RESUMEN Las redes de conocimiento se han convertido en un factor crítico en el desarrollo de la innovación. Sin embargo, la mayoría de los estudios se han centrado en los beneficios de la innovación derivados de la incorporación de redes, pero hay menos estudios sobre las redes de conocimiento de las empresas desde la perspectiva de los atributos de las características. Este estudio analiza los efectos directos e interactivos de la diversidad del conocimiento y el potencial de la combinación de conocimientos sobre el rendimiento de la innovación, y cómo la complementariedad del aprendizaje ambidiestro afecta a la relación entre las redes de conocimiento y el rendimiento de la innovación. El análisis empírico se basa en datos de panel de 116 empresas de la industria automotriz de China entre 2010 y 2018. Los resultados procesados por el modelo de regresión binomial negativa de efectos fijos indican que el potencial combinatorio del conocimiento tiene una relación en forma de U invertida con el rendimiento de la innovación de las empresas, y la diversidad del conocimiento tiene un efecto positivo en el rendimiento de la innovación de las empresas. Existe un efecto interactivo entre el potencial combinatorio del conocimiento y la diversidad del conocimiento, y su coordinación mutua mejora conjuntamente el rendimiento de la innovación empresarial. La complementariedad del aprendizaje ambidiestro modera significativa y positivamente la relación positiva entre el potencial de combinación de conocimientos y el rendimiento de la innovación empresarial. embargo características 11 201 2018 empresarial 1 20 2

ABSTRACT Knowledge networks have become a critical factor in the development of innovation. However, most studies focus on the innovation benefits derived from network embedding, and there are fewer studies on firms’ knowledge networks from the perspective of feature attributes. This study analyzes the direct and interactive effects of knowledge diversity and the combination of knowledge potential on innovation performance. The research also explores how the complementarity of ambidextrous learning affects the relationship between knowledge networks and innovation performance. The empirical analysis is based on panel data from 116 firms in China’s automotive manufacturing industry from 2010-2018. The results processed by the fixed effects negative binomial regression model indicate that the combinatorial potential of knowledge has an inverted U-shaped relationship with firm innovation performance, and knowledge diversity has a positive effect on firm innovation performance. There is an interactive effect between knowledge combination potential and knowledge diversity, and their mutual coordination improves firm innovation performance. The complementarity of ambidextrous learning significantly and positively moderates the positive relationship between the combination potential of knowledge and firm innovation performance. However embedding attributes performance 11 Chinas China s 20102018. 20102018 2010 2018. 2018 2010-2018 Ushaped U shaped 1 2010201 201 2010-201 201020 20 2010-20 20102 2 2010-2 2010-

RESUMO A rede de conhecimento tornou-se um fator crítico para o desenvolvimento da inovação. No entanto, a maioria dos estudos têm se concentrado nos benefícios da inovação derivados da incorporação de redes, mas há menos estudos sobre a rede de conhecimento da empresa do ponto de vista dos atributos de características. Este estudo visa analisar os efeitos diretos e interativos da diversidade de conhecimento e do potencial combinatório de conhecimento no desempenho da inovação, e como a complementaridade da aprendizagem ambidestra afeta a relação entre as redes de conhecimento e o desempenho da inovação. A análise empírica baseia-se em dados de painel de 116 empresas da indústria automobilística da China de 2010 a 2018. Os resultados processados pelo modelo de regressão binomial negativa de efeitos fixos indicam que o potencial combinatório de conhecimento tem uma relação invertida em forma de U com o desempenho da inovação empresarial, e a diversidade de conhecimento tem um efeito positivo no desempenho dessa inovação. Existe um efeito interativo entre o potencial combinatório do conhecimento e sua diversidade, sendo que a coordenação entre eles melhora o desempenho das empresas em matéria de inovação. A complementaridade da aprendizagem ambidestra modera positivamente e de maneira significativa a relação positiva entre o potencial combinatório de conhecimento e o desempenho da inovação empresarial. tornouse tornou entanto características baseiase baseia 11 201 2018 empresarial 1 20 2

