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With the development of economy and society, the consumption of fossil energy is gradually increasing. In order to solve the current energy dilemma, Natural gas hydrate (NGH) is considered as an ideal alternative energy. At the same time, solid fluidization exploitation is an ideal method. However, in the process of that, sand and hydrate ore bodies enter the closed pipeline together, which will block the pipeline and increase the difficulty of exploitation. Therefore, the pre-separation of sand by hydrocyclone plays an important role in solid fluidization exploitation. In this study, the numerical simulation method was used to study the internal flow field characteristics of the hydrocyclone, and the effects of different flow rate, different flow ratio, different sand content and different particle diameter on the phase distribution were investigated. The results show that: at the same axial position, the increase of flow rate and sand content makes the sand phase more distributed at the edge of the flow field. Under the same working conditions, the sand gradually migrates to the center of the flow field with the increase of the axial distance. By calculation, it is obtained that under the optimum working condition of the flow rate is 4.83m3/h, the flow ratio is 20%, the sand content is 20%, and sand diameter is 80μm, the maximum Es is 22.1% and the minimum is 86.1%. Finally, a comprehensive analysis of the hydrocyclone in this study shows that this hydrocyclone is only applicable to rough pre-separation of sand in the process of solid fluidization exploitation. Through the study of the internal flow field characteristics and phase distribution law of the hydrocyclone, this study provides a reference for the practical engineering application of sand phase pre-separation in the solid fluidization exploitation of NGH. [ABSTRACT FROM AUTHOR]

Background: The prevalence of human immunodeficiency virus (HIV) varies markedly among different risk groups in China, spreading fromhigh-risk populations to the general population. Indeed, China is in a critical period of HIV/acquired immunodeficiency syndrome (AIDS) prevention and control; however, data regarding HIV testing, infection and coinfection among infertile couples are lacking. This study aimed to estimate the HIV/AIDS prevalence to identify risk factors among infertile couples in Hunan, China. Methods: A cross-sectional hospital-based study was conducted to evaluate the prevalence of HIV/other infections (hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, and Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium (MG) infections) among 338,432 infertile individuals in Hunan, China, from 2012 to 2018. We calculated linear trends in prevalence using bivariate linear regression. Results: The overall prevalence rates of HIV, chlamydia, gonorrhea, MG, syphilis, and HBV and HCV antibody positivity in this study were 0.04%, 1.73%, 0.05%, 2.60%, 2.15%, 12.01% and 0.56%, respectively. The predominant infection was HBV, followed by MG, syphilis, and chlamydia. Only 1.13% of the participants (382/338432) reported sexually transmitted disease (STD) signs and symptoms suggesting genital tract infection. However, from 2012–2018, the variation in HIV prevalence was not significant (β = 0.000, PTREND = 0.907). The characteristics of the HIV-infected infertile population have not shifted dramatically, with women accounting for 32.56% of HIV cases in China. Overall, 87.60% of HIV-infected individuals have a relatively low education. In total, 37.98% of HIV-positive patients engage in high-risk behaviors. Conclusions: This study expands upon existing knowledge of HIV prevalence in the infertile Chinese population. However, much work is needed to achieve popularization of prevention knowledge and change concept. Routine HIV screening is urgently needed for all adults with high-risk behaviors. [ABSTRACT FROM AUTHOR]

The existing mosquito pesticide repertoire faces great challenges to sustainability, and new classes of pesticides are vitally needed to address established and emerging mosquito-borne infectious diseases. RNA interference- (RNAi-) based pesticides are emerging as a promising new biorational mosquito control strategy. In this investigation, we describe characterization of an interfering RNA pesticide (IRP) corresponding to the mosquito Shaker (Sh) gene, which encodes an evolutionarily conserved voltage-gated potassium channel subunit. Delivery of the IRP to Aedes aegypti adult mosquitoes in the form of siRNA that was injected or provided as an attractive toxic sugar bait (ATSB) led to Sh gene silencing that resulted in severe neural and behavioral defects and high levels of adult mortality. Likewise, when provided to A. aegypti larvae in the form of short hairpin RNA (shRNA) expressed in Saccharomyces cerevisiae (baker's yeast) that had been formulated into a dried inactivated yeast tablet, the yeast IRP induced neural defects and larval death. Although the Sh IRP lacks a known target site in humans or other non-target organisms, conservation of the target site in the Sh genes of multiple mosquito species suggested that it may function as a biorational broad-range mosquito insecticide. In support of this, the Sh IRP induced both adult and larval mortality in treated Aedes albopictus, Anopheles gambiae, and Culex quinquefasciatus mosquitoes, but was not toxic to non-target arthropods. These studies indicated that IRPs targeting Sh could one day be used in integrated biorational mosquito control programs for the prevention of multiple mosquito-borne illnesses. The results of this investigation also suggest that the species-specificity of ATSB technology, a new paradigm for vector control, could be enhanced through the use of RNAi-based pesticides. Author summary: New classes of environmentally-safe pesticides are vitally needed to address established and emerging mosquito-borne infectious diseases. In this investigation, we describe characterization of an interfering RNA pesticide corresponding to the mosquito Shaker gene. Although the pesticide recognizes a conserved target site in the Shaker genes of multiple species of disease vector mosquitoes, it lacks a known target site in humans or other non-target organisms. The pesticide killed adult mosquitoes when it was microinjected or provided to adults as an attractive toxic sugar bait. The pesticide also induced high mortality rates when fed to larvae using a yeast-based expression and delivery system. These studies demonstrated that interfering RNA pesticides targeting the mosquito Shaker gene could one day be used for the biorational control of mosquitoes and the prevention of multiple mosquito-borne illnesses. [ABSTRACT FROM AUTHOR]

