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Malignant glioma is an often fatal type of cancer. Elevated expression of the orphan nuclear receptor estrogen-related receptor alpha (ERRα) is an unfavorable factor for malignant progression and poor prognosis in several cancers, although the mechanism by which this receptor affects the pathophysiology of cancers remains obscure. However, few studies have been conducted in regard to the role of ERRα in glioma. In the current study, we found that elevated expression of ERRα was observed in 107 glioma cases by means of IHC. Clinically, high expression of ERRα was associated with later stages of disease progression and clinical outcome of patients with glioma. ERRα had the ability to promote cell proliferation and migration in glioma cell lines. Moreover, in a xenograft model, we also found that silencing ERRα had an inhibitory effect on the growth of glioma. Further investigation confirmed that ERRα was involved in the carcinogenesis of glioma via the regulation of the Wnt5a signal pathway in vitro and in vivo. Our study was first to show the overexpression of ERRα in glioma tissues and a direct correlation between ERRα expression and clinical prognosis of glioma. Together, these data reveal that ERRα has prognostic significance in glioma, and targeting ERRα may provide a reliable therapeutic strategy for the treatment for human glioma.

Supplementary Figure S1: ERRα expression was regulated by shERRα/lenti-ERRα in U87MG and U251; Supplementary Figure S2: There is a correlation between inhibition rates of XCT790 (5, 10 μM) and ERRα expression levels: Supplementary Figure S3: ERRα overexpression promoted the glioma cell growth in BrdU incorporation; Supplementary Figure S4: ERRα knockdown inhibited glioma growth in vivo; Table S1 shows pathological information of 107 glioma patients; Supplementary Table S2: ERRα expression was significantly high as the glioma pathological grade was increased; Table S3 shows the primer sequences of ERRα and wnt genes; Table S4 shows primers used for detecting putative ERREs.

Camellia perpetua is a rare and unique species in the karst regions in Guangxi of south China, it is a rare camellia group that blooms almost all year round and its peak flowering period is in summer. To understand the rhythm of nectar secretion and the pattern of pollination of this species in different seasons, and exploring the influence of composition and amount of nectar on the behavior of its pollinator species. The average amount of nectar a single flower of C. perpetua was 129.14 ± 4.48 μL in the summer and sugar concentration was 25.77 ± 5.94%, which was 453.66 ± 4.67 μL and 25.77 ± 5.94% in winter, respectively. The rhythm of nectar secretion showed that less nectar was secreted during the day, much more nectar was secreted during the evening and night. The nectar was sucrose dominant in summer and winter, and composed mainly of sucrose, glucose and fructose. There were 18 types of amino acids in C. perpetua in summer, with a total of 1,317 ± 23.68 μg·mL-1, and 9 types of amino acids in winter, with a total of 530 ± 15.96 μg·mL-1. The bee pollinators visited the flowers more frequently in the summer than in the winter, while the birds visited the flowers more frequently in the winter. The change of pollinators’ adaptive behavior may be related to nectar production, sugar concentration and amino acid type and content in different seasons.

Mycorrhizal fungi plays important roles in the seed germination and subsequent growth of orchids. The research of fungi in orchid roots, especially dominant mycorrhizal fungi is critical for orchids protection. In this study, the fungal community and composition of mycorrhizal fungi in roots, rhizomes and rhizosphere soil of Bulbophyllum tianguii grown in three terrestrial environments were analyzed by the second generation sequencing technology. The results of OTU clustering and α and β diversity analysis showed that there were significant differences in fungal communities in roots, rhizomes and rhizosphere soil of B. tianguii. The total number of OTUs in rhizomes was much less than that in roots and rhizosphere soil. The number of OTUs in rhizosphere soil and the diversity of mycorrhizal fungi were the highest. Meanwhile, the species and abundance of mycorrhizal fungi in roots and rhizomes of B. tianguii were different from those in rhizosphere soil. For different elevations, compared with B. tianguii that grow in middle of Tiankeng and top of Tiankeng, the OTUs number of B. tianguii in orchid garden is richest, and the diversity of mycorrhizal fungi in orchid garden was significantly higher than other locations. Among the three different habitats of B. tianguii, the number of OTUs in humus soil and stone habitats was notably higher than tree habitats, and the diversity of mycorrhizal fungi in humus soil was the highest. The analysis of mycorrhizal fungi in different habitats and altitudes of B. tianguii showed that Sebacina and Exophiala were the dominant mycorrhizal fungi in B. tianguii. The results of species annotation, phylogenetic tree and co-occurrence network analysis showed the dominant mycorrhizal fungi of B. tianguii mainly included Sebacina, Cladosporium, Exophiala, Fusarium. This study reveals the symbiotic relationship between Sebacina, Exophiala, Cladosporium and the B. Tianguii. It will provide a theoretical basis for the protection and biological function study of B. Tianguii.