Abstract The study was the first to investigate the content and composition along with the antioxidant activities of polyphenols in the dark tea infusions. The effect of brewing conditions on total polyphenolic contents (TPC) in dark tea infusions was conducted by response surface methodology (RSM), and the composition of polyphenolic compounds was investigated using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS), and DPPH and ABTS assay were used to evaluate the antioxidant activity of dark tea. Results showed that brewing at water/tea radio 50 : 1 mL/g, temperature 92 °C and time 27 min was the best condition to obtain the highest TPC (3.90 mg/mL). The composition of polyphenolic compounds in the infusions included 11 catechins and derivatives, 19 flavones and flavone glycosides, and 1 phenolic acid, and the concentrations of epigallocatechin gallate (91.32 mg/L) and epicatechin-3-O-gallate (23.10 mg/L) was the highest among the quantitative compounds. Moreover, the dark tea had good scavenging activities on DPPH (IC50 = 9.94 μg/mL) and ABTS (IC50 = 17.26 μg/mL) free radicals.

OBJECTIVE: To determine the role of RNA-binding protein with serine-rich domain 1 (RNPS1) in uterine corpus endometrial carcinoma (UCEC), the role of RNPS1 knockdown in UCEC development in vitro and in vivo, and the relationship between RNPS1 and mismatch repair (MMR) in UCEC. METHODS: We predicted the potential function of RNPS1 using bioinformatics systems. The expression of RNPS1 in tissues and cell lines was analyzed by western blotting and immunohistochemistry. The expression of RNPS1 in MMR was assessed using bioinformatics and western blotting. The proliferation and apoptosis of UCEC cells were assessed under RNPS1 knockdown conditions, and RNPS1 regulation in MMR was detected by suppressing Notch signaling. Associations between RNPS1 and gene mutations in UCEC and prognosis were analyzed. RESULTS: The RNPS1 level was higher in UCEC tumors than in normal tissues and tumors or RL952 cells. Prognostic outcomes were worse when UCEC showed abundant RNPS1 expression. Lentiviral RNPS1 knockdown weakened tumor cell proliferation and suppressed biomarker expression, reduced the tumor volume, promoted apoptosis in vitro and in vivo, and inhibited UCEC development. Increased MutS homolog 2 (MSH2) and MutS homolog 6 (MSH6) levels in MMR after RNPS1 knockdown were reversed by inhibiting Notch signaling. Furthermore, RNPS1 was associated with mutations in NAA11, C2orf57, NUPR1, and other genes involved in UCEC prognosis. CONCLUSION: RNPS1 may regulate the expression levels of MSH2 and MSH6 in MMR, enhancing the proliferation, development, and prognosis of UCEC through a Notch signaling pathway in UCEC. Our study offers a new method and strategy for delaying UCEC development through modulating MMR.

SUMMARY: Lumbar disc herniation is considered to be the main pathological factor for the common clinical disease of low back pain. Biomechanical factor is an important cause of lumbar disc herniation, so it is urgent to analyze the stress/strain behavior of intervertebral disc under different loading condition. Slow repetitive loading is considered to be an important factor of spine and disc injuries, and the effect of fatigue load on internal displacement in the intervertebral disc was investigated by applying the optimized digital image correlation technique in this study. The first finding was that fatigue load had a significant effect on the displacement distribution in the intervertebral disc under compression. Superficial AF exhibited the largest axial displacements before fatigue load, while it exhibited the smallest axial displacements after fatigue load. Inner AF exhibited slightly smaller radial displacements than outer AF before fatigue load, while it exhibited significantly greater radial displacements than outer AF displacements after fatigue load. The second finding was that fatigue load had a certain effect on the internal displacement distribution in the flexed intervertebral disc under compression. Middle AF exhibited the smallest axial displacements before fatigue load, while deep AF exhibited the smallest axial displacements after fatigue load. The radial displacement distribution did not change before and after fatigue load, as the radial displacement in outer AF was the smallest, while the radial displacement in inner AF was the largest. The third finding was that with the increase in fatigue time and amplitude, the Young's modulus of the intervertebral disc increased significantly. This study can provide the basis for clinical intervertebral disc disease prevention and treatment? and is important for mechanical function evaluation of artificial intervertebral disc as well.

