NLRP1 restricts porcine deltacoronavirus infection via IL-11 inhibiting the phosphorylation of the ERK signaling pathway.

Continuously emerging highly pathogenic coronaviruses remain a major threat to human and animal health. Porcine deltacoronavirus (PDCoV) is a newly emerging enterotropic swine coronavirus that causes large-scale outbreaks of severe diarrhea disease in piglets. Unlike other porcine coronaviruses, PDCoV has a wide range of species tissue tropism, including primary human cells, which poses a significant risk of cross-species transmission. Nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 1 (NLRP1) has a key role in linking host innate immunity to microbes and the regulation of inflammatory pathways. We now report a role for NLRP1 in the control of PDCoV infection. Overexpression of NLRP1 remarkably suppressed PDCoV infection, whereas knockout of NLRP1 led to a significant increase in PDCoV replication. A mechanistic study revealed that NLRP1 suppressed PDCoV replication in cells by upregulating IL-11 expression, which in turn inhibited the phosphorylation of the ERK signaling pathway. Furthermore, the ERK phosphorylation inhibitor U0126 effectively hindered PDCoV replication in pigs. Together, our results demonstrated that NLRP1 exerted an anti-PDCoV effect by IL-11-mediated inhibition of the phosphorylation of the ERK signaling pathway, providing a novel antiviral signal axis of NLRP1-IL-11-ERK. This study expands our understanding of the regulatory network of NLRP1 in the host defense against virus infection and provides a new insight into the treatment of coronaviruses and the development of corresponding drugs.IMPORTANCECoronavirus, which mainly infects gastrointestinal and respiratory epithelial cells in vivo, poses a huge threat to both humans and animals. Although porcine deltacoronavirus (PDCoV) is known to primarily cause fatal diarrhea in piglets, reports detected in plasma samples from Haitian children emphasize the potential risk of animal-to-human spillover. Finding effective therapeutics against coronaviruses is crucial for controlling viral infection. Nucleotide-binding oligomerization-like receptor (NLR) family pyrin domain-containing 1 (NLRP1), a key regulatory factor in the innate immune system, is highly expressed in epithelial cells and associated with the pathogenesis of viruses. We demonstrate here that NLRP1 inhibits the infection of the intestinal coronavirus PDCoV through IL-11-mediated phosphorylation inhibition of the ERK signaling pathway. Furthermore, the ERK phosphorylation inhibitor can control the infection of PDCoV in pigs. Our study emphasizes the importance of NLRP1 as an immune regulatory factor and may open up new avenues for the treatment of coronavirus infection.

Leading nutrient foraging strategies shaping by root system characteristics along the elevations in rubber (Hevea brasiliensis) plantations.

When it comes to root and mycorrhizal associations that define resource acquisition strategy, there is a need to identify the leading dimension across root physiology, morphology, architecture and whole plant biomass allocation to better predict the plant's responses to multiple environmental constraints. Here, we developed a new framework for understanding the variation in roots and symbiotic fungi by quantifying multiple-scale characteristics, ranging from anatomy to the whole plant. We chose the rubber (Hevea brasiliensis) grown at three elevations to test our framework and to identify the key dimensions for resource acquisition. Results showed that the quantities of absorptive roots and root system architecture, rather than single root traits, played the leading role in belowground resource acquisition. As the elevation increased from the low to high elevation, root length growth, productivity and root mass fraction (RMF) increased by 2.9-, 2.3- and 13.8-fold, respectively. The contribution of RMF to the changes in total root length was 3.6-fold that of specific root length (SRL). Root architecture exhibited higher plasticity than anatomy and morphology. Further, mycorrhizal colonization was highly sensitive to rising elevations with a non-monotonic pattern. By contrast, both leaf biomass and specific leaf area (traits) co-varied with increasing elevation. In summary, rubber trees changed root system architecture by allocating more biomass and lowering the reliance on mycorrhizal fungi rather than improving single root efficiency in adapting to high elevation. Our framework is instructive for traits-based ecology; accurate assessments of forest carbon cycling in response to resource gradient should account for the leading dimension of root system architecture.

