Search

ObjectiveTo evaluate the efficacy and safety of upadacitinib in the treatment of moderate-to-severe atopic dermatitis (AD), and provide reference for rational clinical medication.MethodsPubMed, Medline, Embase, Web of Science, Clinical Trials Website, and Cochrane Library databases were searched from the time of establishment until January 6, 2024, to compile a list of all randomized controlled trials (RCTs) including upadacitinib in the treatment of moderate-to-severe AD. The quality of the included studies was evaluated using the Cochrane Systematic Review. Review Manager 5.3 software was utilized for statistical analysis of outcome measures.ResultsA total of five studies were included in the meta-analysis. The results revealed that the 15 mg and 30 mg upadacitinib significantly improved Eczema Area and Severity Index (EASI) 75% {[Odds Ratio (OR) = 8.58, 95% confidence interval (CI) (5.84-12.60), P < 0.00001] [OR = 15.62, 95% CI (10.89-22.42), P < 0.00001]}, Numerical Rating Scale (NRS) ≥ 4 {[OR = 7.13, 95% CI (5.63-9.01), P < 0.00001] [OR = 11.30, 95% CI (8.93-14.31), P < 0.00001]}, and Investigator's Global Assessment (IGA) 0/1 {[OR = 8.63, 95% CI (6.60-11.27), P < 0.00001] [OR = 16.04, 95% CI (12.26-20.99), P < 0.00001]} compared to placebo. In terms of safety, although 15 mg and 30 mg upadacitinib significantly increased the overall adverse events rate compared to placebo {[OR = 1.31, 95% CI (1.09-1.58), P = 0.004] [OR = 1.85, 95% CI (1.54-2.21), P < 0.00001]}, there was no significant difference in the serious adverse events rate {[OR = 0.73, 95% CI (0.41-1.29), P = 0.28] [OR = 0.69, 95% CI (0.39-1.23), P = 0.21]} and withdrawal rate due to adverse events {[OR = 0.66, 95% CI (0.39-1.11), P = 0.12] [OR = 0.85, 95% CI (0.52-1.38), P = 0.50]} compared to placebo.ConclusionThis meta-analysis preliminarily suggests that upadacitinib is effective and safe for usage in the treatment of moderate-to-severe AD. Additionally, upadacitinib can instantly relieve itchiness and effectively reduce symptoms and signs, with its 30-mg dose being more effective than the 15-mg dose.

ObjectivesTo estimate the proportions of anatomical breast characteristics suggestive of breast hypoplasia among breastfeeding women self-reporting low milk supply. We also explored breast hypoplasia risk factors.DesignOnline survey conducted between October 2021 and January 2022.SettingFive low milk supply Facebook groups.Participants487 women reporting low milk supply with their first child born ≥ 37 weeks gestation within 5 years of participation in this study, and residing in the USA, Australia or the UK. We present data on the primary outcome ('breast type') for 399 women. Women were excluded if the dyad was separated for more than 24 hours during the hospital stay, or if the mother reported removing milk less than 6 times per day from each breast on most days before being aware of having insufficient milk production.Primary and secondary outcome measuresThe proportions of proposed breast hypoplasia markers including atypical breast type, widely spaced breasts, breast asymmetry, stretch marks on the breast and lack of pregnancy breast growth. We also estimated the odds of having breast hypoplasia markers in at-risk groups compared to reference groups, adjusting for covariates.ResultsApproximately 68% reported at least one atypical breast (270/399; 95% CI: 62.9%, 72.1%). Around 47% reported widely spaced breasts (212/449; 95% CI: 42.7%, 52.7%), 72% a lack of pregnancy breast growth (322/449; 95% CI: 68.3%, 77.4%), and 76% stretch marks on the breast (191/250; 95% CI: 70.7%, 81.3%). Multiple logistic regression analyses identified being overweight during pubertal years as a risk factor for atypical breast type and lack of pregnancy breast growth.ConclusionsParticipants in low milk supply Facebook groups reported high rates of breast hypoplasia markers. Being overweight during adolescence was a risk factor for breast hypoplasia markers. These findings should be confirmed in well-conducted large cohort studies to determine the strongest combination of hypoplasia markers in predicting low supply.

This paper constructs a matching index model to research the matching degree of embodied carbon trade and value-added trade among eight regions and 31 provinces in China in 2012 and 2015. The study finds that (1) At the regional level, a mismatch is shown between embodied carbon trade and value-added trade among regions, for example, in 2015, the northwest region has output embodied carbon to the north coast, while input the value-added trades from the north coast. (2) At the provincial level, a mismatch is displayed between embodied carbon transaction and value-added trade, for example, Beijing had a net shift of embodied carbon from Xinjiang in 2015, but Xinjiang had a net transfer of added value from Beijing. Therefore, the Chinese government needs to establish an ecological compensation mechanism to improve the mismatch between embodied carbon trade and value-added trade among Chinese regions (provinces).

Based on the investigation of financial fairness perception and donation intention of individual donors in non-profit organizations (NPOs), this paper uses structural equation model to analyze the impact of individual donors' financial fairness perception on donation intention. The results show that individual donors' perceptions on financial result fairness, financial procedure fairness and financial information fairness all have positive impact on donation intention; among which the perception on financial result fairness only has direct impact on individual donation intention, while the perceptions on financial procedure fairness and financial information fairness have direct and indirect impact on individual donation intention.

In this study, we proposed a novel convolutional neural network (CNN) architecture for classification of benign and malignant breast cancer (BC) in histological images. To improve the delivery and use of feature information, we chose the DenseNet as the basic building block and interleaved it with the squeeze-and-excitation (SENet) module. We conducted extensive experiments with the proposed framework by using the public domain BreakHis dataset and demonstrated that the proposed framework can produce significantly improved accuracy in BC classification, compared with the state-of-the-art CNN methods reported in the literature.

Considering the serious land-based pollution and the weak water exchange ability of western Laizhou Bay, it is essential to conduct an ecological risk assessment of the pollutants in this area. In this study, the ecological risk caused by heavy metals deposited in the surface sediments and those resuspended in the seawater of western Laizhou Bay was evaluated using probabilistic approaches. First, the concentrations of seven heavy metals, namely As, Cd, Cr, Cu, Hg, Pb, and Zn, in the surface sediments and seawater of western Laizhou Bay were detected during the spring and autumn of 2016. The concentrations of As, Cd, Cr, Cu, and Pb were found to be at levels comparable to those in the other global coastal systems, while those of Hg and Zn were lower than those in other coastal areas. Next, an ecological risk assessment of heavy metals in the surface sediments was performed using a typical potential ecological risk index and refined by using a Monte Carlo simulation. The results suggested low risk for the heavy metals detected in the sediments of western Laizhou Bay, with the exception of Hg in September 2016, which showed a probability (0.03%) of moderate risk. Meanwhile, the aquatic ecological risk assessment of the heavy metals was performed by applying a combination of hazard quotient (HQ) and joint probability curve. While the ecological risk of Cd, Hg, and Pb was found to be acceptable, the HQs for Cr, Cu, and Zn were greater than 1, and the overall risk probability of their adverse effects was higher than 0.05, suggesting certain ecological risk. Specifically, in the case of As, the overall risk probability was lower than 0.05, suggesting that its ecological risk was acceptable, although its HQ was greater than 1. Thus, by applying the probabilistic approaches, the ecological risk of the heavy metals in western Laizhou Bay was better characterized in this study, avoiding both overestimation and underestimation of ecological risk.

Presently, China has the largest high-speed rail (HSR) system in the world. However, our understanding of the network structure of the world's largest HSR system remains largely incomplete due to the limited data available. In this study, a publicly available data source, namely, information from a ticketing website, was used to collect an exhaustive dataset on the stations and routes within the Chinese HSR system. The dataset included all 704 HSR stations that had been built as of June, 2016. A classical set of frequently used metrics based on complex network theory were analyzed, including degree centrality, betweenness centrality, and closeness centrality. The frequency distributions of all three metrics demonstrated highly consistent bimodal-like patterns, suggesting that the Chinese HSR network consists of two distinct regimes. The results indicate that the Chinese HSR system has a hierarchical structure, rather than a scale-free structure as has been commonly observed. To the best of our knowledge, such a network structure has not been found in other railway systems, or in transportation systems in general. Follow-up studies are needed to reveal the formation mechanisms of this hierarchical network structure.

