children and adolescents under 12 during the pandemic. 4 studies indicate that the influence of PA on mental health of children and adolescents is determined by the amount of activity, including the extent, intensity, frequency, and duration, etc.ConclusionsIn this narrative synthesis of reports from the class suspension period, reports that PA has a improve on the mental health of children and adolescents to a certain extent. it is found that PA may be helpful in reducing mental health symptoms of children and adolescents who are influenced by class suspension because of the COVID-19 pandemic. Therefore, stakeholders of the mental health of children and adolescents around the world should recommend PA because it is a practicable and beneficial way for long-term mental support.

BackgroundObservational studies have demonstrated an association between white blood cells (WBC) subtypes and type 2 diabetes (T2D) risk. However, it is unknown whether this relationship is causal. We used Mendelian randomization (MR) to investigate the causal effect of WBC subtypes on T2D and glycemic traits.MethodsThe summary data for neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts were extracted from a recent genome-wide association study (n = 173,480). The DIAGRAM and MAGIC consortia offered summary data pertaining to T2D and glycemic characteristics, including fasting glucose (FG) (n = 133,010), glycosylated hemoglobin (HbA1c) (n = 46,368), and homeostatic model assessment-estimated insulin resistance (HOMA-IR) (n = 37,037). A series of MR analyses (univariable MR, multivariable MR, and reverse MR) were used to investigate the causal association of different WBC subtypes with T2D and glycemic traits.ResultsUsing the inverse-variance weighted method, we found one standard deviation increases in genetically determined neutrophil [odd ratio (OR): 1.086, 95% confidence interval (CI): 0.877-1.345], lymphocyte [0.878 (0.766-1.006)], monocyte [1.010 (0.906-1.127)], eosinophil [0.995 (0.867-1.142)], and basophil [0.960 (0.763-1.207)] were not causally associated with T2D risk. These findings were consistent with the results of three pleiotropy robust methods (MR-Egger, weighted median, and mode-based estimator) and multivariable MR analyses. Reverse MR analysis provided no evidence for the reverse causation of T2D on WBC subtypes. The null causal effects of WBC subtypes on FG, HbA1c, and HOMA-IR were also identified.ConclusionsWBCs play no causal role in the development of insulin resistance and T2D. The observed association between these factors may be explained by residual confounding.

The unique infinite self-renewal ability and multidirectional differentiation potential of stem cells provide a strong support for the clinical treatment. In light of the growing demands for stem cell storage, how to ensure personal privacy security and comply with strict ethical supervision requirements is particularly important. In order to solve the problem of low security of traditional encryption algorithm, we proposed a double encryption protection (DEP) algorithm for stem cell bank privacy data based on improved AES and chaotic encryption technology. Firstly, we presented the hash value key decomposition algorithm, through the hash value dynamic coding, cyclic shift, conversion calculation to get the key of each subsystem in the built algorithm. Secondly, DEP algorithm for privacy data is realized with two level of encryption. The first level of encryption protection algorithm used AES as the main framework, adding dynamic coding and byte filling based on DNA coding, and carries out dynamic shift of rows and simplified mixing of columns. The second level of encryption protection algorithm conducted random encoding, operation, diffusion and decoding based on the results of our proposed sequence conversion algorithm. Finally, we raised two evaluation indexes, the number of characters change rate (NCCR) and the unified average change intensity of text (UACIT) to measure the sensitivity of encryption algorithms to changes in plain information. The experimental results of using DEP shown that the average values of histogram variance, information entropy, NCCR and UACIT are116.7883, 7.6688, 32.52% and 99.67%, respectively. DEP algorithm has a large key space, high key sensitivity, and enables dynamic encryption of private data in stem cell bank. The encryption scheme provided in this study ensures the security of the private information of stem cell bank in private cloud environment, and also provides a new method for the encryption of similar high confidentiality data.

In this study, the numerical direct shear tests were conducted to investigate the shear mechanical properties of joint networks under constant normal stiffness (CNS) boundary conditions. The influence of random joint number on shear stress (τ), dilation (normal displacement, δv) and normal stress (σn) of rock mass were studied quantitatively with fixed main slip surface. At the same time, the internal stress evolution process and failure process were analyzed. The results reveal that the number of random joints (γ) has little effect on the shear and normal stresses. The normal displacement of the sample generally decreases as the number of random joints increases. In addition, the normal displacement of the specimen is absorbed by the random joints when the number of random joints in the specimen increases to a certain level: when γ is greater than 6 and the shear displacement (μ) reaching 10 mm, the specimen exhibits shear contraction. Therefore, the internal random joints mainly control the failure mode and dilatancy performance of the specimen, while the main joint of the rock controls the shear stress of the specimen.

BackgroundThe effects of multiple meteorological factors on influenza activity remain unclear in Chongqing, the largest municipality in China. We aimed to fix this gap in this study.MethodsWeekly meteorological data and influenza surveillance data in Chongqing were collected from 2012 to 2019. Distributed lag nonlinear models (DLNMs) were conducted to estimate the effects of multiple meteorological factors on influenza activity.ResultsInverted J-shaped nonlinear associations between mean temperature, absolute humidity, wind speed, sunshine and influenza activity were found. The relative risks (RRs) of influenza activity increased as weekly average mean temperature fell below 18.18°C, average absolute humidity fell below 12.66 g/m3, average wind speed fell below 1.55 m/s and average sunshine fell below 2.36 hours. Taking the median values as the references, lower temperature, lower absolute humidity and windless could significantly increase the risks of influenza activity and last for 4 weeks. A J-shaped nonlinear association was observed between relative humidity and influenza activity; the risk of influenza activity increased with rising relative humidity with 78.26% as the break point. Taking the median value as the reference, high relative humidity could increase the risk of influenza activity and last for 3 weeks. In addition, we found the relationship between aggregate rainfall and influenza activity could be described with a U-shaped curve. Rainfall effect has significantly higher RR than rainless effect.ConclusionsOur study shows that multiple meteorological factors have strong associations with influenza activity in Chongqing, providing evidence for developing a meteorology-based early warning system for influenza to facilitate timely response to upsurge of influenza activity.

The analysis and simulation of the interactions that occur in group situations is important when humans and artificial agents, physical or virtual, must coordinate when inhabiting similar spaces or even collaborate, as in the case of human-robot teams. Artificial systems should adapt to the natural interfaces of humans rather than the other way around. Such systems should be sensitive to human behaviors, which are often social in nature, and account for human capabilities when planning their own behaviors. A limiting factor relates to our understanding of how humans behave with respect to each other and with artificial embodiments, such as robots. To this end, we present CongreG8 (pronounced 'con-gre-gate'), a novel dataset containing the full-body motions of free-standing conversational groups of three humans and a newcomer that approaches the groups with the intent of joining them. The aim has been to collect an accurate and detailed set of positioning, orienting and full-body behaviors when a newcomer approaches and joins a small group. The dataset contains trials from human and robot newcomers. Additionally, it includes questionnaires about the personality of participants (BFI-10), their perception of robots (Godspeed), and custom human/robot interaction questions. An overview and analysis of the dataset is also provided, which suggests that human groups are more likely to alter their configuration to accommodate a human newcomer than a robot newcomer. We conclude by providing three use cases that the dataset has already been applied to in the domains of behavior detection and generation in real and virtual environments. A sample of the CongreG8 dataset is available at https://zenodo.org/record/4537811.

