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Killer cell lectin-like receptor G1 (KLRG1) has traditionally been regarded as an inhibitory receptor of T cell exhaustion in chronic infection and inflammation. However, its exact role in hepatitis B virus (HBV) infection remains elusive. CD8+ T cells from 190 patients with chronic hepatitis B were analyzed ex vivo for checkpoint and apoptosis markers, transcription factors, cytokines and subtypes in 190 patients with chronic hepatitis B. KLRG1+ and KLRG1- CD8+ T cells were sorted for transcriptome analysis. The impact of the KLRG1-E-cadherin pathway on the suppression of HBV replication mediated by virus-specific T cells was validated in vitro. As expected, HBV-specific CD8+ T cells expressed higher levels of KLRG1 and showed an exhausted molecular phenotype and function. However, despite being enriched for the inhibitory molecules, thymocyte selection-associated high mobility group box protein (TOX), eomesodermin (EOMES), and Helios, CD8+ T cells expressing KLRG1 produced significant levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, perforin, and granzyme B, demonstrating not exhausted but active function. Consistent with the in vitro phenotypic assay results, RNA sequencing (RNA-seq) data showed that signature effector T cell and exhausted T cell genes were enriched in KLRG1+ CD8+ T cells. Furthermore, in vitro testing confirmed that KLRG1-E-cadherin binding inhibits the antiviral efficacy of HBV-specific CD8+ T cells. Based on these findings, we concluded that KLRG1+ CD8+ T cells are not only a terminally exhausted subgroup but also exhibit functional diversity, despite inhibitory signs in HBV infection.

Green development, an essential part of sustainable development transformation, is spatially correlated intra- and inter-regionally. However, previous research has not fully addressed the spatial characteristics of green development. This study investigates the spatial correlation structures, core–peripheral positions, and factors impacting the spatial network formation of China’s green development. Based on the green development evaluation index system modified by the entropy method, this study applies social network analysis, block model analysis, and quadratic assignment procedure analysis to data from 30 provinces in China. The results confirm the spatial spillover effect is overwhelmingly present in China’s green development. The findings further distinguish the core roles of provinces including Hunan, Tianjin, Zhejiang, Henan, and Xinjiang, and underline factors of green economic growth, governmental policy support, spatial adjacency, and geographic distance as significantly affecting the spatial network formation of China’s green development. Policy recommendations for green development are then put forward.

Objectives This paper aimed to identify the technology frontiers of artificial intelligence-assisted pathology based on patent citation network. Methods Patents related to artificial intelligence-assisted pathology were searched and collected from the Derwent Innovation Index (DII), which were imported into Derwent Data Analyzer (DDA, Clarivate Derwent, New York, NY, USA) for authority control, and imported into the freely available computer program Ucinet 6 for drawing the patent citation network. The patent citation network according to the citation relationship could describe the technology development context in the field of artificial intelligence-assisted pathology. The patent citations were extracted from the collected patent data, selected highly cited patents to form a co-occurrence matrix, and built a patent citation network based on the co-occurrence matrix in each period. Text clustering is an unsupervised learning method, an important method in text mining, where similar documents are grouped into clusters. The similarity between documents are determined by calculating the distance between them, and the two documents with the closest distance are combined. The method of text clustering was used to identify the technology frontiers based on the patent citation network, which was according to co-word analysis of the title and abstract of the patents in this field. Results 1704 patents were obtained in the field of artificial intelligence-assisted pathology, which had been currently undergoing three stages, namely the budding period (1992–2000), the development period (2001–2015), and the rapid growth period (2016–2021). There were two technology frontiers in the budding period (1992–2000), namely systems and methods for image data processing in computerized tomography (CT), and immunohistochemistry (IHC), five technology frontiers in the development period (2001–2015), namely spectral analysis methods of biomacromolecules, pathological information system, diagnostic biomarkers, molecular pathology diagnosis, and pathological diagnosis antibody, and six technology frontiers in the rapid growth period (2016–2021), namely digital pathology (DP), deep learning (DL) algorithms—convolutional neural networks (CNN), disease prediction models, computational pathology, pathological image analysis method, and intelligent pathological system. Conclusions Artificial intelligence-assisted pathology was currently in a rapid development period, and computational pathology, DL and other technologies in this period all involved the study of algorithms. Future research hotspots in this field would focus on algorithm improvement and intelligent diagnosis in order to realize the precise diagnosis. The results of this study presented an overview of the characteristics of research status and development trends in the field of artificial intelligence-assisted pathology, which could help readers broaden innovative ideas and discover new technological opportunities, and also served as important indicators for government policymaking.

ObjectiveAlthough progress has been made in tuberculosis (TB) treatment, China still remains one of the high-burden TB countries. One important reason that has not received sufficient scholarly attention is that Chinese individuals tend to underestimate the threat of TB. This contributed to the high rate of delay in seeking TB treatment and noncompliance with doctors' regimen. Hence, this research examined how TB knowledge affected Chinese parents' risk perceptions and their efficacy appraisal in TB treatment, and how their risk perception and efficacy appraisal affected their intentions to seek timely TB treatment for their children and adhere to doctors' regimen.MethodsWe conducted an online cross-sectional survey with 1129 parents of children attending kindergarten, primary school, and middle school in Shajing, a region with high TB incidence in China. Perceived severity of TB threat to self and to others, perceived susceptibility, response efficacy, and self-efficacy were measured, in addition to TB knowledge and intentions to seek timely TB treatment and adhere to doctors' regimens.ResultsOrdinal least squares regression demonstrated that TB knowledge was positively associated with perceived severity of TB threat to self, perceived severity of TB threat to others, perceived susceptibility, response efficacy, and self-efficacy, but it did not affect their medical decisions. In addition, binary logistic regression revealed that response efficacy and self-efficacy predicted both intentions positively, and perceived severity of TB threat to self only enhanced Chinese individuals' intention to follow doctors' regimens.ConclusionHealth education aimed at knowledge improvement may be effective in changing one's perceptions of the given health threat but may not be effective to change their behavior. Thus, practitioners need to focus on changing Chinese parents' perceptions of TB rather than simply improving their knowledge. Specifically, it is necessary to lower their efficacy in self-management and enhance their perceived infectiousness of TB.

This study calculates the effect of different types of land circulation on farmers' decision-making regarding agricultural planting structure, using field survey data involving 1,120 households in Hubei province, China, and PSM (propensity score matching) and GPSM (general propensity score matching) methods. Results from PSM showed that land circulation could significantly increase farmers' decisions to plant food crops, which confirms the positive effect of rural land circulation on the "grain orientation" of crop planting structure. Results from GPSM further indicate that the total land circulation, the paddy land circulation, and the dry land circulation all have significantly positive effects on planting structure adjustment towards "grain orientation." Additionally, planting structure adjustment towards "grain orientation" increases as the scale of land circulation increases, and the former shows a higher rate of increase than the latter, which confirms that rural land circulation facilitates an adjustment in structure towards planting food crops.

Artificial intelligence (AI) assisted human brain research is a dynamic interdisciplinary field with great interest, rich literature, and huge diversity. The diversity in research topics and technologies keeps increasing along with the tremendous growth in application scope of AI-assisted human brain research. A comprehensive understanding of this field is necessary to assess research efficacy, (re)allocate research resources, and conduct collaborations. This paper combines the structural topic modeling (STM) with the bibliometric analysis to automatically identify prominent research topics from the large-scale, unstructured text of AI-assisted human brain research publications in the past decade. Analyses on topical trends, correlations, and clusters reveal distinct developmental trends of these topics, promising research orientations, and diverse topical distributions in influential countries/regions and research institutes. These findings help better understand scientific and technological AI-assisted human brain research, provide insightful guidance for resource (re)allocation, and promote effective international collaborations.