Plant height (PH) is an important trait in soybean, as taller plants may have higher yields but may also be at risk for lodging. Many genes act jointly to influence PH throughout development. To map the quantitative trait loci (QTL) controlling PH, we used the unconditional variable method (UVM) and conditional variable method (CVM) to analyze PH data for a four-way recombinant inbred line (FW-RIL) population derived from the cross of (Kenfeng14 × Kenfeng15) × (Heinong48 × Kenfeng19). We identified 7, 8, 16, 19, 15, 27, 17, 27, 22, and 24 QTL associated with PH at 10 developmental stages, respectively. These QTL mapped to 95 genomic regions. Among these QTL, 9 were detected using UVM and CVM, and 89 and 66 were only detected by UVM or CVM, respectively. In total, 36 QTL controlling PH were detected at multiple developmental stages and these made unequal contributions to genetic variation throughout development. Among 19 novel regions discovered in our study, 7 could explain over 10% of the phenotypic variation and contained only one single QTL. The unconditional and conditional QTL detected here could be used in molecular design breeding across the whole developmental procedure.

ObjectiveThis study evaluated whether frequent (fortnightly) audit and feedback cycles over a sustained period of time (>12 months) increased clinician adherence to recommended guidelines in acquired brain injury rehabilitation.DesignA before and after study design.SettingA metropolitan inpatient brain injury rehabilitation unit.ParticipantsClinicians; medical, nursing and allied health staff.InterventionsFortnightly cycles of audit and feedback for 14 months. Each fortnight, medical file and observational audits were completed against 114 clinical indicators.Main outcome measureAdherence to guideline indicators before and after intervention, calculated by proportions, Mann-Whitney U and Chi square analysis.ResultsClinical and statistical significant improvements in median clinical indicator adherence were found immediately following the audit and feedback program from 38.8% (95% CI 34.3 to 44.4) to 83.6% (95% CI 81.8 to 88.5). Three months after cessation of the intervention, median adherence had decreased from 82.3% to 76.6% (95% CI 72.7 to 83.3, pConclusionA fortnightly audit and feedback program increased clinicians' adherence to guideline recommendations in an inpatient acquired brain injury rehabilitation setting. We propose future studies build on the evidence-based method used in the present study to determine effectiveness and develop an implementation toolkit for scale-up.

[This corrects the article DOI: 10.1371/journal.pone.0104282.].

BackgroundIn view of the irreversible pathology of progressive exacerbation, the societal burden of chronic kidney disease (CKD) is increasing along with the rise in total health expenditure. Meanwhile, disparities remain among urban and rural citizens with different types of health insurance. This study aimed to assess the socioeconomic disparities between hospitalized CKD patients in urban and rural areas.MethodA total of 501 CKD inpatients with urban or rural medical insurance (UMI or RMI, respectively) were selected from the top six tertiary hospitals in Wuhan. Demographic and socioeconomic data were collected as influencing factors. Data evaluation was performed using univariate and multivariate analyses.ResultSocioeconomic characteristics showed differences among hospitalized CKD patients with different health insurances. Patients with RMI were younger, and reported lower education levels, poor domestic economic conditions, shorter duration, and less frequent hospital stays than those with UMI (PConclusionsCare delivery and reimbursement models should be re-designed and implemented to improve equity among different CKD patients. The national health education should also be enhanced to prevent CKD and provide early treatment.

Pod number is an important factor that influences yield in soybean. Here, we used two associated recombinant inbred line (RIL) soybean populations, RIL3613 (containing 134 lines derived from Dongnong L13 × Heihe 36) and RIL6013 (composed of 156 individuals from Dongnong L13 × Henong 60), to identify quantitative trait loci (QTLs) regulating the vertical distribution and quantity of seeds and seed pods. The numbers of pods were quantified in the upper, middle, and lower sections of the plant, as well as in the plants as a whole, and QTLs regulating these spatial traits were mapped using an inclusive complete interval mapping method. A total of 21 and 26 QTLs controlling pod-number-related traits were detected in RIL3613 and RIL6013, respectively, which explained 1.25-11.6698% and 0.0001-7.91% of the phenotypic variation. A total of 34 QTLs were verified by comparison with previous research, were identified in both populations, or were found to regulate multiple traits, indicating their authenticity. These results enhance our understanding of the vertical distribution of pod-number-related traits and support molecular breeding for seed yield.

BACKGROUND:Elevated serum uric acid (sUA) concentrations are common in the general population and are associated with chronic metabolic conditions and adverse clinical outcomes. We evaluated secular trends in the burden of hyperuricaemia from 2006-2014 within the Irish health system. METHODS:Data from the National Kidney Disease Surveillance Programme was used to determine the prevalence of elevated sUA in adults, age > 18 years, within the Irish health system. Hyperuricaemia was defined as sUA > 416.4 μmol/L in men and > 339.06 μmol/L in women, and prevalence was calculated as the proportion of patients per year with mean sUA levels above sex-specific thresholds. Temporal trends in prevalence were compared from 2006 to 2014 while general estimating equations (GEE) explored variation across calendar years expressed as odds ratios (OR) and 95% Confidence intervals (CI). RESULTS:From 2006 to 2014, prevalence of hyperuricaemia increased from 19.7% to 25.0% in men and from 20.5% to 24.1% in women, P

Leaf coloration is one of the most important and attractive characteristics of Ananas comosus var. bracteatus. The chimeric character is not stable during the in vitro tissue culturing. Many regenerated plants lost economic values for the loss of the chimeric character of leaves. In order to reveal the molecular mechanisms involved in the albino phenotype of the leaf cells, the physiological and transcriptional differences between complete white (CWh) and green (CGr) leaf cells of A. comosus var. bracteatus were analyzed. A total of 1,431 differentially expressed unigenes (DEGs) in CGr and CWh leaves were identified using RNA-seq. A comparison to the COG, GO and KEGG annotations revealed DEGs involved in chlorophyll biosynthesis, chloroplast development and photosynthesis. Furthermore, the measurement of main precursors of chlorophyll in the CWh leaves confirmed that the rate-limiting step in chlorophyll biosynthesis, and thus the cause of the albino phenotype of the white cells, was the conversion of pyrrole porphobilinogen (PBG) to uroporphyrinogen III (Uro III). The enzyme activity of porphobilinogen deaminase (PBGD) and uroporporphyrinogn III synthase (UROS), which catalyze the transition of PBG to Uro III, was significantly decreased in the CWh leaves. Our data showed the transcriptional differences between the CWh and CGr plants and characterized key steps in chlorophyll biosynthesis of the CWh leaves. These results contribute to our understanding of the mechanisms and regulation of pigment biosynthesis in the CWh leaf cells of A. comosus var. bracteatus.

The present study was aimed to unravel the inhibitory mechanisms of curcumin for lung cancer metastasis via constructing a miRNA-transcription factor (TF)-target gene network. Differentially expressed miRNAs between human high-metastatic non-small cell lung cancer 95D cells treated with and without curcumin were identified using a TaqMan human miRNA array followed by real-time PCR, out of which, the top 6 miRNAs (miR-302b-3p, miR-335-5p, miR-338-3p, miR-34c-5p, miR-29c-3p and miR-34a-35p) with more verified target genes and TFs than other miRNAs as confirmed by a literature review were selected for further analysis. The miRecords database was utilized to predict the target genes of these 6 miRNAs, TFs of which were identified based on the TRANSFAC database. The findings of the above procedure were used to construct a miRNA-TF-target gene network, among which miR-34a-5p, miR-34c-5p and miR-302b-3p seemed to regulate CCND1, WNT1 and MYC to be involved in Wnt signaling pathway through the LEF1 transcription factor. Therefore, we suggest miR-34a-5p/miR-34c-5p/miR-302b-3p -LEF1-CCND1/WNT1/MYC axis may be a crucial mechanism in inhibition of lung cancer metastasis by curcumin.

