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China's economy has shifted from the stage of high-speed growth to the stage of high-quality development. This paper selects panel data of 30 provinces, municipalities directly under the Central Government and autonomous regions (except Tibet) in mainland China with the time dimension of 2006–2016, selects indicators from five dimensions of innovation, coordination, greenness, openness and sharing, uses principal component analysis to construct a system of indicators of high-quality economic development, and uses the spatial Durbin model to empirically the impact of government investment behavior in the three industries on the regional economic high-quality development was studied. The results show that: first, there is a significant positive spatial correlation between China's economic quality development. Second, government investment in different industries has different effects on the quality development of the economy. Investment in the tertiary industry can boost employment, raise income level, promote economic quality development, and enhance sharing, coordination and innovation; investment in the secondary industry can enhance innovation, but because of the "crowding-out effect", it will reduce openness and sharing, and is not conducive to promoting economic quality development; investment in the primary industry can Investment in the primary industry can significantly improve coordination, but it will reduce innovation, greenness, openness and sharing, which will also have a negative impact on the overall high-quality economic development. Third, there is a significant spatial spillover effect of government investment behavior on regional economic quality development, and the economic quality development of this region will have an impact on neighboring regions. Finally, based on the research results, this paper puts forward countermeasure suggestions for promoting high-quality economic development. [ABSTRACT FROM AUTHOR]

The genetic modification of cattle has many agricultural and biomedical applications. However, random integration often leads to the unstable or differentially expression of the exogenous genes, which limit the application and development of transgenic technologies. Finding a safe locus suitable for site-specific insertion and efficient expression of exogenous genes is a good way to overcome these hurdles. In this study, we efficiently integrated three targeted vector into the cattle Rosa26 (cRosa26) by CRISPR/Cas9 technology in which EGFP was driven by CAG, EF1a, PGK and cRosa26 endogenous promoter respectively. The CRISPR/Cas9 knock-in system allows highly efficient gene insertion of different expression units at the cRosa26 locus. We also find that in the four cell lines, EGFP was stable expressed at different times, and the CAG promoter has the highest activity to activate the expression of EGFP, when compared with the cRosa26, EF1a and PGK promoter. Our results proved that cRosa26 was a locus that could integrate different expression units efficiently, and supported the friendly expression of different expression units. Our findings described here will be useful for a variety of studies using cattle. [ABSTRACT FROM AUTHOR]

Exposures to heavy metals have been linked to prostate cancer risk. The relationship of these exposures with serum prostate-specific antigen (PSA), a marker used for prostate cancer screening, is unknown. We examined whether total urinary arsenic, urinary dimethylarsonic acid, blood cadmium, blood lead, and total blood mercury levels are associated with elevated PSA among presumably healthy U.S. men. Prostate cancer-free men, aged ≥40 years, were identified from the 2003–2010 National Health and Nutrition Examination Survey. Logistic regression analyses with survey sample weights were used to examine the association between heavy metal levels and elevated PSA for the total population and stratified by black and white race, after adjusting for confounders. There were 5,477 men included. Approximately 7% had elevated PSA. Men with an elevated PSA had statistically significantly higher levels of blood cadmium and blood lead compared to men with a normal PSA (p-values ≤ 0.02), with black men having higher levels. After adjusting for age, race/ethnicity, body mass index, smoking, and education, there was no association found between any of the heavy metal levels and elevated PSA for the total population. In addition, there was no association found when stratified by black and white race. Further investigation is warranted in a larger cohort of men who persistently are exposed to these heavy metals. [ABSTRACT FROM AUTHOR]

Background: Anxiety is burdensome and common in youth. Sedentary behaviour has been identified as potentially modifiable dangerous factors for many diseases. Nevertheless, little is known about the relationship between sedentary behaviour and the risk of anxiety symptoms in youth. Therefore, we aimed to examine the association among youth in 24 low- and middle-income countries (LMICs). Methods: Data from the Global School-based Student Health Survey (GSHS) were analyzed in 59587 youth aged 12–15 years. Most of the country-wide data were nationally representative. Anxiety symptoms were self-reported. Multivariable logistic regression and meta-analyses of country-wise estimates were conducted. Results: The prevalence of anxiety symptoms was 10.3%. Countrywide meta-analysis demonstrated that sedentary behaviour of >2 h/day (vs.≤2 h/day) was associated with an increased risk of anxiety symptoms (OR = 1.22; 95% CI = 1.10–1.37). Conclusions: This study provides multi-national evidence of the dangerous effect of sedentary behaviour against anxiety symptoms among youth in LMICs. Decreasing the level of sedentary behaviour during adolescence could be an important target for reducing the prevalence of anxiety. [ABSTRACT FROM AUTHOR]

The beet armyworm, Spodoptera exigua, is a significant agricultural pest of numerous crops and has caused serious economic losses in China. To effectively control this pest, we analyzed its genetic variation, population genetic structure and demographic history. We used mitochondrial DNA (mtDNA) fragments of the cytochrome oxidase subunit I (COI) and eight nuclear microsatellite loci to investigate genetic diversity and population genetic structure of S. exigua populations at 14 sampling sites in western China. Both mtDNA and microsatellite data indicated low levels of genetic diversity among all populations. A moderate genetic differentiation among some S. exigua populations was detected. Neighbor-joining dendrograms, STRUCTURE, and principal coordinate analysis (PCoA) revealed two genetically distinct groups: the KEL group and the remaining population group. Isolation by distance (IBD) results showed a weak significant correlation between geographic distance and genetic differentiation. Haplotype networks, neutrality testing, and mismatch distribution analysis indicated that the beet armyworm experienced a recent rapid expansion without a recent genetic bottleneck in western China. Thus, the results of this population genetic study can help with the development of strategies for managing this highly migratory pest. [ABSTRACT FROM AUTHOR]

Objectives: Crashes due to motorcyclists colliding with an open car door can cause devastating injuries. In Taiwan, such crashes typically occur when the motorcyclist is travelling alongside a row of parallel-parked cars, and a driver suddenly opens the door in front of or next to the motorcycle without determining whether it is safe to do so. Injuries resulting from motorcycle door crashes tend to be severe. This study examined the factors that contribute to motorcycle door crashes. Methods: By using linked data from the National Traffic Crash Dataset and Emergency Medical Service for Taipei City for the years 2010–2015, this study estimated a mixed multinomial logit model to predict the likelihood of three types of door crashes: driver-door crashes, left passenger-door crashes, and right passenger-door crashes. Results: Data on 8237 motorcycle door crashes were extracted from the two datasets and matched. The results from the mixed multinomial logit model revealed that illegal parking, older car occupants, teenage car occupants, intoxicated car occupants and motorcyclists, and motorcycle speeding contribute to driver-door crashes; and female passengers and taxis as the type of vehicle involved in crash are associated with left passenger-door crashes. Conclusions: Our study suggested that controlling motorcycle speed, and prosecuting illegal parking and drink driving/riding may constitute effective countermeasures. The “Dutch Reach” intervention measure, which is commonly adopted in Europe for bicycle door crashes, should be applied in Taiwan to curb motorcycle door crashes, especially for elderly car occupants. [ABSTRACT FROM AUTHOR]

Quantifying the temporal and spatial patterns of temperature sensitivity (Q10) of soil respiration (Rs) as well as its controlling factors is critical to reveal the response the soil ecological processes to global warming and improve carbon budget estimations at a regional scale. The seasonal and annual variations in the temperature response of Rs were assessed during the two growing seasons in 2011 and 2012 in four different vegetation sites in a meadow steppe of the Songnen Plain, China. The Q10 values across all sites exhibited significant seasonal variations with a minimum value (1.81–2.34) occurring during summer and a peak value (3.82–4.54) occurring in either spring or autumn. The mean seasonal Q10 values showed no significant differences among the four different vegetation types. On the annual scale, however, the Chloris virgata site had significantly higher annual Q10 values (3.67–4.22) than the other three community sites in 2011 and 2012 and over the two years (2.01–3.67), indicating that the response of the Rs to climate warming may vary with vegetation type. The soil temperature and moisture had interactive effects on the variations of Q10 values. Soil temperature was the dominant factor influencing Q10 values, while soil moisture was an additional contributor to the variations of Q10. Due to the significant temporal and spatial variations in soil respiration response to temperature, acclimation of Rs to temperature variation should be taken into account in forecasting future terrestrial carbon cycle and its feedback to global warming. [ABSTRACT FROM AUTHOR]

