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In the prefabricated construction industry, consumers are sensitive to the construction delivery time, and different power structures are very common. This research uses methods of Stackelberg game, Nash game and supply chain coordination, introduces a manufacturer crashing strategy into a prefabricated construction supply chain and investigates the assembler pricing, manufacturer crashing, and supply chain coordination strategies under three different power structures. It finds that adopting a crashing strategy improves the supply chain's profit, while the dynamic wholesale price contract achieves supply chain coordination. Meanwhile, when consumer time and price sensitivity are low, it is easier to achieve high profits in the supply chain under unequal power distribution. Conversely, the supply chain profit is higher in the case of a Nash game. This study innovatively introduces the thought of power structure and crashing strategy into the prefabricated construction supply chain, and provides the optimal price and delivery time under three different power structures for prefabricated construction enterprises and realizes supply chain coordination. The conclusion can provide decision suggestions for the prefabricated construction enterprises under different competitive environments. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the prevalence of Toxoplasma gondii (T. gondii) among patients in Guangzhou city, South China, and to identify susceptible patient populations and analyze the causes of infection differences. Methods: From May 2020 to May 2022, a total of 637 sera were collected from patients, and 205 sera were collected from health participants as health control. All sera were examined by colloidal gold kits to detect the positivity of antibodies against T. gondii. And the positivity of antibodies in sera was confirmed with ARCHITECT i2000SR system. Results: The prevalence of T. gondii infection in patients was 7.06% (45/637), which was lower than the prevalence in health participants 4.88% (10/205). Among patients, 34 (5.34%) were positive only for IgG, 10 (1.57%) were only for IgM, and 1 (0.16%) was positive for both IgG and IgM. There was a significant difference in prevalence between male and female patients, but not among different age groups or diseases groups. The prevalence of T. gondii infection in diseases groups varied. The prevalence was relatively high in patients with the disorders of thyroid gland and the malignant neoplasms of digestive organs, which suggests that caution should be taken to avoid T. gondii infection in these patients. Surprisingly, the prevalence was quite low in diffuse Large B-cell Lymphoma (DLBC) patients. This may be due to the overexpression of TNF-α in tumor tissues of DLBC patients and the higher protein level of TNF-α in sera of DLBC patients. Conclusion: This study provides a systematic exploration of the prevalence of T. gondii infection in patients in a tertiary hospital. Our data contributes to a better understanding of the epidemic investigation of T. gondii among patients in South China, which can help the prevention and treatment of the disease caused by T. gondii infection. [ABSTRACT FROM AUTHOR]

Infecting a wide range of hosts, members of Reovirales (formerly Reoviridae) consist of a genome with different numbers of segmented double stranded RNAs (dsRNA) encapsulated by a proteinaceous shell and carry out genome replication and transcription inside the virion. Several cryo-electron microscopy (cryo-EM) structures of reoviruses with 9, 10 or 11 segmented dsRNA genomes have revealed insights into genome arrangement and transcription. However, the structure and genome arrangement of 12-segmented Reovirales members remain poorly understood. Using cryo-EM, we determined the structure of mud crab reovirus (MCRV), a 12-segmented dsRNA virus that is a putative member of Reovirales in the non-turreted Sedoreoviridae family, to near-atomic resolutions with icosahedral symmetry (3.1 Å) and without imposing icosahedral symmetry (3.4 Å). These structures revealed the organization of the major capsid proteins in two layers: an outer T = 13 layer consisting of VP12 trimers and unique VP11 clamps, and an inner T = 1 layer consisting of VP3 dimers. Additionally, ten RNA dependent RNA polymerases (RdRp) were well resolved just below the VP3 layer but were offset from the 5-fold axes and arranged with D5 symmetry, which has not previously been seen in other members of Reovirales. The N-termini of VP3 were shown to adopt four unique conformations; two of which anchor the RdRps, while the other two conformations are likely involved in genome organization and capsid stability. Taken together, these structures provide a new level of understanding for capsid stabilization and genome organization of segmented dsRNA viruses. Author summary: Mud crab reovirus (MCRV), a putative member of the Sedoreoviridae family in Reovirales, infects an economically important crab, Scylla serrata, and has resulted in serious economic loss for the crab aquaculture. In this study, we report the structure of MCRV, which has allowed us to examine the detailed structural elements that might be responsible for capsid stability, as well as those involved in genome packaging and RdRp organization. The arrangement of viral polymerases inside the capsid differ from what has been seen in other viruses of the same order, as ten of the vertices are occupied by RdRp in a symmetrical organization not seen elsewhere. In addition, the VP11 protein is analogous to the "clamp" protein of turreted reovirads. [ABSTRACT FROM AUTHOR]

Rotenone is a commonly used insecticidal chemical in agriculture and it is an inhibitor of mitochondrial complex Ⅰ. Previous studies have found that rotenone induces the production of reactive oxygen species (ROS) by inhibiting electron transport in the mitochondria of somatic and germ cells. However, there is little precise information on the effects of rotenone exposure in porcine oocytes during in vitro maturation, and the mechanisms underlying these effects have not been determined. The Cumulus-oocyte complexes were supplemented with different concentrations of rotenone to elucidate the effects of rotenone exposure on the meiotic maturation of porcine oocytes during in vitro maturation for about 48 hours. First, we found that the maturation rate and expansion of cumulus cells were significantly reduced in the 3 and 5 μM rotenone-treated groups. Subsequently, the concentration of rotenone was determined to be 3 μM. Also, immunofluorescence, western blotting, and image quantification analyses were performed to test the rotenone exposure on the meiotic maturation, total and mitochondrial ROS, mitochondrial function and biogenesis, mitophagy and apoptosis in porcine oocytes. Further experiments showed that rotenone treatment induced mitochondrial dysfunction and failure of mitochondrial biogenesis by repressing the level of SIRT1 during in vitro maturation of porcine oocytes. In addition, rotenone treatment reduced the ratio of active mitochondria to total mitochondria, increased ROS production, and decreased ATP production. The levels of LC3 and active-caspase 3 were significantly increased by rotenone treatment, indicating that mitochondrial dysfunction induced by rotenone increased mitophagy but eventually led to apoptosis. Collectively, these results suggest that rotenone interferes with porcine oocyte maturation by inhibiting mitochondrial function. [ABSTRACT FROM AUTHOR]

Prefabricated construction has attracted worldwide concern and promotion due to its environmental friendliness, high quality, and high efficiency. In China, the application of prefabricated construction still lags due to its high cost. To improve prefabricated construction development, the Chinese government and provinces have launched subsidy policies for different objects that offer subsidies to the assembler, the manufacturer, or consumers. Subsidy policies for different subsidy objects have different impacts on the manufacturer wholesale price and assembler retail price and assembly rate and make their decisions more complicated. Therefore, this study uses game theory and builds three models to analyze the effects of government subsidies on manufacturer pricing, assembler pricing, assembly rate decisions, and profit. We find that government subsidy policies can bring more profit to prefabricated construction enterprises, reduce their costs, and benefit the promotion of prefabricated construction. Through comparison and numerical analysis, we also find that when the government subsidizes enterprises more, it is better to subsidize the assembler, because it is good for all three parties. First, consumers can obtain a lower retail price. Second, enterprises can obtain more profits. Finally, for the government, this approach can increase the demand for prefabricated construction and increase the assembly rate, which is conducive to the promotion of prefabricated construction. When the government subsidizes customers more, it is better for the assembler and the manufacturer to subsidize customers, because they can obtain more profits. It is better for the government and customers to subsidize the assembler or the manufacture, because consumers can get the lower retail price. Although the assembly rate and enterprises' profits are not optimal, they have also been improved. In addition, when the government directly subsidizes enterprises, the enterprises will actively cooperate with the subsidy policy and are more willing to adopt prefabricated construction. This approach will benefit the promotion of prefabricated construction. [ABSTRACT FROM AUTHOR]