In the study of emotional memory bias in depressed individuals, most previous studies have used emotional materials, but there were significant differences in the effects of different emotion-inducing methods on face memory. In the present study, two experiments were conducted to explore the effects of different emotion-inducing methods on memory between healthy participants and non-clinically depressed participants. The results from experiment 1 showed that when feedback was used as induction, the memory performance of the non-clinical depression group was significantly higher than that of the healthy group under the condition of negative feedback. Under positive and neutral feedback, there were no significant differences between the two groups. In experiment 2, when emotional materials were used as a mode of induction, no significantly difference in each emotional condition between the healthy and depressed groups was found. The results of the present study show that different methods of emotional induction have different effects on depressed participants. Compared with the emotion induced by the emotional material, the non-clinical depressed participants had a better memory effect induced by negative emotional events.

Japanese encephalitis (JE) is an acute infectious disease caused by the Japanese encephalitis virus (JEV) and is transmitted by mosquitoes. Meteorological conditions are known to play a pivotal role in the spread of JEV. In this study, a zero-inflated generalised additive model and a long short-term memory model were used to assess the relationship between the meteorological factors and population density of Culex tritaeniorhynchus as well as the incidence of JE and to predict the prevalence dynamics of JE, respectively. The incidence of JE in the previous month, the mean air temperature and the average of relative humidity had positive effects on the outbreak risk and intensity. Meanwhile, the density of all mosquito species in livestock sheds (DMSL) only affected the outbreak risk. Moreover, the region-specific prediction model of JE was developed in Chongqing by used the Long Short-Term Memory Neural Network. Our study contributes to a better understanding of the JE dynamics and helps the local government establish precise prevention and control measures.

The quantitative understanding of human behavior is a key issue in modern science. Recently, inhomogeneous human activities have been described by bursts (consecutive activities separated by long periods of inactivity) and characterized by fat-tailed inter-event time (interval between two activities) distributions. However, the dynamics between number of activities and activity duration are still unclear. In this study, we analyzed 133 million toll-free call records from China to study the dynamics between call frequency and call duration. We confirmed that both call frequency and call duration exhibit circadian cycles and weekly cycles. By analyzing intraday patterns of these two metrics, we found the opposite volatility and clustered distributions. Results of clustering analysis showed that calling activity to toll-free numbers can be clustered into four clusters. In the "Work" cluster, the distribution of call duration was significantly different from that in the other clusters. The corresponding time of "Work" cluster was much shorter than estimates based on common sense. Intraday patterns and clustering results showed that both call frequency and call duration are primarily related to circadian cycles, the nature of human beings, and that work is a secondary factor that affects these variables. Moreover, we found a strong positive correlation between call frequency and call duration, as well as polarization of joint probability. The polarization indicates two extremes in inhomogeneous calling activity to toll-free numbers, i.e., either people are very busy or very idle. The empirical probability of the extreme was approximately four times that of random probability. Our findings may have great usage for studying the dynamics of inhomogeneous human behavior.

IntroductionThe ST-4821 complex (cc4821) is a leading cause of serogroup C and serogroup B invasive meningococcal disease in China where diverse strains in two phylogenetic groups (groups 1 and 2) have acquired fluoroquinolone resistance. cc4821 was recently prevalent among carriage isolates in men who have sex with men in New York City (USA). Genome-level population studies have thus far been limited to Chinese isolates. The aim of the present study was to build upon these with an extended panel of international cc4821 isolates.MethodsGenomes of isolates from Asia (1972 to 2017), Europe (2011 to 2018), North America (2007), and South America (2014) were sequenced or obtained from the PubMLST Neisseria database. Core genome comparisons were performed in PubMLST.ResultsFour lineages were identified. Western isolates formed a distinct, mainly serogroup B sublineage with alleles associated with fluoroquinolone susceptibility (MIC DiscussionThe previously identified cc4821 group 2 was resolved into three separate lineages. Clustering of western isolates was surprising given the overall diversity of cc4821. Possible association of this cluster with the anogenital niche is worthy of monitoring given concerns surrounding antibiotic resistance and potential subcapsular vaccine escape.

Free amino acids are an important indicator of the freshness of yellow tea. This study investigated a novel procedure for predicting the free amino acid (FAA) concentration of yellow tea. It was developed based on the combined spectral and textural features from hyperspectral images. For the purposes of exploration and comparison, hyperspectral images of yellow tea (150 samples) were captured and analyzed. The raw spectra were preprocessed with Savitzky-Golay (SG) smoothing. To reduce the dimension of spectral data, five feature wavelengths were extracted using the successive projections algorithm (SPA). Five textural features (angular second moment, entropy, contrast, correlation, and homogeneity) were extracted as textural variables from the characteristic grayscale images of the five characteristic wavelengths using the gray-level co-occurrence matrix (GLCM). The FAA content prediction model with different variables was established by a genetic algorithm-support vector regression (GA-SVR) algorithm. The results showed that better prediction results were obtained by combining the feature wavelengths and textural variables. Compared with other data, this prediction result was still very satisfactory in the GA-SVR model, indicating that data fusion was an effective way to enhance hyperspectral imaging ability for the determination of free amino acid values in yellow tea.

Lipid raft is an important element for the cellular entry of some viruses, including coronavirus infectious bronchitis virus (IBV). However, the exact role of lipid rafts in the cellular membrane during the entry of IBV into host cells is still unknown. In this study, we biochemically fractionated IBV-infected cells via sucrose density gradient centrifugation after depleting plasma membrane cholesterol with methyl-β-cyclodextrin or Mevastatin. Our results demonstrated that unlike IBV non-structural proteins, IBV structural proteins co-localized with lipid raft marker caveolin-1. Infectivity assay results of Vero cells illustrated that the drug-induced disruption of lipid rafts significantly suppressed IBV infection. Further studies revealed that lipid rafts were not required for IBV genome replication or virion release at later stages. However, the drug-mediated depletion of lipid rafts in Vero cells before IBV attachment significantly reduced the expression of viral structural proteins, suggesting that drug treatment impaired the attachment of IBV to the cell surface. Our results indicated that lipid rafts serve as attachment factors during the early stages of IBV infection, especially during the attachment stage.

Liriomyza trifolii is a highly-invasive leafmining insect that causes significant damage to vegetables and horticultural crops worldwide. Relatively few studies have quantified gene expression in L. trifolii using real-time quantitative PCR (RT-qPCR), which is a reliable and sensitive technique for measuring gene expression. RT-qPCR requires the selection of reference genes to normalize gene expression data and control for internal differences between samples. In this study, nine housekeeping genes from L. trifolii were selected for their suitability in normalizing gene expression using geNorm, Normfinder, BestKeeper, the ΔCt method and RefFinder. HSP21.7, which encodes heat shock protein 21.7, was used as a target gene to validate the expression of candidate reference genes. Results indicated that ACTIN and 18S were optimal for developmental stage and low temperature, TUB and 18S showed the most stable expression for sex, and GAPDH and ACTIN were the best reference genes for monitoring gene expression at high temperature. Selection and validation of appropriate reference genes are critical steps in normalizing gene expression levels, which improve the accuracy and quality of expression data. Results of this study provide vital information on reference genes and is valuable in developing a standardized RT-qPCR protocol for functional genomics research in L. trifolii.

The polyphagous agromyzid fly, Liriomyza trifolii, is a significant and important insect pest of ornamental and vegetable crops worldwide. The adaptation of insects to different environments is facilitated by heat shock proteins (HSPs), which play an important role in acclimation to thermal stress. In this study, we cloned and characterized five HSP-encoding genes of L. trifolii (Lthsp20, Lthsp40, Lthsp60, Lthsp70, and Lthsp90) and monitored their expression under different thermal stresses using real-time quantitative PCR. Pupae of L. trifolii were exposed to 19 different temperatures ranging from -20 to 45°C. The results revealed that Lthsp20, Lthsp40, Lthsp70 and Lthsp90 were significantly upregulated in response to both heat and cold stress, while Lthsp60 was induced only by heat temperatures. The temperatures of the onset (Ton) and maximal (Tmax) expression of the five Lthsps were also determined and compared with published Ton and Tmax values of homologous genes in L. sativae and L. huidobrensis. Although L. trifolii occurs primarily in southern China, it has cold tolerance comparable with the other two Liriomyza species. Based on the heat shock proteins expression patterns, L. trifolii has the capacity to tolerate extreme temperatures and the potential to disseminate to northern regions of China.