Escore de Risco Clínico Simples para Prever a Mortalidade Pós-Alta Hospitalar em Pacientes Chineses Hospitalizados por Insuficiência Cardíaca / A Simple Clinical Risk Score to Predict Post-Discharge Mortality in Chinese Patients Hospitalized with Heart Failure

Resumo Fundamento Doenças cardiovasculares são a principal causa de morte na China. Entretanto, os esforços atuais para se identificar os fatores de risco de morte em pacientes hospitalizados com insuficiência cardíaca (IC) estão direcionados principalmente para a mortalidade durante a internação e a mortalidade após 30 dias nos Estados Unidos. Dessa forma, é necessário um modelo semelhante ao modelo utilizado para prever o risco considerado para procedimentos cirúrgicos cardiovasculares em pacientes para avaliar o risco de pacientes internados com diagnóstico de IC. Objetivo Identificar variáveis que podem prever a mortalidade por IC um ano após a alta hospitalar, e desenvolver um escore de risco para avaliar o risco de morte no período de um ano. Métodos No presente estudo, 1.742 pacientes chineses com IC foram divididos aleatoriamente em dois grupos: um grupo de amostra de derivação e um grupo de amostra de teste. O método de simulação Monte Carlo via Cadeias de Markov foi usado para identificar variáveis que podem prever a mortalidade um ano após a alta hospitalar. Variáveis com uma frequência >1% na análise bivariada, e que foram consideradas clinicamente significativas, foram qualificadas para análises de modelagens posteriores. A probabilidade posterior de que uma variável estava estatística e significativamente associada ao resultado foi calculada como o número total de vezes em que o IC de 95% da variável não coincidiu com 1 (ou seja, o ponto de referência), dividido pelo número total de iterações. Uma variável com uma probabilidade de 0,9 ou mais alta foi considerado um fator de risco robusto para prever o resultado, e foi incluída na lista final de variáveis. O nível de significância estatística adotado foi 5%. Resultados Cinco variáveis que pudessem prever de maneira robusta a mortalidade um ano após a alta hospitalar foram identificadas: idade, sexo feminino, escore da New York Heart Association (Associação de Cardiologia de Nova Iorque) >3, diâmetro do átrio esquerdo, e índice de massa corporal. Os modelos de derivação e de teste tiveram uma área de curva característica de operação do receptor de 0,79. Essas variáveis selecionadas foram utilizadas para avaliar o escore de risco de mortalidade por IC após um ano, e este foi dividido em três grupos (baixo, moderado e alto). O grupo de alto risco corresponde a aproximadamente 86% das mortes, e o grupo de risco moderado corresponde a 12% das mortes. Conclusão Um escore de risco de 5 variáveis simples pode ser utilizado para avaliar a mortalidade um ano após a alta hospitalar de pacientes internados com IC.

Abstract Background Cardiovascular diseases are the leading causes of death in China. However, present efforts to identify the risk factors for death in patients hospitalized with heart failure (HF) are primarily focused on in-hospital mortality and 30-day mortality in the United States. Thus, a model similar to the model used for predicting the risk in patients considered for cardiovascular surgical procedures is needed to evaluate the risk of the patients admitted with a diagnosis of HF. Objective To identify variables that can predict post-discharge one-year HF mortality and develop a risk score to assess the risk of dying within one year. Methods In the present study, 1,742 Chinese patients with HF were randomly divided into two groups: a derivation sample group and a test sample group. A Markov Chain Monte Carlo simulation method was used to identify variables that can predict the one-year post-discharge mortality. Variables with a frequency of >1% in the bivariate analysis and that were considered clinically meaningful were eligible for further modeling analyses. The posterior probability that a variable was statistically and significantly associated with the outcome was calculated as the total number of times that the variable's 95% CI did not overlap with 1 (i.e., the reference point) divided by the total number of iterations. A variable with a probability of 0.9 or higher was considered a robust risk factor for predicting the outcome, and this was included in the final variable list. The level of statistical significance adopted was 5%. Results Five variables that could robustly predict the one-year post-discharge mortality were identified: age, female gender, New York Heart Association functional classification score >3, left atrial diameter, and body mass index. Both derivation and test models had a receiver operating curve area of 0.79. These selected variables were used to assess the one-year HF mortality risk score, and these were divided into three groups (low, moderate, and high). The high-risk group corresponds to nearly 86% of the deaths, while the moderate group corresponds to 12% of the deaths. Conclusion A simple 5-variable risk score can be used to assess the one-year post-discharge mortality of hospitalized Chinese patients with HF.

A Simple Clinical Risk Score to Predict Post-Discharge Mortality in Chinese Patients Hospitalized with Heart Failure. / Escore de Risco Clínico Simples para Prever a Mortalidade Pós-Alta Hospitalar em Pacientes Chineses Hospitalizados por Insuficiência Cardíaca.

