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BackgroundSalidroside (SAL), the main component of Rhodiola rosea extract, is a flavonoid with biological activities, such as antioxidative stress, anti-inflammatory, and hypolipidemic. In this study, the potential therapeutic targets and mechanisms of SAL against oxidative stress in retinal ganglion cells (RGCs) were investigated on the basis of in-vitro experiments, network pharmacology, and molecular docking techniques.MethodsRGC oxidative stress models were constructed, and cell activity, reactive oxygen species (ROS), and apoptosis levels were examined for differences. The genes corresponding to rhodopsin, RGCs, and oxidative stress were screened from GeneCards, TCMSP database, and an analysis platform. The intersection of the three was taken, and a Venn diagram was drawn. Protein interactions, GO functional enrichment, and KEGG pathway enrichment data were analyzed by STRING database, Cytohubba plugin, and Metascape database. The key factors in the screening pathway were validated using qRT-PCR. Finally, molecular docking prediction was performed using MOE 2019 software, molecular dynamic simulations was performed using Gromacs 2018 software.ResultsIn the RGC oxidative stress model in vitro, the cell activity was enhanced, ROS was reduced, and apoptosis was decreased after SAL treatment. A total of 16 potential targets of oxidative stress in SAL RGCs were obtained, and the top 10 core targets were screened by network topology analysis. GO analysis showed that SAL retinal oxidative stress treatment mainly involved cellular response to stress, transcriptional regulatory complexes, and DNA-binding transcription factor binding. KEGG analysis showed that most genes were mainly enriched in multiple cancer pathways and signaling pathways in diabetic complications, nonalcoholic fatty liver, and lipid and atherosclerosis. Validation by PCR, molecular docking and molecular dynamic simulations revealed that SAL may attenuate oxidative stress and reduce apoptosis in RGCs by regulating SIRT1, NRF2, and NOS3.ConclusionThis study initially revealed the antioxidant therapeutic effects and molecular mechanisms of SAL on RGCs, providing a theoretical basis for subsequent studies.

With the world population growth, energy consumption and the rapid development of industrial economy, a large amount of carbon emissions has brought destruction and threats to the earth's environment on which human beings depend. The development of low-carbon economy has become the consensus of governments all over the world and has been vigorously advocated & promoted. This paper focuses on the top five global GDP nations in 2022: The United States, China, Japan, Germany, and Britain. A comprehensive evaluation index system of urban low-carbon economic development level is constructed from four dimensions: economic development level, environmental quality, energy consumption emission intensity and social development speed by using literature review and field interview. The evaluation measures are determined using the TOPSIS evaluation method with entropy weight and the grey relational model, providing a comprehensive assessment of the low-carbon economy's development level in these five countries." Judging from the comprehensive evaluation score, the overall development of low-carbon economy in American cities is in good condition and has reached the development standard of low-carbon economy; Germany and Japan rank second and third, and they are low-carbon economies. Britain ranks fourth in comprehensive evaluation, although it belongs to a low-carbon economy country, but there is still a certain gap with Germany and Japan; There is still a big gap between China and the other four countries. Based on the measurement and evaluation outcomes, it presents recommendations and strategies to foster the growth of low-carbon economies, offering valuable insights for the advancement of such economies across different nations. The research results guide countries all over the world to reduce carbon emissions in the process of economic development, protect the earth environment on which human beings depend, and make a better tomorrow for sustainable development.

This study aimed to investigate the cause of a foodborne disease outbreak in Huzhou on August 14, 2023. Multiple enteropathogens were detected using FilmArray, and the pathogen was subsequently isolated and cultured from anal swabs of the cases and stream water. The isolated strains were identified using VITEK MS, and antimicrobial susceptibility test, pulsed field gel electrophoresis (PFGE) molecular typing, and whole genome sequencing (WGS) were performed on the isolates of Plesiomonas shigelloides. Gene annotation and sequence alignment were used to analyze the virulence genes and drug resistance genes of the strains. A phylogenetic tree was constructed based on single nucleotide polymorphism (SNP), and homology analysis was conducted to trace the origin of P. shigelloides. A total of 7 strains of P.shigelloides were isolated, with 3 from stream water and 4 from anal swabs. All 7 strains exhibited the same PFGE pattern and showed resistance to amikacin, trimethoprim-sulfamethoxazole, chloramphenicol, tetracycline, cefazolin, streptomycin, and florfenicol. The isolated strains carried the same resistance genes and virulence factors. In the sequences of the isolated strains from this outbreak, 11 mutation sites were detected. The phylogenetic tree based on SNP sites showed that these strains were homologous. This foodborne disease outbreak caused by P.shigelloides was the first reported in Huzhou. WGS can be used as a complementary method to PFGE for epidemiological investigations of disease outbreaks.

Under the background of global climate change, rainstorm and flood disasters have become the most serious cataclysm. Under the circumstances of an increasingly severe risk situation, it is necessary to enhance urban disaster resilience. Based on the disaster resilience process of prevention, absorption, and enhancement, and considering the safety factors such as personnel, facility, environment and management, this paper forms a dual dimension of the urban disaster resilience assessment model covering the key elements of urban disaster response and the core capacity of urban disaster recovery. Furthermore, if taking into account the characteristics of rainstorm and flood disasters, the paper screens the key indicators to build up an assessment index system of an urban rainstorm and flood disaster. The practical application was implemented in Beijing to have an assessment of the ability to recover from rainstorm and flood disasters in all districts of Beijing. And then, some pertinent suggestions for enhancing the resilience of Beijing to rainstorm and flood disasters were proposed.

Chronic low-grade inflammation is regarded to an important signature of atherosclerosis (AS). Macrophage (Mψ) and related polarization have been demonstrated to play a crucial role in the occurrence and development of AS inflammation. Butyrate, a bioactive molecule produced by the intestinal flora, has been increasingly demonstrated to exhibit a vital role for regulating the inflammation in chronic metabolic diseases. However, the effectiveness and multiple anti-inflammation mechanisms of butyrate on AS still need to be further understood. ApoE-/- mice fed with high-fat diet as AS model were administered with sodium butyrate (NaB) for 14 weeks of treatment. Our results showed that the atherosclerotic lesion in the AS group was dramatically reduced after NaB intervention. Moreover, deteriorated routine parameters of AS including body weights (BWs), low-density lipoprotein (LDL-C), triglyceride (TG), total cholesterol (TC) were significantly reversed by NaB administration. Abnormal elevated plasma and aorta pro-inflammatory indicators including interleukin (IL)-1β, IL-6, IL-17A, tumor necrosis factor (TNF)-α and lipopolysaccharide (LPS), as well as reduced anti-inflammatory IL-10 in plasma were respectively rectified after NaB administration. Consistently, accumulated Mψ and associated imbalance of polarization in the arota were attenuated with NaB treatment. Importantly, we demonstrated that the suppression of Mψ and associated polarization of NaB was dependent on binding G-protein coupled receptor (GPR) and inhibiting histone deacetylase HDAC3. Moreover, we found that intestinal butyrate-producing bacteria, anti-inflammatory bacteria and intestinal tight junction protein zonula occludens-1 (ZO)-1 may contribute to this effectiveness. Intriguingly, according to transcriptome sequencing of atherosclerotic aorta, 29 elevated and 24 reduced miRNAs were found after NaB treatment, especially miR-7a-5p, suggesting that non-coding RNA may possess a potential role in the protection of NaB against AS. Correlation analysis showed that there were close complicated interactions among gut microbiota, inflammation and differential miRNAs. Collectively, this study revealed that dietary NaB may ameliorate atherosclerotic inflammation by regulating Mψ polarization via GPR43/HDAC-miRNAs axis in ApoE-/- mice.

BackgroundAs the world's largest coal producer, China was accounted for about 46% of global coal production. Among present coal mining risks, methane gas (called gas in this paper) explosion or ignition in an underground mine remains ever-present. Although many techniques have been used, gas accidents associated with the complex elements of underground gassy mines need more robust monitoring or warning systems to identify risks. This paper aimed to determine which single method between the PCA and Entropy methods better establishes a responsive weighted indexing measurement to improve coal mining safety.MethodsQualitative and quantitative mixed research methodologies were adopted for this research, including analysis of two case studies, correlation analysis, and comparative analysis. The literature reviewed the most-used multi-criteria decision making (MCDM) methods, including subjective methods and objective methods. The advantages and disadvantages of each MCDM method were briefly discussed. One more round literature review was conducted to search publications between 2017 and 2019 in CNKI. Followed two case studies, correlation analysis and comparative analysis were then conducted. Research ethics was approved by the Shanxi Coking Coal Group Research Committee.ResultsThe literature searched a total of 25,831publications and found that the PCA method was the predominant method adopted, and the Entropy method was the second most widely adopted method. Two weighting methods were compared using two case studies. For the comparative analysis of Case Study 1, the PCA method appeared to be more responsive than the Entropy. For Case Study 2, the Entropy method is more responsive than the PCA. As a result, both methods were adopted for different cases in the case study mine and finally deployed for user acceptance testing on 5 November 2020.ConclusionsThe findings and suggestions were provided as further scopes for further research. This research indicated that no single method could be adopted as the better option for establishing indexing measurement in all cases. The practical implication suggests that comparative analysis should always be conducted on each case and determine the appropriate weighting method to the relevant case. This research recommended that the PCA method was a dimension reduction technique that could be handy for identifying the critical variables or factors and effectively used in hazard, risk, and emergency assessment. The PCA method might also be well-applied for developing predicting and forecasting systems as it was sensitive to outliers. The Entropy method might be suitable for all the cases requiring the MCDM. There is also a need to conduct further research to probe the causal reasons why the PCA and Entropy methods were applied to each case and not the other way round. This research found that the Entropy method provides higher accuracy than the PCA method. This research also found that the Entropy method demonstrated to assess the weights of the higher dimension dataset was higher sensitivity than the lower dimensions. Finally, the comprehensive analysis indicates a need to explore a more responsive method for establishing a weighted indexing measurement for warning applications in hazard, risk, and emergency assessments.

