Structured mathematical modelling on innovation management in project-oriented small construction firms.

The significance of innovation management in triggering and sustaining increase in corporations of distinct size, age or enterprise type, is receiving growing attention, yet scant empirical research have been carried out in project-oriented service firms, in particular small-scaled enterprises. This study aims to identify how innovation management in small construction firms could enable them to pursue innovation and achieve greater business performance. Data collection comprises 157 empirical surveys leading to a conceptual framework modelled using the structural equation modelling approach. The findings show that entrepreneurship and networking have a direct and considerable influence on both technological and non-technological innovation, which consequently improves firm performance.

Pareidolia in a Built Environment as a Complex Phenomenological Ambiguous Stimuli.

Pareidolia is a kind of misperception caused by meaningless, ambiguous stimuli perceived with meaning. Pareidolia in a built environment may trigger the emotions of residents, and the most frequently observed pareidolian images are human faces. Through a pilot experiment and an in-depth questionnaire survey, this research aims to compare built environmental pareidolian phenomena at different time points (6 a.m., 12 p.m., 2 a.m.) and to determine people's sensitivity and reactions towards pareidolia in the built environment. Our findings indicate that the differences in stress level do not influence the sensitivity and reactions towards pareidolia in the built environment; however, age does, and the age of 40 seems to be a watershed. Females are more likely to identify pareidolian faces than males. Smokers, topers, and long-term medicine users are more sensitive to pareidolian images in the built environment. An unexpected finding is that most pareidolian images in built environments are much more easily detected in the early morning and at midnight but remain much less able to be perceived at midday. The results help architects better understand people's reactions to pareidolia in the built environment, thus allowing them to decide whether to incorporate it appropriately or avoid it consciously in building design.

Metabolic response of Lactobacillus acidophilus exposed to amoxicillin.

Drug-induced diarrhea is a common adverse drug reaction, especially the one caused by the widespread use of antibiotics. The reduction of probiotics is one reason for intestinal disorders induced by an oral antibiotic. However, the intrinsic mechanism of drug-induced diarrhea is still unknown. In this study, we used metabolomics methods to explore the effects of the classic oral antibiotic, amoxicillin, on the growth and metabolism of Lactobacillus acidophilus, while scanning electron microscopy (SEM) and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were employed to evaluate changes in cell activity and morphology. The results showed that cell viability gradually decreased, while the degree of cell wall rupture increased, with increasing amoxicillin concentrations. A non-targeted metabolomics analysis identified 13 potential biomarkers associated with 9 metabolic pathways. The data showed that arginine and proline metabolism, nicotinate and nicotinamide metabolism, pyrimidine metabolism, glycine, serine and threonine metabolism, beta-alanine metabolism, glycerolipid metabolism, tryptophan metabolism, steroid hormone biosynthesis, and histidine metabolism may be involved in the different effects exerted by amoxicillin on L. acidophilus. This study provides potential targets for screening probiotics regulators and lays a theoretical foundation for the elucidation of their mechanisms.

Urinary metabonomics study of anti-depressive mechanisms of Millettia speciosa Champ on rats with chronic unpredictable mild stress-induced depression.

As a traditional Chinese medicine (TCM), Millettia speciosa Champ (MSC), exerts a wide range of pharmacological activities. Our research group previously found that MSC has antidepressant effects, but the specific antidepressant mechanisms remain unclear. Therefore, in this study, urine metabolomics based on ultra-performance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) combined with pharmacodynamics was used to explore the pathogenesis of depression and the antidepressant effects of MSC. The results showed that MSC treatment could significantly improve chronic unpredictable mild stress (CUMS)-induced depression. Urine metabolic showed that the profiles of the CUMS model group were significantly separated from the control group, while the drug-treated groups were closer to the control group, especially the MSC group treated with a 14 g/kg dose of MSC. Furthermore, 9 metabolites, including glutaric acid, L-isoleucine, L-Dopa, sebacic acid, 3-methylhistidine, allantoin, caprylic acid, tryptophol, and 2-phenylethanol glucuronide, were identified as potential biomarkers of depression. Metabolic pathway analysis showed that these potential biomarkers were mainly involved in valine, leucine, and isoleucine biosynthesis, aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine degradation, tyrosine metabolism, histidine metabolism, fatty acid biosynthesis, and pentose and glucuronate interconversions. Through Receiver operating characteristic (ROC) analysis and Pearson correlation analysis, the combination of L-isoleucine, sebacic acid, and allantoin, were further screened out as potential pharmacodynamic biomarkers associated with the efficacy of MSC. This study suggests that the integration of metabolomics with pharmacodynamics helps to further understand the pathogenesis of depression and provides novel insight into the efficacy of TCM.