The aim of this study was to determine the effect of rotenone stress on Aphis glycines Matsumura (Hemiptera: Aphididae) populations in different habitats of Northeast China. The changes in kinase expression activity of endogenous substances (proteins, total sugars, trehalose, cholesterol, and free amino acids), detoxifying enzymes (cytochrome P450 and glutathione S-transferase), and metabolic enzymes (proteases and phosphofructokinases) in specimens from three populations were compared before and after stress with rotenone at median lethal concentration (LC50) and their response mechanisms were analyzed. Following a 24 h treatment with rotenone, the average LC50 rotenone values in A. glycines specimens from field populations A and B, and a laboratory population were 4.39, 4.61, and 4.03 mg/L, respectively. The degree of changes in the kinase expression activity of endogenous substances also differed, which indicated a difference in the response of A. glycines specimens from varying habitats to LC50 rotenone stress. The content of endogenous substances, detoxifying enzymes, and metabolic enzymes, except for that of free amino acids, changed significantly in all populations treated with rotenone at LC50 compared with that in the control (P < 0.05). The decrease in protein and trehalose content, and the obstruction of cholesterol transportation owing to decreased feeding in stressed individuals were the causes of A. glycines death after rotenone treatment. Aphis glycines resistance to rotenone may be related to cytochrome P450 expression.

The genus Angelica encompasses 80 species worldwide. Among them, only Angelica sinensis is widely used in China and Japan. To explore the quality and geographical distribution of A. sinensis, we collected 1,530 plants from Gansu Province and analyzed them for their contents of chlorogenic acid (CA), ferulic acid (FA), senkyunolide I(SI), senkyunolide A(SA), senkyunolide H (SH), coniferyl ferulate (CF), ligustilide (LI), and butenyl phthalide (BP) using UPLC. We also assessed the relationship between the ecological environment and quality of A. sinensis through maximum entropy modeling and a geographical information system. The habitat suitability distribution demonstrated that the most influential ecological factors for the growth of A. sinensis were altitude, precipitation during March, May, and December, precipitation during the wettest month, and the soil pH. The most suitable areas for cultivation are concentrated to the south of Gansu Province, including Linxia Hui Autonomous Prefecture, Dingxi City, Tianshui City, south of Wuwei City, east of Gannan Tibetan Autonomous Prefecture, north of Longnan City, and northwest of Pingliang City. The quality suitability regionalization analysis divulged that the most influential ecological factors for the index components of A. sinensis were the altitude, sunshine, rainfall, temperature, and soil pH. The highest quality A. sinensis grow in Dingxi City, Tangchang, Lixian, and Wen counties in Longnan City, Wushan County in Tianshui City, Lintan, Zhouqu, and Zhuoni counties in Gannan Tibetan Autonomous Prefecture, Kangle and Linxia counties in Linxia Hui Autonomous Prefecture. The experiment yielded highly accurate results (accuracy of 0.955), suggesting that the results were consistent with the actual distribution of A. sinensis in Gansu. The inferences of this research will naturally draw the attention of the authorities in the fields of natural resources and agriculture departments and provide a scientific basis for the rational selection of A. sinensis cultivation areas.

ObjectiveTo develop and validate an interactive nomogram to predict healthcare-associated infections (HCAIs) in the intensive care unit (ICU).MethodsA multicenter retrospective study was conducted to review 2017 data from six hospitals in Guizhou Province, China. A total of 1,782 ICU inpatients were divided into either a training set (n = 1,189) or a validation set (n = 593). The patients' demographic characteristics, basic clinical features from the previous admission, and their need for bacterial culture during the current admission were extracted from electronic medical records of the hospitals to predict HCAI. Univariate and multivariable analyses were used to identify independent risk factors of HCAI in the training set. The multivariable model's performance was evaluated in both the training set and the validation set, and an interactive nomogram was constructed according to multivariable regression model. Moreover, the interactive nomogram was used to predict the possibility of a patient developing an HCAI based on their prior admission data. Finally, the clinical usefulness of the interactive nomogram was estimated by decision analysis using the entire dataset.ResultsThe nomogram model included factor development (local economic development levels), length of stay (LOS; days of hospital stay), fever (days of persistent fever), diabetes (history of diabetes), cancer (history of cancer) and culture (the need for bacterial culture). The model showed good calibration and discrimination in the training set [area under the curve (AUC), 0.871; 95% confidence interval (CI), 0.848-0.894] and in the validation set (AUC, 0.862; 95% CI, 0.829-0.895). The decision curve demonstrated the clinical usefulness of our interactive nomogram.ConclusionsThe developed interactive nomogram is a simple and practical instrument for quantifying the individual risk of HCAI and promptly identifying high-risk patients.

Clinical studies in type 2 diabetes (T2D) primarily focused on the single nucleotide polymorphisms (SNPs) located in protein-coding regions. Recently, the SNPs located in noncoding regions have also been recognized to play an important role in disease susceptibility. The super enhancer is a cluster of transcriptional enhancers located in noncoding regions. It plays a critical role in cell-type specific gene expression. However, the exact mechanism of the super enhancer SNPs for T2D remains unclear. In this study, we integrated genome-wide association studies (GWASs) and T2D cell/tissue-specific histone modification ChIP-seq data to identify T2D-associated SNPs in super enhancer, followed by comprehensive bioinformatics analyses to further explore the functional importance of these SNPs. We identified several interesting T2D super enhancer SNPs. Interesting, most of them were clustered within the same or neighboring super enhancers. A number of SNPs are involved in chromatin interactive regulation and/or potentially influence the binding affinity of transcription factors. Gene Ontology (GO) analysis showed a significant enrichment in several well-known signaling pathways and regulatory process, e.g. WNT signaling pathway, which plays a key role in T2D metabolism. Our results highlighted the potential functional importance of T2D super enhancer SNPs, which may yield novel insights into the pathogenesis of T2D.

BackgroundSystemic sclerosis (SSc) is characterized by excessive fibrosis throughout the body. This leads to the release of extracellular matrix (ECM) fragments into circulation, where they may be quantified as biomarkers. The objectives were to investigate levels of ECM turnover biomarkers and the diagnostic power of these.MethodsDiffuse SSc patients (n = 40) fulfilling the ACR/EULAR 2013 classification criteria and asymptomatic controls were included. Patients were divided into early (10 years of symptoms; n = 20) diffuse SSc. Biomarkers of type I (C1M), III (C3A, C3M), IV (C4M), V (C5M) and VI (C6M) collagen degradation and type I (PRO-C1), II (PRO-C2), III (PRO-C3), IV (PRO-C4), V (PRO-C5) and VI (PRO-C6) collagen formation were measured in serum. Repeated measures ANOVA was used to test for differences in biomarker levels and the area under the receiver operating characteristic curve (AUC) was used to investigate the ability of the biomarkers to separate groups.ResultsIn early diffuse SSc, formation biomarkers of type III, IV, V and VI collagen were significantly increased compared to asymptomatic controls (p0.85 when assessing asymptomatic controls vs. diffuse SSc. Biomarkers of type VI collagen (PRO-C6 and C6M) turnover had the best separation with an AUC's of >0.90.ConclusionFormation biomarkers of ECM turnover were shown to be significantly different between asymptomatic controls and diffuse SSc. This pilot study suggest that serological biomarkers of the ECM turnover is potentially applicable in SSc.

Long non-coding RNAs (lncRNAs), tentatively identified as non-protein coding RNA, are transcripts more than 200nt in length and accounting for 98% of the whole genome of human being. Accumulating evidence showed aberrant expressions of lncRNAs are strongly correlated to the development of cancers. In this study, AF113014 is a new lncRNA identified from Microarray. We found AF113014 is differentially expressed between HCC cell lines and normal hepatocytes. Functionally, AF113014 inhibited proliferation of HCC cells both in vitro and in vivo, whereas the opposite effect was observed when AF113014 knockdown. Moreover, we identified that Egr2, a tumor suppressor gene, was a downstream target gene of AF113014. Furthermore, we discovered that AF113014 up-regulated Egr2 expression through interacting with miR-20a by using dual-luciferase reporter assay, qRT-PCR and Western blotting analysis. Our data provides a new insight for understanding the mechanisms of HCC.

