Effect of Xiangsha Liu Junzitang Combined with Phlegm-removing and Detoxifying Traditional Chinese Medicine on Immune Escape in Lewis Lung Cancer Mice / 中国实验方剂学杂志

ObjectiveTo study the effect and mechanism of Xiangsha Liu Junzitang combined with phlegm-removing and detoxifying traditional Chinese medicine on immune escape in Lewis lung cancer mice. MethodA total of 60 specific-pathogen-free （SPF）-grade C57BL/6J male mice were injected subcutaneously with 0.2 mL of Lewis cell suspension （containing 2×106 cells·mL-1） in the right mid-axillary line. After 7 days， the mice that had been successfully modeled were randomly divided into six groups： the model group， the cisplatin group， the Xiangsha Liu Junzitang low-， medium-， and high-dose groups， and the combined group， with 10 mice in each group. The Xiangsha Liu Junzitang low-， medium- and high-dose groups were gavaged with 17.88， 35.75， 71.50 g·kg-1 Xiangsha Liu Junzitang solution once a day， respectively， and the dosage of cisplatin intraperitoneally injected into the mice was converted to 5 mg·kg-1 twice a week， and the tumour volumes of each group were measured every two days. The intervention lasted for 14 consecutive days. At the end of treatment， the tumour mass of mice in each group was weighed and the tumour inhibition rate was calculated. The morphological characteristics of tumours in each group were observed by hematoxylin-eosin （HE） staining. Fluorescent quantitative real-time polymerase chain reaction （Real-time PCR） assay was used to detect messenger ribonucleic acid （mRNA） contents of the natural killer group 2 member D （NKG2D） receptor， ribonucleic acid export-1 （RAE-1）， and γ interferon （IFN-γ） in the tumour tissues of each group. NKG2D， RAE-1， and IFN-γ mRNA in tumour tissues of each group. Immunohistochemistry （IHC） and Western blot were applied to detect the expressions of RAE-1， NKG2D， and IFN-γ in tumour tissues of each group， and Western blot was used to detect the expressions of interleukin-6 （IL-6）， Janus kinase 2 （JAK2）， p-JAK2， signal transducer and activator of transcription 3 （STAT3）， and p-STAT3 in tumour tissues of each group， as well as the protein levels of NKG2D， and RAE-1 in spleen tissues of each group. ResultCompared with that in the model group， the tumour mass decreased in all dose groups of Xiangsha Liu Junzitang， with no statistically significant difference. The tumour volume was reduced （P<0.05， P <0.01）. The pathological morphology was improved. The mRNA contents of NKG2D， RAE-1 and IFN-γ were increased in the medium-dose group （P<0.05， P<0.01）， and the protein expressions of NKG2D， RAE-1， and IFN-γ in tumour tissues were elevated （P<0.05， P<0.01）， and p-JAK2 and p-STAT3 protein expressions were decreased （P<0.05， P<0.01）. In spleen tissues， the protein expressions of NKG2D and RAE-1 in all dose groups of Xiangsha Liu Junzitang were significantly elevated （P<0.01）. Compared with those in the cisplatin group， NKG2D， RAE-1 and IFN-γ mRNA contents were elevated in the middle-dose group of Xiangsha Liu Junzitang， and the difference was not statistically significant. IHC showed that the protein expressions of NKG2D and IFN-γ in the combined group were significantly elevated （P<0.01）， and Western blot results showed that the protein expressions of RAE-1， NKG2D and IFN-γ were elevated （P<0.05， P<0.01）. p-JAK2 and p-STAT3 protein expressions were decreased in the combined group （P<0.05， P<0.01）. NKG2D and RAE-1 protein expressions were significantly increased in spleen tissues of the medium-dose groups and the combined group （P<0.01）. ConclusionXiangsha Liu Junzitang combined with phlegm-removing and detoxifying traditional Chinese medicine can inhibit the growth of tumours in Lewis lung cancer mice by up-regulating the expressions of RAE-1/NKG2D， promoting the activation of NK cells， and inhibiting immune escape， the mechanism of which may be related to down-regulation of the JAK2/STAT3 pathway.

Response of early-cycle common bean cultivars with carioca, black and speckled grains to top-dressing nitrogen fertilization

The aim was to evaluate the agronomic and qualitative attributes of early-cycle common bean cultivars with different grains types grains in response to top-dressing nitrogen (N) doses. The experiment was carried out using a randomized block design, in a split-plot scheme, with 4 replicates. The plots consisted of the cultivars IAC Nuance, IAC 1849 Polaco and IAC Veloz, with speckled, Carioca and black grains, respectively. The subplots were formed by N doses applied as top-dressing: 0 kg ha-1, 60 kg ha-1 (applied in the stage of third trifoliate leaf), 120 kg ha-1 (1/2 applied at third trifoliate leaf stage + 1/2 applied at the floral bud stage) and 180 kg ha-1 (1/3 applied at the first trifoliate leaf stage + 1/3 applied at the third trifoliate leaf stage + 1/3 applied at the floral bud stage). IAC Veloz stood out for grain yield, showing the highest grain yield in the lowest N doses, being classified as efficient to the use of N. The cultivars IAC Nuance and IAC 1849 Polaco reached maximum yields with 155 and 163 kg ha-1 of N. The IAC Nuance was the most responsive, increasing grain yield by up to 25.3% due to nitrogen fertilization. Increasing N doses applied as top-dressing increased the sieve yield and crude protein content of the common bean cultivars, with IAC Nuance standing out. The cultivars showed good grain quality, and IAC 1849 Polaco and IAC Veloz had the shortest cooking time and IAC Veloz also had the fastest hydration.