RESUMEN: La hernia de disco lumbar se considera el principal factor patológico para la enfermedad clínica común del dolor lumbar. El factor biomecánico es una causa importante de hernia de disco lumbar, por lo que es urgente analizar el comportamiento de esfuerzo / tensión del disco intervertebral bajo diferentes condiciones de carga. La carga repetitiva lenta se considera un factor importante de lesiones de columna y disco, y en este estudio el efecto de la carga de fatiga sobre el desplazamiento interno en el disco intervertebral se investigó mediante la aplicación de la técnica de correlación de imagen digital optimizada. El primer hallazgo fue que la carga de fatiga tuvo un efecto significativo en la distribución del desplazamiento en el disco intervertebral bajo compresión. El AF superficial exhibió los desplazamientos axiales más grandes antes de la carga de fatiga, mientras que exhibió los desplazamientos axiales más pequeños después de la carga de fatiga. El AF interno exhibió desplazamientos radiales ligeramente más pequeños que el AF externo antes de la carga de fatiga, mientras que exhibió desplazamientos radiales significativamente mayores que los desplazamientos AF externos después de la carga de fatiga. El segundo hallazgo fue que la carga de fatiga tenía un cierto efecto sobre la distribución del desplazamiento interno en el disco intervertebral flexionado bajo compresión. El AF medio exhibió los desplazamientos axiales más pequeños antes de la carga de fatiga, mientras que el AF profundo exhibió los desplazamientos axiales más pequeños después de la carga de fatiga. La distribución del desplazamiento radial no cambió antes ni después de la carga de fatiga, ya que el desplazamiento radial en la FA externa fue el más pequeño, mientras que el desplazamiento radial en la FA interna fue el más grande. El tercer hallazgo fue que con el aumento del tiempo de fatiga y la amplitud, el módulo de Young del disco intervertebral aumentó significativamente. Este estudio puede proporcionar la base para la prevención y el tratamiento clínico de la enfermedad del disco intervertebral, y también es importante para la evaluación de la función mecánica del disco intervertebral artificial.

RESUMO OBJETIVO: O objetivo deste estudo é investigar a expressão de Id-1 em tecidos de adenocarcinoma colorretal em humanos e investigar sua correlação com os parâmetros patológicos clínicos de câncer colorretal. MÉTODOS: Os níveis de expressão de proteína e mRNA Id-1 em 50 amostras de tecido colorretal normal e 50 amostras de tecido de adenocarcinoma colorretal foram detectados através de reação em cadeia de polimerase precedida de transcrição reversa e western blot. Além disso, a proteína Id-1 foi detectada através de imuno-histoquímica. A correlação entre a expressão de Id-1 e características clínico-patológicas foi analisada. RESULTADOS: O nível de expressão de mRNA Id-1 em tecidos de adenocarcinoma colorretal e tecidos colorretais normais foi de 0,96 ± 0,03 versus 0,20 ± 0,04, respectivamente; a diferença foi estatisticamente significativa (P= 0,011). Além disso, a expressão da proteína Id-1 foi maior em tecidos de adenocarcinoma colorretal do que em tecidos colorretais normais (0,82 ± 0,04 versus 0,31 ± 0,02, P= 0,020). Além disso, a taxa de expressão positiva de proteínas Id-1 foi maior em tecidos de adenocarcinoma colorretal do que em tecidos colorretais normais (72,00% vs. 24,00%, X2=23,431, p=0,000). A expressão de Id-1 foi correlacionada com a profundidade da invasão tumoral, estágio TNM, metástases linfonodais, invasão vascular e metástase hepática (P<0,01). Todavia, essa expressão não se correlacionou com o tamanho do tumor e graus de diferenciação (P>0,05). CONCLUSÃO: A alta expressão de Id-1 em tecidos de adenocarcinoma colorretal desempenham um importante papel no processo do câncer, e é esperado que se torne um novo indicador de monitoramento de tumores para o diagnóstico clínico, tratamento e estimativa de prognóstico.