The hepatitis B virus (HBV) infection could activate the immune system and induce extensive inflammatory response. As the most important inflammatory factor, interleukins are critical for anti-viral immunity. Here we investigated whether interleukin-34 (IL-34) play a role in HBV infection.In this study, we first found that both serum IL-34 and IL-34 mRNA in PBMCs in chronic HBV patients was significantly decreased compared to the healthy controls. Furthermore, both IL-34 protein and mRNA levels were declined hepatoma cells expressing HBV. In addition, the clinical parameters analysis found that serum IL-34 was significantly associated with HBV DNA (P = 0.0066), ALT (P = 0.0327), AST (P = 0.0435), TB (P = 0.0406), DB (P = 0.0368) and AFP (P = 0.0225). Correlation analysis also found that serum IL-34 negatively correlated with HBV DNA copies, ALT and AST. In vitro studies found that IL-34 treatment in HepAD38 and HepG2.2.15 cells markedly inhibited HBV DNA, total RNA, 3.5kb mRNA and HBc protein. In vivo studies further demonstrated IL-34 treatment in HBV transgenic mice exhibited greater inhibition on HBV DNA, total RNA, 3.5kb mRNA and HBc protein, suggesting the effect to IL-34 on HBV is likely due to host innate or adaptive immune response.Our study identified a novel interleukin, IL-34, which has anti-viral activity in HBV replication in hepatocytes in vitro and in vivo. These data suggest a rationale for the use of IL-34 in the HBV treatment.

Cordyceps sensu lato is a genus of arthropod-pathogenic fungi, which have been used traditionally as medicinal in Asia. Within the genus, Ophiocordyceps sinensis is the most coveted and expensive species in China. Nevertheless, harvesting wild specimens has become a challenge given that natural populations of the fungus are decreasing and because large-scale culture of it has not yet been achieved. The worldwide demand for products derived from cultivable fungal species with medicinal properties has increased recently. In this study, we propose a new species, Cordyceps nidus, which parasitizes underground nests of trapdoor spiders. This species is phylogenetically related to Cordyceps militaris, Cordyceps pruinosa, and a sibling species of Cordyceps caloceroides. It is found in tropical rainforests from Bolivia, Brazil, Colombia and Ecuador. We also investigated the medicinal potential of this fungus based on its biochemical properties when grown on four different culture media. The metabolic profile particularly that of nucleosides, in polar and non-polar extracts was determined by UPLC, and then correlated to their antimicrobial activity and total phenolic content. The metabolome showed a high and significant dependency on the substrate used for fungal growth. The mass intensities of nucleosides and derivative compounds were higher in natural culture media in comparison to artificial culture media. Among these compounds, cordycepin was the predominant, showing the potential use of this species as an alternative to O. sinensis. Furthermore, methanol fractions showed antimicrobial activity against gram-positive bacteria, and less than 3.00 mg of gallic acid equivalents per g of dried extract were obtained when assessing its total phenolic content by modified Folin-Ciocalteu method. The presence of polyphenols opens the possibility of further exploring the antioxidant capacity and the conditions that may enhance this characteristic. The metabolic composition and biochemical activity indicate potential use of C. nidus in pharmaceutical applications.

Phytophthora root rot caused by Phytophthora capsici (P. capsici) is a serious limitation to pepper production in Southern China, with high temperature and humidity. Mapping PRR resistance genes can provide linked DNA markers for breeding PRR resistant varieties by molecular marker-assisted selection (MAS). Two BC1 populations and an F2 population derived from a cross between P. capsici-resistant accession, Criollo de Morelos 334 (CM334) and P. capsici-susceptible accession, New Mexico Capsicum Accession 10399 (NMCA10399) were used to investigate the genetic characteristics of PRR resistance. PRR resistance to isolate Byl4 (race 3) was controlled by a single dominant gene, PhR10, that was mapped to an interval of 16.39Mb at the end of the long arm of chromosome 10. Integration of bulked segregant analysis (BSA) and Specific Length Amplified Fragment sequencing (SLAF-seq) provided an efficient genetic mapping strategy. Ten polymorphic Simple Sequence Repeat (SSR) markers were found within this region and used to screen the genotypes of 636 BC1 plants, delimiting PhR10 to a 2.57 Mb interval between markers P52-11-21 (1.5 cM away) and P52-11-41 (1.1 cM). A total of 163 genes were annotated within this region and 31 were predicted to be associated with disease resistance. PhR10 is a novel race specific gene for PRR, and this paper describes linked SSR markers suitable for marker-assisted selection of PRR resistant varieties, also laying a foundation for cloning the resistance gene.

A key challenge in thyroid carcinoma is preoperatively diagnosing malignant thyroid nodules. A novel diagnostic test that measures the expression of a 3-gene signature (DPP4, SCG5 and CA12) has demonstrated promise in thyroid carcinoma assessment. However, more reliable prediction methods combining clinical features with genomic signatures with high accuracy, good stability and low cost are needed.25 clinical information were recorded in 771 patients. Feature selection and validation were conducted using random forest. Thyroid samples and clinical data were obtained from 142 patients at two different hospitals, and expression of the 3-gene signature was measured using quantitative PCR. The predictive abilities of three models (based on the selected clinical variables, the gene expression profile, and integrated gene expression and clinical information) were compared. Seven clinical characteristics were selected based on a training set (539 patients) and tested in three test sets, yielding predictive accuracies of 82.3% (n = 232), 81.4% (n = 70), and 81.9% (n = 72). The predictive sensitivity, specificity, and accuracy were 72.3%, 80.5% and 76.8% for the model based on the gene expression signature, 66.2%, 81.8% and 74.6% for the model based on the clinical data, and 83.1%, 84.4% and 83.8% for the combined model in a 10-fold cross-validation (n = 142).These findings reveal that the integrated model, which combines clinical data with the 3-gene signature, is superior to models based on gene expression or clinical data alone. The integrated model appears to be a reliable tool for the preoperative diagnosis of thyroid tumors.

OBJECTIVES:Anti-muscarinic acetylcholine type-3 receptor (anti-M3R) autoantibodies have been suggested to be pathogenic for primary Sjögren's syndrome (pSS), and the second extracellular loop of M3R is suspected to carry a disease-promoting epitope. In this study, we aimed to evaluate the pathogenicity of autoantibodies against peptides derived from the second extracellular loop of M3R in mice and to determine whether those autoantibodies could be used as biomarker for pSS. METHODS:BALB/c mice were immunized with modified linear or cyclic peptides of the second extracellular loop of M3R. The function of exocrine glands was evaluated by measuring the secretion of saliva and tears. The histological evaluations were performed by using H&E staining or direct immunofluorescence staining. Autoantibodies against linear or cyclic peptides of the second extracellular loop of M3R in human and mice were determined using ELISA. RESULTS:Immunization induced mice to produce autoantibodies against the linear or cyclic peptides of the second extracellular loop of M3R, and those autoantibodies could bind onto salivary glands. However, those mice showed neither impairment in the secretion of tears or saliva nor histological abnormality in the exocrine glands. Furthermore, passive transfer of the IgG isolated from the immunized mice into healthy mice did not induced the dysfunction of the exocrine glands. The prevalence of autoantibodies against the peptides of the second extracellular loop of M3R was low in pSS patients, and it did not differ significantly from that in healthy controls. CONCLUSIONS:Our results suggest that the autoantibodies against peptides of the second extracellular loop of M3R are not pathogenic in vivo and they are not suitable as biomarkers for pSS diagnosis.

A novel actinobacterium, designated strain JXJ CY 19T, was isolated from a culture mat of Microcystis aeruginosa FACHB-905 collected from Dianchi Lake, South-west China. 16S rRNA gene sequences comparison of strain JXJ CY 19T and the available sequences in the GenBank database showed that the strain was closely related to Modestobacter marinus 42H12-1T (99.1% similarity) and Modestobacter roseus KLBMP 1279T (99.0%). The isolate had meso-diaminopimelic in the cell wall with whole-cell sugars of mannose, rhamnose, ribose, glucose, galactose, and arabinose. The menaquinone detected was MK-9(H4), while the major cellular fatty acids include C17:1 ω8c, C15:0 iso, C15:1 iso G and C16:0 iso. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside and an unidentified phospholipid. The DNA-DNA hybridization values between strains JXJ CY 19T and the closely related type strains Modestobacter marinus CGMCC 4.5581T and Modestobacter roseus NBRC 108673T were determined to be 50.8 ± 0.8% and 44.1 ± 1.7%, respectively. The DNA G+C content was 71.9 mol%. On the basis of the above taxonomic data and differences in physiological characters from the closely related type strains, strain JXJ CY 19T was recognized as a novel species of the genus Modestobacter, for which the name Modestobacter lacusdianchii sp. nov. (JXJ CY 19T = KCTC 39600T = CPCC 204352T) is proposed. The type strain JXJ CY 19T can solubilize calcium phosphate tribasic (Ca3(PO4)2), phytin and L-α-phosphatidylcholine. The phosphate-solubilizing property of the novel actinobacterium could be a possible factor for the increase in growth of Microcystis aeruginosa FACHB-905 in ecosystem where the amount of available soluble phosphate is limited such as Dianchi Lake.

