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1.
    
Since 2008, European and German legislative initiatives for climate protection and reduced dependency on fossil resources led to the introduction of biofuels as CO2-reduced alternatives in the heating oil sector. In the case of biodiesel, customers were confronted with accelerated microbial contaminations during storage. Since then, other fuel alternatives, like hydrogenated vegetable oils (HVOs), gas-to-liquid (GtL) products, or oxymethylene ether (OME) have been developed. In this study, we use online monitoring of microbial CO2 production and the simulation of onset of microbial contamination to investigate the contamination potential of fuel alternatives during storage. As references, fossil heating oil of German refineries are used. Biodiesel blends with fossil heating oils confirmed the promotion of microbial activity. In stark contrast, OMEs have an antimicrobial effect. The paraffinic Fischer–Tropsch products and biogenic hydrogenation products demonstrate to be at least as resistant to microbial contamination as fossil heating oils despite allowing a diversity of representative microbes. Through mass spectrometry, elemental analysis, and microbial sequencing, we can discuss fuel properties that affect microbial contaminations. In summary, novel, non-fossil heating oils show clear differences in microbial resistance during long-term storage. Designing blends with an intrinsic resistance against microbial contamination and hence reduced activity might be an option.  相似文献   

2.
    
At standard doses used for schizophrenia or bipolar disorder, quetiapine has been associated with weight gain and increased levels of triglycerides, to­tal cholesterol and low‐density lipoprotein (LDL) cholesterol, which are risk factors for cardiovascular morbidity and mortality. However, this drug is also commonly used off‐label at low doses for anxiolytic or hypnotic purposes, and its cardiovascular safety at these doses is unknown. We aimed to assess the risk of major adverse cardiovascular events with use of low‐dose quetiapine compared to use of Z‐drug hypnotics in a nationwide, active comparator‐controlled cohort study. The cohort included new users of either drugs in Denmark from 2003 to 2017, aged 18‐85 years, without history of ischemic stroke, myocardial infarction, cancer, and severe mental illness. The main outcome was the occurrence of major adverse cardiovascular events, defined as non‐fatal myocardial infarction or ischemic stroke, or death from cardiovascular causes. Selective serotonin reuptake inhibitors (SSRIs) were used as an alternative comparator in sensitivity analyses. Altogether, we compared 60,566 low‐dose quetiapine users with 454,567 Z‐drug users, followed for 890,198 person‐years in intent‐to‐treat analysis, and 330,334 person‐years in as‐treated analysis. In intention‐to‐treat analysis, low‐dose quetiapine was associated with an increased risk of major adverse cardiovascular events (adjusted hazard ratio, aHR=1.13, 95% CI: 1.02‐1.24, p=0.014) and cardiovascular death (aHR=1.26, 95% CI: 1.11‐1.43, p<0.001). In as‐treated analysis, continuous low‐dose quetiapine use was associated with increased risk of major adverse cardiovascular events (aHR=1.52, 95% CI: 1.35‐1.70, p<0.001), non‐fatal ischemic stroke (aHR=1.37, 95% CI: 1.13‐1.68, p=0.002) and cardiovascular death (aHR=1.90, 95% CI: 1.64‐2.19, p<0.001). The risk of major adverse cardiovascular events was greater in women (aHR=1.28, p=0.02) and those aged ≥65 years at initiation (aHR=1.24, p<0.001). Compared to SSRIs, low‐dose quetiapine use was associated with an increased risk of major adverse cardiovascular events (aHR=1.42, p<0.001), non‐fatal ischemic stroke (aHR=1.27, p=0.0028) and cardiovascular death (aHR=1.72, p<0.001). So, we conclude that the use of low‐dose quetiapine is associated with an increased risk of major adverse cardiovascular events, especially in women and the elderly. On the basis of these findings, we suggest that use of off‐label low‐dose quetiapine for sedative or hypnotic purposes should be discouraged.  相似文献   

3.
    