Vascular endothelial growth factor (VEGF) plays critical roles in angiogenesis and vasculogenesis, which are associated with post-stroke functional recovery. However, the effects of the VEGFA polymorphisms on the outcome of ischemic stroke (IS) have been rarely reported. We therefore investigated the associations of +936C/T variant (rs3025039) with the susceptibilities and the 90-day outcomes from 494 IS patients and 337 healthy controls in Chinese population through the establishment of logistic multivariate regression model. Stroke severity at admission and outcome of 90 days were respectively assessed according to the National Institutes of Health Stroke Scale and the modified Rankin Scale. The analysis showed that there were no significant associations of the rs3025039 genotypes with the susceptibility (P = 0.229) and the severity (P = 0.734). However, when we divided the 308 IS patients into two groups according to the different outcomes, we found that the rs3025039 TC+TT genotype significantly increased the risk of poor recovery [adjusted odds ratio (OR), 1.99; 95% confidence interval (CI), 1.18-3.37]. Interestingly, we observed another 3'UTR variant, +1451C/T (rs3025040), exhibited strong linkage disequilibrium (r2 = 1.0) with +936C/T and was located in a predicted microRNA-binding site. The rs3025040 T allele significantly decreased the luciferase activities in four cell lines, which indicated a potential disruption of the miRNA-mRNA interaction that would result in lower VEGF expression levels. Our data suggested that the +936C/T variants significantly increased the risk of poorer stroke outcome by affecting the bindings of miR-199a and miR-199b to VEGF mRNA at the rs30250340 polymorphic site.

[This corrects the article DOI: 10.1371/journal.pone.0161170.].

The objective of this study was to validate the reliability and validity of the safety attitudes questionnaire (SAQ) in Heilongjiang province, northern China.The SAQ was distributed to 27 public hospitals in five cities across Heilongjiang province. The Cronbach's α, item-dimension and dimension-dimension correlations were calculated. Descriptive analyses and confirmatory factor analysis were also performed.The recovery rate of the questionnaire was 84.45%. The validity and reliability measures of the SAQ were acceptable. The goodness-of-fit index from the confirmatory factor analysis showed a reasonable model fit (CFI = 0.93, GFI = 0.91, RMSEA = 0.05). The Cronbach's α value for the scale was 0.91 and ranged from 0.66 to 0.91 for each of the scales. The SAQ showed good internal consistency reliability.The SAQ had satisfactory psychometric properties and could be a useful tool to measure safety attitudes in public hospitals in Heilongjiang province in China.

Identifying temporal variation in hospitalization rates may provide insights about disease patterns and thereby inform research, policy, and clinical care. However, the majority of medical conditions have not been studied for their potential seasonal variation. The objective of this study was to apply a data-driven approach to characterize temporal variation in condition-specific hospitalizations. Using a dataset of 34 million inpatient discharges gathered from hospitals in New York State from 2008-2011, we grouped all discharges into 263 clinical conditions based on the principal discharge diagnosis using Clinical Classification Software in order to mitigate the limitation that administrative claims data reflect clinical conditions to varying specificity. After applying Seasonal-Trend Decomposition by LOESS, we estimated the periodicity of the seasonal component using spectral analysis and applied harmonic regression to calculate the amplitude and phase of the condition's seasonal utilization pattern. We also introduced four new indices of temporal variation: mean oscillation width, seasonal coefficient, trend coefficient, and linearity of the trend. Finally, K-means clustering was used to group conditions across these four indices to identify common temporal variation patterns. Of all 263 clinical conditions considered, 164 demonstrated statistically significant seasonality. Notably, we identified conditions for which seasonal variation has not been previously described such as ovarian cancer, tuberculosis, and schizophrenia. Clustering analysis yielded three distinct groups of conditions based on multiple measures of seasonal variation. Our study was limited to New York State and results may not directly apply to other regions with distinct climates and health burden. A substantial proportion of medical conditions, larger than previously described, exhibit seasonal variation in hospital utilization. Moreover, the application of clustering tools yields groups of clinically heterogeneous conditions with similar seasonal phenotypes. Further investigation is necessary to uncover common etiologies underlying these shared seasonal phenotypes.

Despite Apolipoprotein E (ApoE) being one of the main apolipoproteins in the blood, the association between its genotype and the high cholesterol or blood glucose levels commonly seen in clinical practice is inconclusive. Such research is also lacking in the Han population. The aim of this study was to investigate the association between APOE genotype, diabetes, and plasma glucose and lipid levels. We included 243 community-dwelling elderly residents in this study. Participant APOE genotypes were assessed and were simultaneously tested for weight, height, blood glucose, triglycerides, cholesterol, and high- and low-density lipoprotein. In addition, gender, age, years of education, cognitive function, and medical history was recorded. Subjects were divided into 3 groups based on APOE genotype: APOE ε2 group (ε2/ε2 and ε2/ε3), APOE ε3 group (ε3/ε3), and APOE ε4 group (ε2/ε4, ε3/ε4 and ε4/ε4). Comparisons between groups were conducted for the incidence of diabetes, high blood pressure, and dementia, as well as for differences in body-mass index, fasting plasma glucose, and blood lipids. The APOE ε3/ε3 genotype exhibited the highest frequency (70.4%) among the subjects. Participants in the APOE ε3 group demonstrated significantly higher levels of fasting plasma glucose than those in the APOE ε2 and APOE ε4 groups (P

OBJECTIVE:The fraction of circulating cell-free fetal (cff) DNA in maternal plasma is a critical parameter for aneuploidy screening with non-invasive prenatal testing, especially for those samples located in equivocal zones. We developed an approach to quantify cff DNA fractions directly with sequencing data, and increased cff DNAs by optimizing library construction procedure. METHODS:Artificial DNA mixture samples (360), with known cff DNA fractions, were used to develop a method to determine cff DNA fraction through calculating the proportion of Y chromosomal unique reads, with sequencing data generated by Ion Proton. To validate our method, we investigated cff DNA fractions of 2,063 pregnant women with fetuses who were diagnosed as high risk of fetal defects. The z-score was calculated to determine aneuploidies for chromosomes 21, 18 and 13. The relationships between z-score and parameters of pregnancies were also analyzed. To improve cff DNA fractions in our samples, two groups were established as follows: in group A, the large-size DNA fragments were removed, and in group B these were retained, during library construction. RESULTS:A method to determine cff DNA fractions was successfully developed using 360 artificial mixture samples in which cff DNA fractions were known. A strong positive correlation was found between z-score and fetal DNA fraction in the artificial mixture samples of trisomy 21, 18 and 13, as well as in clinical maternal plasma samples. There was a positive correlation between gestational age and the cff DNA fraction in the clinical samples, but no correlation for maternal age. Moreover, increased fetal DNA fractions were found in group A compared to group B. CONCLUSION:A relatively accurate method was developed to determine the cff DNA fraction in maternal plasma. By optimizing, we can improve cff DNA fractions in sequencing samples, which may contribute to improvements in detection rate and reliability.