We study the effect of subtle changes on the evolution in the scale-free (SF) networks. Three extended models are evolved based on competition and inner anti-preferential deletion in growth and preferential attachment processes. By nonlinear and dynamic controlling on randomness and determinacy, three models can self-organize into scale-free networks, and diverse scaling exponents appear. Moreover, the model with more determinacy has more stringent parameter control than randomness, especially in the edge deletion. Our results suggest that the nature of the topology universality and dissimilarity in SF networks may be the subtle changes of randomness and determinacy.

The hepatitis B virus (HBV) infection is accompanied by the induction of oxidative stress, especially mediated by HBV X protein (HBx). Oxidative stress has been implicated in a series of pathological states, such as DNA damage, cell survival and apoptosis. However, the host factor by which cells protect themselves under this oxidative stress is poorly understood.In this study, we first confirmed that HBV infection significantly induced oxidative stress. Moreover, viral protein HBx plays a major role in the oxidative stress induced by HBV. Importantly, we found that mitochondrial protein SIRT3 overexpression could decrease reactive oxygen species (ROS) induced by HBx while SIRT3 knockdown increased HBx-induced ROS. Importantly, SIRT3 overexpression abolished oxidative damage of HBx-expressing cells as evidenced by γH2AX and AP sites measurements. In contrast, SIRT3 knockdown promoted HBx-induced oxidative damage. In addition, we also observed that oxidant H2O2 markedly promoted HBV replication while the antioxidant N-acetyl-L-cysteine (NAC) inhibited HBV replication. Significantly, SIRT3 overexpression inhibited HBV replication by reducing cellular ROS level.Collectively, these data suggest HBx expression induces oxidative stress, which promotes cellular oxidative damage and viral replication during HBV pathogenesis. Mitochondrial protein SIRT3 protected HBx expressing-cells from oxidative damage and inhibited HBV replication possibly by decreased cellular ROS level. These studies shed new light on the physiological significance of SIRT3 on HBx-induced oxidative stress, which can contribute to the liver pathogenesis.

This paper aims to identify the key fields and their key technical points of oncology by patent analysis.Patents of oncology applied from 2006 to 2012 were searched in the Thomson Innovation database. The key fields and their key technical points were determined by analyzing the Derwent Classification (DC) and the International Patent Classification (IPC), respectively. Patent applications in the top ten DC occupied 80% of all the patent applications of oncology, which were the ten fields of oncology to be analyzed. The number of patent applications in these ten fields of oncology was standardized based on patent applications of oncology from 2006 to 2012. For each field, standardization was conducted separately for each of the seven years (2006-2012) and the mean of the seven standardized values was calculated to reflect the relative amount of patent applications in that field; meanwhile, regression analysis using time (year) and the standardized values of patent applications in seven years (2006-2012) was conducted so as to evaluate the trend of patent applications in each field. Two-dimensional quadrant analysis, together with the professional knowledge of oncology, was taken into consideration in determining the key fields of oncology. The fields located in the quadrant with high relative amount or increasing trend of patent applications are identified as key ones. By using the same method, the key technical points in each key field were identified. Altogether 116,820 patents of oncology applied from 2006 to 2012 were retrieved, and four key fields with twenty-nine key technical points were identified, including "natural products and polymers" with nine key technical points, "fermentation industry" with twelve ones, "electrical medical equipment" with four ones, and "diagnosis, surgery" with four ones.The results of this study could provide guidance on the development direction of oncology, and also help researchers broaden innovative ideas and discover new technological opportunities.

Viral genotype shift in chronic hepatitis B (CHB) patients during antiviral therapy has been reported, but the underlying mechanism remains elusive.38 CHB patients treated with ADV for one year were selected for studying genotype shift by both deep sequencing and Sanger sequencing method.Sanger sequencing method found that 7.9% patients showed mixed genotype before ADV therapy. In contrast, all 38 patients showed mixed genotype before ADV treatment by deep sequencing. 95.5% mixed genotype rate was also obtained from additional 200 treatment-naïve CHB patients. Of the 13 patients with genotype shift, the fraction of the minor genotype in 5 patients (38%) increased gradually during the course of ADV treatment. Furthermore, responses to ADV and HBeAg seroconversion were associated with the high rate of genotype shift, suggesting drug and immune pressure may be key factors to induce genotype shift. Interestingly, patients with genotype C had a significantly higher rate of genotype shift than genotype B. In genotype shift group, ADV treatment induced a marked enhancement of genotype B ratio accompanied by a reduction of genotype C ratio, suggesting genotype C may be more sensitive to ADV than genotype B. Moreover, patients with dominant genotype C may have a better therapeutic effect. Finally, genotype shifts was correlated with clinical improvement in terms of ALT.Our findings provided a rational explanation for genotype shift among ADV-treated CHB patients. The genotype and genotype shift might be associated with antiviral efficiency.

BACKGROUND/AIM:Recent genome-wide association studies have identified several loci influencing lipid levels. The present study focused on the triglycerides (TG)-associated locus, the APOA4-APOA5-ZNF259-BUD13 gene cluster on chromosome 11, to explore the role of genetic variants in this gene cluster in the development of increasing TG levels and coronary heart disease (CHD). METHODOLOGY/PRINCIPAL FINDINGS:Six single nucleotide polymorphisms (SNPs), rs4417316, rs651821, rs6589566, rs7396835, rs964184 and rs17119975, in the APOA4-APOA5-ZNF259-BUD13 gene cluster were selected and genotyped in 5374 healthy Chinese subjects. There were strong significant associations between the six SNPs and TG levels (P < 1.0 × 10(-8)). Moreover, a weighted genotype score was found to be associated with TG levels (P = 3.28 × 10(-13)). The frequencies of three common haplotypes were observed to be significantly different between the high TG group and the low TG group (P < 0.05). However, no significant effects were found for the SNPs regarding susceptibility to CHD in the Chinese case-control populations. CONCLUSIONS/SIGNIFICANCE:This study highlights the genotypes, genotype scores and haplotypes of the APOA4-APOA5-ZNF259-BUD13 gene cluster that were associated with TG levels in a Chinese population; however, the genetic variants in this gene cluster did not increase the risk of CHD in the Chinese population.

In China, approximately 30,000 babies are born with hearing impairment each year. However, the molecular factors causing congenital hearing impairment in the Xiamen area of Fujian province have not been evaluated. To provide accurate genetic testing and counseling in the Xiamen area, we investigated the molecular etiology of non-syndromic deafness in a deaf population from Xiamen. Unrelated students with hearing impairment (n = 155) who attended Xiamen Special Education School in Fujian Province were recruited for this study. Three common deafness-related genes, GJB2, SLC26A4, and mtDNA12SrRNA, were analyzed using all-exon sequencing. GJB2 mutations were detected in 27.1% (42/155) of the entire cohort. The non-syndromic hearing loss (NSHL) hotspot mutations c.109G>A (p.V37I) and c.235delC were found in this population, whereas the Caucasian hotspot mutation c.35delG was not. The allelic frequency of the c.109G>A mutation was 9.03% (28/310), slightly higher than that of c.235delC (8.39%, 26/310), which is the most common GJB2 mutation in most areas of China. The allelic frequency of the c.109G>A mutation was significantly higher in this Xiamen's deaf population than that in previously reported cohorts (P = 0.00). The SLC26A4 mutations were found in 16.77% (26/155) of this cohort. The most common pathogenic allele was c.IVS7-2A>G (6.13%, 19/310), and the second most common was the c.1079C>T (p.A360V) mutation (1.94%, 6/310) which has rarely been reported as a hotspot mutation in other studies. The mutation rate of mtDNA12SrRNA in this group was 3.87% (6/155), all being the m.A1555G mutation. These findings show the specificity of the common deaf gene-mutation spectrum in this area. According to this study, there were specific hotspot mutations in Xiamen deaf patients. Comprehensive sequencing analysis of the three common deaf genes can help portray the mutation spectrum and develop optimal testing strategies for deaf patients in this area.