Abstract The fermentation of cellulose at 55°C by different associations of the 3 bacteria Clostridium thermocellum, Methanobacterium sp. and Methanosarcina MP, was studied. C. thermocellum alone produced acetate, lactate, ethanol, H2 and CO2. The co-culture C. thermocellum-Methanobacterium sp. produced more acetate and less ethanol than the monoculture of Clostridium .
Methanosarcina MP used acetate only in the triculture including Methanobacterium sp. When methanol was added (5 mM) to the triculture, Methanosarcina MP had a shorter lag phase on acetate and degraded much more acetate. maximum methane production was 8.5 mmol CH4/g cellulose degraded.  相似文献   

4.
    
In this study, high‐throughput sequencing (HTS) was used to compare and analyze the microbial diversity and succession during the brewing process of xiaoqu Baijiu. A total of 34 phyla and 378 genera of bacteria, as well as four phyla, 32 genera of fungi were detected. At the phylum level, Firmicutes, Proteobacteria, Ascomycota, and Mucoromycota were the dominant groups. During the brewing process of xiaoqu Baijiu, the dominant bacteria were Weissella and unidentified Rickettsiales within the first 2 days of brewing, followed by Lactobacillus at 3 days until to the end of brewing. The dominant fungi were Rhizopus, Saccharomyces, and Issatchenkia. The relative abundance of Rhizopus decreased with the extension of brewing time, while the relative abundance of Saccharomyces increased, and Saccharomyces became the dominant species at the second day of brewing. This study revealed the diversity and changes of the microbial community during the brewing process of xiaoqu Baijiu, providing theoretical support and laying a foundation for future study on the contribution of microbial metabolism during brewing of xiaoqu Baijiu, thereby promoting the development of xiaoqu Baijiu industry.  相似文献   

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Transmission electron microscopy has historically been indispensable for virology research, as it offers unique insight into virus function. In the past decade, as cryo‐electron microscopy (cryo‐EM) has matured and become more accessible, we have been able to peer into the structure of viruses at the atomic level and understand how they interact with the host cell, with drugs or with antibodies. Perhaps, there was no time in recent history where cryo‐EM was more needed, as SARS‐CoV‐2 has spread around the globe, causing millions of deaths and almost unquantifiable economic devastation. In this concise review, we aim to mark the most important contributions of cryo‐EM to understanding the structure and function of SARS‐CoV‐2 proteins, from surface spikes to the virus core and from virus‐receptor interactions to antibody binding.  相似文献   

7.
    
Diabetic osteoporosis is secondary osteoporosis and a serious complication of diabetes with a high incidence rate and poor prognosis. The specific mechanism of diabetic osteoporosis is unclear, and prevention and treatment options are limited. Recently, melatonin has been found to prevent and treat diabetic osteoporosis. Herein, we investigated the mechanism whereby melatonin inhibits osteoclastogenesis and identified a new target for osteoporosis treatment. We established an in vitro osteoblast–osteoclast co‐culture system as a diabetic osteoporosis model. Osteoclastogenesis was determined using tartrate‐resistant acid phosphatase staining and cathepsin K expression. Real‐time PCR was used to ascertain expression of microRNA mir‐882, targeting Rev‐Erbα. Western blotting was performed to detect the expression of Rev‐Erbα, receptor activator of NF‐kB ligand (RANKL), and osteoprotegerin (OPG), and ELISA was utilized to analyse the secreted form of RANKL. High glucose promoted osteoclastogenesis and elevated the RANKL/OPG ratio in osteoblasts, while melatonin reversed these effects. High glucose inhibited Rev‐Erbα expression, while melatonin promoted its expression. Conversely, high glucose promoted mir‐882 expression, while melatonin inhibited it. We infer that melatonin inhibits RANKL expression in osteoblasts via the mir‐882/Rev‐Erbα axis, thus inhibiting osteoclastogenesis. Our findings provide insights into diabetic osteoporosis and identify a new therapeutic target for osteoporosis.  相似文献   

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9.
    