Studies in Caucasians have shown that values of hematological indices could be affected by a wide variety of factors. However, parallel work in other ethnical populations, particularly from the Asia-Pacific region, is lacking. Therefore, we designed this study to explore the association between clinical/laboratory parameters and hemogram levels. Adult individuals who came to our hospital for health exams were screened. Information on demographics and laboratory profiles was obtained. We analyzed the impacts of these parameters on the variation of hemogram. Overall, 26,497 adults were included in the current analysis after excluding those with abnormal hemogram. Multivariate regression analysis showed increasing age and male gender negatively affected the number of platelets, whereas a higher serum apolipoprotein B level was associated with an elevated platelet count. Gender and serum albumin level were the major determinants of variation in hemoglobin level. A modestly increased white cell count was seen in men as well as individuals with elevated apolipoprotein B levels, but it was inversely correlated with changes in age and serum albumin levels. Conversely, some variables, although statistically significantly associated with the hematological indices, only provided a trivial explanation for the heterogeneity observed. We further established predictive models for the approximate estimation of hematological indices in healthy adults. Our data indicate that age, gender, and serum levels of apolipoprotein B and albumin affect hematological indices in various ways. We also demonstrate that variation in hemogram could be successfully predicted by a number of clinical and laboratory parameters. [ABSTRACT FROM AUTHOR]

The conformational conversion of pentameric C-reactive protein (pCRP) to monomeric CRP (mCRP) has been shown to play important roles in the action of CRP in inflammation regulation. In vivo studies revealed the origin of mCRP and provided insights into how pCRP dissociation affected its functions. However, the interplay and exact bioactivities of CRP isoforms still remain uncertain due to the rapid conformational conversion and complex milieu in vivo. Herein, we have used surface-immobilization of pCRP to generate a preservable intermediate with dual antigenicity expression of both pCRP and mCRP. The intermediate has been further shown to exhibit modified bioactivities, such as a high affinity with solution-phase pCRP and an enhanced capacity of complement interaction. These results thus not only provide the conformational conversion details of CRP, but also propose a simple way in vitro to study how the functions of CRP are tuned by distinct isoforms. [ABSTRACT FROM AUTHOR]

The bioactive, signaling lipid, sphingosine-1-phosphate (S1P), and its analog, fingolimod (FTY720), have previously shown neuroprotective effects against ischemic brain injury. However, the underlying mechanisms have not yet been fully clarified. The roles of autophagy in ischemic stroke are being increasingly recognized. In the present study, we sought to determine whether the S1P pathway is involved in neuronal autophagy and investigate its possible mechanisms following stroke. Interestingly, we found that FTY720 significantly attenuates infarct volumes and reduces neuronal apoptosis on days 1 and 3 post stroke, accompanied by amelioration of functional deficits. Additionally, FTY720 was found to decrease the induction of autophagosome proteins, microtubule-associated protein 1 light chain 3(LC3-II) and Beclin1, following ischemic stroke in a dose-dependent manner. Meanwhile, protein levels of the mammalian target of rapamycin (mTOR) and the 70-kDa ribosomal protein, S6 kinase1 (p70S6K), were also up-regulated in FTY720-treated animals, and the nonspecific SphK inhibitor, N,N-dimethylsphingosine (DMS), was found to cause a reverse effect. Our results indicate that modulation of the S1P signaling pathway by FTY720 could effectively decrease neuronal autophagy through the mTOR/p70S6K pathway and attenuate ischemic brain injury in mice. [ABSTRACT FROM AUTHOR]

Tea plants [Camellia sinensis (L.) O. Kuntze] are an important leaf-type crop that are widely used for the production of non-alcoholic beverages in the world. Exposure to excessive amounts of heavy metals adversely affects the quality and yield of tea leaves. To analyze the molecular responses of tea plants to heavy metals, a reliable quantification of gene expression is important and of major importance herein is the normalization of the measured expression levels for the target genes. Ideally, stably expressed reference genes should be evaluated in all experimental systems. In this study, 12 candidate reference genes (i.e., 18S rRNA, Actin, CYP, EF-1α, eIF-4α, GAPDH, MON1, PP2AA3, TBP, TIP41, TUA, and UBC) were cloned from tea plants, and the stability of their expression was examined systematically in 60 samples exposed to diverse heavy metals (i.e., manganese, aluminum, copper, iron, and zinc). Three Excel-based algorithms (geNorm, NormFinder, and BestKeeper) were used to evaluate the expression stability of these genes. PP2AA3 and 18S rRNA were the most stably expressed genes, even though their expression profiles exhibited some variability. Moreover, commonly used reference genes (i.e., GAPDH and TBP) were the least appropriate reference genes for most samples. To further validate the suitability of the analyzed reference genes, the expression level of a phytochelatin synthase gene (i.e., CsPCS1) was determined using the putative reference genes for data normalizations. Our results may be beneficial for future studies involving the quantification of relative gene expression levels in tea plants. [ABSTRACT FROM AUTHOR]

Computational modelling of mechanisms underlying processes in the real world can be of great value in understanding complex biological behaviours. Uptake in general biology and ecology has been rapid. However, it often requires specific data sets that are overly costly in time and resources to collect. The aim of the current study was to test whether a generic behavioural ecology model constructed using published data could give realistic outputs for individual species. An individual-based model was developed using the Pattern-Oriented Modelling (POM) strategy and protocol, based on behavioural rules associated with insect movement choices. Frugivorous Tephritidae (fruit flies) were chosen because of economic significance in global agriculture and the multiple published data sets available for a range of species. The Queensland fruit fly (Qfly), Bactrocera tryoni, was identified as a suitable individual species for testing. Plant canopies with modified architecture were used to run predictive simulations. A field study was then conducted to validate our model predictions on how plant architecture affects fruit flies’ behaviours. Characteristics of plant architecture such as different shapes, e.g., closed-canopy and vase-shaped, affected fly movement patterns and time spent on host fruit. The number of visits to host fruit also differed between the edge and centre in closed-canopy plants. Compared to plant architecture, host fruit has less contribution to effects on flies’ movement patterns. The results from this model, combined with our field study and published empirical data suggest that placing fly traps in the upper canopy at the edge should work best. Such a modelling approach allows rapid testing of ideas about organismal interactions with environmental substrates in silico rather than in vivo, to generate new perspectives. Using published data provides a saving in time and resources. Adjustments for specific questions can be achieved by refinement of parameters based on targeted experiments. [ABSTRACT FROM AUTHOR]

Exosomes are small, cell-secreted vesicles that transfer proteins and genetic information between cells. This intercellular transmission regulates many physiological and pathological processes. Therefore, exosomes have emerged as novel biomarkers for disease diagnosis and as nanocarriers for drug delivery. Here, we report an easy-to-adapt and highly versatile methodology to modulate exosome composition and conjugate exosomes for intracellular delivery. Our strategy combines the metabolic labeling of newly synthesized proteins or glycan/glycoproteins of exosome-secreting cells with active azides and bioorthogonal click conjugation to modify and functionalize the exosomes. The azide-integrated can be conjugated to a variety of small molecules and proteins and can efficiently deliver conjugates into cells. The metabolic engineering of exosomes diversifies the chemistry of exosomes and expands the functions that can be introduced into exosomes, providing novel, powerful tools to study the roles of exosomes in biology and expand the biomedical potential of exosomes. [ABSTRACT FROM AUTHOR]

Peanut, a high-oil crop with about 50% oil content, is either crushed for oil or used as edible products. Fatty acid composition determines the oil quality which has high relevance to consumer health, flavor, and shelf life of commercial products. In addition to the major fatty acids, oleic acid (C18:1) and linoleic acid (C18:2) accounting for about 80% of peanut oil, the six other fatty acids namely palmitic acid (C16:0), stearic acid (C18:0), arachidic acid (C20:0), gadoleic acid (C20:1), behenic acid (C22:0), and lignoceric acid (C24:0) are accounted for the rest 20%. To determine the genetic basis and to improve further understanding on effect of FAD2 genes on these fatty acids, two recombinant inbred line (RIL) populations namely S-population (high oleic line ‘SunOleic 97R’ × low oleic line ‘NC94022’) and T-population (normal oleic line ‘Tifrunner’ × low oleic line ‘GT-C20’) were developed. Genetic maps with 206 and 378 marker loci for the S- and the T-population, respectively were used for quantitative trait locus (QTL) analysis. As a result, a total of 164 main-effect (M-QTLs) and 27 epistatic (E-QTLs) QTLs associated with the minor fatty acids were identified with 0.16% to 40.56% phenotypic variation explained (PVE). Thirty four major QTLs (>10% of PVE) mapped on five linkage groups and 28 clusters containing more than three QTLs were also identified. These results suggest that the major QTLs with large additive effects would play an important role in controlling composition of these minor fatty acids in addition to the oleic and linoleic acids in peanut oil. The interrelationship among these fatty acids should be considered while breeding for improved peanut genotypes with good oil quality and desired fatty acid composition. [ABSTRACT FROM AUTHOR]