Backgroud: Flowering at the right time is a very important factor affecting the stable annual yield of longan. However, a lack of knowledge of the regulatory mechanism and key genes of longan flowering restricts the healthy development of the longan industry. Therefore, identifying the relevant genes and analyzing their regulatory mechanism are essential for scientific research and the development of the longan industry. Here, we isolated a LEAFY homologue gene from longan, DlLFY, and identified its function. Results: DlLFY contains a 1167 bp open reading frame and encodes 388 amino acids. The amino acid sequence has a typical LFY/FLO family domain. DlLFY was expressed in all the tested tissues, expect for leaf, pericarp, and ulp, with the highest expression occurring in flower buds. The expression of DlLFY was significant upregulated at the early flower induction stage in “SX” (“Shixia”). The results of subcellular localization and transactivation analysis show that DlLFY is a kind of typical transcript factor with transcriptional activator. Moreover, overexpression of DlLFY in Arabidopsis promoted early flowering and restrained growth, resulting in reduced plant height and number and area of rosette leaves of transgenic plants. DNA affinity purification sequencing (DAP-Seq) analysis showed that 13 flower-related genes corresponding to five homologous genes of Arabidopsis may be the binding sites and putative target genes. Among these five flower-related genes, only AtTFL1 was strongly inhibited in transgenic lines. Conclusion: Taken together, these results indicate that DlLFY plays a pivotal role in controlling longan flowering, possibly by negatively regulating TFL1.

BackgroundRadiotherapy plays an important effect on the standard therapy of esophageal squamous cell carcinoma (ESCC). However, the efficacy of the therapy is limited and a few patients do not achieve satisfactory treatment results due to the existence of radiation resistance. Therefore, it is necessary to identify the potential predictive biomarkers and treatment targets for ESCC.MethodsWe performed the whole-exome sequencing to determine the germline and somatic mutations in ESCC. Functional enrichment and pathway-based protein-protein interaction analyses were used to ascertain potential regulatory networks. Cell survival and cell death after treatment with radiotherapy were determined by CCK-8 and LDH release assays in ESCC cells. The correlations of NOTCH1 and tumor immune infiltration were also analyzed in ESCC.ResultsOur results showed that 344 somatic and 65 germline differentially mutated genes were detected to be radiosensitivity-related loci. The tumor mutational burdens (TMB) or microsatellite instability (MSI) were not significantly correlated with the response to radiotherapy in ESCC patients. Pathway-based protein-protein interaction analyses implied several hub genes with most nodes (such as PIK3CA, NOTCH1, STAT3 and KDR). The in vitro studies showed that the knockdown of NOTCH1 inhibited cell survival and rendered more cell death after the treatment with radiotherapy in ESCC cells, while NOTCH1 overexpression had the opposite effects. Moreover, NOTCH1, frequently up-regulated in ESCC, was negatively correlated with activated B cell and immature dendritic cell in ESCC. High expression of NOTCH1 was accompanied with the low levels of some immunotherapy-related cells, including CD8(+) T cells and NK cells.ConclusionsThese results indicate the differences of the germline mutations and somatic mutations between the radiosensitive and radioresistence groups in ESCC and imply that NOTCH1 plays important roles in regulating the radiosensitivity of ESCC. The findings might provide the biomarkers and potential treatment targets for improving the sensitivity to radiotherapy in ESCC.

The role of hypoxia-regulated long non-coding RNA (lncRNA) in the development of head and neck squamous cell carcinoma (HNSCC) remains to be elucidated. In the current study, we initially screened hypoxia-regulated lncRNA in HNSCC cells by RNA-seq, before focusing on the rarely annotated lncRNA USP2 antisense RNA 1 (USP2-AS1). We determined that USP2-AS1 is a direct target of HIF1α and is remarkably elevated in HNSCC compared with matched normal tissues. Patients with a higher level of USP2-AS1 suffered a poor prognosis. Next, loss- and gain-of-function assays revealed that USP2-AS1 promoted cell proliferation and invasion in vitro and in vivo. Mechanically, RNA pulldown and LC–MS/MS demonstrated that the E3 ligase DDB1- and CUL4-associated factor 13 (DCAF13) is one of the binding partners to USP2-AS1 in HNSCC cells. In addition, we assumed that USP2-AS1 regulates the activity of DCAF13 by targeting its substrate ATR. Moreover, the knockdown of DCAF13 restored the elevated cell proliferation and growth levels achieved by USP2-AS1 overexpression. Altogether, we found that lncRNA USP2-AS1 functions as a HIF1α-regulated oncogenic lncRNA and promotes HNSCC cell proliferation and growth by interacting and modulating the activity of DCAF13.

This paper attempts to use nonlinear differential equations as a research model. The purpose of this paper is to analyze the risk of financial management. This paper uses the chaos theory of a general nonlinear system to study the differential relationship of financial trouble. We use them to research and solve the management problems of the economic system. Then, this paper proposes a model related to the evolution of the economic system and the prediction of financial and financial risks. The research results show that the method proposed in this paper can realize the synchronization and balance point control of general economic chaotic systems.

Mycorrhizal fungi plays important roles in the seed germination and subsequent growth of orchids. The research of fungi in orchid roots, especially dominant mycorrhizal fungi is critical for orchids protection. In this study, the fungal community and composition of mycorrhizal fungi in roots, rhizomes and rhizosphere soil of

Golden Camellia species are highly specific to certain soil environments. Most species are only native to calcareous soils in karst regions, except for a few that grow only in acidic soils. Our aim is to elucidate the adaptation mechanisms of the species of calcareous-soil golden Camellia (CSC) and acidic-soil golden Camellia (ASC) to habitat soils through plant–soil nutrient characteristics and their relationships. We investigated 30 indices for soils and plants. Compared with ASC, CSC had more fertile soil, while their plant tissues exhibited stronger Ca, P, and Mn and weaker K storage, which may be important mechanisms for adapting to habitat soils. However, ASC showed a higher biological absorption coefficient (BAC) for nutrients, which may contribute to the adaptation of ASC to relatively barren acidic soils. Both CSC and ASC showed much higher BAC and accumulation of Ca than other nutrients. We also found that the concentrations of nutrients in the different tissues varied considerably between species. Correlation analysis revealed 135 significant relationships between the 30 indices, with the soil pH and soil Ca levels being the most important factors influencing the nutrient uptake network. This information helps in understanding the adaptation mechanisms of karst plants to habitat soils.

