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BackgroundGender disparity is pervasive in academic medicine. This study aimed to assess the disparity between men and women with regard to first and senior author positions in primary studies on liver cancer over the last two decades.MethodsWe conducted a review of articles published in high-impact factor journals of the field of Gastroenterology and Hepatology in 2005, 2010, 2015 and 2020. First and senior authors of all ages were considered as the study population. The authors' genders were determined using the online artificial intelligence tool genderize.io (https://genderize.io/). The disparity between men and women authors was assessed using the linear-by-linear association test.Results665 original articles from 10 journals were reviewed. The point prevalence of first women authors was 25.0% compared with 75.0% for men. The point prevalence of senior women authors was 16.3% compared with 83.7% for men. From 2000 to 2020, the proportion of first women authors increased 14.4% to 26.8% compared with 85.6%-73.2% for men (P = 0.009), and the proportion of senior women authors increased from 7.4% to 19.5%, compared with 92.6%-80.5% for men (P = 0.035). The factor independently associated with a reduced representation of women among first authors was the region of author. The factor independently associated with a reduced representation of women among senior authors was the impact factor of journals.ConclusionThe findings indicated a remarkable increase in the proportion of women, both first and senior authors, over the past two decades in the field of liver cancers. However, the representation of women authors in this area is far less than that of men.

During the operation of drilling rigs, bolts are subjected to significant loads, rendering bolt groups vulnerable to failure due to uneven load distribution. This study investigates the multi-bolt load distribution characteristics of eight-gear and four-gear symmetric transmission mechanisms in drilling rigs. The spring stiffness method is utilized to analyze multi-bolt load distribution. A finite element model of the bolted connection is developed by integrating the structural shape and transmission mechanism. The model’s accuracy is validated through a rack strain test under various loads. Based on the finite element analysis results, this study proposes an evaluation method for bolted connections using relative deformation difference. The impacts of bolt pitch, end distance, preload, and thickness of the derrick connection plate under different load positions on the connection are examined. This paper presents a methodology and conclusions that can inform the design of bolted connections for heavy-duty drive systems.

COVID-19 has brought a great challenge to the medical system. A key scientific question is how to make a balance between home quarantine and staying in the hospital. To this end, we propose a game-based susceptible-exposed-asymptomatic -symptomatic- hospitalized-recovery-dead model to reveal such a situation. In this new framework, time-varying cure rate and mortality are employed and a parameter m is introduced to regulate the probability that individuals are willing to go to the hospital. Through extensive simulations, we find that (1) for low transmission rates (β < 0.2), the high value of m (the willingness to stay in the hospital) indicates the full use of medical resources, and thus the pandemic can be easily contained; (2) for high transmission rates (β > 0.2), large values of m lead to breakdown of the healthcare system, which will further increase the cumulative number of confirmed cases and death cases. Finally, we conduct the empirical analysis using the data from Japan and other typical countries to illustrate the proposed model and to test how our model explains reality.

Mobile robot path planning has attracted much attention as a key technology in robotics research. In this paper, a reformative bat algorithm (RBA) for mobile robot path planning is proposed, which is employed as the control mechanism of robots. The Doppler effect is applied to frequency update to ameliorate RBA. When the robot is in motion, the Doppler effect can be adaptively compensated to prevent the robot from prematurely converging. In the velocity update and position update, chaotic map and dynamic disturbance coefficient are introduced respectively to enrich the population diversity and weaken the limitation of local optimum. Furthermore, Q-learning is incorporated into RBA to reasonably choose the loudness attenuation coefficient and the pulse emission enhancement coefficient to reconcile the trade-off between exploration and exploitation, while improving the local search capability of RBA. The simulation experiments are carried out in two different environments, where the success rate of RBA is 93.33% and 90%, respectively. Moreover, in terms of the results of success rate, path length and number of iterations, RBA has better robustness and can plan the optimal path in a relatively short time compared with other algorithms in this field, thus illustrating its validity and reliability. Eventually, by the aid of the Robot Operating System (ROS), the experimental results of real-world robot navigation indicate that RBA has satisfactory real-time performance and path planning effect, which can be considered as a crucial choice for dealing with path planning problems.

Background and aims At present, it is difficult and risky to diagnose splenic lesions by conventional needle biopsy using computed tomography (CT) or ultrasound (US). Endoscopic ultrasound (EUS)-guided tissue acquisition is increasingly being used as a new technique to determine the tissue diagnosis of splenic lesions. Therefore, our goal was to determine the efficacy and safety of EUS-guided tissue acquisition for splenic lesions. Methods We performed a systematic review and meta-analysis to evaluate the pooled sensitivity and specificity of EUS-guided tissue acquisition for the diagnosis of splenic lesions using Metadisc. The Quality Assessment of Diagnostic Accuracy Studies Questionnaire, a quality assessment tool, was used to scrutinize the quality of the studies. Results Six eligible studies between January 2000 and June 2022 were identified, and a total number of 62 patients (aged range from 19 to 84) were enrolled. One patient was excluded because of insufficient specimens. The pooled sensitivity and specificity of included studies were 0.85 [95% confidence interval (CI), 0.73–0.93] and 0.77 (95% CI, 0.46–0.95), respectively. The pooled positive likelihood ratio (LR) was 2.38 (95% CI, 1.24–4.57), the pooled negative LR was 0.31 (95% CI, 0.17–0.55), the pooled diagnostic odds ratio (DOR) was 8.67 (95% CI, 2.80–26.82), the area under the summary receiver operating characteristic (SROC) curve was 0.8100 (Standard Error 0.0813). Conclusion EUS-guided tissue acquisition is a safe technique with high sensitivity in the diagnosis of splenic lesions. However, because of the small sample sizes, more studies with more cases are needed to further validate these results.

IntroductionInflammatory bowel disease is a relapsing chronic gastrointestinal inflammatory disease. Idiopathic pulmonary fibrosis is a rare but serious extraintestinal pulmonary manifestation of inflammatory bowel disease. However, the relationship between these two conditions is unclear. Therefore, this study aims to elucidate this relationship through a systematic review and meta-analysis, focusing on the risk of idiopathic pulmonary fibrosis in patients with inflammatory bowel disease.MethodsThe systematic review will be outlined according to the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols and its extension statement for reporting systematic reviews incorporating network meta-analyses of healthcare interventions: checklist and explanations. Original articles published in any language will be searched in the following databases: PubMed, Web of Science, EMBASE, Google Scholar, and Ovid. Observational studies that reveal an association measure between idiopathic pulmonary fibrosis and inflammatory bowel disease will be included (cross sectional, cohort, and case-control trials). Two independent reviewers will be assigned to evaluate study quality using the Newcastle-Ottawa scale for assessing the quality of non-randomized studies in meta-analyses. Sensitivity analyses will be conducted based on the quality of included studies. All relevant studies will be assessed based on the study type, sample size, inflammatory bowel disease subtype, odds ratio, confidence interval, treatment strategy, and follow-up. The Grading of Recommendations Assessment, Development, and Evaluation approach will be used to rate the quality of the evidence.DiscussionThe results of this meta-analysis may show that patients with inflammatory bowel disease are at higher risk of developing idiopathic pulmonary fibrosis. This study will be the first meta-analysis to focus on the association between inflammatory bowel disease and idiopathic pulmonary fibrosis. Exploring the relationship between the two conditions may further enhance our understanding of the pathogenesis of inflammatory bowel disease and idiopathic pulmonary fibrosis and promote the development of related research fields.

