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Introduction: Twenty-four-hour movement behaviors: moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior (SB), and sleep are crucial factors affecting older adults’ health. Using a compositional data analysis approach, this study examined the associations of time spent in these four movement behaviors with cardiometabolic health, physical fitness, and mental health among older adults. Furthermore, this study identified the estimated changes in aforementioned health outcomes by reallocating SB time to other movement behaviors. Methods: A population-based cross-sectional study of 4562 participants (67.68 ± 5.03 yr; 55.8% female) were implemented in Hubei China between July 25 and November 19, 2020. Measures included demographics, movement behaviors, cardiometabolic indicators (body mass index, waist circumference, waist–hip ratio, percentage body fat, systolic and diastolic blood pressure), physical fitness, and mental health outcomes (depressive symptoms and loneliness). Compositional data analyses were implemented in R. Results: MVPA and sleep time were associated with greater health outcomes (all P < 0.001), except blood pressure (P = 0.13–0.83). LPA time was associated with waist circumference (B = 0.313, P = 0.009), waist–hip ratio (B = 0.003, P = 0.003), physical fitness (B = 0.36, P < 0.001), and mental health indicators (both P < 0.001). Reallocating 30-min SB to MVPA and sleep was associated with predicated improvements in all health outcomes, except blood pressure, whereas reallocating 30-min SB to LPA resulted in predicted improvements in physical fitness (0.187 units), depressive symptoms (−0.264 units), and loneliness (−0.395 units). For dose–effect relationships, reallocating 5–60 min of SB to MVPA showed greatest benefits for all health outcomes. Conclusions: This study provides timely empirical evidence for future interventions and policymaking on promoting healthy aging during the post–COVID-19 era. The findings underline the importance of including 24-h movement behaviors in future health promotion among older adults. [ABSTRACT FROM AUTHOR]

Persistent scatterers synthetic aperture radar interferometry (PSInSAR) technology has been applied in the context of deformation monitoring of transportation infrastructures such as bridges, highways, and railways. However, extracting and interpreting information from long-time series displacement obtained using PS-InSAR is a complex and demanding task. In this study, time series analysis was used to post-process the displacement time series derived from PSInSAR using 100 stripmap mode images collected by TerraSAR-X satellite during 13 April 2010 and 13 December 2019. Seasonal and trend decomposition using loess (STL) and variational modal decomposition (VMD) were combined to estimate the different periodic and trend components of the total displacement time series. Temperature correlation was then generated by associating the different period components with the temperature change. The results show that the deformation of Sihui overpass, Sifang overpass and Shibalidian overpass in Beijing Fourth Ring Road highway is obvious. The trend components obtained by STL decomposition of the selected typical points are primarily nonlinear deformation, and the deformation of Sifang overpass, Shibalidian overpass and Liuxiang overpass slows to varying degrees. After decomposing the displacement time series into several intrinsic mode functions (imf) with finite bandwidth using VMD, the thermal expansion phenomenon is pronounced on the main bridge and approach bridge of some overpasses. Seasonal imf1 is an annual periodic that appears to be highly positively correlated with temperature change. Seasonal imf2 is a period term of greater than one year that confirms that the bridges exhibit other periodic seasonal components in addition to the seasonal deformation of annual period. The thermal expansion characteristics of different periodic seasonal components that are explored in this study can provide valuable information for better understanding the thermal expansion evolution process, and these findings are important scientific significance for bridge structure health monitoring. [ABSTRACT FROM AUTHOR]

In synchrotron radiation X-ray imaging, the imaging field of view and spatial resolution are mutually restricted, which makes it impossible to have both a large field of view and high resolution when carrying out experiments. Constructing an oversampled image through the micro-scanning method and using the deconvolution algorithm to eliminate the point spread function introduced by pixel overlap can increase the resolution under a fixed imaging field of view, thereby improving the ratio of the field of view to the spatial resolution. In this paper, numerical simulation and synchrotron radiation experiments are carried out with a different number of micro-scanning steps. In numerical simulation experiments only affected by the image pixel size, as the number of micro-scanning steps increases, the ability of the oversampled image with deconvolution to improve the resolution is stronger. The achievable resolution of the oversampled image with deconvolution is basically the same as that of the sample image. In the synchrotron radiation experiments, the resolution of the oversampled image with deconvolution in the 2 x 2 mode is significantly improved. However, as the number of micro-scanning steps increases, the resolution improvement is limited, or even no longer improved. Finally, by analyzing the results of numerical simulation and synchrotron radiation experiments, three factors (four other factors affecting the resolution besides the camera resolution, translational accuracy of micro-scanning, and the signal-to-noise ratio of projections) affecting the micro-scanning method are proposed and verified by experiments. [ABSTRACT FROM AUTHOR]

Background: Skeletal muscle growth and development are closely associated with the quantity and quality of pork production. We performed a transcriptomic analysis of 12 Longissimus dorsi muscle samples from Tibetan piglets at four postnatal stages of 0, 14, 30, and 60 days using RNA sequencing. Results: According to the pairwise comparisons between the libraries of the muscle samples at the four postnatal stages, a total of 4115 differentially expressed genes (DEGs) were identified in terms of |log2(fold change)| ≥ 1 and an adjusted P value < 0.01. Short-time series expression miner (STEM) analysis of the DEGs identified eight significantly different expression profiles, which were divided into two clusters based on the expression pattern. DEGs in cluster I displayed a pattern of decreasing to a nadir, and then a rise, and the significantly enriched gene ontology (GO) terms detected using them were involved in multiple processes, of which the cell cycle, immunocyte activation and proliferation, as well as actin cytoskeleton organization, were the top three overrepresented processes based on the GO terms functional classification. DEGs in cluster II displayed a pattern of increasing to a peak, then declining, which mainly contributed to protein metabolism. Furthermore, besides the pathways related to immune system, a few diseases, and protein metabolism, the DEGs in clusters I and II were significantly enriched in pathways related to muscle growth and development, such as the Rap1, PI3K-Akt, AMPK, and mTOR signaling pathways. Conclusions: This study revealed GO terms and pathways that could affect the postnatal muscle growth and development in piglets. In addition, this study provides crucial information concerning the molecular mechanisms of muscle growth and development as well as an overview of the piglet transcriptome dynamics throughout the postnatal period in terms of growth and development. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical efficacy of butylphthalide in treating patients with stroke attributed to intracranial artery stenosis (ICAS). Methods: In this retrospective study, records of 163 patients with stroke attributed to ICAS admitted to Jiaxing Second Hospital from January 2021 to January 2023 were retrospectively analyzed. Patients were divided into two groups based on the treatment received: control group (patients received routine treatment, n=55) and observation group (patients treated with butylphthalide on a routine basis, n=58). Changes in levels of cerebrovascular reactivity (CVR), breath-holding index (BHI), pulsatility index (PI), and middle cerebral artery mean flow velocity (Vm) between the two groups before and after treatment were compared. In addition, cognitive function, neurological function, and living ability were compared between the two groups before and after treatment, as well as the overall clinical efficacy of the treatment. Results: The baseline data was comparable between the two groups (P>0.05). After the treatment, CVR, BHI, and Vm indicators in the observation group were significantly higher than those in the control group, while the levels of PI indexes were significantly lower than those in the control group (P<0.05). Montreal Cognitive Assessment (MoCA) and Barthel scale scores of the observation group were significantly higher compared to the control group, while the scores of National Institutes of Health Stroke Scale (NIHSS) were significantly lower (P<0.05). Conclusions: Butylphthalide in addition to routine treatment can effectively improve cerebrovascular reserve function, promote neurological and cognitive dysfunction recovery, and enhance daily living ability of patients with stroke caused by ICAS. [ABSTRACT FROM AUTHOR]