SUMMARY BACKGROUND: This study aims to investigate the expression of Id-1 in human colorectal adenocarcinoma tissues and explore its correlation with the clinical pathological parameters of colorectal cancer. METHODS: The Id-1 mRNA and protein expression levels of 50 specimens of normal colorectal tissues and 50 specimens of colorectal adenocarcinoma tissues were detected using reverse-transcription polymerase chain reaction and western blot. Furthermore, Id-1 protein was detected using immunohistochemistry. The correlation between the expression of Id-1 and clinicopathologic features was analyzed. RESULTS: The mRNA expression level of Id-1 in colorectal adenocarcinoma tissues and normal colorectal tissues was 0.96 ± 0.03 vs. 0.20 ± 0.04, respectively; and the difference was statistically significant (P=0.011). Furthermore, Id-1 protein expression was higher in colorectal adenocarcinoma tissues than in normal colorectal tissues (0.82 ± 0.04 vs. 0.31 ± 0.02, P=0.020). In addition, the positive protein expression rate of Id-1 was higher in colorectal adenocarcinoma tissues than in normal colorectal tissues (72.00% vs. 24.00%, X2=23.431, P=0.000). The expression of Id-1 was correlated with the depth of tumor invasion, TNM stage, lymph node metastasis, vessel invasion, and liver metastasis (P<0.01). However, this expression was not correlated with tumor size and differentiation degrees (P>0.05). CONCLUSIONS: The high Id-1 expression in colorectal adenocarcinoma tissues play an important role in the process of cancer, and is expected to become a new tumor monitoring indicator for clinical diagnosis, treatment, and prognosis judgment.

ABSTRACT Heroin is known to enhance catabolism and inhibit anabolism of purine nucleotides, leading to purine nucleotide deficiencies in rat brains. Here, we determined the effect of exogenous purine nucleotide administration on purine nucleotide metabolism in the brains of heroin-dependent rats. Heroin was administrated in increasing doses for 9 consecutive days to induce addiction, and the biochemical changes associated with heroin and purine nucleotide administration were compared among the treated groups. HPLC was performed to detect the absolute concentrations of purine nucleotides in the rat brain cortices. The enzymatic activities of adenosine deaminase (ADA) and xanthine oxidase (XO) in the treated rat cortices were analyzed, and qRT-PCR was performed to determine the relative expression of ADA, XO, adenine phosphoribosyl transferase (APRT), hypoxanthine-guaninephosphoribosyl transferase (HGPRT), and adenosine kinase (AK). Heroin increased the enzymatic activity of ADA and XO, and up-regulated the transcription of ADA and XO. Alternatively, heroin decreased the transcription of AK, APRT, and HGPRT in the rat cortices. Furthermore, purine nucleotide administration alleviated the effect of heroin on purine nucleotide content, activity of essential purine nucleotide metabolic enzymes, and transcript levels of these genes. Our findings therefore represent a novel, putative approach to the treatment of heroin addiction.

The porous fluorescent SiO2 nanoparticles encapsulating photosensitizer Ru(bpy)3Cl2were prepared by Stöber method and used as a carrier to immobilize glucose oxidase (GOD) to form the bifunctional porous SiO2 complex nanoparticles (BPSCNp) with the properties of enzymatic catalysis and optical oxygen sensing. The optimal immobilization conditions are as follows: hexadecyltrimethyl ammonium bromide (APTES) concentration of 2% (v/v), glutaraldehyde (GA) concentration of 1.0% (v/v), and pH of 6.5, GOD amount of 4.0 mg in 40 mg of carrier. BPSCNp showed maximal catalytic activity at pH 6.0 and 50 °C. After immobilization, the thermal storage and operation stability of GOD were improved remarkably. After kept at 4 °C for 30 days, BPSCNp and free GOD retained 68% and 35% of initial activity, respectively. BPSCNp maintained 58% of its initial activity after 7 consecutive operations and 30% after 15 consecutive operations. The fluorescence of BPSCNp could be quenched effectively by oxygen. There was a good linear relationship between tanΦ0/tanφ and O2 concentration in the range of 0 to ca. 90%. BPSCNp had a highly reproducible response to oxygen with the response time of 20 s. BPSCNp might be used as the sensing material and have potential application in multi parameter fiber optic biosensor based on enzyme catalysis and oxygen consumption.

Clinical isolates of carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae) strains are being increased worldwide. Five pan-resistant K. pneumoniae strains have been isolated from respiratory and ICU wards in a Chinese hospital, and reveal strong resistance to all β-lactams, fluoroquinolones and aminoglycosides. Totally 27 β-lactamase genes and 2 membrane pore protein (porin) genes in 5 K. pneumoniae strains were screened by polymerase chain reaction (PCR). The results indicated that all of 5 K. pneumoniae strains carried blaTEM-1 and blaDHA-1 genes, as well as base deletion and mutation of OmpK35 or OmpK36 genes. Compared with carbapenem-sensitive isolates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the resistant isolates markedly lacked the protein band of 34-40 kDa, which might be the outer membrane proteins of OmpK36 according to the electrophoresis mobility. In addition, the conjugation test was confirmed that blaDHA-1 mediated by plasmids could be transferred between resistant and sensitive strains. When reserpine (30 µg/mL) and carbonyl cyanide m-chlorophenylhydrazone (CCCP) (50 µg/mL) were added in imipenem and meropenem, the MICs had no change against K. pneumoniae strains. These results suggest that both DHA-1 β-lactamase and loss or deficiency of porin OmpK36 may be the main reason for the cefoxitin and carbapenem resistance in K. pneumoniae strains in our hospital.