Material decomposition (MD) is an important application of computer tomography (CT). For phase contrast imaging, conventional MD methods are categorized into two types with respect to different operation sequences, i.e., "before" or "after" image reconstruction. Both categories come down to two-step methods, which have the problem of noise amplification. In this study, we incorporate both phase and absorption (PA) information into MD process, and correspondingly develop a simultaneous algebraic reconstruction technique (SART). The proposed method is referred to as phase & absorption material decomposition-SART (PAMD-SART). By iteratively solving an optimization problem, material composition and substance quantification are reconstructed directly from absorption and differential phase projections. Comparing with two-step MD, the proposed one-step method is superior in noise suppression and accurate decomposition. Numerical simulations and synchrotron radiation based experiments show that PAMD-SART outperforms the classical MD method (image-based and dual-energy CT iterative method), especially for the quantitative accuracy of material equivalent atomic number.

Background and objectiveAccumulating evidence shows that long noncoding RNAs (lncRNAs) possess great potential in the diagnosis and prognosis of prostate cancer (PCa). Therefore, this study aimed to construct an lncRNA-based signature to more accurately predict the prognosis of different PCa patients, so as to improve patient management and prognosis.MethodsThrough univariate and multivariate Cox regression analysis, this study constructed a 4 lncRNAs-based prognosis nomogram for the classification and prediction of survival risk in patients with PCa based on TCGA data. Then we used the data of TCGA and ICGC to verify the performance of our prediction model. The receiver operating characteristic curve was plotted for detecting and validating our prediction model sensitivity and specificity. In addition, Cox regression analysis was conducted to examine whether the signature's prediction ability was independent of additional clinicopathological variables. Possible biological functions for those prognostic lncRNAs were predicted on those 4 protein-coding genes (PCGs) related to lncRNAs.ResultsFour lncRNAs (HOXB-AS3, YEATS2-AS1, LINC01679, PRRT3-AS1) were extracted after COX regression analysis for classifying patients into high and low-risk groups by different OS rates. As suggested by ROC analysis, our proposed model showed high sensitivity and specificity. Independent prognostic capability of the model from other clinicopathological factors was indicated through further analysis. Based on functional enrichment, those action sites for prognostic lncRNAs were mostly located in the extracellular matrix and cell membrane, and their functions are mainly associated with the adhesion, activation and transport of the components across the extracellular matrix or cell membrane.ConclusionOur current study successfully identifies a novel candidate, which can provide more convincing evidence for prognosis in addition to the traditional clinicopathological indicators to predict the PCa survival, and laying the foundation for offering potentially novel therapeutic treatment. Additionally, this study sheds more lights on the PCa-related molecular mechanisms.

With the development of economic integration, Beijing has become more closely connected with surrounding areas, which gradually formed the Beijing metropolitan area (BMA). The authors define the scope of BMA from two dimensions of space and time. BMA is determined to be the built-up area of Beijing and its surrounding 10 districts. Designed questionnaire survey the personal characteristics, family characteristics, and travel characteristics of residents from 10 districts in the surrounding BMA. The statistical analysis of questionnaires shows that the supply of public transportation is insufficient and cannot meet traffic demand. Further, the travel mode prediction model of Softmax regression machine learning algorithm for BMA (SRBM) is established. To further verify the prediction performance of the proposed model, the Multinomial Logit Model (MNL) and Support Vector Machine (SVM), model are introduced to compare the prediction accuracy. The results show that the constructed SRBM model exhibits high prediction accuracy, with an average accuracy of 88.35%, which is 2.83% and 18.11% higher than the SVM and MNL models, respectively. This article provides new ideas for the prediction of travel modes in the Beijing metropolitan area.

Next Generation Sequencing (NGS) is a powerful tool getting into the field of clinical examination. Its preliminary application in pre-implantation comprehensive chromosomal screening (PCCS) of assisted reproduction (test-tube baby) has shown encouraging outcomes that improves the success rate of in vitro fertilization. However, the conventional NGS library construction is time consuming. In addition with the whole genome amplification (WGA) procedure in prior, makes the single cell NGS assay hardly be accomplished within an adequately short turnover time in supporting fresh embryo implantation. In this work, we established a concise single cell sequencing protocol, ChromInst, in which the single cell WGA and NGS library construction were integrated into a two-step PCR procedure of ~ 2.5hours reaction time. We then validated the feasibility of ChromInst for overnight PCCS assay by examining 14 voluntary donated embryo biopsy samples in a single sequencing run of Miseq with merely 13M reads production. The good compatibility of ChromInst with the restriction of Illumina sequencing technique along with the good library yield uniformity resulted superior data usage efficiency and reads distribution evenness that ensures precisely distinguish of 6 normal embryos from 8 abnormal one with variable chromosomal aneuploidy. The superior succinctness and effectiveness of this protocol permits its utilization in other time limited single cell NGS applications.

Emulsified volatile anesthetic can be directly injected into the circulation and eliminated from blood through lungs. Taking advantage of the unique pharmacokinetics of the emulsified volatile anesthetics, we aimed to develop a less traumatic method to differentially deliver them to the spinal cord of rabbit. Sixteen New Zealand White rabbits were randomly assigned to the isoflurane or sevoflurane group. A catheter was placed into the descending aorta, and emulsified isoflurane (8mg/kg/h) or sevoflurane (12mg/kg/h) was given respectively. The concentration and partial pressure of the anesthetics in the jugular and femoral vein were measured. Our results showed that the partial pressure for isoflurane was 3.91±1.11 mmHg and 12.61±1.60 mmHg (1.0MAC), and for sevoflurane was 3.89±1.00 mmHg and 19.92±1.84mmHg (1.0MAC), in the jugular vein and femoral vein, respectively. There was significant difference between jugular and femoral vein partial pressure for both isoflurane and sevoflurane groups (both P < 0.001). In conclusion, a simple and minimally invasive method has been successfully developed to selectively deliver isoflurane and sevoflurane to the spinal cord in the rabbit. Before the anesthetics taking action on the brain, 69% of isoflurane and 81% of sevoflurane were removed through lungs. This method can be used to investigate sites and mechanisms of volatile anesthetic action.

The multi-domain protein UHRF1 is essential for DNA methylation maintenance and binds DNA via a base-flipping mechanism with a preference for hemi-methylated CpG sites. We investigated its binding to hemi- and symmetrically modified DNA containing either 5-methylcytosine (mC), 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC), or 5-carboxylcytosine (caC). Our experimental results indicate that UHRF1 binds symmetrically carboxylated and hybrid methylated/carboxylated CpG dyads in addition to its previously reported substrates. Complementary molecular dynamics simulations provide a possible mechanistic explanation of how the protein could differentiate between modification patterns. First, we observe different local binding modes in the nucleotide binding pocket as well as the protein's NKR finger. Second, both DNA modification sites are coupled through key residues within the NKR finger, suggesting a communication pathway affecting protein-DNA binding for carboxylcytosine modifications. Our results suggest a possible additional function of the hemi-methylation reader UHRF1 through binding of carboxylated CpG sites. This opens the possibility of new biological roles of UHRF1 beyond DNA methylation maintenance and of oxidised methylcytosine derivates in epigenetic regulation.