1H NMR-based urinary metabonomic study of the antidiabetic effects of Rubus Suavissimus S. Lee in STZ-induced T1DM rats.

Long-term hyperglycemia associated with diabetes mellitus (DM) causes damage to various organs and tissues, including the eyes, kidneys, heart, blood vessels and nerves. Rubus Suavissimus S. Lee (RS), a shrub whose leaves are used in traditional Chinese medicine (TCM), has been shown to exert hypoglycemic effects in DM patients. However, the underlying mechanism is unclear. This was investigated in the present study in a rat model of streptozotocin-induced type 1 diabetes mellitus (T1DM) by 1H NMR analysis. We identify 9 metabolites whose levels were altered in T1DM rats compared to control rats, namely, lactate, acetate, pyruvate, succinate, 2-oxoglutarate, citrate, creatinine, allantoin, and hippurate, which are mostly related to glycolysis/gluconeogenesis, pyruvate metabolism, TCA cycle, and other metabolism. The observed pathologic changes in the levels of these metabolites in T1DM rats were reversed by treatment with RS. Thus, RS exerts effects in T1DM rats by regulating the three abnormal metabolic pathways synergistically. These findings provide supporting evidence for the therapeutic efficacy of this TCM formulation in the treatment of DM.

"Nomen Omen": Exploring Connected Healthcare through the Perspective of Name Omen.

Background: The evolution of names, from "medical informatics" to "connected health", implies that the evolvement of technology in health care has been shifted from technology-oriented to healthcare-oriented implementation. Connected healthcare, a healthcare platform of remote monitoring and self-management through technological measures, is suggested to contribute to the efficiency, cost-effectiveness, and satisfaction of healthcare recipient enhancement. However, limited understanding of related connected health (CH) terminology may constrain its implementation. Whether CH is a buzzword only or a practice that can contribute to an aging society is controversial. Objective: This study aims to distinguish CH-related terminology and to identify the trend of CH through reviewing its definition, initiation, development, and evolvement, in order to offer management insights and implications. The objective is to understand what is connected and who is cared about in the connected health model so that better applications can be addressed for the benefit of society. Method: This study reviews the evolution of names, from "medical informatics" in the 1970s to "connected health" after 2000, as well as relevant literature of CH, including e-health, telemedicine, telehealth, telecare, and m-health, to discover the trend of technology-related healthcare innovations. Results: The current status and issues facing accessibility, quality, and cost were presented. Its future trends will be explored through reviewing how changes in healthcare are managed, in addition to its operation and practice. Pre-conditions and requirements for implementing CH are identified to select a typical case to study. Findings suggest that areas with a complete business ecosystem-isolated locations, advanced information technology, aging in population, integrated health, and social care system-are prevalent for designing friendly CH environments. Conclusion: The evidence and tendency of technological convergence create a demand for innovation and partnering with start-up companies that offer a competitive advantage in innovation.

The study of neuroprotective effect of ferulic acid based on cell metabolomics.

Ferulic acid (FA), a naturally derived phenolic compound, has antioxidant and antidepressant-like effects. It is still a challenge to study its mechanism due to the complexity of the pathophysiology of depression. In this study, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to perform metabolomics studies based on biochemical changes in differentiated rat pheochromocytoma (PC12) cells treated with corticosterone-induced neurological damage after FA treatment. A total of 31 metabolites were identified as potential biomarkers for corticosterone-induced PC12 cells injury. Among them, 24 metabolites were regulated after FA treatment. Pathway analysis revealed that these metabolites were mainly involved in the amino acid metabolism, energy metabolism and glycerophospholipid metabolism. In addition, based on the results of metabolomics, three cell signaling pathways related to glutamate were discovered. To further study the interactions between FA and major targets in three signaling pathways, a molecular docking method was employed. The results showed that FA had the strongest binding power with protein kinase B (AKT). Furthermore, the result of mRNA changes analyzed by quantitative real time RT-PCR indicated that AKT and protein kinase A (PKA) in the signaling pathway were up regulated after treatment with FA compared with model group. This study shows that strategies based on cell metabolomics associated with molecular docking and molecular biology is a helpful tool to elucidate the neuroprotective mechanism of FA.