Prefabricated construction (PC) has attracted wide spread attention as a model of sustainable development for the construction industry of the future. Although the PC has many advantages, it is still at an initial stage in China. Based on the current conditions in China, this study focuses on the interrelationships of factors affecting PC promotion. Firstly, through a comprehensive review of relevant literatures and expert recommendations, 5 factors were identified: policy factor, technical factor, management factor, market factor and cost factor. Next, the data were collected through a questionnaire survey, and the questionnaire data were processed using SPSS 24.0 and AMOS 22.0. The overall relationships of each factor were quantitatively analyzed with Structural Equation Modeling (SEM). The results show that the policy factor plays a dominant role, while the management factor and market factors are also significant. This study also provides decision makers with relevant information about the factors involved, which will be helpful in devising appropriate strategies for the wider adoption of PC. [ABSTRACT FROM AUTHOR]

Fairness concern behavior is extremely common in social life, and many scholars are beginning to pay attention to this behavior. In this study, we investigate a two-echelon construction supply chain that consists of a general contractor and a subcontractor under cap-and-trade policy. We study the carbon emission reduction decisions and profit distribution mechanism in the construction supply chain with fairness concern and cap-and-trade. We use the Nash bargaining model to describe the fairness concerns of the construction supply chain members and use the co-opetition model to portray the profit distribution. We show that the fairness concern can impose an adverse influence on firms' profits and decrease the magnitude of their carbon emission reductions. The subcontractor's fairness concern causes greater losses to the construction supply chain's profit. We further demonstrate the impact of fairness concern on the optimal decisions of the general contractor and the subcontractor through numerical analysis. [ABSTRACT FROM AUTHOR]

School socioeconomic status (SES) is studied primarily as a variable to explain academic achievement; however, few previous studies have investigated how SES can influence individual student's academic achievement. The present study used a national representative sample of 10,784 grade 7 to 9 students (53.2% boys and 46.8% girls) in mainland China to examine the links between school SES and students' math and Chinese achievements, including the math and Chinese teacher-student relationships as mediating factors. The parents provided family socioeconomic information and the students reported on their teacher-student relationships. Achievements in math and Chinese were assessed using standardized tests. Multilevel mediation analyses revealed that school SES was positively related to students' math and Chinese achievements. Moreover, the link between school SES and students' math achievement was partially mediated by students' perception of the math teacher-student relationship. The Chinese teacher-student relationship had no mediating effect. This study indicated that school SES can influence individual student's academic achievement via their perception of teacher-student relationship. The poverty and lack of resources is obvious, yet low SES schools could make efforts in improving teacher-student relationship's quality to promote students' academic performance. Meanwhile, low SES schools should receive more attention from policymakers to improve teaching quality and school climate. Furthermore, the study findings could be used for future research on the gap between low and high SES schools. [ABSTRACT FROM AUTHOR]

Background: The evaluation of childhood trauma is essential for the treatment of schizophrenia. The short form of Childhood Trauma Questionnaire (CTQ-SF) is a widely used measure of the experience of childhood trauma in the general population. Nevertheless, data regarding the psychometric property of CTQ-SF for assessing childhood trauma of patients with schizophrenia are very limited. Methods: Two hundred Chinese inpatients with schizophrenia completed the Chinese CTQ-SF, the Child Psychological Maltreatment Scale (CPMS), the Impact of Events Scale-Revised (IES-R), and the Dissociative Experiences Scale-II (DES-II). To assess test-retest reliability of the CTQ-SF, all patients completed the CTQ-SF again two weeks later. Concurrent and convergent validity was assessed by analyzing Pearson bivariate correlation coefficients between CTQ-SF and CPMS, IES-R, and DES-II. Results: The Cronbach’s α coefficient of the Chinese CTQ-SF was 0.81, and the two-week re-test reliability was 0.81 (P<0.01). The criterion-related validity coefficients of CTQ-SF with the CMPS, IES-R and DES-II were 0.61, 0.41, and 0.51, respectively. Conclusion: The Chinese CTQ-SF has satisfactory psychometric properties to measure childhood abuse or neglect in Chinese inpatients with schizophrenia. [ABSTRACT FROM AUTHOR]

Cognitive impairment has been observed in patients with major depressive disorder (MDD). However, it remains unclear whether the deficits in specific cognitive domains are present in first-episode, drug-naïve patients or medicated patients. In the present study, using the CogState battery (CSB) Chinese language version, we evaluated the visual, working, and verbal memory in first-episode drug-naive patients and medicated patients with MDD in a Chinese population. We measured the cognitive function in first-episode drug-naïve patients (n = 36), medicated MDD patients (n = 71), and age- and sex-matched healthy control subjects (n = 59) in a Chinese population. The CSB composite scores in both first-episode drug-naive patients and medicated patients were significantly poorer than those in the healthy control subjects. The CSB sub-scores, including visual, working, and verbal memory were also significantly poorer in both patient groups than those in the healthy control subjects. In contrast, processing speed, attention/vigilance, executive function, spatial working memory, and social cognition were no different from healthy controls, whereas the executive function was significantly better in the medicated patients than in the healthy control subjects and first-episode drug-naïve patients. These findings suggest an impairment in the visual, working, and verbal memory in first-episode, drug-naive MDD patients in a Chinese population. [ABSTRACT FROM AUTHOR]

Our previous research demonstrated that tilianin protects the myocardium in a myocardial ischemia reperfusion injury (MIRI) rat model and has prominent pharmacological potential as a cardiovascular drug. Our study aimed to investigate the molecular signaling implicated in the improvement of myocardial survival induced by tilianin, a flavonoid antioxidant. Tilianin (2.5, 5, and 10 mg/kg/d) or saline was orally administered to rats for 14 days. On the 15th day, ischemia was induced by ligating the left anterior descending artery for 45 min, followed by 4 h of reperfusion. The levels of MIRI-induced serum myocardial enzymes and cardiomyocyte apoptosis as well as infarct size were examined to assess the cardioprotective effects. Cardiac tissues were collected for western blot analyses to determine the protein expression of anti-apoptotic signaling molecules. In MIRI-treated rats, our results revealed that pre-administration of high dose-tilianin the reduced release of LDH, MDA, and CK-MB and increased the plasma SOD level, and significantly attenuated the infarct size. Western blot analysis showed that a remarkable rise in expression of Bcl-2 and XIAP, and decline in expression of Bax, Smac/Diablo, HtrA2/Omi, cleaved caspase-3, caspase-7 and caspase-9 was observed in the myocardium. The apoptosis index of cardiomyocytes further supports the cardioprotective effect of tilianin. Additionally, compared with the MIRI model group, pretreatment with high dose-tilianin group upregulated phosphorylated Akt and PI3K. In contrast, using the PI3K inhibitor LY294002 to block Akt activation effectively inhibited the protective effects of tilianin against MIRI. Tilianin pretreatment was beneficial for activating the PI3K/Akt signaling pathway and inhibiting myocardial apoptosis. [ABSTRACT FROM AUTHOR]

Dempster-Shafer evidence theory has been extensively used in many information fusion systems since it was proposed by Dempster and extended by Shafer. Many scholars have been conducted on conflict management of Dempster-Shafer evidence theory in past decades. However, how to determine a potent parameter to measure evidence conflict, when the given environment is in an open world, namely the frame of discernment is incomplete, is still an open issue. In this paper, a new method which combines generalized conflict coefficient, generalized evidence distance, and generalized interval correlation coefficient based on ordered weighted averaging (OWA) operator, to measure the conflict of evidence is presented. Through ordered weighted average of these three parameters, the combinatorial coefficient can still measure the conflict effectively when one or two parameters are not valid. Several numerical examples demonstrate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

How to quantify the uncertain information in the framework of Dempster-Shafer evidence theory is still an open issue. Quite a few uncertainty measures have been proposed in Dempster-Shafer framework, however, the existing studies mainly focus on the mass function itself, the available information represented by the scale of the frame of discernment (FOD) in the body of evidence is ignored. Without taking full advantage of the information in the body of evidence, the existing methods are somehow not that efficient. In this paper, a modified belief entropy is proposed by considering the scale of FOD and the relative scale of a focal element with respect to FOD. Inspired by Deng entropy, the new belief entropy is consistent with Shannon entropy in the sense of probability consistency. What’s more, with less information loss, the new measure can overcome the shortage of some other uncertainty measures. A few numerical examples and a case study are presented to show the efficiency and superiority of the proposed method. [ABSTRACT FROM AUTHOR]