This study examined the roles of visual and olfactory responses during foraging and courtship in butterfly Papilio xuthus. P. xuthus showed obvious orientation to color in the range of 350-500 nm. Visits of P. xuthus females and males to blue, purple, and red artificial cloth flowers were ♀ 54.90% and ♂ 39.22%, ♀ 19.61% and ♂ 35.29%, and ♀ 9.80% and ♂ 19.61%, respectively. Application of 10% honey on these artificial flowers resulted in an increase of 3.41 and 3.26 fold in flower visits by the butterfly compared to controls. When 10% honey water was sprayed on flower branches without colorful flowers, branch visiting was very low, only seven times for females and two times for males, indicating that colors might be more critical than odor for foraging even though visual and olfactory perceptions both play important roles during foraging. During courtship, four types of chasing were observed in a natural population of P. Xuthus; the four types are males chasing females (49%), males chasing males (25%), females chasing males (13%), and females chasing females (10%). However, when odorless artificial models of butterflies were used, no significant differences were observed among these types of chasing, indicating that olfactory perception was crucial for the butterfly during courtship. Profiling volatile organic chemicals (VOCs) and individual bioassays revealed that VOCs contents of butterflies were not related to recognizing sex partners; by contrast, some level of α-farnesene, increased the frequency of male chasing female. This could be due to that α-farnesene is easy to be detected by butterflies because of its volatility and higher content in female.

Seed dispersal is a key component of the interactions between plants and animals. There is little research on the effects of lizard seed dispersal, which is more common on islands than elsewhere. In this study, the effects of the passage of Capparis spinosa seeds through Teratoscincus roborowskii lizard digestive tracts on the seed coats, water uptake rates and germination rates were investigated. In addition, the spatial patterns of fecal deposition by lizards in various microhabitats were assessed. Our results showed that the mean retention time (MRT) of mealworms was significantly longer than that of C. spinosa seeds in both adult and juvenile lizards. The defecation rate of C. spinosa tended to be lower than that of mealworms, which might be beneficial for seed dispersal. It was determined that the longer MRT of C. spinosa seeds enhanced the permeability of the seed coats, which promoted fast water uptake, broke seed dormancy and increased the seed germination rate. Furthermore, the seeds that passed through the digestive tracts of lizards were deposited in favorable germination microhabitats. By enhancing seed germination and depositing intact and viable seeds in safe potential recruitment sites, the lizard T. roborowskii acts, at least qualitatively, as an effective disperser of C. spinosa.

Phosphate (Pi) transporters play critical roles in Pi acquisition and homeostasis. However, little is known about these transporters in oilseed rape. Therefore, the aim of the present study was to characterize the members of the PHT1 gene family in allotetraploid Brassica napus and to analyze their expression profiles in response to environmental stresses. In total, 49 PHT1 family members were identified in B. napus, including 27 genes in the A subgenome and 22 in the C subgenome. Most of the PHT1 proteins were predicted to localize to the plasma membrane. Phylogenetic analysis suggested that the members of the PHT1 gene family can be divided into seven clades, with the introns/exons and protein motifs conserved in each clade. Collinearity analysis revealed that most of the BnaPHT1 genes shared syntenic relationships with PHT1 members in Arabidopsis thaliana, B. rapa, and B. oleracea, and that whole-genome duplication (polyploidy) played a major driving force for BnaPHT1 evolution in addition to segmental duplication. Transcript abundance analysis showed that a broad range of expression patterns of individual BnaPHT1 genes occurred in response to phosphorus (P) deficiency. In addition, the expression levels of BnaPHT1 genes can be regulated by different nutrient stresses, including nitrogen (N), potassium (K), sulfur (S) and iron (Fe) stresses. Moveover, salt and drought stresses can regulate the transcript abundances of BnaPHT1s, as well as phytohormones including auxin and cytokinin. Gene coexpression analysis based on the RNA-seq data implied that BnaPHT1s might cooperate with each other as well as with other genes to regulate nutrient homeostasis in B. napus. Further analysis of the promoters revealed that GT-1, DRE and P1BS elements are widely distributed within the promoter regions of BnaPHT1 genes. Our results indicate that BnaPHT1s might be involved in cross-talk for sensing the external status of P, N, K, S and Fe, as well as salt and drought stresses. Moreover, these processes might be mediated by phytohormones. Our findings provide the first step in the complex genetic dissection of the Pi transport system in plants and implicate multiple transcriptional regulation, which probably refers to new roles of PHT1 genes in B. napus.

Coaxial technique is extensively applied to facilitate percutaneous lung lesion biopsy. However, the impact of coaxial technique on diagnostic accuracy remains undecided. We reviewed 485 patients who underwent percutaneous CT-guided needle biopsies of lung lesions in our hospital. All of these biopsies were performed using either a cutting needle alone (n = 268) or a cutting needle combined with a coaxial needle (n = 217). The diagnostic accuracy and complications resulting from the two techniques were then compared. The diagnostic accuracies of the two techniques were comparably high, at 98.2% (with coaxial technique) and 95.9% (without coaxial technique), p = 0.24. Subgroup analysis discovered that for patients with lesions measuring < 1.5 cm and needle path length ≥ 4 cm, the coaxial technique achieved a higher diagnostic accuracy (95.5% vs. 72.7%, p = 0.023). The biopsy was well tolerated in all of the patients. Pneumothorax occurred less often in patients who were biopsied with the coaxial technique (19 versus 43, p = 0.024). Thus, the application of the coaxial technique could improve diagnostic accuracy in patients with small and deep lung lesions, and could reduce the risk of pneumothorax. The combined use of cutting needles with coaxial needles is the preferred technique for performing percutaneous CT-guided lung biopsies.

Voluntary participation, as an additional strategy involved in repeated games, has been proved to be an efficient way to promote the evolution of cooperation theoretically and empirically. Besides, current studies show that the coevolution of teaching activity can promote cooperation. Thus, inspired by aforementioned above, we investigate the effect of coevolution of teaching activity on the evolution of cooperation for prisoner's dilemma game with voluntary participation: when the focal player successfully enforces its strategy on the opponent, his teaching ability will get an increase. Through numerical simulation, we have shown that voluntary participation could effectively promote the fraction of cooperation, which is also affected by the value of increment. Furthermore, we investigate the influence of the increment value on the density of different strategies and find that there exists an optimal increment value that plays an utmost role on the evolutionary dynamics. With regard to this observation, we unveil that an optimal value of increment can lead to strongest heterogeneity in agents' teaching ability, further promoting the evolution of cooperation.

China harbors diversified forest types, from tropical rainforest to boreal coniferous forest, and has implemented large-scale reforestation/afforestation programs over the past several decades. However, little information is available on changes in China's forest area and the causes. In this study, we used the classified forest distribution thematic map derived from Normalized Difference Vegetation Index (NDVI) datasets and a revised IPAT model to examine China's forest area change and the possible driving factors from 1982 to 2006. Overall, NDVI-derived forest areas were numerically consistent with those reported in the 3rd, 4th, 5th, and 6th National Forest Inventories, respectively. Over the past 25 years, China's forest area was estimated to have an average of 169.18 million hectares with an annual increase of 0.15 million hectares (c.a. a total net increment of 3.60 million hectares), which is equivalent to 0.089% of the relative annual change rate. However, a large difference in the changing rate and direction of forest area at the province level was found; for instance, forest area has declined in 10 provinces, mainly in Northeastern and Southern China, while 21 provinces showed an increase. The changes were most likely attributed to the policy regarding the import and export of timber and affluence (per capita gross domestic product), and both contributed more than 80% of the total contribution of the six factors of the revised IPAT model.

In China, medical staff of children's hospitals are commonly exposed to violence. However, few studies on medical violence are conducted in the settings of children's hospitals. The aim of this study is to assess the incidence, magnitude, consequences, and potential risk factors of workplace violence (WPV) against medical staff of children's hospitals.A retrospective cross-sectional design was used. A self-administered questionnaire was utilized to collect data on 12 children's hospitals. The questionnaires were distributed to a stratified proportional random sample of 2,400 medical staff; 1,932 valid questionnaires were collected. A chi-square test and multiple logistic regression analysis were conducted.A total of 68.6% of respondents had experienced at least one WPV incident involving non-physical and/or physical violence in the past year. The perpetrators were mainly family members of patients (94.9%). Most of the WPV occurred during the day shift (70.7%) and in wards (41.8%). Males were 1.979 times (95% CI, 1.378 to 2.841) more likely than females to experience physical violence. Emergency departments were more exposed to physical violence than other departments. Oncology was 2.733 times (95% CI, 1.126 to 6.633) more exposed to non-physical violence than the emergency department. As a result of WPV, victims felt aggrieved and angry, work enthusiasm declined, and work efficiency was reduced. However, only 5.6% of the victims received psychological counseling.Medical staff are at high risk of violence in China's children's hospitals. Hospital administrators and related departments should pay attention to the consequences of these incidents. There is a need for preventive measures to protect medical staff and provide a safer workplace environment. Our results can provide reference information for intervention strategies and safety measures.