OBJECTIVE:Hepatocellular carcinoma (HCC) has become a pressing health problem facing the world today due to its high morbidity, high mortality, and late discovery. As a diagnostic criteria of HCC, the exact threshold of Alpha-fetoprotein (AFP) is controversial. Therefore, this study was aimed to systematically estimate the performance of AFP in diagnosing HCC and to clarify its optimal threshold. METHODS:Medline and Embase databases were searched for articles indexed up to November 2019. English language studies were included if both the sensitivity and specificity of AFP in the diagnosis of HCC were provided. The basic information and accuracy data included in the studies were extracted. Combined estimates for sensitivity and specificity were statistically analyzed by random-effects model using MetaDisc 1.4 and Stata 15.0 software at the prespecified threshold of 400 ng/mL, 200 ng/mL, and the range of 20-100 ng/mL. The optimal threshold was evaluated by the area under curve (AUC) of the summary receiver operating characteristic (SROC). RESULTS:We retrieved 29,828 articles and included 59 studies and 1 review with a total of 11,731 HCC cases confirmed by histomorphology and 21,972 control cases without HCC. The included studies showed an overall judgment of at risk of bias. Four studies with AFP threshold of 400 ng/mL showed the summary sensitivity and specificity of 0.32 (95%CI 0.31-0.34) and 0.99 (95%CI 0.98-0.99), respectively. Four studies with AFP threshold of 200 ng/mL showed the summary sensitivity and specificity of 0.49 (95%CI 0.47-0.50) and 0.98 (95%CI 0.97-0.99), respectively. Forty-six studies with AFP threshold of 20-100 ng/mL showed the summary sensitivity and specificity of 0.61 (95%CI 0.60-0.62) and 0.86 (95%CI 0.86-0.87), respectively. The AUC of SROC and Q index of 400 ng/mL threshold were 0.9368 and 0.8734, respectively, which were significantly higher than those in 200 ng/mL threshold (0.9311 and 0.8664, respectively) and higher than those in 20-100 ng/mL threshold (0.8330 and 0.7654, respectively). Furthermore, similar result that favored 400 ng/mL were shown in the threshold in terms of AFP combined with ultrasound. CONCLUSION:AFP levels in serum showed good accuracy in HCC diagnosis, and the threshold of AFP with 400 ng/mL was better than that of 200 ng/mL in terms of sensitivity and specificity no matter AFP is used alone or combined with ultrasound.

Endophytic fungi play an important role in plant growth. The composition and structure of endophytes vary in different plant tissues, which are specific habitats for endophyte colonization. To analyze the diversity and structural composition of endophytic fungi from toothed clubmoss (Huperzia serrata) that was artificially cultivated for 3 years, we investigated endophytic fungi from the roots, stems and leaves using comparative sequence analysis of the ITS2 region of the fungal rRNA genes sequenced with high-throughput sequencing technology. Seven fungal phyla were identified, and fungal diversity and structure varied across different tissues, with the most distinctive community features found in the roots. A total of 555 operational taxonomic units (OTUs) were detected, and 198 were common to all samples, and 43, 16, 16 OTUs were unique to the root, stem, leaf samples, respectively. Taxonomic classification showed that Ascomycota and Basidiomycota were dominant phyla, and Cladosporium, Oidiodendron, Phyllosticta, Sebacina and Ilyonectria were dominant genera. The relative abundance heat map at the genus level suggested that H. serrata had characteristic endophytic fungal microbiomes. Line discriminant analysis effect size analysis and principal coordinate analysis demonstrated that fungal communities were tissue-type and tissue-site specific. Overall, our study provides new insights into the complex composition of endophytic fungi in H. serrata.

AimThis study aimed to explore factors may affect the length of hospital stay after laparoscopic appendectomy.MethodsThe data of 636 patients undergoing laparoscopic appendectomy between July 2016 and July 2019 in Beijing Tsinghua Changgung Hospital were retrospectively analyzed. The patients were divided into group A (hospital stay ≤3 days, 348 patients) and group B (hospital stay >3 days, 288 patients) according to their hospital stay.Sex, age, disease onset time(time from onset to admission), nausea, vomiting, diarrhea, peritonitis, comorbidities, and history of appendicitis; preoperative body temperature (T), white blood cell (WBC) count, percentage of neutrophilic granulocytes, and preoperative C-reactive protein (CRP) level; time from diagnosis to surgery. appendix diameter, appendicolith, and ascites in ultrasound or CT; surgical time(the surgery start time was the time of skin incision, and the end time was the time the anesthesia intubation was removed), intraoperative blood loss (the volume of blood infiltrating into a gauze was calculated by weighing the gauze infiltrated with water and calculating the volume of water), intraoperative adhesions or effusions, and stump closure methods, convert to open appendectomy, appendix pathology(perforated or gangrenous appendicitis were defined as complicated appendicitis and simple or suppurative appendicitis were defined as uncomplicated appendicitis) and antibiotic treatment schemes were analyzed.ResultsSignificant differences were detected between group A and group B in age (37.10 ± 13.52y vs 42.94 ± 15.57y, PConclusionsThe patient with appendicitis was older and had peritonitis, higher preoperative WBC count or CRP level, longer time from diagnosis to surgery, appendicolith, and complicated appendicitis, predicting a prolonged hospital stay. Shorter surgical time and the use of silk ligation for stump closure and cephalosporins + metronidazole for antibiotic treatment might be better choices to obtain a shorter hospital stay.

Wind energy is one of the most important renewable resources and plays a vital role in reducing carbon emission and solving global warming problem. Every country has made a corresponding energy policy to stimulate wind energy industry development based on wind energy production, consumption, and distribution. In this paper, we focus on forecasting wind energy consumption from a macro perspective. A novel power-driven fractional accumulated grey model (PFAGM) is proposed to solve the wind energy consumption prediction problem with historic annual consumption of the past ten years. PFAGM model optimizes the grey input of the classic fractional grey model with an exponential term of time. For boosting prediction performance, a heuristic intelligent algorithm WOA is used to search the optimal order of PFAGM model. Its linear parameters are estimated by using the least-square method. Then validation experiments on real-life data sets have been conducted to verify the superior prediction accuracy of PFAGM model compared with other three well-known grey models. Finally, the PFAGM model is applied to predict China's wind energy consumption in the next three years.

BackgroundBoth obesity and the metabolic syndrome have been independently associated with increased asthma morbidity. However, it is unclear whether metabolic syndrome limits the beneficial effects of weight loss on asthma.ObjectivesTo evaluate whether bariatric weight loss is associated with improved asthma control, and whether this association varies by metabolic syndrome status.MethodsWe determined the changes in asthma control, defined by the Asthma Control Test (ACT), before and after bariatric surgery among participants with asthma in the multi-center Longitudinal Assessment of Bariatric Surgery (LABS) study, stratifying our analysis by the presence or absence of metabolic syndrome.ResultsAmong 2,458 LABS participants, 555 participants had an asthma diagnosis and were included in our analysis. Of these, 78% (n = 433) met criteria for metabolic syndrome (MetSyn) at baseline. In patients without MetSyn, mean ACT increased from 20.4 at baseline to 22.1 by 12-24 months, ending at 21.3 at 60 months. In contrast, among those with MetSyn there was no significant improvement in ACT scores. The proportion of patients without MetSyn with adequate asthma control (ACT >19) increased from 58% at baseline to 78% and 82% at 12 and 60 months, respectively, whereas among those with MetSyn, it was 73.8% at baseline, 77.1% at 12 months, dropping to 47.1% at 60 months (p = 0.004 for interaction between metabolic syndrome and time). Having MetSyn also increased the likelihood of losing asthma control during follow-up (HR = 1.92, 95% confidence interval [CI] 1.24-2.97, p = 0.003).ConclusionsMetabolic syndrome may negatively modify the effect of bariatric surgery-induced weight loss on asthma control.

To study the characterization of Fe3O4@Au-C225 composite targeted MNPs.Fe3O4@Au-C225 was prepared by the absorption method. The immunosorbent assay was used to evaluate its absorption efficiency at C225 Fc. ZETA SIZER3000 laser particle size analyzer, ultraviolet photometer and its characteristics were analyzed by VSM. the targeting effect of Fe3O4@Au-C225 composite targeted MNPs on U251 cells in vitro were detected by 7.0 Tesla Micro-MR; and subcutaneous transplanted human glioma in nude mice were performed the targeting effect in vivo after tail vein injection of Fe3O4@Au-C225 composite targeted MNPs by MRI.The self-prepared Fe3O4@Au composite MNPs can adsorb C225 with high efficiency of adsorption so that Fe3O4@Au-C225 composite targeted MNPs were prepared successfully. Fe3O4@Au-C225 composite targeted MNPs favorably targeted human glioma cell line U251 in vitro; Fe3O4@Au-C225 composite targeted MNPs have good targeting ability to xenografted glioma on nude mice in vivo, and can be traced by MRI.The Fe3O4@Au-C225 composite targeted MNPs have the potential to be used as a tracer for glioma in vivo.