Objective: Shandong indigenous pig breeds are important Chinese pig resources. Their progressive population decline in recent decades has attracted attention towards their conservation. Conservation genetics of these indigenous breeds are essential for developing a conservation and utilization scheme. Methods: A high-density single nucleotide polymorphism (HD-SNP) chip-based comparative analysis of genetic characteristics was performed for seven Shandong indigenous pig breeds in the context of five Western commercial breeds. Results: The results showed that Shandong indigenous pig breeds varied greatly in genetic diversity, effective population size, inbreeding level, and genetic distance with the Western commercial breeds. Specifically, Laiwu and Dapulian displayed low genetic diversity, and had a genetically distant relationship with the Western commercial breeds (average F statistics [FST] value of 0.3226 and 0.2666, respectively). Contrastingly, the other five breeds (Yantai, Licha, Yimeng, Wulain, and Heigai) displayed high genetic diversity within breed and had some extent of mixture pattern with the Western commercial breeds, especially Duroc and Landrace (FST values from 0.1043 to 0.2536). Furthermore, intensive gene flow was discovered among the seven Shandong indigenous breeds, particularly Wulian, Licha, and Heigai, as indicated by the large cluster formed in the principal component analysis scatterplot and small population differentiation (average of 0.1253) among them. Conclusion: Our study advances the understanding of genetic characteristics of Shandong indigenous breeds and provides essential information for developing an appropriate conservation and utilization scheme for these breeds. [ABSTRACT FROM AUTHOR]

A low cost, rapid and sensitive preparation method of silica gel supported ionic liquid (SGSIL) combined with matrix solid phase dispersion (MSPD) followed by high performance liquid chromatography (HPLC) with ultraviolet detection (UV) is proposed, and it was applied to determine the seven active compounds in Salvia Miltiorrhiza herb. SGSIL and ionic liquid [BMIM]BF4 were used as the adsorbent and the green elution reagent in the MSPD procedure. Several extraction conditions including type of filler and elution solvent, the volume of elution solvent, material liquid ratio were optimized. Under the optimum conditions, the SGSIL-MSPD-HPLC method showed a low limit of detection (LOD, S/N = 3) of 0.0122-0.8788 µg/mL for standard solution, limit of quantification (LOQ, S/N = 10) of 0.0406-2.9292 ag/mL for standard solution, wide linear range from 1.56 to 2000 ag/mL for all compounds for standard solution, correlation coefficients (r) of more than 0.9990, acceptable reproducibility (relative standard deviations, RSDs < 3.54%), and precision of RSDs < 3.36% for intra-day, RSDs < 3.50% for inter-day. The satisfactory recoveries ranged from 96.4 to 102.5, with RSDs less than 3.45%. The developed SGSIL-MSPD method is easier and more suitable for the determination of the seven active compounds in Salvia Miltiorrhiza herb than the traditional ultrasonic extraction. It was an effective and efficient method for the extraction and quantification of the seven active compounds in traditional Chinese herbal samples. [ABSTRACT FROM AUTHOR]

The electron transport properties of bis[2-(2-hydroxyphenyl)-pyridine] beryllium (Bepp2) are investigated by impedance spectroscopy over a frequency range of 10 Hz to 13MHz. The Cole-Cole plots demonstrate that the Bepp2-based device can be represented by a single parallel resistance Rp and capacitance Cp network with a series resistance Rs. The current-voltage characteristics and the variation of Rp with applied bias voltage indicate the electron conduction of space-charge-limited current with exponential trap distributions in Bepp2. It can be seen that the electron mobility exhibits strong field-dependence in low electric field region and almost saturate in high electric field region. It is experimentally found that Bepp2 shows dispersion transport and becomes weak as the electric field increases. The activation energy is determined to be 0.043 eV by temperature-dependent conductivity, which is consistent with the result obtained from the temperature-dependent current density characteristics. The electron mobility reaches the orders of 10-6-10-5 cm2 V-1 s-1, depending on the electric field. [ABSTRACT FROM AUTHOR]

Insulin resistance is a manifestation of both diabetes mellitus and obesity. Insulin signaling and its impairment in obesity and type 2 diabetes continue to excite researchers. Permanent increase in acute-phase serum amyloid A (A-SAA) level has been observed and correlated to both obesity and insulin resistance in humans. In this study, we explored the mechanism of recombinant serum amyloid A (Rh-SAA) mediating insulin resistance and JNK activation of 3T3-L1 adipocytes. We could observe the effect of Rh-SAA on insulin sensitivity of 3T3-LI adipocytes under the intervention of JNK inhibitors. We selected three experimental groups viz. (i) NC Group: Adipocytes without Rh-SAA intervention,;(ii) Rh-SAA Group: A dipocytes with 20µg/mL Rh- SAA intervention; and (iii) JNK Inhibitor Group: Adipocytes pretreated with 50 μmol/L JNK inhibitor SP600125 12 h before 20 µg/mL Rh-SAA intervention. All the three groups were incubated for 48 h, the glucose transport rate of the adipocytes was measured by³H-2-DG, and the level of JNK activation was examined using Western blotting. Compared with the NC group, glucose uptake in the adipocytes treated with 20µg/mL Rh-SAA for 48 h decreased by 26% (P <0.01). The glucose uptake increased by 15% (P <0.05) in the JNK Inhibitor group. Western blotting showed that the expression levels of p-JNK in the NC group and Rh-SAA group and JNK inhibitor group were 100, 166 and 107%, respectively. Compared with NC group, the phosphorylation of JNK increased by 66% (P <0.01), but JNK inhibitor group showed no significant difference between Rh- SAA group (P <0.01) and NC group (P <0.05). Results suggested that intervening activity of JNK is expected to be an effective treatment for insulin resistance related diseases. [ABSTRACT FROM AUTHOR]

Objective: Intramuscular fat (IMF) content plays an important role in meat quality. Identification of single nucleotide polymorphisms (SNPs) and genes related to pig IMF, especially using pig populations with high IMF content variation, can help to establish novel molecular breeding tools for optimizing IMF in pork and unveil the mechanisms that underlie fat metabolism. Methods: We collected muscle samples of 453 Chinese Lulai black pigs, measured IMF content by Soxhlet petroleum-ether extraction method, and genotyped genome-wide SNPs using GeneSeek Genomic Profiler Porcine HD BeadChip. Then a genome-wide association study was performed using a linear mixed model implemented in the GEMMA software. Results: A total of 43 SNPs were identified to be significantly associated with IMF content by the cutoff p<0.001. Among these significant SNPs, the greatest number of SNPs (n = 19) were detected on Chr.9, and two linkage disequilibrium blocks were formed among them. Additionally, 17 significant SNPs are mapped to previously reported quantitative trait loci (QTLs) of IMF and confirmed previous QTLs studies. Forty-two annotated genes centering these significant SNPs were obtained from Ensembl database. Overrepresentation test of pathways and gene ontology (GO) terms revealed some enriched reactome pathways and GO terms, which mainly involved regulation of basic material transport, energy metabolic process and signaling pathway. Conclusion: These findings improve our understanding of the genetic architecture of IMF content in pork and facilitate the follow-up study of fine-mapping genes that influence fat deposition in muscle. [ABSTRACT FROM AUTHOR]

Habitat loss and fragmentation are considered to be the leading drivers of biodiversity loss. The small-island effect (SIE) can be used to predict species extinctions resulting from habitat loss and has important implications for species conservation. However, to date, no study has explicitly evaluated the prevalence of SIEs in habitat islands. Here, we compiled 90 global datasets to systematically investigate the prevalence and underlying factors determining the ubiquity of SIEs in habitat island systems. Among the 90 datasets, SIEs were unambiguously detected in 36 cases.We found significant effects of habitat island types and taxon groups on the threshold area of SIEs. The number of islands, area range, species range, island type and taxon group were key variables that determined the prevalence of SIEs. Our study demonstrates that SIEs occur in 40% of cases and thus are common in habitat islands.We conclude that conservation biologists and applied ecologists should consider the prevalence of SIEs when making management strategies in fragmented landscapes. [ABSTRACT FROM AUTHOR]

Permutation polynomials over finite fields constitute an active research area. Permutation trinomials attract researchers' interest due to their simple algebraic form and some additional extraordinary properties. In this paper, we present six new classes of permutation trinomials over F2n which have explicit forms by determining the solutions of some equations. [ABSTRACT FROM AUTHOR]