Voluntary participation, demonstrated to be a simple yet effective mechanism to promote persistent cooperative behavior, has been extensively studied. It has also been verified that the aspiration-based win-stay-lose-learn strategy updating rule promotes the evolution of cooperation. Inspired by this well-known fact, we combine the Win-Stay-Lose-Learn updating rule with voluntary participation: Players maintain their strategies when they are satisfied, or players attempt to imitate the strategy of one randomly chosen neighbor. We find that this mechanism maintains persistent cooperative behavior, even further promotes the evolution of cooperation under certain conditions.

The doctor-patient relationship has been a major focus of society. Hospitals' efforts to improve the quality of their medical services have been to reduce the probability of doctor-patient conflicts. In this study, we aimed to determine the gap between expectations and perceptions of service quality according to patients to provide reference data for creating strategies to improve health care quality.Twenty-seven hospitals in 15 provinces (municipalities directly beneath the central government) were selected for our survey; we sent out 1,589 questionnaires, of which 1,520 were collected (response rate 95.65%) and 1,303 were valid (85.72% effective recovery rate). Paired t-tests were used to analyze whether there were significant differences between patients' expectations and perceived service quality. A binary logistic regression analysis was used to determine whether there were significant differences in the gap between expectation and perception of service quality according to patients' demographic characteristics.There was a significant difference between the expected and perceived service quality (p < 0.05) according to patients both before and after receiving medical services. Furthermore, the service quality gap of each service dimension was negative. Specifically, the gaps in service quality were as follows: economy, responsiveness, empathy, assurance, reliability, and tangibles. Overall, we can conclude that patients' perceptions of service quality are lower than their expectations.According to the study results, the quality of health care services as perceived by patients was lower than expected. Hospitals should make adjustments according to the actual situation and should strive to constantly improve the quality of medical services for patients.

BACKGROUND:Recently, academic studies suggest that global growth of airway allergic disease has a close association with dietary changes including reduced consumption of fiber. Therefore, appropriate dietary fiber supplementation might be potential to prevent airway allergic disease (AAD). OBJECTIVE:We investigated whether dietary fiber intake suppressed the induction of AAD and tried to elucidate the possible underlying mechanisms. METHODS:The control mice and AAD model mice fed with 4% standard-fiber chow, while low-fiber group of mice fed with a 1.75% low-fiber chow. The two fiber-intervened groups including mice, apart from a standard-fiber diet, were also intragastric (i.g.) administrated daily with poorly fermentable cellulose or readily fermentable pectin (0.4% of daily body weight), respectively. All animals except normal mice were sensitized and challenged with ovalbumin (OVA) to induce airway allergic inflammation. Hallmarks of AAD were examined by histological analysis and ELISA. The variation in intestinal bacterial composition was assessed by qualitative analysis of 16S ribosomal DNA (rDNA) content in fecal samples using real-time PCR. RESULTS:Low-fiber diet aggravated inflammatory response in ovalbumin-induced allergic mice, whereas dietary fiber intake significantly suppressed the allergic responses, attenuated allergic symptoms of nasal rubbing and sneezing, decreased the pathology of eosinophil infiltration and goblet cell metaplasia in the nasal mucosa and lung, inhibited serum OVA-specific IgE levels, and lowered the levels of Th2 cytokines in NALF and BALF, but, increased Th1 (IFN-γ) cytokines. Additionally, dietary fiber intake also increased the proportion of Bacteroidetes and Actinobacteria, and decreased Firmicutes and Proteobacteria. Levels of probiotic bacteria, such as Lactobacillus and Bifidobacterium, were upgraded significantly. CONCLUSION:Long-term deficiency of dietary fiber intake increases the susceptibility to AAD, whereas proper fiber supplementation promotes effectively the balance of Th1/Th2 immunity and then attenuates allergic inflammatory responses significantly, as well as optimizes the structure of intestinal microbiota, which suggests potential for novel preventive and therapeutic intervention.

[This corrects the article DOI: 10.1371/journal.pone.0164640.].

Improving seed oil yield and quality are central targets in rapeseed (Brassica napus) breeding. The primary goal of our study was to examine and compare the potential and the limits of marker-assisted selection and genome-wide prediction of six important seed quality traits of B. napus. Our study is based on a bi-parental population comprising 202 doubled haploid lines and a diverse validation set including 117 B. napus inbred lines derived from interspecific crosses between B. rapa and B. carinata. We used phenotypic data for seed oil, protein, erucic acid, linolenic acid, stearic acid, and glucosinolate content. All lines were genotyped with a 60k SNP array. We performed five-fold cross-validations in combination with linkage mapping and four genome-wide prediction approaches in the bi-parental population. Quantitative trait loci (QTL) with large effects were detected for erucic acid, stearic acid, and glucosinolate content, blazing the trail for marker-assisted selection. Despite substantial differences in the complexity of the genetic architecture of the six traits, genome-wide prediction models had only minor impacts on the prediction accuracies. We evaluated the effects of training population size, marker density and phenotyping intensity on the prediction accuracy. The prediction accuracy in the independent and genetically very distinct validation set still amounted to 0.14 for protein content and 0.17 for oil content reflecting the utility of the developed calibration models even in very diverse backgrounds.

Accelerated fibrosis in patients co-infected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) has been a major cause of mortality in the highly active anti-retroviral therapy (HAART) era. However, the role of co-infection in accelerating the progression of liver fibrosis, particularly with regard to the effects of co-infection on hepatic stellate cells (HSCs), remains unclear. We hypothesized that HIV and HCV induce liver fibrosis synergistically by altering the regulation of epimorphin production, and thereby indirectly alter HSC function. Here, we examined the effects of epimorphin on HSC proliferation and invasion, and the changes in fibrogenesis-related gene activity in HSCs (LX2) in the presence of inactivated CXCR4-tropic HIV and HCV (JFH1). The combination of HIV and HCV significantly increased epimorphin expression, which increased the proliferation and invasion capabilities of HSCs. Epimorphin also induced the expression of profibrogenic tissue inhibitor of metalloproteinase 1 (TIMP1) in an extracellular signal-regulated kinase (ERK)-dependent manner. These data indicated that the effects of HIV/HCV co-infection on hepatic fibrosis might be mediated in part by EPM. Strategies to limit the expression of EPM might represent a novel therapeutic approach to prevent the progression of hepatic fibrosis during HIV/HCV co-infection.

Cooperation theories assume that interacting individuals can change their strategies under different expected payoffs, depending on their social status or social situations. When looking at sex differences in cooperation, the existing studies have found that the genders cooperate at similar frequencies. However, the majority of the data originate within Western human societies. In this paper, we explore whether there are gender differences in cooperation in China. An Iterated Prisoner's Dilemma game with a punishment option was used to gather data about Southwest Chinese subjects in a culture in which men have a hierarchical advantage over women. Results indicate that men invested into partners significantly more than women did (34% ♂ vs. 24% ♀) while women, in turn, were more likely to defect (65% ♀ vs. 50% ♂). In this region, women have customarily held less economic power and they are used to obtain a payoff typically lower than men. We suggest that the women's willingness to invest in cooperation has decreased throughout evolutionary time, providing us with an illustration of a culturally-driven shift towards a disparity in gender cooperation interests.