Changes in intestinal nitric oxide metabolism are discussed to contribute for the development of intestinal barrier dysfunction in non‐alcoholic fatty liver disease (NAFLD). To induce steatosis, female C57BL/6J mice were pair‐fed with a liquid control diet (C) or a fat‐, fructose‐ and cholesterol‐rich diet (FFC) for 8 weeks. Mice received the diets ± 2.49 g L‐arginine/kg bw/day for additional 5 weeks. Furthermore, mice fed C or FFC ± L‐arginine/kg bw/day for 8 weeks were concomitantly treated with the arginase inhibitor Nω‐hydroxy‐nor‐L‐arginine (nor‐NOHA, 0.01 g/kg bw). Liver damage, intestinal barrier function, nitric oxide levels and arginase activity in small intestine were assessed. Also, arginase activity was measured in serum from 13 patients with steatosis (NAFL) and 14 controls. The development of steatosis with beginning inflammation was associated with impaired intestinal barrier function, increased nitric oxide levels and a loss of arginase activity in small intestine in mice. L‐arginine supplementation abolished the latter along with an improvement of intestinal barrier dysfunction; nor‐NOHA attenuated these effects. In patients with NAFL, arginase activity in serum was significantly lower than in healthy controls. Our data suggest that increased formation of nitric oxide and a loss of intestinal arginase activity is critical in NAFLD‐associated intestinal barrier dysfunction.  相似文献   

10.
    
Population genetic structure in the marine environment can be influenced by life‐history traits such as developmental mode (biphasic, with distinct adult and larval morphology, and direct development, in which larvae resemble adults) or habitat specificity, as well as geography and selection. Developmental mode is thought to significantly influence dispersal, with direct developers expected to have much lower dispersal potential. However, this prediction can be complicated by the presence of geophysical barriers to dispersal. In this study, we use a panel of 8,020 SNPs to investigate population structure and biogeography over multiple spatial scales for a direct‐developing species, the New Zealand endemic marine isopod Isocladus armatus. Because our sampling range is intersected by two well‐known biogeographic barriers (the East Cape and the Cook Strait), our study provides an opportunity to understand how such barriers influence dispersal in direct developers. On a small spatial scale (20 km), gene flow between locations is extremely high, suggestive of an island model of migration. However, over larger spatial scales (600 km), populations exhibit a clear pattern of isolation‐by‐distance. Our results indicate that I. armatus exhibits significant migration across the hypothesized barriers and suggest that large‐scale ocean currents associated with these locations do not present a barrier to dispersal. Interestingly, we find evidence of a north‐south population genetic break occurring between Māhia and Wellington. While no known geophysical barrier is apparent in this area, it coincides with the location of a proposed border between bioregions. Analysis of loci under selection revealed that both isolation‐by‐distance and adaption may be contributing to the degree of population structure we have observed here. We conclude that developmental life history largely predicts dispersal in the intertidal isopod I. armatus. However, localized biogeographic processes can disrupt this expectation, and this may explain the potential meta‐population detected in the Auckland region.  相似文献   

11.
    