BACKGROUND: Cardiovascular diseases are the leading causes of death in China. However, present efforts to identify the risk factors for death in patients hospitalized with heart failure (HF) are primarily focused on in-hospital mortality and 30-day mortality in the United States. Thus, a model similar to the model used for predicting the risk in patients considered for cardiovascular surgical procedures is needed to evaluate the risk of the patients admitted with a diagnosis of HF. OBJECTIVE: To identify variables that can predict post-discharge one-year HF mortality and develop a risk score to assess the risk of dying within one year. METHODS: In the present study, 1,742 Chinese patients with HF were randomly divided into two groups: a derivation sample group and a test sample group. A Markov Chain Monte Carlo simulation method was used to identify variables that can predict the one-year post-discharge mortality. Variables with a frequency of >1% in the bivariate analysis and that were considered clinically meaningful were eligible for further modeling analyses. The posterior probability that a variable was statistically and significantly associated with the outcome was calculated as the total number of times that the variable's 95% CI did not overlap with 1 (i.e., the reference point) divided by the total number of iterations. A variable with a probability of 0.9 or higher was considered a robust risk factor for predicting the outcome, and this was included in the final variable list. The level of statistical significance adopted was 5%. RESULTS: Five variables that could robustly predict the one-year post-discharge mortality were identified: age, female gender, New York Heart Association functional classification score >3, left atrial diameter, and body mass index. Both derivation and test models had a receiver operating curve area of 0.79. These selected variables were used to assess the one-year HF mortality risk score, and these were divided into three groups (low, moderate, and high). The high-risk group corresponds to nearly 86% of the deaths, while the moderate group corresponds to 12% of the deaths. CONCLUSION: A simple 5-variable risk score can be used to assess the one-year post-discharge mortality of hospitalized Chinese patients with HF.

FUNDAMENTO: Doenças cardiovasculares são a principal causa de morte na China. Entretanto, os esforços atuais para se identificar os fatores de risco de morte em pacientes hospitalizados com insuficiência cardíaca (IC) estão direcionados principalmente para a mortalidade durante a internação e a mortalidade após 30 dias nos Estados Unidos. Dessa forma, é necessário um modelo semelhante ao modelo utilizado para prever o risco considerado para procedimentos cirúrgicos cardiovasculares em pacientes para avaliar o risco de pacientes internados com diagnóstico de IC. OBJETIVO: Identificar variáveis que podem prever a mortalidade por IC um ano após a alta hospitalar, e desenvolver um escore de risco para avaliar o risco de morte no período de um ano. MÉTODOS: No presente estudo, 1.742 pacientes chineses com IC foram divididos aleatoriamente em dois grupos: um grupo de amostra de derivação e um grupo de amostra de teste. O método de simulação Monte Carlo via Cadeias de Markov foi usado para identificar variáveis que podem prever a mortalidade um ano após a alta hospitalar. Variáveis com uma frequência >1% na análise bivariada, e que foram consideradas clinicamente significativas, foram qualificadas para análises de modelagens posteriores. A probabilidade posterior de que uma variável estava estatística e significativamente associada ao resultado foi calculada como o número total de vezes em que o IC de 95% da variável não coincidiu com 1 (ou seja, o ponto de referência), dividido pelo número total de iterações. Uma variável com uma probabilidade de 0,9 ou mais alta foi considerado um fator de risco robusto para prever o resultado, e foi incluída na lista final de variáveis. O nível de significância estatística adotado foi 5%. RESULTADOS: Cinco variáveis que pudessem prever de maneira robusta a mortalidade um ano após a alta hospitalar foram identificadas: idade, sexo feminino, escore da New York Heart Association (Associação de Cardiologia de Nova Iorque) >3, diâmetro do átrio esquerdo, e índice de massa corporal. Os modelos de derivação e de teste tiveram uma área de curva característica de operação do receptor de 0,79. Essas variáveis selecionadas foram utilizadas para avaliar o escore de risco de mortalidade por IC após um ano, e este foi dividido em três grupos (baixo, moderado e alto). O grupo de alto risco corresponde a aproximadamente 86% das mortes, e o grupo de risco moderado corresponde a 12% das mortes. CONCLUSÃO: Um escore de risco de 5 variáveis simples pode ser utilizado para avaliar a mortalidade um ano após a alta hospitalar de pacientes internados com IC.

HepatoScore-14: Measures of Biological Heterogeneity Significantly Improve Prediction of Hepatocellular Carcinoma Risk.