Cytokinins (CKs) regulate plant development and growth via a two-component signaling pathway. By forward genetic screening, we isolated an Arabidopsis mutant named grow fast on cytokinins 1 (gfc1), whose seedlings grew larger aerial parts on MS medium with CK. gfc1 is allelic to a previously reported cutin mutant defective in cuticular ridges (dcr). GFC1/DCR encodes a soluble BAHD acyltransferase (a name based on the first four enzymes characterized in this family: Benzylalcohol O-acetyltransferase, Anthocyanin O-hydroxycinnamoyltransferase, anthranilate N-hydroxycinnamoyl/benzoyltransferase and Deacetylvindoline 4-O-acetyltransferase) with diacylglycerol acyltransferase (DGAT) activity in vitro and is necessary for normal cuticle formation on epidermis in vivo. Here we show that gfc1 was a CK-insensitive mutant, as revealed by its low regeneration frequency in vitro and resistance to CK in adventitious root formation and dark-grown hypocotyl inhibition assays. In addition, gfc1 had de-etiolated phenotypes in darkness and was therefore defective in skotomorphogenesis. The background expression levels of most type-A Arabidopsis Response Regulator (ARR) genes were higher in the gfc1 mutant. The gfc1-associated phenotypes were also observed in the cutin-deficient glycerol-3-phosphate acyltransferase 4/8 (gpat4/8) double mutant [defective in glycerol-3-phosphate (G3P) acyltransferase enzymes GPAT4 and GPAT8, which redundantly catalyze the acylation of G3P by hydroxyl fatty acid (OH-FA)], but not in the cutin-deficient mutant cytochrome p450, family 86, subfamily A, polypeptide 2/aberrant induction of type three 1 (cyp86A2/att1), which affects the biosynthesis of some OH-FAs. Our results indicate that some acyltransferases associated with cutin formation are involved in CK responses and skotomorphogenesis in Arabidopsis.

Improving farming practices of soil and water conservation has profound effects on the yield of wheat (Triticum aestivum L.) in dryland farming regions of the Loess Plateau in China. Mulching has proven to be an effective practice to increase crop yield, and possibly contribute to replenishing groundwater. This evaluation study collected and analyzed the data of 1849 observations published in 38 papers using meta-analysis to investigate effects of the mulching practices on wheat yield in terms of different rainfall and regions in comparison with conventional tillage. The main results of the study follow. The effects of the mulching practices were ranked in the order of RFM (ridge-furrow mulching) > MTMC (mulching with two materials combined) > MOM (mulching with other materials) > WSM (wheat straw mulching) > FM (flat mulching). The effects of the mulching practices at the different levels of rainfall during the wheat growing season were in the order: (< 150 mm) > (> 250 mm) > (150-250 mm). The effects of the mulching practices in the different regions were in the order of Henan > Shanxi > Shaanxi > Gansu. WSM, MTMC and FM performed better in improving wheat yield for rainfall of < 150, 150-250 and > 250 mm during the growing season, respectively. The wheat yield with FM, MTMC, MOM and MOM was higher than those with the other mulching practices in Shaanxi, Gansu, Henan and Shanxi. The wheat yield with RFM was 27.4% higher than that with FM, indicating that RFM was the most effective practice to improve wheat yield among all the practices. These findings have important implications for choosing appropriate crop field management to improve wheat yield.

The family Accipitridae is one of the largest groups of non-passerine birds, including 68 genera and 243 species globally distributed. In the present study, we determined the complete mitochondrial sequences of two species of accipitrid, namely Aquila fasciata and Buteo lagopus, and conducted a comparative mitogenome analysis across the family. The mitogenome length of A. fasciata and B. lagopus are 18,513 and 18,559 bp with an A + T content of 54.2% and 55.0%, respectively. For both the two accipitrid birds mtDNAs, obvious positive AT-skew and negative GC-skew biases were detected for all 12 PCGs encoded by the H strand, whereas the reverse was found in MT-ND6 encoded by the L strand. One extra nucleotide'C'is present at the position 174 of MT-ND3 gene of A. fasciata, which is not observed at that of B. lagopus. Six conserved sequence boxes in the Domain II, named boxes F, E, D, C, CSBa, and CSBb, respectively, were recognized in the CRs of A. fasciata and B. lagopus. Rates and patterns of mitochondrial gene evolution within Accipitridae were also estimated. The highest dN/dS was detected for the MT-ATP8 gene (0.32493) among Accipitridae, while the lowest for the MT-CO1 gene (0.01415). Mitophylogenetic analysis supported the robust monophyly of Accipitriformes, and Cathartidae was basal to the balance of the order. Moreover, we performed phylogenetic analyses using two other data sets (two mitochondrial loci, and combined nuclear and mitochondrial loci). Our results indicate that the subfamily Aquilinae and all currently polytypic genera of this subfamily are monophyletic. These two novel mtDNA data will be useful in refining the phylogenetic relationships and evolutionary processes of Accipitriformes.

Activation of the nuclear hormone receptor, PPARγ, with pharmacological agonists promotes a contractile vascular smooth muscle cell phenotype and reduces oxidative stress and cell proliferation, particularly under pathological conditions including vascular injury, restenosis, and atherosclerosis. However, pharmacological agonists activate both PPARγ-dependent and -independent mechanisms in multiple cell types confounding efforts to clarify the precise role of PPARγ in smooth muscle cell structure and function in vivo. We, therefore, designed and characterized a mouse model with smooth muscle cell-targeted PPARγ overexpression (smPPARγOE). Our results demonstrate that smPPARγOE attenuated contractile responses in aortic rings, increased aortic compliance, caused aortic dilatation, and reduced mean arterial pressure. Molecular characterization revealed that compared to littermate control mice, aortas from smPPARγOE mice expressed lower levels of contractile proteins and increased levels of adipocyte-specific transcripts. Morphological analysis demonstrated increased lipid deposition in the vascular media and in smooth muscle of extravascular tissues. In vitro adenoviral-mediated PPARγ overexpression in human aortic smooth muscle cells similarly increased adipocyte markers and lipid uptake. The findings demonstrate that smooth muscle PPARγ overexpression disrupts vascular wall structure and function, emphasizing that balanced PPARγ activity is essential for vascular smooth muscle homeostasis.

MicroRNAs (miRNAs) represent a class of endogenous non-coding small RNAs that play important roles in multiple biological processes by degrading targeted mRNAs or repressing mRNA translation. Thousands of miRNAs have been identified in many plant species, whereas only a limited number of miRNAs have been predicted in M. acuminata (A genome) and M. balbisiana (B genome). Here, previously known plant miRNAs were BLASTed against the Expressed Sequence Tag (EST) and Genomic Survey Sequence (GSS), a database of banana genes. A total of 32 potential miRNAs belonging to 13 miRNAs families were detected using a range of filtering criteria. 244 miRNA:target pairs were subsequently predicted, most of which encode transcription factors or enzymes that participate in the regulation of development, growth, metabolism, and other physiological processes. In order to validate the predicted miRNAs and the mutual relationship between miRNAs and their target genes, qRT-PCR was applied to detect the tissue-specific expression levels of 12 putative miRNAs and 6 target genes in roots, leaves, flowers, and fruits. This study provides some important information about banana pre-miRNAs, mature miRNAs, and miRNA target genes and these findings can be applied to future research of miRNA functions.