We study the post -2000 productivity slowdown in Canada. Due to data limitation, the causes of the slowdown have not been studied systematically. Unlike most previous studies that focus directly on the actual productivity, in this paper we decompose the actual productivity into two components: technological frontier and technical efficiency. Technological frontier measures the maximum level of productivity potential related to firm-specific technology development while technical efficiency reflects the ability/technique in achieving the potential. Using a constructed rich micro data, we find that Canada's productivity slowdown cannot be largely explained by factors such as R&D, ICTs and intangibles that are considered to be important to productivity. Instead, we show that the productivity slowdown in Canada was mainly due to the retreat of aggregate technological frontier, driven by large and high-productivity firms.

Compared to other G7 countries, Canada performed relatively well after the global financial crisis in both aggregate labour productivity and multifactor productivity (MFP) growth, which is in sharp contrast to its relatively weak performance in the 2000s. The objective of this article is to analyse the sources of Canada’s superior performance by comparing it to other G7 countries. In particular, the article examines industry productivity performance, estimates the contribution of individual industries to both aggregate labour productivity and MFP growth, and highlights the differences between Canada and other G7 countries before and after 2010. To this end, this article develops a methodology to more precisely identify the underlying forces at the industry level that have either propelled or hindered productivity growth, and thereby identify which industries have been at the heart of the changes in productivity performance.

The superior productivity performance of outward foreign direct investment (FDI) firms is attributable to both ex ante advantages gained within the home market and ex post learning, which emanates from MNE experiences in host markets. Learning is modeled as a function of firm-level R&D efforts, absorptive capacity, and host-country characteristics. Using a firm-level panel database on all firms in Canada, a large-scale econometric analysis is undertaken to show that the host-country environment is central to MNE learning. We also quantify results in the extant literature on the share of the superior productivity exhibited by FDI firms into that which emanates from the home market, and that which is linked to ex post learning, finding 79% attributable to the selection effect, and 21% to the learning effect. The implications of these results are that, since productivity is endogenous to FDI, firms which are below a threshold level required to be successful internationally ex ante can nevertheless succeed if learning can move these MNEs above the required threshold for success ex post. As such, this research provides insights into strategies and host-country environments which lead to ex post productivity improvements for firms undertaking outward FDI, and hence informs the FDI decision at the firm level.

There have been strong evidence showing a declining trend of firm dynamism in many other OECD countries over the last three decades. However, so far there has no compelling evidence that points to ...

In this study, sweet-potato-vine-based porous carbon (SPVPC) was prepared using zinc chloride as an activating and pore-forming agent. The optimised SPVPC exhibited abundant porous structures with a high specific surface area of 1397.8 m2 g−1. Moreover, SPVPC exhibited excellent adsorption characteristics for removing methylene blue (MB) from aqueous solutions. The maximum adsorption capacity for MB reached 653.6 mg g−1, and the reusability was satisfactory. The adsorption kinetics and isotherm were in good agreement with the pseudo-second-order kinetics and Langmuir models, respectively. The adsorption mechanism was summarised as the synergistic effects of the hierarchically porous structures in SPVPC and various interactions between SPVPC and MB. Considering its low cost and excellent adsorption performance, the prepared porous carbon is a promising adsorbent candidate for dye wastewater treatment.

In this study, the effects of bagging treatment on fruit appearance and internal quality, including fruit shape index, single fruit weight, fruit vitamin C, soluble solids, titratable acid, chlorophyll and carotenoid content, were studied by using ‘Donghong’ kiwifruit as experimental material. Meanwhile, the pesticide residues of bagged and non-bagged (NB) kiwifruit were compared and analyzed. Results showed that the pericarp color of bagged kiwifruit is lighter in green than that of NB group, with uniform color, cleaner appearance and no scabs and spots. Single fruit weight and transverse meridians of bagged kiwifruits were significantly increased. Interestingly, we found single bagging treatment had little effect on the internal quality of ‘Donghong’ kiwifruit. After pesticide treatment, the fruit shape of kiwifruit was rounder, significantly increased the weight, chlorophyll content of fruit, and decreased the content of vitamin C and carotenoids. In addition, bagging + pesticide treatment had additive effect on these characters. After bagging, the residues of pyraclostrobin and β-cypermethrin in ‘Donghong’ kiwifruit were significantly lower than those in the control. However, the residue of difenoconazole residues did not show significant difference. Bagging treatment has the ability to improve the appearance and reduce the residue of some pesticides. Meanwhile, the application of some pesticides can improve the single fruit weight and fruit quality. Therefore, bagging is a scientific and effective cultivation method in the green production of ‘Donghong’ kiwifruit.