BACKGROUND AND AIMS: Therapeutic, clinical trial entry and stratification decisions for hepatocellular carcinoma (HCC) are made based on prognostic assessments, using clinical staging systems based on small numbers of empirically selected variables that insufficiently account for differences in biological characteristics of individual patients' disease. APPROACH AND RESULTS: We propose an approach for constructing risk scores from circulating biomarkers that produce a global biological characterization of individual patient's disease. Plasma samples were collected prospectively from 767 patients with HCC and 200 controls, and 317 proteins were quantified in a Clinical Laboratory Improvement Amendments-certified biomarker testing laboratory. We constructed a circulating biomarker aberration score for each patient, a score between 0 and 1 that measures the degree of aberration of his or her biomarker panel relative to normal, which we call HepatoScore. We used log-rank tests to assess its ability to substratify patients within existing staging systems/prognostic factors. To enhance clinical application, we constructed a single-sample score, HepatoScore-14, which requires only a subset of 14 representative proteins encompassing the global biological effects. Patients with HCC were split into three distinct groups (low, medium, and high HepatoScore) with vastly different prognoses (medial overall survival 38.2/18.3/7.1 months; P < 0.0001). Furthermore, HepatoScore accurately substratified patients within levels of existing prognostic factors and staging systems (P < 0.0001 for nearly all), providing substantial and sometimes dramatic refinement of expected patient outcomes with strong therapeutic implications. These results were recapitulated by HepatoScore-14, rigorously validated in repeated training/test splits, concordant across Myriad RBM (Austin, TX) and enzyme-linked immunosorbent assay kits, and established as an independent prognostic factor. CONCLUSIONS: HepatoScore-14 augments existing HCC staging systems, dramatically refining patient prognostic assessments and therapeutic decision making and enrollment in clinical trials. The underlying strategy provides a global biological characterization of disease, and can be applied broadly to other disease settings and biological media.

Microarray profiling and functional analysis of differentially expressed plasma exosomal circular RNAs in Graves' disease.

BACKGROUND: Circulating RNA (circRNA) regulates various bioactivities in cells. A better understanding of the exosomal circRNA can provide novel insights into the pathogenesis and treatment of Graves' disease (GD). We aimed to profile the differentially expressed circRNAs (DEcRs) in plasma exosomes of patients with GD and speculate and probe the functions of the DEcR by comprehensive bioinformatics analyses. METHODS: Serum exosomes were isolated from five primary GD patients and five healthy controls via ultracentrifugation. After verification with transmission electron microscopy, exosome samples were subjected to microarray profiling using human circRNA microarrays. Two up-regulated and two down-regulated DEcRs were selected for validation in plasma exosomes from 20 GD and 20 healthy control participants using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). The circRNA/microRNA/mRNA interaction network was then assembled and the analysis of the Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways was utilized to predict the potential functions of the DEcR associated genes. RESULTS: There were 15 DEcRs revealed in primary GD cases. The intronic circRNA hsa_circRNA_000102 was confirmed as an up-regulated component in plasma exosomes from patients with GD. The circRNA/microRNA/mRNA interaction network unveiled the most potential targeting microRNAs of hsa_circRNA_000102 and its associated genes. The functional analyses predicted involvement of hsa_circRNA_000102 associated genes in pathways of immune system activation, such as viral infection and interferon-beta signaling. CONCLUSIONS: hsa_circRNA_000102 is a differentially up-regulated plasma exosomal circRNA in patients with GD. Our study highlights multiple pathways, particularly virus infection and interferon-beta signaling, for mediating immune activation in Graves' disease.

Comparison of the effect of two internal fixation methods for proximal clavicle fractures.

OBJECTIVE To compare the effect of two internal fixation methods in the treatment of proximal clavicle fractures. METHODS Fifty patients with proximal clavicle fractures received surgical treatment. They were divided into a clavicular T-plate group and a double mini-plates group. The duration of the operation, blood loss during the operation, fracture healing time, and incision infection were evaluated between the two groups. RESULTS Operation time (t=2.063, P=0.058), intraoperative bleeding (t=1.979, P=0.062), and fracture healing time (t=1.082, P=0.066) were not statistically significant in the two groups. The patients were followed up for 12-18 months; one patient in the T-plate group had early removal of nails, but no clinical symptoms. At the 2-month follow-up, the ASES score in the double mini-plates group was significantly better than in the T-plate group (P<0.001); but at the 6-month follow-up, 1-week before removal of internal fixation and the final follow-up, the two groups had no significant differences (P>0.05). CONCLUSIONS Both internal fixations have similar clinical results in the duration of operation, blood loss during the operation, and fracture healing time. The double mini-plates fixation presents advantages by reducing complications and speeding fracture healing; thus it is a more effective method to treat proximal clavicle fractures.

A Prediction Model to Help with Oncologic Mediastinal Evaluation for Radiation: HOMER.