NAC (NAM, ATAF1, 2 and CUC2) family is a plant-specific transcription factor and it controls various plant developmental processes. In the current study, 124 NAC members were identified in Zea mays and were phylogenetically clustered into 13 distinct subfamilies. The whole genome duplication (WGD), especially an additional WGD event, may lead to expanding ZmNAC members. Different subfamily has different expansion rate, and NAC subfamily preference was found during the expansion in maize. Moreover, the duplication events might occur after the divergence of the lineages of Z. mays and S. italica, and segmental duplication seemed to be the dominant pattern for the gene duplication in maize. Furthermore, the expansion of ZmNAC members may be also related to gain and loss of introns. Besides, the restriction of functional divergence was discovered after most of the gene duplication events. These results could provide novel insights into molecular evolution and expansion analysis of NAC family in maize, and advance the NAC researches in other plants, especially polyploid plants. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a rare degenerative condition of the motor neurons. Over 10% of ALS cases are linked to monogenic mutations, with the remainder thought to be due to other risk factors, including environmental factors, genetic polymorphisms, and possibly gene-environmental interactions. We examined the association between ALS and an intermediate CAG repeat expansion in the ATXN2 gene using a meta-analytic approach. Observational studies were searched with relevant disease and gene terms from MEDLINE, EMBASE, and PsycINFO from January 2010 through to January 2014. All identified articles were screened using disease terms, gene terms, population information, and CAG repeat information according to PRISMA guidelines. The final list of 17 articles was further evaluated based on the study location, time period, and authors to exclude multiple usage of the same study populations: 13 relevant articles were retained for this study. The range 30–33 CAG repeats in the ATXN2 gene was most strongly associated with ALS. The meta-analysis revealed that the presence of an intermediate CAG repeat (30-33) in the ATXN2 gene was associated with an increased risk of ALS [odds ratio (OR) = 4.44, 95%CI: 2.91–6.76)] in Caucasian ALS patients. There was no significant difference in the association of this CAG intermediate repeat expansion in the ATXN2 gene between familial ALS cases (OR = 3.59, 1.58–8.17) and sporadic ALS cases (OR = 3.16, 1.88–5.32). These results indicate that the presence of intermediate CAG repeat expansion in the ATXN2 gene is a specific genetic risk factor for ALS, unlike monogenic mutations with an autosomal dominant transmission mode, which cause a more severe phenotype of ALS, with a higher prevalence in familial ALS. [ABSTRACT FROM AUTHOR]

Aims: The asymptomatic nature of early-stage esophageal squamous cell carcinoma (ESCC) results in late presentation and consequent dismal prognosis This study characterized 14-3-3σ protein expression in the multi-stage development of ESCC and determined its correlation with clinical features and prognosis. Materials and Methods: Western blot was used to examine 14-3-3σ protein expression in normal esophageal epithelium (NEE), low grade intraepithelial neoplasia (LGIN), high grade intraepithelial neoplasia (HGIN), ESCC of TNM I to IV stage and various esophageal epithelial cell lines with different biological behavior. Immunohistochemistry was used to estimate 14-3-3σ protein in 110 biopsy samples of NEE, LGIN or HGIN and in 168 ESCC samples all of whom had follow-up data. Support vector machine (SVM) was used to develop a classifier for prognosis. Results: 14-3-3σ decreased progressively from NEE to LGIN, to HGIN, and to ESCC. Chemoresistant sub-lines of EC9706/PTX and EC9706/CDDP showed high expression of 14-3-3σ protein compared with non-chemoresistant ESCC cell lines and immortalized NEC. Furthermore, the downregulation of 14-3-3σ correlated significantly with histological grade (P = 0.000) and worse prognosis (P = 0.004). Multivariate Cox regression analysis indicated that 14-3-3σ protein (P = 0.016) and T stage (P = 0.000) were independent prognostic factors for ESCC. The SVM ESCC classifier comprising sex, age, T stage, histological grade, lymph node metastasis, clinical stage and 14-3-3σ, distinguished significantly lower- and higher-risk ESCC patients (91.67% vs. 3.62%, P = 0.000). Conclusions: Downregulation of 14-3-3σ arises early in the development of ESCC and predicts poor survival, suggesting that 14-3-3σ may be a biomarker for early detection of high-risk subjects and diagnosis of ESCC. Our seven-feature SVM classifier for ESCC prognosis may help to inform clinical decisions and tailor individual therapy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the secular trend in incidence of and mortality from Type 1 diabetes mellitus (T1DM) in Taiwan, 1999–2010. Methods: All 7,225 incident cases of T1DM were retrospectively retrieved from Taiwan's National Health Insurance Research Database from 1999 to 2010. Trend of bi-annual age- and sex-specific incidence rates of T1DM was calculated and tested with Poisson regression model. Standardized mortality ratios (SMRs) were calculated, using age-, sex-, and calendar years-specific mortality rates of the general population as the reference, to estimate the relative mortality risk of T1DM. Results: The number of male and female T1DM was 3,471 (48%) and 3,754 (52%), respectively. The annual number of incident T1DM increased from 543 in 1999 to 737 in 2010. The overall bi-annual incidence rate rose from 1999–00 to 2003–04 and mildly declined thereafter rose to 2009–10, with an insignificant trend (P = 0.489) over the study period. Regardless of gender, the higher age-specific incidence rate was noted in the younger groups (<30 years) and highest at <15 years. The incidence rates in younger groups were constantly higher in female population than in male one. The SMR from all causes was significantly increased at 3.00 (95% Confidence Interval (CI) 2.83–3.16) in patients with T1DM. The sex-specific SMR was 2.66 (95% CI 2.46–2.85) and 3.58 (95% CI 3.28–3.87) for male and female patients, respectively. For both sexes, the age-specific SMR peaked at 15–29 years. Conclusions: Among T1DM patients in Taiwan, there were significant increasing trends in males and female aged <15 years. We also noted a significantly increased overall and sex-specific SMR from all causes in patients with TIDM which suggests a need for improvements in treatment and care of patients with T1DM. [ABSTRACT FROM AUTHOR]

The expression of polypyrimidine tract-binding protein (PTB) is up-regulated in many types of cancer. Here, we studied the role of PTB in the growth of non small cell lung cancer cells. Data showed that PTB overexpression inhibited the growth of H1299 cells at least by inhibiting DNA synthesis. Quantitative real-time PCR and Western blot analyses showed that PTB overexpression in H1299 cells specifically induced the expression of p19Ink4d, an inhibitor of cyclin-dependent kinase 4. Repression of p19Ink4d expression partially rescued PTB-caused proliferation inhibition. PTB overexpression also inhibited the growth and induced the expression of p19Ink4d mRNA in A549 cells. However, Western blot analyses failed to detect the presence of p19Ink4d protein in A549 cells. To address how PTB induced p19Ink4d in H1299 cells, we showed that PTB might up-regulate the activity of p19Ink4d gene (CDKN2D) promoter. Besides, PTB lacking the RNA recognition motif 3 (RRM3) was less effective in growth inhibition and p19Ink4d induction, suggesting that RNA-binding activity of PTB plays an important role in p19Ink4d induction. However, immunoprecipitation of ribonuclearprotein complexes plus quantitative real-time PCR analyses showed that PTB might not bind p19Ink4d mRNA, suggesting that PTB overexpression might trigger the other RNA-binding protein(s) to bind p19Ink4d mRNA. Subsequently, RNA electrophoretic mobility-shift assays revealed a 300-base segment (designated as B2) within the 3′UTR of p19Ink4d mRNA, with which the cytoplasmic lysates of PTB-overexpressing cells formed more prominent complexes than did control cell lysates. Insertion of B2 into a reporter construct increased the expression of the chimeric luciferase transcripts in transfected PTB-overexpressing cells but not in control cells; conversely, overexpression of B2-containing reporter construct in PTB-overexpressing cells abolished the induction of p19Ink4d mRNA. In sum, we have shown that PTB plays as a negative regulator in H1299 cell proliferation at least by inducing p19Ink4d expression at transcriptional and post-transcriptional levels. [ABSTRACT FROM AUTHOR]

The Qinghai-Tibetan Plateau (QTP) has become one of the hotspots for phylogeographical studies due to its high species diversity. However, most previous studies have focused on the effects of the Quaternary glaciations on phylogeographical structures and the locations of glacial refugia, and little is known about the effects of the aridization of interior Asia on plant population structure and speciation. Here the chloroplast DNA (cpDNA) trnT-trnF and trnS-trnfM sequences were used to investigate the differentiation and phylogeographical history of 14 Ephedra species from the QTP and northern China, based on a sampling of 107 populations. The phylogeographical analysis, together with phylogenetic reconstruction based on combined four cpDNA fragments (rbcL, rpl16, rps4, and trnS-trnfM), supports three main lineages (eastern QTP, southern QTP, and northern China) of these Ephedra species. Divergence of each lineage could be dated to the Middle or Late Miocene, and was very likely linked to the uplift of the QTP and the Asian aridification, given the high drought and/or cold tolerance of Ephedra. Most of the Ephedra species had low intraspecific variation and lacked a strong phylogeographical structure, which could be partially attributed to clonal reproduction and a relatively recent origin. In addition, ten of the detected 25 cpDNA haplotypes are shared among species, suggesting that a wide sampling of species is helpful to investigate the origin of observed haplotypes and make reliable phylogeographical inference. Moreover, the systematic positions of some Ephedra species are discussed. [ABSTRACT FROM AUTHOR]