Pelvic organ prolapse (POP) is a common gynecological disorder; however, the genetic components remain largely unidentified. Exome sequencing has been widely used to identify pathogenic gene mutations of several diseases because of its high chromosomal coverage and accuracy. In this study, we performed whole exome sequencing (WES), for the first time, on 8 peripheral blood DNA samples from representative POP cases. After filtering the sequencing data from the dbSNP database (build 138) and the 1000 Genomes Project, 2 missense variants in WNK1, c.2668G > A (p.G890R) and c.6761C> T (p.P2254L), were identified and further validated via Sanger sequencing. In validation stage, the c.2668G > A (p.G890R) variant and 8 additional variants were detected in 11 out of 161 POP patients. All these variants were absent in 231 healthy controls. Functional experiments showed that fibroblasts from the utero-sacral ligaments of POP with WNK1 mutations exhibited loose and irregular alignment compared with fibroblasts from healthy controls. In sum, our study identified a novel gene, WNK1, for POP susceptibility, expanded the causal mutation spectrums of POP, and provided evidence for the genetic diagnosis and medical management of POP in the future.

Hydrogen sulfide (H2S), as a potential gaseous messenger molecule, has been suggested to play important roles in a wide range of physiological processes in plants. The aim of present study was to investigate which set of proteins is involved in H2S-regulated metabolism or signaling pathways. Spinacia oleracea seedlings were treated with 100 µM NaHS, a donor of H2S. Changes in protein expression profiles were analyzed by 2-D gel electrophoresis coupled with MALDI-TOF MS. Over 1000 protein spots were reproducibly resolved, of which the abundance of 92 spots was changed by at least 2-fold (sixty-five were up-regulated, whereas 27 were down-regulated). These proteins were functionally divided into 9 groups, including energy production and photosynthesis, cell rescue, development and cell defense, substance metabolism, protein synthesis and folding, cellular signal transduction. Further, we found that these proteins were mainly localized in cell wall, plasma membrane, chloroplast, mitochondria, nucleus, peroxisome and cytosol. Our results demonstrate that H2S is involved in various cellular and physiological activities and has a distinct influence on photosynthesis, cell defense and cellular signal transduction in S. oleracea leaves. These findings provide new insights into proteomic responses in plants under physiological levels of H2S.

BackgroundOver-expressed eukaryotic initiation factor 3a (eIF3a) in non-small cell lung cancer (NSCLC) contributed to cisplatin sensitivity. However, the role of eIF3a in oncogenesis was still controversial. This study was designed to investigate the prognostic impact of eIF3a and p27 in radically resected NSCLC patients.MethodsThe expression levels of subcellular eIF3a and p27 were evaluated immunohistochemically in 537 radically resected NSCLC samples, and another cohort of 210 stage II NSCLC patients. Disease specific survival (DSS) and disease free survival (DFS) were analyzed by Kaplan-Meier method and Cox regression model.ResultsThe subcellular expression of eIF3a was strongly correlated with status of p27 (Spearman rank coefficient correlation for cytoplasmic eIF3a and p27=0.653, for nuclear staining=0.716). Moreover, survival analysis revealed favorable prognostic impact of nuclear eIF3a, p27, and the combination high nuclear staining on NSCLC (Hazards Ratio=0.360, 95%CI=0.109-0.782, P=0.028). In addition, interaction research between biomarkers and chemotherapy status disclosed cisplatin-based regimen trend to prolong DSS of stage II NSCLC patients with high eIF3a-C (P=0.036)and low p27-N (P=0.031).ConclusionsOur findings suggested altered eIF3a expression closely correlated with p27 status, and the association was of prognostic value for resected NSCLC. Altered expression of eIF3a and p27 predicted prognosis of NSCLC independently.

Acid rain (AR) is a serious environmental issue inducing harmful impacts on plant growth and development. It has been reported that Liquidambar formosana, considered as an AR-sensitive tree species, was largely injured by AR, compared with Schima superba, an AR-tolerant tree species. To clarify the different responses of these two species to AR, a comparative proteomic analysis was conducted in this study. More than 1000 protein spots were reproducibly detected on two-dimensional electrophoresis gels. Among them, 74 protein spots from L. formosana gels and 34 protein spots from S. superba gels showed significant changes in their abundances under AR stress. In both L. formosana and S. superba, the majority proteins with more than 2 fold changes were involved in photosynthesis and energy production, followed by material metabolism, stress and defense, transcription, post-translational and modification, and signal transduction. In contrast with L. formosana, no hormone response-related protein was found in S. superba. Moreover, the changes of proteins involved in photosynthesis, starch synthesis, and translation were distinctly different between L. formosana and S. superba. Protein expression analysis of three proteins (ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit, ascorbate peroxidase and glutathione-S-transferase) by Western blot was well correlated with the results of proteomics. In conclusion, our study provides new insights into AR stress responses in woody plants and clarifies the differences in strategies to cope with AR between L. formosana and S. superba.

Endometrioid endometrial carcinoma (EEC) is the most dominant subtype of endometrial cancer. Aberrant transcriptional regulation has been implicated in EEC. Herein, we characterized mRNA and miRNA transcriptomes by RNA sequencing in EEC to investigate potential molecular mechanisms underlying the pathogenesis. Total mRNA and small RNA were simultaneously sequenced by next generation sequencing technology for 3 pairs of stage I EEC and adjacent non-tumorous tissues. On average, 52,716,765 pair-end 100 bp mRNA reads and 1,669,602 single-end 50 bp miRNA reads were generated. Further analysis indicated that 7 miRNAs and 320 corresponding target genes were differentially expressed in the three stage I EEC patients. Six of all the seven differentially expressed miRNAs were targeting on eleven differentially expressed genes in the cell cycle pathway. Real-time quantitative PCR in sequencing samples and other independent 21 pairs of samples validated the miRNA-mRNA differential co-expression, which were involved in cell cycle pathway, in the stage I EEC. Thus, we confirmed the involvement of hsa-let-7c-5p and hsa-miR-99a-3p in EEC and firstly found dysregulation of hsa-miR-196a-5p, hsa-miR-328-3p, hsa-miR-337-3p, and hsa-miR-181c-3p in EEC. Moreover, synergistic regulations among these miRNAs were detected. Transcript sequence variants such as single nucleotide variant (SNV) and short insertions and deletions (Indels) were also characterized. Our results provide insights on dysregulated miRNA-mRNA co-expression and valuable resources on transcript variation in stage I EEC, which implies the new molecular mechanisms that underlying pathogenesis of stage I EEC and supplies opportunity for further in depth investigations.

BACKGROUND: Due to the increase incidents of premarital sex and the lack of reproductive health services, college students are at high risk of HIV/AIDS infections in China. This study was designed to examine the predictors of consistency of condom use among college students based on the Information-Motivation-Behavioral Skills (IMB) model and to describe the relationships between the model constructs. METHODS: A cross-sectional study was conducted to assess HIV/AIDS related information, motivation, behavioral skills and preventive behavior among college students in five colleges and universities in Nanjing, China. An anonymous questionnaire survey was conducted for data collection, and the structural equation model (SEM) was used to assess the IMB model. RESULTS: A total of 3183 participants completed this study. The average age was 19.90 years (SD = 1.43, range 16 to 25). 342 (10.7%) participants of them reported having had premarital sex, among whom 30.7% reported having had a consistent condom use, 13.7% with the experience of abortion (including the participants whose sex partner has the same experience), 32.7% of participants had experience of multiple sex partners. The final IMB model provided acceptable fit to the data (CFI = 0.992, RMSEA = 0.028). Preventive behavior was significantly predicted by behavioral skills (β = 0.754, P

Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase that is implicated in plethora of biological processes, including metabolism, aging, stress response, and tumorigenesis. Telomerase (TERT) is essential for telomere maintenance. Activation of TERT is considered a crucial step in tumorigenesis, and therefore it is a potential therapeutic target against cancer. We have recently found that SIRT1 expression is highly elevated in hepatocellular carcinoma, and the depletion of SIRT1 leads to substantial reduction in TERT mRNA and protein expression. However, the underlying molecular mechanism of SIRT1-dependent TERT expression remains uncharacterized. Here, we elucidated if SIRT1 regulates TERT expression via transcriptional, epigenetic and post-transcriptional mechanisms. We report that depletion of SIRT1 does not lead to significant change in transcriptional activity and CpG methylation patterns of the TERT promoter, nor does it affect mRNA stability or 3'-UTR regulation of TERT. Intriguingly, depletion of SIRT1 is associated with substantial induction of acetylated histone H3-K9 and reduction of trimethyl H3-K9 at the TERT gene, which are known to be associated with gene activation. Our data revealed that SIRT1 regulates histone acetylation and methylation at the TERT promoter. We postulated that SIRT1 may regulate TERT expression via long-range interaction, or via yet unidentified histone modifications.