Genetic variation and early adverse environmental events work together to increase risk for schizophrenia. γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in adult mammalian brain, plays a major role in normal brain development, and has been strongly implicated in the pathobiology of schizophrenia. GABA synthesis is controlled by two glutamic acid decarboxylase (GAD) genes, GAD1 and GAD2, both of which produce a number of alternative transcripts. Genetic variants in the GAD1 gene are associated with increased risk for schizophrenia, and reduced expression of its major transcript in the human dorsolateral prefrontal cortex (DLPFC). No consistent changes in GAD2 expression have been found in brains from patients with schizophrenia. In this work, with the use of RNA sequencing and PCR technologies, we confirmed and tracked the expression of an alternative truncated transcript of GAD2 (ENST00000428517) in human control DLPFC homogenates across lifespan besides the well-known full length transcript of GAD2. In addition, using quantitative RT-PCR, expression of GAD2 full length and truncated transcripts were measured in the DLPFC of patients with schizophrenia, bipolar disorder and major depression. The expression of GAD2 full length transcript is decreased in the DLPFC of schizophrenia and bipolar disorder patients, while GAD2 truncated transcript is increased in bipolar disorder patients but decreased in schizophrenia patients. Moreover, the patients with schizophrenia with completed suicide or positive nicotine exposure showed significantly higher expression of GAD2 full length transcript. Alternative transcripts of GAD2 may be important in the growth and development of GABA-synthesizing neurons as well as abnormal GABA signaling in the DLPFC of patients with schizophrenia and affective disorders.

Panax ginseng C. A. Meyer is a highly valued medicinal plant. Cylindrocarpon destructans is a destructive pathogen that causes root rot and significantly reduces the quality and yield of P. ginseng. However, an efficient method to control root rot remains unavailable because of insufficient understanding of the molecular mechanism underlying C. destructans-P. ginseng interaction. In this study, C. destructans-induced transcriptomes at different time points were investigated using RNA sequencing (RNA-Seq). De novo assembly produced 73,335 unigenes for the P. ginseng transcriptome after C. destructans infection, in which 3,839 unigenes were up-regulated. Notably, the abundance of the up-regulated unigenes sharply increased at 0.5 d postinoculation to provide effector-triggered immunity. In total, 24 of 26 randomly selected unigenes can be validated using quantitative reverse transcription (qRT)-PCR. Gene ontology enrichment analysis of these unigenes showed that "defense response to fungus", "defense response" and "response to stress" were enriched. In addition, differentially expressed transcription factors involved in the hormone signaling pathways after C. destructans infection were identified. Finally, differentially expressed unigenes involved in reactive oxygen species and ginsenoside biosynthetic pathway during C. destructans infection were indentified. To our knowledge, this study is the first to report on the dynamic transcriptome triggered by C. destructans. These results improve our understanding of disease resistance in P. ginseng and provide a useful resource for quick detection of induced markers in P. ginseng before the comprehensive outbreak of this disease caused by C. destructans.

In high efficiency video coding (HEVC), coding tree contributes to excellent compression performance. However, coding tree brings extremely high computational complexity. Innovative works for improving coding tree to further reduce encoding time are stated in this paper. A novel low complexity coding tree mechanism is proposed for HEVC fast coding unit (CU) encoding. Firstly, this paper makes an in-depth study of the relationship among CU distribution, quantization parameter (QP) and content change (CC). Secondly, a CU coding tree probability model is proposed for modeling and predicting CU distribution. Eventually, a CU coding tree probability update is proposed, aiming to address probabilistic model distortion problems caused by CC. Experimental results show that the proposed low complexity CU coding tree mechanism significantly reduces encoding time by 27% for lossy coding and 42% for visually lossless coding and lossless coding. The proposed low complexity CU coding tree mechanism devotes to improving coding performance under various application conditions.

Individuals with tetraplegia lack independent mobility, making them highly dependent on others to move from one place to another. Here, we describe how two macaques were able to use a wireless integrated system to control a robotic platform, over which they were sitting, to achieve independent mobility using the neuronal activity in their motor cortices. The activity of populations of single neurons was recorded using multiple electrode arrays implanted in the arm region of primary motor cortex, and decoded to achieve brain control of the platform. We found that free-running brain control of the platform (which was not equipped with any machine intelligence) was fast and accurate, resembling the performance achieved using joystick control. The decoding algorithms can be trained in the absence of joystick movements, as would be required for use by tetraplegic individuals, demonstrating that the non-human primate model is a good pre-clinical model for developing such a cortically-controlled movement prosthetic. Interestingly, we found that the response properties of some neurons differed greatly depending on the mode of control (joystick or brain control), suggesting different roles for these neurons in encoding movement intention and movement execution. These results demonstrate that independent mobility can be achieved without first training on prescribed motor movements, opening the door for the implementation of this technology in persons with tetraplegia.

High-efficiency video compression technology is of primary importance to the storage and transmission of digital medical video in modern medical communication systems. To further improve the compression performance of medical ultrasound video, two innovative technologies based on diagnostic region-of-interest (ROI) extraction using the high efficiency video coding (H.265/HEVC) standard are presented in this paper. First, an effective ROI extraction algorithm based on image textural features is proposed to strengthen the applicability of ROI detection results in the H.265/HEVC quad-tree coding structure. Second, a hierarchical coding method based on transform coefficient adjustment and a quantization parameter (QP) selection process is designed to implement the otherness encoding for ROIs and non-ROIs. Experimental results demonstrate that the proposed optimization strategy significantly improves the coding performance by achieving a BD-BR reduction of 13.52% and a BD-PSNR gain of 1.16 dB on average compared to H.265/HEVC (HM15.0). The proposed medical video coding algorithm is expected to satisfy low bit-rate compression requirements for modern medical communication systems.

Abnormal glucose metabolism is an independent risk factor for poor outcome following acute ischemic stroke. However, the relationship between initial hemoglobin A1c level and functional outcome (defined by modified Rankin Scale scores) following small-artery occlusion, a subtype of ischemic stroke, is unknown. The aim of the present study was to evaluate this association among patients diagnosed with small-artery occlusion.Data on 793 patients diagnosed with small-artery occlusion from October 25, 2012 to June 30, 2015 were collected from the stroke registry of the Department of Neurorehabilitation of HuanHu Hospital. Hemoglobin A1c values at admission were classified into three groups according to tertiles (

This study investigated the effect of rain-shelter cultivation on the biosynthesis of flavonoids and volatiles in grapes, with an aim of determining whether rain-shelter application could help to improve the sensory attributes and quality of grapes. Vitis vinifera L. Chardonnay grapes, grown in the Huaizhuo basin region of northern China, were selected within two consecutive years. A rain-shelter roof was constructed using a colorless polyethylene (PE) film with a light transmittance of 80%. Results showed that rain-shelter treatment did not affect the accumulation of soluble solids during grape maturation. However, the allocation of assimilated carbon in phenolic and volatile biosynthetic pathways varied significantly, leading to alterations in polyphenolic and volatile profiles. The rain-shelter cultivation enhanced the concentration of flavan-3-ols via the flavonoid-3'5'-hydroxylase (F3'5'H) pathway, but reduced the level of flavonols and flavan-3-ols via the flavonoid-3'-hydroxylase (F3'H) pathway. In addition, the rain-shelter cultivation significantly enhanced the synthesis of fatty acid-derived volatiles, isoprene-derived terpenoids and amino acid-derived branched-chain aliphatics, but led to a decrease in the accumulation of isoprene-derived norisoprenoids and amino acid-derived benzenoids. Principal component analysis revealed some key compounds that differentiated the grapes cultivated under open-field and rain-shelter conditions. Moreover, the effect of the rain-shelter application on the accumulation of these compounds appeared to be vintage dependent. The alteration of their profiles caused by the rain-shelter treatment was significant in the vintage that received higher rainfall, which usually took place in the first rapid growth and veraison phases.