In order to realize the stability control of the planar inverted pendulum system, which is a typical multi-variable and strong coupling system, a new fuzzy-evidential controller based on fuzzy inference and evidential reasoning is proposed. Firstly, for each axis, a fuzzy nine-point controller for the rod and a fuzzy nine-point controller for the cart are designed. Then, in order to coordinate these two controllers of each axis, a fuzzy-evidential coordinator is proposed. In this new fuzzy-evidential controller, the empirical knowledge for stabilization of the planar inverted pendulum system is expressed by fuzzy rules, while the coordinator of different control variables in each axis is built incorporated with the dynamic basic probability assignment (BPA) in the frame of fuzzy inference. The fuzzy-evidential coordinator makes the output of the control variable smoother, and the control effect of the new controller is better compared with some other work. The experiment in MATLAB shows the effectiveness and merit of the proposed method. [ABSTRACT FROM AUTHOR]

Objective: To assess stereoacuity in a population-based sample of children and to examine ocular and systemic parameters related to stereoacuity. Methods: Using a random cluster sampling method, four- to 18-year-old children from kindergartens, elementary schools, junior high schools and senior high schools from a rural area and an urban area in the East Chinese province of Shandong were included in the school-based cross-sectional study. All participants underwent a comprehensive eye examination including assessment of cycloplegic refraction and measurement of stereoacuity using the Titmus Stereo test. Results: Out of 6364 eligible children, 5780 (90.8%) children with a mean age of 10.1 ± 3.2 years (range: 4 to 18 years) participated. Mean (± standard deviation) stereoacuity was 50.2 ± 50.6 arc seconds. Stereoacuity improved significantly (P<0.01) from the age group of 4 years to the age group of 6 to 7 years, then showed a plateau, deteriorated (P = 0.001) for both sexes from the age group of 9 years to the age group of 12 years (P<0.001), after which it improved (P = 0.001) again in the age group of 16 years or older to the pre-puberty values. In multivariate analysis, larger angle of binocular disparity (i.e., lower stereoacuity) was significantly associated with lower best corrected visual acuity (logMAR; P<0.001), higher intereye difference in refractive error (spherical equivalent) (P<0.001), higher cylindrical refractive error (P<0.001), higher refractive error (spherical value; P<0.001), higher intereye difference in best corrected visual acuity (logMAR) (P = 0.001), higher intereye difference in axial length (P = 0.001), and rural region of habitation (P = 0.006). Conclusions: Stereoacuity as tested with the Titmus Stereo test improved significantly from an age of 4 years to an age of 6 and 7 years, then remained constant, temporarily deteriorated for both sexes in pre-puberty and puberty, after which it improved again to pre-puberty or better values at the age of 16 years or older. Lower stereoacuity was associated with lower best corrected visual acuity and higher intereye difference in best corrected visual acuity, higher cylindrical and spherical refractive errors, higher inter-eye difference in refractive error, higher intereye difference in axial length, and rural region of habitation. [ABSTRACT FROM AUTHOR]

Matrix-assisted laser desorption–ionization-time-of-flight mass spectrometry (MALDI–TOF MS) was used to establish a rapid, simple, and accurate method to differentiate among strains of Microcystis aeruginosa, one of the most prevalent types of bloom-forming cyanobacteria. M. aeruginosa NIES-843, for which a complete genome has been sequenced, was used to characterize ribosomal proteins as biomarkers and to optimize conditions for observing ribosomal proteins as major peaks in a given mass spectrum. Thirty-one of 52 ribosomal subunit proteins were detected and identified along the mass spectrum. Fifty-five strains of M. aeruginosa from different habitats were analyzed using MALDI–TOF MS; among these samples, different ribosomal protein types were observed. A polygenetic analysis was performed using an unweighted pair-group method with arithmetic means and different ribosomal protein types to classify the strains into five major clades. Two clades primarily contained toxic strains, and the other three clades contained exclusively non-toxic strains. This is the first study to differentiate cyanobacterial strains using MALDI–TOF MS. [ABSTRACT FROM AUTHOR]

Pretreatment plasma D-dimer levels have been reported to predict survival in several types of malignancies. The aim of this study was to evaluate the prognostic value of D-dimer levels in patients with newly diagnosed natural killer/T-cell lymphoma (NKTCL). The cut-off value of D-dimer to predict survival was set as 1.2 μg/mL based on the receiver operating curve analysis. Patients with a D-dimer level ≥ 1.2 μg/mL had significantly more adverse clinical features, including poor performance status, advanced stage diseases, B symptoms, elevated serum lactic dehydrogenase levels, involvement of regional lymph nodes, more extranodal diseases, and higher International Prognostic Index and natural killer/T-cell lymphoma prognostic index scores. A D-dimer level ≥ 1.2 μg/mL was significantly associated with inferior 3-year overall survival (OS, 13.0 vs. 68.5%, P < 0.001). In the multivariate analysis, a D-dimer level ≥ 1.2 μg/mL remained an independent predictor for worse OS (HR: 3.13, 95% CI: 1.47–6.68, P = 0.003) after adjusting for other confounding prognostic factors. Among patients with Ann Arbor stage I-II diseases, those with a D-dimer level ≥ 1.2 μg/mL had a significantly worse survival than those with a D-dimer level < 1.2 μg/mL (3 year-OS: 76.2 vs. 22.2%, P < 0.001). Survival of early-stage patients with a high D-dimer level was similar to that of the advanced-stage patients. In conclusion, pretreatment plasma D-dimer level may serve as a simple but effective predictor of prognosis in patients with NKTCL. [ABSTRACT FROM AUTHOR]

Enterovirus 71 (EV71) is the main pathogen responsible for hand, foot and mouth disease with severe neurological complications and even death in young children. We have recently identified a highly potent anti-EV71 neutralizing monoclonal antibody, termed D5. Here we investigated the structural basis for recognition of EV71 by the antibody D5. Four three-dimensional structures of EV71 particles in complex with IgG or Fab of D5 were reconstructed by cryo-electron microscopy (cryo-EM) single particle analysis all at subnanometer resolutions. The most critical EV71 mature virion-Fab structure was resolved to a resolution of 4.8 Å, which is rare in cryo-EM studies of virus-antibody complex so far. The structures reveal a bivalent binding pattern of D5 antibody across the icosahedral 2-fold axis on mature virion, suggesting that D5 binding may rigidify virions to prevent their conformational changes required for subsequent RNA release. Moreover, we also identified that the complementary determining region 3 (CDR3) of D5 heavy chain directly interacts with the extremely conserved VP1 GH-loop of EV71, which was validated by biochemical and virological assays. We further showed that D5 is indeed able to neutralize a variety of EV71 genotypes and strains. Moreover, D5 could potently confer protection in a mouse model of EV71 infection. Since the conserved VP1 GH-loop is involved in EV71 binding with its uncoating receptor, the scavenger receptor class B, member 2 (SCARB2), the broadly neutralizing ability of D5 might attribute to its inhibition of EV71 from binding SCARB2. Altogether, our results elucidate the structural basis for the binding and neutralization of EV71 by the broadly neutralizing antibody D5, thereby enhancing our understanding of antibody-based protection against EV71 infection. [ABSTRACT FROM AUTHOR]

Background: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) in the elderly has rarely been reported. This study aimed to explore the clinical characteristics and prognosis of this entity. Methods: In situ hybridization (ISH) analysis of Epstein-Barr virus (EBV) and immunohistochemistry was performed in 230 tumor specimens from consecutive de novo DLBCL patients over 50 years old. A matched-case control analysis (1:3) was utilized to compare EBV-positive and EBV-negative DLBCL in the elderly. Results: A total of 16 patients (7.0%) were diagnosed with EBV-positive DLBCL. Of these 16 cases, the median age was 62 years, with a male to female ratio of 11:5. Elderly EBV-positive DLBCL patients had a higher incidence of non-germinal center B-cell (non-GCB) subtypes (87.5%) and high Ki67 (75%) and CD30 expression (93.8%). For EBV-positive patients undergoing initial chemotherapy, 7 of 16 (43.8%) had complete remission, 2 (12.5%) had partial remission, 2 (12.5%) had stable disease, and 5 (31.3%) had progressive disease. The median overall survival was 9 months for the EBV-positive patients. A matched-case control analysis suggested that EBV-positive patients had inferior survival outcomes compared with EBV-negative patients (3-year progression-free survival [PFS]: 25% vs. 76.7%, respectively; 3-year overall survival [OS]: 25% vs. 77.4%, respectively; P<0.001). Conclusion: EBV-positive DLBCL of the elderly is associated with an inferior clinical course and inferior survival outcomes. The role of EBV in this disease and the optimal management of this subgroup warrants further investigation. [ABSTRACT FROM AUTHOR]