Oxidative stress may play an important role in the pathogenesis of keratoconus (KC). Mitochondrial DNA (mtDNA) is involved in mitochondrial function, and the mtDNA content, integrity, and transcript level may affect the generation of reactive oxygen species (ROS) and be involved in the pathogenesis of KC. We designed a case-control study to research the relationship between KC and mtDNA integrity, content and transcription. One-hundred ninety-eight KC corneas and 106 normal corneas from Chinese patients were studied. Quantitative real-time PCR was used to measure the relative mtDNA content, transcript levels of mtDNA and related genes. Long-extension PCR was used to detect mtDNA damage. ROS, mitochondrial membrane potential and ATP were measured by respective assay kit, and Mito-Tracker Green was used to label the mitochondria. The relative mtDNA content of KC corneas was significantly lower than that of normal corneas (P = 9.19×10-24), possibly due to decreased expression of the mitochondrial transcription factor A (TFAM) gene (P = 3.26×10-3). In contrast, the transcript levels of mtDNA genes were significantly increased in KC corneas compared with normal corneas (NADH dehydrogenase subunit 1 [ND1]: P = 1.79×10-3; cytochrome c oxidase subunit 1 [COX1]: P = 1.54×10-3; NADH dehydrogenase subunit 1, [ND6]: P = 4.62×10-3). The latter may be the result of increased expression levels of mtDNA transcription-related genes mitochondrial RNA polymerase (POLRMT) (P = 2.55×10-4) and transcription factor B2 mitochondrial (TFB2M) (P = 7.88×10-5). KC corneas also had increased mtDNA damage (P = 3.63×10-10), higher ROS levels, and lower mitochondrial membrane potential and ATP levels compared with normal corneas. Decreased integrity, content and increased transcript level of mtDNA are associated with KC. These changes may affect the generation of ROS and play a role in the pathogenesis of KC.

To evaluate visual outcomes and complications after phacoemulsification in eyes with cataract and previous radial keratotomy (RK) cuts using different sizes of clear corneal incisions.The study was a retrospective study. Thirty eyes with cataract and previous RK underwent phacoemulsification and intraocular lens (IOL) implantation. Among them 7 eyes had 8 RK cuts, 13 eyes had 12 RK cuts, and 10 eyes had 16 RK cuts. Phacoemulsification and IOL implantation were performed through a 2.0-3.2 mm clear corneal incision by a single surgeon. In the 8 RK cuts group, 3.2 mm clear corneal incisions were used in 4 eyes, and 3.0 mm clear corneal incisions were used in 3 eyes. In the 12 RK cuts group, 3.2 mm clear corneal incisions were used in 6 eyes, and 2.2 mm clear corneal incisions were used in 7 eyes. In the 16 RK cuts group, 3.2 mm clear corneal incisions were used in 5 eyes, and 2.0 mm clear corneal incisions were used in 5 eyes. Patients were followed up 1 day, 1 week, 1 month, 3 months, 6 months, 1 year, 2 years, and 3 years postoperatively and were examined for the dehiscence of RK cuts during or after the surgery, post-operative best-corrected visual acuity (BCVA), corneal astigmatism, corneal endothelial cell density and complications.Successful phacoemulsification with IOL implantation was performed in all eyes. No wound dehiscence was noted in any eyes with 8 or 12 RK cuts. Wound dehiscence was noted in 2 eyes with 16 RK cuts. The dehiscence of RK cuts was closed successfully by injecting an air bubble with or without viscoelastic agent into the anterior chamber at the end of surgery. During the follow-up, the cuts were well apposed in all eyes, and no new dehiscence of RK cuts was noted. At the last follow-up, mean BCVA (0.2 ± 0.18 logMAR) was better than preoperative BCVA(0.45±0.19 logMAR) (P < 0.001). There was no significant difference between the long-term preoperative and postoperative mean corneal astigmatism (P = 0.3). However, there was a significant reduction in postoperative corneal endothelial cell density (1866.5±773.9 / mm2 vs 2421.7±655.7 / mm2) (P < 0.001).Phacoemulsification and IOL implantation with clear corneal incisions in eyes with previous RK were associated with good surgical outcomes. Wound dehiscence was not specificaly related to the size of clear corneal incision during phacoemulsification in these eyes.

BACKGROUND:Hand, foot, and mouth disease (HFMD) is known to be a highly contagious childhood illness. In recent years, the number of reported cases of HFMD has significantly increased in mainland China. This study aims at the epidemiological features, spatiotemporal patterns of HMFD at the county/district level in mainland China. METHODS:Data on reported HFMD cases for each county from 1 January 2008 to 31 December 2012 were obtained from the Chinese Center for Disease Control and Prevention. Cluster analysis, spatial autocorrelation, and retrospective scan methods were used to explore the spatiotemporal patterns of the disease. RESULTS:The annual incidences varied greatly among the counties, ranging from 0 to 74.31‰ with the median of 5.42‰ (interquartile range: 1.54‰-13.55‰) during 2008-2012 in mainland China. Counties close to provincial capital cities generally had higher incidences than rural counties. A seasonal distribution was observed between the northern and southern China, of which dual epidemic were shown in southern China and usually only one in northern China. Based on the global and local spatial autocorrelation analysis, we found that the spatial distribution of HFMD was presented a significant clustering pattern for each year (P

Chronic non-progressive pneumonia, a disease that has become a worldwide epidemic has caused considerable loss to sheep industry. Mycoplasma ovipneumoniae (M. ovipneumoniae) is the causative agent of interstitial pneumonia in sheep, goat and bighorn. We here have identified by immunogold and immunoblotting that elongation factor Tu (EF-Tu) and heat shock protein 70 (HSP 70) are membrane-associated proteins on M. ovipneumonaiea. We have evaluated the humoral and cellular immune responses in vivo by immunizing BALB/c mice with both purified recombinant proteins rEF-Tu and rHSP70. The sera of both rEF-Tu and rHSP70 treated BALB/c mice demonstrated increased levels of IgG, IFN-γ, TNF-α, IL-12(p70), IL-4, IL-5 and IL-6. In addition, ELISPOT assay showed significant increase in IFN-γ+ secreting lymphocytes in the rHSP70 group when compared to other groups. Collectively our study reveals that rHSP70 induces a significantly better cellular immune response in mice, and may act as a Th1 cytokine-like adjuvant in immune response induction. Finally, growth inhibition test (GIT) of M. ovipneumoniae strain Y98 showed that sera from rHSP70 or rEF-Tu-immunized mice inhibited in vitro growth of M. ovipneumoniae. Our data strongly suggest that EF-Tu and HSP70 of M. ovipneumoniae are membrane-associated proteins capable of inducing antibody production, and cytokine secretion. Therefore, these two proteins may be potential candidates for vaccine development against M. ovipneumoniae infection in sheep.

Species identification of Nocardia is not straightforward due to rapidly evolving taxonomy, insufficient discriminatory power of conventional phenotypic methods and also of single gene locus analysis including 16S rRNA gene sequencing. Here we evaluated the ability of a 5-locus (16S rRNA, gyrB, secA1, hsp65 and rpoB) multilocus sequence analysis (MLSA) approach as well as that of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) in comparison with sequencing of the 5'-end 606 bp partial 16S rRNA gene to provide identification of 25 clinical isolates of Nocardia. The 5'-end 606 bp 16S rRNA gene sequencing successfully assigned 24 of 25 (96%) clinical isolates to species level, namely Nocardia cyriacigeorgica (n = 12, 48%), N. farcinica (n = 9, 36%), N. abscessus (n = 2, 8%) and N. otitidiscaviarum (n = 1, 4%). MLSA showed concordance with 16S rRNA gene sequencing results for the same 24 isolates. However, MLSA was able to identify the remaining isolate as N. wallacei, and clustered N. cyriacigeorgica into three subgroups. None of the clinical isolates were correctly identified to the species level by MALDI-TOF MS analysis using the manufacturer-provided database. A small "in-house" spectral database was established incorporating spectra of five clinical isolates representing the five species identified in this study. After complementation with the "in-house" database, of the remaining 20 isolates, 19 (95%) were correctly identified to species level (score ≥ 2.00) and one (an N. abscessus strain) to genus level (score ≥ 1.70 and < 2.00). In summary, MLSA showed superior discriminatory power compared with the 5'-end 606 bp partial 16S rRNA gene sequencing for species identification of Nocardia. MALDI-TOF MS can provide rapid and accurate identification but is reliant on a robust mass spectra database.