Alpinia oxyphylla Miq. (A. oxyphylla) is an important edible and traditional herbal medicine. In this study, the complete chloroplast genome of A. oxyphylla was sequenced, analysed, and compared to five species in the Zingiberaceae family. The size of the A. oxyphylla chloroplast genome was 161351 bp, which consisted of a large single-copy (LSC, 87248 bp) and small single-copy (SSC, 16175 bp) region separated by a pair of inverted repeats (IRa and IRb, 28964 bp each). The genome encoded 132 unique genes, including 87 protein-coding genes, 37 tRNAs and four rRNAs. The GC content of the genome was 36.17%. A total of 53 simple sequence repeats (SSRs) and 80 long repeats were identified in the A. oxyphylla chloroplast genome. The chloroplast genome of A. oxyphylla shared the highest sequence similarity of >90% with the chloroplast genome of A. zerumbet, and six chloroplast genomes in the Zingiberaceae family were compared by using CGView Comparison Tool (CCT). According to the phylogenetic tree, the Zingiberaceae family is divided into two categories, which coincide with the classification of the characteristics of sun-like and shade-like in plants. Our results reveal the phototrophic component of NADH-dehydrogenase (ndhB and ndhC), photosystem II (psbZ) and ATP synthase (atpE, atpF) exhibit adaptive evolution under different environments, and the strength of light is an important trigger for the adaptations at the chloroplast level. [ABSTRACT FROM AUTHOR]

New mosquito control strategies are vitally needed to address established and emerging arthropod-borne infectious diseases. Here we describe the characterization of a yeast interfering RNA larvicide that was developed through the genetic engineering of Saccharomyces cerevisiae (baker’s yeast) to express a short hairpin RNA targeting the Aedes aegypti synaptotagmin (Aae syt) gene. The larvicide effectively silences the Aae syt gene, causes defects at the larval neural synapse, and induces high rates of A. aegypti larval mortality in laboratory, simulated-field, and semi-field trials. Conservation of the interfering RNA target site in multiple mosquito species, but not in humans or other non-target species, suggested that it may function as a broad-range mosquito larvicide. In support of this, consumption of the yeast interfering RNA larvicide was also found to induce high rates of larval mortality in Aedes albopictus, Anopheles gambiae, and Culex quinquefasciatus mosquito larvae. The results of these studies suggest that this biorational yeast interfering RNA larvicide may represent a new intervention that can be used to combat multiple mosquito vectors of human diseases. [ABSTRACT FROM AUTHOR]

Object manipulation requires well-coordinated force vectors involving both magnitudes and directions. Despite extensive studies about force magnitudes during manipulation, relatively little is known how the muscle fatigue could affect the directional coordination of fingertip forces. This study aims to examine the effects of muscle fatigue on inter-digit coordination of force directions during precision grip. Sixteen female subjects performed precision grip with their thumb and index finger before and after fatigue tasks, which required subjects to produce continuous submaximal pinch strength on the apparatus for a duration more than 200 s. Both their left and right hands were evaluated using the same testing protocol. The means and standard deviations of the coordination angle and the projection angle were applied to quantify the directional coordination across the digits and the force vector direction of each individual digit. Results showed that fatigue led to significant reduction in the mean values of coordination angle and that of projection angle of the index finger in the ipsilateral hand (p < 0.05). Meanwhile, fatigue induced increases in both the standard deviations of coordination angle and projection angle of both digits in the ipsilateral hand (p < 0.05). These results imply that the muscle fatigue could interfere with the grasping stability by altering the directional coordination of all the involved digits and the control of force directions for each individual digit. These findings provide insights into fatigue-related changes of force directional regulation and coordination in dexterous manipulation. [ABSTRACT FROM AUTHOR]

Turnovers of sex-determining systems represent important diversifying forces across eukaryotes. Shifts in sex chromosomes—but conservation of the master sex-determining genes—characterize distantly related animal lineages. Yet in plants, in which separate sexes have evolved repeatedly and sex chromosomes are typically homomorphic, we do not know whether such translocations drive sex-chromosome turnovers within closely related taxonomic groups. This phenomenon can only be demonstrated by identifying sex-associated nucleotide sequences, still largely unknown in plants. The wild North American octoploid strawberries (Fragaria) exhibit separate sexes (dioecy) with homomorphic, female heterogametic (ZW) inheritance, yet sex maps to three different chromosomes in different taxa. To characterize these turnovers, we identified sequences unique to females and assembled their reads into contigs. For most octoploid Fragaria taxa, a short (13 kb) sequence was observed in all females and never in males, implicating it as the sex-determining region (SDR). This female-specific “SDR cassette” contains both a gene with a known role in fruit and pollen production and a novel retrogene absent on Z and autosomal chromosomes. Phylogenetic comparison of SDR cassettes revealed three clades and a history of repeated translocation. Remarkably, the translocations can be ordered temporally due to the capture of adjacent sequence with each successive move. The accumulation of the “souvenir” sequence—and the resultant expansion of the hemizygous SDR over time—could have been adaptive by locking genes into linkage with sex. Terminal inverted repeats at the insertion borders suggest a means of movement. To our knowledge, this is the first plant SDR shown to be translocated, and it suggests a new mechanism (“move-lock-grow”) for expansion and diversification of incipient sex chromosomes. [ABSTRACT FROM AUTHOR]