Waterlogging is a common adverse environmental condition that limits plant growth. Sesame (Sesamum indicum) is considered a drought-tolerant oil crop but is typically susceptible to harmful effects from waterlogging. The present study used comparative analysis to explore the waterlogging stress response associated with two sesame genotypes. The RNA-seq dataset generated during a time course of 0, 3, 9 and 15 h of waterlogging as well as 20 h post-drainage indicated that stress gradually suppressed the expression of sesame genes, with 9 h as the critical time point for the response of sesame to waterlogging stress. Of the 19,316 genes expressed during waterlogging, 72.1% were affected significantly. Sesame of both tolerant and susceptible genotypes showed decreased numbers of upregulated differentially expressed genes (DEGs) but increased numbers of downregulated DEGs at the onset of waterlogging. However, the tolerant-genotype sesame exhibited 25.5% more upregulated DEGs and 29.7% fewer downregulated DEGs than those of the susceptible-genotype strain between 3 and 15 h. The results indicated that the tolerant sesame displayed a more positive gene response to waterlogging. A total of 1,379 genes were significantly induced and commonly expressed in sesame under waterlogging conditions from 3 to 15 h regardless of tolerance level; of these genes, 98 are known homologous stress responsive genes, while the remaining 1,281 are newly reported here. This gene set may represent the core genes that function in response to waterlogging, including those related mainly to energy metabolism and phenylpropanoid biosynthesis. Furthermore, a set of 3,016 genes functioning in energy supply and cell repair or formation was activated in sesame recovery from waterlogging stress. A comparative analysis between sesame of the tolerant and susceptible genotypes revealed 66 genes that may be candidates for improving sesame tolerance to waterlogging. This study provided a comprehensive picture of the sesame gene expression pattern in response to waterlogging stress. These results will help dissect the mechanism of the sesame response to waterlogging and identify candidate genes to improve its tolerance.

Plant root exudates affect root-knot nematodes egg hatch. Chemicals in root exudates can attract nematodes to the roots or result in repellence, motility inhibition or even death. However, until recently little was known about the relationship between tomato root exudates chemicals and root-knot nematodes. In this study, root exudates were extracted from three tomato rootstocks with varying levels of nematode resistance: Baliya (highly resistant, HR), RS2 (moderately resistant, MR) and L-402 (highly susceptible, T). The effects of the root exudates on Meloidogyne incognita (M. incognita) egg hatch, survival and chemotaxis of second-stage juveniles (J2) were explored. The composition of the root exudates was analysed by gas chromatography/mass spectrometry (GC/MS) prior to and following M. incognita inoculation. Four compounds in root exudates were selected for further analysis and their allopathic effect on M. incognita were investigated. Root exudates from each tomato rootstocks (HR, MR and T strains) suppressed M. incognita egg hatch and increased J2 mortality, with the highest rate being observed in the exudates from the HR plants. Exudate from HR variety also repelled M. incognita J2 while that of the susceptible plant, T, was demonstrated to be attractive. The relative amount of esters and phenol compounds in root exudates from HR and MR tomato rootstocks increased notably after inoculation. Four compounds, 2,6-Di-tert-butyl-p-cresol, L-ascorbyl 2,6-dipalmitate, dibutyl phthalate and dimethyl phthalate increased significantly after inoculation. The egg hatch of M. incognita was suppressed by each of the compound. L-ascorbyl 2,6-dipalmitate showed the most notable effect in a concentration-dependent manner. All four compounds were associated with increased J2 mortality. The greatest effect was observed with dimethyl phthalate at 2 mmol·L-1. Dibutyl phthalate was the only compound observed to repel M. incognita J2 with no effect being detected in the other compounds. Each of the four compounds were correlated with a reduction in disease index in the susceptible cultivar, T, and tomato seedlings irrigated with L-ascorbyl 2,6-dipalmitate at 2 mmol·L-1 showed the best resistance to M. incognita. Taken together, this study provided a valuable contribution to understanding the underlying mechanism of nematode resistance in tomato cultivars.

Background and purposeThe relationship between plasma level of total homocysteine (tHcy) and white matter hyperintensities (WMHs), especially in patients with acute ischemic stroke (AIS), is controversial. The present study investigated the association between these two as well as WMH locations in a large cohort of patients with AIS.MethodsConsecutive patients were reviewed from a prospective ischemic stroke database. Clinical data, including tHcy level and WMHs, were assessed. WMHs were assessed using the Fazekas scale and Age-Related White Matter Changes (ARWMC) visual grading scale. The association between tHcy and WMH locations was investigated by using multivariate logistic regression analyses.ResultsA total of 923 out of 1,205 patients were examined. The average age was 58.9 ± 11.9 years; 31.6% were female. Elevated tHcy level was significantly associated with WMHs. For the highest tHcy quartile, the odds ratio (OR) (95% confidence interval; CI) was 1.891 (1.257; 2.843) according to the Fazekas scale and 1.781 (1.185; 2.767) according to the ARWMC scale when compared to the lowest quartile. However, in a subgroup analysis, only WMHs in the periventricular area and left or right frontal areas were found to be independently associated with tHcy level. For the highest tHcy quartile, the OR (95% CI) was 1.761 (1.172; 2.648) for the periventricular WMHs, 1.768 (1.134; 2.756)for the left frontal WMHs, and 1.890 (1.206; 2.960)for the right frontal WMHs.ConclusionsIn patients with AIS, plasma tHcy level is related to WMHs, especially WMHs distributed within the periventricular and frontal areas.

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is the etiologic agent of KS, the most common AIDS-related malignancy. The majority of KS tumor cells harbor latent KSHV virus but only a small percentage undergoes spontaneous lytic replication. Viral reactivation from latency is crucial for the pathogenesis and development of KS, but the cellular mechanisms underlying the switch between viral latency and replication are not well understood.The level of let-7 miRNAs and MAP4K4 in KSHV infected 293T cells were quantified by real-time PCRs. Let-7 expression was silenced by the miRNA sponge technique. In let-7a transfected 293T cells, the expression of MAP4K4 was measured by real-time PCR and western blot. Luciferease expression was employed to examine the effect of let-7a on the 3'-untranslated region (UTR) of the MAP4K4 gene in 293T cells. Real-time PCR was used to quantify the KSHV copy numbers in BC-3 cells in which the expression of let-7a and/or MAP4K4 were altered. Finally, ERK, JNK and p38 protein production and their phosphorylation status were detected by western blots in let-7a or MAP4K4 transfected BCBL-1 cells.The expression of microRNA let-7 was dramatically decreased in KSHV infected 293T cells, but that of MAP4K4 was increased significantly. Let-7a is physically associated with and targets the MAP4K4 3'UTR, and inhibits MAP4K4 expression at both mRNA and protein levels. MAP4K4 stimulates KSHV reactivation from latency, whereas let-7a inhibits the function of MAP4K4 by reversing the function of MAP4K4 on JNK, phospho-JNK and phospho-ERK1/2 levels.Our results establish that let-7a specifically suppresses MAP4K4 expression, and further inhibits KSHV reactivation by interfering with the function of MAP4K4 on the MAPK pathway, highlighting let-7a as a potential treatment for KS.