Rationale: When stereotactic ablative radiotherapy is an option for patients with non-small cell lung cancer (NSCLC), distinguishing between N0, N1, and N2 or N3 (N2|3) disease is important.Objectives: To develop a prediction model for estimating the probability of N0, N1, and N2|3 disease.Methods: Consecutive patients with clinical-radiographic stage T1 to T3, N0 to N3, and M0 NSCLC who underwent endobronchial ultrasound-guided staging from a single center were included. Multivariate ordinal logistic regression analysis was used to predict the presence of N0, N1, or N2|3 disease. Temporal validation used consecutive patients from 3 years later at the same center. External validation used three other hospitals.Measurements and Main Results: In the model development cohort (n = 633), younger age, central location, adenocarcinoma, and higher positron emission tomography-computed tomography nodal stage were associated with a higher probability of having advanced nodal disease. Areas under the receiver operating characteristic curve (AUCs) were 0.84 and 0.86 for predicting N1 or higher (vs. N0) disease and N2|3 (vs. N0 or N1) disease, respectively. Model fit was acceptable (Hosmer-Lemeshow, P = 0.960; Brier score, 0.36). In the temporal validation cohort (n = 473), AUCs were 0.86 and 0.88. Model fit was acceptable (Hosmer-Lemeshow, P = 0.172; Brier score, 0.30). In the external validation cohort (n = 722), AUCs were 0.86 and 0.88 but required calibration (Hosmer-Lemeshow, P < 0.001; Brier score, 0.38). Calibration using the general calibration method resulted in acceptable model fit (Hosmer-Lemeshow, P = 0.094; Brier score, 0.34).Conclusions: This prediction model can estimate the probability of N0, N1, and N2|3 disease in patients with NSCLC. The model has the potential to facilitate decision-making in patients with NSCLC when stereotactic ablative radiotherapy is an option.

Microarray profiling and functional analysis of differentially expressed plasma exosomal circular RNAs in Graves disease

BACKGROUND: Circulating RNA (circRNA) regulates various bioactivities in cells. A better understanding of the exosomal circRNA can provide novel insights into the pathogenesis and treatment of Graves' disease (GD). We aimed to profile the differentially expressed circRNAs (DEcRs) in plasma exosomes of patients with GD and speculate and probe the functions of the DEcR by comprehensive bioinformatics analyses. METHODS: Serum exosomes were isolated from five primary GD patients and five healthy controls via ultracentrifugation. After verification with transmission electron microscopy, exosome samples were subjected to microarray profiling using human circRNA microarrays. Two up-regulated and two down-regulated DEcRs were selected for validation in plasma exosomes from 20 GD and 20 healthy control participants using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). The circRNA/microRNA/mRNA interaction network was then assembled and the analysis of the Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways was utilized to predict the potential functions of the DEcR associated genes. RESULTS: There were 15 DEcRs revealed in primary GD cases. The intronic circRNA hsa_circRNA_000102 was confirmed as an up-regulated component in plasma exosomes from patients with GD. The circRNA/microRNA/mRNA interaction network unveiled the most potential targeting microRNAs of hsa_circRNA_000102 and its associated genes. The functional analyses predicted involvement of hsa_circRNA_000102 associated genes in pathways of immune system activation, such as viral infection and interferon-beta signaling. CONCLUSIONS: hsa_circRNA_000102 is a differentially up-regulated plasma exosomal circRNA in patients with GD. Our study highlights multiple pathways, particularly virus infection and interferon-beta signaling, for mediating immune activation in Graves' disease.

Comparison of the effect of two internal fixation methods for proximal clavicle fractures

SUMMARY OBJECTIVE To compare the effect of two internal fixation methods in the treatment of proximal clavicle fractures. METHODS Fifty patients with proximal clavicle fractures received surgical treatment. They were divided into a clavicular T-plate group and a double mini-plates group. The duration of the operation, blood loss during the operation, fracture healing time, and incision infection were evaluated between the two groups. RESULTS Operation time (t=2.063, P=0.058), intraoperative bleeding (t=1.979, P=0.062), and fracture healing time (t=1.082, P=0.066) were not statistically significant in the two groups. The patients were followed up for 12-18 months; one patient in the T-plate group had early removal of nails, but no clinical symptoms. At the 2-month follow-up, the ASES score in the double mini-plates group was significantly better than in the T-plate group (P<0.001); but at the 6-month follow-up, 1-week before removal of internal fixation and the final follow-up, the two groups had no significant differences (P>0.05). CONCLUSIONS Both internal fixations have similar clinical results in the duration of operation, blood loss during the operation, and fracture healing time. The double mini-plates fixation presents advantages by reducing complications and speeding fracture healing; thus it is a more effective method to treat proximal clavicle fractures.