Efficient conversion of cellulosic sugars in cellulosic hydrolysates is important for economically viable production of biofuels from lignocellulosic biomass, but the goal remains a critical challenge. The present study reports a new approach for simultaneous fermentation of cellobiose and xylose by using the co-culture consisting of recombinant Saccharomyces cerevisiae specialist strains. The co-culture system can provide competitive advantage of modularity compared to the single culture system and can be tuned to deal with fluctuations in feedstock composition to achieve robust and cost-effective biofuel production. This study characterized fermentation kinetics of the recombinant cellobiose-consuming S. cerevisiae strain EJ2, xylose-consuming S. cerevisiae strain SR8, and their co-culture. The motivation for kinetic modeling was to provide guidance and prediction of using the co-culture system for simultaneous fermentation of mixed sugars with adjustable biomass of each specialist strain under different substrate concentrations. The kinetic model for the co-culture system was developed based on the pure culture models and incorporated the effects of product inhibition, initial substrate concentration and inoculum size. The model simulations were validated by results from independent fermentation experiments under different substrate conditions, and good agreement was found between model predictions and experimental data from batch fermentation of cellobiose, xylose and their mixtures. Additionally, with the guidance of model prediction, simultaneous co-fermentation of 60 g/L cellobiose and 20 g/L xylose was achieved with the initial cell densities of 0.45 g dry cell weight /L for EJ2 and 0.9 g dry cell weight /L SR8. The results demonstrated that the kinetic modeling could be used to guide the design and optimization of yeast co-culture conditions for achieving simultaneous fermentation of cellobiose and xylose with improved ethanol productivity, which is critically important for robust and efficient renewable biofuel production from lignocellulosic biomass. [ABSTRACT FROM AUTHOR]

Reduced knee flexion is a leading feature of post-stroke gait, but the causes have not been well understood. The purpose of this study was to investigate the relationship between the knee flexion and the lower-limb muscle activation within the stance-to-swing phases of gait cycle in the post-stroke hemiplegic patients. Ten stroke patients and 10 age- and gender-matched healthy subjects participated in the experiment. The lower-limb kinematic signals and the surface electromyography (sEMG) signals of the left and right rectus femoris (RF), biceps femoris (BF) and lateral gastrocnemius (GS) were recorded during walking. The angle range (AR) of knee flexion, the root mean square (RMS) and the mean frequency (MNF) of sEMG signals were calculated from the terminal stance (TSt) to the initial swing (ISw) phases of gait cycle. Stroke patients showed lower bilateral AR of knee flexion and lower RMS of GS on the paretic side, but higher MNF of RF on the non-paretic side compared with the controls. Within the stroke patients, significant differences were found between their paretic and non-paretic limbs in the AR of knee flexion, as well as in the RMS and MNF of GS (p < 0.05). Regression analysis showed that the RMS of BF, MNF of BF and MNF of GS explained 82.1% of variations in AR of knee flexion on paretic side (r2 = 0.821). But the RMS and MNF of all the muscles (including the RF, GS and BF) could explain 65.6% of AR of knee flexion variations on the non-paretic side (r2 = 0.656), and 45.2% of variations for the healthy subjects (r2 = 0.452). The reduced knee flexion during gait was associated with altered magnitude and frequency of muscle contractions and with simplified muscle synergy in the post-stroke hemiplegic patients. Identifying the muscles that are responsible for knee stiffness may facilitate improvement of rehabilitation strategy for post-stroke gait. [ABSTRACT FROM AUTHOR]

Objectives: Aspiration after stroke has been associated with aspiration pneumonia, which contributes to increased mortality of stroke. Laryngeal elevation is a core mechanism for protection from aspiration. Few studies have explored the predictive value of laryngeal elevation velocity for aspiration after stroke. This study aimed to explore the ability of laryngeal elevation velocity to predict aspiration in patients with acute ischemic stroke. Methods: This was a prospective cohort study that included consecutive acute ischemic stroke patients treated at a teaching hospital during a 10-month period. Patients underwent magnetic resonance imaging (MRI) to confirm the diagnosis of acute ischemic stroke. Patients who were at risk of aspiration and could swallow 5 ml of diluted barium (40%, w/v) for a videofluoroscopic swallowing (VFS) study were included. The association between abnormal indices in the oral and pharyngeal phase of the VFS study and aspiration was examined using univariate analyses. These indices included the lip closure, tongue movement and control, laryngeal elevation velocity and range, the latency of pharyngeal swallowing, pharyngeal transit time (PTT), abnormal epiglottis tilt, residual barium in the pharynx, and the duration of upper esophageal sphincter (UES) opening. The laryngeal elevation velocity (%/s) was calculated as the range of laryngeal elevation (%) from the resting position to the maximum superior position or to the position where the laryngeal vestibule is fully closed divided by the corresponding duration of laryngeal elevation. The range of laryngeal elevation (%) was the percentage calculated as the distance between the resting laryngeal position and the maximum superior excursion position or position where the laryngeal vestibule is fully closed divided by the distance between the resting laryngeal position and the lowest edge of the mandible. A logistic regression analysis was used to determine the predictive value for aspiration secondary to reduced laryngeal elevation velocity after adjusting for the effects of other indices. Intrarater and interrater reliability were calculated using Pearson’s correlation coefficients. Results: Data from 89 patients were analyzed. This cohort included 71 males and 18 females with a mean age of 59.31±11.46 years. The mean time from stroke onset to the VFS study was 3 days (1–7). Twenty one (23%) patients aspirated while swallowing 5 ml of diluted barium (40%, w/v). Aspiration was associated with age, the velocity (%/s) of laryngeal elevation and duration, delayed pharyngeal phase, pharyngeal transit time, abnormal epiglottic tilt, and invalid laryngeal elevation before true swallowing, and duration of upper esophageal sphincter (UES) opening. After adjusting for the effects of the indices mentioned above, logistic regression analysis revealed that a reduced of laryngeal elevation velocity before vestibule closure was predictive of aspiration independently (OR, 0.993; 95% CI, 0.987–1.000). Discussions: Reduced laryngeal elevation velocity for laryngeal elevated to position where laryngeal vestibule is fully closed was an independent predictor of aspiration in patients with acute ischemic stroke. This may be related to a decreased contraction velocity of the muscles involved in hyolaryngeal elevation. Therapeutic methods aimed at improving laryngeal elevation velocity may decrease aspiration events and pneumonias after stroke. [ABSTRACT FROM AUTHOR]