This study aimed to determine the microbial diversity at different soil depths (0–5 and 5–20 cm) in a subtropical orchard during different seasons (i.e., spring, summer and autumn) to advance knowledge of the roles of microbes in orchard ecosystem balance. In tracking experiments conducted in an orchard (established in 1996), the phospholipid fatty acid (PLFA) biomarker method was employed to determine the soil microbial system. The total PLFA concentration did not vary significantly between soil depths but changed between seasons. It peaked in the summer at 258.97 ± 23.48 μg g soil-1 from 0–5 cm and at 270.99 ± 58.94 μg g soil-1 from 5–20 cm. A total of 33 microbial fatty acid biomarkers were observed and identified in the sampled soil. The quantities of PLFAs for 29 microbial groups varied significantly between seasons, except for 15:0 iso 3OH, 15:1 iso G, 16:0 2OH, and 17:0 iso 3OH. The bacterial PLFAs and fungal and actinomycetic PLFAs in the orchard soil collected in summer were significantly more abundant than those collected in the spring or autumn (P < 0.01). The number of soil microorganism species (richness) and the Simpson and Shannon-Wiener indexes were all highest in summer. The total PLFAs, bacterial PLFAs, fungal PLFAs, actinomycetic PLFAs, richness, and Simpson and Shannon-Wiener indexes were all significantly negatively correlated with soil pH, total organic carbon (TOC), total nitrogen (TN) and the cation exchange capacity (CEC) (P < 0.05). [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the curative effect of external therapies of traditional Chinese medicine on constipation in patients with chronic renal failure and to provide scientific theoretical basis for clinical practice. Method: We searched the English database of PubMed, EMBASE, the Cochrane Library and the Web of Science and Chinese database of CNKI, Wan fang database, VIP Database and China Biomedical Literature Database up to December 2022. Randomized controlled trials (RCTs) involving constipation in patients with CRF that compared external therapies of traditional Chinese medicine and routine treatment to routine treatment were eligible for the analysis. A meta-analysis of the outcome indicators including total efficiency, weekly defecation times, defecation time, defecation difficulty score, patient-assessment of constipation quality of life and adverse events of treatment were performed. The analysis was performed by using Review Manager version 5.3. Result: A total of 23 studies were included, with 1764 patients. Meta-analysis results showed that compared with the control group, the test group could significantly increase weekly defecation times(MD = 0.94, 95%CI(0.70, 1.18), Z = 7.74, P < 0.00001), reduce defecation time(MD = -2.92, 95%CI(-3.69, -2.16), Z = 7.49, P < 0.00001), reduce defecation difficulty score(MD = -1.92, 95%CI(-2.45, -1.39), Z = 7.11, P < 0.00001), improve the quality of life in patients with constipation(MD = -7.57, 95%CI(-10.23, -4.91), Z = 5.58, P < 0.00001) and obtain a higher total effective rate of treatment(OR = 4.53, 95%CI(3.27, 6.29), Z = 9.07, P < 0.00001). In terms of safety, there was no statistical significance in the incidence of adverse events between two groups(OR = 0.35, 95%CI(0.04, 2.95), Z = 0.96, P = 0.34). Conclusion: The combination of external therapies of traditional Chinese medicine and routine treatment could achieve an excellent curative effect, and there was no specific adverse event. However because of the limited level of current evidence, more high-quality trials are needed in the future.5 [ABSTRACT FROM AUTHOR]

Salmonella, one of the major causes of foodborne infections, can cause bacterial foodborne illness. We investigated the serotype distribution, multidrug resistance (MDR), and β-lactamase resistance genes of human Salmonella isolates collected from clinical specimens in Guizhou, China, between 2013 and 2018. A total of 363 Salmonella isolates were collected from clinical specimens at 17 surveillance hospitals. Twenty-four serotypes were identified by sliding agglutination test. S. Enteritidis (33.9%), Salmonella 4,[5],12:i:- (24.0%), S. Typhimurium (16.3%), S. London (6.3%), and S. Derby (3.9%) were the top five serotypes. In 2018, the most common serotype changed from S. Enteritidis to S. Typhimurium. Among the 363 Salmonella isolates, 97.5% of isolates were resistant to at least one class of antimicrobial agents. For cephalosporins, ceftriaxone had the highest resistance rate of 10.5%, and cefepime and cefoxitin were 8.0% and 2.2%, respectively. Three hundred and one (82.9%) Salmonella isolates showed MDR. Salmonella 4,[5],12:i:- had the highest MDR rate with 94.2%, followed by S. London (91.3%) and S. Typhimurium (88.1%). Multidrug resistance rates of Salmonella isolates in Guizhou from 2013 to 2017 increased from 75.8% to 86.7%. Sixteen isolates (4.4%) showed extensive drug resistance. One hundred thirty-four antimicrobial resistance patterns were found. Two hundred and forty-one (66.4%) isolates carried at least one β-lactamase resistance gene. The blaTEM gene (61.2%) was the most prevalent resistant gene in all Salmonella isolates, followed by the blaCTX-M gene (6.1%) and blaOXA-1 gene (4.1%). Our findings showed that the MDR rate of Salmonella isolates from Guizhou province increased year by year. Therefore, systematic and long-term surveillance on MDR Salmonella isolates from clinical patients should be further strengthened. [ABSTRACT FROM AUTHOR]

Benggang is one of the most serious soil erosion problems in tropical and subtropical areas in southern China. Little work has been reported on the surface properties of soil colloidal particle and its influence on soil swelling of different soil layers in collapsing wall of Benggang. In this present work, the effects of sodium concentration on soil swelling, and the correlations between soil swelling rates and soil colloidal surface properties were comprehensively evaluated by carefully examining soil physicochemical properties and soil colloidal surface properties of red, sandy and detritus soil layers from a collapsing wall. Our results showed that the soil swelling rates of red, sandy and detritus soil layers all exponentially decreased with increasing initial water contents. The relationship between soil swelling rate and the thickness of shear plane showed an extremely significant negative correlation for red soil layer and no correlation for sandy and detritus soil layers. Moreover, the elevating sodium concentrations reduced the thickness of shear plane from 39.69 to 0.76 nm for red soil layer, followed from 22.56 to 0.79 nm for sandy soil layer and from 18.61 to 0.64 nm for detritus soil layer. These findings indicated that the soil particle interactions played a crucial role in the development and occurrence of Benggang. This work will be helpful in understanding the mechanisms of soil mass loss on the gully head and collapsing wall of Benggang. [ABSTRACT FROM AUTHOR]

Background/Aims: Typical approach for increasing apheresis platelet collections is to recruit new donors. Here, we investigated the effectiveness of an alternative strategy: optimizing donor scheduling, prior to recruitment, at a hospital-based blood donor center. Methods: Analysis of collections, during the 89 consecutive months since opening of donor center, was performed. Linear regression and segmented time-series analyses were performed to calculate growth rates of collections and to test for statistical differences, respectively. Results: Pre-intervention donor scheduling capacity was 39/month. In the absence of active donor recruitment, during the first 29 months, the number of collections rose gradually to 24/month (growth-rate of 0.70/month). However, between month-30 and -55, collections exhibited a plateau at 25.6 ± 3.0 (growth-rate of -0.09/month) (p<0.0001). This plateau-phase coincided with donor schedule approaching saturation (65.6 ± 7.6% schedule booked). Scheduling capacity was increased by following two interventions: adding an apheresis instrument (month-56) and adding two more collection days/week (month-72). Consequently, the scheduling capacity increased to 130/month. Post-interventions, apheresis platelet collections between month-56 and -81 exhibited a spontaneous renewed growth at a rate of 0.62/month (p<0.0001), in absence of active donor recruitment. Active donor recruitment in month-82 and -86, when the donor schedule had been optimized to accommodate further growth, resulted in a dramatic but transient surge in collections. Conclusion: Apheresis platelet collections plateau at nearly 2/3rd of the scheduling capacity. Optimizing the scheduling capacity prior to active donor recruitment is an effective strategy to increase platelet collections at a hospital-based donor center. [ABSTRACT FROM AUTHOR]

A plantation of 5-year-old poplar Populus × euramericana cv. ‘Neva’ was used to study the regulatory effects of root pruning on nutrients, photosynthetic characteristics, and water-use efficiency (WUE) of leaves and growth rates of diameter at breast height (DBH; 1.3 m), tree height, and volume. Six root-pruning treatments were conducted with different combinations of intensity (at a distance of six, eight or ten times DBH from the trunk) and orientation (on two or four sides of the trees). Results showed that the N, P, K, photosynthetic rate, transpiration rate, and stomatal conductance of leaves were all significantly decreased by root pruning over the initial period following root pruning (30 days), but increased in the subsequent investigations. The values of the above indexes peaked in 8–2 treatment (i.e., eight times DBH distance on two sides). The leaf WUE in 8–2 treatment, and average growth rates of DBH, tree height and volume, were the highest among all treatments within 3 years of root pruning. The results indicated that the root pruning based on the appropriate selection of intensity and orientation had significant positive effects on leaf nutrients, photosynthesis, and growth of trees in a closed-canopy poplar plantation. [ABSTRACT FROM AUTHOR]