RESUMO OBJETIVO Comparar o efeito de dois métodos de fixação interna no tratamento de fraturas da clavícula proximal. MÉTODOS Cinquenta pacientes com fraturas da clavícula proximal receberam tratamento cirúrgico. Eles foram divididos em um grupo de placa T clavicular e um grupo de miniplacas duplas. A duração da operação, perda de sangue durante a operação, tempo de cura da fratura e infecção na incisão foram avaliados nos dois grupos. RESULTADOS O tempo de operação (t=2,063, P=0,058), perda de sangue durante a operação (t=1,979, P=0,062) e tempo de cura das fraturas (t=1,082, P=0,066) não foram estatisticamente significativos nos dois grupos. Os pacientes foram acompanhados por 12-18 meses; um dos pacientes do grupo da placa T teve retirada antecipada dos parafusos, mas não apresentou sintomas clínicos. Aos dois meses de acompanhamento, a pontuação ASES no grupo de miniplacas duplas foi significativamente melhor do que a do grupo de placas T (P<0,001). Porém, no acompanhamento de seis meses, uma semana antes da remoção da fixação interna e do acompanhamento final, os dois grupos não apresentavem diferenças significativas (P>0,05). CONCLUSÃO Ambas técnicas de fixação interna têm resultados clínicos semelhantes quanto a duração da operação, perda de sangue durante a operação e tempo de cura da fratura. A fixação de miniplacas duplas apresenta vantagens quanto a redução das complicações e cura mais rápida da fratura, sendo, portanto, um método mais eficaz para tratar fraturas da clavícula proximal.

Synthesis and antitumor activity of aza-brazilan derivatives containing imidazolium salt pharmacophores.

The synthesis of a series of novel aza-brazilan derivatives containing imidazolium salt pharmacophores is presented. The biological activity of such imidazolium salts was further evaluated in vitro against a panel of human tumor cell lines. The results suggest that the electron-withdrawing group on the aza-brazilan moiety, substituted 5,6-dimethyl-benzimidazole ring and substitution of the imidazolyl-3-position with a 4-methylbenzyl group were essential for modulating the cytotoxic activity. Compounds 55 and 39, bearing a 4-methylbenzyl substituent at position-3 of 5,6-dimethyl-benzimidazole, were found to be the most potent compounds with IC50 values of 0.52-1.30 µM and 0.56-1.51 µM against four human tumor cell lines investigated. Particularly, compound 57 exhibited inhibitory activity against the MCF-7 cell line with an IC50 value of 0.35 µM and was 56-fold more sensitive than DDP. Moreover, compound 55 inhibited cell proliferation through inducing G0/G1 cell cycle arrest and apoptosis in SMMC-7721 cells.

Socioeconomic indicators as predictors of smoking cessation among Spanish-Speaking Mexican Americans.

Objective: Smoking-related illnesses are the leading cause of death among Latinos, and within this ethnic group, Mexican Americans are the largest subgroup in the U.S. Understanding the factors associated with successful smoking cessation could inform interventions for this population. Although socioeconomic status (SES) is a powerful predictor of cessation outcomes in the general U.S. population, it has generally been a poor predictor of quitting smoking among Latinos. Within a sample of Spanish-speaking Mexican Americans (n = 199), this study examined a broad array of objective and subjective indicators of SES (i.e. income, education, employment, subjective social status, financial strain, insurance status) as predictors of smoking cessation. Design: Data for the current study came from a longitudinal cohort study examining the pathways linking the social determinants of health with smoking cessation. Generalized estimating equation modeling examined the association of each predictor variable with smoking abstinence across quit day, and the 3 and 26-weeks post-quit time points. Results: Results indicated that both low financial strain and insurance status predicted an increased likelihood of abstinence when controlling for covariates in the intention-to-treat analyses (p = .02 and p = .01, respectively). However, these models only approached significance in the multiple imputation analyses (all ps > .05). Other indicators of SES (i.e. income, education, employment) that have been predictive of cessation in other populations were not predictive of abstinence in this sample. Conclusions: These findings suggest that SES may indeed influence smoking cessation among Spanish-speaking Mexican Americans similarly to its influence in other populations, but that capturing the construct of SES may require assessing a broader range of SES indicators. Specifically, low financial strain and having insurance predicted a greater likelihood of achieving smoking abstinence, whereas other indicators of SES (i.e. income, education) were not predictive.

Predicting Lung Function Following Lobectomy: A New Method to Adjust for Inherent Selection Bias.

