We studied the corrosion of Roman copper alloy coins that experienced alternations or progressive changes in their burial environment. We used coins that were still embedded in soil or in a... Show moreWe studied the corrosion of Roman copper alloy coins that experienced alternations or progressive changes in their burial environment. We used coins that were still embedded in soil or in a concretion selected from three professional excataved sites - Berlicum and Krommenie in the Netherlands and Kempraten in Switserland. mCT scanning and neutron scanning were used to record the 3-D properties of these coins prior to (destructive) analyses. It proved possible to tentatively identify the coins. Microscope observations and SEM-EDX analyses revealed complex corrosion processes, related to changing burial environments. In soil horizon with fluctuating groundwater levels in a region with upwelling reducing, iron-rich groundwater, the copper in a gunmetal coin is essentially replaced by iron oxides while tin remains and forms tin-oxide bands. Fluctuating redox conditions in marine-influenced environments was shown to transform a copper-alloy coin into strongly laminated copper sulphides with embedded gypsum crystals, with an outer surface of copper and copper-iron sulphides. Burial of bronze in a charcoal rich layer probably caused temporary highly alkaline soil conditions. This caused most of the copper to leach from this coin, leaving behind a laminated tin-dominated mass, with only a limited amount of (malachite) corrosion products remaining in the surrounding groundmass. In all three cases, corrosion processes tend to be anisotropic, probably because of cold-hammering of the coins during their manufacture. Such corrosion processes on massive copper alloy coins may produce features that may lead to their incorrect classification as subferrati, i.e. copper alloy coins with an iron core. Our results may help in future to distinguish strongly corroded massive coins from subferrati. Show less
Perianal fistulas are defined as pathological connections between the anorectal canal and the perianal skin. Most perianal fistulas are cryptoglandular fistulas, which are thought to originate from... Show morePerianal fistulas are defined as pathological connections between the anorectal canal and the perianal skin. Most perianal fistulas are cryptoglandular fistulas, which are thought to originate from infected anal glands. The remainder of the fistulas mainly arises as complications of Crohn's disease (CD), trauma, or as a result of malignancies. Fistulas in CD are considered as a consequence of a chronic and transmural inflammatory process in the distal bowel and can, in some cases, even precede the diagnosis of CD. Although both cryptoglandular and CD-associated fistulas might look similar macroscopically, they differ considerably in their complexity, treatment options, and healing rate. Therefore, it is of crucial importance to differentiate between these two types of fistulas. In this review, the differences between CD-associated and cryptoglandular perianal fistulas in epidemiology, pathogenesis, and clinical management are discussed. Finally, a flow chart is provided for physicians to guide them when dealing with patients displaying their first episode of perianal fistulas. Show less
Chlorpyrifos is a widely used organophosphorus insecticide because of its high efficiency and overall effectiveness, and it is commonly detected in aquatic ecosystems. However, at present, the... Show moreChlorpyrifos is a widely used organophosphorus insecticide because of its high efficiency and overall effectiveness, and it is commonly detected in aquatic ecosystems. However, at present, the impact of chlorpyrifos on the aquatic micro-ecological environment is still poorly understood. Here, we established aquatic microcosm systems treated with 0.2 and 2.0 µg/L chlorpyrifos, and employed omics biotechnology, including metagenomics and 16S rRNA gene sequencing, to investigate the effect of chlorpyrifos on the composition and functional potential of the aquatic and zebrafish intestinal microbiomes after 7 d and 14 d chlorpyrifos treatment. After 14 d chlorpyrifos treatment, the aquatic microbial community was adversely affected in terms of its composition, structure, and stability, while its diversity showed only a slight impact. Most functions, especially capacities for environmental information processing and metabolism, were destroyed by chlorpyrifos treatment for 14 d. We observed that chlorpyrifos increased the number of risky antibiotic resistance genes and aggravated the growth of human pathogens. Although no clear effects on the structure of the zebrafish intestinal microbial community were observed, chlorpyrifos treatment did alter the metabolic capacity of the zebrafish. Our study highlights the ecological risk of chlorpyrifos to the aquatic environment and provides a theoretical basis for the rational use of pesticides in agricultural production. Show less