During hepatitis B virus (HBV) infection, three viral envelope proteins of HBV are overexpressed in the endoplasmic reticulum (ER). The large S protein (LHBs) and truncated middle S protein (MHBst) have been documented to play roles in regulating host gene expression and contribute to hepatic disease development. As a predominant protein at the ultrastructural level in biopsy samples taken from viremic patients, the role of the middle S protein (MHBs) remains to be understood despite its high immunogenicity. When we transfected hepatocytes with an enhanced green fluorescent protein (EGFP)-tagged MHBs expressing plasmid, the results showed that expression of MHBs cause an upregulation of IL-6 at the message RNA and protein levels through activating the p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa B (NF-κB) pathways. The use of specific inhibitors of the signaling pathways can diminish this upregulation. The use of BAPTA-AM attenuated the stimulation caused by MHBs. We further found that MHBs accumulated in the endoplasmic reticulum and increased the amount of glucose regulated protein 78 (GRP78/BiP). Our results provide a possibility that MHBs could be involved in liver disease progression.

Heavy fine particulate matter (PM2.5) air pollution occurs frequently in China. However, epidemiological research on the association between short-term exposure to PM2.5 pollution and respiratory disease morbidity is still limited. This study aimed to explore the association between PM2.5 pollution and hospital emergency room visits (ERV) for total and cause-specific respiratory diseases in urban areas in Beijing.Daily counts of respiratory ERV from Jan 1 to Dec 31, 2013, were obtained from ten general hospitals located in urban areas in Beijing. Concurrently, data on PM2.5 were collected from the Beijing Environmental Protection Bureau, including 17 ambient air quality monitoring stations. A generalized-additive model was used to explore the respiratory effects of PM2.5, after controlling for confounding variables. Subgroup analyses were also conducted by age and gender.A total of 92,464 respiratory emergency visits were recorded during the study period. The mean daily PM2.5 concentration was 102.1±73.6 μg/m3. Every 10 μg/m3 increase in PM2.5 concentration at lag0 was associated with an increase in ERV, as follows: 0.23% for total respiratory disease (95% confidence interval [CI]: 0.11%-0.34%), 0.19% for upper respiratory tract infection (URTI) (95%CI: 0.04%-0.35%), 0.34% for lower respiratory tract infection (LRTI) (95%CI: 0.14%-0.53%) and 1.46% for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) (95%CI: 0.13%-2.79%). The strongest association was identified between AECOPD and PM2.5 concentration at lag0-3 (3.15%, 95%CI: 1.39%-4.91%). The estimated effects were robust after adjusting for SO2, O3, CO and NO2. Females and people 60 years of age and older demonstrated a higher risk of respiratory disease after PM2.5 exposure.PM2.5 was significantly associated with respiratory ERV, particularly for URTI, LRTI and AECOPD in Beijing. The susceptibility to PM2.5 pollution varied by gender and age.

Trichoderma harzianum strain SQR-T037 is a biocontrol agent that has been shown to enhance the uptake of nutrients (macro- and microelements) by plants in fields. The objective of this study was to investigate the contribution of SQR-T037 to P and microelement (Fe, Mn, Cu and Zn) nutrition in tomato plants grown in soil and in hydroponic conditions. Inoculation with SQR-T037 significantly improved the biomass and nutrient uptake of tomato seedlings grown in a nutrient-limiting soil. So we investigated the capability of SQR-T037 to solubilise sparingly soluble minerals in vitro via four known mechanisms: acidification by organic acids, chelation by siderophores, redox by ferric reductase and hydrolysis by phytase. SQR-T037 was able to solubilise phytate, Fe2O3, CuO, and metallic Zn but not Ca3(PO4)2 or MnO2. Organic acids, including lactic acid, citric acid, tartaric acid and succinic acid, were detected by HPLC and LC/MS in two Trichoderma cultures. Additionally, we inoculated tomato seedlings with SQR-T037 using a hydroponic system with specific nutrient deficiencies (i.e., nutrient solutions deficient in P, Fe, Cu or Zn and supplemented with their corresponding solid minerals) to better study the effects of Trichoderma inoculation on plant growth and nutrition. Inoculated seedlings grown in Cu-deficient hydroponic conditions exhibited increases in dry plant biomass (92%) and Cu uptake (42%) relative to control plants. However, we did not observe a significant effect on seedling biomass in plants grown in the Fe- and Zn-deficient hydroponic conditions; by contrast, the biomass decreased by 82% in the P-deficient hydroponic condition. Thus, we demonstrated that Trichoderma SQR-T037 competed for P (phytate) and Zn with tomato seedlings by suppressing root development, releasing phytase and/or chelating minerals. The results of this study suggest that the induction of increased or suppressed plant growth occurs through the direct effect of T. harzianum on root development, in combination with indirect mechanisms, such as mineral solubilisation (including solubilisation via acidification, redox, chelation and hydrolysis).

PurposeTo evaluate prevalence and associated factors for myopia in high school students in Beijing.MethodsGrade 10 and 11 high school students were randomly selected from nine randomly selected districts of Beijing. The students underwent non-cylcoplegic auto-refractometry and an interview.ResultsOut of 4798 eligible students, 4677 (93.4%) students (mean age:16.9±0.7years;range:16-18 years) participated. Mean refractive error of right eyes and left eyes was -2.78±2.29 diopters and -2.59±2.50 diopters, respectively. Prevalence of myopia (defined as ≤ -1.00 diopters in the worse eye) was 80.7% (95% Confidence Interval (CI): 79.6-81.8%). Out of 3773 students with myopia, 1525 (40.4%) wore glasses daily. In multiple logistic regression analysis, a higher prevalence of myopia was associated with female sex (odds ratio (OR) = 1.31;95%CI:1.11-1.55), Han ethnicity (OR = 1.64;95%CI:1.28-2.11), attending key schools (OR = 1.48;95%CI:1.24,1.77), higher family income (OR = 1.37;95%CI:1.09-1.71), longer time spent for near work (OR = 1.43;95%CI:1.06-1.93), shorter near work distance (OR = 1.87;95%CI:1.55-2.26), lower frequency of active rest during studying (OR = 1.40;95%CI:1.16-1.70), and parental myopia (OR = 2.28;95%CI:1.80-2.87). The interaction between distance from near work and time spent for near work was statistically (P = 0.03) significant. In multiple logistic regression analysis, higher prevalence of high myopia (≤-6.0 diopters) was associated with studying in key schools (OR = 1.38;95%CI:1.05,1.81), lower frequency of active rest during studying (OR = 1.40;95%CI:1.09,1.79), and a higher number of myopic parents (OR = 2.66;95%CI:2.08,3.40).ConclusionsA prevalence of about 80% for myopia and a prevalence of about 10% for high myopia in students aged 16 to 18 years and attending classes of grade 10 and 11 in a Chinese metropolitan region is another example of the high prevalence of moderate and high myopia in metropolitan areas of China. With this young myopic generation getting older, myopia as cause for visual impairment and blindness may further increase in importance. Future studies may address whether active rests during studying with looking into the distance are preventive against myopia development or progression.

Relapsed, refractory lymphoma remains to be a challenge and lacks efficient treatment. Some tumor cells escape from treatment, become resistant to chemotherapeutic agents, and rapidly regenerate into large tumors. Lymphoma cells induce accumulation of Gr-1(+-)CD11b(+) myeloid derived suppressor cells (MDSCs) in lymphatic organs and their vicinity. MDSCs enable tumor cells to escape from immune cells mediated surveillance and attack. Gemcitabine is a chemotherapeutic agent that eliminates both tumor cells and MDSCs, improving the immune environment favorable for subsequent treatment. We evaluated the effects of low dose gemcitabine combined with intra-tumorally delivered dendritic cells (DCs) for the treatment of A20 large-size lymphoma. We showed that MDSCs increased markedly in lymphoma-bearing mice, and that gemcitabine significantly increased the apoptosis of MDSCs. Treatment of lymphoma with either gemcitabine or intra-tumoral DCs alone could not inhibit tumor growth or rescue lymphoma-bearing mice. Treatment of lymphoma with small dose gemcitabine followed by intra-tumorally injected DCs significantly improved the efficacy of either individual treatment by reducing MDSCs, inducing onsite DCs maturation, eliminating tumor cells, inhibiting tumor growth and relapse, and extending the survival of the lymphoma-bearing mice, partly through the induction of the IFNγ secreting cells and the activation of cytotoxic lymphocytes. We showed that NK cells and CD8(+ )T cells were the major effectors to mediate the inhibition of tumor growth. Thus, the observation that gemcitabine synergizes DCs mediated immunotherapy to improve the efficacy of large size lymphoma treatment provides an experimental basis for the combination of chemotherapy and immunotherapy for the efficient treatment of relapsed or refractory lymphoma.