BACKGROUND: Predictions that overestimate post-lobectomy lung function are more likely than underestimates to lead to lobectomy. Studies of post-lobectomy lung function have included only surgical patients, so overestimates are overrepresented. This selection bias has led to incorrect estimates of prediction bias, which has led to inaccurate threshold values for determining lobectomy eligibility. OBJECTIVE: The objective of this study was to demonstrate and adjust for this selection bias in order to arrive at correct estimates of prediction bias, the 95% limits of agreement, and adjusted threshold values for determining when exercise testing is warranted. METHODS: We conducted a retrospective study of patients evaluated for lobectomy. We used multiple imputations to determine postoperative results for patients who did not have surgery because their predicted postoperative values were low. We combined these results with surgical patients to adjust for selection bias. We used the Bland-Altman method and the bivariate normal distribution to determine threshold values for surgical eligibility. RESULTS: Lobectomy evaluation was performed in 114 patients; 79 had lobectomy while 35 were ineligible based on predicted values. Prediction bias using the Bland-Altman method changed significantly after controlling for selection bias. To achieve a postoperative FEV1 > 30% and DLCO ≥30%, a predicted FEV1 > 46% and DLCO ≥53% were required. Compared to current guidelines, using these thresholds would change management in 17% of cases. CONCLUSION: The impact of selection bias on estimates of prediction accuracy was significant but can be corrected. Threshold values for determining surgical eligibility should be reassessed.

Anhedonia and smoking cessation among Spanish-speaking Mexican-Americans.

OBJECTIVE: Smoking cessation is associated with improved health and reduced risk of disease. Understanding specific factors that are associated with smoking cessation is important both for identifying those who may have the greatest difficulty quitting smoking and tailoring smoking cessation interventions accordingly. Low positive affect/anhedonia, a key transdiagnostic symptom of several psychiatric disorders, is associated with lower levels of smoking cessation in the general population, but to date, few studies have examined factors influencing smoking cessation among Spanish-speaking Mexican-American smokers. METHODS: The current study examined whether low positive affect/anhedonia was inversely related to cessation status across 3 time points among Spanish-speaking Mexican-American smokers (N = 199) who were making a smoking quit attempt. RESULTS: Using multilevel modeling, the between-person low positive affect/anhedonia score was found to be inversely associated with smoking at quit day, 3 and 26 weeks after quit while controlling for relevant covariates (i.e., age, gender, education, income, relationship status, heaviness of smoking index) but not when controlling for other symptoms of depression. CONCLUSIONS: Contrary to prior research, the results of this study did not confirm the unique predictive role of low positive affect/anhedonia among Mexican Americans, suggesting that risk factors for this group may be different from other populations and cessation approaches may also need to differ. (PsycINFO Database Record

Patellar Resurfacing: Does It Affect Outcomes of Distal Femoral Replacement After Distal Femoral Resection?

BACKGROUND: Patellar resurfacing after routine arthroplasty remains controversial. Few studies have specifically examined the effect of patellar resurfacing on outcomes after resection of the distal part of the femur and reconstruction with a megaprosthesis. Our objective was to compare the outcomes of megaprosthesis reconstructions of the distal part of the femur with and without patellar resurfacing after resection of a distal femoral tumor. METHODS: We retrospectively reviewed the clinical records of patients with a femoral tumor who underwent resection of the distal part of the femur and endoprosthetic reconstruction between 1993 and 2013. We excluded patients who had had extra-articular knee resection, patellectomy, revision, reconstruction with an expandable prosthesis, or a proximal tibial replacement associated with the distal femoral replacement. We compared demographic characteristics, surgical variables, anterior knee pain, range of motion, extensor lag, Insall-Salvati ratio, Insall-Salvati patellar tendon insertion ratio, impingement, patellar degenerative disease, additional patellar procedures, complications, and Musculoskeletal Tumor Society (MSTS) score between the patellar resurfacing and nonresurfacing groups. RESULTS: One hundred and eight patients--sixty without patellar resurfacing and forty-eight with patellar resurfacing--were included in the study. The mean age was 33.9 years (range, twelve to seventy-five years). There were fifty-four men and fifty-four women. The mean duration of follow-up was 4.5 years (range, 0.7 to twenty years). There was no significant difference in anterior knee pain between the groups (p = 0.51). Anterior knee pain did not significantly affect the range of motion, extensor lag, or reoperation or complication rate. Patellar degenerative disease occurred in 48% of the nonresurfaced knees but was not associated with focal pain. Complication rates were similar in the two groups, although peripatellar calcifications were significantly more common in the resurfacing group (19% versus 2%; p = 0.005). There was no significant difference in the mean MSTS score between the nonresurfacing (81%) and resurfacing (71%) groups (p = 0.34). CONCLUSIONS: There were no differences in anterior knee pain, range of motion, extensor lag, or MSTS score between the patients with and those without patellar resurfacing. There were no cases of patellar component loosening or revision. In light of the similar outcomes in the two groups, the decision to resurface should be left up to the individual surgeon, who should take into account preoperative peripatellar pain and the status of the patella at the time of resection. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Six1 induces protein synthesis signaling expression in duck myoblasts mainly via up-regulation of mTOR.