ObjectivesTo elaborately decipher the mouse and human bladders at single‐cell levels.Materials and MethodsWe collected more than 50,000 cells from multiple datasets and created, up to date, the largest integrated bladder datasets. Pseudotime trajectory of urothelium and interstitial cells, as well as dynamic cell‐cell interactions, was investigated. Biological activity scores and different roles of signaling pathways between certain cell clusters were also identified.ResultsThe glucose score was significantly high in most urothelial cells, while the score of H3 acetylation was roughly equally distributed across all cell types. Several genes via a pseudotime pattern in mouse (Car3, Dkk2, Tnc, etc.) and human (FBLN1, S100A10, etc.) were discovered. S100A6, TMSB4X, and typical uroplakin genes seemed as shared pseudotime genes for urothelial cells in both human and mouse datasets. In combinational mouse (n = 16,688) and human (n = 22,080) bladders, we verified 1,330 and 1,449 interactive ligand‐receptor pairs, respectively. The distinct incoming and outgoing signaling was significantly associated with specific cell types. Collagen was the strongest signal from fibroblasts to urothelial basal cells in mouse, while laminin pathway for urothelial basal cells to smooth muscle cells (SMCs) in human. Fibronectin 1 pathway was intensely sent by myofibroblasts, received by urothelial cells, and almost exclusively mediated by SMCs in mouse bladder. Interestingly, the cell cluster of SMCs 2 was the dominant sender and mediator for Notch signaling in the human bladder, while SMCs 1 was not. The expression of integrin superfamily (the most common communicative pairs) was depicted, and their co‐expression patterns were located in certain cell types (eg, Itgb1 and Itgb4 in mouse and human basal cells).ConclusionsThis study provides a complete interpretation of the normal bladder at single‐cell levels, offering an in‐depth resource and foundation for future research.  相似文献   

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Endometrial cancer (EC) is the most common gynaecological malignancy with increasing incidence in developed countries. As gold standard, hysteroscopy confirms only 30% of suspected ECs. The detection of EC cells in the vagina by fluorescence in situ hybridization (FISH) after a smear test could reduce invasive procedures in the future. Using array‐based comparative genome hybridization (aCGH) on 65 endometrial carcinomas, most frequently imbalanced regions of the tumour genome were identified. Bacterial artificial chromosomes were used to generate FISH‐probes homologue to these human regions. The FISH test was hybridized on swabs specimens collected from the vaginal cavity. Samples from six patients without EC were selected as a negative control and on 13 patients with known EC as a positive control. To distinguish between benign and EC cases, the cut‐off value has been defined. A first validation of this EC‐FISH Test was performed with swabs from 41 patients with suspected EC. The most common genomic imbalances in EC are around the CTNNB1, FBXW7 and APC genes. The cut‐off is defined at 32% of analysed cells without diploid signal pattern. This differs significantly between the positive and negative controls (p < 0.001). In a first validation cohort of 41 patients with suspected EC, the EC‐FISH Test distinguishes patients with and without EC with a sensitivity of 91% and a specificity of 83%. The negative predictive value is 96%. This is the first report of a non‐invasive EC‐FISH Test to predict EC in women with suspected EC.  相似文献   

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16.
    
Understanding the types and magnitude of human‐caused mortality is essential for maintaining viable large carnivore populations. We used a database of cause‐specific mortality to examine how hunting regulations and landscape configurations influenced human‐caused mortality of North American gray wolves (Canis lupus). Our dataset included 21 studies that monitored the fates of 3564 wolves and reported 1442 mortalities. Human‐caused mortality accounted for 61% of mortality overall, with 23% due to illegal harvest, 16% due to legal harvest, and 12% the result of management removal. The overall proportion of anthropogenic wolf mortality was lowest in areas with an open hunting season compared to areas with a closed hunting season or mixed hunting regulations, suggesting that harvest mortality was neither fully additive nor compensatory. Proportion of mortality from management removal was reduced in areas with an open hunting season, suggesting that legal harvest may reduce human‐wolf conflicts or alternatively that areas with legal harvest have less potential for management removals (e.g., less livestock depredation). Proportion of natural habitat was negatively correlated with the proportion of anthropogenic and illegal harvest mortality. Additionally, the proportion of mortality due to illegal harvest increased with greater natural habitat fragmentation. The observed association between large patches of natural habitat and reductions in several sources of anthropogenic wolf mortality reiterate the importance of habitat preservation to maintain wolf populations. Furthermore, effective management of wolf populations via implementation of harvest may reduce conflict with humans. Effective wolf conservation will depend on holistic strategies that integrate ecological and socioeconomic factors to facilitate their long‐term coexistence with humans.  相似文献   

17.
    