This study aimed to determine the effects of root pruning on the physicochemical characteristics and microbial activities of poplar rhizosphere soil. The root systems of 5-year-old poplar (Populus×euramericana cv. ‘Neva’) trees were manually pruned at 6, 8, or 10 times diameter at breast height (DBH) from the trunk (severe, moderate, and light, respectively) along both inter-row sides. Moderate root pruning significantly increased the concentrations of amino acids, organic acids, and total sugars in the root exudates and decreased the pH of rhizosphere soil. This treatment also increased the contents of available nitrogen, phosphorus, potassium, and total organic carbon as well as high-, medium-, and low-activity organic carbon in rhizosphere soil. Moreover, moderate pruning increased the contents of microbial biomass carbon and nitrogen, and enhanced basal respiration, in addition to decreasing the metabolic quotients in rhizosphere soil by 8.9%, 5.0%, and 11.4% compared with control, light, and severe root pruning treatments, respectively. Moderate pruning increased the growth rates of DBH, tree height, and volume to the highest levels. Furthermore, these indices were not significantly different between the light root pruning and control groups, but varied significantly between severe and moderate root-pruning treatments. Thus, root pruning, depending on the distance from the trunk, significantly influences the physicochemical properties and microbial activities in poplar rhizosphere soil. [ABSTRACT FROM AUTHOR]

Nontyphoidal Salmonella is a bacterial and foodborne pathogen that poses a severe public health threat. However, the genetic diversity of different serogroups of nontyphoidal Salmonella in Guizhou is unknown. This study aimed to obtain the RNA secondary structure of the typical direct repeat sequences, the characteristics of clustered regularly interspaced short palindromic repeats (CRISPR) genotypes, and the genetic diversity of different serogroups of nontyphoidal Salmonella strains. The 342 nontyphoidal Salmonella strains were collected from nine cities (prefectures) of Guizhou province during 2013–2018, serotyped by slide agglutination, and examined the molecular genotypes by CRISPR method. The strains were divided into five serogroups. The dominant serogroup was group B (47.08%), followed by group D1 (36.55%). One hundred and thirty-five CRISPR genotypes were detected with 108 novel spacer sequences amongst 981 unique spacer sequences. The diversity of nontyphoidal Salmonella CRISPR loci was not only the deletion, duplication, or point mutation of spacer sequences but also the acquisition of new spacer sequences to form novel genotypes. The CRISPR genotyping was an effective typing method that could reveal the genetic diversity of different nontyphoidal Salmonella serotypes except for S. Enteritidis. [ABSTRACT FROM AUTHOR]

Thyroid-carcinoma (THCA) is the most common malignancy with an increasing incidence. Recent evidence has emphasized the role of microRNA (miRNA) in THCA. However, knowledge concerning the roles of miRNAs in THCA is still limited. We therefore use a miRNA-target gene differential regulatory network (MGDRN) to identify key miRNAs and characterize their synergistic regulation in THCA. Both miRNA-target gene interactions from multiple databases and negative expression correlations between miRNA-target genes were used to characterize the interactions. Then, two regulatory networks involving normal and tumor conditions were constructed, respectively. The MGDRN was finally constructed using different interactions between the above two regulatory networks. By analyzing topological features of the MGDRN, four miRNAs (hsa-mir-152-3p, hsa-mir-148a, hsa-mir-130b and hsa-mir-15b) are identified as key miRNAs in THCA. Over-expression of mir-152-3p inhibited proliferation and colony formation of TPC-1 cells. Furthermore, mir-152-3p negatively regulated ERBB3 by binding to the 3'-UTR of ERBB3, and down-regulation of ERBB3 by small interfering (si)RNAs inhibited proliferation and colony formation of TPC-1 cells, indicating that mir-152-3p acted as an anti-tumor miRNA by negatively regulating ERBB3. Finally, two synergistically dysregulated modules were identified which may contribute to the initiation and progression of THCA. Overall, the results provided a better understanding of the molecular basis of THCA, and suggested novel treatment strategies for this cancer. [ABSTRACT FROM AUTHOR]

Bacterial blight, which is caused by Xanthomonas oryzae pv. oryzae (Xoo), is one of the most devastating rice diseases worldwide. The development and use of disease-resistant cultivars have been the most effective strategy to control bacterial blight. Identifying the genes mediating bacterial blight resistance is a prerequisite for breeding cultivars with broad-spectrum and durable resistance. We herein describe a genome-wide association study involving 172 diverse Oryza sativa ssp. indica accessions to identify loci influencing the resistance to representative strains of six Xoo races. Twelve resistance loci containing 121 significantly associated signals were identified using 317,894 single nucleotide polymorphisms, which explained 13.3–59.9% of the variability in lesion length caused by Xoo races P1, P6, and P9a. Two hotspot regions (L11 and L12) were located within or nearby two cloned R genes (xa25 and Xa26) and one fine-mapped R gene (Xa4). Our results confirmed the relatively high resolution of genome-wide association studies. Moreover, we detected novel significant associations on chromosomes 2, 3, and 6–10. Haplotype analyses of xa25, the Xa26 paralog (MRKc; LOC_Os11g47290), and a Xa4 candidate gene (LOC_11g46870) revealed differences in bacterial blight resistance among indica subgroups. These differences were responsible for the observed variations in lesion lengths resulting from infections by Xoo races P1 and P9a. Our findings may be relevant for future studies involving bacterial blight resistance gene cloning, and provide insights into the genetic basis for bacterial blight resistance in indica rice, which may be useful for knowledge-based crop improvement. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) has a poor prognosis with high in-hospital mortality. Hepatic and circulating inflammatory cytokines, such as fibrinogen like protein 2 (fgl2), FasL/Fas, and TNFα/TNFR1, play a significant role in the pathophysiology of ACLF. This study aimed to investigate the therapeutic effect of recombinant adenoviral vectors carrying constructed DNA code for non-native microRNA (miRNA) targeting mouse fgl2 (mfgl2) or both mFas and mTNFR1 on murine hepatitis virus (MHV)-3-induced fulminant hepatitis in BALB/cJ mice. Artificial miRNA eukaryotic expression plasmids against mfgl2, mFas, and mTNFR1 were constructed, and their inhibitory effects on the target genes were confirmed in vitro. pcDNA6.2-mFas-mTNFR1- miRNA，which expresses miRNA against both mFas and mTNFR1 simultaneously，was constructed. To construct a miRNA adenovirus expression vector against mfgl2, pcDNA6.2-mfgl2-miRNA was cloned using Gateway technology. Ad-mFas-mTNFR1- miRNA was also constructed by the same procedure. Adenovirus vectors were delivered by tail-vein injection into MHV-3-infected BALB/cJ mice to evaluate the therapeutic effect. 8 of 18 (44.4%) mice recovered from fulminant viral hepatitis in the combined interference group treated with Ad-mfgl2-miRNA and Ad-mFas-mTNFR1-miRNA. But only 4 of 18 (22.2%) mice receiving Ad-mfgl2-miRNA and 3 of 18 (16.7%) mice receiving Ad-mFas-mTNFR1- miRNA survived. These adenovirus vectors significantly ameliorated inflammatory infiltration, fibrin deposition, hepatocyte necrosis and apoptosis, and prolonged survival time. Our data illustrated that combined interference using adenovirus-mediated artificial miRNAs targeting mfgl2, mFas, and mTNFR1 might have significant therapeutic potential for the treatment of fulminant hepatitis. [ABSTRACT FROM AUTHOR]