Phenylethanoid glycosides (PhGs), a class of polyphenolic compounds, are considered one of major bioactive constituents of Cistanche deserticola Y.C. Ma (CD), whose extract is orally used in traditional Chinese medicine. Although previous pharmacological studies have reported that PhGs exert many activities, their intestinal transport profiles have not been clarified. In this study, we investigated the intestinal permeability of a PhG-rich extract (PRE) from CD as an integrated system in the Caco-2 cell monolayer model using a bioassay system. The results showed that PRE is primarily transported via poorly absorbed passive diffusion down a concentration gradient without efflux, which provides the pharmacokinetic basis for the clinical application of PhGs in CD. We also determined the intestinal permeability of three major PhGs [acteoside (AC), isoacteoside (IS) and echinacoside (EC)] by HLPC. Furthermore, we developed a novel HPLC-fluorescence detection method to accurately determine the flux amount of AC and IS. As expected, the transport characteristics of the three PhGs are consistent with those of PRE, indicating that the present bioassay system is appropriate and reliable for the evaluation of the transport characteristics of active ingredient groups (AIG) in PRE. Moreover, this system may also be suitable for other plant extracts given appropriate bioactivity.

Intravenous (i.v.) tissue-type plasminogen activator (tPA) is the only approved noninvasive therapy for acute ischemic stroke (AIS). However, after tPA treatment, the outcome of patients with different subtypes of stroke according to their vascular risk factors remains to be elucidated. We aim to explore the relationship between the outcome and different risk factors in patients with different subtype of acute strokes treated with i.v. tPA. Records of patients in this cohort were reviewed. Data collected and analysed included the demographics, vascular risk factors, baseline National Institutes of Health Stroke Scale (NIHSS) scores, 90-day modified Rankin Scores (mRS), and subtypes of stroke. By using the 90-day mRS, patients were dichotomized into favorable versus unfavorable outcome in each subtype of stroke. We identified the vascular risk factors that are likely associated with the poor outcome in each subtype. Among 570 AIS patients received i.v. tPA, 217 were in the large artery atherosclerosis (LAA) group, 146 in the small vessel occlusion (SVO) group, and 140 in the cardioaortic embolism (CE) group. Lower NIHSS score on admission was related to favorable outcome in patients in all subtypes. Patients with history of dyslipidemia were likely on statin treatment before their admission and hence less likely to have elevated cholesterol level on admission. Therefore, there was a possible paradoxical effect on the outcome in patients with LAA and SVO subtypes of strokes. SVO patients with history of diabetes had higher risk of unfavorable outcome. SVO patients had favorable outcome if their time from onset to treatment was short. In conclusion, the outcome of patients treated with i.v. tPA may be related to different vascular risk factors associated with different subtypes of stroke.

It is well known that the efficacy of intravenous (i.v.) tissue plasminogen activator (tPA) is time-dependent when used to treat patients with acute ischemic strokes.Our study examines the safety issue of giving IV tPA without complete blood count (CBC) resulted.This is a retrospective observational study by examining the database from Huashan Hospital in China and OSF/INI Comprehensive Stroke Center in United States. Patient data collected included demographics, occurrence of symptomatic intracranial hemorrhage, door to needle intervals, National Institute of Health Stroke Scale scores on admission, CBC results on admission and follow-up modified Rankin Scale scores. Linear regression and multivariable logistic regression analysis were used to identify factors that would have an impact on door-to-needle intervals.Our study included 120 patients from Huashan Hospital and 123 patients from INI. Among them, 36 in Huashan Hospital and 51 in INI received i.v. tPA prior to their CBC resulted. Normal platelet count was found in 98.8% patients after tPA was given. One patient had thrombocytopenia but no hemorrhagic event. A significantly shorter door to needle interval (DTN) was found in the group without CBC resulted. There was also a difference in treatment interval between the two hospitals. Door to needle intervals had a strong correlation to onset to treatment intervals and NIHSS scores on admission.In patients presented with acute ischemic stroke, the risk of developing hemorrhagic event is low if i.v. tPA is given before CBC has resulted. The door to needle intervals can be significantly reduced.

As DRAM is facing the scaling difficulty in terms of energy cost and reliability, some nonvolatile storage materials were proposed to be the substitute or supplement of main memory. Phase Change Memory (PCM) is one of the most promising nonvolatile memory that could be put into use in the near future. However, before becoming a qualified main memory technology, PCM should be designed reliably so that it can ensure the computer system's stable running even when errors occur. The typical wear-out errors in PCM have been well studied, but the transient errors, that caused by high-energy particles striking on the complementary metal-oxide semiconductor (CMOS) circuit of PCM chips or by resistance drifting in multi-level cell PCM, have attracted little focus. In this paper, we propose an innovative mechanism, Local-ECC-Global-ECPs (LEGE), which addresses both soft errors and hard errors (wear-out errors) in PCM memory systems. Our idea is to deploy a local error correction code (ECC) section to every data line, which can detect and correct one-bit errors immediately, and a global error correction pointers (ECPs) buffer for the whole memory chip, which can be reloaded to correct more hard error bits. The local ECC is used to detect and correct the unknown one-bit errors, and the global ECPs buffer is used to store the corrected value of hard errors. In comparison to ECP-6, our method provides almost identical lifetimes, but reduces approximately 50% storage overhead. Moreover, our structure reduces approximately 3.55% access latency overhead by increasing 1.61% storage overhead compared to PAYG, a hard error only solution.

Recent studies suggest that high-salt diet is associated with cognitive decline in human and mouse. The fact that genetic factors account for less than 50% cases of sporadic Alzheimer's disease (AD) highlights the important contribution of environmental factors, such as high-salt diet, in AD pathogenesis. However, whether and how high-salt diet fits the "amyloid cascade" hypothesis remains unexplored. Here, we show sodium chloride (NaCl) could increase Aβ levels in the medium of HEK293 cells overexpressing amyloid precursor protein (APP) or C99 fragment. NaCl treatment dose not affect APP level, gamma secretase level or activity. Instead, NaCl treatment suppresses the capacity of cells to clear Aβ and reduces Apolipoprotein E (ApoE) level. Finally, NaCl treated THP-1 or BV2 cells are inefficient in clearing Aβ when co-cultured with rat primary neurons. Our study suggests that high-salt diet may increase AD risk by directly modulating Aβ levels.

Many steel-based cities in China were established between the 1950s and 1960s. After more than half a century of development and boom, these cities are starting to decline and industrial transformation is urgently needed. This paper focuses on evaluating the transformation capability of resource-based cities building an evaluation model. Using Text Mining and the Document Explorer technique as a way of extracting text features, the 200 most frequently used words are derived from 100 publications related to steel- and other resource-based cities. The Expert Evaluation Method (EEM) and Analytic Hierarchy Process (AHP) techniques are then applied to select 53 indicators, determine their weights and establish an index system for evaluating the transformation capability of the pillar industry of China's steel-based cities. Using real data and expert reviews, the improved Fuzzy Relation Matrix (FRM) method is applied to two case studies in China, namely Panzhihua and Daye, and the evaluation model is developed using Fuzzy Comprehensive Evaluation (FCE). The cities' abilities to carry out industrial transformation are evaluated with concerns expressed for the case of Daye. The findings have policy implications for the potential and required industrial transformation in the two selected cities and other resource-based towns.