Precision genetic engineering accelerates the genetic improvement of livestock for agriculture and biomedicine. We have recently reported our success in producing gene-modified goats using the CRISPR/Cas9 system through microinjection of Cas9 mRNA and sgRNAs targeting the MSTN and FGF5 genes in goat embryos. By investigating the influence of gene modification on the phenotypes of Cas9-mediated goats, we herein demonstrate that the utility of this approach involving the disruption of FGF5 results in increased number of second hair follicles and enhanced fiber length in Cas9-mediated goats, suggesting more cashmere will be produced. The effects of genome modifications were characterized using H&E and immunohistochemistry staining, quantitative PCR, and western blotting techniques. These results indicated that the gene modifications induced by the disruption of FGF5 had occurred at the morphological and genetic levels. We further show that the knockout alleles were likely capable of germline transmission, which is essential for goat population expansion. These results provide sufficient evidences of the merit of using the CRISPR/Cas9 approach for the generation of gene-modified goats displaying the corresponding mutant phenotypes.

Debridement, the removal of diseased, nonviable tissue, is critical for clinicians to readily assess wound status and prepare the wound bed for advanced therapeutics or downstream active healing. Removing necrotic slough and eschar through surgical or mechanical methods is less specific and may be painful for patients. Enzymatic debridement agents, such as Clostridial collagenase, selectively and painlessly degrade devitalized tissue. In addition to its debriding activities, highly-purified Clostridial collagenase actively promotes healing, and our past studies reveal that extracellular matrices digested with this enzyme yield peptides that activate cellular migratory, proliferative and angiogenic responses to injury in vitro, and promote wound closure in vivo. Intriguingly, while collagenase Santyl® ointment, a sterile preparation containing Clostridial collagenases and other non-specific proteases, is a well-accepted enzymatic debridement agent, its role as an active healing entity has never been established. Based on our previous studies of pure Clostridial collagenase, we now ask whether the mixture of enzymes contained within Santyl® produces matrix-derived peptides that promote cellular injury responses in vitro and stimulate wound closure in vivo. Here, we identify novel collagen fragments, along with collagen-associated peptides derived from thrombospondin-1, multimerin-1, fibronectin, TGFβ-induced protein ig-h3 and tenascin-C, generated from Santyl® collagenase-digested human dermal capillary endothelial and fibroblastic matrices, which increase cell proliferation and angiogenic remodeling in vitro by 50-100% over controls. Using an established model of impaired healing, we further demonstrate a specific dose of collagenase from Santyl® ointment, as well as the newly-identified and chemically-synthesized ECM-derived peptides significantly increase wound re-epithelialization by 60-100% over saline-treated controls. These results not only confirm and extend our earlier studies using purified collagenase- and matrix-derived peptides to stimulate healing in vitro and in vivo, but these Santyl®-generated, matrix-derived peptides may also represent exciting new opportunities for creating advanced wound healing therapies that are enabled by enzymatic debridement and potentially go beyond debridement.

Drought stress can seriously affect tuberization, yield and quality of potato plant. However, the precise molecular mechanisms governing potato stolon's response to drought stress and water supply are not very well understood. In this work, a potato (Solanum tuberosum L.) variant, Ningshu 4, was subjected to severe drought stress treatment (DT) and re-watering treatment (RWT) at tuber bulking stage. Strand-specific cDNA libraries of stolon materials were constructed for paired-end transcriptome sequencing analyses and differentially expressed gene (DEG) examination. In comparison to untreated-control (CT) plants, 3189 and 1797 DEGs were identified in DT and RWT plants and 4154 solely expressed DEGs were screened out from these two comparison groups. Interestingly, 263 genes showed opposite expression patterns in DT and RWT plants. Among them, genes homologous to Protein Phosphatase 2C (PP2C), Aspartic protease in guard cell 1 (ASPG1), auxin-responsive protein, Arabidopsis pseudo response regualtor 2 (APRR2), GA stimulated transcripts in Arabidopsis 6 (GASA6), Calmodulin-like protein 19 (CML19), abscisic acid 8'-hydroxylases and calcium-transporting ATPase, et al. were related with drought-stress and water stimulus response. Sixteen DEGs involved in starch synthesis, accumulation and tuber formation exhibited significantly different expression upon re-watering. In addition, 1630, 1527 and 1596 transcription factor encoding genes were detected in CT, DT and RWT. DEGs of ERF, bHLH, MYB, NAC, WRKY, C2H2, bZIP and HD-ZIP families accounted for 50% in three comparison groups, respectively. Furthermore, characteristics of 565 gene ontology (GO) and 108 Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) were analyzed with the 4154 DEGs. All these results suggest that the drought- and water-stimulus response could be implemented by the regulated expression of metabolic pathway DEGs, and these genes were involved in the endogenous hormone biosynthesis and signal transduction pathways. Our data provide more direct information for future study on the interaction between key genes involved in various metabolic pathways under drought stress in potato.

As a devastating holoparasitic weed, Orobanche aegyptiaca Persoon. (Egyptian broomrape) causes serious damage to agricultural production and threatens economic development, which has raised widespread concern. The present study was conducted to determine whether lilies have the potential to be used as 'trap crops' for controlling O. aegyptiaca Persoon. In the experiments, the ability of three popular lily cultivars (Lilium Oriental hybrids 'Sorbonne', Lilium LA (Longiflorum hybrids x Asiatic hybrids) hybrids 'Ceb Dazzle', and Lilium Longiflorum hybrids (L. formosanum x L. longiflorum) 'L. formolongo') to induce O. aegyptiaca Persoon. seed germination was assessed. Parts of the three lily cultivars, including the rhizosphere soil and underground and above-ground organs, all induced "suicidal germination" of parasitic O. aegyptiaca Persoon. seed at four growth stages. Specifically, Sorbonne and Ceb Dazzle behaved with similar allelopathy, and the bulb, scale leaf and aerial stem exhibited stronger allelopathic effects on O. aegyptiaca Pers. germination compared to other organs. Aqueous L. formolongo leaf extracts may contain more stable, effective stimulants given that they induced the highest germination rate at 76.7% even though the extracts were serially diluted. We speculate that these organs may be advantageous in further isolating and purifying economical active substances that can be substitutes for GR24. These results indicate that lilies have the potential to be used as a trap crops or can be processed into green herbicide formulations that can be applied in agriculture production to rapidly deplete the seed bank of O. aegyptiaca Persoon. parasitic weeds in soil.

Zebrafish is a widely used animal model with well-characterized background in developmental biology. The fate of human adipose-derived stem cells (ADSCs) after their xenotransplantation into the developing embryos of zebrafish is unknown. Therefore, human ADSCs were firstly isolated, and then transduced with lentiviral vector system carrying a green fluorescent protein (GFP) reporter gene, and followed by detection of their cell viability and the expression of cell surface antigens. These GFP-expressing human ADSCs were transplanted into the zebrafish embryos at 3.3-4.3 hour post-fertilization (hpf). Green fluorescent signal, the proliferation and differentiation of human ADSCs in recipient embryos were respectively examined using fluorescent microscopy and immunohistochemical staining. The results indicated that human ADSCs did not change their cell viability and the expression levels of cell surface antigens after GFP transduction. Microscopic examination demonstrated that green fluorescent signals of GFP expressed in the transplanted cells were observed in the embryos and larva fish at post-transplantation. The positive staining of Ki-67 revealed the survival and proliferation of human ADSCs in fish larvae after transplantation. The expression of CD105 was observable in the xenotransplanted ADSCs, but CD31 expression was undetectable. Therefore, our results indicate that human ADSCs xenotransplanted in the zebrafish embryos not only can survive and proliferate at across-species circumstance, but also seem to maintain their undifferentiation status in a short term. This xenograft model of zebrafish embryos may provide a promising and useful technical platform for the investigation of biology and physiology of stem cells in vivo.