In semi-arid areas of China, the ridge-furrow mulched with plastic film (RF) cultivation system is a common water-saving agricultural technique where the shortage of water resources has become a serious problem. Therefore, we aimed to explore whether this cultivation is actually an improvement over the traditional flat planting (TF) method while testing two deficit irrigation (150, 75 mm) levels to grow winter wheat. Furthermore, we examined the responses of the anti-oxidative defence system and photosynthetic capacity of winter wheat flag leaves under three simulated rainfall (275, 200 and 125 mm) conditions. The results showed that the RF system with 150 mm deficit irrigation and 200 mm simulated rainfall condition (RF2150) treatment raised soil water content (%) at the jointing and flowering stages and achieved higher net photosynthesis rates (Pn) in flag leaves. Furthermore, such improvements were due to the reduction of malondialdehyde (MDA) content and oxidative damage during different growth stages of winter wheat. The RF2150 treatment significantly increased the activities of superoxide dismutase (SOD); peroxidise (POD), catalase (CAT) and ascorbate peroxidase (APX) and the content of soluble protein (SP) during different growth stages of winter wheat. Furthermore, RF2150 treatment attained the highest value at the flowering stage, while also exhibiting significant declines in contents of proline, MDA, H2O2 and O2 in flag leaves. The higher free H2O2 and O2 scavenging capacity and better anti-oxidative enzyme activities under the RF2150 treatment were due to the lower level of lipid peroxidation, which effectively protected the photosynthetic machinery. The net photosynthetic rate of flag leaves was positively correlated with SOD, POD, CAT, APX and SP activities, and negatively correlated with proline, MDA, H2O2 and O2 contents. We concluded that the RF2150 treatment was the better water-saving management strategy because it significantly delayed flag leaf senescence and caused the increases in SWC, WUE, Pn, antioxidant enzyme activities and grain yield of winter wheat grown in semi-arid regions of China.

Soil respiration induced by biological soil crusts (BSCs) is an important process in the carbon (C) cycle in arid and semi-arid ecosystems, where vascular plants are restricted by the harsh environment, particularly the limited soil moisture. However, the interaction between temperature and soil respiration remains uncertain because of the number of factors that control soil respiration, including temperature and soil moisture, especially in BSC-dominated areas. In this study, the soil respiration in moss-dominated crusts and lichen-dominated crusts was continuously measured using an automated soil respiration system over a one-year period from November 2015 to October 2016 in the Shapotou region of the Tengger Desert, northern China. The results indicated that over daily cycles, the half-hourly soil respiration rates in both types of BSC-covered areas were commonly related to the soil temperature. The observed diel hysteresis between the half-hourly soil respiration rates and soil temperature in the BSC-covered areas was limited by nonlinearity loops with semielliptical shapes, and soil temperature often peaked later than the half-hourly soil respiration rates in the BSC-covered areas. The average lag times between the half-hourly soil respiration rates and soil temperature for both types of BSC-covered areas were two hours over the diel cycles, and they were negatively and linearly related to the volumetric soil water content. Our results highlight the diel hysteresis phenomenon that occurs between soil respiration rates and soil temperatures in BSC-covered areas and the negative response of this phenomenon to soil moisture, which may influence total C budget evaluations. Therefore, the interactive effects of soil temperature and moisture on soil respiration in BSC-covered areas should be considered in global carbon cycle models of desert ecosystems.

BackgroundTemporomandibular disorders (TMDs) have the highest prevalence in women of reproductive age. The role of estrogen in TMDs and especially in TMDs related pain is not fully elucidated. Voltage-gated sodium channel 1.7 (Nav1.7) plays a prominent role in pain perception and Nav1.7 in trigeminal ganglion (TG) is involved in the hyperalgesia of inflamed Temporomandibular joint (TMJ). Whether estrogen could upregulate trigeminal ganglionic Nav1.7 expression to enhance hyperalgesia of inflamed TMJ remains to be explored.MethodsEstrous cycle and plasma levels of 17β-estradiol in female rats were evaluated with vaginal smear and enzyme linked immunosorbent assay, respectively. Female rats were ovariectomized and treated with 17β-estradiol at 0 μg, 20 μg and 80 μg, respectively, for 10 days. TMJ inflammation was induced using complete Freund's adjuvant. Head withdrawal thresholds and food intake were measured to evaluate the TMJ nociceptive responses. The expression of Nav1.7 in TG was examined using real-time PCR and western blot. The activity of Nav1.7 promoter was examined using luciferase reporter assay. The locations of estrogen receptors (ERα and ERβ), the G protein coupled estrogen receptor (GPR30), and Nav1.7 in TG were examined using immunohistofluorescence.ResultsUpregulation of Nav1.7 in TG and decrease in head withdrawal threshold were observed with the highest plasma 17β-estradiol in the proestrus of female rats. Ovariectomized rats treated with 80 μg 17β-estradiol showed upregulation of Nav1.7 in TG and decrease in head withdrawal threshold as compared with that of the control or ovariectomized rats treated with 0 μg or 20 μg. Moreover, 17β-estradiol dose-dependently potentiated TMJ inflammation-induced upregulation of Nav1.7 in TG and also enhanced TMJ inflammation-induced decrease of head withdrawal threshold in ovariectomized rats. In addition, the estrogen receptor antagonist, ICI 182,780, partially blocked the 17β-estradiol effect on Nav1.7 expression and head withdrawal threshold in ovariectomized rats. ERα and ERβ, but not GPR30, were mostly co-localized with Nav1.7 in neurons in TG. In the nerve growth factor-induced and ERα-transfected PC12 cells, 17β-estradiol dose-dependently enhanced Nav1.7 promoter activity, whereas mutations of the estrogen response element at -1269/-1282 and -1214/-1227 in the promoter completely abolished its effect on the promoter activity.ConclusionEstradiol could upregulate trigeminal ganglionic Nav1.7 expression to contribute to hyperalgesia of inflamed TMJ.

Progesterone receptor membrane component 1 (PGRMC1) is widely observed with an elevated level in multiple human cancers. However, the roles of PGRMC1 in renal cancer are not clear and merit further study. In this report, we made a systematic, integrative biological assessment for PGRMC1 in renal cell carcinoma (RCC) by a quantitative proteomic identification, immunohistochemical detection, and its clinic pathologic significance analysis. We found that PGRMC1 abundance is increased by 3.91-fold in RCC tissues compared with its autologous para-cancerous tissues by a quantitative proteome identification. To validate the proteomic result with more confidence, 135 clinic RCC tissues were recruited to measure PGRMC1 abundance by immunohistochemical staining, and 63.7% RCC samples (n = 86) showed a higher abundance of PGRMC1 than the noncancerous counterparts. And the elevated PGRMC1 level was related to the tumor malignancy degree and overall survival of RCC patients. Meanwhile the average serum PGRMC1 concentration for RCC patients (n = 18) was significantly increased by 1.67 fold compared with healthy persons. Moreover an exogenous elevated abundance of PGRMC1 by plasmid transfections significantly enhanced cell proliferation of renal cancer cells in vitro. Our findings demonstrate PGRMC1, which promotes RCC progression phenotypes in vitro and in vivo, is a novel potential biomarker and therapeutic target for RCC.

Increasing studies have shown that mature spermatozoa contain many transcripts including mRNAs and miRNAs. However, the expression profile of long non-coding RNAs (lncRNAs) in mammalian sperm has not been systematically investigated. Here, we used highly purified RNA to investigate lncRNA expression profiles in mouse mature sperm by stranded-specific RNA-seq. We identified 20,907 known and 4,088 novel lncRNAs transcripts, and the existence of intact lncRNAs was confirmed by RT-PCR and fluorescence in situ hybridization on two representative lncRNAs. Compared to round spermatids, 1,794 upregulated and 165 downregulated lncRNAs and 4,435 upregulated and 3,920 downregulated mRNAs were identified in sperm. Based on the "Cis and Trans" RNA-RNA interaction principle, we found 14,259 targeted coding genes of differently expressed lncRNAs. In terms of Gene ontology (GO) analysis, differentially expressed lncRNAs targeted genes mainly related to nucleic acid metabolic, protein modification, chromatin and histone modification, heterocycle compound metabolic, sperm function, spermatogenesis and other processes. In contrast, differentially expressed transcripts of mRNAs were highly enriched for protein metabolic process and RNA metabolic, spermatogenesis, sperm motility, cell cycle, chromatin organization, heterocycle and aromatic compound metabolic processes. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that the differentially expressed lncRNAs were involved in RNA transport, mRNA surveillance pathway, PI3K-Akt signaling pathway, AMPK signaling pathway, protein processing in endoplasmic reticulum. Metabolic pathways, mRNA surveillance pathway, AMPK signaling pathway, cell cycle, RNA transport splicesome and endocytosis incorporated with the differentially expressed mRNA. Furthermore, many lncRNAs were specifically expressed in testis/sperm, and 880 lncRNAs were conserved between human and mouse. In summary, this study provides a preliminary database valuable for identifying lncRNAs critical in the late stage of spermatogenesis or important for sperm function regulation, fertilization and early embryo development.