Objective: Cluster of differentiation 4 protein (CD4) gene is an important immune related gene which plays a significant role in T cell development and host resistance during viral infection. Methods: In order to unravel the relationship of CpG island methylation level of CD4 gene with its gene expression and T lymphocyte subpopulation traits, we used one typical Chinese indigenous breed (Dapulian, DP) and one commercial breed (Landrace), then predicted the CpG island of CD4 gene, determined the methylation status of CpG sites by bisulfite sequencing polymerase chain reaction (BSP), and carried out the correlation analyses of methylation frequencies of CpG sites with mRNA expression and T lymphocyte subpopulation traits. Results: There was one CpG island predicted in the upstream -2 kb region and exon one of porcine CD4 gene, which located 333 bp upstream from the start site of gene and contained nine CpG sites. The correlation analysis results indicated that the methylation frequency of CpG_2 significantly correlated with CD4 mRNA expression in the DP and Landrace combined population, though it did not reach significance level in DP and Landrace separately. Additionally, 15 potential binding transcription factors (TFs) were predicted within the CpG island, and one of them (Jumonji) contained CpG_2 site, suggesting that it may influence the CD4 gene expression through the potential binding TFs. We also found methylation frequency of CpG_2 negatively correlated with T lymphocyte subpopulation traits CD4+CD8-CD3-, CD4-CD8+CD3- and CD4+/CD8+, and positively correlated with CD4-CD8+CD3+ and CD4+CD8+CD3+ (for all correlation, p<0.01) in DP and Landrace combined population. Thus, the CpG_2 was a critical methylation site for porcine CD4 gene expression and T lymphocyte subpopulation traits. Conclusion: We speculated that increased methylation frequency of CpG_2 may lead to the decreased expression of CD4, which may have some kind of influence on T lymphocyte subpopulation traits and the immunity of DP population. [ABSTRACT FROM AUTHOR]

The small-island effect (SIE) has become more and more part of the theoretical framework of island biogeography and biodiversity research. However, previous methods for the detection of SIEs are often flawed in one way or another, including not accounting for model complexity, not comparing all relevant models, and not including islands with no species. Therefore, the existence and the prevalence of the SIE may be dubious. In this study, after controlling for all these methodological shortcomings, we tested for the existence of the SIE in amphibian assemblages on subtropical landbridge islands created by the inundation of the Thousand Island Lake, China. We used the line transect method to determine the distribution of amphibian assemblages on 23 study islands during 3 breeding seasons from 2009 to 2011. To evaluate whether an SIE exists in amphibian assemblages, we compared the fit of a simple linearized power model with two most widely used breakpoint regression models. The information-theoretic multimodel inference approach based on Akaike's information criterion identified the left-horizontal SIE model as the best single model. Thus, we found strong evidence for the existence of an SIE in our system. The upper limit of the SIE for amphibian assemblages was 39.95ha. Below this threshold area, amphibian richness varied independently of island size. The SIE in amphibian assemblages may be due to episodic disturbances, stochastic events, and nutrient subsidies from the lake. Our results indicate that all the islands >39.95 ha should be protected for the effective conservation of amphibian assemblages in our system. [ABSTRACT FROM AUTHOR]

Melatonin, a derivative of tryptophan, was first detected in plant species in 1995 and it has been shown to be a diverse regulator during plant growth and development, and in stress responses. Recently, great progress has been made towards determining the detailed functions of melatonin in plant responses to abiotic stress. Melatonin priming improves plant tolerance to cold, heat, salt, and drought stresses through regulation of genes involved in the DREB/ CBF, HSF, SOS, and ABA pathways, respectively. As a scavenger of free radicals, melatonin also directly detoxifies reactive oxygen species, thus alleviating membrane oxidation. Abiotic stress-inhibited photosynthesis is partially recovered and metabolites accumulate in the presence of melatonin, leading to improved plant growth, delayed leaf senescence, and increased stress tolerance. In this review, we summarize the interactions of melatonin with phytohormones to regulate downstream gene expression, protein stabilization, and epigenetic modification in plants. Finally, we consider the need for, and approaches to, the identification of melatonin receptors and components during signaling transduction pathways. [ABSTRACT FROM AUTHOR]

UV light suppresses experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS, in mice and may be responsible for the decreased incidence of MS in equatorial regions. To test this concept further, we applied commercially available sunblock preparations to mice before exposing them to UV radiation. Surprisingly, some of the sunblock preparations blocked EAE without UV radiation. Furthermore, various sunblock preparations had variable ability to suppress EAE. By examining the components of the most effective agents, we identified homosalate and octisalate as the components responsible for suppressing EAE. Thus, salates may be useful in stopping the progression of MS, and may provide new insight into mechanisms of controlling autoimmune disease. [ABSTRACT FROM AUTHOR]

Environmental stress poses a global threat to plant growth and reproduction, especially drought stress. Zinc finger proteins comprise a family of transcription factors that play essential roles in response to various abiotic stresses. Here, we found that ZAT18 (At3g53600), a nuclear C2H2 zinc finger protein, was transcriptionally induced by dehydration stress. Overexpression (OE) of ZAT18 in Arabidopsis improved drought tolerance while mutation of ZAT18 resulted in decreased plant tolerance to drought stress. ZAT18 was preferentially expressed in stems, siliques, and vegetative rosette leaves. Subcellular location results revealed that ZAT18 protein was predominantly localized in the nucleus. ZAT18 OE plants exhibited less leaf water loss, lower content of reactive oxygen species (ROS), higher leaf water content, and higher antioxidant enzyme activities after drought treatment when compared with the wild type (WT). RNA sequencing analysis showed that 423 and 561 genes were transcriptionally modulated by the ZAT18 transgene before and after drought treatment, respectively. Pathway enrichment analysis indicated that hormone metabolism, stress, and signaling were over-represented in ZAT18 OE lines. Several stress-responsive genes including COR47, ERD7, LEA6, and RAS1, and hormone signaling transduction-related genes including JAZ7 and PYL5 were identified as putative target genes of ZAT18. Taken together, ZAT18 functions as a positive regulator and plays a crucial role in the plant response to drought stress. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the microorganism profile, fermentation quality and rumen digestibility in vitro of maize-stalk silage at different maturity stages. Maize-stalk samples were harvested at the stages milk-ripe, dough, fully ripe, and fully ripe exposed to air for 3 or 10 days. Silage pH, ammonia-N and chemical composition were measured. Thirteen representative lactic acid bacteria (LAB) strains isolated from the raw materials were categorised into five profile clusters: Leuconostoc citreum (23.1%), Weissella paramesenteroides (15.4%), Lactococcus garvieae (23.1%), Enterococcus faecalis (7.7%), and Lactobacillus paraplantarum (30.8%). The total LABnumbers in silages with raw materials reaped at the stages milk-ripe, dough, fully ripe, and fully ripe exposed to air for 3 or 10 days, respectively, were approximately 8, 6, 10, 3.5 and 10 log CFU g-1. The dominant LAB types of maize-stalk silage at different stages were all different. The epiphytic pathogens Escherichia coli, aerobic bacteria, filamentous fungi and Saccharomycetes were found in silages of all stages. There were significant differences (P < 0.001) in crude protein, ether extract, dry matter, acid detergent fibre and organic matter of silage at different stages; however, no significant difference (P > 0.05) was observed in dry matter digestibility after 24 h of fermentation in vitro, with NH3-N varying from 0.7±0.1 to 1.7±0.3 mg L-1. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are one family of small noncoding RNAs that function to modulate the activity of specific mRNA targets in animals. To understand the role of miRNAs in regulating genes involved in the host immune response to RNA viruses, we profiled and characterized the miRNAs of swine peripheral blood mononuclear cells (PBMC) stimulated with poly I:C, a synthetic dsRNA analog, by miRNA-sequencing (miRNA-seq). We identified a total of 905 miRNAs, of which 503 miRNAs were firstly exploited herein with no annotation in the latest miRBase 21.0. Expression analysis demonstrated that poly I:C stimulation can elicit significantly differentially expressed (DE) miRNAs in Dapulian (n = 20), one Chinese indigenous breed, as well as Landrace (n = 23). By integrating the mRNA expression profiles of the same sample with miRNA profiles, we carried out function analyses of the target genes of these DE miRNAs, with the results indicating that target genes were most enriched in some immune-related pathways and gene ontology (GO) terms, suggesting that DE miRNAs play an important role in the regulation of host to poly I:C stimulation. Furthermore, we also detected 43 and 61 significantly DE miRNAs between the two breeds in the control sample groups and poly I:C stimulation groups, respectively, which may be involved in regulation of the different characteristics of the two breeds. This study describes for the first time the PBMC miRNA transcriptomic response to poly I:C stimulation in pigs, which not only contributes to a broad view of the pig miRNAome but improves our understanding of miRNA function in regulating host immune response to RNA viruses. [ABSTRACT FROM AUTHOR]