Background:Several observational studies have investigated the association between -607 C/A polymorphism of IL-18 gene and cancer risk; however, the results were inconsistent. Therefore, we performed a meta-analysis to derive a more precise estimation of the association to help us better understand the relationship between -607 C/A polymorphism of IL-18 gene promoter and risk of cancer. Methods:A literature search was carried out using PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) database between January 1966 and February 2013. Fixed-effect and random-effect models were used to estimate the pooled odds ratio (OR) and the corresponding 95% confidence intervals (CIs). Results:A total of 22 case-control studies including 4100 cancer cases and 4327 controls contributed to the analysis. Significant association between -607C/A polymorphism in IL-18 gene promoter and cancer risk was observed (CA vs CC:OR =1.221, 95% CI: 1.096, 1.360; Pheterogeneity=0.219; AA/CA vs. CC:OR =1.203, 95% CI: 1.057, 1.369; Pheterogeneity=0.064). In the subgroup analysis by ethnicity, -607C/A polymorphism significantly increased risk of cancer among Asian population (AA/CA vs. CC:OR =1.197, 95% CI: 1.023,1.401; Pheterogeneity=0.088); however, no significant association was found in Caucasian or African population. The -607C/A polymorphism was associated with a significantly increased risk of nasopharyngeal carcinoma (CA vs CC:OR =1.330, 95% CI: 1.029,1.719; Pheterogeneity=0.704; AA/CA vs. CC:OR =1.323, 95% CI: 1.037,1.687; Pheterogeneity=0.823) and esophageal cancer (AA/CA vs. CC:OR =1.289, 95% CI: 1.002,1.658; Pheterogeneity=0.700). Conclusions:The present meta-analysis suggests that the -607C/A polymorphisms in IL-18 gene promoter is associated with a significantly increased risk of cancer, especially for nasopharyngeal carcinoma and esophageal cancer and in Asian population. More studies with larger sample size, well controlled confounding factors are warranted to validate this association. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovar 4,[5],12:i:-, a monophasic variant of Salmonella Typhimurium lacking the phase 2 flagellin, is one of the common serotypes causing Salmonellosis worldwide. However, information on Salmonella serovar 4,[5],12:i:- from Guizhou Province has lacked so far. This study aimed to investigate the antimicrobial resistance, the presence of antimicrobial resistance genes and virulence genes, and characterize the MLST genotypes of Salmonella serovar 4,[5],12:i:- isolates from Guizhou province, China. We collected 363 non-typhoid Salmonella (NTS) isolates of Guizhou from 2013 to 2018. Biochemical identification, serogroups testing, and specific multiplex polymerase chain reaction (mPCR) assay were conducted to identify Salmonella 4,[5],12:i:- isolates. Isolates were determined the antimicrobial resistance by the micro broth dilution method, detected the presence of antimicrobial resistance genes and virulence genes by PCR, and examined the molecular genotyping by Multilocus sequence typing (MLST). Eighty-seven Salmonella 4,[5],12:i:- isolates were detected, accounting for 23.9% (87/363) of the total NTS isolates. All Salmonella 4,[5],12:i:- isolates showed highly resistant to sulfaoxazole (93.1%), streptomycin (90.8%), ampicillin (88.5%), tetracycline (86.2%) and doxycycline (86.2%). A high proportion (94.2%) of multi-drug resistance (MDR) isolates were found. Most (83.9%) Salmonella 4,[5],12:i:- isolates carried four antimicrobial resistance genes, especially blaTEM-1, strA-strB, sul2, and tetB genes. Salmonella 4,[5],12:i:- isolates showed a high rate of invA, sseL, mgtC, siiE, sopB, gipA, gtgB, sspH1, and sspH2 (72.4%~98.9%). On the contrary, none of the isolates were detected the spvC and pefA genes. MLST analysis revealed three sequence types (STs), and ST34 (97.7%) was the dominant sequence type. This study is the first report of Salmonella 4,[5],12:i:- in humans from Guizhou province, China. The data might be useful for rational antimicrobial usage against Salmonella 4,[5],12:i:- infections, risk management, and public health strategies in Guizhou. [ABSTRACT FROM AUTHOR]

Objective:We aimed to estimate the Lanzhou lamb rotavirus (LLR) vaccination coverage (VC) and timeliness among children aged 2 to 59 months in Guangzhou, China. Methods:An electronic system-based VC survey was conducted using stratified cluster random sampling. Results:We reported an overall Lanzhou lamb rotavirus vaccine coverage of 25.3% among children aged 2-59 months (2-8 months, 2.6%) in Guangzhou, China. Conclusion:Great efforts should be taken to increase LLR VC in eligible children in Guangzhou, China. [ABSTRACT FROM AUTHOR]

Background: The incidence of follicular lymphoma (FL) in Taiwan has not been well investigated since its inclusion as a histological subtype in the Taiwan Cancer Registry in 2008. The purpose of this study was to describe the incidence patterns of FL in Taiwan and compare the trends with those in other racial groups in the United States. Materials and methods: We conducted an epidemiological study using population-based data from the Taiwan Cancer Registry, Ministry of Health and Welfare, and the 18 Surveillance, Epidemiology, and End Results (SEER) registries to evaluate the FL incidence from 2008 to 2017. We calculated the annual percent change (APC) to describe the trends in the incidence of FL in subpopulations defined by race and sex over time. Results: The annual age-adjusted incidence rate of FL in Taiwan increased significantly from 0.59 per 100,000 persons in 2008 to 0.82 per 100,000 persons in 2017, with an APC of 3.2. By contrast, the incidence rate in whites in the United States during the same period decreased from 3.42 to 2.74 per 100,000 persons, with an APC of −2.1. We found no significant change for the blacks (APC, −1.5%), Hispanics (APC, −0.7%), and Asians or Pacific Islanders (APC, +0.7%). The temporal trend was similar between the males and females. The relative frequency of FL among the incident non-Hodgkin lymphoma (NHL) cases also increased significantly in Taiwan from 7.64% in 2008 to 11.11% in 2017 (APC = 3.8). The relative frequency of FL among the incident NHL cases in the whites decreased from 2008 to 2012 (APC, −3.8%) and then stabilized after 2012 (APC, −0.2%). By contrast, little change in relative frequency of FL among the incident NHL cases was observed in the blacks, Hispanics, and APIs between 2008 and 2017. Conclusion: We found increases in the incidence of FL and the relative frequency of FL among the incident NHL cases in both males and females in Taiwan from 2008 to 2017. The FL incidence rates were unchanged for all races and sex groups in the United States, except for the decreases in the whites. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) is an established marker of inflammation with pattern-recognition receptor-like activities. Despite the close association of the serum level of CRP with the risk and prognosis of several types of cancer, it remains elusive whether CRP contributes directly to tumorigenesis or just represents a bystander marker. We have recently identified recurrent mutations at the SNP position -286 (rs3091244) in the promoter of CRP gene in several tumor types, instead suggesting that locally produced CRP is a potential driver of tumorigenesis. However, it is unknown whether the -286 site is the sole SNP position of CRP gene targeted for mutation and whether there is any association between CRP SNP mutations and other frequently mutated genes in tumors. Herein, we have examined the genotypes of three common CRP non-coding SNPs (rs7553007, rs1205, rs3093077) in tumor/normal sample pairs of 5 cancer types (n = 141). No recurrent somatic mutations are found at these SNP positions, indicating that the -286 SNP mutations are preferentially selected during the development of cancer. Further analysis reveals that the -286 SNP mutations of CRP tend to co-occur with mutated APC particularly in rectal cancer (p = 0.04; n = 67). By contrast, mutations of CRP and p53 or K-ras appear to be unrelated. There results thus underscore the functional importance of the -286 mutation of CRP in tumorigenesis and imply an interaction between CRP and Wnt signaling pathway. [ABSTRACT FROM AUTHOR]

Emerging studies have indicated that microRNAs are involved in the development and progression of cancer. Here we found that miR-202-3p was frequently down-regulated in gastric cancer tissues. Overexpression of miR-202-3p in gastric cancer cells MKN-28 and BGC-823, markedly suppressed cell proliferation and induced cell apoptosis both in vitro and in vivo. Furthermore, Gli1 expression was frequently positive in gastric cancer tissues and inversely correlated with miR-133b expression. We demonstrate that the transcriptional factor Gli1 was a target of miR-202-3p and plays an essential role as a mediator of the biological effects of miR-202-3p in gastric cancer. MiR-202-3p also inhibited the expression of γ-catenin and BCL-2. Taken together, these findings suggest that miR-202-3p may function as a novel tumor suppressor in gastric cancer and its anti-tumor activity may attribute the direct targeting and inhibition of Gli1. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether external suction is more advantageous than water seal in patients undergoing selective pulmonary resection (SPR) for lung neoplasm. Summary of Background Data: Whether external suction should be routinely applied in postoperative chest drainage is still unclear, particularly for lung neoplasm patients. To most surgeons, the decision is based on their clinical experience. Methods: Randomized control trials were selected. The participants were patients undergoing SPR with lung neoplasm. Lung volume reduction surgery and pneumothorax were excluded. Suction versus non-suction for the intervention. The primary outcome was the incidence of persistent air leak (PAL). The definition of PAL was air leak for more than 3–7 days. The secondary outcomes included air leak duration, time of drainage, postoperative hospital stay and the incidence of postoperative pneumothorax. Studies were identified from literature collections through screening. Bias was analyzed and meta-analysis was used. Results: From the 1824 potentially relevant trials, 6 randomized control trials involving 676 patients were included. There was no difference between external suction and water seal in decreasing the incidence of PAL [95% confidence interval (CI) 0.81−2.16; z = 1.10; P = 0.27]. Regarding secondary outcomes, there were no differences in time of drainage (95% CI−0.36−1.56, P = 0.22), postoperative hospital stay (95% CI -.31−.54, P = 0.87) or incidence of postoperative pneumothorax (95% CI 0.18−.02, P = 0.05) between external suction and water seal. Conclusions: For participants, no differences are identified in terms of PAL incidence, drainage time, length of postoperative hospital stay or incidence of postoperative pneumothorax between external suction and water seal. The bias analysis should be emphasized. To the limitations of the bias and methodological differences among the included studies, we have no recommendation on whether external suction should be routinely applied after lung neoplasm SPR. More high-quality randomized controlled trials are needed. Systematic Review Registration: None. [ABSTRACT FROM AUTHOR]