Cassava (Manihot esculenta) is an important tropical subsistence crop that is severely affected by cassava brown streak disease (CBSD) in East Africa. The disease is caused by Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV). Both have a (+)-sense single-stranded RNA genome with a 5' covalently-linked viral protein, which functionally resembles the cap structure of mRNA, binds to eukaryotic translation initiation factor 4E (eIF4E) or its analogues, and then enable the translation of viral genomic RNA in host cells. To characterize cassava eIF4Es and their potential role in CBSD tolerance and susceptibility, we cloned five eIF4E transcripts from cassava (accession TMS60444). Sequence analysis indicated that the cassava eIF4E family of proteins consisted of one eIF4E, two eIF(iso)4E, and two divergent copies of novel cap-binding proteins (nCBPs). Our data demonstrated experimentally the coding of these five genes as annotated in the published cassava genome and provided additional evidence for refined annotations. Illumina resequencing data of the five eIF4E genes were analyzed from 14 cassava lines tolerant or susceptible to CBSD. Abundant single nucleotide polymorphisms (SNP) and biallelic variations were observed in the eIF4E genes; however, most of the SNPs were located in the introns and non-coding regions of the exons. Association studies of non-synonymous SNPs revealed no significant association between any SNP of the five eIF4E genes and the tolerance or susceptibility to CBSD. However, two SNPs in two genes were weakly associated with the CBSD responses but had no direct causal-effect relationship. SNPs in an intergenic region upstream of eIF4E_me showed a surprising strong association with CBSD responses. Digital expression profile analysis showed differential expression of different eIF4E genes but no significant difference in gene expression was found between susceptible and tolerant cassava accessions despite the association of the intergenic SNPs with CBSD responses.

Nitrogen and phosphorous are critical determinants of plant growth and productivity, and both plant growth and root morphology are important parameters for evaluating the effects of supplied nutrients. Previous work has shown that the growth of Acer mono seedlings is retarded under nursery conditions; we applied different levels of N (0, 5, 10, and 15 g plant-1) and P (0, 4, 6 and 8 g plant-1) fertilizer to investigate the effects of fertilization on the growth and root morphology of four-year-old seedlings in the field. Our results indicated that both N and P application significantly affected plant height, root collar diameter, chlorophyll content, and root morphology. Among the nutrient levels, 10 g N and 8 g P were found to yield maximum growth, and the maximum values of plant height, root collar diameter, chlorophyll content, and root morphology were obtained when 10 g N and 8 g P were used together. Therefore, the present study demonstrates that optimum levels of N and P can be used to improve seedling health and growth during the nursery period.

The most common cause of gastric cancer is infection with helicobacter pylori (HP), but the associated molecular mechanism is not well understood. In the present study, we found a marked increase in the expression of B7-H1, a member of the B7 co-stimulatory family of molecules that bind to programmed death-1 (PD-1) and play a critical immunoregulatory role in the cell-mediated immune response, in HP-positive gastric cancer tissue. Infection of cultured gastric cancer cells with HP promoted B7-H1 expression and inhibited miR-152 and miR-200b expression. We further demonstrated that these two miRNAs targeted B7-H1 mRNA and suppressed B7-H1 expression in gastric cancer cells. Finally, B7-H1 expression was found to correlate with miR-152 and miR-200b levels in gastric tumor tissues from human patients. Our findings suggest a novel mechanism by which HP infection promotes gastric cancer and also suggest potential targets, i.e., miR-152 and miR-200b, for the prevention and treatment of gastric cancer.

To translate and cross-culturally adapt the anterior cruciate ligament-return to sport after injury (ACL-RSI) into simplified Chinese [ACL-RSI (Cn)].In this diagnostic study, the translation, cross-culturally adaptation, and validation of the ACL-RSI was performed according to international guidelines. A total of 112 patients with ACL reconstruction participated in this study. All were capable of competitive sports before the injury and completed the Knee Injury and Osteoarthritis Outcome (KOOS), the International Knee Documentation Committee (IKDC), the Tampa Scale of Kinesiophobia (TSK), and the Tegner activity score. Forty-eight patients completed the ACL-RSI (Cn) twice within two weeks. The validity was tested using seven premade hypotheses. Internal consistency, reliability, and measurement error was assessed.At meanly 15.6 months postoperative, 81 (72.3%) patients returned to sport, with 57 (50.9%) to competitive sport and 24 (21.4%) to recreational sport. Thirty-one (27.7%) patients didn't return to any sport, with 19 (17.0%) still had planned to return, and 12 (10.7%) gave up sport. The ACL-RSI (Cn) demonstrated excellent validity with all hypotheses confirmed. The outcome of ACL-RSI (Cn) was strongly correlated the KOOS subscale quality of life (r = 0.66, p

OBJECTIVES:More than 900 students and teachers at many schools in Jiaxing city developed acute gastroenteritis in February 2014. An immediate epidemiological investigation was conducted to identify the pathogen, infection sources and route of transmission. METHODS:The probable cases and confirmed cases were defined as students or teachers with diarrhoea or vomiting present since the term began in February 2014. An active search was conducted for undiagnosed cases among students and teachers. Details such as demographic characteristics, gastrointestinal symptoms, and drinking water preference and frequency were collected via a uniform epidemiological questionnaire. A case-control study was implemented, and odds ratios (ORs) and 95% confidence intervals were calculated. Rectal swabs from several patients, food handlers and barrelled water factory workers, as well as water and food samples, were collected to test for potential bacteria and viruses. RESULTS:A total of 924 cases fit the definition of the probable case, including 8 cases of laboratory-confirmed norovirus infection at 13 schools in Jiaxing city between February 12 and February 21, 2014. The case-control study demonstrated that barrelled water was a risk factor (OR: 20.15, 95% CI: 2.59-156.76) and that bottled water and boiled barrelled water were protective factors (OR: 0.31, 95% CI: 0.13-0.70, and OR: 0.36, 95% CI: 0.16-0.77). A total of 11 rectal samples and 8 barrelled water samples were detected as norovirus-positive, and the genotypes of viral strains were the same (GII). The norovirus that contaminated the barrelled water largely came from the asymptomatic workers. CONCLUSIONS:This acute gastroenteritis outbreak was caused by barrelled water contaminated by norovirus. The outbreak was controlled after stopping the supply of barrelled water. The barrelled water supply in China represents a potential source of acute gastroenteritis outbreaks due to the lack of surveillance and supervision. Therefore, more attention should be paid to this area.

BACKGROUND:Our previous genome-wide association study (GWAS) identified three independent single nucleotide polymorphisms (SNPs) in human major histocompatibility complex (MHC) region showing association with esophageal squamous cell carcinoma (ESCC). In this study, we increased GWAS sample size on MHC region and performed validation in an independent ESCC cases and normal controls with aim to find additional loci at MHC region showing association with an increased risk to ESCC. METHODS:The 1,077 ESCC cases and 1,733 controls were genotyped using Illumina Human 610-Quad Bead Chip, and 451 cases and 374 controls were genotyped using Illumina Human 660W-Quad Bead Chip. After quality control, the selected SNPs were replicated by TaqMan genotyping assay on another 2,026 ESCC cases and 2,384 normal controls. RESULTS:By excluding low quality SNPs in primary GWAS screening, we selected 2,533 SNPs in MHC region for association analysis, and identified 5 SNPs with p

Knowledge of protein function is important for biological, medical and therapeutic studies, but many proteins are still unknown in function. There is a need for more improved functional prediction methods. Our SVM-Prot web-server employed a machine learning method for predicting protein functional families from protein sequences irrespective of similarity, which complemented those similarity-based and other methods in predicting diverse classes of proteins including the distantly-related proteins and homologous proteins of different functions. Since its publication in 2003, we made major improvements to SVM-Prot with (1) expanded coverage from 54 to 192 functional families, (2) more diverse protein descriptors protein representation, (3) improved predictive performances due to the use of more enriched training datasets and more variety of protein descriptors, (4) newly integrated BLAST analysis option for assessing proteins in the SVM-Prot predicted functional families that were similar in sequence to a query protein, and (5) newly added batch submission option for supporting the classification of multiple proteins. Moreover, 2 more machine learning approaches, K nearest neighbor and probabilistic neural networks, were added for facilitating collective assessment of protein functions by multiple methods. SVM-Prot can be accessed at http://bidd2.nus.edu.sg/cgi-bin/svmprot/svmprot.cgi.