Dinâmica comparada: fluxos dos escravizados africanos em São Paulo, Minas Gerais e Maranhão (1804-1848) / Comparative dynamics: flows of enslaved Africans in São Paulo, Minas Gerais and Maranhão (1804-1848) / Dinámica comparada: flujos de africanos esclavizados en São Paulo, Minas Gerais y Maranhão (1804-1848)

Analisamos comparativamente informes demográficos de qualidade aceitável acerca dos escravizados nascidos na África para Minas Gerais, São Paulo e Maranhão de 1804 a 1848. As parcelas dos nascidos na África em relação aos escravizados e às razões de sexo de todos os cativos, de acordo com as idades, auxiliaram-nos a remontar a dinâmica retrospectiva da chegada dos africanos às regiões. Supondo certas hipóteses e procedimentos, a partir das coortes etárias, estimamos as proporções de africanos e as razões de sexo da população cativa para os períodos anteriores aos das listas nominativas de habitantes. A dinâmica retrospectiva da introdução de africanos reconstruída mostrou-se bastante correlacionada à história econômica das diferentes regiões estudadas.

We compare the surviving enslaved people present in demographic censuses of acceptable quality for Minas Gerais, São Paulo and Maranhão from 1804 to 1848. The share of those born in Africa in relation to slaves and the sex ratio of all captives according to their ages helped us find the retrospective dynamics of the arrival of Africans to these regions. When using age cohorts, we estimate, assuming certain hypotheses and procedures, the proportions of Africans and the sex ratios of the captive population for periods prior to those of the nominative lists of inhabitants. The retrospective dynamics of the reconstructed introduction of these Africans proved to be closely correlated with the economic history of the different regions analyzed.

Analizamos comparativamente a los sobrevivientes esclavizados presentes en los informes demográficos evaluados como de calidad aceptable para Minas Gerais, São Paulo y Maranhão entre 1804 y 1848. La proporción de los nacidos en África en relación con los esclavizados y la proporción de sexos de todos los cautivos, según las edades, nos ayudaron a trazar la dinámica retrospectiva de la llegada de africanos a estas regiones. Utilizando las cohortes de edad, estimamos, asumiendo ciertas hipótesis y procedimientos, las proporciones de africanos y las proporciones de sexos de la población cautiva para períodos anteriores a las listas nominativas de habitantes. La dinámica retrospectiva de la introducción reconstruida de africanos demostró estar altamente correlacionada con la historia económica de las diferentes regiones estudiadas.

Exportación y sanitación internacional en empresas productoras de prendas de alpaca de Huancayo y Lima / Exportation and international sanitation in companies producing alpaca garments in Huancayo and Lima

El Perú se considera un país potencia en cuanto a la exportación textil de la alpaca, cuya fibra natural es muy fina, ligera y con alto valor a nivel mundial. Para el año 2019, la exportación total de fibra de alpaca en Perú llegó a un total de 23 países, incluyendo mercados en Europa, Asia y Norteamérica. La tendencia en el comercio exterior incluyendo las empresas textiles de alpaca, se ha dirigido a garantizar el cuidado del medio ambiente y la inocuidad de los productos respecto a la salud humana. Se realizó un estudio desde el paradigma post-positivista, con enfoque cualitativo y el método hermenéutico, para interpretar la situación de exportación y sanitación internacional en empresas peruanas productoras de prendas de alpaca en Huancayo y Lima. Se obtuvo información a partir de cuatro informantes voluntarios de cada empresa acerca de aspectos relacionados con exportación de las prendas de alpaca: competitividad, promoción, proveedores, producción, calidad de producto, valor agregado, calidad de servicio, mercados destino, demanda y herramientas de inteligencia comercial, entre otros. Asimismo, se indagó sobre la concepción y cumplimiento del Reglamento Sanitario Internacional. Las empresas evaluadas, emplean excelente materia prima, garantizan un control de calidad de sus productos ofreciendo textiles competitivos que se distribuyen en diversos mercados internacionales, emplean herramientas de comercialización que favorecen la identificación de regulaciones arancelarias y la capacitación de su personal. No obstante, muestran carencias en el cumplimiento del RSI, requiriendo adoptar medidas que garanticen la salud pública al comercializar sus productos(AU)

Peru is considered a powerful country in terms of alpaca textile exports, whose natural fiber is very fine, light and highly valued worldwide. For the year 2019, the total export of alpaca fiber in Peru reached a total of 23 countries, including markets in Europe, Asia and North America. The trend in foreign trade, including alpaca textile companies, has been aimed at guaranteeing care for the environment and the safety of products with respect to human health. A study was carried out from the post-positivist paradigm, with a qualitative approach and the hermeneutical method, to interpret the export situation and international sanitation in Peruvian companies that produce alpaca garments in Huancayo and Lima. Information was obtained from four volunteer informants from each company about aspects related to the export of alpaca garments: competitiveness, promotion, suppliers, production, product quality, added value, service quality, destination markets, demand and marketing tools. commercial intelligence, among others. Likewise, the conception and compliance with the International Health Regulations were inquired about. The evaluated companies use excellent raw material, guarantee quality control of their products by offering competitive textiles that are distributed in various international markets, use marketing tools that favor the identification of tariff regulations and the training of their personnel. However, they show deficiencies in compliance with the RSI, requiring the adoption of measures that guarantee public health when marketing their products(AU)