In this study, 69 lactobacilli isolated from Tibetan Qula, a raw yak milk cheese, were screened for their potential use as probiotics. The isolates were tested in terms of: Their ability to survive at pH 2.0, pH 3.0, and in the presence of 0.3% bile salts; tolerance of simulated gastric and intestinal juices; antimicrobial activity; sensitivity against 11 specific antibiotics; and their cell surface hydrophobicity. The results show that out of the 69 strains, 29 strains (42%) had survival rates above 90% after 2 h of incubation at pH values of 2.0 or 3.0. Of these 29 strains, 21 strains showed a tolerance for 0.3% bile salt. Incubation of these 21 isolates in simulated gastrointestinal fluid for 3 h revealed survival rates above 90%; the survival rate for 20 of these isolates remained above 90% after 4 h of incubation in simulated intestinal fluid. The viable counts of bacteria after incubation in simulated gastric fluid for 3 h and simulated intestinal fluid for 4 h were both significantly different compared with the counts at 0 h (p<0.001). Further screening performed on the above 20 isolates indicated that all 20 lactobacilli strains exhibited inhibitory activity against Micrococcus luteus ATCC 4698, Bacillus subtilis ATCC 6633, Listeria monocytogenes ATCC 19115, and Salmonella enterica ATCC 43971. Moreover, all of the strains were resistant to vancomycin and streptomycin. Of the 20 strains, three were resistant to all 11 elected antibiotics (ciprofloxacin, erythromycin, tetracycline, penicillin G, ampicillin, streptomycin, polymyxin B, vancomycin, chloramphenicol, rifampicin, and gentamicin) in this study, and five were sensitive to more than half of the antibiotics. Additionally, the cell surface hydrophobicity of seven of the 20 lactobacilli strains was above 70%, including strains Lactobacillus casei 1,133 (92%), Lactobacillus plantarum 1086-1 (82%), Lactobacillus casei 1089 (81%), Lactobacillus casei 1138 (79%), Lactobacillus buchneri 1059 (78%), Lactobacillus plantarum 1141 (75%), and Lactobacillus plantarum 1197 (71%). Together, these results suggest that these seven strains are good probiotic candidates, and that tolerance against bile acid, simulated gastric and intestinal juices, antimicrobial activity, antibiotic resistance, and cell surface hydrophobicity could be adopted for preliminary screening of potentially probiotic lactobacilli. [ABSTRACT FROM AUTHOR]

From the enediyne class of antitumor antibiotics, uncialamycin is among the rarest and most potent, yet one of the structurally simpler, making it attractive for chemical synthesis and potential applications in biology and medicine. In this article we describe a streamlined and practical enantioselective total synthesis of uncialamycin that is amenable to the synthesis of novel analogues and renders the natural product readily available for biological and drug development studies. Starting from hydroxy- or methoxyisatin, the synthesis features a Noyori enantioselective reduction, a Yamaguchi acetylide-pyridinium coupling, a stereoselective acetylide-aldehyde cyclization, and a newly developed annulation reaction that allows efficient coupling of a cyanophthalide and a p-methoxy semiquinone aminal to forge the anthraquinone moiety of the molecule. Overall, the developed streamlined synthesis proceeds in 22 linear steps (14 chromatographic separations) and 11% overall yield. The developed synthetic strategies and technologies were applied to the synthesis of a series of designed uncialamycin analogues equipped with suitable functional groups for conjugation to antibodies and other delivery systems. Biological evaluation of a select number of these analogues led to the identification of compounds with low picomolar potencies against certain cancer cell lines. These compounds and others like them may serve as powerful payloads for the development of antibody drug conjugates (ADCs) intended for personalized targeted cancer therapy. [ABSTRACT FROM AUTHOR]

The development of two iterative asymmetric hydration approaches to the synthesis of all syn- and syn/anti/syn-1,3,5,7-tetraol motifs is described. These pseudo-symmetric products are synthetic precursors for 1,3-hexol products. The utility of the route to the all syn1,3,5,7-tetraol diastereoisomer was demonstrated with its use in the synthesis of cryptocaryols A and B, as well as, stereoisomers. [ABSTRACT FROM AUTHOR]

Polyinosinic-polycytidylic acid (poly I:C), a synthetic dsRNA analog, has been demonstrated to have stimulatory effects similar to viral dsRNA. To gain deep knowledge of the host transcriptional response of pigs to poly I:C stimulation, in the present study, we cultured and stimulated peripheral blood mononuclear cells (PBMC) of piglets of one Chinese indigenous breed (Dapulian) and one modern commercial breed (Landrace) with poly I:C, and compared their transcriptional profiling using RNA-sequencing (RNA-seq). Our results indicated that poly I:C stimulation can elicit significantly differentially expressed (DE) genes in Dapulian (g = 290) as well as Landrace (g = 85). We also performed gene set analysis using the Gene Set Enrichment Analysis (GSEA) package, and identified some significantly enriched gene sets in Dapulian (g = 18) and Landrace (g = 21). Most of the shared DE genes and gene sets were immune-related, and may play crucial rules in the immune response of poly I:C stimulation. In addition, we detected large sets of significantly DE genes and enriched gene sets when comparing the gene expression profile between the two breeds, including control and poly I:C stimulation groups. Besides immune-related functions, some of the DE genes and gene sets between the two breeds were involved in development and growth of various tissues, which may be correlated with the different characteristics of the two breeds. The DE genes and gene sets detected herein provide crucial information towards understanding the immune regulation of antiviral responses, and the molecular mechanisms of different genetic resistance to viral infection, in modern and indigenous pigs. [ABSTRACT FROM AUTHOR]

Aberrant glycosylation is highly associated with cancer progression. The aim of this study was to compare bifucosylated N-glycans in sera obtained from healthy controls and breast cancer patients, with the goal of identifying a potential indicator for monitoring the recurrence and metastasis of breast cancer. A unique structural pattern of bifucosylated N-glycan, with both core and antennary fucosylation, was identified in breast cancer patients. The spectrum of antennary fucosylation was a composite of the standard spectra of Lewis X and H2, indicating a mixture of the two epitopes. Permethylated N-glycans of the glycoproteins extracted from 91 breast cancer patients and 43 healthy controls were detected using linear ion-trap quadrupole-electrospray ionization mass spectrometry, which appeared to be a highly sensitive and useful approach in the detection and identification of N-glycans. To evaluate MS profile data, several statistical tools were applied, including Student's t-test, partial least squares discriminant analysis and receiver-operating characteristic curve. The results showed that the measurement of bifucosylation degree and CEA levels had an improved diagnostic performance compared with that of CEA alone. We compared the potential of bifucosylated N-glycan as an indicator of breast cancer recurrence with the current clinical biomarkers, i.e., CEA, CA 15-3 and CA125. The result revealed that, compared with CEA, CA 15-3 and CA125, the bifucosylation degree of N-glycans could be a more reliable indicator of breast cancer recurrence. [ABSTRACT FROM AUTHOR]

Background: In the past two decades, the under-5 mortality rate in China has fallen substantially, but progress with regards to the Millennium Development Goal (MDG) 4 at the subnational level has not been quantified. We aimed to estimate under-5 mortality rates in mainland China for the years 1970 to 2012.Methods: We estimated the under-5 mortality rate for 31 provinces in mainland China between 1970 and 2013 with data from censuses, surveys, surveillance sites, and disease surveillance points. We estimated under-5 mortality rates for 2851 counties in China from 1996 to 2012 with the reported child mortality numbers from the Annual Report System on Maternal and Child Health. We used a small area mortality estimation model, spatiotemporal smoothing, and Gaussian process regression to synthesise data and generate consistent provincial and county-level estimates. We compared progress at the county level with what was expected on the basis of income and educational attainment using an econometric model. We computed Gini coefficients to study the inequality of under-5 mortality rates across counties.Findings: In 2012, the lowest provincial level under-5 mortality rate in China was about five per 1000 livebirths, lower than in Canada, New Zealand, and the USA. The highest provincial level under-5 mortality rate in China was higher than that of Bangladesh. 29 provinces achieved a decrease in under-5 mortality rates twice as fast as the MDG 4 target rate; only two provinces will not achieve MDG 4 by 2015. Although some counties in China have under-5 mortality rates similar to those in the most developed nations in 2012, some have similar rates to those recorded in Burkina Faso and Cameroon. Despite wide differences, the inter-county Gini coefficient has been decreasing. Improvement in maternal education and the economic boom have contributed to the fall in child mortality; more than 60% of the counties in China had rates of decline in under-5 mortality rates significantly faster than expected. Fast reduction in under-5 mortality rates have been recorded not only in the Han population, the dominant ethnic majority in China, but also in the minority populations. All top ten minority groups in terms of population sizes have experienced annual reductions in under-5 mortality rates faster than the MDG 4 target at 4.4%.Interpretation: The reduction of under-5 mortality rates in China at the country, provincial, and county level is an extraordinary success story. Reductions of under-5 mortality rates faster than 8.8% (twice MDG 4 pace) are possible. Extremely rapid declines seem to be related to public policy in addition to socioeconomic progress. Lessons from successful counties should prove valuable for China to intensify efforts for those with unacceptably high under-5 mortality rates.Funding: National "Twelfth Five-Year" Plan for Science and Technology Support, National Health and Family Planning Commission of The People's Republic of China, Program for Changjiang Scholars and Innovative Research Team in University, the National Institute on Aging, and the Bill & Melinda Gates Foundation. [ABSTRACT FROM AUTHOR]