Total gastrectomy (TG) has shown to be superior regarding low risk of recurrence and readmission to distal subtotal gastrectomy (DG) for treatment of distal stomach cancer, but the incidence of postoperative morbidity and mortality in TG cannot be ignored. Therefore, we performed a meta-analysis to compare the effectiveness between TG and DG for distal stomach cancer.A search in PubMed, EMBASE, the Cochrane Library, Web of Science, Chinese Biomedical Database through January 2016 was performed. Eligible studies in comparing of TG and DG for distal gastric cancer were included in this meta-analysis. Review Manager 5.2 software from the Cochrane Collaboration was used for the performance of meta-analysis and STATA 12.0 software for meta-regression analysis.Ten retrospective cohort studies and one randomized control trial involving 5447 patients were included. The meta-analysis showed no significant difference of postoperative mortality (RR = 1.48, 95%CI = 0. 90-2.44,p = 0.12), intraoperative blood loss (MD = 24.34, 95%CI = -3.31-51.99, p = 0.08) and length of hospital stay(MD = 0.76, 95%CI:-0.26-1.79, p = 0.15). TG procedure could retrieve more lymph nodes than DG(MD = 4.33, 95% CI = 2.34-6.31, p0.05). We pooled the data together, the accumulated 5-year Overall Survival rates of TG and DG groups were 49.6% (919/1852) vs.55.9%(721/1290) respectively. Meta-analysis revealed a favoring trend to DG procedure and there was a statistical difference between the two groups (RR = 0.91,95% CI = 0.85-0.97,p = 0.006).Based on current retrospective evidences, we found that in spite of similar postoperative mortality, TG for distal gastric cancer provided a high risk of five-year Overall Survival rate. DG procedure can be a recommendation for distal gastric cancer, whereas due to lack of high quality RCTs in multicenter and the relatively small sample size of long-term outcomes, further comparative studies are still needed.

The present study aimed to investigate the prevalence of central obesity among adults with normal BMI and its association with metabolic diseases in Jilin Province, China.A population-based cross-sectional study was conducted in 2012 in Jilin Province of China. Information was collected by face to face interview. Descriptive data analysis and 95% confidence intervals (CI) of prevalence/frequency were conducted. Log-binomial regression analyses were used to find the independent factors associated with central obesity and to explore the adjusted association between central obesity and metabolic diseases among adults with normal BMI.Among the adult residents with normal BMI in Jilin Province, 55.6% of participants with central obesity self-assessed as normal weight and 27.0% thought their body weight were above normal. 12.7% of central obesity people took methods to lose weight, while 85.3% didn't. Female, older people and non-manual worker had higher risk to be central obesity among adults with normal BMI. Hypertension, diabetes and hyperlipidemia were significantly associated with central obesity among adults with normal BMI, the PRs were 1.337 (1.224-1.461), 1.323 (1.193-1.456) and 1.261 (1.152-1.381) separately when adjusted for gender, age and BMI.Hypertension, diabetes and hyperlipidemia were significantly associated with central obesity among adults with normal BMI in Jilin Province, China. The low rates of awareness and control of central obesity among adults with normal BMI should be improved by government and health department.

Leaf shape, including leaf size, leaf dissection index (LDI), and venation distribution, strongly impacts leaf physiology and the forces of momentum exerted on leaves or the canopy under windy conditions. Yet, little has been known about how leaf shape affects the morphological response of trees to wind load. We studied eight Quercus species, with different leaf shapes, to determine the morphological response to simulated wind load. Quercus trees with long elliptical leaves, were significantly affected by wind load (P< 0.05), as indicted by smaller specific leaf area (SLA), stem base diameter and stem height under windy conditions when compared to the control. The Quercus trees with leaves characterized by lanceolate or sinuous edges, showed positive morphological responses to wind load, such as bigger leaf thickness, larger stem diameter, allocation to root biomass, and smaller stem height (P< 0.05). These morphological responses to wind can reduce drag and increase the mechanical strength of the tree. Leaf dissection index (LDI), an important index of leaf shape, was correlated with morphological response to wind load (P< 0.05), including differences in SLA, in stem base diameter and in allocation to root biomass. These results suggest that trees with higher LDI, such as those with more and/or deeper lobes, are better adapted to wind load.

BACKGROUND:Beta (β)-human chorionic gonadotropin (β-HCG) is used to confirm the diagnosis and plan treatment of intracranial germinomas. However, the cutoff values of serum β-HCG in diagnosis of intracranial germinomas reported in the literature are inconsistent. To establish an appropriate cutoff value of serum β-HCG for diagnosis of intracranial germinomas, we retrospectively reviewed the records of intracranial tumor patients who received serum β-HCG and α-fetoprotein (AFP) tests for diagnostic purposes at our hospital from 2005 to 2014. METHODS:A total of 93 intracranial germinomas and 289 intracranial non-germ cell tumors were included in this study. Receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of 3 cutoffs (0.1, 0.4, and 0.5 mIU/mL) for diagnosing intracranial germinomas. The serum β-HCG level of intracranial germinoma patients was further analyzed to investigate the effect of metastasis status and tumor location on serum β-HCG level. RESULTS:The area under the ROC curve was 0.81 (P < .001), suggesting β-HCG is an effective marker. Of the 3 cutoff values, 0.1 mIU/mL possessed a highest sensitivity (66.67%) and good specificity (91%). Although there was no β-HCG level difference between metastatic and non-metastatic intracranial germinoma patients, the diagnostic rate of metastatic neurohypophyseal germinomas was significantly higher than that of its non-metastatic counterpart (P < .05), implying that the location of the germinoma might need to be considered when β-HCG is used as a marker to predict metastasis. CONCLUSIONS:Determining an optimal cutoff of serum β-HCG is helpful for assisting the diagnosis of intracranial germinoma.

This study aims to investigate the biological role of RhoB in clear cell renal cell carcinoma (ccRCC). The expression of RhoB was examined in specimens of patients and cell lines by Western blot and Immunohistochemistry. The correlation between RhoB expression and clinicopathologic variables was also analyzed. The effects of RhoB on cell proliferation, cell cycle, cell apoptosis, and invasion/migration were detected by over-expression and knockdown of RhoB level in ccRCC cells via plasmids and RNAi. The results showed that RhoB was low-expressed in ccRCC surgical specimens and cell lines compared with adjacent normal renal tissues and normal human renal proximal tubular epithelial cell lines (HKC), and its protein expression level was significantly associated with the tumor pathologic parameter embracing tumor size(P = 0.0157), pT stage(P = 0.0035), TNM stage(P = 0.0024) and Fuhrman tumor grade(P = 0.0008). Further, over-expression of RhoB remarkably inhibited the cancer cell proliferation, colony formation and promoted cancer cell apoptosis, and aslo reduced the invasion and migration ability of ccRCC cells. Interestingly, up-regulation of RhoB could induce cell cycle arrest in G2/M phase and led to cell cycle regulators(CyclineB1,CDK1) and pro-apoptotic protein(casp3,casp9) aberrant expression. Moreover, knockdown of RhoB in HKC cells promoted cell proliferation and migration. Taken together, our study indicates that RhoB expression is decreased in ccRCC carcinogenesis and progression. Up-regulation of RhoB significantly inhibits ccRCC cell malignant phenotype. These findings show that RhoB may play a tumor suppressive role in ccRCC cells, raising its potential value in futural therapeutic target for the patients of ccRCC.

Reperfusion after a period of ischemia results in reperfusion injury (IRI) which involves activation of the inflammatory cascade. In cardiac IRI, IgM natural antibodies (NAb) play a prominent role through binding to altered neoepitopes expressed on damaged cells. Beta 2 Glycoprotein I (β2GPI) is a plasma protein that binds to neoepitopes on damaged cells including anionic phospholipids through its highly conserved Domain V. Domain I of β2GPI binds circulating IgM NAbs and may provide a link between the innate immune system, IgM NAb binding and cardiac IRI. This study was undertaken to investigate the role of Β2GPI and its Domain V in cardiac IRI using wild-type (WT), Rag-1 -/- and β2GPI deficient mice. Compared with control, treatment with Domain V prior to cardiac IRI prevented binding of endogenous β2GPI to post-ischemic myocardium and resulted in smaller myocardial infarction size in both WT and β2GPI deficient mice. Domain V treatment in WT mice also resulted in less neutrophil infiltration, less apoptosis and improved ejection fraction at 24 h. Rag-1 -/- antibody deficient mice reconstituted with IgM NAbs confirmed that Domain V prevented IgM NAb induced cardiac IRI. Domain V remained equally effective when delivered at the time of reperfusion which has therapeutic clinical relevance.Based upon this study Domain V may function as a universal inhibitor of IgM NAb binding in the setting of cardiac IRI, which offers promise as a new therapeutic strategy in the treatment of cardiac IRI.

Cerium oxide nanoparticles (CeO2 NPs) have been shown to have significant interactions in plants. Previous study reported the specific-species phytotoxicity of CeO2 NPs by lettuce (Lactuca sativa), but their physiological impacts and vivo biotransformation are not yet well understood, especially in relative realistic environment. Butterhead lettuce were germinated and grown in potting soil for 30 days cultivation with treatments of 0, 50, 100, 1000 mg CeO2 NPs per kg soil. Results showed that lettuce in 100 mg·kg-1 treated groups grew significantly faster than others, but significantly increased nitrate content. The lower concentrations treatment had no impact on plant growth, compared with the control. However, the higher concentration treatment significantly deterred plant growth and biomass production. The stress response of lettuce plants, such as Superoxide dismutase (SOD), Peroxidase (POD), Malondialdehyde(MDA) activity was disrupted by 1000 mg·kg-1 CeO2 NPs treatment. In addition, the presence of Ce (III) in the roots of butterhead lettuce explained the reason of CeO2 NPs phytotoxicity. These findings demonstrate CeO2 NPs modification of nutritional quality, antioxidant defense system, the possible transfer into the food chain and biotransformation in vivo.