Intervening Effects of Total Alkaloids of Corydalis saxicola Bunting on Rats With Antibiotic-Induced Gut Microbiota Dysbiosis Based on 16S rRNA Gene Sequencing and Untargeted Metabolomics Analyses.

Gut microbiota dysbiosis induced by antibiotics is strongly connected with health concerns. Studying the mechanisms underlying antibiotic-induced gut microbiota dysbiosis could help to identify effective drugs and prevent many serious diseases. In this study, in rats with antibiotic-induced gut microbiota dysbiosis treated with total alkaloids of Corydalis saxicola Bunting (TACS), urinary and fecal biochemical changes and cecum microbial diversity were investigated using 16S rRNA gene sequencing analysis and untargeted metabolomics. The microbial diversity results showed that 10 genera were disturbed by the antibiotic treatment, and two of them were obviously restored by TACS. The untargeted metabolomics analysis identified 34 potential biomarkers in urine and feces that may be the metabolites that are most related to the mechanisms underlying antibiotic-induced gut microbiota dysbiosis and the therapeutic effects of TACS treatment. The biomarkers were involved in six metabolic pathways, comprising pathways related to branched-chain amino acid (BCAA), bile acid, arginine and proline, purine, aromatic amino acid, and amino sugar and nucleotide sugar metabolism. Notably, there was a strong correlation between these metabolic pathways and two gut microbiota genera (g__Blautia and g__Intestinibacter). The correlation analysis suggested that TACS might synergistically affect four of these metabolic pathways (BCAA, bile acid, arginine and proline, and purine metabolism), thereby modulating gut microbiota dysbiosis. Furthermore, we performed a molecular docking analysis involving simulating high-precision docking and using molecular pathway maps to illuminate the way that ligands (the five main alkaloid components of TACS) act on a complex molecular network, using CYP27A1 (a key enzyme in the bile acid synthesis pathway) as the target protein. This study provides a comprehensive overview of the intervening effects of TACS on the host metabolic phenotype and gut microbiome in rats with gut microbiota dysbiosis, and it presents new insights for the discovery of effective drugs and the best therapeutic approaches.

Comparative analysis of the compatibility effects of Danggui-Sini Decoction on a blood stasis syndrome rat model using untargeted metabolomics.

Danggui-Sini Decoction (DSD) is one of the most widely used traditional Chinese medicine formulae (TCMF) for treating various diseases caused by cold coagulation and blood stasis due to its effect of nourishing blood to warm meridians in clinical use. However, studies of the mechanism of how it dispels blood stasis and its compatible regularity are challenging because of the complex pathophysiology of blood stasis syndrome (BSS) and the complexity of DSD, with multiple active ingredients acting on different targets. Observing variations of endogenous metabolites in rats with BSS after administering DSD may further our understanding of the mechanism of BSS and the compatible regularity of DSD. In this study, to understand the pathogenesis of BSS and assess the compatibility effects of DSD, an ultra-performance liquid chromatography quadrupole-time of flight mass spectrometry-based untargeted metabolomics approach was used. Serum metabolic profiles in rats with BSS that was induced by an ice water bath associated with subcutaneous injection of epinephrine hydrochloride were compared with the intervention groups which were administered with DSD or its compatibility. Using pattern recognition analysis, a clear separation between the BSS model and control group was observed; DSD and its compatibility intervention groups were clustered closer toward the control than the model group, which corroborates results of hemorheology studies. In addition, 20 metabolites were considered as potential biomarkers associated with the development of BSS. Nine metabolites were regulated by DSD in intervening blood stasis, they were considered to be correlated with the effect of nourishing blood to warm meridians. Additionally, the results suggested that the intervention effect of DSD on BSS may involve regulating four pathways, namely, arachidonic acid metabolism, glycerophospholipid metabolism, bile acid biosynthesis, and pyruvate metabolism. Moreover, each functional unit (monarch, minister, and assistant) in DSD regulates different metabolites and metabolic pathways to achieve different effects on dispelling blood stasis; however, their intervention efficacies are inferior to the holistic formula, which may be due to the synergism of the bioactive ingredients in seven herbs of DSD. This study demonstrated that metabolomics is a powerful tool for evaluating the efficacy and compatibility effects of traditional Chinese medicine (TCM).