Drought stress is one of the disadvantageous environmental conditions for plant growth and reproduction. Given the importance of abscisic acid (ABA) to plant growth and abiotic stress responses, identification of novel components involved in ABA signalling transduction is critical. In this study, we screened numerous Arabidopsis thaliana mutants by seed germination assay and identified a mutant mlp43 (major latex protein-like 43) with decreased ABA sensitivity in seed germination. The mlp43 mutant was sensitive to drought stress while the MLP43-overexpressed transgenic plants were drought tolerant. The tissue-specific expression pattern analysis showed that MLP43 was predominantly expressed in cotyledons, primary roots and apical meristems, and a subcellular localization study indicated that MLP43 was localized in the nucleus and cytoplasm. Physiological and biochemical analyses indicated that MLP43 functioned as a positive regulator in ABA- and drought-stress responses in Arabidopsis through regulating water loss efficiency, electrolyte leakage, ROS levels, and as well as ABA-responsive gene expression. Moreover, metabolite profiling analysis indicated that MLP43 could modulate the production of primary metabolites under drought stress conditions. Reconstitution of ABA signalling components in Arabidopsis protoplasts indicated that MLP43 was involved in ABA signalling transduction and acted upstream of SnRK2s by directly interacting with SnRK2.6 and ABF1 in a yeast two-hybrid assay. Moreover, ABA and drought stress down-regulated MLP43 expression as a negative feedback loop regulation to the performance of MLP43 in ABA and drought stress responses. Therefore, this study provided new insights for interpretation of physiological and molecular mechanisms of Arabidopsis MLP43 mediating ABA signalling transduction and drought stress responses. [ABSTRACT FROM AUTHOR]

A prevalent cerebrovascular disease like the acute cerebral infarction is caused by cerebral thrombosis or arteriosclerosis that can result in ischemic necrosis of brain tissues. Treatment drugs of higher efficiency are required to be developed for acute cerebral infarction. Physalin A (PA) is a major compound from Physalis alkekengi L. and has pharmacological properties. However, the neuroprotective effects of PA are less reported and the mechanism remains unclear. The acute cerebral infarction cell model was constructed by treating PC12 cells with oxygenglucose deprivation/reoxygenation (OGD/R). The impacts of PA on cell viability were determined by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) releasing assays. Immunoblot and Enzyme-linked Immunosorbent assay (ELISA) were conducted to examine PA effects on inflammation. PA effects on pyroptosis were detected by performing immunoblot and immunostaining. Moreover, immunoblot was further conducted to confirm the mechanism. In this study, the survival and inhibition of the pyroptosis of OGD/Rinduced PC12 cells were regulated by PA. Furthermore, PA suppressed the inflammation. PA inhibited mitogen-activated protein kinase (MAPK) pathway activation, and the activation of MAPK pathway reversed the neuroprotective effect of PA. Therefore, PA exerts neuroprotective effects by suppressing OGD/R-induced cellular pyroptosis and inflammatory responses in nerve cells. [ABSTRACT FROM AUTHOR]

The pathophysiology of idiopathic trigeminal neuralgia (ITN) has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo) analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected). Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002). Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN. [ABSTRACT FROM AUTHOR]

Study Question: What are the genetic loci that increase susceptibility to nonsyndromic cryptorchidism, or undescended testis?Summary Answer: A genome-wide association study (GWAS) suggests that susceptibility to cryptorchidism is heterogeneous, with a subset of suggestive signals linked to cytoskeleton-dependent functions and syndromic forms of the disease.What Is Known Already: Population studies suggest moderate genetic risk of cryptorchidism and possible maternal and environmental contributions to risk. Previous candidate gene analyses have failed to identify a major associated locus, although variants in insulin-like 3 (INSL3), relaxin/insulin-like family peptide receptor 2 (RXFP2) and other hormonal pathway genes may increase risk in a small percentage of patients.Study Design, Size, Duration: This is a case-control GWAS of 844 boys with nonsyndromic cryptorchidism and 2718 control subjects without syndromes or genital anomalies, all of European ancestry.Participants/materials, Setting, Methods: All boys with cryptorchidism were diagnosed and treated by a pediatric specialist. In the discovery phase, DNA was extracted from tissue or blood samples and genotyping performed using the Illumina HumanHap550 and Human610-Quad (Group 1) or OmniExpress (Group 2) platform. We imputed genotypes genome-wide, and combined single marker association results in meta-analyses for all cases and for secondary subphenotype analyses based on testis position, laterality and age, and defined genome-wide significance as P = 7 × 10(-9) to correct for multiple testing. Selected markers were genotyped in an independent replication group of European cases (n = 298) and controls (n = 324). We used several bioinformatics tools to analyze top (P < 10(-5)) and suggestive (P < 10(-3)) signals for significant enrichment of signaling pathways, cellular functions and custom gene lists after multiple testing correction.Main Results and the Role Of Chance: In the full analysis, we identified 20 top loci, none reaching genome-wide significance, but one passing this threshold in a subphenotype analysis of proximal testis position (rs55867206, near SH3PXD2B, odds ratio = 2.2 (95% confidence interval 1.7, 2.9), P = 2 × 10(-9)). An additional 127 top loci emerged in at least one secondary analysis, particularly of more severe phenotypes. Cytoskeleton-dependent molecular and cellular functions were prevalent in pathway analysis of suggestive signals, and may implicate loci encoding cytoskeletal proteins that participate in androgen receptor signaling. Genes linked to human syndromic cryptorchidism, including hypogonadotropic hypogonadism, and to hormone-responsive and/or differentially expressed genes in normal and cryptorchid rat gubernaculum, were also significantly overrepresented. No tested marker showed significant replication in an independent population. The results suggest heterogeneous, multilocus and potentially multifactorial susceptibility to nonsyndromic cryptorchidism.Limitations, Reasons For Caution: The present study failed to identify genome-wide significant markers associated with cryptorchidism that could be replicated in an independent population, so further studies are required to define true positive signals among suggestive loci.Wider Implications Of the Findings: As the only GWAS to date of nonsyndromic cryptorchidism, these data will provide a basis for future efforts to understand genetic susceptibility to this common reproductive anomaly and the potential for additive risk from environmental exposures.Study Funding/competing Interests: This work was supported by R01HD060769 (the Eunice Kennedy Shriver National Institute for Child Health and Human Development (NICHD)), P20RR20173 (the National Center for Research Resources (NCRR), currently P20GM103464 from the National Institute of General Medical Sciences (NIGMS)), an Institute Development Fund to the Center for Applied Genomics at The Children's Hospital of Philadelphia, and Nemours Biomedical Research. The authors have no competing interests to declare. [ABSTRACT FROM AUTHOR]

Winter wheat is a suitable crop to be ensiled for animal feed and China has the largest planting area of this crop in the world. During the ensiling process, lactic acid bacteria (LAB) play the most important role in the fermentation. We investigated the natural population of LAB in whole-crop wheat (WCW) and examined the quality of whole-crop wheat silage (WCWS) with and without LAB inoculants. Two Lactobacillus plantarum subsp. plantarum strains, Zhengzhou University 1 (ZZU 1) selected from corn and forage and grass 1 (FG 1) from a commercial inoculant, were used as additives. The silages inoculated with LAB strains (ZZU 1 and FG 1) were better preserved than the control, with lower pH values (3.5 and 3.6, respectively) (p<0.05) and higher contents of lactic acid (37.5 and 34.0 g/kg of fresh matter (FM), respectively) (p<0.05) than the control. Sixty LAB strains were isolated from fresh material and WCWS without any LAB inoculation. These LAB strains were divided into the following four genera and six species based on their phenotypic, biochemical and phylogenetic characteristics: Leuconostoc pseudomesenteroides, Leuconostoc citreum, Weissella cibaria, Lactococcus lactis subsp. lactis, Lactobacillus buchneri, and Lactobacillus plantarum subsp. plantarum. However, the prevalent LAB, which was predominantly heterofermentative (66.7%), consisted of Leuconostoc pseudomesenteroides, Leuconostoc citreum, Weissella cibaria, and Lactobacillus buchneri. This study revealed that most of isolated LAB strains from control WCWS were heterofermentative and could not grow well at low pH condition; the selective inoculants of Lactobacillus strains, especially ZZU 1, could improve WCWS quality significantly. [ABSTRACT FROM AUTHOR]