BackgroundAnti-tuberculosis (anti-TB) drug-induced liver injury (ADLI) is one of the most common adverse effects associated with TB treatment. Cytochrome P450 (CYP) 1A1 and glutathione S-transferase (GST) P1 are important phase I/II metabolizing enzymes involved in drug metabolism and detoxification. Genetic polymorphism and CpG island methylation have been reported as factors influencing the expression of CYP1A1 and GSTP1.ObjectiveThis study aimed to determine the potential relationships of CYP1A1 and GSTP1 polymorphisms and CpG island methylation with ADLI risk.DesignThis was a population-based one-to-one matched case-control study.SettingThe subjects were patients with TB receiving treatment in China from December 2010 to June 2013.PatientsIn total, 127 patients with TB and ADLI (case group) and 127 patients with TB but without liver injury (control group) were included in this study. Subjects were matched in terms of sex, age, and therapeutic regimen.MethodsThe general condition of each patient was assessed using questionnaires. The CYP1A1 MspI and GSTP1 Ile105Val polymorphisms as well as methylation status were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism and the methylation-specific PCR method.ResultsWe found no significant difference in GSTP1 and CYP1A1 genotypes between the two groups, probably because the sample size was not large enough; however, patients with ADLI had significantly higher GSTP1 and CYP1A1 promoter methylation rates than control subjects [odds ratio (OR) = 2.467 and 2.000, respectively]. After adjusting for drinking, which significantly differed between the groups as per univariate analysis, we found that hypermethylation of GSTP1 and CYP1A1 promoters was associated with ADLI (OR = 2.645 and 2.090, respectively).ConclusionHypermethylation of CpG islands of GSTP1 and CYP1A1 promoters may thus play important roles in the development of ADLI and provide evidence of being used as novel markers for ADLI risk prediction.

Many human (different serotypes) and nonhuman adenovirus vectors are being used for gene delivery. However, the current system for isolating recombinant adenoviral vectors is either time-consuming or expensive, especially for the generation of recombinant non-human adenoviral vectors. We herein report a new and simple cloning approach for the rapid generation of a porcine adenovirus (PAdV-3) vector which shows promise for gene transfer to human cells and evasion of human adenovirus type 5 (HAdV-5) immunity. Based on the final cloning plasmid, pFPAV3-CcdB-Cm, and our modified SLiCE strategy (SLiCE cloning and lethal CcdB screening), the process for generating recombinant PAdV-3 plasmids required only one step in 3 days, with a cloning efficiency as high as 620 ± 49.56 clones/ng and zero background (100% accuracy). The recombinant PAdV-3 plasmids could be successfully rescued in porcine retinal pigment epithelium cells (VR1BL), which constitutively express the HAdV-5 E1 and PAdV-3 E1B 55k genes, and the foreign genes were highly expressed at 24 h after transduction into swine testicle (ST) cells. In conclusion, this strategy for generating recombinant PAdV-3 vectors based on our modified SLiCE cloning system was rapid and cost-efficient, which could be used as universal cloning method for modification the other regions of PAdV-3 genome as well as other adenoviral genomes.

Optimal guidance is essential for the soft landing task. However, due to its high computational complexities, it is hardly applied to the autonomous guidance. In this paper, a computationally inexpensive optimal guidance algorithm based on the radial basis function neural network (RBFNN) is proposed. The optimization problem of the trajectory for soft landing on asteroids is formulated and transformed into a two-point boundary value problem (TPBVP). Combining the database of initial states with the relative initial co-states, an RBFNN is trained offline. The optimal trajectory of the soft landing is determined rapidly by applying the trained network in the online guidance. The Monte Carlo simulations of soft landing on the Eros433 are performed to demonstrate the effectiveness of the proposed guidance algorithm.

Soil infertility is the main barrier to dryland agricultural production in China. To provide a basis for the establishment of a soil amelioration technical system for rainfed fields in the semiarid area of northwest China, we conducted a four-year (2007-2011) field experiment to determine the effects of wheat straw incorporation on the arid soil nutrient levels of cropland cultivated with winter wheat after different straw incorporation levels. Three wheat straw incorporation levels were tested (H: 9000 kg hm(-2), M: 6000 kg hm(-2), and L: 3000 kg hm(-2)) and no straw incorporation was used as the control (CK). The levels of soil nutrients, soil organic carbon (SOC), soil labile organic carbon (LOC), and enzyme activities were analyzed each year after the wheat harvest. After straw incorporation for four years, the results showed that variable straw amounts had different effects on the soil fertility indices, where treatment H had the greatest effect. Compared with CK, the average soil available N, available P, available K, SOC, and LOC levels were higher in the 0-40 cm soil layers after straw incorporation treatments, i.e., 9.1-30.5%, 9.8-69.5%, 10.3-27.3%, 0.7-23.4%, and 44.4-49.4% higher, respectively. On average, the urease, phosphatase, and invertase levels in the 0-40 cm soil layers were 24.4-31.3%, 9.9-36.4%, and 42.9-65.3% higher, respectively. Higher yields coupled with higher nutrient contents were achieved with H, M and L compared with CK, where these treatments increased the crop yields by 26.75%, 21.51%, and 7.15%, respectively.

Gallbladder carcinoma is an aggressive malignancy with high mortality mainly due to the limited potential for curative resection and its resistance to chemotherapeutic agents. Here, we show that the histone deacetylase inhibitors (HDACIs) trichostatin-A (TSA) and suberoylanilide hydroxamic acid (SAHA) reduce the proliferation and induce apoptosis of gallbladder carcinoma cells by suppressing the AKT/mammalian target of rapamycin (mTOR) signaling. Gallbladder carcinoma SGC-996 cells were treated with different concentrations of TSA and SAHA for different lengths of time. Cell proliferation and morphology were assessed with MTT assay and microscopy, respectively. Cell cycle distribution and cell apoptosis were analyzed with flow cytometry. Western blotting was used to detect the proteins related to apoptosis, cell cycle, and the AKT/mTOR signaling pathway. Our data showed that TSA and SAHA reduced SGC-996 cell viability and arrested cell cycle at the G1 phase in a dose- and time-dependent manner. TSA and SAHA promoted apoptosis of SGC-996 cells, down-regulated the expression of cyclin D1, c-Myc and Bmi1, and decreased the phosphorylation of AKT, mTOR p70S6K1, S6 and 4E-BP1. Additionally, the mTOR inhibitor rapamycin further reduced the cell viability of TSA- and SAHA-treated SGC-996 cells and the phosphorylation of mTOR, whereas the mTOR activator 1,2-dioctanoyl-sn-glycero-3-phosphate (C8-PA) exerted the opposite influence. Our results demonstrate that histone deacetylase inhibitors (HDACIs) suppress the proliferation of gallbladder carcinoma cell via inhibition of AKT/mTOR signaling. These findings offer a mechanistic rationale for the application of HDACIs in gallbladder carcinoma treatment.

In this study, we sought to identify differentially expressed proteins in the serum of patients with sarcoidosis or tuberculosis and to evaluate these proteins as markers for the differential diagnosis of sarcoidosis and sputum-negative tuberculosis.Using protein microarrays, we identified 3 proteins exhibiting differential expression between patients with sarcoidosis and tuberculosis. Elevated expression of these proteins was verified using the enzyme-linked immunosorbent assay (ELISA) and was further confirmed by immunohistochemistry. Receiver operating characteristic (ROC) curve, logistic regression analysis, parallel, and serial tests were used to evaluate the diagnostic efficacy of the proteins.Intercellular Adhesion Molecule 1(ICAM-1) and leptin were screened for differentially expressed proteins relevant to sarcoidosis and tuberculosis. Using ROC curves, we found that ICAM-1 (cutoff value: 57740 pg/mL) had an area under the curve (AUC), sensitivity, and specificity of 0.718, 62.3%, and 79.5% respectively, while leptin (cutoff value: 1193.186 pg/mL) had an AUC, sensitivity, and specificity of 0.763, 88.3%, and 65.8%, respectively. Logistic regression analysis revealed that the AUC, sensitivity, and specificity of combined leptin and ICAM-1 were 0.787, 89.6%, and 65.8%, respectively, while those of combined leptin, ICAM-1, and body mass index (BMI) were 0.837, 90.9%, and 64.4%, respectively, which had the greatest diagnostic value. Parallel and serial tests indicated that the BMI-leptin parallel with the ICAM-1 serial was the best diagnostic method, achieving a sensitivity and specificity of 86.5% and 73.1%, respectively. Thus, our results identified elevated expression of ICAM-1 and leptin in serum and granulomas of sarcoidosis patients.ICAM-1 and leptin were found to be potential markers for the diagnosis of sarcoidosis and differential diagnosis of sarcoidosis and sputum-negative tuberculosis.