BACKGROUND: Antinuclear antibodies (ANA), smooth muscle antibodies (SMA) and antibodies to a soluble liver antigen/liver pancreas (anti-SLA/LP) are useful markers that can help clinicians to diagnose and classify autoimmune hepatitis (AIH). OBJECTIVES: To determine whether ANA, SMA and anti-SLA/LP help to accurately diagnose patients with AIH. SEARCH STRATEGY: The PubMed, CNKI, WANFANG, and SinoMed databases were accessed to retrieve studies published in English and Chinese. Studies published up to October 2013 were reviewed. SELECTION CRITERIA: Studies on the diagnostic value of ANA, SMA or anti-SLA/LP in the diagnosis of known or suspected AIH were included. DATA COLLECTION AND ANALYSIS: Two authors evaluated studies independently and rated their methodological quality using quality assessment of diagnostic accuracy studies (QUADAS) tools; relevant data were abstracted. The random-effects method was used to summarize sensitivities, specificities, positive and negative likelihood ratios, and diagnostic odds ratios (DORs) from all 29 studies. RESULTS: The pooled sensitivity, specificity, positive and negative likelihood ratios, and DOR for ANA were 0.650 (95% confidence interval [CI], 0.619 to 0.680), 0.751 (95%CI, 0.737 to 0.764), 3.030 (95%CI, 2.349 to 3.910), 0.464 (95%CI, 0.356 to 0.604), and 7.380 (95%CI, 4.344 to 12.539), respectively. For SMA, the values were 0.593 (95%CI, 0.564 to 0.621), 0.926 (95%CI, 0.917 to 0.934), 11.740 (95%CI, 7.379 to 18.678), 0.449 (95%CI, 0.367 to 0.549), and 31.553 (95%CI, 17.147 to 58.060), respectively. Finally, for anti-SLA/LP, the values were 0.194 (95%CI, 0.168 to 0.222), 0.989 (95%CI, 0.985 to 0.993), 11.089 (95%CI, 7.601 to 16.177), 0.839 (95%CI, 0.777 to 0.905), and 16.867 (95%CI, 10.956 to 25.967), respectively. AUTHORS' CONCLUSIONS: ANA provided moderate sensitivity and specificity, while SMA gave moderate sensitivity and high specificity, and anti-SLA/LP exhibited low sensitivity and high specificity. All three antibodies were limited by their unsatisfactory sensitivities and lack of consistency.

Berberine is a primary component of the most functional extracts of Coptidis rhizome used in traditional Chinese medicine for centuries. Recent reports indicate that Berberine has the potential to prevent and treat Alzheimer's disease (AD). The previous studies reported that Calyculin A (CA) impaired the axonal transport in neuroblastoma-2a (N2a) cells. Berberine attenuated tau hyperphosphorylation and cytotoxicity induced by CA. Our study aimed at investigating the effects of Berberine on the axonal transport impairment induced by CA in N2a cells. The results showed that Berberine could protect the cell from CA -induced toxicity in metabolism and viability, as well as hyperphosphorylation of tau and neurofilaments (NFs). Furthermore, Berberine could reverse CA-induced axonal transport impairment significantly. Berberine also partially reversed the phosphorylation of the catalytic subunit of PP-2A at Tyrosine 307, a crucial site negatively regulating the activity of PP-2A, and reduced the levels of malondialdehyde and the activity of superoxide dismutase, markers of oxidative stress, induced by CA. The present work for the first time demonstrates that Berberine may play a role in protecting against CA-induced axonal transport impairment by modulating the activity of PP-2A and oxidative stress. Our findings also suggest that Berberine may be a potential therapeutic drug for AD.

Lung cancer is one of the most common cancers and is the leading cause of death worldwide. Platinum-based chemotherapy is the main treatment method in lung cancer patients. Our previous studies indicated that single nucleotide polymorphisms (SNPs) in some transporter genes played important role in platinum-based chemotherapy efficacy. The aim of this study was to investigate the association of SNPs in transporter genes and platinum-based chemotherapy efficacy. The main polymorphisms on transporters OCT2, LRP, AQP2, AQP9 and TMEM205 genes were genotyped in 338 lung cancer patients. The rs195854 in genotypic model, rs896412 in genotypic and recessive models for all subjects showed significant association with chemotherapy response. In stratification analysis, TMEM205 rs896412, OCT2 rs1869641 and rs195854, AQP9 rs1516400 and AQP2 rs7314734 showed significant relation to chemotherapy response. In conclusion, the genetic polymorphisms in OCT2, AQP2, AQP9 and TMEM205 may contribute to chemotherapy response in lung cancer patients.

The two-gram salt-restriction-spoons, which can be used to reduce the salt intake of people, had been handed out for free by the Chinese government to the citizens several years ago, but only a small fraction of residents use such a spoon currently. Since no studies have been conducted to investigate relevant influencing factors, this study was designed to explore the determinants of salt-restriction-spoon using behavior (SRB) in China.This cross-sectional study was conducted in Beijing, China. Altogether 269 rural residents and 244 urban residents aged over 18 were selected by convenience sampling method in 2012. Variables measured in a questionnaire designed according to the Health Belief Model (HBM) included socio-demographics, perceived susceptibility, perceived severity, perceived benefits, perceived objective barriers, perceived subjective barriers, self-efficacy, knowledge of hypertension, cues to action, and SRB. Answers to the questionnaire were obtained from all the participants, and 24-hour urine samples were collected to determine the 24-hour urinary sodium excretion (24HUNa). Path analyses were used to explore the determinants of SRB.Approximately 22.7% and 45.3% of residents used a salt-restriction-spoon everyday in the rural and urban areas, respectively. The average 24HUNa was 211.19±98.39 mmol for rural residents and 109.22±58.18 mmol for urban residents. Path analyses shown that perceived objective barriers, perceived benefits, perceived severity, knowledge and age were related to SRB and 24HUNa for both rural and urban participants, among which perceived objective barrier (β = - 0.442 and β = - 0.543, respectively) was the most important determinant.Improvement of the current salt-restriction-spoon and education on the right usage of the salt-restriction-spoon, the severity of hypertension, and the benefit of salt reduction are necessary, especially among those who are relatively young but at risk of hypertension, those who have lower education levels, and those who live in the rural areas.

Overexpressed Human epidermal growth factor receptor 2 (HER2) drives the biology of 20% breast cancer and is a prediction of a poor prognosis for patients. HER2-targeted therapies significantly improve outcomes for HER2-positive patients. Traditional Chinese herbs/medicines have been used to treat breast cancer patients including HER2-positive patients in Asia for decades. Although the traditional medicines demonstrate efficacy in clinics for HER2-positive patients, the mechanism is largely unknown. In this article, we screened a 10,000 natural product library in 6 different cell lines representing breast cancer, and assessed the ability of each drug to cause cytotoxicity through a high-throughput screening approach. We have identified eight natural compounds that selectively inhibit the proliferation of HER2-positive cells. Two of the hit compounds, peonidin-3-glucoside and cyaniding-3-glucoside, are both extracts from black rice. They inhibit the phospho-HER2 and phospho-AKT and were confirmed to induce HER2-psotive breast cancer cells apoptosis both in vitro and in vivo. Peonidin-3-glucoside and cyaniding-3-glucoside treatments significantly reduced the tumor size and volume in vivo compared to the control group. There is no significant difference of antitumorgenic effects between peonidin-3-glucoside and cyaniding-3-glucoside treatments.