Ginger (Zingiber officinale), the type species of Zingiberaceae, is one of the most widespread medicinal plants and spices. Here, we report a high-quality, chromosome-scale reference genome of ginger 'Zhugen', a traditionally cultivated ginger in Southwest China used as a fresh vegetable, assembled from PacBio long reads, Illumina short reads, and high-throughput chromosome conformation capture (Hi-C) reads. The ginger genome was phased into two haplotypes, haplotype 1 (1.53 Gb with a contig N50 of 4.68 M) and haplotype 0 (1.51 Gb with a contig N50 of 5.28 M). Homologous ginger chromosomes maintained excellent gene pair collinearity. In 17,226 pairs of allelic genes, 11.9% exhibited differential expression between alleles. Based on the results of ginger genome sequencing, transcriptome analysis, and metabolomic analysis, we proposed a backbone biosynthetic pathway of gingerol analogs, which consists of 12 enzymatic gene families, PAL, C4H, 4CL, CST, C3'H, C3OMT, CCOMT, CSE, PKS, AOR, DHN, and DHT. These analyses also identified the likely transcription factor networks that regulate the synthesis of gingerol analogs. Overall, this study serves as an excellent resource for further research on ginger biology and breeding, lays a foundation for a better understanding of ginger evolution, and presents an intact biosynthetic pathway for species-specific gingerol biosynthesis.

Diabetic cardiomyopathy can cause cardiac dysfunction and eventually lead to heart failure and sudden death. Long noncoding RNA (lncRNA) Gas5 has been reported to play a function in cardiomyocyte. Here we studied the function of Gas5 on newborn mouse cardiomyocyte (NMC) apoptosis to detect its molecular mechanism. High-glucose treatment was implemented to induce the apoptosis of NMC in this study. And terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, JC-1 assay, and flow cytometry analysis were conducted to know about the apoptosis of NMC when Gas5 and Tcf3 were silenced. Meanwhile, RNA pull-down assay and luciferase reporter assay were conducted to verify the binding of RNAs. Finally, rescue assay was implemented to evaluate the influence on apoptosis situation affected by competing endogenous RNA pathways. Tcf3 was found to bind to the Gas5 promoter to activate the expression of Gas5. Meanwhile, Gas5 and Tcf3 were both found to promote the apoptosis of NMC. Also, mmu-miR-320-3p could bind to Gas5 and Tcf3. Moreover, the Gas5/miR-320-3p/Tcf3 pathway was found to modulate the apoptosis of NMC. In conclusion, Tcf3-activated lncRNA Gas5 regulates NMC apoptosis in diabetic cardiomyopathy.

Research and development (R&D) is critical to innovation that enhances productivity. Going beyond a simple relationship between R&D and firm productivity performance, this article investigates what co-investments and other business operating conditions facilitate R&D in improving productivity. Using a rich micro database for Canada, we show that the actual effect of R&D on productivity depends on a number of factors that play important roles in determining R&D efficiency in im-proving productivity. These factors include adopting certain management practices, making investments in ICT, and maintaining a skilled workforce. In addition, the article shows that firm size, foreign ownership and market power are important positive forces in improving R&D efficiency. The findings highlight the complexity of R&D in improving productivity.

Camellia nitidissima Chi, is a rare and endangered plant that is narrowly distributed in South China and North Vietnam. In this study, seven polymorphic microsatellite markers were used to investigate the genetic diversity, recent population bottlenecks as well as population structure of twelve remnant populations of the plant. Our results indicated that, despite their severely fragmented natural range, C. nitidissima remnants maintained a moderate level of genetic variability, and only a bottlenecked population was detected by the clear evidences. No significant correlation was found between genetic diversity and population size. Significantly high genetic differences among populations were found, and the twelve populations could be classified into two distinct genetic groups. AMOVA indicated that 16.14% (16.73%, after one suspected artificial population was excluded) of the molecular variation was attributable to regional divergences (between Nanning and Fangcheng), and the majority of genetic variation existed within populations which were 69.24% (70.63%, after one suspected artificial population was excluded). For conservation management plans, the genetic resources of the two distinct groups are of equal importance for conservation, separate management unit for each of them should be considered. Given that all remnant populations are small and isolated, and many plants are illegally dug out for commercial purposes, management efforts in terms of habitat protection and legal protection, as well as transplantations and reintroductions, would be necessary for this species.

BackgroundPancreatic cancer (PC) is one of the most lethal human cancers, and radiation therapy (RT) is an important treating option. Many patients diagnosed with PC do not achieve objective responses because of the existence of intrinsic and acquired radioresistance. Therefore, biomarkers, which predict radiotherapy benefit in PC, are eagerly needed to be identified.MethodsWhole-exome sequencing of six pancreatic ductal adenocarcinoma patients (PDAC) (three with a good response and three with a poor response) who had received radical surgery and then radiotherapy has been performed as standard of care treatment. Somatic and germline variants and the mutational signatures were analyzed with bioinformatics tools and public databases. Functional enrichment and pathway-based protein-protein interaction analyses were utilized to address the possibly mechanism in radioresistance. MTT, LDH, and colony formation assay were applied to evaluate cell growth and colony formation ability.ResultsIn the present study, somatic mutations located in 441 genes were detected to be radiosensitivity-related loci. Seventeen genes, including the Smad protein family members (SMAD3 and SMAD4), were identified to influence the radiosensitivity in PDAC. The SMAD3 and SMAD4 genes mutate differently between radiosensitive and radioresistant PDAC patients. Mutation of SMAD3 potentiates the effects of ionizing radiation (IR) on cell growth and colony formation in PDAC cells, whereas mutation of SMAD4 had the opposite effects. SMAD3 and SMAD4 regulate the radiosensitivity of PDAC, at least in part, by P21 and FOXO3a, respectively.ConclusionsThese results indicate that mutations of SMAD3 and SMAD4 likely cause the difference of response to radiotherapy in PDAC, which might be considered as the biomarkers and potential targets for the radiotherapy of pancreatic cancer.