Nasopharyngeal carcinoma (NPC) is a malignant tumor of the head and neck region, which frequently occurs in Southeast Asia, especially in the south of China. It is known that the mammalian target of rapamycin (mTOR) pathway plays a central role in regulating cellular functions, including proliferation, growth, survival, mobility, and angiogenesis. Aberrant expression of the mTOR signaling pathway molecules has been found in many types of cancer. However, whether the alterations of p-Akt, p-p70S6K and p-4EBP1 protein expression are associated with clinicopathological features and prognostic implications in NPC have not been reported. The purposes of the present study are to investigate the association between the expression of p-Akt, p-p70S6K and p-4EBP1 proteins and clinicopathological features in NPC by immunohistochemistry. The results showed that the positive percentage of p-Akt, p-p70S6K and p-4EBP1 proteins expression in NPC (47.2%, 73.0% and 61.7%, respectively) was significantly higher than that in the non-cancerous nasopharyngeal control tissue (33.3%, 59.1% and 47.0%, respectively). There was a significantly higher positive expression of p-Akt in undifferentiated non-keratinizing nasopharyngeal carcinoma than that in differentiated non-keratinizing nasopharyngeal carcinoma (P = 0.014). Additionally, positive expression of p-p70S6K and p-4EBP1 proteins, and positive expression of either of p-Akt, p-p70S6K and p-4EBP1 were significantly correlated inversely with overall survival rates of NPC patients (P = 0.023, P = 0.033, P = 0.008, respectively). Spearman's rank correlation test showed that expression of p-Akt in NPC was significantly associated with expression of p-p70S6K (r = 0.263, P

Recent studies have revealed that long non-coding RNAs participate in all steps of cancer initiation and progression by regulating protein-coding genes at the epigenetic, transcriptional, and post-transcriptional levels. Long non-coding RNAs are in turn regulated by other genes, forming a complex regulatory network. The regulation networks between the p53 tumor suppressor and these RNAs in nasopharyngeal carcinoma remains unclear. The aims of this study were to investigate the regulatory roles of the TP53 gene in regulating long non-coding RNA expression profiles and to study the function of a TP53-regulated long non-coding RNA (LOC401317) in the nasopharyngeal carcinoma cell line HNE2. Long non-coding RNA expression profiling indicated that 133 long non-coding RNAs were upregulated in the human NPC cell line HNE2 cells following TP53 overexpression, while 1057 were downregulated. Among these aberrantly expressed long non-coding RNAs, LOC401317 was the most significantly upregulated one. Further studies indicated that LOC401317 is directly regulated by p53 and that ectopic expression of LOC401317 inhibits HNE2 cell proliferation in vitro and in vivo by inducing cell cycle arrest and apoptosis. LOC401317 inhibited cell cycle progression by increasing p21 expression and decreasing cyclin D1 and cyclin E1 expression and promoted apoptosis through the induction of poly(ADP-ribose) polymerase and caspase-3 cleavage. Collectively, these results suggest that LOC401317 is directly regulated by p53 and exerts antitumor effects in HNE2 nasopharyngeal carcinoma cells.

Low boron (B) seriously limits the growth of oilseed rape (Brassica napus L.), a high B demand species that is sensitive to low B conditions. Significant genotypic variations in response to B deficiency have been observed among B. napus cultivars. To reveal the genetic basis for B efficiency in B. napus, quantitative trait loci (QTLs) for the plant growth traits, B uptake traits and the B efficiency coefficient (BEC) were analyzed using a doubled haploid (DH) population derived from a cross between a B-efficient parent, Qingyou 10, and a B-inefficient parent, Westar 10. A high-density genetic map was constructed based on single nucleotide polymorphisms (SNPs) assayed using Brassica 60 K Infinium BeadChip Array, simple sequence repeats (SSRs) and amplified fragment length polymorphisms (AFLPs). The linkage map covered a total length of 2139.5 cM, with 19 linkage groups (LGs) and an average distance of 1.6 cM between adjacent markers. Based on hydroponic evaluation of six B efficiency traits measured in three separate repeated trials, a total of 52 QTLs were identified, accounting for 6.14-46.27% of the phenotypic variation. A major QTL for BEC, qBEC-A3a, was co-located on A3 with other QTLs for plant growth and B uptake traits under low B stress. Using a subset of substitution lines, qBEC-A3a was validated and narrowed down to the interval between CNU384 and BnGMS436. The results of this study provide a novel major locus located on A3 for B efficiency in B. napus that will be suitable for fine mapping and marker-assisted selection breeding for B efficiency in B. napus.

To compare the true non-enhanced (TNE) and virtual non-enhanced (VNE) data sets in patients who underwent gastric preoperative dual-energy CT (DECT) and to evaluate potential radiation dose reduction by omitting a TNE scan.A total of 74 patients underwent gastric DECT. The mean CT values, length, image quality and effective radiation doses for VNE and TNE images were compared.There was no statistical difference in maximal thickness of gastric tumors and maximal diameter of enlarged lymph nodes among the TNE and VNE images (P>0.05). The mean CT value differences between TNE and VNE were statistically significant for all tissue types, except for aorta attenuation measurements (P

Maintaining an appropriate balance of carbon to nitrogen metabolism is essential for rice growth and yield. Glutamine synthetase is a key enzyme for ammonium assimilation. In this study, we systematically analyzed the growth phenotype, carbon-nitrogen metabolic status and gene expression profiles in GS1;1-, GS1;2-overexpressing rice and wildtype plants. Our results revealed that the GS1;1-, GS1;2-overexpressing plants exhibited a poor plant growth phenotype and yield and decreased carbon/nitrogen ratio in the stem caused by the accumulation of nitrogen in the stem. In addition, the leaf SPAD value and photosynthetic parameters, soluble proteins and carbohydrates varied greatly in the GS1;1-, GS1;2-overexpressing plants. Furthermore, metabolite profile and gene expression analysis demonstrated significant changes in individual sugars, organic acids and free amino acids, and gene expression patterns in GS1;1-, GS1;2-overexpressing plants, which also indicated the distinct roles that these two GS1 genes played in rice nitrogen metabolism, particularly when sufficient nitrogen was applied in the environment. Thus, the unbalanced carbon-nitrogen metabolic status and poor ability of nitrogen transportation from stem to leaf in GS1;1-, GS1;2-overexpressing plants may explain the poor growth and yield.

Recent clinical studies indicated that angiotensin receptor blockers (ARBs) would decrease the risk of bone fractures in the elderly populations. There is little known about the role of the ARBs in the process of fracture healing. The purpose of the present study was to verify the hypothesis that systemic treatment with telmisartan has the ability to promote fracture healing. In this study, femur fractures were produced in 96 mature male BALB/c mice. Animals were treated with the ARBs telmisartan or vehicle. Fracture healing was analysed after 2, 5 and 10 weeks postoperatively using X-ray, biomechanical testing, histomorphometry, immunohistochemistry and micro-computed tomography (micro-CT). Radiological analysis showed the diameter of the callus in the telmisartan treated animals was significantly increased when compared with that of vehicle treated controls after two weeks of fracture healing. The radiologically observed promotion of callus formation was confirmed by histomorphometric analyses, which revealed a significantly increased amount of bone formation when compared with vehicle-treated controls. Biomechanical testing further showed a significantly greater peak torque at failure, and a higher torsional stiffness in telmisartan-treated animals compared with controls. There was an increased fraction of PCNA-positive cells and VEGF-positive cells in telmisartan-treated group compared with vehicle-treated controls. From the three-dimensional reconstruction of the bony callus, telmisartan-treated group significantly increased the values of BV/TV by 21.7% and CsAr by 26.0% compared to the vehicle-treated controls at 5 weeks post-fracture. In summary, we demonstrate in the current study that telmisartan could promote fracture healing in a mice model via increasing mechanical strength and improving microstructure. The most mechanism is probably by an increase of cell proliferation and neovascularization associated with a decreased VEGF expression in hypertrophic chondrocytes.