Bile acid coordinates microbiota homeostasis and systemic immunometabolism in cardiometabolic diseases

Cardiometabolic disease (CMD), characterized with metabolic disorder triggered cardiovascular events, is a leading cause of death and disability. Metabolic disorders trigger chronic low-grade inflammation, and actually, a new concept of metaflammation has been proposed to define the state of metabolism connected with immunological adaptations. Amongst the continuously increased list of systemic metabolites in regulation of immune system, bile acids (BAs) represent a distinct class of metabolites implicated in the whole process of CMD development because of its multifaceted roles in shaping systemic immunometabolism. BAs can directly modulate the immune system by either boosting or inhibiting inflammatory responses via diverse mechanisms. Moreover, BAs are key determinants in maintaining the dynamic communication between the host and microbiota. Importantly, BAs via targeting Farnesoid X receptor (FXR) and diverse other nuclear receptors play key roles in regulating metabolic homeostasis of lipids, glucose, and amino acids. Moreover, BAs axis per se is susceptible to inflammatory and metabolic intervention, and thereby BAs axis may constitute a reciprocal regulatory loop in metaflammation. We thus propose that BAs axis represents a core coordinator in integrating systemic immunometabolism implicated in the process of CMD. We provide an updated summary and an intensive discussion about how BAs shape both the innate and adaptive immune system, and how BAs axis function as a core coordinator in integrating metabolic disorder to chronic inflammation in conditions of CMD.

Recent advances in drug development targeting bile acids transporters and related disease / 药学学报

Bile acids (BAs) are a major component of bile salt, which plays a vital role in the metabolism of lipids in humans. Ninety-five percent of bile acids are recycled by the enterohepatic circulation (EHC), and therefore EHC is essential for bile acid homeostasis. There are four transporters that mediate the transmembrane transport of bile acids, each of which plays an important role in the enterohepatic circulation. Gene defects in bile acid transporters can lead to disorders of the enterohepatic circulation, ultimately leading to clinical phenotypes such as metabolic diseases and even death. Bile transporter expression is altered in patients with various metabolic disease states, suggesting that disruption of bile acid transporters may be a pivotal pathological mechanism for the development of metabolism diseases. Thus, many drugs targeting bile acid transporters are being developed. We provide a concise overview of the progress of bile acid transporters research, discuss the relationship between different bile acid transporters and disease development, and summarize the current progress in drug development targeting bile acid transporters.

The Role of m6A Modification of Circular RNA in Tumors / 中国生物化学与分子生物学报

Circular RNA (circRNA) is a novel RNA with circular structures. It is conserved in various species, and characterized by high stability, high expression levels and tissue specificity. Meanwhile, it could serve as microRNA (miRNA) sponges, bind to RNA-binding proteins, or regulate transcription and protein translation. With the development of high-throughput sequencing and bioinformatics, circRNA was reported to participate in the pathogenesis of cancer. N6-methyladenosine (m6A) modification is the most common type of RNA modification in eukaryote RNA, which is a dynamic and reversible process regulated by m6A methyltransferase, m6A demethylase and m6A-binding proteins. M6A modification isinvolved in the regulation of RNA nuclear export, splicing, stability, translation and degradation, thus playing a key role in the occurrence and development of multiple human diseases, such as cancers, cardiovascular diseases. Recently, some researches demonstrated that m6A modification of circRNA was essential in the occurrence and development of malignant tumors, such as cervical cancer, colorectal carcinoma, hepatocellular carcinoma, non-small cell lung cancer, poorly differentiated adenocarcinoma of the stomach. In the current manuscript, we summarized the mechanism of m6A RNA modification, the roles of m6A modification in regulation of circRNA, and the effects of circRNA m6A modification on tumor. The potential clinical application value of m6A-modified circRNA was further discussed, as to provide some new ideas and ways for early diagnosis, clinical treatment and prognosis of tumors.

Econometric ridge regression models of risk-sensitive sunflower yield / Modelos economométricos de regressão de rendimento de girassol sensível ao risco

The article considers econometric ridge regression models of the risk-sensitive sunflower yield on the example of an export-oriented agricultural crop. In particular, we have proved that despite the functional mulcollinearity of the predictors in the sunflower yield model with respect to risk caused by the algorithm peculiarities of the hierarchy analysis methods, the ridge regression procedure makes it possible to obtain its complete specification and provide biased but stable estimates of the forecast parameters in the case of uncertain input variables. It has been substantiated that the rational value of the displacement parameters is expedient to be established using a graphical interpretation of the ridge wake as the border of fast and slow fluctuations in the estimates of the ridge regression coefficients. Econometric models were calculated using SPSS Statistics, Mathcad and FAR-AREA 4.0 software. The empirical basis for forecast calculations was the assessment of trends in sunflower production in all categories of farms in the Rostov region of Russia for the period of 2008-2018. The calculation results of econometric models made it possible to develop three author's scenarios for the sunflower production in the region, namely, inertial, moderate, and optimistic ones that consider the export-oriented strategy of the agro-industrial complex.(AU)