Tuberculosis caused by the pathogen Mycobacterium tuberculosis (MTB), remains a significant threat to global health. Elucidating the mechanisms of essential MTB genes provides an important theoretical basis for drug exploitation. Gene mtsp17 is essential and is conserved in the Mycobacterium genus. Although Mtsp17 has a structure closely resembling typical steroidogenic acute regulatory protein-related lipid transfer (START) family proteins, its biological function is different. This study characterizes the transcriptomes of Mycobacterium smegmatis to explore the consequences of mtsp17 downregulation on gene expression. Suppression of the mtsp17 gene resulted in significant down-regulation of 3% and upregulation of 1% of all protein-coding genes. Expression of desA1, an essential gene involved in mycolic acid synthesis, and the anti-SigF antagonist MSMEG_0586 were down-regulated in the conditional Mtsp17 knockout mutant and up-regulated in the Mtsp17 over-expression strain. Trends in the changes of 70 of the 79 differentially expressed genes (Log2 fold change > 1.5) in the conditional Mtsp17 knockout strain were the same as in the SigF knockout strain. Our data suggest that Mtsp17 is likely an activator of desA1 and Mtsp17 regulates the SigF regulon by SigF regulatory pathways through the anti-SigF antagonist MSMEG_0586. Our findings indicate the role of Mtsp17 may be in transcriptional regulation, provide new insights into the molecular mechanisms of START family proteins, and uncover a new node in the regulatory network of mycobacteria. [ABSTRACT FROM AUTHOR]

Purpose: Since the outbreak in late December 2019 in Wuhan, China, coronavirus disease-2019 (COVID-19) has become a global pandemic. We analyzed and compared the clinical, laboratory, and radiological characteristics between survivors and non-survivors and identify risk factors for mortality. Methods: Clinical and laboratory variables, radiological features, treatment approach, and complications were retrospectively collected in two centers of Hubei province, China. Cox regression analysis was conducted to identify the risk factors for mortality. Results: A total of 432 patients were enrolled, and the median patient age was 54 years. The overall mortality rate was 5.09% (22/432). As compared with the survivor group (n = 410), those in the non-survivor group (n = 22) were older, and they had a higher frequency of comorbidities and were more prone to suffer from dyspnea. Several abnormal laboratory variables indicated that acute cardiac injury, hepatic damage, and acute renal insufficiency were detected in the non-survivor group. Non-surviving patients also had a high computed tomography (CT) score and higher rate of consolidation. The most common complication causing death was acute respiratory distress syndrome (ARDS) (18/22, 81.8%). Multivariate Cox regression analysis revealed that hemoglobin (Hb) <90 g/L (hazard ratio, 10.776; 95% confidence interval, 3.075–37.766; p<0.0001), creatine kinase (CK-MB) >8 U/L (9.155; 2.424–34.584; p = 0.001), lactate dehydrogenase (LDH) >245 U/L (5.963; 2.029–17.529; p = 0.001), procalcitonin (PCT) >0.5 ng/ml (7.080; 1.671–29.992; p = 0.008), and CT score >10 (39.503; 12.430–125.539; p<0.0001) were independent risk factors for the mortality of COVID-19. Conclusions: Low Hb, high LDH, PCT, and CT score on admission were the predictors for mortality and could assist clinicians in early identification of poor prognosis among COVID-19 patients. [ABSTRACT FROM AUTHOR]

The rice stem borer (RSB), Chilo suppressalis (Lepidoptera: Pyralidae), is an important agricultural pest that has caused serious economic losses in the major rice-producing areas of China. To effectively control this pest, we investigated the genetic diversity, genetic differentiation and genetic structure of 16 overwintering populations in the typical bivoltine areas of northern China based on 12 nuclear microsatellite loci. Moderate levels of genetic diversity and genetic differentiation among the studied populations were detected. Neighbour-joining dendrograms, Bayesian clustering and principal coordinate analysis (PCoA) consistently divided these populations into three genetic clades: western, eastern and northern/central. Isolation by distance (IBD) and spatial autocorrelation analyses demonstrated no correlation between genetic distance and geographic distance. Bottleneck analysis illustrated that RSB populations had not undergone severe bottleneck effects in these regions. Accordingly, our results provide new insights into the genetic relationships of overwintering RSB populations and thus contribute to developing effective management strategies for this pest. [ABSTRACT FROM AUTHOR]

Erinacine A-enriched Hericium erinaceus mycelia is a well-established potential therapeutic agent for neurodegenerative disorders. However, the effect of erinacine A-enriched H. erinaceus mycelia on promoting longevity remains unclear. This is the first study to investigate the effect of erinacine A-enriched H. erinaceus mycelia on lifespan-prolonging activity in Drosophila melanogaster and senescence-accelerated P8 (SAMP8) mice. Two hundred D. melanogaster and 80 SAMP8 mice of both sexes were randomly divided into four groups and were administered with either the standard, low-dose, mid-dose, or high-dose erinacine A-enriched H. erinaceus mycelia. After treatment, the lifespan was measured in D. melanogaster, and the lifespan, food intake and oxidative damage were evaluated in SAMP8 mice. Results showed that supplementation with erinacine A-enriched H. erinaceus mycelia extended the lifespan in both D. melanogaster and SAMP8 by a maximum of 32% and 23%, respectively, compared to the untreated controls. Moreover, erinacine A-enriched H. erinaceus mycelia decreased TBARS levels and induced the anti-oxidative enzyme activities of superoxide dismutase, catalase, and glutathione peroxidase. Together, these findings suggest that erinacine A-enriched H. erinaceus mycelia supplement could promote longevity, mediated partly through the induction of endogenous antioxidants enzymes. [ABSTRACT FROM AUTHOR]

Objectives: Previous studies have found that Panax quinquefolius saponins (PQS) combined with dual antiplatelet therapy (DAPT) of aspirin and clopidogrel enhances antithrombotic effects while reducing gastric mucosal injury induced by DAPT. We investigated the effects of the combined drug therapy (PQS+DAPT) through the COX/PG pathways. Methods: Acute myocardial infarction (AMI) was induced in Wistar rats by ligation of the left anterior descending (LAD) coronary artery, and the animals were randomly divided into Model, DAPT, and PQS+DAPT groups. Rats in the sham group did not undergo artery ligation. They were intragastrically treated for 14 days. Myocardial infarct size; myocardial pathology; platelet aggregation rate, CD62p activation, concentrations of thromboxane B2 (TXB2), 6-keto-PGF1α, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI), the TXB2/6-keto-PGF1α ratio were measured. The ultrastructure of the gastric mucosa was observed by scanning electron microscopy. The expression of PGE2 and 6-keto-PGF1α in gastric mucosa was measured by radioimmunoassay, and levels of COX-1, COX-2, and VEGF in gastric mucosa were assessed using immunohistochemistry. Results: The addition of Panax quinquefolius saponins (PQS+DAPT) to standard DAPT therapy significantly decreased the myocardial infarct area, degree of myocardial lesions, TXB2 and PAI levels, and the TXB2/6-keto-PGF1α ratio, while increasing 6-keto-PGF1α and t-PA levels and reducing the degree of gastric mucosal injury. Expression of PGE2, 6-keto-PGF1α, COX-2, and VEGF in the gastric mucosa was upregulated in the PQS+DAPT group compared with the standard DAPT group. Conclusion: PQS increases the degree of DAPT inhibition of myocardial necrosis and antiplatelet effects in AMI rats, as well as reducing damage to the gastric mucosa caused by DAPT. The mechanism may be related to inhibition of TXB2 and PAI activity and elevation of 6-keto-PGF1α and t-PA levels in blood, and may be associated with upregulated expression of COX-2, PGE2, PGI2, and VEGF in gastric tissue. [ABSTRACT FROM AUTHOR]

Cell-penetrating peptides (CPPs) have been increasingly used to deliver various molecules, both in vitro and in vivo. However, there are no reports of CPPs being used in porcine fetal fibroblasts (PFFs). The increased use of transgenic pigs for basic research and biomedical applications depends on the availability of technologies for efficient genetic-modification of PFFs. Here, we report that three CPPs (CPP5, TAT, and R9) can efficiently deliver active Cre recombinase protein into PFFs via an energy-dependent endocytosis pathway. The three CPP–Cre proteins can enter PFFs and subsequently perform recombination with different efficiencies. The recombination efficacy of CPP5–Cre was found to be nearly 90%. The rate-limiting step for CPP–Cre-mediated recombination was the step of endosome escape. HA2 and chloroquine were found to improve the recombination efficiency of TAT–Cre. Furthermore, we successfully obtained marker-free transgenic pigs using TAT–Cre and CPP5–Cre. We provide a framework for the development of CPP-based farm animal transgenic technologies that would be beneficial to agriculture and biomedicine. [ABSTRACT FROM AUTHOR]

