Abstract Purpose This study employees cash flow rights and the contestability of multiple large shareholders to explore the impact of multiple large shareholders on investment efficiency in Chinese setting. Theoretical framework We introduce Asymmetric Information Theory and Theory of Principal and Agent o support our study. Design/methodology/approach Empirical study (including PSM method, IV method, threshold method and so on) is used in this study. Moreover, this paper selects the non-financial listed companies of A share enlisted in both the Shanghai and the Shenzhen Stock Markets from the period of 2007 to 2016 as the sample. Findings Our findings show a positive correlation between multiple large shareholders and absinvestment among Chinese listed firms. Practical & social implications of research Different from the previous views that multiple large shareholders have positive governance effects, we provide evidence that multiple large shareholders have negative governance effects. And we provide new evidence that controlling shareholders would collude with multiple large shareholders to seek for excess private benefits by enhancing enterprise absinvestment. Originality/value This study contributes to the literature in several important ways. First, it shows a positive correlation between multiple large shareholders and absinvestment, which extends the research of Jiang et al. (2018), which found that multiple large shareholders can profoundly enhance investment efficiency. Second, this paper is the first to introduce a threshold model to study the impact of controlling shareholders on the relation between multiple large shareholders and absinvestent, demonstrating that the positive relation between them is strengthened by promoting the governance effect of controlling shareholders. setting Designmethodologyapproach Design methodology approach including Moreover nonfinancial non financial 200 201 sample firms effects Originalityvalue Originality value ways First al 2018, 2018 , (2018) Second absinvestent 20 (2018 2 (201 (20 (2 (

ABSTRACT Dwarf mutants are valuable materials for investigating plant gene function and developing new crop varieties. In the present study, dwarf mutant (D-CK) and wild-type (W-CK) Sophora davidii (Franch.) Skeels plants foliarly sprayed with distilled water were used as controls, and dwarf mutants were treated with different concentrations of gibberellin A3 (GA3; 20, 40 and 60 mg L-1), brassinosteroid (BR; 12.5, 25 and 50 mg L-1); and auxin indole-3-acetic acid (IAA; 12.5, 25 and 50 mg L-1) to study the changes in plant height at 20, 40 and 60 d after exogenous hormone spraying. The changes in endogenous contents of IAA, GA3, BR, abscisic acid (ABA), jasmonic acid (JA), and salicylic acid (SA) and IAA:ABA ratio in the dwarf mutant plants were also measured at 20, 40 and 60 d after exogenous hormone application. The dwarf mutants reverted to the W-CK height phenotype after 60 d of exogenous spraying with different concentrations of GA3 and BR (except 50 mg·L-1), but after exogenous spraying with IAA, dwarf mutants did not revert to the W-CK height phenotype. Compared with D-CK plants, endogenous GA3, BR and IAA contents in dwarf mutant plants increased to some extent with exogenous spraying of GA3, BR and IAA. The results indicated that exogenous spraying of different concentrations of GA3 and BR regulated S. davidii plant height by promoting the secretion of endogenous GA3, BR, IAA and SA and inhibiting endogenous ABA secretion in dwarf mutant. The height of mutants was sensitive to exogenous GA3 and BR but not to exogenous IAA.