Ginger (Zingiber officinale), the type species of Zingiberaceae, is one of the most widespread medicinal plants and spices. Here, we report a high-quality, chromosome-scale reference genome of ginger ‘Zhugen’, a traditionally cultivated ginger in Southwest China used as a fresh vegetable, assembled from PacBio long reads, Illumina short reads, and high-throughput chromosome conformation capture (Hi-C) reads. The ginger genome was phased into two haplotypes, haplotype 1 (1.53 Gb with a contig N50 of 4.68 M) and haplotype 0 (1.51 Gb with a contig N50 of 5.28 M). Homologous ginger chromosomes maintained excellent gene pair collinearity. In 17,226 pairs of allelic genes, 11.9% exhibited differential expression between alleles. Based on the results of ginger genome sequencing, transcriptome analysis, and metabolomic analysis, we proposed a backbone biosynthetic pathway of gingerol analogs, which consists of 12 enzymatic gene families, PAL, C4H, 4CL, CST, C3’H, C3OMT, CCOMT, CSE, PKS, AOR, DHN, and DHT. These analyses also identified the likely transcription factor networks that regulate the synthesis of gingerol analogs. Overall, this study serves as an excellent resource for further research on ginger biology and breeding, lays a foundation for a better understanding of ginger evolution, and presents an intact biosynthetic pathway for species-specific gingerol biosynthesis.

The highly contagious COVID-19 virus spread across the world in a matter of months, beginning in the second half of 2019 and being declared a global pandemic by March, 2020. To limit its continued ...

Liusong Yang,1 Guoqiang Ren,2 Jianmin Tang2 1Department of Neurosurgery, Huashan Hospital North, Fudan University, Shanghai 201907, People’s Republic of China; 2Department of Pathology, Huashan Hospital North, Fudan University, Shanghai 201907, People’s Republic of ChinaCorrespondence: Liusong Yang Tel +86 21 66895203Email yangls72@hotmail.comBackground: Intracranial angiomatous meningioma (AM) is a rare subtype of meningioma. Here, we investigated the clinical and pathological features of AMs.Materials and Methods: We performed a retrospective study of 23 intracranial AMs verified by postoperative pathology at Huashan Hospital North between 2013 and 2018. Clinical data, radiological and pathological findings, and information on treatment and outcomes were collected and analyzed. Additionally, the literature on intracranial AMs was reviewed.Results: The sample comprised 13 men and 10 women with AMs. The mean age was 54.2 years, and the mean duration of symptoms was 14.9 months. Headache and epilepsy were the most common symptoms. The most common AMs locations were the cerebral convexity and parasagittal/falx region. The rates of vascular signs, homogeneous enhancement, and peritumoral brain edema (PTBE) on magnetic resonance images were high. Histologically, besides typical meningioma cells, AMs had an abundant vascular component and low Ki-67 index. The extent of PTBE was related to microvessel density (MVD) of tumors, but not to the expression of MMP9 or VEGF. Simpson grade I resection was achieved in 15 cases, and grade II resection was achieved in 7 cases. Twenty-one cases were followed up, and they all had favorable outcomes without recurrence.Conclusion: AM is a type of meningioma with a rich blood supply and distinct clinical and pathological features. It showed a slight male predominance and was common at the cerebral convexity or parasagittal/falx region. Histologically, it showed benign biological characteristics despite frequent and severe PTBE, and the extent of PTBE was related to MVD of tumors. Simpson I resection is the best treatment, and the prognosis is usually good after total tumor removal, while gamma knife is recommended for small residual tumor.Keywords: angiomatous meningioma, clinical characteristic, radiology, pathohistology, prognosis

Background and Aims: Studies have shown that dipeptidyl peptidase-4 (DDP-4) inhibitors have anti-atherosclerotic effects. However, in the PROLOGUE study, sitagliptin failed to slow the progression of carotid intima-media thickness (CIMT) relative to conventional therapy. We conducted a post hoc analysis of the PROLOGUE study and compared the effects of sitagliptin and conventional therapy on changes in CIMT in subgroups with or without hyperuricemia. Methods: The PROLOGUE study was a randomized controlled trial of 442 patients with type 2 diabetes mellitus (T2DM). Patients were randomized to receive sitagliptin added therapy or conventional therapy. Based on the serum uric acid levels of all study populations in the PROLOGUE study, we divided them into hyperuricemia subgroup ( n = 104) and non-hyperuricemia subgroup ( n = 331). The primary outcome was changed in carotid intima-media thickness (CIMT) parameters compared with baseline during the 24 months treatment period. Results: In the hyperuricemia subgroup, compared with the conventional therapy group, the changes in the mean internal carotid artery (ICA)-IMT and max ICA-IMT at 24 months were significantly lower in the sitagliptin group [−0.233 mm, 95% confidence interval (CI) (−0.419 to 0.046), p = 0.015 and −0.325 mm, 95% CI (−0.583 to −0.068), p = 0.014], although there was no significant difference in the common carotid artery CIMT. Conclusion: The results of our analysis indicated that sitagliptin attenuated the progression of CIMT than conventional therapy in T2DM and hyperuricemia patients.

Many commentators and researchers have attributed the manufacturing success in China to its ownership reforms. Using a micro database from the Chinese National Bureau of Statistics, this paper documents and quantifies this development. With systematic and robust analyses, it shows that the development of private ownership indeed played an essential role in improving firm performance and the allocation and utilization of production resources in the Chinese manufacturing sector. In addition, the paper estimates the contributions of firms under different ownership to manufacturing growth, showing that the development of private ownership was the driving force of manufacturing growth in China. The strong credible evidence has important policy implications for further maintaining sustainable development in China.