Despite the application of antibiotics, Streptococcus pneumoniae (SP)-induced meningitis continues to be a life-threatening disease with a high fatality rate and an elevated risk of serious neurological sequelae, particularly in developing countries. In this study, the contribution of the co-stimulatory molecule B7 homolog 3 (B7-H3) to the pathogenesis of experimental SP-induced meningitis was investigated. Mice were challenged with the intracerebroventricular injection of serotype 3 SP with or without B7-H3. The clinical status of mice with SP-induced meningitis was examined by body weight loss and spontaneous motor activity with neurological scoring. Coronal brain sections were analyzed by counting Nissl-positive neurons and terminal deoxynucleotidyl transferase- mediated dUTP nick end-labeling (TUNEL)-positive cells. Protein expression of neuron-specific enolase (NSE) and S100B in brain tissues was examined with immunohistochemical staining. All experiments were performed in a randomized and blinded setting. By the intracerebroventricular injection of SP suspension, a murine model of pneumococcal meningitis was successfully established. In this SP-induced meningitis model, B7-H3 deteriorated the clinical status, as manifested by a decreased neurological score and increased body weight loss. Following the B7-H3 challenge, the number of Nissl-positive cells decreased and TUNEL-stained positive cells increased in the brain tissues of mice with SP meningitis, which demonstrates the enhancement of neuronal necrosis and apoptosis, respectively. Protein expression of NSE was decreased, while that of S100B was increased. These in vivo findings indicate that B7-H3 aggravates brain injury during the pathological process of experimental SP-induced meningitis. [ABSTRACT FROM AUTHOR]

Based on a single-factor experiment, Box-Behnken design was used to optimize the ultrasound-assisted extraction process of Trametes robiniophila (Huaier) polysaccharides (HPs). The optimum conditions were predicted as follows: ratio of water to raw material, 46.0 mL/g; extraction temperature, 68.9 °C; ultrasonic power, 51.3 W; and extraction time, 36.8 min. Under these conditions, the highest yield of HPs obtained was 36.8 ± 0.12%, which was in good agreement with the predicted value 36.6%. Additionally, chemical analysis of HPs showed a high content (85.3 ± 1.3%) of carbohydrates containing fucose, arabinose, xylose, mannose, galactose and glucose, with molar percentages 5.82%, 13.11%, 16.88%, 15.85%, 11.40% and 36.94%, respectively. Besides, HPs demonstrated appreciable antioxidant potential on ABTS, superoxide anion and hydroxyl radicals in vitro. These may further provide theoretical basis for the widely application of HPs in medicine and health care products. [ABSTRACT FROM AUTHOR]

In terrestrial ecosystems, deep soils are a major reservoir of organic carbon (C). Improving knowledge of how deep soil organic carbon (SOC) mineralization responds to fresh C supply and nitrogen (N) availability is essential to better understand whether this C pool will react to climate change. However, little is known about the effects of C and N inputs on SOC mineralization and microbial communities in forest deep soils. To quantify the effects of C and N inputs on SOC mineralization, we apply two species of 13C-labeled leaf litters and ammonium chloride solution while incubating soils collected from 60 cm to 70 cm depth in a coniferous forest in subtropical China. The soil phospholipid fatty acid (PLFA) profiles are also determined to establish the effects of C and N supply on microbial community structure, and the δ13C in PLFAs is used to establish pathways of leaf litter-derived C flux among microbial communities. The addition of leaf litters stimulates deep SOC mineralization, indicating that the stability of deep SOC is attributed to a lack of fresh C input, but the addition of Michelia macclurei litter with higher C:P ratio has a greater positive priming effect than adding Pinus massoniana litter. N addition reduces the magnitude of positive priming and alters the direction of priming in soils with P. massoniana litter addition, suggesting that N deposition may suppress deep SOC mineralization and favor the maintenance of SOC storage. Leaf litter addition enhances the biomass of individual PLFA and increases the fungi:bacteria ratio, suggesting that microbes are limited by energy and that soil microbial community composition is modified by C inputs. N addition decreases the fungi:bacteria ratio, but increases the Gram-positive:Gram-negative bacteria ratio. The highest 13C-enrichment and distribution of litter-derived C are found in 16:0 and 18:1ω9c PLFAs, but litter species and N addition do not affect total PLFA-C and litter-derived PLFA-C. These results support the views that a lack of fresh C supply and N deposition may prevent the mineralization of SOC pool in deep layers and that the utilization of labile substrate by 16:0 and 18:1ω9c populations promotes positive SOC priming. [ABSTRACT FROM AUTHOR]

Inhibition of mTOR signaling enhances antitumor memory lymphocytes. However, pharmacologic mTOR inhibition also enhances regulatory T-cell (Treg) activity. To counter this effect, Treg control was added to mTOR inhibition in preclinical models. Tregs were controlled with CD4-depleting antibodies because CD4 depletion has high translational potential and already has a well-established safety profile in patients. The antitumor activity of the combination therapy was CD8 dependent and controlled growth of syngeneic tumors even when an adoptive immunotherapy was not used. Lymphocytes resulting from the combination therapy could be transferred into naive mice to inhibit aggressive growth of lung metastases. The combination therapy enhanced CD8 memory formation as determined by memory markers and functional studies of immune recall. Removal of FoxP3- expressing T lymphocytes was the mechanism underlying immunologic memory formation following CD4 depletion. This was confirmed using transgenic DEREG (depletion of regulatory T cells) mice to specifically remove Foxp3+ T cells. It was further confirmed with reciprocal studies where stimulation of immunologic memory because of CD4 depletion was completely neutralized by adoptively transferring tumor-specific Foxp3+ T cells. Also contributing to tumor control, Tregs that eventually recovered following CD4 depletion were less immunosuppressive. These results provide a rationale for further study of mTOR inhibition and CD4 depletion in patients. [ABSTRACT FROM AUTHOR]

Investigating gene expression of immune cells of whole blood or peripheral blood mononuclear cells (PBMC) under polyinosinic:polycytidylic acid (poly I:C) stimulation is valuable for understanding the immune response of organism to RNA viruses. Quantitative real-time PCR (qRT-PCR) is a standard method for quantification of gene expression studies. However, the reliability of qRT-PCR data critically depends on proper selection of reference genes. In the study, using two different analysis programs, geNorm and NormFinder, we systematically evaluated the gene expression stability of six candidate reference genes (GAPDH, ACTB, B2M, RPL4, TBP, and PPIA) in samples of whole blood and PBMC with or without poly I:C stimulation. Generally, the six candidate genes performed a similar trend of expression stability in the samples of whole blood and PBMC, but more stably expressed in whole blood than in PBMC. geNorm ranked B2M and PPIA as the best combination for gene expression normalization, while according to NormFinder, TBP was ranked as the most stable reference gene, followed by B2M and PPIA. Comprehensively considering the results from the two programs, we recommended using the geometric mean of the three genes, TBP, PPIA and B2M, to normalize the gene expression of whole blood and PBMC with poly I:C stimulation. Our study is the first detailed survey of the gene expression stability in whole blood and PBMC with or without poly I:C stimulation and should be helpful for investigating the molecular mechanism involved in porcine whole blood and PBMC in response to poly I:C stimulation. [ABSTRACT FROM AUTHOR]