Limited information is available regarding spatiotemporal variations of particles with median aerodynamic diameter < 2.5 μm (PM2.5) at high resolutions, and their relationships with meteorological factors in Beijing, China. This study aimed to detect spatiotemporal change patterns of PM2.5 from August 2013 to July 2014 in Beijing, and to assess the relationship between PM2.5 and meteorological factors.Daily and hourly PM2.5 data from the Beijing Environmental Protection Bureau (BJEPB) were analyzed separately. Ordinary kriging (OK) interpolation, time-series graphs, Spearman correlation coefficient and coefficient of divergence (COD) were used to describe the spatiotemporal variations of PM2.5. The Kruskal-Wallis H test, Bonferroni correction, and Mann-Whitney U test were used to assess differences in PM2.5 levels associated with spatial and temporal factors including season, region, daytime and day of week. Relationships between daily PM2.5 and meteorological variables were analyzed using the generalized additive mixed model (GAMM).Annual mean and median of PM2.5 concentrations were 88.07 μg/m3 and 71.00 μg/m3, respectively, from August 2013 to July 2014. PM2.5 concentration was significantly higher in winter (P < 0.0083) and in the southern part of the city (P < 0.0167). Day to day variation of PM2.5 showed a long-term trend of fluctuations, with 2-6 peaks each month. PM2.5 concentration was significantly higher in the night than day (P < 0.0167). Meteorological factors were associated with daily PM2.5 concentration using the GAMM model (R2 = 0.59, AIC = 7373.84).PM2.5 pollution in Beijing shows strong spatiotemporal variations. Meteorological factors influence the PM2.5 concentration with certain patterns. Generally, prior day wind speed, sunlight hours and precipitation are negatively correlated with PM2.5, whereas relative humidity and air pressure three days earlier are positively correlated with PM2.5.

Over the past decades, studies have reported that the combinatorial regulation of transcription factors (TFs) and microRNAs (miRNAs) is essential for the appropriate execution of biological events and developmental processes. Dysregulations of these regulators often cause diseases. However, there are no available resources on the regulatory cascades of TFs and miRNAs in the context of human diseases. To fulfill this vacancy, we established the TMREC database in this study. First, we integrated curated transcriptional and post-transcriptional regulations to construct the TF and miRNA regulatory network. Next, we identified all linear paths using the Breadth First Search traversal method. Finally, we used known disease-related genes and miRNAs to measure the strength of association between cascades and diseases. Currently, TMREC consists of 74,248 cascades and 25,194 cascade clusters, involving in 412 TFs, 266 miRNAs and 545 diseases. With the expanding of experimental support regulation data, we will regularly update the database. TMREC aims to help experimental biologists to comprehensively analyse gene expression regulation, to understand the aetiology and to predict novel therapeutic targets. TMREC is freely available at http://bioinfo.hrbmu.edu.cn/TMREC/.

To introduce a practical method of subretinal injection in mice and evaluate injection-induced retinal detachment (RD) and damage using a dynamic imaging system, electrophysiology, and histology.After full dilation of a 2-month-old C57BL/6J mouse pupil, the cornea near the limbus was punctured with a 30 ½-gague disposable beveled needle. A 33 ½-gauge blunt needle was inserted through the corneal perforation into the anterior chamber, avoiding the lens before going deeper into the vitreous cavity, and penetrating the inner retina to reach the subretinal space. The mice were divided into four groups: in group 1, about 80-100% of the retina was filled with subretinally injected solution; in group 2, approximately 50-70% of the retina was filled with injected solution; in group 3, the procedures were stopped before solution injection; and non-injected eyes were used as the negative control in group 4. An optical coherence tomography (OCT) imaging system was used to monitor retinal reattachment during the first three days following the injections. Histological and functional changes were examined by light microscopy and electroretinography (ERG) at five weeks post-injection.After a short-term training, a 70% success rate with 50% or more coverage (i.e., retinal blebs occupied 50% or more retinal area and filled with the injected solution) with minimal injection-related damages can be achieved. Bleb formation was associated with retinal detachment (RD) between the neuroretina and the retinal pigment epithelium (RPE) layer. Partial RD could be observed at post-injection day 1, and by day 2 most of the retina had reattached. At 5 weeks post-injection, compared to uninjected control group 4, the b-wave amplitudes of ERG decreased 22% in group 1, 16% in group 2, and 7% in group 3; the b-wave amplitudes were statistically different between the uninjected group and the groups with either 50-70% or 80-100% coverage. The subretinal injection-induced RD reattached and became stable at five weeks post-injection, although some photoreceptor damage could still be observed in and around the injection sites, especially in 80-100% coverage group.Trans-corneal subretinal injection is effective and practical, although subretinal injection-related damages can cause some morphological and functional loss.

OBJECTIVE:In China, policy and social taboo prevent unmarried adolescents from accessing sexual and reproductive health (SRH) services. Research is needed to determine the SRH needs of highly disadvantaged groups, such as adolescent female sex workers (FSWs). This study describes SRH knowledge, contraception use, pregnancy, and factors associated with unmet need for modern contraception among adolescent FSWs in Kunming, China. METHODS:A cross-sectional study using a one-stage cluster sampling method was employed to recruit adolescents aged 15 to 20 years, and who self-reported having received money or gifts in exchange for sex in the past 6 months. A semi-structured questionnaire was administered by trained peer educators or health workers. Multivariable logistic regression was conducted to determine correlates of low knowledge and unmet need for modern contraception. RESULTS:SRH knowledge was poor among the 310 adolescents surveyed; only 39% had heard of any long-acting reversible contraception (implant, injection or IUD). Despite 98% reporting not wanting to get pregnant, just 43% reported consistent condom use and 28% currently used another form of modern contraception. Unmet need for modern contraception was found in 35% of adolescents, and was associated with having a current non-paying partner, regular alcohol use, and having poorer SRH knowledge. Past abortion was common (136, 44%). In the past year, 76% had reported a contraception consultation but only 27% reported ever receiving SRH information from a health service. CONCLUSIONS:This study demonstrated a low level of SRH knowledge, a high unmet need for modern contraception and a high prevalence of unintended pregnancy among adolescent FSWs in Kunming. Most girls relied on condoms, emergency contraception, or traditional methods, putting them at risk of unwanted pregnancy. This study identifies an urgent need for Chinese adolescent FSWs to be able to access quality SRH information and effective modern contraception.

BACKGROUND:Evidence has shown that psoriasis is closely associated with infection; however, the mechanism of this association remains unclear. In mammalian cells, viral or bacterial infection is accompanied by the release of cytosolic DNA, which in turn triggers the production of type-I interferons (IFNs). Type I IFNs and their associated genes are significantly upregulated in psoriatic lesions. RIG-I is also highly upregulated in psoriatic lesions and is responsible for IFN production. However, RIG-I mediated regulatory signaling in psoriasis is poorly understood. METHODS:We screened a cDNA library and identified potential RIG-I interacting partners that may play a role in psoriasis. RESULTS:We found that serine/arginine-rich splicing factor 1 (SRSF1) could specifically interact with RIG-I to facilitate RIG-I mediated production of type-I IFN that is triggered by cytosolic DNA. We found SRSF1 associates with RNA polymerase III and RIG-I in a DNA-dependent manner. In addition, treatment with a TNFα inhibitor downregulated SRSF1 expression in peripheral blood mononuclear cells (PBMCs) from psoriasis vulgaris patients. DISCUSSION:Based on the abundance of pathogenic cytosolic DNA that is detected in psoriatic lesions, our finding that RIG-I interacts with SRSF1 to regulate type-I IFN production reveals a critical link regarding how cytosolic DNA specifically activates aberrant IFN expression. These data may provide new therapeutic targets for the treatment of psoriasis.