O artigo considera modelos econométricos de regressão de rendimento de girassol sensível ao risco sobre o exemplo de uma cultura agrícola orientada para a exportação. Em particular, provamos que apesar da multicolinearidade funcional dos preditores no modelo de rendimento de girassol com relação ao risco causado pelas peculiaridades dos algoritmos dos métodos de análise hierárquica, o procedimento de regressão de cristas permite obter sua especificação completa e fornecer estimativas tendenciosas, mas estáveis dos parâmetros de previsão no caso de variáveis de entrada incertas. Foi comprovado que o valor racional dos parâmetros de deslocamento é conveniente de ser estabelecido usando uma interpretação gráfica da esteira da crista como fronteira das flutuações rápidas e lentas nas estimativas dos coeficientes de regressão da crista. Os modelos econométricos foram calculados usando o software SPSS Statistics, Mathcad e FAR-AREA 4.0. A base empírica para os cálculos de previsão foi a avaliação das tendências da produção de girassol em todas as categorias de fazendas na região de Rostov na Rússia para o período de 2008-2018. Os resultados dos cálculos dos modelos econométricos permitiram desenvolver três cenários de autor para a produção de girassol na região, a saber, os cenários inercial, moderado e otimista que consideram a estratégia orientada à exportação do complexo agroindustrial.(AU)

Agricultores Tradicionales Produciendo para el Mercado Agroexportador: Causas y Consecuencias de Dicho Cambio Productivo / Traditional Farmers Producing for the Agro-Export Market: Causes and Consequences of Such Productive Change / Agricultores Tradicionais Produzindo para o Mercado Agroexportador: Causas e Consequências De Dita Mudança Produtiva

Resumen Introducción. En el municipio de El Peñol, Antioquia, la incursión de pequeños y medianos productores al mercado agroexportador de la gulupa (Passifflora edulis Sims) es hoy una realidad reconocida, que, asumida como caso de estudio, permite aportar a la comprensión de un fenómeno particular: el tránsito de agricultores tradicionales-locales hacia la producción para el mercado internacional, asunto sobre del que versa el presente estudio. Objetivo. Identificar y analizar las causas y consecuencias de la incursión de pequeños y medianos productores de El Peñol, Antioquia, al mercado agroexportador de la gulupa. Materiales y métodos. La investigación, de índole cualitativa, se centró en analizar las múltiples narrativas expuestas por los propios actores localmente asociados al cultivo de gulupa sobre las causas y consecuencias del fenómeno estudiado. La información se recolectó mediante entrevistas a profundidad, posteriormente analizadas en su contenido. Resultados. Entre las causas de la incursión al mercado global destacan las ventajas ofrecidas por el cultivo ante la inestabilidad de los precios de los productos tradicionales, el conocimiento previo de la especie y la oportunidad de tránsito hacia una agricultura más limpia. Entre las consecuencias, el mejoramiento de las condiciones socioeconómicas familiares, la reafirmación de la vocación agrícola de pequeños y medianos productores y la alta dependencia de la intermediación realizada por las empresas agroexportadoras. Conclusiones. Las causas y consecuencias del cambio productivo presentan un carácter multidimensional y ambivalente, situación que induce a explorar el fenómeno más allá de su dimensión económica, dando cuenta, simultáneamente, de sus bondades y riesgos.

Abstract Introduction. In the municipality of El Peñol, Antioquia, the incursion of small and medium producers to the agricultural export market of gulupa (Passifflora edulis Sims) is currently a recognized reality. Subject which, assumed as a case study, contributes to the understanding of a particular phenomenon: the movement of traditional-local farmers towards production for the international market, an issue addressed by this research. Objective. Identify and analyze the causes and consequences of the incursion of small and medium producers from El Peñol, Antioquia, to the agricultural export market of the gulupa. Materials and methods. The research was qualitative and focused on analyzing the multiple narratives presented by the local actors, associated with the gulupa crops about the causes and consequences of the phenomenon studied. The information was collected through in-depth interviews, subsequently analyzing its content. Results. Among the causes of the global market incursion, the advantages offered by the crop are highlighted due to the instability of the prices of traditional products, the prior knowledge of the gulupa and the opportunity to move towards a cleaner agriculture. Among the consequences are the improvement of family socioeconomic conditions, the reaffirmation of the agricultural vocation of small and medium producers and the high dependence on intermediation carried out by agro-exporting companies. Conclusions. The causes and consequences of productive change have a multidimensional and ambivalent character, a situation that leads to explore the phenomenon beyond its economic dimension, while simultaneously presenting simultaneously its benefits and risks.