ABSTRACT Objective: The tyrosine-protein kinase inhibitor, genistein, can inhibit cell malignant transformation and has an antitumor effect on various types of cancer. It has been shown that both genistein and KNCK9 can inhibit colon cancer. This research aimed to investigate the suppressive effects of genistein on colon cancer cells and the association between the application of genistein and KCNK9 expression level. Methods: The Cancer Genome Atlas (TCGA) database was used to study the correlation between the KCNK9 expression level and the prognosis of colon cancer patients. HT29 and SW480 colon cancer cell lines were cultured to examine the inhibitory effects of KCNK9 and genistein on colon cancer in vitro, and a mouse model of colon cancer with liver metastasis was established to verify the inhibitory effect of genistein in vivo. Results: KCNK9 was overexpressed in colon cancer cells and was associated with a shorter Overall Survival (OS), a shorter Disease-Specific Survival (DFS), and a shorter Progression-Free Interval (PFI) of colon cancer patients. In vitro experiments showed that downregulation of KCNK9 or genistein application could suppress cell proliferation, migration, and invasion abilities, induce cell cycle quiescence, promote cell apoptosis, and reduce epithelialmesenchymal transition of the colon cancer cell line. In vivo experiments revealed that silencing of KCNK9 or application of genistein could inhibit hepatic metastasis from colon cancer. Additionally, genistein could inhibit KCNK9 expression, thereby attenuating Wnt/β-catenin signaling pathway. Conclusion: Genistein inhibited the occurrence and progression of colon cancer through Wnt/β-catenin signaling pathway that could be mediated by KCNK9. Objective tyrosineprotein tyrosine protein inhibitor KNCK KCNK Methods TCGA (TCGA patients HT HT2 SW SW48 Results OS, OS , (OS) DiseaseSpecific Disease Specific DFS, DFS (DFS) ProgressionFree Progression Free PFI (PFI proliferation migration abilities quiescence apoptosis line Additionally Wnt/βcatenin Wntβcatenin Wnt/β catenin Wnt β Conclusion SW4 (OS (DFS βcatenin Wntβ

Abstract The effects of optimization of microwave-assisted extraction (MAE) and microencapsulation on the total xanthone content (TXC), total phenolic content (TPC), and antioxidant activity of mangosteen rind extract were studied. Response surface methodology (RSM) was employed with Box-Behnken design to generate fifteen optimization responses by incorporating three independent variables, namely soaking time, solvent-to-feed (S/F) ratio and extraction time. The highest extraction yield (19.43%) was obtained in the third response. TXC and TPC results fitted well, with high R-squared values (0.83-0.91), into the generated models, but not the antioxidant activity data. The interactive effects of S/F ratio and extraction time significantly increased the yields of TXC (46.62 mg α-mangostin/g crude extract) and TPC (46.30 mg gallic acid equivalent/g crude extract), but longer soaking time showed adverse effect. All the results obtained from the optimized models were validated using experimental data which showed desirability index of 0.88. The optimized parameters of MAE were established as 20:1 S/F ratio and 9 min extraction time, without soaking process. Despite the intact morphology of microcapsules observed, spray drying microencapsulation only preserved TXC partially (63.54%) but denatured more than 85% of TPC. Future investigation on the microencapsulation of mangosteen rind extract is required.

Resumo A autofagia desempenha um papel importante na manutenção da homeostase celular através da degradação de proteínas desnaturadas e outras macromoléculas biológicas. Nos últimos anos, muitos pesquisadores se concentraram no mecanismo da autofagia em parasitas apicomplexos, mas pouco se sabe sobre esse processo na coccidia aviária. No presente estudo, a clonagem, sequenciamento e caracterização de gene relacionado à autofagia Etatg8 foram investigados pela PCR quantitativa em tempo real (RT-qPCR), mancha ocidental (WB), ensaios indiretos de imunofluorescência (IFAs) e microscopia eletrônica de transmissão (TEM), respectivamente. Os resultados mostraram que o gene Etatg8 de E. tenella possui uma ORF de 375 bp, codificando uma proteína de 124 aminoácidos com estrutura e propriedades semelhantes à de outros apicomplexos. RT-qPCR revelou que Etatg8 é expresso durante os quatro estágios de desenvolvimento de E. tenella. Entretanto, seus níveis transcricionais foram significativamente mais elevados na fase de oocisto não esporulados. Os ensaios de manchas ocidental (WB) e de imunofluorescência (IFA) mostraram que a proteína EtATG8 foi lipidada para ligar-se à membrana do autofagossomo sob condições de deficiência nutritiva (em presença de rapamicina) e se agregar no citoplasma de esporozoítas e merozoítas. No entanto, o processo de produção de membrana do autofagossomo pode ser inibido por um inibidor de autofagia (3-meetiladeninatiladenina, 3-MA). Em conclusão, foi demonstrado que E. tenella tem um mecanismo de autofagia conservado, semelhante ao de outros parasitas apicomplexos, e que EtATG8 pode ser usado como um marcador para futuras pesquisas sobre autofagia direcionada à coccidiose aviária.