Objective We propose for the first time that D-dimer to creatinine ratio (DCR) may serve as a new clinical biomarker and explore its association with ST-segment elevation myocardial infarction (STEMI). Methods 347 STEMI patients with complete D-dimer and creatinine were included in the analysis. According to the median of DCR value, patients were divided into the lower DCR group (DCR Results High DCR group had higher Gensini score compared with the low DCR group ( P Conclusions As a new and useful clinical biomarker, DCR was positively correlated with coronary Gensini score in STEMI patients.

Resume : Les multinationales ont longtemps ete reconnues comme des piliers importants de l'economie canadienne, puisque ces entreprises sont responsables de la majorite des exportations du pays et d'une part importante de l'emploi. En meme temps, selon une opinion largement repandue, les multinationales seraient moins ancrees dans l'economie canadienne et auraient par consequent plus tendance a proceder a des delocalisations: c'est cette perception que les auteurs tentent de verifier dans cet article, grâce a des combinaisons de donnees canadiennes au niveau des entreprises. Les resultats montrent que les multinationales (etrangeres et canadiennes) ont effectivement plus tendance a proceder a des delocalisations, mais que cela n'est pas necessairement du au fait qu'elles sont moins ancrees dans l'economie canadienne. Les auteurs observent egalement differentes associations entre les delocalisations et certaines caracteristiques des entreprises (dont la productivite) selon le type de delocalisation (intra-entreprise ou inter-entreprise, par exemple) et la nature des activites delocalisees (certains types de services ou la production de biens, par exemple). Abstract: Multinational enterprises (MNEs) have long been recognized as important pillars of Canada's national economy, accounting for the majority of its exports and an important share of its employment. At the same time, there is a widespread perception that MNEs are less rooted in the local economy and are thus more likely to conduct offshoring. In this study, we investigate the latter claim by combining various Canadian firm-level data sets. We find that MNEs (both Canadian and foreign headquartered) are indeed more likely to offshore but suggest that it is not necessarily because they are less rooted in the Canadian economy. We also show different associations between offshoring and firm characteristics (including productivity) depending on the type of offshoring (e.g., intrafirm or interfirm offshoring) and the type of business activity offshored (e.g., certain types of service vs. goods production).

Using the Longitudinal Annual Survey of Manufacturers for Canada, this paper aims to better understand the productivity dynamics of entrants and exits as well as the factors associated with their productivity performance. It shows that entrants and exits are lower in labour productivity relative to continuing plants partly because they are smaller in size, less capital intensive, and less associated with exporting, being foreign-controlled and belonging to multi-plant firm structure. It also finds that after controlling for those factors, surviving entrants are less productive when they enter and that they improve their productivity over time to become as productive as continuing plants by around year five after entry. Exits, on the other hand, are found to be less productive than continuing plants after controlling for those factors, and the gap becomes larger as they get closer to exit.

Background: The bioactive compounds of ginger (Zingiber officinale), including gingerols, diarylheptanoids, and flavonoids, are important for human health because of their anticancer, anti-oxidant, and anti-inflammatory properties. Results: The UPLC/Q-TOF-MS profiles of four ginger samples, Zingiber officinale 'Yujiang No.1' (YJ), Zingiber officinale 'Shandong dajiang' (SD), Zingiber officinale 'Shandong xiaojiang' (SX) and Zingiber officinale 'Luoping xiaohuangjiang' (LP) were compared to gain insight into the differences in their rhizome content. A total of 1,810 metabolites were detected across the four varieties with 111, 72, 57, and 92 metabolites shared between the LP/YJ, SX/YJ, SX/SD and LP/SD ginger samples, respectively, with a p value of < 0.05 and a fold change of ≥1. Among the four libraries, 186 differentially expressed metabolites were identified. The metabolic pathways associated with the production of the bioactive compounds of ginger included those for stilbenoid, diarylheptanoid, and gingerol biosynthesis, flavonoid biosynthesis, steroid hormone biosynthesis, and diterpenoid biosynthesis. Among the differentially accumulated metabolites, gingerols and α-zingiberene were found in higher amounts in the SD and LP than in the SX and YJ varieties. The steroid hormones and terpenoids were found in higher amounts in LP than the other ginger samples. Conclusion: The LP and SD varieties could be utilized as a source of medicinal ginger, while SX and YJ are more suited to incorporation into food because of their lighter taste related to their lower content of gingerols. The differences in active ingredients combined with analysis of the KEGG pathway allowed prediction of the metabolite synthetic pathways involved in the ginger component biosynthesis and lays the foundation for the further development and use of specific ginger varieties as medicinal resources.