Background: Pathogenic species of Leptospira cause leptospirosis, a global zoonotic disease. Our previous work showed that leptospires survive and replicate in human macrophages but are killed in murine macrophages. However, the mechanism responsible for the different intracellular fates of leptospires within the macrophages of different hosts remains unclear. Results: The present study demonstrates that infection with Leptospira interrogans caused significant up-regulation of reactive oxygen species (ROS) and superoxide in J774A.1 cells but did so to a lesser extent in THP-1 cells. The up-regulation of ROS and superoxide was significantly inhibited by the NADPH oxidase inhibitor apocynin. The damaged leptospires and remnants of leptospires within membrane-bound vacuoles were significantly inhibited by apocynin in J774A.1 cells but were less inhibited in THP-1 cells. In addition, apocynin significantly prevented damage to leptospires and the co-localization of L. interrogans with lysosomes in J774A.1 cells but did so to a lesser extent in THP-1 cells. Furthermore, the relative fluorescence intensity levels of intracellular leptospires and the viability of the intracellular leptospires increased in apocynin pretreated J774A.1 and THP-1 cells after 2 h of infection. Conclusions: The present study, based on our previous findings, further demonstrated that ROS contributed substantially to the bactericidal ability of mouse macrophages to kill intracellular leptospires. However, ROS did not contribute as much in human macrophages, which partially explains the different intracellular fates of L. interrogans in human and mouse macrophages. [ABSTRACT FROM AUTHOR]

Growth factor receptor bound protein-7 (Grb7) is a multi-domain adaptor protein that is co-opted by numerous tyrosine kinases involved in various cellular signaling and functions. The molecular mechanisms underlying the regulation of Grb7 remain unclear. Here, we revealed a novel negative post-translational regulation of Grb7 by the peptidyl-prolyl cis/trans isomerase, Pin1. Our data show that phosphorylation of Grb7 protein on the Ser194-Pro motif by c-Jun N-terminal kinase facilitates its binding with the WW domain of Pin1. Subsequently, Grb7 is degraded by the ubiquitin- and proteasome-dependent proteolytic pathway. Indeed, we found that Pin1 exerts its peptidyl-prolyl cis/trans isomerase activity in the modulation of Grb7 protein stability in regulation of cell cycle progression at the G2-M phase. This study illustrates a novel regulatory mechanism in modulating Grb7-mediated signaling, which may take part in pathophysiological consequences. [ABSTRACT FROM AUTHOR]

Background: A novel avian-origin influenza A(H7N9) caused a major outbreak in Mainland China in early 2013. Exposure to live poultry was believed to be the major route of infection. There are limited data on how the general public changes their practices regarding live poultry exposure in response to the early outbreak of this novel influenza and the frequency of population exposure to live poultry in different areas of China. Methodology: This study investigated population exposures to live birds from various sources during the outbreak of H7N9 in Guangzhou city, China in 2013 and compared them with those observed during the 2006 influenza A(H5N1) outbreak. Adults were telephone-interviewed using two-stage sampling, stratified by three residential areas of Guangzhou: urban areas and two semi-rural areas in one of which (Zengcheng) A(H7N9) virus was detected in a chicken from wet markets. Logistic regression models were built to describe practices protecting against avian influenza, weighted by age and gender, and then compare these practices across residential areas in 2013 with those from a comparable 2006 survey. Principal Findings: Of 1196 respondents, 45% visited wet markets at least daily and 22.0% reported buying live birds from wet markets at least weekly in April-May, 2013, after the H7N9 epidemic was officially declared in late March 2013. Of those buying live birds, 32.3% reported touching birds when buying and 13.7% would slaughter the poultry at home. Although only 10.1% of the respondents reported raising backyard birds, 92.1% of those who did so had physical contact with the birds they raised. Zengcheng respondents were less likely to report buying live birds from wet markets, but more likely to buy from other sources when compared to urban respondents. Compared with the 2006 survey, the prevalence of buying live birds from wet markets, touching when buying and slaughtering birds at home had substantially declined in the 2013 survey. Conclusion/Significance: Although population exposures to live poultry were substantially fewer in 2013 compared to 2006, wet markets and backyard poultry remained the two major sources of live bird exposures for the public in Guangzhou in 2013. Zengcheng residents seemed to have reduced buying live birds from wet markets but not from other sources in response to the detection of H7N9 virus in wet markets. [ABSTRACT FROM AUTHOR]

Background: The Solitaire AB stent is one of many assistant stents used for treating wide-necked cerebral aneurysm, and has been used since 2003. However, large sample studies on its safety and effectiveness are lacking. The objective of this study was to evaluate the effectiveness and safety of the Solitaire AB stent in the coil embolization of wide-necked cerebral aneurysms. Methods: Retrospective review of the clinical and image data of 116 patients with wide-necked cerebral aneurysms who had been enrolled at six interventional neuroradiology centers from February 2010 to February 2014 and had been treated by coil embolization; in total, 120 Solitaire AB stents were used. The degree of aneurysm occlusion was examined using digital subtraction angiography (DSA) immediately after the procedure and during follow-up, and was graded using the modified Raymond classification. We also observed complications to evaluate the safety and effectiveness of this therapy. Results: The 120 Solitaire AB stents (4 mm × 15 mm, four stents; 4 mm × 20 mm, 16 stents; 6 mm × 20 mm, 36 stents; 6 mm × 30 mm, 64 stents) were inserted to treat 120 wide-necked cerebral aneurysms. All stents were inserted successfully. DSA immediately post-surgery revealed 55 cases of complete occlusion, 59 cases of neck remnant, and six cases of aneurysm remnant. Perioperatively, there were four cases of hemorrhage and four cases of stent thrombosis. The follow-up spanned 3–37 months; of 92 patients examined by DSA at the 6-month follow up, 12 had disease recurrence. Conclusions: The Solitaire AB stent is effective with a good technical success rate and short-term effect for assisting coil embolization of wide-necked cerebral aneurysms. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is associated with high morbidity and mortality. Urinary tract infection (UTI) may be associated with sepsis or septic shock, and cause sudden deterioration of renal function. This study investigated the clinical characteristics and change of renal function to identify the risk factors for development of AKI in UTI patients. This retrospective study was conducted in a tertiary referral center. From January 2006 to January 2013, a total of 790 UTI patients necessitating hospital admission were included for final analysis. Their demographic and clinical characteristics and comorbidities were collected and compared. Multivariate logistic regression analysis was performed to evaluate the risk factors for AKI in UTI patients. There were 97 (12.3%) patients developing AKI during hospitalization. Multivariate logistic regression analysis showed that patients with older age (OR 1.02, 95% CI 1.00–1.04, P = 0.04), diabetes mellitus (DM) (OR 2.23, 95% CI 1.35–3.68, P = 0002), upper UTI (OR 2.63, 95% CI 1.53–4.56, P = 0001), afebrile during hospitalization (OR 1.71, 95% CI 1.04–2.83, P = 0036) and lower baseline eGFR [baseline eGFR 45–59 mL/min/1.73 m2 (OR 2.12, 95% CI 1.12–4.04, P = 0.022), baseline eGFR 30-44 mL/min/1.73 m2 (OR 4.44, 95% CI 2.30–8.60 P < 0.001) baseline eGFR < 30 mL/min/1.73 m2 (OR 4.72, 95% CI 2.13–10.45, P <0.001), respectively] were associated with increased risk for development of AKI. were associated with increased risk for development of AKI. Physicians should pay attention to UTI patients at risk of AKI (advancing age, DM, upper UTI, afebrile, and impaired baseline renal function). [ABSTRACT FROM AUTHOR]

Sodium salicylate (NaSal), a tinnitus inducing agent, can activate serotonergic (5-HTergic) neurons in the dorsal raphe nucleus (DRN) and can increase serotonin (5-HT) level in the inferior colliculus and the auditory cortex in rodents. To explore the underlying neural mechanisms, we first examined effects of NaSal on neuronal intrinsic properties and the inhibitory synaptic transmissions in DRN slices of rats by using whole-cell patch-clamp technique. We found that NaSal hyperpolarized the resting membrane potential, decreased the input resistance, and suppressed spontaneous and current-evoked firing in GABAergic neurons, but not in 5-HTergic neurons. In addition, NaSal reduced GABAergic spontaneous and miniature inhibitory postsynaptic currents in 5-HTergic neurons. We next examined whether the observed depression of GABAergic activity would cause an increase in the excitability of 5-HTergic neurons using optogenetic technique in DRN slices of the transgenic mouse with channelrhodopsin-2 expressed in GABAergic neurons. When the GABAergic inhibition was enhanced by optical stimulation to GABAergic neurons in mouse DRN, NaSal significantly depolarized the resting membrane potential, increased the input resistance and increased current-evoked firing of 5-HTergic neurons. However, NaSal would fail to increase the excitability of 5-HTergic neurons when the GABAergic synaptic transmission was blocked by picrotoxin, a GABA receptor antagonist. Our results indicate that NaSal suppresses the GABAergic activities to raise the excitability of local 5-HTergic neural circuits in the DRN, which may contribute to the elevated 5-HT level by NaSal in the brain. [ABSTRACT FROM AUTHOR]