Calcaneal quantitative ultrasound (QUS), which is used in the evaluation of osteoporosis, is believed to be intimately associated with the characteristics of the proximal femur. However, the specific associations of calcaneal QUS with characteristics of the hip sub-regions remain unclear.A cross-sectional assessment of 53 osteoporotic patients was performed for the skeletal status of the heel and hip.We prospectively enrolled 53 female osteoporotic patients with femoral fractures. Calcaneal QUS, dual energy X-ray absorptiometry (DXA), and hip structural analysis (HSA) were performed for each patient. Femoral heads were obtained during the surgery, and principal compressive trabeculae (PCT) were extracted by a three-dimensional printing technique-assisted method. Pearson's correlation between QUS measurement with DXA, HSA-derived parameters and Young's modulus were calculated in order to evaluate the specific association of QUS with the parameters for the hip sub-regions, including the femoral neck, trochanteric and Ward's areas, and the femoral shaft, respectively.Significant correlations were found between estimated BMD (Est.BMD) and BMD of different sub-regions of proximal femur. However, the correlation coefficient of trochanteric area (r = 0.356, p = 0.009) was higher than that of the neck area (r = 0.297, p = 0.031) and total proximal femur (r = 0.291, p = 0.034). Furthermore, the quantitative ultrasound index (QUI) was significantly correlated with the HSA-derived parameters of the trochanteric area (r value: 0.315-0.356, all p

To assess the efficacy of midazolam for anxiety control in third molar extraction surgery.Electronic retrievals were conducted in Medline (via PubMed, 1950-2013.12), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 3), Embase (via OVID 1974-2013.12), and the System for Information on Grey Literature in Europe (SIGLE). The bibliographies of relevant clinical trials were also checked. Randomized controlled trials satisfying the inclusion criteria were evaluated, with data extraction done independently by two well-trained investigators. Disagreements were resolved by discussion or by consultation with a third member of the review team.Ten studies were included, but meta-analysis could not be conducted because of the significant differences among articles. All but one article demonstrated that midazolam could relieve anxiety. One article demonstrated that propofol offered superior anxiolysis, with more rapid recovery than with midazolam. Compared with lorazepam and diazepam, midazolam did not distinctly dominate in its sedative effect, but was safer. Two articles used midazolam in multidrug intravenous sedation and proved it to be more effective than midazolam alone.It was found, by comparison and analysis, that midazolam might be effective for use for anxiety control during third molar extraction and can be safely administered by a dedicated staff member. It can also be used with other drugs to obtain better sedative effects, but the patient's respiratory function must be monitored closely, because multidrug sedation is also more risky.

The risk of stroke after a transient ischemic attack (TIA) for patients with a positive diffusion-weighted image (DWI), i.e., transient symptoms with infarction (TSI), is much higher than for those with a negative DWI. The aim of this study was to validate the predictive value of a web-based recurrence risk estimator (RRE; http://www.nmr.mgh.harvard.edu/RRE/) of TSI.Data from the prospective hospital-based TIA database of the First Affiliated Hospital of Zhengzhou University were analyzed. The RRE and ABCD2 scores were calculated within 7 days of symptom onset. The predictive outcome was ischemic stroke occurrence at 90 days. The receiver-operating characteristics curves were plotted, and the predictive value of the two models was assessed by computing the C statistics.A total of 221 eligible patients were prospectively enrolled, of whom 46 (20.81%) experienced a stroke within 90 days. The 90-day stroke risk in high-risk TSI patients (RRE ≥4) was 3.406-fold greater than in those at low risk (P

The Cre/loxP system is increasingly exploited for genetic manipulation of DNA in vitro and in vivo. It was previously reported that inactive ''split-Cre'' fragments could restore Cre activity in transgenic mice when overlapping co-expression was controlled by two different promoters. In this study, we analyzed recombination activities of split-Cre proteins, and found that no recombinase activity was detected in the in vitro recombination reaction in which only the N-terminal domain (NCre) of split-Cre protein was expressed, whereas recombination activity was obtained when the C-terminal (CCre) or both NCre and CCre fragments were supplied. We have also determined the recombination efficiency of split-Cre proteins which were co-expressed in hair roots of transgenic tobacco. No Cre recombination event was observed in hair roots of transgenic tobacco when the NCre or CCre genes were expressed alone. In contrast, an efficient recombination event was found in transgenic hairy roots co-expressing both inactive split-Cre genes. Moreover, the restored recombination efficiency of split-Cre proteins fused with the nuclear localization sequence (NLS) was higher than that of intact Cre in transgenic lines. Thus, DNA recombination mediated by split-Cre proteins provides an alternative method for spatial and temporal regulation of gene expression in transgenic plants.

As one of the most severe pollutants, cadmium has been reported to be harmful to plant cells, but the effects of cadmium on gymnosperm pollen germination and tube growth and the mechanism of this involvement are still unclear. Here, we report that cadmium not only strongly inhibited P. wilsonii pollen germination and tube growth, but also significantly altered tube morphology in a dose-dependent manner. Time-lapse images obtained with a laser scanning confocal microscope revealed that endocytosis was dramatically inhibited by cadmium stress. Further investigation with ER-Tracker dye indicated that cadmium stress reduced the number of the Golgi apparatus, and induced dilation of ER. Additionally, Lyso-Tracker staining showed that cadmium distinctly promoted the formation of acidic organelles in pollen tubes, likely derived from the dilated ER. Taken together, our studies indicated that P. wilsonii pollens were highly susceptible to cadmium stress, and that cadmium stress strongly inhibited pollen germination and tube growth by disrupting the endomembrane organelles, inhibiting endo/exocytosis, and forming acidic vacuoles, resulting in swollen tube tips and irregularly broadened tube diameters. These findings provide a new insight into the effects of cadmium toxicity on the tip growth of pollen tubes.

The piRNA pathway plays an important role in maintaining genome stability in the germ line by silencing transposable elements (TEs) from fly to mammals. As a highly conserved piRNA pathway component, Piwi is widely expressed in both germ cells and somatic cells in the Drosophila ovary and is required for piRNA production in both cell types. In addition to its known role in somatic cap cells to maintain germline stem cells (GSCs), this study has demonstrated that Piwi has novel functions in somatic cells and germ cells of the Drosophila ovary to promote germ cell differentiation. Piwi knockdown in escort cells causes a reduction in escort cell (EC) number and accumulation of undifferentiated germ cells, some of which show active BMP signaling, indicating that Piwi is required to maintain ECs and promote germ cell differentiation. Simultaneous knockdown of dpp, encoding a BMP, in ECs can partially rescue the germ cell differentiation defect, indicating that Piwi is required in ECs to repress dpp. Consistent with its key role in piRNA production, TE transcripts increase significantly and DNA damage is also elevated in the piwi knockdown somatic cells. Germ cell-specific knockdown of piwi surprisingly causes depletion of germ cells before adulthood, suggesting that Piwi might control primordial germ cell maintenance or GSC establishment. Finally, Piwi inactivation in the germ line of the adult ovary leads to gradual GSC loss and germ cell differentiation defects, indicating the intrinsic role of Piwi in adult GSC maintenance and differentiation. This study has revealed new germline requirement of Piwi in controlling GSC maintenance and lineage differentiation as well as its new somatic function in promoting germ cell differentiation. Therefore, Piwi is required in multiple cell types to control GSC lineage development in the Drosophila ovary.