The serum 1,3-beta-D-glucan (BG) assay aids in the early diagnosis of invasive fungal diseases (IFDs) and has been approved for their diagnosis. However, reports on the screening performance of BG are scarce. We performed a meta-analysis of data extracted from only prospective cohort studies to evaluate the screening performance of the BG assay in the diagnosis of IFDs. We specifically searched 4 databases (the PubMed, Web of Science, Elsevier, and Cochrane Collaboration databases) according to EORTC-MSG criteria. A total of 1068 patients in 11 studies were analyzed. Deeks’ funnel plot asymmetry test suggested a low likelihood of publication bias for the included studies (p = 0.055). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve, with 95% confidence intervals, were 0.75(0.63,0.84), 0.87(0.81,0.92), 5.85(3.96,8.63), 0.30(0.20,0.45), 19.53(11.16,34.18), and 0.89(0.86,0.91), respectively. The findings of this meta-analysis suggest that the BG assay is a useful screening tool with high sensitivity and specificity for discriminating between patients with and without IFDs. In clinical practice, BG assay results should be evaluated together with clinical and microbiological findings. [ABSTRACT FROM AUTHOR]

Background: Asthma is a complex inflammatory disorder involving the activation and invasion of various immune cells. GPR97 is highly expressed in some immunocytes, including mast cells and eosinophils, which play critical roles in asthma development. However, the role of Gpr97 in regulating airway inflammation in asthma has rarely been reported. In this study, we investigated the potential role of Gpr97 in the development of allergic asthma in mice. Methods: Relevant airway asthmatic mouse models were constructed with both wild-type and Gpr97-/- mice sensitized to 250 μg ovalbumin (OVA). The levels of interleukin IL-4, IL-6 and IFN-γ, which are involved in OVA-induced asthma, in the bronchoalveolar lavage fluid (BALF) and the IgE level in the serum were examined by enzyme-linked immunosorbent assay (ELISA). The invasion of mast cells and eosinophils into lung tissues was assessed by immunohistochemical and eosinophil peroxidase activity assays, respectively. Goblet cell hyperplasia and mucus production were morphologically evaluated with periodic acid-Schiff (PAS) staining. Results: In our study, no obvious alteration in the inflammatory response or airway remodeling was found in the Gpr97-deficient mice with OVA-induced asthma. Neither the secretion of cytokines, including IL-4, IL-6 and IFN-γ, nor inflammatory cell recruitment was altered in the Gpr97-deficient mice. Moreover, Gpr97 deficiency did not affect airway remodeling or mucus production in the asthma mouse model. Conclusion: Our findings imply that Gpr97 might not be required for the development of airway inflammation in OVA-induced allergic asthma in mice. [ABSTRACT FROM AUTHOR]

The genetic diversity, evolution, distribution, and taxonomy of some coronaviruses dominant in birds other than chickens remain enigmatic. In this study we sequenced the genome of a newly identified coronavirus dominant in ducks (DdCoV), and performed a large-scale surveillance of coronaviruses in chickens and ducks using a conserved RT-PCR assay. The viral genome harbors a tandem repeat which is rare in vertebrate RNA viruses. The repeat is homologous to some proteins of various cellular organisms, but its origin remains unknown. Many substitutions, insertions, deletions, and some frameshifts and recombination events have occurred in the genome of the DdCoV, as compared with the coronavirus dominant in chickens (CdCoV). The distances between DdCoV and CdCoV are large enough to separate them into different species within the genus Gammacoronavirus. Our surveillance demonstrated that DdCoVs and CdCoVs belong to different lineages and occupy different ecological niches, further supporting that they should be classified into different species. Our surveillance also demonstrated that DdCoVs and CdCoVs are prevalent in live poultry markets in some regions of China. In conclusion, this study shed novel insight into the genetic diversity, evolution, distribution, and taxonomy of the coronaviruses circulating in chickens and ducks. [ABSTRACT FROM AUTHOR]

Ann Arbor stage has limited utility in the prognostication and treatment decision making in patients with NK/T-cell lymphoma (NKTCL), as NKTCL is almost exclusively extranodal and the majority is localized at presentation for which radiotherapy is the most important treatment and local invasiveness is the most important prognostic factor. In this study, we attempted to establish a TNM (Tumor-Node-Metastasis) staging system for nasal NKTCL (N-NKTCL). The staging rules of other head and neck cancers were used as reference along with the data of our 271 eligible patients. The primary tumor was classified into T1 to T4, and cervical lymph node metastasis was classified into N0 to N2 according to the extent of involvement. Any lesions outside the head and neck were classified as M1. N-NKTCL thereby was classified into four stages: stage I comprised T1-2N0M0; stage II comprised T1-2N1M0 and T3N0M0; stage III comprised T3N1M0, T1-3N2M0, and T4N0-2M0; and stage IV comprised TanyNanyM1. This staging system showed excellent performance in prognosticating survival. In the current series, the 5-year survival rates of patients with stages I, II, III, and IV N-NKTCL were 92%, 64%, 23%, and 0, respectively. Moreover, the predictive value of several currently used factors was abrogated in the presence of the TNM stage. The TNM staging system is highly effective in stratifying tumor burden and survival risk, which may have significant implications in the treatment decision making for patients with N-NKTCL. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the influence of various time intervals on the composition of the supragingival plaque microbiome, especially the dynamic core microbiome, and to find a suitable observation interval for further studies on oral microbiota. Methods and Materials: Eight qualified volunteers whose respective age ranges from 25 to 28 years participated in the present study. The supragingival plaque was collected from the buccogingival surface of the maxillary first molar at eight time slots with different intervals (day 0, 1 day, 3 days, 1 week, 2 weeks, 3 weeks, 1 month, and 3 months). Bioinformatic analyses was performed based on 16S rDNA pyrosequencing (454 sequencing platform) targeting at the hypervariable V4–V5 region, in order to assess the diversity and variation of the supragingival plaque microbiome. Results: A total of 359,565 qualified reads for 64 samples were generated for subsequent analyses, which represents 8,452 operational taxonomic units identified at 3% dissimilarity. The dynamic core microbiome detected in the current study included five phyla, 12 genera and 13 species. At the genus level, the relative abundance of bacterial communities under the “1 day,” “1 month,” and “3 months” intervals was clustered into sub-category. At the species level, the number of overlapping species remained stable between the “1 month” and “3 months” intervals, whereas the number of dynamic core species became stable within only 1 week. Conclusions: This study emphasized the impact of different time intervals (days, weeks and months) on the composition, commonality and diversity of the supragingival microbiome. The analyses found that for various types of studies, the time interval of a month is more suitable for observing the general composition of the supragingival microbiome, and that a week is better for observing the dynamic core microbiome. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the distribution of the (CCR) and its associated factors in children. Methods: Using a random cluster sampling method, the school-based, cross-sectional Shandong Children Eye Study included children aged 4 to 18 years from the rural county of Guanxian and the city of Weihai in the province of Shandong in East China. CCR was measured by ocular biometry. Results: CCR measurements were available for 5913 (92.9%) out of 6364 eligible children. Mean age was 10.0±3.3 years, and mean CCR was 7.84±0.27 mm (range: 6.98 to 9.35 mm). In multivariate linear regression analysis, longer CCR (i.e. flatter cornea) was significantly associated with the systemic parameters of male sex (P<0001;standardized regression coefficient beta: -0.08;regression coefficient B:-0.04; 95% Confidence Interval (CI):-0.05,-0.03), younger age (P<0.001;beta:-0.37;B:-0.03;95%CI:-0.04,-0.03), taller body height (P = 0.002;beta:0.06;B:0.001;95%CI:0.000,0.001), lower level of education of the father (P = 0.001;beta:-0.04;B:-0.01;95%CI:-0.02,-0.01) and maternal myopia (P<0.001;beta:-0.07;B:-0.04;95%CI:-0.06,-0.03), and with the ocular parameters of longer ocular axial length (P<0.001;beta:0.59;B:0.13;95%CI:0.12,0.14), larger horizontal corneal diameter (P<0.001;beta:0.19;B:0.13;95%CI:0.11,0.14), and smaller amount of cylindrical refractive error (P = 0.001;beta:-0.09;B:-0.05;95%CI:-0.06,-0.04). Conclusions: Longer CCR (i.e., flatter corneas) (mean:7.84±0.27mm) was correlated with male sex, younger age, taller body height, lower paternal educational level, maternal myopia, longer axial length, larger corneas (i.e., longer horizontal corneal diameter), and smaller amount of cylindrical refractive error. These findings may be of interest for elucidation of the process of emmetropization and myopization and for corneal refractive surgery. [ABSTRACT FROM AUTHOR]