Resumo Introdução. No município de El Peñol, Antioquia, a incursão de pequenos e médios produtores no mercado agrícola de exportação da gulupa (Passifflora edulis Sims) é uma realidade hoje reconhecida, que, assumida como estudo de caso, permite contribuir para a compreensão de um fenômeno particular: o trânsito de agricultores tradicionais locais para a produção para o mercado internacional, assunto sobre o qual o estudo trata. Objetivo. Identificar e analisar as causas e consequências da incursão de pequenos e médios produtores de El Peñol, Antioquia, no mercado de exportação agrícola da gulupa. Materiais e métodos. A pesquisa, de ordem qualitativa, teve como objetivo analisar as múltiplas narrativas apresentadas pelos próprios atores associados ao cultivo da gulupa sobre as causas e consequências do fenômeno estudado. As informações foram coletadas por meio de entrevistas em profundidade, posteriormente analisadas em seu conteúdo. Resultados. Entre as causas da incursão no mercado global, destacam-se as vantagens oferecidas pela gulupa, dada a instabilidade dos preços dos produtos tradicionais, o conhecimento prévio da espécie e a oportunidade de avançar para uma agricultura mais limpa. Entre as consequências, estão a melhoria das condições socioeconômicas da família, a reafirmação da vocação agrícola dos pequenos e médios produtores e a alta dependência de intermediação realizada pelas empresas agroexportadoras. Conclusões. As causas e consequências da mudança produtiva têm um caráter multidimensional e ambivalente, situação que leva a explorar o fenômeno além de sua dimensão econômica, percebido, ao mesmo tempo, seus benefícios e riscos.

CRISPR-Cas9: A method for establishing rat models of drug metabolism and pharmacokinetics

The 2020 Nobel Prize in Chemistry recognized CRISPR-Cas9, a super-selective and precise gene editing tool. CRISPR-Cas9 has an obvious advantage in editing multiple genes in the same cell, and presents great potential in disease treatment and animal model construction. In recent years, CRISPR-Cas9 has been used to establish a series of rat models of drug metabolism and pharmacokinetics (DMPK), such as

Causes of death of beef cattle raised in feedlots / Causas de morte de bovinos de corte criados em confinamentos

The causes of death of cattle kept in pre-export feedlots (PEFs) and in feedlot for finishing for slaughter are described. Two studies were conducted: a retrospective study of mortality cases in feedlots from 2000 to 2017 registered at the "Laboratório Regional de Diagnóstico" of the "Faculdade de Veterinária" of the "Universidade Federal de Pelotas"; and a prospective study from January 2018 to August 2019, following up 22 feedlots for finishing and six PEFs for the export of live cattle. From January 2000 to August 2019 samples of 150 cases of diseases that affected feedlot cattle were received from 22 feedlots for finishing and 115 of the six PEFs followed. Mortality considering all diagnosed diseases was significantly higher in feedlots for finishing (p<0.05), than in PEFs for the export of live cattle, of 1% and 0.12%, respectively. Diseases of the digestive system were the most important causes, of death in feedlots regardless of its purpose. Acidosis presented the highest mortality rates both in feedlot for finishing (3.33%) as in PEFs for export (0.95%). In all cases the disease occurred due to failure in the adaptation of animals to the ingestion of concentrated foods. Bovine tick fever and pneumonia presented mortality rates of 0.13% and 0.09%, respectively in PEFs. In the feedlot for finishing seneciosis was the second cause of death due to cattle coming from areas with high infestation by the plant. In the present study, it was possible to identify the main diseases that occur in cattle feedlots for finishing or for the export of live animals in the southern region of Rio Grande do Sul. These diseases are known in other systems of cattle breeding and can be prevented or controlled through management, chemoprophylaxis or vaccination, minimizing losses due to mortality.(AU)

Descrevem-se as causas de morte de bovinos mantidos confinados em estabelecimentos pré-embarque (EPEs) para exportação de animais vivos e em estabelecimentos de terminação para abate. Foram realizados dois estudos: um retrospectivo dos casos de mortalidade em confinamentos de 2000 a 2017 registrados no Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas; e um estudo prospectivo de janeiro de 2018 a agosto de 2019, acompanhando-se 22 confinamentos de terminação e seis EPEs para exportação de bovinos vivos. No total, de janeiro de 2000 a agosto de 2019 foram recebidos no LRD-UFPel amostras de 150 casos de enfermidades que afetaram bovinos confinados, 35 provenientes de 22 confinamentos de terminação e 115 dos seis EPEs acompanhados. A mortalidade considerando-se todas as enfermidades diagnosticadas foi significativamente maior nos confinamentos para terminação (p<0,05), do que nos EPEs para exportação de bovinos vivos, de 1% e 0,12%, respectivamente. As doenças do sistema digestivo foram as causas de morte mais importante nos confinamentos, independente da finalidade. Acidose apresentou as maiores taxas de mortalidade tanto nos confinamentos para terminação (3,33%) como nos EPEs para exportação (0,95%). Em todos os casos a doença ocorreu devido a falha na adaptação dos animais à ingestão de alimentos concentrados. Tristeza parasitária bovina e pneumonias apresentaram taxas de mortalidade de 0,13% e 0,09, respectivamente em EPEs de exportação. Nos confinamentos para terminação a seneciose foi a segunda causa de morte devido aos bovinos serem provenientes de áreas com alta infestação pela planta. Este estudo permitiu identificar as principais enfermidades diagnosticadas em confinamentos para terminação de bovinos ou para exportação de bovinos vivos na região Sul do Rio Grande do Sul. Observou-se que são doenças que ocorrem em outros sistemas de criação de bovinos e que podem ser prevenidas ou controladas por meio de manejo, quimioprofilaxia ou vacinação, minimizando prejuízos por mortalidade de animais.(AU)