Understanding the pathology resulting from Staphylococcus aureus and Pseudomonas aeruginosa polymicrobial wound infections is of great importance due to their ubiquitous nature, increasing prevalence, growing resistance to antimicrobial agents, and ability to delay healing. Methicillin-resistant S. aureus USA300 is the leading cause of community-associated bacterial infections resulting in increased morbidity and mortality. We utilized a well-established porcine partial thickness wound healing model to study the synergistic effects of USA300 and P. aeruginosa on wound healing. Wound re-epithelialization was significantly delayed by mixed-species biofilms through suppression of keratinocyte growth factor 1. Pseudomonas showed an inhibitory effect on USA300 growth in vitro while both species co-existed in cutaneous wounds in vivo. Polymicrobial wound infection in the presence of P. aeruginosa resulted in induced expression of USA300 virulence factors Panton-Valentine leukocidin and α-hemolysin. These results provide evidence for the interaction of bacterial species within mixed-species biofilms in vivo and for the first time, the contribution of virulence factors to the severity of polymicrobial wound infections.

Dendrobium spp. are traditional Chinese medicinal plants, and the main effective ingredients (polysaccharides and alkaloids) have pharmacologic effects on gastritis infection, cancer, and anti-aging. Previously, we confirmed endophytic xylariaceous fungi as the dominant fungi in several Dendrobium species of tropical regions from China. In the present study, the diversity, taxonomy, and distribution of culturable endophytic xylariaceous fungi associated with seven medicinal species of Dendrobium (Orchidaceae) were investigated. Among the 961 endophytes newly isolated, 217 xylariaceous fungi (morphotaxa) were identified using morphological and molecular methods. The phylogenetic tree constructed using nuclear ribosomal internal transcribed spacer (ITS), large subunit of ribosomal DNA (LSU), and beta-tubulin sequences divided these anamorphic xylariaceous isolates into at least 18 operational taxonomic units (OTUs). The diversity of the endophytic xylariaceous fungi in these seven Dendrobium species was estimated using Shannon and evenness indices, with the results indicating that the dominant Xylariaceae taxa in each Dendrobium species were greatly different, though common xylariaceous fungi were found in several Dendrobium species. These findings implied that different host plants in the same habitats exhibit a preference and selectivity for their fungal partners. Using culture-dependent approaches, these xylariaceous isolates may be important sources for the future screening of new natural products and drug discovery.

AIM: The role of Sirtuin 1 (SIRT 1) in carcinogenesis is controversial. This study was to explore the association between the SIRT1 expression and the clinical characteristics, the responsiveness to chemotherapy and prognosis in Non-small cell lung cancer (NSCLC). METHODS: We enrolled 295 patients with inoperable advanced stage of NSCLC, namely, stage III (A+B) and IV NSCLC. All patients had received platinum-based chemotherapy after diagnosis and the chemotherapy response were evaluated. All patients were followed up for overall survival (OS) and progression free survival (PFS). In vitro, H292 cells were tranfected with SIRT1 small interfering RNA (siRNA). The cell biological behaviors and chemosensitivity to cisplatin treatment were studied. The in vivo tumorgenesis and metastasis assays were performed in nude mice. RESULTS: We found that the SIRT1 expressions were significantly associated with the tumor stage, tumor size and differentiation status. Patients with high SIRT 1 expressions had a significantly higher chance to be resistant to chemotherapy than those with low SIRT 1 expression. Patients with high expression of SIRT1 had significantly shorter OS and DFS than those with low expression. Cox analyses confirmed that the SIRT 1 expression was a strong predictor for a poor OS and PFS in NSCLC patients underwent Platinum-based chemotherapy. In vitro studies revealed that the reduced expression SIRT 1 by siRNA technique significantly inhibited cell proliferation, migration and invasion. More importantly, SIRT1 si-RNA significantly enhanced the chemosensitivity of H292 cells to cisplatin treatment. The in vivo tumorgenesis and metastasis assays showed that SIRT1 knockdown dramatically reduced the tumor volume and the metastatic ability in nude mice. CONCLUSION: Collectively, our data suggest that the SIRT1 expression may be a molecular marker associated with the NSLCLC clinical features, treatment responsiveness and prognosis of advanced NSCLC.

BACKGROUND: There is no special instrument to measure skills-based health literacy where it concerns infectious respiratory diseases. This study aimed to explore and evaluate a new skills-based instrument on health literacy regarding respiratory infectious diseases. METHODS: This instrument was designed to measure not only an individual's reading and numeracy ability, but also their oral communication ability and their ability to use the internet to seek information. Sixteen stimuli materials were selected to enable measurement of the skills, which were sourced from the WHO, China CDC, and Chinese Center of Health Education. The information involved the distribution of epidemics, immunization programs, early symptoms, means of disease prevention, individual's preventative behavior, use of medications and thermometers, treatment plans and the location of hospitals. Multi-stage stratified cluster sampling was employed to collect participants. Psychometric properties were used to evaluate the reliability and validity of the instrument. RESULTS: The overall degree of difficulty and discrimination of the instrument were 0.693 and 0.482 respectively. The instrument demonstrated good internal consistency reliability with a Cronbach's alpha of 0.864. As for validity, six factors were extracted from 30 items, which together explained 47.3% of the instrument's variance. And based on confirmatory factor analysis, the items were grouped into five subscales representing prose, document, quantitative, oral and internet based information seeking skills (χ(2) = 9.200, P>0.05, GFI = 0.998, TLI = 0.988, AGFI = 0.992, RMSEA = 0.028). CONCLUSION: The new instrument has good reliability and validity, and it could be used to assess the health literacy regarding respiratory infectious disease status of different groups.

ObjectiveTo evaluate the effect of an improved salt-restriction spoon on the attitude of salt-restriction, the using rate of salt-restriction-spoon, the actual salt intake, and 24-hour urinary sodium excretion (24HUNa).DesignA community intervention study.SettingTwo villages in Beijing.Participants403 local adult residents being responsible for home cooking.InterventionParticipants were randomly assigned to the intervention group or the control group. Those in the intervention group were provided with an improved salt-restriction-spoon and health education, and were informed of their actual salt intake and 24HUNa. Not any intervention was given to those in the control group.Main outcome measuresThe scores on the variables of Health Belief Model, the using rate of salt-restriction-spoon, the actual salt intake, and 24HUNa.AnalysisCovariance analyses, Chi-square tests, Student's t tests, and repeated measures analyses of variance.ResultsAfter 6 months of intervention, the intervention group felt significantly less objective barriers, and got access to significantly more cues to action as compared to the control group. The using rate and the correctly using rate of salt-restriction-spoon were significantly higher in the intervention group. The daily salt intake decreased by 1.42 g in the intervention group and by 0.28 g in the control group, and repeated measures analysis of variance showed significant change over time (F = 7.044, PConclusionsThe intervention effect was acceptable, therefore, the improved salt-restriction-spoon and corresponding health education could be considered as an alternative for salt reduction strategy in China and other countries where salt intake comes mainly from home cooking.

Keratinocyte migration during re-epithelization is crucial in wound healing under biochemical and biomechanical microenvironment. However, little is known about the underlying mechanisms whereby mechanical tension and cocultured fibroblasts or keratinocytes modulate the migration of keratinocytes or fibroblasts. Here we applied a tensile device together with a modified transwell assay to determine the lateral and transmembrane migration dynamics of human HaCaT keratinocytes or HF fibroblasts. A novel pattern of asymmetric migration was observed for keratinocytes when they were cocultured with non-contact fibroblasts, i.e., the accumulative distance of HaCaT cells was significantly higher when moving away from HF cells or migrating from down to up cross the membrane than that when moving close to HF cells or when migrating from up to down, whereas HF migration was symmetric. This asymmetric migration was mainly regulated by EGF derived from fibroblasts, but not transforming growth factor α or β1 production. Mechanical stretch subjected to fibroblasts fostered keratinocyte asymmetric migration by increasing EGF secretion, while no role of mechanical stretch was found for EGF secretion by keratinocytes. These results provided a new insight into understanding the regulating mechanisms of two- or three-dimensional migration of keratinocytes or fibroblasts along or across dermis and epidermis under biomechanical microenvironment.