Day-length is important for regulating the transition to reproductive development (flowering) in plants. In the model plant Arabidopsis thaliana, the transcription factor CONSTANS (CO) promotes expression of the florigen FLOWERING LOCUS T (FT), constituting a key flowering pathway under long-day photoperiods. Recent studies have revealed that FT expression is regulated by changes of histone modification marks of the FT chromatin, but the epigenetic regulators that directly interact with the CO protein have not been identified. Here, we show that the Arabidopsis Morf Related Gene (MRG) group proteins MRG1 and MRG2 act as H3K4me3/H3K36me3 readers and physically interact with CO to activate FT expression. In vitro binding analyses indicated that the chromodomains of MRG1 and MRG2 preferentially bind H3K4me3/H3K36me3 peptides. The mrg1 mrg2 double mutant exhibits reduced mRNA levels of FT, but not of CO, and shows a late-flowering phenotype under the long-day but not short-day photoperiod growth conditions. MRG2 associates with the chromatin of FT promoter in a way dependent of both CO and H3K4me3/H3K36me3. Vice versa, loss of MRG1 and MRG2 also impairs CO binding at the FT promoter. Crystal structure analyses of MRG2 bound with H3K4me3/H3K36me3 peptides together with mutagenesis analysis in planta further demonstrated that MRG2 function relies on its H3K4me3/H3K36me3-binding activity. Collectively, our results unravel a novel chromatin regulatory mechanism, linking functions of MRG1 and MRG2 proteins, H3K4/H3K36 methylations, and CO in FT activation in the photoperiodic regulation of flowering time in plants. [ABSTRACT FROM AUTHOR]

Background: Previous association studies examining the relationship between the APOC1 polymorphism and susceptibility to Alzheimer’s disease (AD) have shown conflicting results, and it is not clear if an APOC1 variant acts as a genetic risk factor in AD etiology across multiple populations. Methods: To confirm the risk association between APOC1 and AD, we designed a case-control study and also performed a meta-analysis of previously published studies. Results: Seventy-nine patients with AD and one hundred fifty-six unrelated controls were included in case-control study. No association was found between the variation of APOC1 and AD in stage 1 of our study. However, our meta-analysis pooled a total of 2092 AD patients and 2685 controls. The APOC1 rs11568822 polymorphism was associated with increased AD risk in Caucasians, Asians and Caribbean Hispanics, but not in African Americans. APOE ε4 carriers harboring the APOC1 insertion allele, were more prevalent in AD patients than controls (χ2 = 119.46, OR = 2.79, 95% CI = 2.31–3.36, P<0.01). Conclusions: The APOC1 insertion allele, in combination with APOE ε4, likely serves as a potential risk factor for developing AD. [ABSTRACT FROM AUTHOR]

Introduction: Nectins are a family of integral protein molecules involved in the formation of functioning Adherens and Tight Junctions (TJ). Aberrant expression is associated with cancer progression but little is known how this effects changes in cell behaviour. This study aimed to ascertain the distribution of Nectins-1 to -4 in human breast cancer and the effect on junctional integrity of Nectin-3 modulation in human endothelial and breast cancer cells. Methods: A human breast tissue cohort was processed for Q-PCR and immunohistochemistry for analysis of Nectin-1/-2/-3/-4. Nectin-3 over-expression was induced in the human breast cancer cell line MDA-MB-231 and the human endothelial cell line HECV. Functional testing was carried out to ascertain changes in cell behaviour. Results: Q-PCR revealed a distinct reduction in node positive tumours and in patients with poor outcome. There was increased expression of Nectin-1/-2 in patients with metastatic disease, Nectin-3/-4 was reduced. IHC revealed that Nectin-3 expression showed clear changes in distribution between normal and cancerous cells. Nectin-3 over-expression in MDA-MB-231 cells showed reduced invasion and migration even when treated with HGF. Changes in barrier function resulted in MDAN3 cells showing less change in resistance after 2h treatment with HGF (p<0.001). Nectin-3 transformed endothelial cells were significantly more adhesive, irrespective of treatment with HGF (p<0.05) and had reduced growth. Barrier function revealed that transformed HECV cells had significantly tighter junctions that wildtype cells when treated with HGF (p<0.0001). HGF-induced changes in permeability were also reduced. Overexpression of Nectin-3 produced endothelial cells with significantly reduced ability to form tubules (p<0.0001). Immunoprecipitation studies discovered hitherto novel associations for Nectin-3. Moreover, HGF appeared to exert an effect on Nectin-3 via tyrosine and threonine phosphorylation. Conclusions: Nectin-3 may be a key component in the formation of cell junctions and be a putative suppressor molecule to the invasion of breast cancer cells. [ABSTRACT FROM AUTHOR]

The rapid discovery of novel viruses using next generation sequencing (NGS) technologies including DNA-Seq and RNA-Seq, has greatly expanded our understanding of viral diversity in recent years. The timely identification of novel viruses using NGS technologies is also important for us to control emerging infectious diseases caused by novel viruses. In this study, we identified a novel duck coronavirus (CoV), distinct with chicken infectious bronchitis virus (IBV), using RNA-Seq. The novel duck-specific CoV was a potential novel species within the genus Gammacoronavirus, as indicated by sequences of three regions in the viral 1b gene. We also performed a survey of CoVs in domestic fowls in China using reverse-transcription polymerase chain reaction (RT-PCR), targeting the viral nucleocapsid (N) gene. A total of 102 CoV positives were identified through the survey. Phylogenetic analysis of the viral N sequences suggested that CoVs in domestic fowls have diverged into several region-specific or host-specific clades or subclades in the world, and IBVs can infect ducks, geese and pigeons, although they mainly circulate in chickens. Moreover, this study provided novel data supporting the notion that some host-specific CoVs other than IBVs circulate in ducks, geese and pigeons, and indicated that the novel duck-specific CoV identified through RNA-Seq in this study is genetically closer to some CoVs circulating in wild water fowls. Taken together, this study shed new insight into the diversity, distribution, evolution and control of avian CoVs. [ABSTRACT FROM AUTHOR]

Background: Internet addiction disorder (IAD) is now recognized internationally and is known to be linked with academic and social impairment. To date, we know little about its associated main biological factors. This study aimed to collect a carefully defined group of adolescents with IAD and an age- and gender-matched typically developing comparison group. We hypothesized that the young people with IAD would have higher rates of self-reported anxiety and depressive symptoms, have altered levels of peripheral blood dopamine, norepinephrine and serotonin. In addition, we hypothesized the hours spent online are correlated with the severity of depression and anxiety among these young people with IAD. Methodology/Principal Finding: A cross-sectional study of 20 adolescents who met Beard’s criteria for IAD and 15 typically developing adolescents (comparison group) was conducted. All the participants completed the Self Rating Depression Scale (SDS), Self Rating Anxiety Scale (SAS), and the Screen for Child Anxiety Related Emotional Disorders (SCARED). Peripheral blood dopamine, serotonin and norepinephrine were assayed. The mean level of norepinephrine was lower in the IAD group than that in the typically developing participants, while dopamine and serotonin levels did not differ. The SDS, SAS and SCARED symptom scores were increased in the adolescents with IAD. A logistic regression analysis revealed that a higher SAS score and lower level of norepinephrine independently predicted IAD group membership. There was no significant correlation between hours spent online and scores of SAS/SDS in IAD group. Conclusions/Significance: Increased self-reported anxiety and lower peripheral blood norepinephrine are independently associated with IAD. [ABSTRACT FROM AUTHOR]