The fermentation inhibitors from the pretreatment of lignocellulosic materials, e.g., acetic acid and furfural, are notorious due to their negative effects on the cell growth and chemical production. However, the metabolic reprogramming of the cells under these stress conditions, especially metabolic response for resistance to mixed inhibitors, has not been systematically investigated and remains mysterious. Therefore, in this study, 13C metabolic flux analysis (13C-MFA), a powerful tool to elucidate the intracellular carbon flux distributions, has been applied to two Saccharomyces cerevisiae strains with different tolerances to the inhibitors under acetic acid, furfural, and mixed (i.e., acetic acid and furfural) stress conditions to unravel the key metabolic responses. By analyzing the intracellular carbon fluxes as well as the energy and cofactor utilization under different conditions, we uncovered varied metabolic responses to different inhibitors. Under acetate stress, ATP and NADH production was slightly impaired, while NADPH tended towards overproduction. Under furfural stress, ATP and cofactors (including both NADH and NADPH) tended to be overproduced. However, under dual-stress condition, production of ATP and cofactors was severely impaired due to synergistic stress caused by the simultaneous addition of two fermentation inhibitors. Such phenomenon indicated the pivotal role of the energy and cofactor utilization in resisting the mixed inhibitors of acetic acid and furfural. Based on the discoveries, valuable insights are provided to improve the tolerance of S. cerevisiae strain and further enhance lignocellulosic fermentation. [ABSTRACT FROM AUTHOR]

Purposes: Recent neuroimaging studies have shown that people with Internet gaming disorder (IGD) have structural and functional abnormalities in specific brain areas and connections. However, little is known about the alterations of the interhemispheric resting-state functional connectivity (rsFC) in participants with IGD. In the present study, we used a newly developed voxel-mirrored homotopic connectivity (VMHC) method to investigate the interhemispheric rsFC of the whole brain in participants with IGD. Methods: We compared interhemispheric rsFC between 17 participants with IGD and 24 healthy controls, group-matched on age, gender, and education status. All participants were provided written informed consent. Resting-state functional and structural magnetic resonance images were acquired for all participants. The rsFC between bilateral homotopic voxels was calculated. Regions showing abnormal VMHC in IGD participants were adopted as regions of interest for correlation analyses. Results: Compared to healthy controls, IGD participants showed decreased VMHC between the left and right superior frontal gyrus (orbital part), inferior frontal gyrus (orbital part), middle frontal gyrus and superior frontal gyrus. Further analyses showed Chen Internet Addiction Scale (CIAS)-related VMHC in superior frontal gyrus (orbital part) and CIAS (r = −0.55, p = 0.02, uncorrected). Conclusions: Our findings implicate the important role of altered interhemispheric rsFC in the bilateral prefrontal lobe in the neuropathological mechanism of IGD, and provide further supportive evidence for the reclassification of IGD as a behavioral addiction. [ABSTRACT FROM AUTHOR]

Potent RNase activities were found in the serum of mammals but the physiological function of the RNases was never well illustrated, largely due to the caveats in methods of RNase activity measurement. None of the existing methods can distinguish between RNases with different target specificities. A systematic study was recently carried out in our lab to investigate the site-specificity of serum RNases on double-stranded RNA substrates, and found that serum RNases cleave double-stranded RNAs predominantly at 5′-U/A-3′ and 5′-C/A-3′ dinucleotide sites, in a manner closely resembling RNase A. Based on this finding, a FRET assay was developed in the current study to measure this site-specific serum RNase activity in human samples using a double stranded RNA substrate. We demonstrated that the method has a dynamic range of 10−5 mg/ml- 10−1 mg/ml using serial dilution of RNase A. The sera of 303 cancer patients were subjected to comparison with 128 healthy controls, and it was found that serum RNase activities visualized with this site-specific double stranded probe were found to be significantly reduced in patients with gastric cancer, liver cancer, pancreatic cancer, esophageal cancer, ovary cancer, cervical cancer, bladder cancer, kidney cancer and lung cancer, while only minor changes were found in breast and colon cancer patients. This is the first report using double stranded RNA as probe to quantify site-specific activities of RNase A in a serum. The results illustrated that RNase A might be further evaluated to determine if it can serve as a new class of biomarkers for certain cancer types. [ABSTRACT FROM AUTHOR]

High-fat diets may promote growth, partly through their protein-sparing effects. However, high-fat diets often lead to excessive fat deposition, which may have a negative impact on fish such as poor growth and suppressive immune. Therefore, this study investigated the effects of a fat-rich diet on the mechanisms of fat deposition in the liver. Three-hundred blunt snout bream (Megalobrama amblycephala) juveniles (initial mass 18.00±0.05 g) were fed with one of two diets (5% or 15% fat) for 8 weeks. β-Oxidation capacity and regulation of rate-limiting enzymes were assessed. Large fat droplets were present in hepatocytes of fish fed the high-fat diet. This observation is thought to be largely owing to the reduced capacity for mitochondrial and peroxisomal β-oxidation in the livers of fish fed the high-fat diet, as well as the decreased activities of carnitine palmitoyltransferase (CPT) I and acyl-CoA oxidase (ACO), which are enzymes involved in fatty-acid metabolism. Study of CPT I kinetics showed that CPT I had a low affinity for its substrates and a low catalytic efficiency in fish fed the high-fat diet. Expression of both CPT I and ACO was significantly down-regulated in fish fed the high-fat diet. Moreover, the fatty-acid composition of the mitochondrial membrane varied between the two groups. In conclusion, the attenuated β-oxidation capacity observed in fish fed a high-fat diet is proposed to be owing to decreased activity and/or catalytic efficiency of the rate-limiting enzymes CPT I and ACO, via both genetic and non-genetic mechanisms. [ABSTRACT FROM AUTHOR]