Background Aroma is one of the most important aspects of fruit quality and can reflect the characteristics of different fruits. Aroma-active compounds can usefully be employed to trace the production areas of two citrus cultivars ('Eureka' lemon and 'Huapi' kumquat) and to evaluate their aroma quality. Results 'Huapi' kumquat peel displayed higher monoterpene and sesquiterpene compound content, whereas 'Eureka' lemon peel exhibited higher monoterpene and monoterpene aldehyde compound content. 'Eureka' lemon peel ('Wanzhou' cultivar) had higher nerol acetate and geraniol acetate compound content. Kumquat peel ('Suichuan' and 'Rongan' cultivars) had higher sesquiterpene content. In addition, 30 and 31 aroma-active compounds were observed in kumquat and lemon, respectively, based on their odor activity values. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) results indicated that classification for production areas based on aroma-active compounds was useful. The selected aroma-active compounds have been checked as aroma quality parameters that could be used with multivariate analysis to establish a model of aroma quality evaluation. Higher aroma quality values from kumquat and lemon were collected from Rongan and Wanzhou cultivars, respectively. Conclusion Aroma-active compounds can be used to discriminate production areas using multivariate statistics. An objective method was established to evaluate the aroma quality of citrus fruits. 'Huapi' kumquat and 'Eureka' lemon, which had the highest aroma quality, was harvested from the Rongan and Wanzhou production areas. This was the first time that the aroma quality of citrus fruits was evaluated using multivariate analysis. © 2019 Society of Chemical Industry.

The aim of this study was to investigate the effects of three different drying methods, freeze drying (FD), vacuum drying (VD) and oven drying (OD) on phenolic contents and antioxidant activities of litchi fruits. 20 polyphenols were exactly identified in the litchi fruits by UPLC-QqQ/MS. Significant losses were observed in the contents of total polyphenols and antioxidant activities in the dried litchi when compared with the fresh litchi. Principle component analysis indicated that there was significant difference of phenolic component between the use of thermal drying (VD and OD) and FD. Our results suggest that FD is the optimum drying method for litchi fruits considering the content of total polyphenols and antioxidant activities.

Purpose It has been suggested that to be successful in the current global economy with increased competition and ever changing markets, especially in the post-crisis context, firms need to focus more on innovation in exploring new ideas and designing new products to develop new markets than on cost-cutting strategies to maintain cost leadership in old markets. However, because of the lack of micro data, this conjecture has not been systematically evaluated. This paper aims to fill this important void by studying the economic performance associated with these two different business strategies using Canadian micro data. Design/methodology/approach The main data for our analysis are from the Survey of Innovation and Business Strategy (2009 and 2012) which is a sample-based survey of Canadian government. The authors used in this research regression models for the econometric analysis of the underlying factors for undertaking certain business strategies and how business strategies link to economic performance. They also used propensity score matching to ensure the group of firms with innovation strategy being comparable to that with cost-cutting. Findings The research shows that firms focusing on product innovation are indeed more productive than firms focusing on cost-cutting, although there is no evidence that these two different strategies make a difference in profitability. The first indication from the research has been that certain characteristics of Canadian firms are very useful predictors for firms to undertake product innovation. They are, among other things, the age of the firms, the single-establishment structure of the business and being multinationals. Research limitations/implications This empirical research opens up many interesting avenues for future research. Some other variables could be integrated into the models to increase the rate of explained variance. Moreover, because this research is based only on the case of Canadian firms and for a relatively short period of four years after the 2008 crisis, an extension to other context and to a longer period of time should be interesting. Practical implications The research has confirmed that Canadian firms adopting long-term business strategies based on product innovation are more productive. Social implications The results truly concur with the vision of the Government of Canada, like some other developed countries, on the importance of innovation and its policies in encouraging business innovation in driving the growth of the Canadian economy and improving the standard of living of country. Originality/value Mainly because of the lack of micro data, the existing researches have not provided solid evidence on why firms are choosing different business strategies when they are operating in the same business conditions and how the financial crisis has affected the undertaking of business strategies. They have not established a clear linkage between economic performance and different business strategies, although there has been some anecdotal evidence about their association. This study aims to bridge the knowledge gaps with theoretical and practical contributions.

Background and Aims Transport of membranes and proteins in eukaryotic cells is mediated by vesicular carriers. Coatomer complex I (COPI)-coated vesicles are involved in the transport between endoplasmic reticulum (ER) and Golgi complex. Several studies indicated that some subunits of COPI were correlated with the cell proliferation of malignant tumors. The present study focused on the function of coatomer protein complex subunit β 2 (COPB2), one of seven proteins in COPI, in prostate cancer (PCa). Methods COPB2 gene expression was first analyzed by immunohistochemistry (IHC) in 15 paired PCa and carcinoma adjacent normal tissue from patients. To investigate the role of COPB2 in PCa, we used lentivirus-mediated small interfering RNA (siRNA) to knockdown COPB2 expression in human PCa cell line PC-3 and assessed it by RT-qPCR. Cellomics ArrayScan VTI imaging and colony formation were conducted to evaluate cell proliferation. Cell cycle phase arrest and apoptosis were assayed by flow cytometry. Results COPB2 gene was upregulated in the PCa tissue. Cell proliferation was significantly inhibited in COPB2-silenced PC-3 cells using both Cellomics ArrayScan VTI imaging and colony formation assays. S-phase cell counts were significantly decreased; G1- and G2-phase cell counts were significantly increased in COPB2-siRNA group than the control group. Apoptosis was significantly increased in COPB2-siRNA cells. Conclusions COPB2 significantly promoted PC-3 cell proliferation and colony formation through the cell cycle and apoptosis pathway. Moreover, COPB2 showed a clinical correlation and may serve as a biomarker for the detection for PCa.