Background: C-reactive protein (CRP) is a biomarker of the inflammatory response, and it shows significant prognostic value for several types of solid tumors. The prognostic significance of CRP for lymphoma has not been fully examined. We evaluated the prognostic role of baseline serum CRP levels in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). Methods: We retrospectively analyzed 185 patients with newly diagnosed ENKTL. The prognostic value of the serum CRP level was evaluated for the low-CRP group (CRP≤10 mg/L) versus the high-CRP group (CRP>10 mg/L). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were evaluated and compared with the newly developed prognostic model. Results: Patients in the high-CRP group tended to display increased adverse clinical characteristics, lower rates of complete remission (P<0.001), inferior progression-free survival (PFS, P = 0.001), and inferior overall survival (OS, P<0.001). Multivariate analysis demonstrated that elevated serum CRP levels, age >60 years, hypoalbuminemia, and elevated lactate dehydrogenase levels were independent adverse predictors of OS. Based on these four independent predictors, we constructed a new prognostic model that identified 4 groups with varying OS: group 1, no adverse factors; group 2, 1 factor; group 3, 2 factors; and group 4, 3 or 4 factors (P<0.001). The novel prognostic model was found to be superior to both the IPI in discriminating patients with different outcomes in the IPI low-risk group and the KPI in distinguishing between the low- and intermediate-low-risk groups, the intermediate-low- and high-intermediate-risk groups, and the high-intermediate- and high-risk groups. Conclusions: Our results suggest that pretreatment serum CRP levels represent an independent predictor of clinical outcome for patients with ENKTL. The prognostic value of the new prognostic model is superior to both IPI and KPI. [ABSTRACT FROM AUTHOR]

Previous studies have shown that motor recovery of stroke can be assessed by the cortical activity and the structural integrity of the corticospinal tract (CST), but little is known about the relation between the cortical activity and the structural integrity during motor recovery. In the present study, we investigated the changes in brain activities evoked by twenty days’ functional electrical stimulation (FES) training in twelve sub-acute stroke patients with unilateral upper-limb disability. We compared cortex activity evoked by wrist movement of eleven stroke patients to that of eleven age-matched healthy subjects to figure out how cortex activity changed after stroke. We also measured the structural integrity represented by the fractional anisotropy (FA) asymmetry of the posterior limb of the internal capsule (PLIC) to find the relationship between the brain activity and the structure integrity. In our study, we found that patients with sub-acute stroke have shown greater activity in the contralesional primary motor cortex (M1) during the affected hand’s movement compared with healthy group, while the activity in ipsilesional M1 was decreased after the therapy compared to that before therapy, and the contralesional non-primary motor cortex showed greater activity after therapy. At the baseline we found that the positive correlation between the FA asymmetry of PLIC and the contralesional non-primary motor cortex activity showed that the greater damaged CST, the greater contralesional non-primary motor cortex recruited. While the negative correlation between them after the FES training indicates that after recovery the non-primary motor cortex plays different role in different stroke phases. Our study demonstrates that functional organization of a residual distributed motor system is related to the degree of disruption to the CST, and the non-primary motor areas plays an important role in motor recovery. [ABSTRACT FROM AUTHOR]

Relationships of foliar carbon isotope composition (δ13C) with foliar C, N, P, K, Ca, Mg contents and their ratios of 219 C3 species leaf samples, obtained in August in 2004 to 2007 from 82 high altitude grassland sites on the Qinghai-Tibet Plateau China, were examined. This was done with reference to the proposition that foliar δ13C increases with altitude and separately for the life-form groups of graminoids, forbs and shrubs and for the genera Stipa and Kobresia. For all samples, foliar δ13C was negatively related to foliar K, P and ∑K+ Ca+ Mg, and positively correlated to foliar C, C/N and C/P. The significance of these correlations differed for the taxonomic and life-form groups. Lack of a relationship of foliar δ13C with foliar N was inconsistent with the majority of studies that have shown foliar δ13C to be positively related to foliar N due to a decrease of Ci/Ca (the ratio between intercellular and atmospheric concentration of CO2) and explained as a result of greater photosynthetic capacity at higher foliar N concentration. However this inconsistency relates to other high altitude studies that have found that photosynthetic capacity remains constant as foliar N increases. After accounting for the altitudinal relationship with foliar δ13C, of the elements only the K effect was significant and was most strongly expressed for Kobresia. It is concluded that factors critical to plant survival and growth at very high altitudes, such as low atmospheric pressure and low temperatures, may preclude expression of relationships between foliar δ13C and foliar elements that have been observed at lower altitudes. [ABSTRACT FROM AUTHOR]

Wnt5a is a non-canonical signaling Wnt. Low expression of WNT5A is correlated with poor prognosis in breast cancer patients. The highly invasive breast cancer cell lines, MDA-MB-231 and 4T1, express very low levels of WNT5A. To determine if enhanced expression of WNT5A would affect metastatic behavior, we generated WNT5A expressing cells from the 4T1 and MDA-MB-231 parental cell lines. WNT5A expressing cells demonstrated cobblestone morphology and reduced in vitro migration relative to controls. Cell growth was not altered. Metastasis to the lung via tail vein injection was reduced in the 4T1-WNT5A expressing cells relative to 4T1-vector controls. To determine the mechanism of WNT5A action on metastasis, we performed microarray and whole-transcriptome sequence analysis (RNA-seq) to compare gene expression in 4T1-WNT5A and 4T1-vector cells. Analysis indicated highly significant alterations in expression of genes associated with cellular movement. Down-regulation of a subset of these genes, Mmp13, Nos2, Il1a, Cxcl2, and Lamb3, in WNT5A expressing cells was verified by semi-quantitative RT-PCR. Significant differences in transcript splicing were also detected in cell movement associated genes including Cd44. Cd44 is an adhesion molecule with a complex genome structure. Variable exon usage is associated with metastatic phenotype. Alternative spicing of Cd44 in WNT5A expressing cells was confirmed using RT-PCR. We conclude that WNT5A inhibits metastasis through down-regulation of multiple cell movement pathways by regulating transcript levels and splicing of key genes like Cd44. [ABSTRACT FROM AUTHOR]

Tulane virus (TV) is a newly isolated cultivatable calicivirus that infects juvenile rhesus macaques. Here we report a 6.3 Å resolution cryo-electron microscopy structure of the TV virion. The TV virion is about 400 Å in diameter and consists of a T = 3 icosahedral protein capsid enclosing the RNA genome. 180 copies of the major capsid protein VP1 (∼57 KDa) are organized into two types of dimers A/B and C/C and form a thin, smooth shell studded with 90 dimeric protrusions. The overall capsid organization and the capsid protein fold of TV closely resemble that of other caliciviruses, especially of human Norwalk virus, the prototype human norovirus. These close structural similarities support TV as an attractive surrogate for the non-cultivatable human noroviruses. The most distinctive feature of TV is that its C/C dimers are in a highly flexible conformation with significantly reduced interactions between the shell (S) domain and the protruding (P) domain of VP1. A comparative structural analysis indicated that the P domains of TV C/C dimers were much more flexible than those of other caliciviruses. These observations, combined with previous studies on other caliciviruses, led us to hypothesize that the enhanced flexibility of C/C dimer P domains are likely required for efficient calicivirus-host cell interactions and the consequent uncoating and genome release. Residues in the S-P1 hinge between the S and P domain may play a critical role in the flexibility of P domains of C/C dimers. [ABSTRACT FROM AUTHOR]