The A2DS2 score was recently developed from the Berlin Stroke Registry for predicting in-hospital pneumonia after acute ischemic stroke and performed well in an external validation in the North-west Germany Stroke Registry. It could be a useful tool for risk stratification in clinical practice or stroke trials. We aimed to prospectively validate the predictive value of A2DS2 score in a Chinese stroke population.The prognostic model was used to predict stroke-associated pneumonia (SAP) from Henan Province Stroke Registry (HNSR) in which data were prospectively collected. The receiver-operating characteristic curves were plotted, and the C statistics were calculated to assess the discrimination ability. The Hosmer-Lemeshow goodness-of-fit test and the plot of observed versus predicted SAP risk were used to assess model calibration.Among 1142 eligible patients, the overall in-hospital SAP was 18.8%, which ranged from 9.0% in patients with lower A2DS2 scores (0-4) to 65.0% in those with higher scores of 5 to 10 (P for trend

Genkwanin is one of the major non-glycosylated flavonoids in many herbs with anti-inflammatory activities. Although its anti-inflammatory activity in vivo has been reported, the potential molecular mechanisms remain obscure. In this study, by pharmacological and genetic approaches, we explore the anti-inflammatory effects of genkwanin in LPS-activated RAW264.7 macrophages. Genkwanin potently decreases the proinflammatory mediators, such as iNOS, TNF-α, IL-1β and IL-6, at the transcriptional and translational levels without cytotoxicity, indicating the excellent anti-inflammatory potency of genkwanin in vitro. Mechanism study shows that genkwanin significantly suppresses the p38- and JNK-mediated AP-1 signaling pathway and increases the mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) expression at the posttranscriptional level. We also confirmed that microRNA-101 (miR-101) is a negative regulator of MKP-1 expression. Moreover, regardless of miR-101-deficient cells or miR-101-abundant cells, the suppression effects of genkwanin on supernatant proinflammatory mediators' levels are far less than that in respective negative control cells, suggesting that genkwanin exerts anti-inflammatory effect mainly through reducing miR-101 production. However, genkwanin can't affect the level of phospho-Akt (p-Akt), indicating that the phosphorylation of Akt may be not responsible for the effect of genkwanin on miR-101 production. We conclude that genkwanin exerts its anti-inflammatory effect mainly through the regulation of the miR-101/MKP-1/MAPK pathway.

Adipose tissue is a key regulator of energy homestasis. The amount of adipose tissue is largely determined by adipocyte differentiation (adipogenesis), a process that is regulated by the concerted actions of multiple transcription factors and cofactors. Based on in vitro studies in murine 3T3-L1 preadipocytes and human primary preadipocytes, the transcriptional cofactor and acetyltransferase Tip60 was recently identified as an essential adipogenic factor. We therefore investigated the role of Tip60 on adipocyte differentiation and function, and possible consequences on energy homeostasis, in vivo. Because homozygous inactivation results in early embryonic lethality, Tip60+/- mice were used. Heterozygous inactivation of Tip60 had no effect on body weight, despite slightly higher food intake by Tip60+/- mice. No major effects of heterozygous inactivation of Tip60 were observed on adipose tissue and liver, and Tip60+/- displayed normal glucose tolerance, both on a low fat and a high fat diet. While Tip60 mRNA was reduced to 50% in adipose tissue, the protein levels were unaltered, suggesting compensation by the intact allele. These findings indicate that the in vivo role of Tip60 in adipocyte differentiation and function cannot be properly addressed in Tip60+/- mice, but requires the generation of adipose tissue-specific knock out animals or specific knock-in mice.

ObjectiveTo examine whether serum uric acid (SUA) is associated with 2-hour postload glucose (2-h PG) in Chinese with impaired fasting plasma glucose (IFG) and/or HbA1c (IA1C).Research design and methodsAnthropometric and biochemical examinations, such as SUA concentration, were performed in 3763 individuals from all the villages in Baqiao County, China. A 75-g oral glucose tolerance test (OGTT) was conducted in 1197 Chinese with prediabetes as having IFG (110 ≤ fasting plasma glucose [FPG] ResultsThe present study included 1197 participants with IFG and/or IA1C (mean age 56.5 ± 10.3 years; 50.6% men). In multivariate linear regression, after adjustment for gender, age, smoking and drinking, body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP), lipid profiles, logarithmic transformed C-reactive protein (log-CRP), estimated glomerular filtration rate (e-GFR), FPG and HbA1c, with a 1-mg/dl increment of SUA, 2-h PG increased by 5.04 ± 0.72 (PConclusionsSUA is significantly associated with 2-h PG in Chinese with IFG and/or IA1C.

Programmed cell death (PCD) is a genetically-based cell death mechanism with vital roles in eukaryotes. Although there is limited consensus on similar death mode programs in prokaryotes, emerging evidence suggest that PCD events are operative. Here we present cell death events in a cyanobacterium living endophytically in the fern Azolla microphylla, suggestive of PCD. This symbiosis is characterized by some unique traits such as a synchronized development, a vertical transfer of the cyanobacterium between plant generations, and a highly eroding cyanobacterial genome. A combination of methods was used to identify cell death modes in the cyanobacterium. Light- and electron microscopy analyses showed that the proportion of cells undergoing cell death peaked at 53.6% (average 20%) of the total cell population, depending on the cell type and host developmental stage. Biochemical markers used for early and late programmed cell death events related to apoptosis (Annexin V-EGFP and TUNEL staining assays), together with visualization of cytoskeleton alterations (FITC-phalloidin staining), showed that all cyanobacterial cell categories were affected by cell death. Transmission electron microscopy revealed four modes of cell death: apoptotic-like, autophagic-like, necrotic-like and autolytic-like. Abiotic stresses further enhanced cell death in a dose and time dependent manner. The data also suggest that dynamic changes in the peptidoglycan cell wall layer and in the cytoskeleton distribution patterns may act as markers for the various cell death modes. The presence of a metacaspase homolog (domain p20) further suggests that the death modes are genetically programmed. It is therefore concluded that multiple, likely genetically programmed, cell death modes exist in cyanobacteria, a finding that may be connected with the evolution of cell death in the plant kingdom.

While the effects of hypoxia on gene expression have been investigated in the CNS to some extent, we currently do not know what role epigenetics plays in the transcription of many genes during such hypoxic stress. To start understanding the role of epigenetic changes during hypoxia, we investigated the long-term effect of hypoxia on gene expression and DNA methylation in hippocampal neuronal cells. Primary murine hippocampal neuronal cells were cultured for 7 days. Hypoxic stress of 1% O2, 5% CO2 for 24 hours was applied on Day 3, conditions we found to maximize cellular hypoxic stress response without inducing cell death. Cells were returned to normoxia for 4 days following the period of hypoxic stress. On Day 7, Methyl-Sensitive Cut Counting (MSCC) was used to identify a genome-wide methylation profile of the hippocampal cell lines to assess methylation changes resulting from hypoxia. RNA-Seq was also done on Day 7 to analyze changes in gene transcription. Phenotypic analysis showed that neuronal processes were significantly shorter after 1 day of hypoxia, but there was a catch-up growth of these processes after return to normoxia. Transcriptome profiling using RNA-Seq revealed 369 differentially expressed genes with 225 being upregulated, many of which form networks shown to affect CNS development and function. Importantly, the expression level of 59 genes could be correlated to the changes in DNA methylation in their promoter regions. CpG islands, in particular, had a strong tendency to remain hypomethylated long after hypoxic stress was removed. From this study, we conclude that short-term, sub-lethal hypoxia results in long-lasting changes to genome wide DNA methylation status and that some of these changes can be highly correlated with transcriptional modulation in a number of genes involved in functional pathways that have been previously implicated in neural growth and development.