Reduced neutrophil apoptosis plays an important role in the pathogenesis of acute exacerbation chronic obstructive pulmonary disease (AECOPD). The p38 mitogen-activated protein kinase (MAPK) signaling pathway is involved in neutrophil apoptosis. 1α,25-Dihydroxyvitamin D3 (1α,25VitD3) can induce tumor cell apoptosis. The aim of this study was to assess the effects of 1α,25VitD3 on peripheral blood neutrophil apoptosis in AECOPD and examine the role of the p38 MAPK signaling pathway.The study enrolled 36 AECOPD patients and 36 healthy volunteers. Venous blood samples were obtained from both groups. Serum 25-hydroxyvitamin D (25-(OH) D) levels in peripheral venous blood were assayed using liquid chromatography-tandem mass spectrometry (LC-MS/MS); the neutrophils were separated and cultured with SB203580 (a p38 inhibitor) and 1α,25VitD3. Neutrophil apoptosis was measured using flow cytometry, and phospho-p38 MAPK protein expression was detected by Western blot. Statistical analysis was performed using analysis of variance. Student's t-test and Pearson's correlation coefficient were used for the between-group differences and correlation analysis, respectively.The 25-(OH) D levels were lower in AECOPD patients than in healthy controls, and the peripheral blood neutrophil apoptosis results were similar. 1α,25VitD3 increased the apoptosis rate and the level of phospho-p38 MAPK in peripheral blood neutrophils of AECOPD patients. SB203580 partly inhibited 1α,25VitD3-induced peripheral blood neutrophil apoptosis and phospho-p38 MAPK overexpression. The 25-(OH) D levels were positively correlated with increased peripheral blood neutrophil apoptosis and phospho-p38 MAPK levels. In addition, expression of the phospho-p38 MAPK protein was also positively correlated with peripheral blood neutrophil apoptosis.Our results suggest that 1α,25VitD3 induces peripheral blood neutrophil apoptosis through the p38 MAPK signaling pathway in AECOPD patients.

Periventricular leukomalacia (PVL) is a common ischemic brain injury in premature infants for which there is no effective treatment. The objective of this study was to determine whether transplanted mouse oligodendrocyte progenitor cells (OPCs) have neuroprotective effects in a rat model of PVL. Hypoxia-ischemia (HI) was induced in 3-day-old rat pups by left carotid artery ligation, followed by exposure to 6% oxygen for 2.5 h. Animals were assigned to OPC transplantation or sham control groups and injected with OPCs or PBS, respectively, and sacrificed up to 6 weeks later for immunohistochemical analysis to investigate the survival and differentiation of transplanted OPCs. Apoptosis was evaluated by double immunolabeling of brain sections for caspase-3 and neuronal nuclei (NeuN), while proliferation was assessed using a combination of anti-Nestin and -bromodeoxyuridine antibodies. The expression of brain-derived neurotrophic factor (BDNF) and Bcl-2 was examined 7 days after OPC transplantation. The Morris water maze was used to test spatial learning and memory. The results showed that transplanted OPCs survived and formed a myelin sheath, and stimulated BDNF and Bcl-2 expression and the proliferation of neural stem cells (NSC), while inhibiting HI-induced neuronal apoptosis relative to control animals. Moreover, deficits in spatial learning and memory resulting from HI were improved by OPC transplantation. These results demonstrate an important neuroprotective role for OPCs that can potentially be exploited in cell-based therapeutic approaches to minimize HI-induced brain injury.

PTEN-Long is a translational variant of PTEN (Phosphatase and Tensin Homolog). Like PTEN, PTEN-Long is able to antagonize the PI3K-Akt pathway and inhibits tumor growth. In this study, we investigated the role PTEN-Long plays in the development and progression of clear cell renal cell carcinoma (ccRCC) and explored the therapeutic possibility using proteinaceous PTEN-Long to treat ccRCC. We found that the protein levels of PTEN-Long were drastically reduced in ccRCC, which was correlated with increased levels of phosphorylated Akt (pAkt). Gain of function experiments showed overexpression of PTEN-Long in the ccRCC cell line 786-0 suppressed PI3K-Akt signaling, inhibited cell proliferation, migration and invasion, and eventually induced cell death. When purified PTEN-Long was added into cultured 786-0 cells, it entered cells, blocked Akt activation, and induced apoptosis involving Caspase 3 cleavage. Furthermore, PTEN-Long inhibited proliferation of 786-0 cells in xenograft mouse model. Our results implicated that understanding the roles of PTEN-Long in renal cell carcinogenesis has therapeutic significance.

Mining elite genes within rice landraces is of importance for the improvement of cultivated rice. An association mapping for 12 agronomic traits was carried out using a core collection of rice consisting of 150 landraces (Panel 1) with 274 simple sequence repeat (SSR) markers, and the mapping results were further verified using a Chinese national rice micro-core collection (Panel 2) and a collection from a global molecular breeding program (Panel 3). Our results showed that (1) 76 significant (P10% explained ratio of genetic variation; (2) A total of seven aforementioned trait-marker associations were verified within Panel 2 and 3 when using a general linear model (GLM) and 55 SSR markers of the 76 significant trait-marker associations. However, no significant trait-marker association was found to be identical within three panels when using the MLM model; (3) several desirable alleles of the loci which showed significant trait-marker associations were identified. The research provided important information for further mining these elite genes within rice landraces and using them for rice breeding.

Clinical studies have suggested an association between dyslipidemia and tendon injuries or chronic tendon pain; the mechanisms underlying this association are not yet known. The objectives of this study were (1) to evaluate the impact of a high fat diet on the function of load-bearing tendons and on the distribution in tendons of oxidized low density lipoprotein (oxLDL), and (2) to examine the effect of oxLDL on tendon fibroblast proliferation and gene expression.Gene expression (Mmp2, Tgfb1, Col1a1, Col3a1), fat content (Oil Red O staining), oxLDL levels (immunohistochemistry) and tendon biomechanical properties were examined in mice (C57Bl/6 or ApoE -/-) receiving a standard or a high fat diet. Human tendon fibroblast proliferation and gene expression (COL1A1, COL3A1, MMP2) were examined following oxLDL exposure.In both types of mice (C57Bl/6 or ApoE -/-), consumption of a high fat diet led to a marked increase in oxLDL deposition in the load-bearing extracellular matrix of the tendon. The consumption of a high fat diet also reduced the failure stress and load of the patellar tendon in both mouse types, and increased Mmp2 expression. ApoE -/- mice exhibited more pronounced reductions in tendon function than wild-type mice, and decreased expression of Col1a1 compared to wild type mice. Human tendon fibroblasts responded to oxLDL by increasing their proliferation and their mRNA levels of MMP2, while decreasing their mRNA levels for COL1A1 and COL3A1.The consumption of a high fat diet resulted in deleterious changes in tendon function, and these changes may be explained in part by the effects of oxLDL, which induced a proliferative, matrix-degrading phenotype in human tenocytes.

Skin ulceration syndrome (SUS) is considered to be a major constraint for the stable development of Apostichopus japonicus culture industries. In this study, we investigated protein changes in the coelomocytes of A. japonicus challenged by Vibrio splendidus using isobaric tags for relative and absolute quantification (iTRAQ) over a 96 h time course. Consequently, 228 differentially expressed proteins were identified in two iTRAQs. A comparison of the protein expression profiles among different time points detected 125 proteins primarily involved in response to endogenous stimuli at 24 h. At 48 h, the number of differentially expressed proteins decreased to 67, with their primary function being oxidation reduction. At the end of pathogen infection, proteins responsive to amino acid stimuli and some metabolic processes were classified as the predominant group. Fifteen proteins were differentially expressed at all time points, among which eight proteins related to pathologies in higher animals were shown to be down-regulated after V. splendidus infection: paxillin, fascin-2, aggrecan, ololfactomedin-1, nesprin-3, a disintegrin-like and metallopeptidase with thrombospondin type 1 motif (Adamts7), C-type lectin domain family 4 (Clec4g) and n-myc downstream regulated gene 1 (Ndrg1). To gain more insight into two SUS-related miRNA (miR-31 and miR-2008) targets at the protein level, all 129 down-regulated proteins were further analyzed in combination with RNA-seq. Twelve and eight proteins were identified as putative targets for miR-31 and miR-2008, respectively, in which six proteins (5 for miR-31 and 1 for miR-2008) displayed higher possibilities to be regulated at the level of translation. Overall, the present work enhances our understanding of the process of V. splendidus-challenged sea cucumber and provides a new method for screening miRNAs targets at the translation level.