We report quantifying the strengths of different types of hydrogen bonds in hydrogen-bond networks (HBNs) via measurement of the adiabatic electron detachment energy of the conjugate base of a small covalent polyol model compound (i.e., (HOCH2CH2CH(OH)CH2)2CHOH) in the gas phase and the pKa of the corresponding acid in DMSO. The latter result reveals that the hydrogen bonds to the charged center and those that are one solvation shell further away (i.e., primary and secondary) provide 5.3 and 2.5 pKa units of stabilization per hydrogen bond in DMSO. Computations indicate that these energies increase to 8.4 and 3.9 pKa units in benzene and that the total stabilizations are 16 (DMSO) and 25 (benzene) pKa units. Calculations on a larger linear heptaol (i.e., (HOCH2CH2CH(OH)CH2CH(OH)CH2)2CHOH) reveal that the terminal hydroxyl groups each contribute 0.6 pKa units of stabilization in DMSO and 1.1 pKa units in benzene. All of these results taken together indicate that the presence of a charged center can provide a powerful energetic driving force for enzyme catalysis and conformational changes such as in protein folding due to multiple hydrogen bonds in a HBN. [ABSTRACT FROM AUTHOR]

Autonomous navigation airborne forward-looking synthetic aperture radar (SAR) observes the anterior inferior wide area with a short cross-track dimensional linear array as azimuth aperture. This is an application scenario that is drastically different from that of side-looking space-borne or air-borne SAR systems, which acquires azimuth synthetic aperture with along-track dimension platform movement. High precision imaging with a combination of pseudo-polar formatting and overlapped sub-aperture algorithm for autonomous navigation airborne forward-looking SAR imaging is presented. With the suggested imaging method, range dimensional imaging is operated with wide band signal compression. Then, 2D pseudo-polar formatting is operated. In the following, azimuth synthetic aperture is divided into several overlapped sub-apertures. Intra sub-aperture IFFT (Inverse Fast Fourier Transform), wave front curvature phase error compensation, and inter sub-aperture IFFT are operated sequentially to finish azimuth high precision imaging. The main advantage of the proposed algorithm is its extremely high precision and low memory cost. The effectiveness and performance of the proposed algorithm are demonstrated with outdoor GBSAR (Ground Based Synthetic Aperture Radar) experiments, which possesses the same imaging geometry as the airborne forward-looking SAR (short azimuth aperture, wide azimuth swath). The profile response of the trihedral angle reflectors, placed in the imaging scene, reconstructed with the proposed imaging algorithm and back projection algorithm are compared and analyzed. [ABSTRACT FROM AUTHOR]

An increasing number of studies suggest that the activation of innate immunity with the development of a chronic low grade inflammatory response is a factor in the pathogenesis of diabetic nephropathy (DN). Advanced glycation end products (AGEs), chemokines and matrix metalloproteinases (MMPs) are known to be important in inflammatory reactions in DN. In the present study, the inter-regulation of MMP2 and fractalkine was observed between monocytes (U937) and human renal mesangial cells (HRMCs) and its potential pathophysiological role in DN. The expression of fractalkine and MMP2 was analyzed by RT-PCR, western blot analysis and enzyme linked immunosorbent assay. The chemotaxis and adhesiveness of HRMCs to U937 cells was detected with a transwell system, co culture and fluorescent staining, respectively. The results showed a decreased expression of MMP2 and an increased expression of fractalkine by AGEs in HRMCs. Fractalkine downregulated the mRNA expression and activity of MMP2, and the reduced MMP2 activity was reversed with an anti fractalkine antibody. Conversely, MMP2 upregulated fractalkine mRNA and protein expression in HRMCs, which led to an increase in chemotaxis and a decrease in monocytic adhesion to HRMCs. In conclusion, these observations suggest a crosstalk between monocytes and HRMCs via the interaction of MMP2 and fractalkine, which may represent a therapeutic target to impede the inflammatory process associated with DN. [ABSTRACT FROM AUTHOR]

The airborne downward looking sparse linear array three dimensional synthetic aperture radar (DLSLA 3-D SAR) operates nadir observation with the along-track synthetic aperture formulated by platform movement and the cross-track synthetic aperture formulated by physical sparse linear array. Considering the lack of DLSLA 3-D SAR data in the current preliminary study stage, it is very important and essential to develop DLSLA 3-D SAR simulation (echo generation simulation and image reconstruction simulation, including point targets simulation and 3-D distributed scene simulation). In this paper, DLSLA 3-D SAR imaging geometry, the echo signal model and the heterogeneous parallel technique are discussed first. Then, heterogeneous parallel echo generation simulation with time domain correlation and the frequency domain correlation method is described. In the following, heterogeneous parallel image reconstruction simulation with two imaging algorithms, e.g., 3-D polar format algorithm, polar formatting and L1 regularization algorithm is discussed. Finally, the point targets and the 3-D distributed scene simulation are demonstrated to validate the effectiveness and performance of our proposed heterogeneous parallel simulation technique. The 3-D distributed scene employs airborne X-band DEM and P-band Circular SAR image of the same area as simulation scene input. [ABSTRACT FROM AUTHOR]

The first total syntheses and structural elucidation of cryptocaryol A and cryptocaryol B were achieved in 23 and 25 linear steps, respectively. The synthesis relied on the use of a key pseudo-Cs symmetric pentaol intermediate, which in a stereochemically divergent manner was converted into either enantiomer as well as diastereomers. This synthetic effort enabled the first structure-activity relationships of this class of PDCD4 stabilizing natural products. [ABSTRACT FROM AUTHOR]

The enzymatic condition for producing the anti-obesity hydrolysates from fish water-soluble protein was optimized with the aid of response surface methodology, which also derived a statistical model for experimental validation. Compared with neutral protease, papain and protamex, the porcine pancreas lipase inhibitory rate of hydrolysates from fish water-soluble protein was higher with alkaline protease. Results showed that the model terms were significant, the terms of lack of fit were not significant, and the optimal conditions for the hydrolysis by alkaline protease were initial pH 11, temperature 39°C, enzyme dosage 122 U/mL and 10 h of hydrolysis time. Under these conditions, the porcine pancreas lipase and the a-amylase inhibitory rate could reach 53.04% ± 1.32% and 20.03 ± 0.89%, while predicted value were 54.63% ± 1.75%, 21.22% ± 0.70%, respectively. In addition, Lineweaver-Burk plots showed noncompetitive inhibition. The Ki value calculated was 84.13 mg/mL. These results demonstrated that fish water-soluble protein could be used for obtaining anti-obesity hydrolysates. [ABSTRACT FROM AUTHOR]

Nestedness is a pattern frequently reported for faunal assemblages in fragmented systems. Although nestedness has been documented for a wide range of taxa, it is rarely tested in snake assemblages. To arrive at robust generalizations about processes and mechanisms structuring island biotas, it is important to examine under-represented taxa such as snakes for the insights they may offer. We tested for the existence of nestedness and underlying causal mechanisms using snake data collected on islands in the Thousand Island Lake, China. We used the line-transect method to survey snake occupancy and abundance on 20 islands during two breeding seasons in 2009 and 2010. We used the recently developed metric WNODF to estimate nestedness. We used Spearman rank correlations to examine the associations of nestedness and habitat variables (area, isolation, and habitat diversity) as well as life-history traits (body size, clutch size, geographical range size and area requirement) related to species extinction and immigration tendencies. Snake assemblages were significantly nested and were shaped by extinction processes mediated through area effects and habitat nestedness. The nestedness of snake assemblages was not due to passive sampling or selective colonization. From a conservation viewpoint, our results indicate that we should protect both the largest island with the most species-rich community and habitat-rich islands to maximize the number of species preserved. [ABSTRACT FROM AUTHOR]

Bermudagrass (Cynodon dactylon) is a widely used warm-season turfgrass and one of the most drought tolerant species. Dissecting the natural variation in drought tolerance and physiological responses will bring us powerful basis and novel insight for plant breeding. In the present study, we evaluated the natural variation of drought tolerance among nine bermudagrass varieties by measuring physiological responses after drought stress treatment through withholding water. Three groups differing in drought tolerance were identified, including two tolerant, five moderately tolerant and two susceptible varieties. Under drought stress condition, drought sensitive variety (Yukon) showed relative higher water loss, more severe cell membrane damage (EL), and more accumulation of hydrogen peroxide (H2O2) and malondialdehyde (MDA), while drought tolerant variety (Tifgreen) exhibited significantly higher antioxidant enzymes activities. Further results indicated that drought induced cell injury in different varieties (Yukon, SR9554 and Tifgreen) exhibited liner correlation with leaf water content (LWC), H2O2 content, MDA content and antioxidant enzyme activities. Additionally, Tifgreen plants had significantly higher levels of osmolytes (proline level and soluble sugars) when compared with Yukon and SR9554 under drought stress condition. Taken together, our results indicated that natural variation of drought stress tolerance in bermudagrass varieties might be largely related to the induced changes of water status, osmolyte accumulation and antioxidant defense system. [ABSTRACT FROM AUTHOR]