FUNDAMENTO: O Imatinib é um inibidor do receptor tirosina-quinase que foi confirmada como exercendo um efeito inibidor sobre a atividade do receptor do PDGF, fator de crescimento plaquetário (PDGFRα e PDGFRβ). OBJETIVO: Investigar o efeito protetor do Imatinib na fibrose miocárdica em acetato de deoxicorticosterona (DOCA)/ratos com hipertensão induzida por sal. MÉTODOS: Sessenta ratos Sprague-Dawley machos, uninefrectomizados foram distribuídos em três grupos: ratos controles (grupo CON): grupo deoxicorticosterona (grupo DOCA); grupo deoxicorticosterona e Imatinib (grupo DOCA IMA). A Pressão Arterial Sistólica (PAS) foi medida quinzenalmente. Foi estudada a porção apical do ventrículo esquerdo. Foram empregados: coloração vermelho sirius, coloração de hematoxilina-eosina, imuno-histoquímica e ensaio de western blot. RESULTADOS: A PAS nos grupos DOCA e IMA+DOCA foi maior que no grupo CON nos dias 14 e 28. Os animais do grupo DOCA apresentaram fibrose intersticial e perivascular grave no dia 28, e as expressões de PI, PIII, tenascina-C e fibronectina foram significativamente maiores que nos grupos DOCA+IMA e CON. Quando comparados com o grupo CON, os grupos DOCA e DOCA+IMA apresentaram resposta inflamatória de tecido miocárdico e infiltração de monócitos/macrófagos de diferentes graus. As expressões proteicas do PDGF-A, PDGF-C e PDGFRα foram significativamente maiores nos grupos DOCA e DOCA+IMA que no grupo CON, mas a expressão proteica do p-PDGFRα no grupo DOCA+IMA foi menor que no DOCA. CONCLUSÃO: O Imatinib pode exercer efeitos inibitórios sobre a fibrose miocárdica em ratos com hipertensão induzida por DOCA/sal, os quais podem ser atribuídos à inibição da atividade do PDGFR-α.

BACKGROUND: Imatinib is a tyrosine kinase receptor inhibitor that has been confirmed to exert inhibitory effect on the platelet derived growth factor PDGF receptor (PDGFRα and PDGFRβ) activity. OBJECTIVE: To investigate the protective effect of imatinib on the myocardial fibrosis in deoxycorticosterone-acetate (DOCA)/salt induced hypertensive rats. METHODS: Sixty male uninephrectomized Sprague-Dawley rats were assigned to three groups: control rats (CON group); deoxycorticosterone group (DOCA group); deoxycorticosterone and imatinib group (DOCA+IMA group). Systolic blood pressure (SBP) was measured biweekly. The apical portion of the left ventricle was studied. Sirius-Red staining, Hematoxylin-Eosin staining, immunohistochemistry and Western blot assay were employed. RESULTS: SBP in the DOCA group and DOCA+IMA group was higher than that in the CON group on day 14 and 28. Animals in the DOCA group showed severe interstitial and perivascular fibrosis on day 28, and the expressions of PI, PIII, tenascin-C and fibronectin were significantly higher than those in the DOCA+IMA group and CON group. When compared with the CON group, myocardial tissue inflammatory response and monocyte/macrophage infiltration of different degrees were observed in the DOCA group and DOCA+IMA group. Protein expressions of PDGF-A, PDGF-C and PDGFRα were signiflcantly higher in the DOCA and DOCA+IMA groups than those in the CON group, but the p-PDGFRα protein expression in the DOCA+IMA group was lower than that in the DOCA group. CONCLUSION: Imatinib can exert inhibitory effects on myocardial fibrosis in DOCA/salt induced hypertensive rats, which may be attributed to the inhibition of PDGFR-α activity.