Ginsenoside Rb1 (RB1), the most clinically effective constituent of ginseng, possesses a variety of biological activities. The objectives of this study were to investigate the protective effects of RB1 and its underlying mechanism on renal injury induced by intestinal ischemia-reperfusion (IIR) in mice. RB1 was administered prior to inducing IIR achieved by occluding the superior mesenteric artery for 45 min followed by 120 min of reperfusion. All-trans-retinoic acid (ATRA) was used as an inhibitor of NF-E2-related factor-2 (Nrf2) signaling. Adult male C57BL/6J mice were randomly divided into six groups: (1) sham group, (2) IIR group, (3) RB1 group, (4) sham + ATRA group, (5) IIR + ATRA group, and (6) RB1 + ATRA group. Intestinal histology and pathological injury score were observed. Intestinal mucosal injury was also evaluated by measuring serum diamine oxidase (DAO). Renal injury induced by IIR was characterized by increased levels of histological severity score, blood urea nitrogen (BUN), serum creatinine (Scr) and neutrophil gelatinase-associated lipocalin (NGAL), which was accompanied with elevated renal TUNEL-positive cells and the Bcl-2/Bax expression ratio. RB1 significantly reduced renal injury and apoptosis as compared with IIR group, which was reversed by ATRA treatment. Immunohistochemistry and Western blot analysis demonstrated that RB1 significantly upregulated the protein expression of heme oxygenase-1 (HO-1) and Nrf2, which were attenuated by ATRA treatment. Taken together, these results suggest that the protective effects of RB1 pretreatment against renal injury induced by IIR are associated with activation of the Nrf2/ anti-oxidant response element (ARE) pathway. [ABSTRACT FROM AUTHOR]

Background: Post-stroke depression (PSD) is commonly observed among stroke survivors. However, statistical analysis of such data is scarce in developing countries. The purpose of this study is to examine the incidence of PSD and its relationship with stroke characteristics in China. Methods: This was a prospective hospital-based study. Stroke patients were assessed within two weeks after acute ischemic stroke onset and then reevaluated at three months. Hamilton Depression Scale (HAMD) was used for screening depression (PSD). Subjects with HAMD score of ≥7 were further assessed with the World Health Organization Composite International Diagnostic Interview. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIHSS). Stroke outcome was measured by the modified Rankin Scale (mRS). Results: One hundred and two stroke patients were recruited, only ninety-one patients completed del period (men = 53, 63.74%), with mean age 60.0±10.4 years (range, 34–82 years). The incidence of PSD was 27.47% two weeks after stroke. The occurrence of PSD was unrelated with age, stroke type, stroke lesion and the history of disease. In univariate analysis gender, PSD was correlated with female gender. In multivariate logistic regression analysis, poor stroke outcome (mRS≥3) (OR 12.113, CI 1.169 to 125.59, P<0.05) was the important predictors of PSD. Conclusions: The study indicated that gender, functional dependence and stroke outcome are determinants of PSD occurrence during the first 2 weeks after stroke in China. [ABSTRACT FROM AUTHOR]

Taste perception plays an important role in regulating food preference, eating behavior and energy homeostasis. Taste perception is modulated by a variety of factors, including gastric hormones such as ghrelin. Ghrelin can regulate growth hormone release, food intake, adiposity, and energy metabolism. Octanoylation of ghrelin by ghrelin O-acyltransferase (GOAT) is a specific post-translational modification which is essential for many biological activities of ghrelin. Ghrelin and GOAT are both widely expressed in many organs including the gustatory system. In the current study, overall metabolic profiles were assessed in wild-type (WT), ghrelin knockout (ghrelin−/−), and GOAT knockout (GOAT−/−) mice. Ghrelin−/− mice exhibited decreased food intake, increased plasma triglycerides and increased ketone bodies compared to WT mice while demonstrating WT-like body weight, fat composition and glucose control. In contrast GOAT−/− mice exhibited reduced body weight, adiposity, resting glucose and insulin levels compared to WT mice. Brief access taste behavioral tests were performed to determine taste responsivity in WT, ghrelin−/− and GOAT−/− mice. Ghrelin and GOAT null mice possessed reduced lipid taste responsivity. Furthermore, we found that salty taste responsivity was attenuated in ghrelin−/− mice, yet potentiated in GOAT−/− mice compared to WT mice. Expression of the potential lipid taste regulators Cd36 and Gpr120 were reduced in the taste buds of ghrelin and GOAT null mice, while the salt-sensitive ENaC subunit was increased in GOAT−/− mice compared with WT mice. The altered expression of Cd36, Gpr120 and ENaC may be responsible for the altered lipid and salt taste perception in ghrelin−/− and GOAT−/− mice. The data presented in the current study potentially implicates ghrelin signaling activity in the modulation of both lipid and salt taste modalities. [ABSTRACT FROM AUTHOR]

With the prevalence of obesity, artificial, non-nutritive sweeteners have been widely used as dietary supplements that provide sweet taste without excessive caloric load. In order to better understand the overall actions of artificial sweeteners, especially when they are chronically used, we investigated the peripheral and central nervous system effects of protracted exposure to a widely used artificial sweetener, acesulfame K (ACK). We found that extended ACK exposure (40 weeks) in normal C57BL/6J mice demonstrated a moderate and limited influence on metabolic homeostasis, including altering fasting insulin and leptin levels, pancreatic islet size and lipid levels, without affecting insulin sensitivity and bodyweight. Interestingly, impaired cognitive memory functions (evaluated by Morris Water Maze and Novel Objective Preference tests) were found in ACK-treated C57BL/6J mice, while no differences in motor function and anxiety levels were detected. The generation of an ACK-induced neurological phenotype was associated with metabolic dysregulation (glycolysis inhibition and functional ATP depletion) and neurosynaptic abnormalities (dysregulation of TrkB-mediated BDNF and Akt/Erk-mediated cell growth/survival pathway) in hippocampal neurons. Our data suggest that chronic use of ACK could affect cognitive functions, potentially via altering neuro-metabolic functions in male C57BL/6J mice. [ABSTRACT FROM AUTHOR]