Traditionally, cell line generation requires several months and involves screening of over several hundred cell clones for high productivity before dozens are selected as candidate cell lines. Here, we have designed a new strategy for the generation of stable and high-expression cell lines by combining homologous recombination (HR) and fluorescence-activated cell sorting (FACS). High expression was indicated by the expression of secreted green fluorescent protein (SEGFP). Parental cell lines with the highest expression of SEGFP were then selected by FACS and identified by stability analysis. Consequently, HR vectors were constructed using the cassette for SEGFP as the HR region. After transfecting the HR vector, the cells with negative SEGFP expression were enriched by FACS. The complete exchange between SEGFP and target gene (TNFR-Fc) cassettes was demonstrated by DNA analysis. Compared with the traditional method, by integrating the cassette containing the gene of interest into the pre-selected site, the highest producing cells secreted a more than 8-fold higher titer of target protein. Hence, this new strategy can be applied to isolated stable cell lines with desirable expression of any gene of interest. The stable cell lines can rapidly produce proteins for researching protein structure and function and are even applicable in drug discovery.

As function units, network motifs have been detected to reveal evolutionary mechanisms of complex systems, such as biological networks, food webs, engineering networks and social networks. However, emergence of motifs in growing networks may be problematic due to large fluctuation of subgraph frequency in the initial stage. This paper contributes to present a method which can identify the emergence of motif in growing networks. Based on the Erdös-Rényi(E-R) random null model, the variation rate of expected frequency of subgraph at adjacent time points was used to define the suitable detection range for motif identification. Upper and lower boundaries of the range were obtained in analytical form according to a chosen risk level. Then, the statistical metric Z-score was extended to a new one, Z(continuous), which effectively reveals the statistical significance of subgraph in a continuous period of time. In this paper, a novel research framework of motif identification was proposed, defining critical boundaries for the evolutionary process of networks and a significance metric of time scale. Finally, an industrial ecosystem at Kalundborg was adopted as a case study to illustrate the effectiveness and convenience of the proposed methodology.

Tai people are widely distributed in Thailand, Laos and southwestern China and are a large population of Southeast Asia. Although most anthropologists and historians agree that modern Tai people are from southwestern China and northern Thailand, the place from which they historically migrated remains controversial. Three popular hypotheses have been proposed: northern origin hypothesis, southern origin hypothesis or an indigenous origin. We compared the genetic relationships between the Tai in China and their "siblings" to test different hypotheses by analyzing 10 autosomal microsatellites. The genetic data of 916 samples from 19 populations were analyzed in this survey. The autosomal STR data from 15 of the 19 populations came from our previous study (Lin et al., 2010). 194 samples from four additional populations were genotyped in this study: Han (Yunnan), Dai (Dehong), Dai (Yuxi) and Mongolian. The results of genetic distance comparisons, genetic structure analyses and admixture analyses all indicate that populations from northern origin hypothesis have large genetic distances and are clearly differentiated from the Tai. The simulation-based ABC analysis also indicates this. The posterior probability of the northern origin hypothesis is just 0.04 [95%CI: (0.01-0.06)]. Conversely, genetic relationships were very close between the Tai and populations from southern origin or an indigenous origin hypothesis. Simulation-based ABC analyses were also used to distinguish the southern origin hypothesis from the indigenous origin hypothesis. The results indicate that the posterior probability of the southern origin hypothesis [0.640, 95%CI: (0.524-0.757)] is greater than that of the indigenous origin hypothesis [0.324, 95%CI: (0.211-0.438)]. Therefore, we propose that the genetic evidence does not support the hypothesis of northern origin. Our genetic data indicate that the southern origin hypothesis has higher probability than the other two hypotheses statistically, suggesting that the Tai people most likely originated from southern China.

BackgroundHygiene hypothesis demonstrates that the lack of microbial exposure would promote the development of allergic airway disease (AAD). Therefore, the gut microbiota, including Escherichia coli (E. coli), would probably offer a potential strategy for AAD.ObjectiveTo investigate whether E. coli infection is able to suppress the induction of AAD and to elucidate the underlying mechanisms.MethodsNonpathogenic E. coli ATCC 25922 was infected by gavage before AAD phase in three patterns: 10(8) or 10(6) CFU in neonates or 10(8) CFU in adults. Then mice were sensitized and challenged with ovalbumin (OVA) to induce allergic inflammation in both the upper and lower airways. Hallmarks of AAD, in terms of eosinophil infiltration and goblet cell metaplasia in subepithelial mucosa, Th2 skewing of the immune response, and levels of T regulate cells (Tregs), were examined by histological analysis, ELISA, and flow cytometry, respectively.ResultsE. coli, especially neonatally infected with an optimal dose, attenuated allergic responses, including a decrease in nasal rubbing and sneezing, a reduction in eosinophil inflammation and goblet cell metaplasia in subepithelial mucosa, decreased serum levels of OVA-specific IgE, and reduced Th2 (IL-4) cytokines. In contrast, this effect came with an increase of Th1 (IFN-r and IL-2) cytokines, and an enhancement of IL-10-secreting Tregs in paratracheal lymph nodes (PTLN).ConclusionE. coli suppresses allergic responses in mice, probably via a shift from Th1 to Th2 and/or induction of Tregs. Moreover, this infection is age- and dose-dependent, which may open up novel possibilities for new therapeutic interventions.

Helicobacter pylori is cause of chronic gastritis, duodenal ulcer and gastric carcinoma in humans. L-proline is a preferred energy source of the microaerophilic bacterium. Previous analyses revealed that HpputP and HpputA, the genes that are predicted to play a central role in proline metabolism as they encode for the proline transporter and proline dehydrogenase, respectively, are essential for stomach colonization. Here, the molecular basis of proline transport in H. pylori by HpPutP was investigated experimentally for the first time. Measuring radiolabeled substrate transport in H. pylori and E. coli heterologously expressing HpputP as well as in proteoliposomes reconstituted with HpPutP, we demonstrate that the observed proline transport in H. pylori is mediated by HpPutP. HpPutP is specific and exhibits a high affinity for L-proline. Notably, L-proline transport is exclusively dependent on Na(+) as coupling ion, i.e., Na(+)/L-proline symport, reminiscent to the properties of PutP of E. coli even though H. pylori lives in a more acidic environment. Homology model-based structural comparisons and substitution analyses identified amino acids crucial for function. HpPutP-catalyzed proline uptake was efficiently inhibited by the known proline analogs 3,4-dehydro-D,L-proline and L-azetidine-2-carboxylic acid.

Human monocytes/macrophages (M/M(Ф)) of the innate immunity sense and respond to microbial products via specific receptor coupling with stimulatory (such as TLR) and inhibitory (such as Tim-3) receptors. Current models imply that Tim-3 expression on M/M(Ø) can deliver negative signaling to TLR-mediated IL-12 expression through trans association with its ligand Galectin-9 (Gal-9) presented by other cells. However, Gal-9 is also expressed within M/M(Ø), and the effect of intracellular Gal-9 on Tim-3 activities and inflammatory responses in the same M/M(Ø) remains unknown. In this study, our data suggest that Tim-3 and IL-12/IL-23 gene transcriptions are regulated by enhanced or silenced Gal-9 expression within monocytes through synergizing with TLR signaling. Additionally, TLR activation facilitates Gal-9/Tim-3 cis association within the same M/M(Ø) to differentially regulate IL-12/IL-23 expressions through STAT-3 phosphorylation. These results reveal a ligand (Gal-9) compartment-dependent regulatory effect on receptor (Tim-3) activities and inflammatory responses via TLR pathways--a novel mechanism underlying cellular responses to external or internal cues.