Multidrug resistance protein 7 (MRP7, ABCC10) is a recently discovered member of the ATP-binding cassette (ABC) family which are capable of conferring resistance to a variety of anticancer drugs, including taxanes and nucleoside analogs, in vivo. MRP7 is highly expressed in non-small cell lung cancer cells, and Mrp7-KO mice are highly sensitive to paclitaxel, making MRP7 an attractive chemotherapeutic target of non-small cell lung cancer. However, only a few inhibitors of MRP7 are currently identified, with none of them having progressed to clinical trials. We used MRP7-expressing cells to investigate whether tariquidar, a third generation inhibitor of P-glycoprotein, could inhibit MRP7-mediated multidrug resistance (MDR). We found that tariquidar, at 0.1 and 0.3 µM, significantly potentiated the sensitivity of MRP7-transfected HEK293 cells to MRP7 substrates and increased the intracellular accumulation of paclitaxel. We further demonstrated that tariquidar directly impaired paclitaxel efflux and could downregulate MRP7 protein expression in a concentration- and time-dependent manner after prolonged treatment. Our findings suggest that tariquidar, at pharmacologically achievable concentrations, reverses MRP7-mediated MDR through inhibition of MRP7 protein expression and function, and thus represents a promising therapeutic agent in the clinical treatment of chemoresistant cancer patients. [ABSTRACT FROM AUTHOR]

Background: PTPRM has been shown to exhibit homophilic binding and confer cell-cell adhesion in cells including epithelial and cancer cells. The present study investigated the expression of PTPRM in breast cancer and the biological impact of PTPRM on breast cancer cells. Design: Expression of PTPRM protein and gene transcript was examined in a cohort of breast cancer patients. Knockdown of PTPRM in breast cancer cells was performed using a specific anti-PTPRM transgene. The impact of PTPRM knockdown on breast cancer was evaluated using in vitro cell models. Results: A significant decrease of PTPRM transcripts was seen in poorly differentiated and moderately differentiated tumours compared with well differentiated tumours. Patients with lower expression of PTPRM had shorter survival compared with those which had a higher level of PTPRM expression. Knockdown of PTPRM increased proliferation, adhesion, invasion and migration of breast cancer cells. Furthermore, knockdown of PTPRM in MDA-MB-231 cells resulted in increased cell migration and invasion via regulation of the tyrosine phosphorylation of ERK and JNK. Conclusions: Decreased expression of PTPRM in breast cancer is correlated with poor prognosis and inversely correlated with disease free survival. PTPRM coordinated cell migration and invasion through the regulation of tyrosine phosphorylation of ERK and JNK. [ABSTRACT FROM AUTHOR]

Increased vascular permeability is an early event characteristic of tissue ischemia and angiogenesis. Although VEGF family members are potent promoters of endothelial permeability the role of placental growth factor (PlGF) is hotly debated. Here we investigated PlGF isoforms 1 and 2 and present in vitro and in vivo evidence that PlGF-1, but not PlGF-2, can inhibit VEGF-induced permeability but only during a critical window post-VEGF exposure. PlGF-1 promotes VE-cadherin expression via the trans-activating Sp1 and Sp3 interaction with the VE-cadherin promoter and subsequently stabilizes transendothelial junctions, but only after activation of endothelial cells by VEGF. PlGF-1 regulates vascular permeability associated with the rapid localization of VE-cadherin to the plasma membrane and dephosphorylation of tyrosine residues that precedes changes observed in claudin 5 tyrosine phosphorylation and membrane localization. The critical window during which PlGF- 1 exerts its effect on VEGF-induced permeability highlights the importance of the translational significance of this work in that PLGF-1 likely serves as an endogenous anti-permeability factor whose effectiveness is limited to a precise time point following vascular injury. Clinical approaches that would pattern nature's approach would thus limit treatments to precise intervals following injury and bring attention to use of agents only during therapeutic windows. [ABSTRACT FROM AUTHOR]

Relationships of foliar carbon isotope composition (δ(13)C) with foliar C, N, P, K, Ca, Mg contents and their ratios of 219 C3 species leaf samples, obtained in August in 2004 to 2007 from 82 high altitude grassland sites on the Qinghai-Tibet Plateau China, were examined. This was done with reference to the proposition that foliar δ(13)C increases with altitude and separately for the life-form groups of graminoids, forbs and shrubs and for the genera Stipa and Kobresia. For all samples, foliar δ(13)C was negatively related to foliar K, P and ∑K+ Ca+ Mg, and positively correlated to foliar C, C/N and C/P. The significance of these correlations differed for the taxonomic and life-form groups. Lack of a relationship of foliar δ(13)C with foliar N was inconsistent with the majority of studies that have shown foliar δ(13)C to be positively related to foliar N due to a decrease of Ci/Ca (the ratio between intercellular and atmospheric concentration of CO2) and explained as a result of greater photosynthetic capacity at higher foliar N concentration. However this inconsistency relates to other high altitude studies that have found that photosynthetic capacity remains constant as foliar N increases. After accounting for the altitudinal relationship with foliar δ(13)C, of the elements only the K effect was significant and was most strongly expressed for Kobresia. It is concluded that factors critical to plant survival and growth at very high altitudes, such as low atmospheric pressure and low temperatures, may preclude expression of relationships between foliar δ(13)C and foliar elements that have been observed at lower altitudes.

Background: PTPRM has been shown to exhibit homophilic binding and confer cell-cell adhesion in cells including epithelial and cancer cells. The present study investigated the expression of PTPRM in breast cancer and the biological impact of PTPRM on breast cancer cells., Design: Expression of PTPRM protein and gene transcript was examined in a cohort of breast cancer patients. Knockdown of PTPRM in breast cancer cells was performed using a specific anti-PTPRM transgene. The impact of PTPRM knockdown on breast cancer was evaluated using in vitro cell models., Results: A significant decrease of PTPRM transcripts was seen in poorly differentiated and moderately differentiated tumours compared with well differentiated tumours. Patients with lower expression of PTPRM had shorter survival compared with those which had a higher level of PTPRM expression. Knockdown of PTPRM increased proliferation, adhesion, invasion and migration of breast cancer cells. Furthermore, knockdown of PTPRM in MDA-MB-231 cells resulted in increased cell migration and invasion via regulation of the tyrosine phosphorylation of ERK and JNK., Conclusions: Decreased expression of PTPRM in breast cancer is correlated with poor prognosis and inversely correlated with disease free survival. PTPRM coordinated cell migration and invasion through the regulation of tyrosine phosphorylation of ERK and JNK.

Background: Recent research has shown a correlation between immune microenvironment and lymphoma biology. This study aims to investigate the prognostic significance of the immunologically relevant lymphocyte-to-monocyte ratio (LMR), in diffuse large B-cell lymphoma (DLBCL) in the rituximab era., Methodology/principal Findings: We analyzed retrospective data from 438 newly diagnosed DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. We randomly selected 200 patients (training set) to generate a cutoff value for LMR by receiver operating characteristic (ROC) curve analysis. LMR was then analyzed in a testing set (n = 238) and in all patients (n = 438) for validation. The LMR cutoff value for survival analysis determined by ROC curve in the training set was 2.6. Patients with low LMR tended to have more adverse clinical characteristics. Low LMR at diagnosis was associated with worse survival in DLBCL, and could also identify high-risk patients in the low-risk IPI category. Multivariate analysis identified LMR as an independent prognostic factor of survival in the testing set and in all patients., Conclusions/significance: Baseline LMR, a surrogate biomarker of the immune microenvironment, is an effective prognostic factor in DLBCL patients treated with R-CHOP therapy. Future prospective studies are required to confirm our findings.