Background/aims Hypertension is a common public health problem due to its high morbidity and potential risk, which is related to inflammatory actions. Kaempferol (KAE) has anti-inflammation activities. Herein, we explored the effects of KAE on LPS-induced inflammatory injury in human aortic endothelial cells (HAECs). Methods HAECs were treated with KAE before stimulated with LPS or AngII. After miR-203 inhibitor transfection, cell viability and apoptosis were detected by CCK-8 and flow cytometry. The accumulated levels of apoptotic proteins, nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways related proteins, MyD88 and toll-like receptor 4 (TLR4) were both determined by western blot. The concentrations of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were detected by ELISA. Expression of miR-203 was analyzed by qRT-PCR. The target of miR-203 was achieved by luciferase assay. Results LPS successfully induced inflammatory injury as evidenced by decreasing cell viability, increasing apoptosis, and also increasing IL-6, TNF-α concentrations. The apoptotic proteins p53 and cleaved-Caspase-3 were both upregulated while Bcl-2 was downregulated. Moreover, LPS activated NF-κB and MAPK pathways. However KAE reversed the results led by LPS. KAE increased miR-203 expression in LPS or AngII-disposed HAECs. More experiments revealed that transfection with miR-203 inhibitor impaired the inflammation-alleviating effects of KAE. MyD88 and TLR4 were predicated as a target of miR-203, which might be implicated in the protective functions of KAE on HAECs. Conclusion KAE exerted the protective impacts on HAECs against inflammatory injury through inactivation of NF-κB and MAPK pathways, as well as upregulation of miR-203.

No-reflow is one of the major complications of primary percutaneous coronary artery intervention (pPCI) in the treatment of acute ST-segment elevation myocardial infarction (STEMI). Fibrinogen-to-albumin ratio (FAR) has currently emerged as a novel inflammatory marker to predict inflammation in chronic diseases. This study aimed to investigate whether admission FAR values predicts angiographic no-reflow and short-term prognosis in all STEMI patients. A total of 510 consecutive STEMI patients who underwent successful pPCI between September 2016 and May 2018 were included in this study. Patients were divided into groups based on thrombolysis in myocardial infarction (TIMI) flow grades after pPCI. No-reflow was defined as a post-PCI TIMI flow grade of 0, 1, or 2. Angiographic success was defined as TIMI flow grade 3. Fibrinogen, hs-CRP, and admission FAR values were significantly higher among patients with no-reflow. On multivariate analysis, admission FAR was an independent predictor of angiographic no-reflow (p

Integrated management, utilizing different non-chemical methods, is an approach to controlling postharvest losses that is being actively investigated. In the present study, the use of an antagonistic yeast, Candida diversa, combined with harpin (a hypersensitive response elicitor) treatment was evaluated for their ability to prevent infection of kiwifruit after they were artificially inoculated with Botrytis cinerea or Penicillium expansum. Natural infection of treated fruit was also assessed. As a standalone treatment, C. diversa or harpin significantly reduced gray (B. cinerea) and blue mold (P. expansum) infections on kiwifruit, relative to the untreated control fruit, and also reduced the level of natural infection. The combination of C. diversa and harpin treatment, however, provided a superior level of control on fruit, relative to either treatment alone. Harpin did not negatively impact C. diversa growth in kiwifruit wounds. Treatment of kiwifruit with C. diversa and harpin alone or in combination also induced the activity of enzymes involved in defense response, such as polyphenol oxidase, peroxidase and superoxide dismutase. Harpin alone or in combination with C. diversa enhanced accumulation of lignin content in kiwifruit as well. The mode of action by which harpin enhanced biocontrol efficacy of C. diversa may be partially attributed to the elicitation of defense response in kiwifruit. Integrating the use of antagonistic yeast with harpin treatment has potential as an effective method for the control of postharvest decay in kiwifruit.

In the globalized economy, it has become essential for firms to re-organize their production to grow and to be competitive in both domestic and international markets. Over the past decade, offshori...

Objective: Medullary breast carcinoma is a rare breast carcinoma with good prognosis. Although it has been established that axillary lymph node metastasis is a poor prognostic factor, little is known about the relationship between axillary lymph node metastasis and clinicopathological characteristics of medullary breast carcinoma patients. The aim of this study was to identify factors that predict occurrence of axillary lymph node metastasis in medullary breast carcinoma patients. Methods: We performed a retrospective study of axillary lymph node status and the relevant clinicopathological characteristics in 49 triple-negative medullary breast carcinoma patients with axillary lymph node dissection between November 2004 and July 2011. Results: A total of 49 patients were enrolled in the study. Fourteen patients (28.6%) had axillary lymph node metastasis that was confirmed pathologically. Axillary lymph node metastasis was not associated with age, menopausal status, primary tumor size or its location, the degree of inflammation within the tumor or mitotic count. However, we found a statistically significant association between axillary lymph node metastasis and Ki67 labeling index in primary tumors (P < 0.001). Conclusions: There is a positive association between Ki67 labeling index in the primary tumor and axillary lymph node metastasis in triple-negative medullary breast carcinoma patients.

The present paper studies the sources of economic growth and the nature of structural change in the Chinese economy from 1987 to 2008. Using a methodology that evaluates the contribution of an industry to economic growth, the present paper shows that the post-2000 subperiod marked an increased reliance on the services sector as a source of growth in the Chinese economy. Much of the acceleration in real GDP or aggregate labor productivity growth in China in the post-2000 subperiod compared to the pre-2000 period can be traced to an increased contribution from service-producing and high-technology exporting manufacturing industries. The evidence indicates that the Chinese economy has been rebalancing toward domestic consumption and shifting its export sector toward high-technology manufacturing industries.

46 different kinds of liquids inside a quartz glass cell were measured with reflection THz-TDS. The sample signals were analyzed with PCA and SVM algorithm in frequency domain and the liquids could be identified feasibly.