CYP4A11 oxidizes endogenous arachidonic acid to 20-hydroxyeicosatetraenoic acid, a renal vasoconstrictor and natriuretic in humans. Previous studies demonstrated an association between a functional variant (T8590C) of CYP4A11 and essential hypertension, though with conflicting results. To elucidate this relationship, a case-control study and meta-analysis were performed to assess the possible association of essential hypertension with CYP4A11 genetic variations.Associations between the T8590C polymorphism and essential hypertension were examined in 328 unrelated cases and 297 age-matched controls in Han Chinese individuals. High-resolution melting was used to identify the CYP4A11 variant. To further investigate the association, we conducted a meta-analysis including eight studies published previously in July 2012.The frequency of the CYP4A11 T8590C polymorphism showed no significant difference between cases and controls (all P>0.05). However, the meta-analysis showed that the CYP4A11 T8590C polymorphism may increase the risk of essential hypertension in an additive model (OR: 1.15, 95% CI: 1.02-1.29, P = 0.02), a dominant model (OR: 1.06, 95% CI: 1.01-1.32, P = 0.03), a recessive model (OR: 1.52, 95% CI: 1.15-2.02, P = 0.003) and a homozygote contrast (OR: 1.38, 95% CI: 1.07-1.78, P = 0.01). Also, a significant relationship was observed among Caucasians in the additive model, the homozygote contrast, the recessive model and the dominant model (all P0.05).This meta-analysis suggests there is a significant association between the CYP4A11 T8590C variant and essential hypertension, especially in Caucasians. The case-control study did not find a significant association among the Han Chinese population, but the controls were poorly matched and meaningful conclusions cannot therefore be made. Further large-scale studies are needed to clarify whether the CYP4A11 T8590C polymorphism is associated with hypertension risk in Asians or has a gender-specific effect.

Long-palate, lung and nasal epithelium clone 1 (LPLUNC1) gene expression is relatively tissue specific. It is highly expressed in nontumor nasopharyngeal epithelial tissues, but its expression is reduced in nasopharyngeal carcinoma (NPC), indicating that LPLUNC1 may be associated with the tumorigenesis of NPC. To study the effects of LPLUNC1 on NPC tumorigenesis, a full-length LPLUNC1 expression plasmid was stably transfected into the NPC cell line, 5-8F. Our data indicated that LPLUNC1 inhibited NPC cell proliferation in vitro and tumor formation in vivo. LPLUNC1 also delayed cell cycle progression from G1 to S phase and inhibited the expression of cyclin D1, cyclin-dependent kinase 4 (CDK4) and phosphorylated Rb. To further investigate the molecular mechanisms underlying the suppressive effects of LPLUNC1 on NPC tumorigenesis, cDNA microarray was performed. These studies revealed that LPLUNC1 inhibited the expression of certain mitogen-activated protein (MAP) kinases (MAPK) kinases and cell cycle-related molecules. Western blotting confirmed that the expression of MEK1, phosphorylated ERK1/2, phosphorylated JNK1/2, c-Myc and c-Jun were inhibited by LPLUNC1. Furthermore, the transcriptional activity of AP-1 was down-regulated by LPLUNC1, suggesting that the MAPK signaling pathway is regulated by LPLUNC1. Taken together, the present study indicates that LPLUNC1 delays NPC cell growth by inhibiting the MAPK and cyclin D1/E2F pathways and suggests that LPLUNC1 may represent a promising candidate tumor suppressor gene associated with NPC.

BACKGROUND: The mismatch of the elastic modulus between implants and bone tissue can lead to stress shielding, bone resorption and poor osseointegration. Compared with normal bone tissue, this problem is much more serious in osteoporosis. The purpose of this study was designed to find out whether the novel Ti-24Nb-4Zr-7.9Sn (TNZS) implant with low elastic modulus and high strength was suitable for biomedical material, especially in osteoporosis. METHODOLOGY: In vitro study, the viability and Alkaline phosphatase (ALP) activity of osteoblasts on the TNZS and Ti-6V-4V (TAV) were observed. In vivo study, 30 adult female New Zealand rabbits were selected and divided randomly into two groups: sham-operation (SHAM, n=6) and ovariectomised in combination with methylprednisolone treatment (OVX+MP, n=24). Two implants were then placed in the tibia of each OVX + MP group rabbit, one in each side (left: TAV; right: TNZS). The OVX + MP group rabbits were sacrificed at 4 and 12 weeks after the implantation. The osteoporotic bone responses to the TNZS and TAV implants were evaluated by pull-out test, Micro-CT analyses and histological observation. PRINCIPAL FINDINGS: Compared with the TAV group, the TNZS group showed a significant increase (P

BACKGROUND: Oilseed rape (Brassica napus L.) is one of the most important oil crops. A primary limitation to the cultivation of this crop is the lack of available phosphorus (P) in soils. To elucidate the genetic control of P deficiency tolerance in Brassica napus, quantitative trait locus (QTL) for seed yield and yield related-traits in response to P deficiency were identified using a double haploid mapping population (TN DH) derived from a cross between a P-efficient cultivar, Ningyou 7 and a P-inefficient cultivar, Tapidor. RESULTS: Three field trials were conducted to determine seed yield (SY), plant height (PH), number of primary branches (BN), height to the first primary branch (FBH), relative first primary branch height (RBH), pod number per plant (PN), seed number per pod (SN) and seed weight of 1,000 seeds (SW) in 188 lines of TN DH population exposed to low P (LP) and optimal P (OP) conditions. P deficiency decreased PH, BN, SN, PN and SY, and increased FBH and RBH with no effect on SW. Three reproducible LP-specific QTL regions were identified on chromosomes A2, A3 and A5 that controlled SN, PN and SW respectively. In addition, six reproducible constitutive regions were also mapped with two each for SY-LP on A2, and FBH-LP on C6 and one each for PH-LP and SW-LP on A3. About 30 markers derived from 19 orthologous genes involved in Arabidopsis P homeostasis were mapped on 24 QTL regions by comparative mapping between Arabidopsis and Brassica napus. Among these genes, GPT1, MGD2 and SIZ1 were associated with two major loci regulating SY-LP and other yield-related traits on A2 between 77.1 and 95.0 cM. CONCLUSION: The stable QTLs detected under LP conditions and their candidate genes may provide useful information for marker-assisted selection in breeding high-yield B. napus varieties with improved P efficiency.

Mutations in the TARDBP gene, which encodes the Tar DNA binding protein, have been shown to causes of both familial amyotrophic lateral sclerosis (FALS) and sporadic ALS (SALS). Recently, several novel TARDBP exon 6 mutants have been reported in patients with ALS in Europe and America but not in Asia. To further examine the spectrum and frequency of TARDBP exon 6 mutations, we investigated their frequency in ethnic Chinese patients with sporadic ALS. TARDBP exon 6 was screened by direct sequencing in 207 non-SOD1 SALS patients and 230 unrelated healthy controls but no mutations were identified. Our data indicate that exon 6 mutations in TARDBP are not a common cause of SALS in Han Chinese population from Southern Mainland China.

Mycoplasma bovis pneumonia in cattle has been epidemic in China since 2008. To investigate M. bovis pathogenesis, we completed genome sequencing of strain HB0801 isolated from a lesioned bovine lung from Hubei, China. The genomic plasticity was determined by comparing HB0801 with M. bovis strain ATCC® 25523™/PG45 from cow mastitis milk, Chinese strain Hubei-1 from lesioned lung tissue, and 16 other Mycoplasmas species. Compared to PG45, the genome size of HB0801 was reduced by 11.7 kb. Furthermore, a large chromosome inversion (580 kb) was confirmed in all Chinese isolates including HB0801, HB1007, a strain from cow mastitis milk, and Hubei-1. In addition, the variable surface lipoproteins (vsp) gene cluster existed in HB0801, but contained less than half of the genes, and had poor identity to that in PG45, but they had conserved structures. Further inter-strain comparisons revealed other mechanisms of gene acquisition and loss in HB0801 that primarily involved insertion sequence (IS) elements, integrative conjugative element, restriction and modification systems, and some lipoproteins and transmembrane proteins. Subsequently, PG45 and HB0801 virulence in cattle was compared. Results indicated that both strains were pathogenic to cattle. The scores of gross pathological assessment for the control group, and the PG45- and HB0801-infected groups were 3, 13 and 9, respectively. Meanwhile the scores of lung lesion for these three groups were 36, 70, and 69, respectively. In addition, immunohistochemistry detection demonstrated that both strains were similarly distributed in lungs and lymph nodes. Although PG45 showed slightly higher virulence in calves than HB0801, there was no statistical difference between the strains (P>0.05). Compared to Hubei-1, a total of 122 SNP loci were disclosed in HB0801. In conclusion, although genomic plasticity was thought to be an evolutionary advantage, it did not apparently affect virulence of M. bovis strains in cattle.