Abstract Autophagy plays an important role in maintaining cell homeostasis through degradation of denatured proteins and other biological macromolecules. In recent years, many researchers focus on mechanism of autophagy in apicomplexan parasites, but little was known about this process in avian coccidia. In our present study. The cloning, sequencing and characterization of autophagy-related gene (Etatg8) were investigated by quantitative real-time PCR (RT-qPCR), western blotting (WB), indirect immunofluorescence assays (IFAs) and transmission electron microscopy (TEM), respectively. The results have shown 375-bp ORF of Etatg8, encoding a protein of 124 amino acids in E. tenella, the protein structure and properties are similar to other apicomplexan parasites. RT-qPCR revealed Etatg8 gene expression during four developmental stages in E. tenella, but their transcriptional levels were significantly higher at the unsporulated oocysts stage. WB and IFA showed that EtATG8 was lipidated to bind the autophagosome membrane under starvation or rapamycin conditions, and aggregated in the cytoplasm of sporozoites and merozoites, however, the process of autophagosome membrane production can be inhibited by 3-methyladenine. In conclusion, we found that E. tenella has a conserved autophagy mechanism like other apicomplexan parasites, and EtATG8 can be used as a marker for future research on autophagy targeting avian coccidia.

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China and has spread rapidly worldwide. We present a mild SARS-CoV-2 infection in a baby with non-productive cough and normal chest computed tomography, in whom only anal swabs tested positive by real-time PCR testing for SARS-CoV-2. She was given atomization inhalation therapy with recombinant human interferon alfa-1b for 10 days. Her anal swabs remained positive for eight days, whereas her throat swabs were persistently negative by real-time PCR testing. Mild and asymptomatic cases, especially in children, might present with PCR negative pharyngeal/nasal swabs and PCR positive anal swabs. Those patients are potential sources of infection via fecal-oral transmission for COVID-19.

RESUMO OBJETIVO Investigar a eficácia clínica e os possíveis mecanismos da saxagliptina no tratamento do diabetes mellitus tipo 2 (DM2) associado à doença hepática gordurosa não alcoólica (DHGNA). MÉTODOS Um total de 95 DM2 combinados com pacientes com DHGNA foram aleatoriamente divididos em grupo A (grupo saxagliptina), grupo B (grupo glimepirida) e grupo C (glimepirida combinado com grupo fosfatidilcolina polienizada). RESULTADOS Após a intervenção tratamento por 24 w, índice de massa corporal (IMC), relação cintura-quadril (RCQ), hemoglobina glicada (HbA1c), glicemia de jejum (FPG), insulina de jejum (Fins), avaliação do modelo homeostático de insulina resistência (Homa-IR), interleucina-6 (IL-6), triglicérides (TG), colesterol total (CT), alanina aminotransferase (ALT), aspartato aminotransferase (AST), γ-glutamiltransferase (γ-GT) e detecção de esteatose hepática dos sujeitos do estudo foram observados. Ação de esteatose hepática de indivíduos nos grupos A e C foram significativamente diferentes do grupo B; no entanto, não houve diferenças entre os grupos A e C. Os grupos Fins, Homa-IR e IL-6 dos participantes do grupo A foram menores que os dos grupos B e C; no entanto, não houve diferenças significativas entre os dois últimos grupos. CONCLUSÃO Para o DM2 combinado com pacientes com DHGNA, o tratamento com saxagliptina pode não apenas controlar efetivamente a glicemia, mas também atenuar a resistência à insulina e a lesão inflamatória do fígado para melhorar ainda mais o fígado gorduroso.