Inflammatory bowel disease (IBD) is a chronic relapsing inflammation of the intestinal tract with currently not well-understood pathogenesis. In addition to the involvement of immune cells,... Show moreInflammatory bowel disease (IBD) is a chronic relapsing inflammation of the intestinal tract with currently not well-understood pathogenesis. In addition to the involvement of immune cells, increasing studies show an important role for fibroblasts in the pathogenesis of IBD. Previous work showed that glycolysis is the preferred energy source for fibroblasts in fibrotic diseases. 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3) is a key kinase supporting glycolysis. Increased expression of PFKFB3 in several cancers and inflammatory diseases has been previously reported, but the metabolic status of fibroblasts and the role of PFKFB3 in patients with IBD are currently unknown. Therefore, in this study, we evaluated the role of glycolysis and PFKFB3 expression in IBD. Single-sample gene set enrichment analysis (ssGSEA) revealed that glycolysis was significantly higher in IBD intestinal samples, compared to healthy controls, which was confirmed in the validation cohorts of IBD patients. Single-cell sequencing data indicated that PFKFB3 expression was higher in IBD-derived stromal cells. In vitro, PFKFB3 expression in IBD-derived fibroblasts was increased after the stimulation with pro-inflammatory cytokines. Using seahorse real-time cell metabolic analysis, inflamed fibroblasts were shown to have a higher extracellular acidification rate and a lower oxygen consumption rate, which could be reversed by inhibition of JAK/STAT pathway. Furthermore, increased expression of pro-inflammatory cytokines and chemokines in fibroblasts could be reverted by PFK15, a specific inhibitor of PFKFB3. In vivo experiments showed that PFK15 reduced the severity of dextran sulfate sodium (DSS)- and Tcell transfer induced colitis, which was accompanied by a reduction in immune cell infiltration in the intestines. These findings suggest that increased stromal PFKFB3 expression contributes to inflammation and the pathological function of fibroblasts in IBD. Inhibition of PFKFB3 suppressed their inflammatory characteristics. Show less
In the past decades, hundreds of antibiotics have been isolated from microbial metabolites or have been artificially synthesized for protecting humans, animals and crops from microbial infections.... Show moreIn the past decades, hundreds of antibiotics have been isolated from microbial metabolites or have been artificially synthesized for protecting humans, animals and crops from microbial infections. Their everlasting usage results in impacts on the microbial community composition and causes well-known collateral damage to the functioning of microbial communities. Nevertheless, the impact of different antibiotic properties on aquatic microbial communities have so far only poorly been disentangled. Here we characterized the environmental risk of 50 main kinds of antibiotics from 9 classes at a concentration of 10 μg/L for aquatic bacterial communities via metadata analysis combined with machine learning. Metadata analysis showed that the alpha diversity of the bacterial community increased only after treatment with aminoglycoside and β-lactam antibiotics, while its structure was changed by almost all tested antibiotics. The antibiotic treatment also disturbed the functions of the bacterial community, especially with regard to metabolic pathways, including amino acids, cofactors, vitamins, xenobiotics and carbohydrate metabolism. The critical characteristics (atom stereocenter count, number of hydrogen atoms in the antibiotic, and the adipose water coefficient) of antibiotics affecting the composition of the bacterial community in aquatic habitats were screened by machine learning. The key characteristics of antibiotics affecting the function bacterial communities were the number of hydrogen atoms, molecular weight and complexity. In summary, by developing machine learning models and by performing metadata analysis, this study provides the relationship between the properties of antibiotics and their adverse impacts on aquatic microbial communities from a macro perspective. The study also provides guidance for the rational design of antibiotics. Show less
The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical... Show moreThe SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (Δ500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-β levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-β responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design. Show less
Lu, T.; Qu, Q.; Lavoie, M.; Pan, X.; Peijnenburg, W.J.G.M.; Zhou, Z.; ... ; Qian, H. 2020
Scholars are in search of an integrated perspective to explain entrepreneurship in a coherent way. This study sets to contribute to this search with a process framework for understanding similar... Show moreScholars are in search of an integrated perspective to explain entrepreneurship in a coherent way. This study sets to contribute to this search with a process framework for understanding similar patterns of entrepreneurship actions over time in different settings. This research uses the multi-case study approach to observe the entrepreneurial process in 12 technology-based start-ups. The result is a framework of entrepreneurship as a social design process. This translates into a number of concrete insights. First, in addition to the widely accepted path of scanning to discover entrepreneurial idea, two complementary paths towards the initial ideas are added: sensing via experiencing and sensing via visioning. The initial input is vague, simple and incomplete idea, in comparison to detailed business plans. Second, upon identification of the initial idea, the entrepreneur engages in a deliberate conceptualization process to test, develop and evaluate the idea. Third, feedback not only makes the ideas explicit but also serves as the basis for the entrepreneurs__ confidence. Fourth, adaption actions sustain the entrepreneurship process. In conclusion, these findings characterize technology entrepreneurship as a process in which entrepreneurs proactively and iteratively engage in conceptualizing, implementing and adapting actions, until they reach the status of a viable configuration. Show less