Purpose: Excessive use of the Internet has been linked to a variety of negative psychosocial consequences. This study used resting-state functional magnetic resonance imaging (fMRI) to investigate whether functional connectivity is altered in adolescents with Internet gaming addiction (IGA). Methods: Seventeen adolescents with IGA and 24 normal control adolescents underwent a 7.3 minute resting-state fMRI scan. Posterior cingulate cortex (PCC) connectivity was determined in all subjects by investigating synchronized low-frequency fMRI signal fluctuations using a temporal correlation method. To assess the relationship between IGA symptom severity and PCC connectivity, contrast images representing areas correlated with PCC connectivity were correlated with the scores of the 17 subjects with IGA on the Chen Internet Addiction Scale (CIAS) and Barratt Impulsiveness Scale-11 (BIS-11) and their hours of Internet use per week. Results: There were no significant differences in the distributions of the age, gender, and years of education between the two groups. The subjects with IGA showed longer Internet use per week (hours) (p<0.0001) and higher CIAS (p<0.0001) and BIS-11 (p = 0.01) scores than the controls. Compared with the control group, subjects with IGA exhibited increased functional connectivity in the bilateral cerebellum posterior lobe and middle temporal gyrus. The bilateral inferior parietal lobule and right inferior temporal gyrus exhibited decreased connectivity. Connectivity with the PCC was positively correlated with CIAS scores in the right precuneus, posterior cingulate gyrus, thalamus, caudate, nucleus accumbens, supplementary motor area, and lingual gyrus. It was negatively correlated with the right cerebellum anterior lobe and left superior parietal lobule. Conclusion: Our results suggest that adolescents with IGA exhibit different resting-state patterns of brain activity. As these alterations are partially consistent with those in patients with substance addiction, they support the hypothesis that IGA as a behavioral addiction that may share similar neurobiological abnormalities with other addictive disorders. [ABSTRACT FROM AUTHOR]

Economic bioconversion of plant cell wall hydrolysates into fuels and chemicals has been hampered mainly due to the inability of microorganisms to efficiently co-ferment pentose and hexose sugars, especially glucose and xylose, which are the most abundant sugars in cellulosic hydrolysates. Saccharomyces cerevisiae cannot metabolize xylose due to a lack of xylose-metabolizing enzymes. We developed a rapid and efficient xylose-fermenting S. cerevisiae through rational and inverse metabolic engineering strategies, comprising the optimization of a heterologous xylose-assimilating pathway and evolutionary engineering. Strong and balanced expression levels of the XYL1, XYL2, and XYL3 genes constituting the xylose-assimilating pathway increased ethanol yields and the xylose consumption rates from a mixture of glucose and xylose with little xylitol accumulation. The engineered strain, however, still exhibited a long lag time when metabolizing xylose above 10 g/l as a sole carbon source, defined here as xylose toxicity. Through serial-subcultures on xylose, we isolated evolved strains which exhibited a shorter lag time and improved xylose-fermenting capabilities than the parental strain. Genome sequencing of the evolved strains revealed that mutations in PHO13 causing loss of the Pho13p function are associated with the improved phenotypes of the evolved strains. Crude extracts of a PHO13-overexpressing strain showed a higher phosphatase activity on xylulose-5-phosphate (X-5-P), suggesting that the dephosphorylation of X-5-P by Pho13p might generate a futile cycle with xylulokinase overexpression. While xylose consumption rates by the evolved strains improved substantially as compared to the parental strain, xylose metabolism was interrupted by accumulated acetate. Deletion of ALD6 coding for acetaldehyde dehydrogenase not only prevented acetate accumulation, but also enabled complete and efficient fermentation of xylose as well as a mixture of glucose and xylose by the evolved strain. These findings provide direct guidance for developing industrial strains to produce cellulosic fuels and chemicals. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg) rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP), heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4), glycogen synthase1 (Gys1) and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1). In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD. [ABSTRACT FROM AUTHOR]

The goal of this study was to investigate the relationship between resting-state functional connectivity and the severity of post-traumatic stress disorder (PTSD) symptoms in 15 people who developed PTSD following recent trauma. Fifteen participants who experienced acute traumatic events underwent a 7.3-min resting functional magnetic resonance imaging scan within 2 days post-event. All the patients were diagnosed with PTSD within 1 to 6 months after trauma. Brain areas in which activity was correlated with that of the posterior cingulate cortex (PCC) were assessed. To assess the relationship between the severity of PTSD symptoms and PCC connectivity, contrast images representing areas positively correlated with the PCC were correlated with the subject's Clinician-Administered PTSD Scale scores (CAPS) when they were diagnosed. Furthermore, the PCC, medial prefrontal cortex and bilateral amygdala were selected to assess the correlation of the strength of functional connectivity with the CAPS. Resting state connectivity with the PCC was negatively correlated with CAPS scores in the left superior temporal gyrus and right hippocampus/amygdala. Furthermore, the strength of connectivity between the PCC and bilateral amygdala, and even between the bilateral amygdala could predict the severity of PTSD symptoms later. These results suggest that early altered resting-state functional connectivity of the PCC with the left superior temporal gyrus, right hippocampus and amygdala could predict the severity of the disease and may be a major risk factor that predisposes patients to develop PTSD. [ABSTRACT FROM AUTHOR]