Libraries based on an isolated human immunoglobulin G1 (IgG1) constant domain 2 (CH2) have been previously diversified by random mutagenesis. However, native isolated CH2 is not very stable and the generation of many mutations could lead to an increase in immunogenicity. Recently, we demonstrated that engineering an additional disulfide bond and removing seven N-terminal residues results in an engineered antibody domain (eAd) (m01s) with highly increased stability and enhanced binding to human neonatal Fc receptor (FcRn) (Gong et al, JBC, 2009 and 2011). We and others have also previously shown that grafting of the heavy chain complementarity region 3 (CDR-H3 (H3)) onto cognate positions of the variable domain leads to highly diversified libraries from which a number of binders to various antigens have been selected. However, grafting of H3s to non- cognate positions in constant domains results in additional residues at the junctions of H3s and the CH2 framework. Here we describe a new method based on multi-step PCR that allows the precise replacement of loop FG (no changes in its flanking sequences) by human H3s from another library. Using this method and limited mutagenesis of loops BC and DE we generated an eAd phage-displayed library. Panning of this library against an HIV-1 gp41 MPER peptide resulted in selection of a binder, m2a1, which neutralized HIV-1 isolates from different clades with modest activity and retained the m01s capability of binding to FcRn. This result provides a proof of concept that CH2-based antigen binders that also mimic to certain extent other functions of full-size antibodies (binding to FcRn) can be generated; we have previously hypothesized that such binders can be made and coined the term nanoantibodies (nAbs). Further studies in animal models and in humans will show how useful nAbs could be as therapeutics and diagnostics. [ABSTRACT FROM AUTHOR]

Objective The purpose of the study was to investigate the trends and causes of regional disparities of infant mortality rate (IMR) in rural China from 1996 to 2008. Design A population-based, longitudinal study. Setting The national child mortality surveillance network. Population Population of the 79 surveillance counties. Main outcome measure IMR, leading causes of infant death and the RR of IMR. Results The IMR in coastal, inland and remote regions declined by 72.4%, 62.9% and 58.2%, respectively, from 1996 to 2008. Compared with the coastal region, the RR of IMR were 1.7 (95% CI 1.6 to 1.9), 1.9 (95% CI 1.7 to 2.0) and 1.8 (95% CI 1.6 to 2.0) for inland region and 2.6 (95% CI 2.4 to 2.7), 3.2 (95% CI 3.0 to 3.5) and 3.1 (95% CI 2.7 to 3.4) for the remote region during 1996-2000, 2001-2005 and 2006-2008, respectively. The regional disparities existed for both male and female IMRs. The postneonatal mortality showed the highest regional disparities. Pneumonia, birth asphyxia, prematurity/ low birth weight, injuries and diarrhoea were the main contributors to the regional disparities. There were significantly more infants who did not seek healthcare services before death in the remote region relative to the inland and coastal regions. Conclusion The results indicated persistent existence of regional disparities in IMR in rural China. It is worth noting that regional disparities in IMR increased in the remote and coastal regions during 2001-2005 in rural China. These disparities remained unchanged during 2006-2008. The results indicate that strategies to reduce mortality caused by pneumonia, birth asphyxia and diarrhoea are keys to reducing IMR. INSETS: What is already known on this subject;What this papers adds. [ABSTRACT FROM AUTHOR]

The development of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, has been studied in mice that were (i) vitamin D-deficient, (ii) minus the vitamin D receptor, (iii) minus a vitamin D 25-hydroxylase, and (iv) minus the vitamin D 25-hydroxyvitamin D-1α-hydroxylase. EAE development was markedly suppressed in mice lacking the vitamin D receptor and partially suppressed in vitamin D-insufficient mice. However, the absence of either of the two key hydroxylases (i.e.. 25-hydroxylase and 1α-hydroxylase) neither inhibits nor enhances the development of EAE. These results indicate that vitamin D and the vitamin D receptor are required for the development of EAE. The results also suggest that 1,25-dihydroxyvitamin D3 may not play a role in this autoimmune response. [ABSTRACT FROM AUTHOR]

The immunoglobulin (Ig) constant CH2 domain is critical for antibody effector functions. Isolated CH2 domains are promising scaffolds for construction of libraries containing diverse binders that could also confer some effector functions. We have shown previously that an isolated human CH2 domain is relatively unstable to thermally induced unfolding, but its stability can be improved by engineering an additional disulfide bond (Gong, R., Vu, B. K., Feng, Y., Prieto, D. A., Dyba, M. A., Walsh, J. D., Prabakaran, P., Veenstra, T. D., Tarasov, S. G., Ishima, R., and Dimitrov, D. S. (2009) J. Biol. Chem. 284, 14203-14210). We have hypothesized that the stability of this engineered antibody domain could be further increased by removing unstructured residues. To test our hypothesis, we removed the seven N-terminal residues that are in a random coil as suggested by our analysis of the isolated CH2 crystal structure and NMR data. The resulting shortened engineered CH2 (m01s) was highly soluble, monomeric, and remarkably stable, with a melting temperature (Tm) of 82.6 °C, which is about 10 and 30 °C higher than those of the original stabilized CH2 (m01) and CH2, respectively. m01s and m01 were more resistant to protease digestion than CH2. A newly identified anti-CH2 antibody that recognizes a conformational epitope bound to m01s significantly better (>10-fold higher affinity) than to CH2 and slightly better than to m01. m01s bound to a recombinant soluble human neonatal Fc receptor at pH 6.0 more strongly than CH2. These data suggest that shortening the m01 N terminus significantly increases stability without disrupting its conformation and that our approach for increasing stability and decreasing size by removing unstructured regions may also apply to other proteins. [ABSTRACT FROM AUTHOR]

A fundamental question in community ecology is whether general assembly rules determine the structure of natural communities. Although many types of assembly rules have been described, including Diamond's assembly rules, constant body-size ratios, favoured states, and nestedness, few studies have tested multiple assembly rule models simultaneously. Therefore, little is known about the relative importance of potential underlying factors such as interspecific competition, inter-guild competition, selective extinction and habitat nestedness in structuring community composition. Here, we test the above four assembly rule models and examine the causal basis for the observed patterns using bird data collected on islands of an inundated lake. Thousand Island Lake, China. We collected data on presence-absence matrices, body size and functional groups for bird assemblages on 42 islands from 2007 to 2009. To test the above four assembly rule models, we used null model analyses to compare observed species co-occurrence patterns, body-size distributions and functional group distributions with randomly generated assemblages. To ensure that the results were not biased by the inclusion of species with extremely different ecologies, we conducted separate analyses for the entire assemblage and for various subset matrices classified according to foraging guilds. The bird assemblages did not support predictions by several competitively structured assembly rule models, including Diamond's assembly rules, constant body-size ratios, and favoured states. In contrast, bird assemblages were highly significantly nested and were apparently shaped by extinction processes mediated through area effects and habitat nestedness. The nestedness of bird assemblages was not a result of passive sampling or selective colonization. These results were very consistent, regardless of whether the entire assemblage or the subset matrices were analysed. Our results suggest that bird assemblages were shaped by extinction processes mediated through area effects and habitat nestedness, rather than by interspecific or inter-guild competition. From a conservation point of view, our results indicate that we should protect both the largest islands with the most species-rich communities and habitat-rich islands in order to maximize the number of species preserved. [ABSTRACT FROM AUTHOR]

In this work, polyethersulfone (PES) flat sheet ultrafiltration (UF) membranes were prepared by immersion precipitation phase inversion process with polyvinylpyrrolidone (PVP 30K) and acetone as additives. The best preparation condition for PES membranes with high water flux and rejection (to BSA) was decided. It was found that the optimal composition of the polymer casting solution was: 16 wt% (PES), 2 wt% (PVP 30K), and 1 wt% (acetone). Pure water flux of the membrane prepared at this condition reached to 373 L/m² h at 0.1 MPa, and the rejection to BSA was 91%. Compared with other reports, the rejection was slightly low but the flux of the PES membrane was high. When the membrane was used to concentrate gelatin solutions, the rejection value was over 75%. It was found that increasing the feed temperature and transmembrane pressure enhanced the permeation flux, but the rejection decreased slightly. However, increasing the cross-flow velocity of the feed solution simultaneously increased both the permeation flux and the rejection. [ABSTRACT FROM AUTHOR]