SUMMARY OBJECTIVE To investigate the clinical efficacy and the possible mechanisms of saxagliptin in the treatment of type 2 diabetes mellitus (T2DM) combined with non-alcoholic fatty liver disease (NAFLD). METHODS A total of 95 T2DM and NAFLD patients were randomly divided into group A (saxagliptin group), group B (glimepiride group), and group C (glimepiride combined with polyene phosphatidylcholine group). RESULTS After intervention treatment for 24 w, body mass index (BMI), waist-to-hip ratio (WHR), glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), interleukin-6 (IL-6), triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), and quantitative detection of liver steatosis of study subjects were observed, the action of liver steatosis in subjects of groups A and C were significantly different from those of group B; however, there were no differences between groups A and C. The FINS, HOMA-IR, and IL-6 of subjects in group A was lower than those in groups B and C; however, there were no significant differences between the latter two groups. CONCLUSION For T2DM combined with NAFLD patients, the saxagliptin treatment could not only effectively control blood glucose but also attenuate insulin resistance and inflammatory injury of the liver to improve fatty liver further.

Abstract The spin Hamiltonian parameters (SHPs) (g factors and zero-field splittings (ZFSs) D and E) and the local structure for Cr3+ in K2PdCl4 single crystal are theoretically investigated from the perturbation calculations of the SHPs for an orthorhombically distorted octahedral 3d3 cluster. The impurity Cr3+ is found not to occupy the conventional square planar Pd2+ site but to locate at the octahedral K+ site, associated with the relative axial compression ratio ρ( ≈ 11.1%) and the perpendicular bond length variation ratio τ( ≈ 11.7%). The impurity centre exhibits much smaller axial compression distortion and much larger perpendicular orthorhombic distortion than the host K+ site in K2PdCl4 ρ H ≈ 18.6% and τ H ≈ 0) and hence a more regular ligand octahedron, corresponding to the very small ZFSs. The contributions to g-shifts Δ g C T from the CT mechanism are opposite in sign and twenty-one times larger in magnitude compared with Δ g C F from the CF mechanism. For the ZFSs, the CT contributions DCT and ECT are opposite in sign and almost the same in magnitude with respect to the corresponding DCF and ECF.

Abstract Pegylated liposomal doxorubicin is an important antineoplastic agent with activity in a variety of solid tumors. It has a totally different profile of pharmacokinetics and toxicity compared with doxorubicin. It rarely causes side-effects like cardiotoxicity or hair loss, but frequently results in many kinds of mucocutaneous reactions, including palmar-plantar erythrodysesthesia, diffuse follicular rash, intertrigo-like eruption, new formation of melanotic macules, stomatitis and radiation recall dermatitis. We present a rare case of multiple myeloma who immediately developed serious stomatitis and esophatitis associated with minor palmar-plantar erythrodysesthesia after a single course of pegylated liposomal doxorubicin.

Immunoglobulin light chain amyloidosis is the most common acquired systemic amyloidosis. Its presentation is often insidious and progressive, which may delay diagnosis. The authors describe a rare case of immunoglobulin light chain amyloidosis in a 34-year-old man with scleroderma-like manifestation substantiated by multifarious laboratory investigations and the histopathologic feature of involved skin lesions stained with Congo red and crystal violet. This helps to maintain a high clinical suspicion of the disease when confronting similar skin presentation.