Hemiplegic paralysis after stroke may augment postural instability and decrease the balance control ability for standing. The center of mass acceleration (COMacc) is considered to be an effective indicator of postural stability for standing balance control. However, it is less studied how the COMacc could be affected by the muscle activities on lower-limbs in post-stroke hemiplegic patients. This study aimed to examine the effects of hemiplegic paralysis in post-stroke individuals on the amplitude and structural variabilities of COMacc and surface electromyography (sEMG) signals during quiet standing. Eleven post-stroke hemiplegic patients and the same number of gender- and age-matched healthy volunteers participated in the experiment. The sEMG signals of tibialis anterior (TA) and lateral gastrocnemius (LG) muscles of the both limbs, and the COMacc in the anterior-posterior direction with and without visual feedback (VF vs. NVF) were recorded simultaneously during quiet standing. The sEMG and COMacc were analyzed using root mean square (RMS) or standard deviation (SD), and a modified detrended fluctuation analysis based on empirical mode decomposition (EMD-DFA). Results showed that the SD and the scale exponent α of EMD-DFA of the COMacc from the patients were significantly higher than the values from the controls under both VF (p < 0.01) and NVF (p < 0.001) conditions. The RMSs of TA and LG on the non-paretic limbs were significantly higher than those on paretic limbs (p < 0.05) for both the patients and controls (p < 0.05). The TA of both the paretic and non-paretic limbs of the patients showed augmented α values than the TA of the controls (p < 0.05). The α of the TA and LG of non-paretic limbs, and the α of COMacc were significantly increased after removing visual feedback in patients (p < 0.05). These results suggested an increased amplitude variability but decreased structural variability of COMacc, associated with asymmetric muscle contraction between the paretic and the non-paretic limbs in hemiplegic paralysis, revealing a deficiency in integration of sensorimotor information and a loss of flexibility of postural control due to stroke. [ABSTRACT FROM AUTHOR]

Economic bioconversion of plant cell wall hydrolysates into fuels and chemicals has been hampered mainly due to the inability of microorganisms to efficiently co-ferment pentose and hexose sugars, especially glucose and xylose, which are the most abundant sugars in cellulosic hydrolysates. Saccharomyces cerevisiae cannot metabolize xylose due to a lack of xylose-metabolizing enzymes. We developed a rapid and efficient xylose-fermenting S. cerevisiae through rational and inverse metabolic engineering strategies, comprising the optimization of a heterologous xylose-assimilating pathway and evolutionary engineering. Strong and balanced expression levels of the XYL1, XYL2, and XYL3 genes constituting the xylose-assimilating pathway increased ethanol yields and the xylose consumption rates from a mixture of glucose and xylose with little xylitol accumulation. The engineered strain, however, still exhibited a long lag time when metabolizing xylose above 10 g/l as a sole carbon source, defined here as xylose toxicity. Through serial-subcultures on xylose, we isolated evolved strains which exhibited a shorter lag time and improved xylose-fermenting capabilities than the parental strain. Genome sequencing of the evolved strains revealed that mutations in PHO13 causing loss of the Pho13p function are associated with the improved phenotypes of the evolved strains. Crude extracts of a PHO13-overexpressing strain showed a higher phosphatase activity on xylulose-5-phosphate (X-5-P), suggesting that the dephosphorylation of X-5-P by Pho13p might generate a futile cycle with xylulokinase overexpression. While xylose consumption rates by the evolved strains improved substantially as compared to the parental strain, xylose metabolism was interrupted by accumulated acetate. Deletion of ALD6 coding for acetaldehyde dehydrogenase not only prevented acetate accumulation, but also enabled complete and efficient fermentation of xylose as well as a mixture of glucose and xylose by the evolved strain. These findings provide direct guidance for developing industrial strains to produce cellulosic fuels and chemicals. [ABSTRACT FROM AUTHOR]

The fermentation inhibitors from the pretreatment of lignocellulosic materials, e.g., acetic acid and furfural, are notorious due to their negative effects on the cell growth and chemical production. However, the metabolic reprogramming of the cells under these stress conditions, especially metabolic response for resistance to mixed inhibitors, has not been systematically investigated and remains mysterious. Therefore, in this study, 13C metabolic flux analysis (13C-MFA), a powerful tool to elucidate the intracellular carbon flux distributions, has been applied to two Saccharomyces cerevisiae strains with different tolerances to the inhibitors under acetic acid, furfural, and mixed (i.e., acetic acid and furfural) stress conditions to unravel the key metabolic responses. By analyzing the intracellular carbon fluxes as well as the energy and cofactor utilization under different conditions, we uncovered varied metabolic responses to different inhibitors. Under acetate stress, ATP and NADH production was slightly impaired, while NADPH tended towards overproduction. Under furfural stress, ATP and cofactors (including both NADH and NADPH) tended to be overproduced. However, under dual-stress condition, production of ATP and cofactors was severely impaired due to synergistic stress caused by the simultaneous addition of two fermentation inhibitors. Such phenomenon indicated the pivotal role of the energy and cofactor utilization in resisting the mixed inhibitors of acetic acid and furfural. Based on the discoveries, valuable insights are provided to improve the tolerance of S. cerevisiae strain and further enhance lignocellulosic fermentation.

High-fat diets may promote growth, partly through their protein-sparing effects. However, high-fat diets often lead to excessive fat deposition, which may have a negative impact on fish such as poor growth and suppressive immune. Therefore, this study investigated the effects of a fat-rich diet on the mechanisms of fat deposition in the liver. Three-hundred blunt snout bream (Megalobrama amblycephala) juveniles (initial mass 18.00 ± 0.05 g) were fed with one of two diets (5% or 15% fat) for 8 weeks. β-Oxidation capacity and regulation of rate-limiting enzymes were assessed. Large fat droplets were present in hepatocytes of fish fed the high-fat diet. This observation is thought to be largely owing to the reduced capacity for mitochondrial and peroxisomal β-oxidation in the livers of fish fed the high-fat diet, as well as the decreased activities of carnitine palmitoyltransferase (CPT) I and acyl-CoA oxidase (ACO), which are enzymes involved in fatty-acid metabolism. Study of CPT I kinetics showed that CPT I had a low affinity for its substrates and a low catalytic efficiency in fish fed the high-fat diet. Expression of both CPT I and ACO was significantly down-regulated in fish fed the high-fat diet. Moreover, the fatty-acid composition of the mitochondrial membrane varied between the two groups. In conclusion, the attenuated β-oxidation capacity observed in fish fed a high-fat diet is proposed to be owing to decreased activity and/or catalytic efficiency of the rate-limiting enzymes CPT I and ACO, via both genetic and non-genetic mechanisms.