A synchronized dual-wavelength laser speckle contrast imaging (DWLSCI) system and a Doppler optical microangiography (DOMAG) system was developed to determine several ischemic parameters in the cochlea due to a systemic hypoxic challenge. DWLSCI can obtain two-dimensional data, and was used to determine the relative changes in cochlear blood flow, and change in the concentrations of oxyhemoglobin (HbO), deoxyhemoglobin (Hb) and total hemoglobin (HbT) in mice. DOMAG can obtain three-dimensional data, and was used to determine the changes in cochlear blood flow with single vessel resolution. It was demonstrated that during a hypoxic challenge there was an increase in the concentrations of Hb, a decrease in the concentrations of HbO and cochlear blood flow, and a slight decrease in the concentration of HbT. Also, the rate of change in the concentrations of Hb and HbO was quantified during and after the hypoxic challenge. The ability to simultaneously measure these ischemic parameters with high spatio-temporal resolution will allow the detailed quantitative analysis of several hearing disorders, and will be useful for diagnosing and developing treatments.

High yield is the most important goal in crop breeding, and boron (B) is an essential micronutrient for plants. However, B deficiency, leading to yield decreases, is an agricultural problem worldwide. Brassica napus is one of the most sensitive crops to B deficiency, and considerable genotypic variation exists among different cultivars in response to B deficiency. To dissect the genetic basis of tolerance to B deficiency in B. napus, we carried out QTL analysis for seed yield and yield-related traits under low and normal B conditions using the double haploid population (TNDH) by two-year and the BQDH population by three-year field trials. In total, 80 putative QTLs and 42 epistatic interactions for seed yield, plant height, branch number, pod number, seed number, seed weight and B efficiency coefficient (BEC) were identified under low and normal B conditions, singly explaining 4.15-23.16% and 0.53-14.38% of the phenotypic variation. An additive effect of putative QTLs was a more important controlling factor than the additive-additive effect of epistatic interactions. Four QTL-by-environment interactions and 7 interactions between epistatic interactions and the environment contributed to 1.27-4.95% and 1.17-3.68% of the phenotypic variation, respectively. The chromosome region on A2 of SYLB-A2 for seed yield under low B condition and BEC-A2 for BEC in the two populations was equivalent to the region of a reported major QTL, BE1. The B. napus homologous genes of Bra020592 and Bra020595 mapped to the A2 region and were speculated to be candidate genes for B efficiency. These findings reveal the complex genetic basis of B efficiency in B. napus. They provide a basis for the fine mapping and cloning of the B efficiency genes and for breeding B-efficient cultivars by marker-assisted selection (MAS).

Plasmodium requires an obligatory life stage in its mosquito host. The parasites encounter a number of insults while journeying through this host and have developed mechanisms to avoid host defenses. Lysozymes are a family of important antimicrobial immune effectors produced by mosquitoes in response to microbial challenge.A mosquito lysozyme was identified as a protective agonist for Plasmodium. Immunohistochemical analyses demonstrated that Anopheles gambiae lysozyme c-1 binds to oocysts of Plasmodium berghei and Plasmodium falciparum at 2 and 5 days after infection. Similar results were observed with Anopheles stephensi and P. falciparum, suggesting wide occurrence of this phenomenon across parasite and vector species. Lysozyme c-1 did not bind to cultured ookinetes nor did recombinant lysozyme c-1 affect ookinete viability. dsRNA-mediated silencing of LYSC-1 in Anopheles gambiae significantly reduced the intensity and the prevalence of Plasmodium berghei infection. We conclude that this host antibacterial protein directly interacts with and facilitates development of Plasmodium oocysts within the mosquito.This work identifies mosquito lysozyme c-1 as a positive mediator of Plasmodium development as its reduction reduces parasite load in the mosquito host. These findings improve our understanding of parasite development and provide a novel target to interrupt parasite transmission to human hosts.

Changes in forest carbon stocks are a determinant of the regional carbon budget. In the past several decades, China has experienced a pronounced increase in forest area and density. However, few comprehensive analyses have been conducted. In this study, we employed the Forest Identity concept to evaluate the changing status of China's forests over the past three decades, using national forest inventory data of five periods (1977-1981, 1984-1988, 1989-1993, 1994-1998, and 1999-2003). The results showed that forest area and growing stock density increased by 0.51% and 0.44% annually over the past three decades, while the conversion ratio of forest biomass to growing stock declined by 0.10% annually. These developments resulted in a net annual increase of 0.85% in forest carbon sequestration, which is equivalent to a net biomass carbon uptake of 43.8 Tg per year (1 Tg = 10(12) g). This increase can be attributed to the national reforestation/afforestation programs, environmentally enhanced forest growth and economic development as indicated by the average gross domestic product.

Recently, many studies have reported that the SNP+45(T>G) and SNP+276(G>T) polymorphisms in the adiponectin gene are associated with type 2 diabetes (T2DM) in the Chinese Han population. However, the previous studies yielded many conflicting results. Thus, a meta-analysis of the association of the adiponectin gene with T2DM in the Chinese Han population is required. In the current study, we first determined the distribution of the adiponectin SNP+276 polymorphism in T2DM and nondiabetes (NDM) control groups. Our results suggested that the genotype and allele frequencies for SNP+276 did not differ significantly between the T2DM and NDM groups. Then, a meta-analysis of 23 case-control studies of SNP+45, with a total of 4161 T2DM patients and 3709 controls, and 11 case-control studies of SNP+276, with 2533 T2DM patients and 2212 controls, was performed. All subjects were Han Chinese. The fixed-effects model and random-effects model were applied for dichotomous outcomes to combine the results of the included studies. The results revealed a trend towards an increased risk of T2DM for the SNP+45G allele as compared with the SNP+45T allele (OR = 1.34; 95% CI, 1.11-1.62; P

BACKGROUND: Schistosomiasis is a parasitic disease infecting more than 200 million people in the world. Although chemotherapy targeting on killing schistosomes is one of the main strategies in the disease control, there are few effective ways of dealing with liver fibrosis caused by the parasite infection in the chronic and advanced stages of schistosomiasis. For this reason, new strategies and prospective drugs, which exert antifibrotic effects, are urgently required. METHODS AND FINDINGS: The antifibrotic effects of praziquantel were assessed in the murine models of schistosomiasis japonica. Murine fibrosis models were established by cutaneous infection with 14 ± 2 Schistosoma japonicum cercariae. Then, the mice of both chronic (8 weeks post-infection) and advanced (15 weeks post-infection) schistosomiasis were treated by gavage of praziquantel (250 mg/kg, once daily for 3 days) to eliminate worms, and followed by praziquantel anti-fibrosis treatment (300 mg/kg, twice daily for 30 days). The fibrosis-related parameters assessed were areas of collagen deposition, content of hydroxyproline and mRNA expressions of Col1α1, Col3α1, α-SMA, TGF-β, MMP9, TIMP1, IL-4, IL-10, IL-13 and IFN-γ of liver. Spleen weight index, alanine aminotransferase activity and liver portal venous pressure were also measured. The results showed that anti-fibrosis treatment improved liver fibrosis, splenomegaly, hepatic function, as well as liver portal hypertension. In order to confirm the anti-fibrotic properties of praziquantel, we established a CCL(4)-induced model and revealed that CCL(4)-induced liver fibrosis was inhibited by PZQ treatment for 30 days. Furthermore, we analyzed the effects of praziquantel on mouse primary hepatic stellate cells (HSCs). It is indicated that mRNA expressions of Col1α1, Col3α1, α-SMA, TGF-β, MMP9 and TIMP1 of HSCs were all inhibited after praziquantel anti-parasite treatments. CONCLUSIONS: The significant amelioration of hepatic fibrosis by praziquantel treatment validates it as a promising drug of anti-fibrosis and offers potential of a new chemotherapy for hepatic fibrosis resulting from schistosomiasis.