OBJECTIVES:Our study aimed to investigate the impact of fatigue on the severity of stroke and to explore the underlying mechanisms.METHODS:Fatigued male rats underwent middle cerebral artery occlusion and the infarcted brain area was determined. Then, coagulation parameters were assessed in the fatigued group and a control group. In addition, the level of fibrinogen was determined in rats deprived of sleep for various numbers of days. To study whether interleukin-6 was involved in fibrinogen synthesis during fatigue, we also measured levels of interleukin-6 in rats deprived of sleep for various numbers of days. Furthermore, brain injury by middle cerebral artery occlusion was measured in wild-type mice, interleukin-6-/- mice and wild-type mice treated with bezafibrate.RESULTS:More severe cerebral infarction was observed in the fatigued rats, resulting in an infarct ratio of 23.4%. The infarct ratio was significantly increased in the fatigued rats compared with that in the control group (8%, p<0.05). The level of fibrinogen was increased significantly in the fatigued rats compared with that in the control group. In addition, a marked reduction in fibrinogen level was observed in the fatigued interleukin-6-/- mice compared to their wild-type counterparts, whereas no difference was observed between fatigued wild-type mice and interleukin-6-/- rats treated with recombinant human interleukin-6. The reduction in brain injury due to middle cerebral artery occlusion during fatigue was observed in interleukin-6-/- mice and wild-type mice treated with bezafibrate.CONCLUSION:Fatigue could increase stroke severity and was associated with the interleukin-6-induced expression of fibrinogen.

The anti-tumor effect of R-Phycoerythrin (R-PE) from Porphyra haitanensis was studied using cell line HeLa as an in vitro model and Sarcoma-180 (S180) tumor-bearing mice as an in vivo model. The results showed that the combination treatment of R-PE and photodynamic therapy PDT) significantly inhibited the growth of HeLa cells up to 81.5%, with a fair dose-effect relationship, but did not inhibit endothelial cells. The annexin v-fitc/PI fluorescence staining experiments demonstrated that at doses between 0~60µg/mL, apoptosis cells and later stage apoptosis cells or necrosis cells increased significantly as the R-PE dosage increased. DNA electrophoresis showed that after R-PE+PDT treatment of HeLa cells for 24 hours, a light "smear" band between 100~400bp appeared to indicate the degradation of genomic DNA. The QRT-PCR results showed that R-PE+PDT treatment increased caspase-3 and caspase-10 gene expression and decreased the Bcl-2 gene expression level significantly as the R-PE dose increased, implying that R-PE promoted HeLa cell apoptosis. Compared with untreated S180 tumor-bearing mice, R-PE injection significantly inhibited the growth of S180 in tumor-bearing mice up to 41.3% at a dose of 300mg-kg-1. Simultaneously, the significant increase of superoxide dismutase (SOD) activity in serum (p < 0.01) and the decrease of the malondialdehyde (MDA) level in liver suggests that R-PE improved the anti-oxidant ability of the S180 tumor-bearing mice, which may related to its antitumor effect. In addition, the R-PE caused a significant increase (p < 0.05) in the spleen index and thymus index, and a significant increase (p < 0.01) in lymphocyte proliferation, NK cell kill activity and the TNF-α level in the serum of S180 tumor-bearing mice. These results strongly suggest that the antitumor effect of R-PE from Porphyra haitanensis functioned by increasing the immunity and antioxidant ability of S180 tumor-bearing mice, promoting apoptosis by increasing protease gene expression and TNF-α secretion.

YKL-40 has been identified as a growth factor in connective tissue cells and also a migration factor in vascular smooth muscle cells. To a large extent, the increase of serum YKL-40 is attributed to liver fibrosis and asthma. However, the relationship of the expression and clinical/prognostic significance of YKL-40 to the splenomegaly of patients with portal hypertension is unclear. In the present study, the expression of YKL-40 was studied by immunohistochemistry in 48 splenomegaly tissue samples from patients with portal hypertension and in 14 normal spleen specimens. All specimens were quickly stored at -80°C after resection. Primary antibodies YKL-40 (1:150 dilution, rabbit polyclonal IgG) and MMP-9 (1:200 dilution, rabbit monoclonal IgG) and antirabbit immunoglobulins (HRP K4010) were used in this study. The relationship of clinicopathologic features with YKL-40 is presented. The expression of YKL-40 indicated by increased immunochemical reactivity was significantly up-regulated in splenomegaly tissues compared to normal spleen tissues. Overexpression of YKL-40 was found in 68.8% of splenomegaly tissues and was significantly associated with Child-Pugh classification (P = 0.000), free portal pressure (correlation coefficient = 0.499, P < 0.01) and spleen fibrosis (correlation coefficient = 0.857, P < 0.01). Further study showed a significant correlation between YKL-40 and MMP-9 (correlation coefficient = -0.839, P < 0.01), indicating that YKL-40 might be an accelerator of spleen tissue remodeling by inhibiting the expression of MMP-9. In conclusion, YKL-40 is an important factor involved in the remodeling of spleen tissue of portal hypertension patients and can be used as a therapeutic target for splenomegaly.