Economic bioconversion of plant cell wall hydrolysates into fuels and chemicals has been hampered mainly due to the inability of microorganisms to efficiently co-ferment pentose and hexose sugars, especially glucose and xylose, which are the most abundant sugars in cellulosic hydrolysates. Saccharomyces cerevisiae cannot metabolize xylose due to a lack of xylose-metabolizing enzymes. We developed a rapid and efficient xylose-fermenting S. cerevisiae through rational and inverse metabolic engineering strategies, comprising the optimization of a heterologous xylose-assimilating pathway and evolutionary engineering. Strong and balanced expression levels of the XYL1, XYL2, and XYL3 genes constituting the xylose-assimilating pathway increased ethanol yields and the xylose consumption rates from a mixture of glucose and xylose with little xylitol accumulation. The engineered strain, however, still exhibited a long lag time when metabolizing xylose above 10 g/l as a sole carbon source, defined here as xylose toxicity. Through serial-subcultures on xylose, we isolated evolved strains which exhibited a shorter lag time and improved xylose-fermenting capabilities than the parental strain. Genome sequencing of the evolved strains revealed that mutations in PHO13 causing loss of the Pho13p function are associated with the improved phenotypes of the evolved strains. Crude extracts of a PHO13-overexpressing strain showed a higher phosphatase activity on xylulose-5-phosphate (X-5-P), suggesting that the dephosphorylation of X-5-P by Pho13p might generate a futile cycle with xylulokinase overexpression. While xylose consumption rates by the evolved strains improved substantially as compared to the parental strain, xylose metabolism was interrupted by accumulated acetate. Deletion of ALD6 coding for acetaldehyde dehydrogenase not only prevented acetate accumulation, but also enabled complete and efficient fermentation of xylose as well as a mixture of glucose and xylose by the evolved strain. These findings provide direct guidance for developing industrial strains to produce cellulosic fuels and chemicals.

It has been noted that target sites located in the coding region or the 3'-untranslated region (3'-UTR) can be silenced to significantly different levels by the same siRNA, but little is known about at what specificity the silencing was achieved. In an exploration of positional effects on siRNA specificity by luciferase reporter system, we surprisingly discovered that siRNA had greatly elevated tolerance towards mismatches in target sites in the 3'-UTR of the mRNA compared with the same target sites cloned in the coding region. Assessment of changes in protein and mRNA levels suggested that the differential mismatch tolerance might have resulted from location-specific translational repression in the 3'-UTR. Ablation of argonaute proteins by AGO-specific siRNAs revealed that the AGO2 had major impact on siRNA silencing activity against sites in both coding region and 3'-UTR, while the silencing of nonnucleolytic AGO proteins (AGO1, AGO3 and AGO4) did not significantly affect silencing of sites in either region. This paper revealed the discovery that the specificity of an siRNA can be affected by the location of its target site.

The goal of this study was to investigate the relationship between resting-state functional connectivity and the severity of post-traumatic stress disorder (PTSD) symptoms in 15 people who developed PTSD following recent trauma. Fifteen participants who experienced acute traumatic events underwent a 7.3-min resting functional magnetic resonance imaging scan within 2 days post-event. All the patients were diagnosed with PTSD within 1 to 6 months after trauma. Brain areas in which activity was correlated with that of the posterior cingulate cortex (PCC) were assessed. To assess the relationship between the severity of PTSD symptoms and PCC connectivity, contrast images representing areas positively correlated with the PCC were correlated with the subject's Clinician-Administered PTSD Scale scores (CAPS) when they were diagnosed. Furthermore, the PCC, medial prefrontal cortex and bilateral amygdala were selected to assess the correlation of the strength of functional connectivity with the CAPS. Resting state connectivity with the PCC was negatively correlated with CAPS scores in the left superior temporal gyrus and right hippocampus/amygdala. Furthermore, the strength of connectivity between the PCC and bilateral amygdala, and even between the bilateral amygdala could predict the severity of PTSD symptoms later. These results suggest that early altered resting-state functional connectivity of the PCC with the left superior temporal gyrus, right hippocampus and amygdala could predict the severity of the disease and may be a major risk factor that predisposes patients to develop PTSD.

Huntington's disease (HD) is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg) rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP), heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4), glycogen synthase1 (Gys1) and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1). In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD.

Background: Programmed cell death 4 (PDCD4), originally identified as the neoplastic transformation inhibitor, was attenuated in various cancer types. Our previous study demonstrated a continuous down-regulation of PDCD4 expression in the sequence of normal-borderline-malignant ovarian tissue samples and a significant correlation of PDCD4 expression with disease-free survival. The objective of the current study was to further investigate the function and modulation of PDCD4 in ovarian cancer cells., Principal Findings: We demonstrated that ectopic PDCD4 expression significantly inhibited cell proliferation by inducing cell cycle arrest at G(1) stage and up-regulation of cell cycle inhibitors of p27 and p21. Cell migration and invasion were also inhibited by PDCD4. PDCD4 over-expressing cells exhibited elevated phosphatase and tensin homolog (PTEN) and inhibited protein kinase B (p-Akt). In addition, the expression of PDCD4 was up-regulated and it was exported to the cytoplasm upon serum withdrawal treatment, but it was rapidly depleted via proteasomal degradation upon serum re-administration. Treatment of a phosphoinositide 3-kinase (PI3K) inhibitor prevented the degradation of PDCD4, indicating the involvement of PI3K-Akt pathway in the modulation of PDCD4., Conclusion: PDCD4 may play a critical function in arresting cell cycle progression at key checkpoint, thus inhibiting cell proliferation, as well as suppressing tumour metastasis. The PI3K-Akt pathway was implied to be involved in the regulation of PDCD4 degradation in ovarian cancer cells. In response to the stress condition, endogenous PDCD4 was able to shuttle between cell compartments to perform its diverted functions.