As a critical transcription factor, Six1 plays an important role in the regulation of myogenesis and muscle development. However, little is known about its regulatory mechanism associated with muscular protein synthesis. The objective of this study was to investigate the effects of overexpression ofSix1 on the expression of key protein metabolism-related genes in duck myoblasts. Through an experimental model where duck myoblasts were transfected with a pEGFP-duSix1 construct, we found that overexpression of duckSix1 could enhance cell proliferation activity and increase mRNA expression levels of key genes involved in the PI3K/Akt/mTOR signaling pathway, while the expression of FOXO1, MuRF1and MAFbx was not significantly altered, indicating thatSix1 could promote protein synthesis in myoblasts through up-regulating the expression of several related genes. Additionally, in duck myoblasts treated with LY294002 and rapamycin, the specific inhibitors ofPI3K and mTOR, respectively, the overexpression of Six1 could significantly ameliorate inhibitive effects of these inhibitors on protein synthesis. Especially, the mRNA expression levels of mTOR and S6K1 were observed to undergo a visible change, and a significant increase in protein expression of S6K1 was seen. These data suggested that Six1plays an important role in protein synthesis, which may be mainly due to activation of the mTOR signaling pathway.

Antimicrobial and molecular interaction studies on derivatives of curcumin against Streptococcus pneumoniae which caused pneumonia

Background: The antimicrobial properties and molecular interaction analysis of curcumin and its derivatives against three different strains of Streptococcus pneumoniae (Penicillin-susceptible, Penicillin-intermediate and Penicillin-resistant) are studied. Results: These properties were analyzed based on the measurement of the inhibition zone, minimum inhibitory concentration (MIC), and rate of kill revealed that curcumin monoglucoside, curcumin diglucoside and curcumin possessed strong antimicrobial properties even on the Penicillin-resistant strains. Additionally, the molecular docking simulation analyses against Penicillin Binding Protein of S. pneumoniae also confirm that these compounds docked at the active site of the enzyme. Further, the molecular dynamics simulation validates the conformational stability of the docked ligand-protein complexes in the dynamic environment. Conclusion: curcumin monoglucoside, curcumin diglucoside and curcumin can be prescribed for treatment against Penicillin-resistant S. pneumoniae.

Patellar Height Decreasing After Distal Femur Endoprosthesis Reconstruction Does Not Affect Functional Outcome.

INTRODUCTION: The patellar height can influence extensor mechanism and the knee function. Thus, during knee arthroplasty, the surgeon seeks to maintain the correct patellar height. However, it is more difficult to define and maintain the correct patella height in megaprosthesis reconstructions after tumor resections. The objective of this study was to evaluate patellar height after distal femur endoprosthesis reconstruction and its association to knee function. METHODS: This retrospective analysis included 108 patients who underwent distal femur resections and endoprosthesis reconstruction. The minimum follow-up was 1 year or until the patients underwent patellar resurfacing or endoprosthesis revision. Patellar height was calculated using Insall-Salvati ratio (ISR) and Insall-Salvati patellar tendon insertion ratio (PTR) at 2 different times: postoperatively and at the final follow-up. The postoperative ratio was calculated using the best postoperative radiograph taken at least 1 month after the procedure. The final measures were based on the radiograph available at the last follow-up consultation. The ISR and PTR were associated to anterior knee pain (AKP), range of motion (ROM), and extension lag (EXL). RESULTS: The average follow-up was 4.5years. The mean postoperative ISR was 1.02, and the mean ISR at final follow-up was 0.95 (P<.0001). The mean postoperative PTR was 1.45, and the mean PTR at final follow-up was 1.40 (P=.016). There was no association between patellar height and AKP, ROM, and EXL. Patellar height decreases significantly after distal femur resections but does not affect AKP, ROM, and EXL.

Construction of a eukaryotic expression vector for pEGFP-FST and its biological activity in duck myoblasts

Background Follistatin (FST), a secreted glycoprotein, is intrinsically linked to muscle hypertrophy. To explore the function of duck FST in myoblast proliferation and differentiation, the pEGFP-FST eukaryotic expression vector was constructed and identified. The biological activities of this vector were analyzed by transfecting pEGFP-FST into cultured duck myoblasts using Lipofectamine™ 2000 and subsequently determining the mRNA expression profiles of FST and myostatin (MSTN). Results The duck pEGFP-FST vector was successfully constructed and was confirmed to have high liposome-mediated transfection efficiency in duck myoblasts. Additionally, myoblasts transfected with pEGFP-FST had a higher biological activity. Significantly, the overexpression of FST in these cells significantly inhibited the mRNA expression of MSTN (a target gene that is negatively regulated by FST). Conclusions The duck pEGFP-FST vector has been constructed successfully and exhibits biological activity by promoting myoblast proliferation and differentiation in vitro.