A human cell polarity protein Lgl2 regulates influenza A virus nucleoprotein exportation from nucleus in MDCK cells

In this study, the regulatory effect of the overexpression of polarity protein Lgl2 on the nuclear export ofinfluenza A virus nucleoprotein in infected cells was investigated. A stable Tet-Off inducible MDCK cell lineexpressing a fusion protein comprising Lgl2 and an enhanced yellow fluorescent protein were used. TCID50analysis and neuraminidase activity analysis revealed that replication of influenza A virus was inhibited in Lgl2overexpressing cells. By immunofluorescence microscopical observation at different time point post virusinfection, a retention of NP in cellular nucleus was found in Lgl2 overexpressing cells. Compared with normalMDCK cells, change in claudin-1 distribution between cell contacts caused by Lgl2 overexpression impairedthe barrier function of tight junction. These results suggest that changes in cell polarity induced by Lgl2overexpressing will affect virus NP transportation.

Screening of a novel CRM1 targeting inhibitor and its effects on the proliferation and growth of extranodal NK/T cell lymphoma / 中国药科大学学报

@#The purpose of this study was to screen out the novel chromosome maintenance protein 1(CRM1)covalent targeting inhibitors by computer-assisted drug design(CADD), and to study their effects on the proliferation of extranodal nature killer/T cell lymphoma(ENKTL). A novel CRM1 inhibitor LFS-829 was designed based on the molecular structure of LFS-01 by means of ADME/T and covalent docking. The target binding of LFS-829 with CRM1 was analyzed by MALDI-TOF mass spectrometry. The effects of LFS-829 on the proliferation of extranodal NK/T cell lymphoma SNK6 and HANK-1 cells were detected by CCK-8. The cell morphology was observed by live cell workstation. Immunofluorescence experiments were used to analyze the effect of LFS-829 on nuclear export function of CRM1. The changes of NF-κB signaling pathway under different concentrations of LFS-829 were analyzed by Western blot, dual luciferase reporter gene assay and enzyme-linked immunosorbent assay. Apoptosis was detected by flow cytometry, and the expression of proteins related to apoptosis pathway was detected by Western blot. Tests of peripheral blood mononuclear lymphocyte(PBMC)toxicity, platelet toxicity and mouse acute toxicity were done to make sure that it is not harmful to human. LFS-829 could bind covalently to the cysteine residue of the hydrophobic active pocket of CRM1. LFS-829 could selectively kill SNK6 and HANK-1 cells, with IC50 of 366 nmol/L and 158 nmol/L in 72 h, respectively, and cell morphology was significantly changed. LFS-829 at 800 nmol/L significantly inhibited the nuclear export function of CRM1, promoted nuclear assembly of IκB-α, down-regulated the transcriptional activity of NF-κB signaling pathway, significantly up-regulated the expression of apoptotic pathway protein p53, cleaved Caspase 3 and cleaved Caspase 9 and induced apoptosis, with no obvious killing effect on PBMC or platelets. It did not cause substantial tissue damage to mice at the high dose of 300 mg/kg, which shows its great prospect of future application.

Transmission of exchange rate variation to Brazilian pulp export prices / Transmissão da variação da taxa de câmbio para os preços brasileiros de exportação da celulose

ABSTRACT: The aim of this research was to examine the relationship between exchange rate variations and Brazilian export prices for cellulose, which is defined as the exchange rate pass-through, taking the period from January 2000 to March 2019 as a reference. The data were collected on the websites of the Ministry of Development, Industry and Foreign Trade - MDIC, the Institute of Applied Economics - IPEA and the Federal Reserve Bank of St. Louis - FRED. Thus, time series instruments were used, especially the Error Correction Vector Model. Results provided indications that the pass-through degree of exchange rate for cellulose export prices occurred incompletely in the total period and in the second sub-period, and was null in the first sub-period, representing that depreciation of rate exchange rates did not translate into significant competitiveness gains, as they did not significantly reduced export prices.

RESUMO: O objetivo deste trabalho consistiu no exame da relação entre as variações cambiais e os preços de exportação brasileiros da celulose, relação definida como o pass-throughda taxa de câmbio, tendo como referência o período de janeiro de 2000 a março de 2019. Os dados foram coletados nos sites do Ministério do Desenvolvimento, Indústria e Comércio Exterior - MDIC, no Instituto de Economia Aplicada - IPEA e no Federal Reserve Bank of St. Louis - FRED. Neste sentido, fez-se uso dos instrumentais de séries temporais, especialmente do Modelo Vetor de Correção de Erros. Os resultados encontrados forneceram indicações de que o grau de pass-throughda taxa de câmbio para os preços de exportação da celulose ocorreram de forma incompleta no período total e no segundo sub-período, e nula no primeiro sub-período, representando que depreciações da taxa de câmbio não se traduzem em ganhos significativos de competitividade, dado que não reduzem expressivamente os preços de exportação.