Investigation of the hepatoprotective effect of Corydalis saxicola Bunting on carbon tetrachloride-induced liver fibrosis in rats by 1H-NMR-based metabonomics and network pharmacology approaches.

Liver fibrosis is a common consequence of chronic liver diseases resulting from multiple etiologies. Furthermore, prolonged unresolved liver fibrosis may gradually progress to cirrhosis, and eventually evolve into hepatocellular carcinoma (HCC). Corydalis saxicola Bunting (CS), a type of traditional Chinese folk medicine, has been reported to have hepatoprotective effects on the liver. However, the exact mechanism of how it cures liver fibrosis requires further elucidation. In this work, an integrated approach combining proton nuclear magnetic resonance (1H-NMR)-based metabonomics and network pharmacology was adopted to elucidate the anti-fibrosis mechanism of CS. Metabonomic study of serum biochemical changes by carbon tetrachloride (CCl4)-induced liver fibrosis in rats after CS treatment were performed using 1H-NMR analysis. Metabolic profiling by means of partial least squares-discriminate analysis (PLS-DA) indicated that the metabolic perturbation caused by CCl4 was reduced after CS treatment. As a result, lipids, leucine, alanine, acetate, O-acetyl-glycoprotein and creatine were significantly restored after CS treatment, which regulated valine, leucine and isoleucine metabolism; arginine and proline metabolism; lipid metabolism and pyruvate metabolism. Additionally, 157 potential targets of CS and 265 targets of liver fibrosis were identified by means of network pharmacology. Subsequently, 5 target proteins, which are the intersection of potential CS targets and liver fibrosis targets, indicated that CS has potential anti-fibrosis effects through regulating alanine aminotransferase (ALT) activity, the farnesoid X receptor (FXR), cyclooxygenase-2 (COX-2), matrix metalloproteinase-1 (MMP-1) and angiotensinogen. Chelerythrine and sanguinarine were the potential active compounds in CS for treating liver fibrosis through regulating ALT activity. This study is the first report to study the anti-fibrosis effects of CS on the basis of combining a metabonomics and network pharmacology approaches, and it may be a potentially powerful tool to study the efficacy and mechanisms of traditional Chinese folk medicines.

[Antiosteoporotic effects of naringenin on ovariectomy-induced osteoporosis in rat].

To investigate the effect of naringenin on ovariectomy-induced postmenopausal osteoporosis comprehensively and systemically, thirty-two virgin Sprague-Dawley rats about 3-month-old were used and randomly divided into 4 groups: sham control group (Sham), OVX control group (OVX), naringenin treatment group and 17ß-estradiol (E2) treatment group. After 12 weeks treatment with different drugs, 24 h urine were collected, organs were weighed and the organ indies were computed. Uterine pathological changes were observed by making paraffin section. Biochemical parameters and bone turnover markers: serum osteocalcin (BGP) and urine deoxypyridinoline (DPD) were analyzed with automatic biochemical analyzer or ELISA assay. Bone mineral density (BMD) and bone mineral content (BMC) were analyzed by DEXA, bone biomechanical properties was measured by three point bending test and the trabecular bone microarchitecture was evaluated by Micro CT. From the results, we can see that: the gaining of weight and the increasing of bone turnover markers such as serum BGP and urinary DPD could be inhibited by naringenin. The treatment could also enhance the bone strength and prevent the deterioration of trabecular microarchitecture, increase the bone volume, trabecular number and thickness, and decrease the trabecular space. The effects mentioned above were not accompanied with stimulating effects on uterus. Long-term using of naringenin had no obvious influence on other organs and the liver and kidney functions. The study suggests that naringenin had obvious antiosteoporotic effect on ovariectomized rats and it had the potential value for the treatment of postmenopausal osteoporosis.