Traditional Chinese medicine (TCM) including Chinese herbal therapy has been widely practiced in China. However, little is known about Chinese herbal therapy use for hypertension management, which is one of the most prevalent chronic conditions in China. Thus we described Chinese herbal therapy and western drug users, beliefs, hypertension knowledge, and Chinese herbal and western drug adherence and determinants of Chinese herbal therapy use among patients with hypertension in rural areas of Heilongjiang Province, China.This face-to-face cross sectional survey included 665 hypertensive respondents aged 30 years or older in rural areas of Heilongjiang Province, China. Of 665 respondents, 39.7% were male, 27.4% were aged 65 years or older. At the survey, 14.0% reported using Chinese herbal therapy and 71.3% reported using western drug for hypertension management. A majority of patients had low level of treatment adherence (80.6% for the Chinese herbal therapy users and 81.2% for the western drug users). When respondents felt that their blood pressure was under control, 72.0% of the Chinese herbal therapy users and 69.2% of the western drug users sometimes stopped taking their medicine. Hypertensive patients with high education level or better quality of life are more likely use Chinese herbal therapy.Majority of patients diagnosed with hypertension use western drugs to control blood pressure. Chinese herbal therapy use was associated with education level and quality of life.

Astragaloside IV (AGS-IV) is a main active ingredient of Astragalus membranaceus Bunge, a medicinal herb prescribed as an immunostimulant, hepatoprotective, antiperspirant, a diuretic or a tonic as documented in Chinese Materia Medica. In the present study, we employed a high-throughput comparative proteomic approach based on 2D-nano-LC-MS/MS to investigate the possible mechanism of action involved in the neuroprotective effect of AGS-IV against glutamate-induced neurotoxicity in PC12 cells. Differential proteins were identified, among which 13 proteins survived the stringent filter criteria and were further included for functional discussion. Two proteins (vimentin and Gap43) were randomly selected, and their expression levels were further confirmed by western blots analysis. The results matched well with those of proteomics. Furthermore, network analysis of protein-protein interactions (PPI) and pathways enrichment with AGS-IV associated proteins were carried out to illustrate its underlying molecular mechanism. Proteins associated with signal transduction, immune system, signaling molecules and interaction, and energy metabolism play important roles in neuroprotective effect of AGS-IV and Raf-MEK-ERK pathway was involved in the neuroprotective effect of AGS-IV against glutamate-induced neurotoxicity in PC12 cells. This study demonstrates that comparative proteomics based on shotgun approach is a valuable tool for molecular mechanism studies, since it allows the simultaneously evaluate the global proteins alterations.

BACKGROUND AND PURPOSE:Diffusion-weighted imaging (DWI) and perfusion MRI were used to examine the spatiotemporal evolution of stroke lesions in adult macaques with ischemic occlusion. METHODS:Permanent MCA occlusion was induced with silk sutures through an interventional approach via the femoral artery in adult rhesus monkeys (n = 8, 10-21 years old). The stroke lesions were examined with high-resolution DWI and perfusion MRI, and T2-weighted imaging (T2W) on a clinical 3T scanner at 1-6, 48, and 96 hours post occlusion and validated with H&E staining. RESULTS:The stroke infarct evolved via a natural logarithmic pattern with the mean infarct growth rate = 1.38 ± 1.32 ml per logarithmic time scale (hours) (n = 7) in the hyperacute phase (1-6 hours). The mean infarct volume after 6 hours post occlusion was 3.6±2.8 ml (n = 7, by DWI) and increased to 3.9±2.9 ml (n = 5, by T2W) after 48 hours, and to 4.7±2.2ml (n = 3, by T2W) after 96 hours post occlusion. The infarct volumes predicted by the natural logarithmic function were correlated significantly with the T2W-derived lesion volumes (n = 5, r = 0.92, p = 0.01) at 48 hours post occlusion. The final infarct volumes derived from T2W were correlated significantly with those from H&E staining (r = 0.999, p < 0.0001, n = 4). In addition, the diffusion-perfusion mismatch was visible generally at 6 hours but nearly diminished at 48 hours post occlusion. CONCLUSION:The infarct evolution follows a natural logarithmic pattern in the hyperacute phase of stroke. The logarithmic pattern of evolution could last up to 48 hours after stroke onset and may be used to predict the infarct volume growth during the acute phase of ischemic stroke. The nonhuman primate model, MRI protocols, and post data processing strategy may provide an excellent platform for characterizing the evolution of acute stroke lesion in mechanistic studies and therapeutic interventions of stroke disease.

Nodal/TGF signaling pathway has an important effect at early stages of differentiation of human embryonic stem cells in directing them to develop into different embryonic lineages. SMAD3 is a key intracellular messenger regulating factor in the Nodal/TGF signaling pathway, playing important roles in embryonic and, particularly, cardiovascular system development. The aim of this work was to find evidence on whether SMAD3 variations might be associated with ventricular septal defects (VSD) or other congenital heart diseases (CHD).We sequenced the SMAD3 gene for 372 Chinese Han CHD patients including 176 VSD patients and evaluated SNP rs2289263, which is located before the 5'UTR sequence of the gene. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 13.0). The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE.Three heterozygous variants in SMAD3 gene, rs2289263, rs35874463 and rs17228212, were identified. Statistical analyses showed that the rs2289263 variant located before the 5'UTR sequence of SMAD3 gene was associated with the risk of VSD (P value=0.013

Recently, the stable light products and radiance calibrated products from Defense Meteorological Satellite Program's (DMSP) Operational Linescan System (OLS) have been useful for mapping global fossil fuel carbon dioxide (CO2) emissions at fine spatial resolution. However, few studies on this subject were conducted with the new-generation nighttime light data from the Visible Infrared Imaging Radiometer Suite (VIIRS) sensor on the Suomi National Polar-orbiting Partnership (NPP) Satellite, which has a higher spatial resolution and a wider radiometric detection range than the traditional DMSP-OLS nighttime light data. Therefore, this study performed the first evaluation of the potential of NPP-VIIRS data in estimating the spatial distributions of global CO2 emissions (excluding power plant emissions). Through a disaggregating model, three global emission maps were then derived from population counts and three different types of nighttime lights data (NPP-VIIRS, the stable light data and radiance calibrated data of DMSP-OLS) for a comparative analysis. The results compared with the reference data of land cover in Beijing, Shanghai and Guangzhou show that the emission areas of map from NPP-VIIRS data have higher spatial consistency of the artificial surfaces and exhibit a more reasonable distribution of CO2 emission than those of other two maps from DMSP-OLS data. Besides, in contrast to two maps from DMSP-OLS data, the emission map from NPP-VIIRS data is closer to the Vulcan inventory and exhibits a better agreement with the actual statistical data of CO2 emissions at the level of sub-administrative units of the United States. This study demonstrates that the NPP-VIIRS data can be a powerful tool for studying the spatial distributions of CO2 emissions, as well as the socioeconomic indicators at multiple scales.

Recent studies have suggested that miR-590 may play critical roles in cardiovascular disease. This study was designed to determine the effects of miR-590 on lipoprotein lipase (LPL) expression and development of atherosclerosis in apolipoprotein E knockout (apoE-/-) mice and explore the potential mechanisms. En face analysis of the whole aorta revealed that miR-590 significantly decreased aortic atherosclerotic plaque size and lipid content in apoE-/- mice. Double immunofluorescence staining in cross-sections of the proximal aorta showed that miR-590 agomir reduced CD68 and LPL expression in macrophages in atherosclerotic lesions. MiR-590 agomir down-regulated LPL mRNA and protein expression as analyzed by RT-qPCR and western blotting analyses, respectively. Consistently, miR-590 decreased the expression of CD36 and scavenger receptor A1 (SRA1) mRNA and protein. High-performance liquid chromatography (HPLC)analysis confirmed that treatment with miR-590 agomir reduced lipid levels either in plasma orinabdominal cavity macrophages of apoE-/- mice. ELISA analysis showed that miR-590 agomir decreased plasma levels of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), interleukin-1β (IL-1β)and interleukin-6 (IL-6). In contrast, treatment with miR-590 antagomir prevented or reversed these effects. Taken together, these results reveal a novel mechanism of miR-590 effects, and may provide new insights into the development of strategies for attenuating lipid accumulation and pro-inflammatory cytokine secretion.