The impact of agriculture trade and exchange rate on economic growth of Pakistan: an NARDL and asymmetric analysis approach / O impacto do comércio agrícola e da taxa decâmbio no crescimento econômico do Paquistão: uma abordagem de análise NARDL e assimétrica

ABSTRACT: This study contributes to the extant literature on the nexus among agriculture export, import exchange rate and economic growth in Pakistan. We used annual time series data for 1980-2017 and employ the Non-linear Autoregressive Distributed Lag (NARDL) model. The NARDL testing results affirms asymmetric co-integration among the variables. The study main results show: (i) Co-integration test for long run the positive shocks in export and import have positive significant while exchange rate has positive effect the economic growth. (ii) Co-integration test for short run the positive shocks in import has positive significant and while Export and exchange rate have negative significant effect on economic growth. The symmetrical results show: (i) Export has unidirectional granger causality (ii) Exchange rate has bidirectional granger causality (iii) Import has not ganger causality with economic growth. In addition, the results demonstrated that causality relationship can help out policy maker to design such policies which are useful to economic growth of Pakistan, which could further promote foreign trade to gain the maximum level of economic growth.

RESUMO: Este estudo contribui para a literatura existente sobre o nexo entre exportação agrícola, taxa de câmbio de importação e crescimento econômico no Paquistão. Utilizamos dados de séries temporais anuais para 1980-2017 e empregamos o modelo Não-linear Autoregressive Distributed Lag (NARDL). Os resultados dos testes NARDL afirmam a co-integração assimétrica entre as variáveis. Os principais resultados do estudo mostram: (i) no teste de co-integração de longo prazo, os choques positivos nas exportações e importações têm uma significância positiva, enquanto a taxa de câmbio afeta positivamente o crescimento econômico; (ii) Teste de co-integração para curto prazo, os choques positivos nas importações são positivos significativos e, enquanto a exportação e a taxa de câmbio têm um efeito negativo significativo no crescimento econômico. Os resultados simétricos mostram: (i) a exportação tem causalidade unidirecional sobre o crescimento ; (ii) a taxa de câmbio tem causalidade bidirecional sobre o crescimento ; (iii) a importação não tem causalidade sobre o crescimento econômico. Além disso, os resultados demonstraram que a relação de causalidade pode ajudar o formulador de políticas a elaborar políticas úteis ao crescimento econômico do Paquistão, o que poderia promover ainda mais o comércio exterior para obter o nível máximo de crescimento econômico.

Efficiency of midsize enterprises in the free-trade-zone in Barranquilla - Colombia / Eficiencia de las pequeñas y medianas empresas de la zona franca en Barranquilla- Colombia / Eficiência de pequenas e médias empresas na zona franca de Barranquilla - Colombia

Abstract In this investigation, the efficiency of midsize companies in the free-trade-zones of Barranquilla was analyzed. For this, a model supported by Data Envelopment Analysis structure (DEA) was proposed which required a rational analysis to define input and output variables in order to measure and test the efficiency of 63 companies under study in 2016 and 2017. The Chamber of Commerce of Barranquilla with which an empirical analysis was performed to measure the efficiency of the sector provided primary information. The research showed that from 2016-2017 the percentage of efficient enterprises improved from 11.11% to 17.46% while 6.34% of companies maintain their efficiency, 42.85% showed improvements and 50. 79% of companies decreased their efficiency. JEL Classification: M11, F17, F23.

Resumen En esta investigación se analizó la eficiencia de las pequeñas y medianas empresas de la Zona Franca de Barranquilla, para esto se propuso una estructura apoyada en el modelo de Análisis Envolvente de Datos (DEA), lo que requirió un análisis racional para la definición de variables de entrada y salida con el fin de medir y contrastar la eficiencia de 63 empresas objeto de estudio en los año 2016 y 2017, se partió de la información primaria suministrada por la Cámara de Comercio de Barranquilla con lo cual se realizó un análisis empírico que permitió medir la eficiencia del sector La investigación mostró que el porcentaje de empresas eficientes mejoró de a 17.46%, en los años 2016-2017. Así mismo se observó que un 6.34 % de las empresas mantuvieron su eficiencia, un 42.85 % mostraron mejoras y un 50.79 % de empresas desmejoraron su eficiencia en el periodo 2016-2017. Clasificación JEL: M11, F17, F23.

Resumo Nesta pesquisa foi analisada a eficiência das pequenas e médias empresas na Zona de Barranquilla, para isso foi proposta uma estrutura apoiada pelo modelo Data Envelopment Analysis (DEA), que requer uma análise racional para a definição de variáveis de entrada e saída, a fim de medir e contrastar a eficiência de 63 empresas em estudo nos anos 2016 e 2017; isto sob a informação primária fornecida pela Câmara de Comercio de Barranquilla com a qual foi realizada uma análise empírica que permitiu medir a eficiência do setor A pesquisa mostrou que o percentual de empresas eficientes melhorou de para 17,46% nos anos 2016 e 2017. Da mesma forma, observou-se que 6,34% das empresas mantiveram sua eficiência, 42,85% apresentaram melhorias e 50,79% das empresas deterioraram sus eficiência no período 2016-2017. Classificações JEL: M11, F17, F23.