Rat strains differ dramatically in their susceptibility to mammary carcinogenesis. On the assumption that susceptibility genes are conserved across mammalian species and hence inform human carcinogenesis, numerous investigators have used genetic linkage studies in rats to identify genes responsible for differential susceptibility to carcinogenesis. Using a genetic backcross between the resistant Copenhagen (Cop) and susceptible Fischer 344 (F344) strains, we mapped a novel mammary carcinoma susceptibility (Mcs30) locus to the centromeric region on chromosome 12 (LOD score of ∼8.6 at the D12Rat59 marker). The Mcs30 locus comprises approximately 12 Mbp on the long arm of rat RNO12 whose synteny is conserved on human chromosome 13q12 to 13q13. After analyzing numerous genes comprising this locus, we identified Fry, the rat ortholog of the furry gene of Drosophila melanogaster, as a candidate Mcs gene. We cloned and determined the complete nucleotide sequence of the 13 kbp Fry mRNA. Sequence analysis indicated that the Fry gene was highly conserved across evolution, with 90% similarity of the predicted amino acid sequence among eutherian mammals. Comparison of the Fry sequence in the Cop and F344 strains identified two non-synonymous single nucleotide polymorphisms (SNPs), one of which creates a putative, de novo phosphorylation site. Further analysis showed that the expression of the Fry gene is reduced in a majority of rat mammary tumors. Our results also suggested that FRY activity was reduced in human breast carcinoma cell lines as a result of reduced levels or mutation. This study is the first to identify the Fry gene as a candidate Mcs gene. Our data suggest that the SNPs within the Fry gene contribute to the genetic susceptibility of the F344 rat strain to mammary carcinogenesis. These results provide the foundation for analyzing the role of the human FRY gene in cancer susceptibility and progression.

Chronic growth hormone (GH) therapy has been shown to cause insulin resistance, but the mechanism remains unknown. PTEN, a tumor suppressor gene, is a major negative regulator of insulin signaling. In this study, we explored the effect of chronic GH on insulin signaling in the context of PTEN function. Balb/c healthy mice were given recombinant human or bovine GH intraperitoneally for 3 weeks. We found that phosphorylation of Akt was significantly decreased in chronic GH group and the expression of PTEN was significantly increased. We further examined this effect in the streptozotocin-induced Type I diabetic mouse model, in which endogenous insulin secretion was disrupted. Insulin/PI3K/Akt signaling was impaired. However, different from the observation in healthy mice, the expression of PTEN did not increase. Similarly, PTEN expression did not significantly increase in chronic GH-treated mice with hypoinsulinemia induced by prolonged fasting. We conducted in-vitro experiments in HepG2 cells to validate our in-vivo findings. Long-term exposure to GH caused similar resistance of insulin/PI3K/Akt signaling in HepG2 cells; and over-expression of PTEN enhanced the impairment of insulin signaling. On the other hand, disabling the PTEN gene by transfecting the mutant PTEN construct C124S or siPTEN, disrupted the chronic GH induced insulin resistance. Our data demonstrate that PTEN plays an important role in chronic-GH-induced insulin resistance. These findings may have implication in other pathological insulin resistance.

BACKGROUND: Acute lung injury (ALI) is considered to be the major cause of respiratory failure in critically ill patients. Clinical studies have found that in patients with sepsis and after hemorrhage, the elevated level of high mobility group box-1(HMGB-1) in their circulation is highly associated with ALI, but the underlying mechanism remains unclear. Extracellular HMGB-1 has cytokine-like properties and can bind to Toll-like Receptor-4 (TLR4), which was reported to play an important role in the pathogenesis of ALI. The aim of this study was to determine whether HMGB-1 directly contributes to ALI and whether TLR4 signaling pathway is involved in this process. METHODS: Recombinant human HMGB-1 (rhHMGB-1) was used to induce ALI in male Sprague-Dawley rats. Lung specimens were collected 2 h after HMGB-1 treatment. The levels of TNF-α, IL-1β, TLR4 protein, and TLR4 mRNA in lungs as well as pathological changes of lung tissue were assessed. In cell studies, the alveolar macrophage cell line, NR8383, was collected 24 h after rhHMGB-1 treatment and the levels of TNF-α and IL-1β in cultured medium as well as TLR4 protein and mRNA levels in the cell were examined. TLR4-shRNA-lentivirus was used to inhibit TLR4 expression, and a neutralizing anti-HMGB1 antibody was used to neutralize rhHMGB-1 both in vitro and in vivo. RESULTS: Features of lung injury and significant elevation of IL-1β and TNF-α levels were found in lungs of rhHMGB-1-treated animals. Cultured NR8383 cells were activated by rhHMGB-1 treatment and resulted in the release of IL-1β and TNF-α. TLR4 expression was greatly up-regulated by rhHMGB-1. Inhibition of TLR4 or neutralization of HMGB1 with a specific antibody also attenuated the inflammatory response induced by HMGB-1 both in vivo and in vitro. CONCLUSION: HMGB-1 can activate alveolar macrophages to produce proinflammatory cytokines and induce ALI through a mechanism that relies on TLR-4.

This study examines the regulating effect of Sonic Hedgehog (Shh) on the permeability of the blood-brain barrier (BBB) in cerebral ischemia. By employing permanent middle cerebral artery occlusion (pMCAO) model, we find that Shh significantly decreases brain edema and preserves BBB permeability. Moreover, Shh increases zonula occludens-1 (ZO-1), occludin and angiopiotetin-1 (Ang-1) expression in the ischemic penumbra. Blockage of Shh with cyclopamine abolishes the effects of Shh on brain edema, BBB permeability and ZO-1, occludin, Ang-1 expression. Primary brain microvessel endothelial cells (BMECs) and astrocytes were pre-treated with Shh, cyclopamine, Ang-1-neutralizing antibody, and subjected to oxygen-glucose deprivation (OGD). Results show that the Ang-1 protein level in the culture medium of Shh-treated astrocytes is significantly higher. Shh also increased ZO-1, occludin and Ang-1 expression in BMECs, while cyclopamine and Ang-1-neutralizing antibody inhibited the effects of Shh on the ZO-1 and occludin expression, respectively. This study suggests that, under ischemic insults, Shh triggers Ang-1 production predominantly in astrocytes, and the secreted Ang-1 acts on BMECs, thereby upregulating ZO-1 and occludin to repair the tight junction and ameliorate the brain edema and BBB leakage.

Nontypable Haemophilus influenzae (NTHi) and Haemophilus haemolyticus exhibit different pathogenicities, but to date, there remains no definitive and reliable strategy for differentiating these strains. In this study, we evaluated matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) as a potential method for differentiating NTHi and H. haemolyticus. The phylogenetic analysis of concatenated 16S rRNA and recombinase A (recA) gene sequences, outer membrane protein P6 gene sequencing and single-gene PCR were used as reference methods. The original reference database (ORD, provided with the Biotyper software) and new reference database (NRD, extended with Chinese strains) were compared for the evaluation of MALDI-TOF MS. Through a search of the ORD, 76.9% of the NTHi (40/52) and none of the H. haemolyticus (0/20) strains were identified at the species level. However, all NTHi and H. haemolyticus strains used for identification were accurately recognized at the species level when searching the NRD. From the dendrogram clustering of the main spectra projections, the Chinese and foreign H. influenzae reference strains were categorized into two distinct groups, and H. influenzae and H. haemolyticus were also separated into two categories. Compared to the existing methods, MALDI-TOF MS has the advantage of integrating high throughput, accuracy and speed. In conclusion, MALDI-TOF MS is an excellent method for differentiating NTHi and H. haemolyticus. This method can be recommended for use in appropriately equipped laboratories.

Population structure can be a source of both false-positive and false-negative findings in a genome-wide association study. This article proposes an approach that helps to reduce the false-positives. It consists of homogenizing the diseased/healthy phenotype ratio across the cohort, by decreasing the statistical weight of selected individuals. After homogenization, the cohort is statistically handled as if originating from a single well-mixed population. The method was applied to homogenize a Parkinson's disease genome-wide association study cohort.