Background: B-cell activation factor (BAFF) and BAFF-receptor (BAFF-R) play crucial roles in the viability and proliferation of malignant lymphoma cells. Limited information exists regarding expression profiles and the prognostic role of BAFF and BAFF-R in follicular lymphoma (FL). We sought to determine the expression profiles of BAFF and BAFF-R in FL and to evaluate the correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and outcome of FL. Correlation between expression levels of BAFF detected by immunohistochemical (IHC) and serum levels of BAFF was also evaluated., Methods: Paraffin-embedded specimens from 115 patients were immunohistochemically examined for BAFF and BAFF-R expression. Expression levels were dichotomized into low versus high categories based on immunostaining intensity. The correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and patient outcome was assessed. Serum levels of BAFF in 35 of the 115 patients with IHC data were measured by Enzyme-linked Immunosorbent assay (ELISA)., Results: BAFF and BAFF-R were expressed in 88.7% (102/115) and 87.8% (101/115) of the cases, respectively. BAFF expression was significantly correlated with only one clinicopathologic feature: Ann Arbor stage. No significant correlation was found between expression levels of BAFF detected by IHC and serum levels of BAFF detected by ELISA. High expression of BAFF-R, but not BAFF, was significantly correlated with inferior progression-free survival (PFS; P = 0.013) and overall survival (OS; P = 0.03). High expression of BAFF-R, bulky disease, and elevated lactate dehydrogenase were correlated with inferior PFS and OS in multivariate analysis. A prognostic scoring system incorporating these 3 risk factors identified 3 distinct prognostic groups with 5-year PFS of 59.4%, 41.9%, and 10.7% and OS of 91.3%, 79.7%, and 45.8%, respectively., Conclusions: Most patients with FL variably express BAFF and BAFF-R. High expression of BAFF-R, but not BAFF, may be an independent risk factor for PFS and OS in FL.

Background: Compound 48/80 is widely used in animal and tissue models as a "selective" mast cell activator. With this study we demonstrate that compound 48/80 also directly activates enteric neurons and visceral afferents., Methodology/principal Findings: We used in vivo recordings from extrinsic intestinal afferents together with Ca(++) imaging from primary cultures of DRG and nodose neurons. Enteric neuronal activation was examined by Ca(++) and voltage sensitive dye imaging in isolated gut preparations and primary cultures of enteric neurons. Intraluminal application of compound 48/80 evoked marked afferent firing which desensitized on subsequent administration. In egg albumen-sensitized animals, intraluminal antigen evoked a similar pattern of afferent activation which also desensitized on subsequent exposure to antigen. In cross-desensitization experiments prior administration of compound 48/80 failed to influence the mast cell mediated response. Application of 1 and 10 µg/ml compound 48/80 evoked spike discharge and Ca(++) transients in enteric neurons. The same nerve activating effect was observed in primary cultures of DRG and nodose ganglion cells. Enteric neuron cultures were devoid of mast cells confirmed by negative staining for c-kit or toluidine blue. In addition, in cultured enteric neurons the excitatory action of compound 48/80 was preserved in the presence of histamine H(1) and H(2) antagonists. The mast cell stabilizer cromolyn attenuated compound 48/80 and nicotine evoked Ca(++) transients in mast cell-free enteric neuron cultures., Conclusions/significance: The results showed direct excitatory action of compound 48/80 on enteric neurons and visceral afferents. Therefore, functional changes measured in tissue or animal models may involve a mast cell independent effect of compound 48/80 and cromolyn.

Increased vascular permeability is an early event characteristic of tissue ischemia and angiogenesis. Although VEGF family members are potent promoters of endothelial permeability the role of placental growth factor (PlGF) is hotly debated. Here we investigated PlGF isoforms 1 and 2 and present in vitro and in vivo evidence that PlGF-1, but not PlGF-2, can inhibit VEGF-induced permeability but only during a critical window post-VEGF exposure. PlGF-1 promotes VE-cadherin expression via the trans-activating Sp1 and Sp3 interaction with the VE-cadherin promoter and subsequently stabilizes transendothelial junctions, but only after activation of endothelial cells by VEGF. PlGF-1 regulates vascular permeability associated with the rapid localization of VE-cadherin to the plasma membrane and dephosphorylation of tyrosine residues that precedes changes observed in claudin 5 tyrosine phosphorylation and membrane localization. The critical window during which PlGF-1 exerts its effect on VEGF-induced permeability highlights the importance of the translational significance of this work in that PLGF-1 likely serves as an endogenous anti-permeability factor whose effectiveness is limited to a precise time point following vascular injury. Clinical approaches that would pattern nature's approach would thus limit treatments to precise intervals following injury and bring attention to use of agents only during therapeutic windows.

The origin and evolution of microRNA (miRNA) genes, which are of significance in tuning and buffering gene expressions in a number of critical cellular processes, have long attracted evolutionary biologists. However, genome-wide perspectives on their origins, potential mechanisms of their de novo generation and subsequent evolution remain largely unsolved in flowering plants. Here, genome-wide analyses of Oryza sativa and Arabidopsis thaliana revealed apparently divergent patterns of miRNA gene origins. A large proportion of miRNA genes in O. sativa were TE-related and MITE-related miRNAs in particular, whereas the fraction of these miRNA genes much decreased in A. thaliana. Our results show that the majority of TE-related and pseudogene-related miRNA genes have originated through inverted duplication instead of segmental or tandem duplication events. Based on the presented findings, we hypothesize and illustrate the four likely molecular mechanisms to de novo generate novel miRNA genes from TEs and pseudogenes. Our rice genome analysis demonstrates that non-MITEs and MITEs mediated inverted duplications have played different roles in de novo generating miRNA genes. It is confirmed that the previously proposed inverted duplication model may give explanations for non-MITEs mediated duplication events. However, many other miRNA genes, known from the earlier proposed model, were rather arisen from MITE transpositions into target genes to yield binding sites. We further investigated evolutionary processes spawned from de novo generated to maturely-formed miRNA genes and their regulatory systems. We found that miRNAs increase the tunability of some gene regulatory systems with low gene copy numbers. The results also suggest that gene balance effects may have largely contributed to the evolution of miRNA regulatory systems.

Background: Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that social isolation in male mice results in aggressive behavior. However, it is not known how social isolation-induced aggression affects anxiety and depressive-like behavior in isolated male mice subjected to unpredictable chronic mild stress (CMS), an animal model of depression., Methodology/principal Findings: C57/B6 male mice were divided into 3 groups; non-stressed controls, in Group I; isolated mice subjected to the CMS protocol in Group II and aggression by physical contact in socially isolated mice subjected to the CMS protocol in Group III. In the sucrose intake test, ingestion of a 1% sucrose solution by mice in Groups II and III was significantly lower than in Group I. Furthermore, intake of this solution in Group III mice was significantly lower than in Group II mice. In the open field test, mice in Group III, showed reduced locomotor activity and reduced entry and retention time in the central zone, compared to Groups I and II mice. Moreover, the distances moved in 1 hour by Group III mice did not differ between night and morning. In the light/black box test, Groups II and III animals spent significantly less time in the light box compared to Group I animals. In the tail suspension test (TST) and forced swimming test (FST), the immobility times of Group II and Group III mice were significantly longer than in Group I mice. In addition, immobility times in the FST were significantly longer in Group III than in Group II mice., Conclusions/significance: These findings show that social isolation-induced aggression could potentiate anxiety and depressive-like behaviors in isolated male mice subjected to CMS.

Efforts in structural biology have targeted the systematic determination of all protein structures through experimental determination or modeling. In recent years, 3-D electron cryomicroscopy (cryoEM) has assumed an increasingly important role in determining the structures of these large macromolecular assemblies to intermediate resolutions (6-10 A). While these structures provide a snapshot of the assembly and its components in well-defined functional states, the resolution limits the ability to build accurate structural models. In contrast, sequence-based modeling techniques are capable of producing relatively robust structural models for isolated proteins or domains. In this work, we developed and applied a hybrid modeling approach, utilizing cryoEM density and ab initio modeling to produce a structural model for the core domain of a herpesvirus structural protein, VP26. Specifically, this method, first tested on simulated data, utilizes the cryoEM density map as a geometrical constraint in identifying the most native-like models from a gallery of models generated by ab initio modeling. The resulting model for the core domain of VP26, based on the 8.5-A resolution herpes simplex virus type 1 (HSV-1) capsid cryoEM structure and mutational data, exhibited a novel fold. Additionally, the core domain of VP26 appeared to have a complementary interface to the known upper-domain structure of VP5, its cognate binding partner. While this new model provides for a better understanding of the assembly and interactions of VP26 in HSV-1, the approach itself may have broader applications in modeling the components of large macromolecular assemblies.