The present study was conducted to obtain reference values for brachial-ankle pulse wave velocity (baPWV) and to evaluate influencing factors of baPWV according to gender. Using automatic devices, baPWV was measured simultaneously in 2095 subjects. A total of 647 healthy subjects, none of whom presented atherosclerotic risk factors, were analyzed in the present study. Two different statistical methods were used to obtain reference values for baPWV according to subject gender and age. The association between baPWV value and gender, as well as other features, were analyzed. For male subjects, multiple stepwise analysis showed that age, systolic blood pressure (SBP), heart rate (HR), and plasma levels of triglycerides (TG) were independent predictors of baPWV. For female subjects, age, SBP, HR, and plasma levels of uric acid (UA) were independent predictors of baPWV. In male subjects, the upper limits of baPWV values were 1497.43/1425.00, 1518.67/1513.25, 1715.97/1726.50, 1925.20/1971.90, and 2310.18/2115.00 cm/s, obtained using two different statistical methods for the age ranges of 30-39, 40-49, 50-59, 60-69, and 70 and older, respectively. For females, the upper limits of baPWV values were 1426.70/1411.13, 1559.15/1498.95, 1733.50/1739.00, 1958.63/1973.78, and 2720.80/2577.00 cm/s for the age ranges of 30-39, 40-49, 50-59, 60-69, and 70 and older, respectively. Aging is the most important influencing factor for baPWV value and its effect is more prominent in females. The reference values of baPWV according to age and gender may be useful for the clinical diagnosis and preventive therapy of cardiovascular diseases.

Derivados de óleo pesado (temperatura de destilação: 320-340 ºC), obtidos a partir do processo de liquefação direta do carvão, usando carvão Shengli foram tratados com hidrogênio usando catalisadores sulfetados Ni-Mo/Al2O3, Ni-W/Al2O3 e Ni-W/SiO2 respectivamente. Os catalisadores sulfetados foram caracterizados por BET, XRD, H2-TPR e NH3-TPD, respectivamente. As avaliações das propriedades de hidrodenitrogenação (HDN) e hidrodearomatização (HDA) do óleo pesado nos três catalisadores foram realizadas a 400 ºC e 5,0 MPa de pressão inicial de H2. Os catalisadores contendo W mostraram melhores desempenhos do que os catalisadores de Mo para as reações de HDN e HDA. Os catalisadores suportados em Al2O3 apresentaram maior atividade catalítica do que aqueles suportados em SiO2. As atividades dos catalisadores sulfetados foram associadas principalmente à natureza dos sítios ativos, acidez, tamanho do cristalito e da quantidade de espécies redutíveis de enxofre do sulfeto metálico

Heavy oil (distillation temperature: 320-340 ºC) derived from the direct coal liquefaction process using Shengli coal were hydrotreated using sulfided Ni-Mo/Al2O3, Ni-W/Al2O3, and Ni-W/SiO2 catalysts respectively. The sulfided catalysts were characterized by BET, XRD, H2-TPR and NH3-TPD respectively. The evaluations of the hydrodenitrogenation (HDN) and hydrodearomatization (HDA) properties of heavy oil on the three catalysts were carried out at 400 ºC and 5.0 MPa initial H2 pressure. The W-based catalysts displayed better performances than Mo-based catalysts for the HDN and HDA reactions. Al2O3 supported catalysts were found to have higher catalytic activities than on SiO2 supported ones. The activities of sulfided catalysts were associated mainly with the nature of active sites, acidity, metal sulfide crystallite size and the amount of the reducible sulfur species of metal sulfide.