Cats are obligate carnivores and under most circumstances eat only animal products. Owing to the pseudogenization of one of two subunits of the sweet receptor gene, they are indifferent to sweeteners, presumably having no need to detect plant-based sugars in their diet. Following this reasoning and a recent report of a positive correlation between the proportion of dietary plants and the number of Tas2r (bitter receptor) genes in vertebrate species, we tested the hypothesis that if bitter perception exists primarily to protect animals from poisonous plant compounds, the genome of the domestic cat (Felis catus) should have lost functional bitter receptors and they should also have reduced bitter receptor function. To test functionality of cat bitter receptors, we expressed cat Tas2R receptors in cell-based assays. We found that they have at least 7 functional receptors with distinct receptive ranges, showing many similarities, along with some differences, with human bitter receptors. To provide a comparative perspective, we compared the cat repertoire of intact receptors with those of a restricted number of members of the order Carnivora, with a range of dietary habits as reported in the literature. The numbers of functional bitter receptors in the terrestrial Carnivora we examined, including omnivorous and herbivorous species, were roughly comparable to that of cats thereby providing no strong support for the hypothesis that a strict meat diet influences bitter receptor number or function. Maintenance of bitter receptor function in terrestrial obligate carnivores may be due to the presence of bitter compounds in vertebrate and invertebrate prey, to the necessary role these receptors play in non-oral perception, or to other unknown factors. We also found that the two aquatic Carnivora species examined had fewer intact bitter receptors. Further comparative studies of factors driving numbers and functions of bitter taste receptors will aid in understanding the forces shaping their repertoire.

The human heart consists of several cell types with distinct lineage origins. Interactions between these cardiac progenitors are very important for heart formation. The muscle segment homeobox gene family plays a key role in the cell morphogenesis and growth, controlled cellular proliferation, differentiation, and apoptosis, but the relationships between the genetic abnormalities and CHD phenotypes still remain largely unknown. The aim of this work was to evaluate variations in MSX1 and MSX2 for their possible associations with CHD.We sequenced the MSX1 and MSX2 genes for 300 Chinese Han CHD patients and 400 normal controls and identified the variations. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 19.0). The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE.Six variations rs4647952, rs2048152, rs4242182, rs61739543, rs111542301 and rs3087539 were identified in the MSX2 gene, but the genetic heterozygosity of those SNPs was very low. In contrast, the genetic heterozygosity of two variations rs3821949 near the 5'UTR and rs12532 within 3'UTR of the MSX1 gene was considerably high. Statistical analyses showed that rs3821949 and rs12532 were associated with the risk of CHD (specifically VSD).The SNPs rs3821949 and rs12532 in the MSX1 gene were associated with CHD in Chinese Han populations.

Human uveitis is a type of T cell-mediated autoimmune disease that often shows relapse-remitting courses affecting multiple biological processes. As a cytoplasmic process, autophagy has been seen as an adaptive response to cell death and survival, yet the link between autophagy and T cell-mediated autoimmunity is not certain. In this study, based on the differentially expressed genes (GSE19652) between the recurrent versus monophasic T cell lines, whose adoptive transfer to susceptible animals may result in respective recurrent or monophasic uveitis, we proposed grouping annotations on a subcellular layered interactome framework to analyze the specific bioprocesses that are linked to the recurrence of T cell autoimmunity. That is, the subcellular layered interactome was established by the Cytoscape and Cerebral plugin based on differential expression, global interactome, and subcellular localization information. Then, the layered interactomes were grouping annotated by the ClueGO plugin based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The analysis showed that significant bioprocesses with autophagy were orchestrated in the cytoplasmic layered interactome and that mTOR may have a regulatory role in it. Furthermore, by setting up recurrent and monophasic uveitis in Lewis rats, we confirmed by transmission electron microscopy that, in comparison to the monophasic disease, recurrent uveitis in vivo showed significantly increased autophagy activity and extended lymphocyte infiltration to the affected retina. In summary, our framework methodology is a useful tool to disclose specific bioprocesses and molecular targets that can be attributed to a certain disease. Our results indicated that targeted inhibition of autophagy pathways may perturb the recurrence of uveitis.

Histone H3 lysine 36 (H3K36) methylation is known to be associated with transcriptionally active genes, and is considered a genomic marker of active loci. To investigate the changes in H3K36 methylation in pig, we determined the mono-, di-, and tri-methylations of H3K36 (H3K36me1, H3K36me2 and H3K36me3, respectively) in porcine fetal fibroblasts, oocytes and preimplantation embryos by immunocytochemistry using specific antibodies and confocal microscopy. These analyses revealed that only H3K36me3 in porcine fetal fibroblasts consistently colocalized with transcription sites identified as actively synthesizing RNA based on fluorouridine (FU) incorporation. Treatment of cells with flavopiridol, which blocks transcription elongation, completely abrogated both H3K36me3 signals and RNA synthesis. All three types of H3K36 methylation were present and did not significantly differ during oocyte maturation. In parthenogenetic embryos, H3K36me1 and -me2 were detected in 1-cell through blastocyst-stage embryos. In contrast, H3K36me3 was not detected in most 1-cell stage embryos. H3K36me3 signals became detectable in 2-cell stage embryos, peaked at the 4-cell stage, decreased at the 8-cell stage, and then became undetectable at blastocyst stages in both parthenogenetic and in vitro-fertilized (IVF) embryos. Unlike the case in IVF embryos, H3K36me3 could not be demethylated completely during the 1-cell stage in somatic cell nuclear transfer (SCNT) embryos. These results collectively indicate that H3K36me3, but not H3K36me1 or -me2, is associated with transcription elongation in porcine fetal fibroblasts. H3K36me3 is developmentally regulated and may be a histone mark of embryonic gene activation in pig. Aberrant H3K36 tri-methylation occurred during the nuclear reprogramming of SCNT embryos.

A growing body of behavioral and genetic information indicates that taste perception and food sources are highly coordinated across many animal species. For example, sweet taste perception is thought to serve to detect and motivate consumption of simple sugars in plants that provide calories. Supporting this is the observation that most plant-eating mammals examined exhibit functional sweet perception, whereas many obligate carnivores have independently lost function of their sweet taste receptors and exhibit no avidity for simple sugars that humans describe as tasting sweet. As part of a larger effort to compare taste structure/function among species, we examined both the behavioral and the molecular nature of sweet taste in a plant-eating animal that does not consume plants with abundant simple sugars, the giant panda (Ailuropoda melanoleuca). We evaluated two competing hypotheses: as plant-eating mammals, they should have a well-developed sweet taste system; however, as animals that do not normally consume plants with simple sugars, they may have lost sweet taste function, as has occurred in strict carnivores. In behavioral tests, giant pandas avidly consumed most natural sugars and some but not all artificial sweeteners. Cell-based assays revealed similar patterns of sweet receptor responses toward many of the sweeteners. Using mixed pairs of human and giant panda sweet taste receptor units (hT1R2+gpT1R3 and gpT1R2+hT1R3) we identified regions of the sweet receptor that may account for behavioral differences in giant pandas versus humans toward various sugars and artificial sweeteners. Thus, despite the fact that the giant panda's main food, bamboo, is very low in simple sugars, the species has a marked preference for several compounds that taste sweet to humans. We consider possible explanations for retained sweet perception in this species, including the potential extra-oral functions of sweet taste receptors that may be required for animals that consume plants.