Research on exporting competitiveness of pharmaceuticals in China / 中国药科大学学报

@#Pharmaceuticals were chosen as the entry point to analyze the status and characteristics of China′s pharmaceutical exports. An export competitiveness evaluation system was comprehensively constructed by selecting the scale, quality and progress of international trade as three dimensions. Net exports, export contribution rate, international market share, display comparative advantage index, competitive advantage index, Michaely index and export advantage growth index as seven indices. In order to avoid the discrepancy caused by the different angles of each index, the indicators were abstracted into two comprehensive ones through principal component analysis, to measure the export competitiveness of the world′s leading countries and regions in pharmaceuticals import and export directly. The result shows that China′s exporting competitiveness of pharmaceuticals ranks the sixth among the 10 major import and export countries in the world. On this basis, dialectical reference is made from Switzerland with strong export competitiveness of pharmaceutical products, in order to promote the long-term development of the export of pharmaceutical products in China.

Benign Recurrent Intrahepatic Cholestasis Type 2 in Siblings with Novel ABCB11 Mutations / 대한소아소화기영양학회지

Benign recurrent intrahepatic cholestasis (BRIC), a rare cause of cholestasis, is characterized by recurrent episodes of cholestasis without permanent liver damage. BRIC type 2 (BRIC2) is an autosomal recessive disorder caused by ABCB11 mutations. A 6-year-old girl had recurrent episodes of jaundice. At two months of age, jaundice and hepatosplenomegaly developed. Liver function tests showed cholestatic hepatitis. A liver biopsy revealed diffuse giant cell transformation, bile duct paucity, intracytoplasmic cholestasis, and periportal fibrosis. An ABCB11 gene study revealed novel compound heterozygous mutations, including c.2075+3A>G in IVS17 and p.R1221K. Liver function test results were normal at 12 months of age. At six years of age, steatorrhea, jaundice, and pruritus developed. Liver function tests improved following administration of phenylbutyrate and rifampicin. Her younger brother developed jaundice at two months of age and his genetic tests revealed the same mutations as his sister. This is the first report of BRIC2 confirmed by ABCB11 mutations in Korean siblings.

Progressive Familial Intrahepatic Cholestasis in Korea: A Clinicopathological Study of Five Patients

BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive liver diseases that present as neonatal cholestasis. Little is known of this disease in Korea. METHODS: The records of five patients histologically diagnosed with PFIC, one with PFIC1 and four with PFIC2, by liver biopsy or transplant were reviewed, and ATP8B1 and ABCB11 mutation status was analyzed by direct DNA sequencing. Clinicopathological characteristics were correlated with genetic mutations. RESULTS: The first symptom in all patients was jaundice. Histologically, lobular cholestasis with bile plugs was the main finding in all patients, whereas diffuse or periportal cholestasis was identified only in patients with PFIC2. Giant cells and ballooning of hepatocytes were observed in three and three patients with PFIC2, respectively, but not in the patient with PFIC1. Immunostaining showed total loss of bile salt export pump in two patients with PFIC2 and focal loss in two. Lobular and portal based fibrosis were more advanced in PFIC2 than in PFIC1. ATP8B1 and ABCB11 mutations were identified in one PFIC1 and two PFIC2 patients, respectively. One PFIC1 and three PFIC2 patients underwent liver transplantation (LT). At age 7 months, one PFIC2 patient was diagnosed with concurrent hepatocellular carcinoma and infantile hemangioma in an explanted liver. The patient with PFIC1 developed steatohepatitis after LT. One patient showed recurrence of PFIC2 after 10 years and underwent LT. CONCLUSIONS: PFIC is not rare in patients with neonatal cholestasis of unknown origin. Proper clinicopathologic correlation and genetic testing can enable early detection and management.

Combination of mRNA of Repair-related Genes in Rat Skeletal Muscles for Wound Age Estimation / 法医学杂志

Objective To investigate the estimation of early and mid-term wound age by a combination of four mRNAs, the DNA polymerase delta-interacting protein 3 （POLDIP3） mRNA, regulator of chromosome condensation 1 like （RCC1L） mRNA, proline-rich 5 （PRR5） mRNA, and ribonucleic acid export 1 （RAE1） mRNA in rats skeletal muscles. Methods The model of rat skeletal muscle contusion was established, and then contusion area muscle tissue was extracted 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48 h after injury. Histomorphological changes during the repair process after rat skeletal muscle contusion were observed. The relative expressions of Poldip3, Rcc1l, Prr5 and Rae1 mRNAs were detected by reverse transcription real-time quantitative polymerase chain reaction （RT-qPCR）. Different stages of wound age were classified by using the expression patterns of four genes at various time points after injury. The accuracy of the results was verified by Fisher discriminant analysis. Results Histomorphological results showed that the repair process after skeletal muscle contusion occurred with the prolonging of time. Through combination of the expression trends of the four kinds of mRNAs, the 48 h after injury could be divided into three periods, 4-12 h, 16-28 h and 32-48 h. The Fisher discrimination method showed that the classification accuracy rates of the three periods were 83.3%, 75.0% and 73.3%, respectively. Conclusion The classification discrimination based on the relative expression of every gene has a higher accuracy, and the accuracy of wound age estimation with combination of mRNA relative expressions is higher than that with a single indicator. By combining with Fisher discrimination method, this method can be used for early and mid-term wound age estimation.