The SARS‐CoV‐2 infection cycle is a multistage process that relies on functional interactions between the host and the pathogen. Here, we repurposed antiviral drugs against both viral and host enzymes to pharmaceutically block methylation of the viral RNA 2''‐O‐ribose cap needed for viral immune escape. We find that the host cap 2''‐O‐ribose methyltransferase MTr1 can compensate for loss of viral NSP16 methyltransferase in facilitating virus replication. Concomitant inhibition of MTr1 and NSP16 efficiently suppresses SARS‐CoV‐2 replication. Using in silico target‐based drug screening, we identify a bispecific MTr1/NSP16 inhibitor with anti‐SARS‐CoV‐2 activity in vitro and in vivo but with unfavorable side effects. We further show antiviral activity of inhibitors that target independent stages of the host SAM cycle providing the methyltransferase co‐substrate. In particular, the adenosylhomocysteinase (AHCY) inhibitor DZNep is antiviral in in vitro, in ex vivo, and in a mouse infection model and synergizes with existing COVID‐19 treatments. Moreover, DZNep exhibits a strong immunomodulatory effect curbing infection‐induced hyperinflammation and reduces lung fibrosis markers ex vivo. Thus, multispecific and metabolic MTase inhibitors constitute yet unexplored treatment options against COVID‐19.  相似文献   

18.
    
Treatment of multiple malignant solid tumours with programmed death (PD)‐1/PD ligand (PD‐L) 1 inhibitors has been reported. However, the efficacy and immune adverse effects of combination therapies are controversial. This meta‐analysis was performed with PubMed, Web of Science, Medline, EMBASE and Cochrane Library from their inception until January 2020. Random‐effect model was adopted because of relatively high heterogeneity. We also calculated hazard ratio (HR) of progression‐free survival (PFS), overall survival (OS) and risk ratio (RR) of adverse events (AEs), the incidence of grade 3‐5 AEs by tumour subgroup, therapeutic schedules and therapy lines. Nineteen articles were selected using the search strategy for meta‐analysis. Combined PD‐1/PD‐L1 inhibitors prolonged OS and PFS (HR 0.72, P < 0.001) and (HR 0.66, P < 0.001). In addition, incidence of all‐grade and grade 3‐5 AEs was not significant in the two subgroup analyses (HR 1.01, P = 0.31) and (HR 1.10, P = 0.07), respectively. Our meta‐analysis indicated that combination therapy with PD‐1/PD‐L1 inhibitors had greater clinical benefits and adverse events were not increased significantly.  相似文献   

19.
    
Acanthamoeba polyphaga Mimivirus, a complex virus that infects amoeba, was first reported in 2003. It is now known that its DNA genome encodes for nearly 1,000 proteins including enzymes that are required for the biosynthesis of the unusual sugar 4‐amino‐4,6‐dideoxy‐d‐glucose, also known as d‐viosamine. As observed in some bacteria, the pathway for the production of this sugar initiates with a nucleotide‐linked sugar, which in the Mimivirus is thought to be UDP‐d‐glucose. The enzyme required for the installment of the amino group at the C‐4′ position of the pyranosyl moiety is encoded in the Mimivirus by the L136 gene. Here, we describe a structural and functional analysis of this pyridoxal 5′‐phosphate‐dependent enzyme, referred to as L136. For this analysis, three high‐resolution X‐ray structures were determined: the wildtype enzyme/pyridoxamine 5′‐phosphate/dTDP complex and the site‐directed mutant variant K185A in the presence of either UDP‐4‐amino‐4,6‐dideoxy‐d‐glucose or dTDP‐4‐amino‐4,6‐dideoxy‐d‐glucose. Additionally, the kinetic parameters of the enzyme utilizing either UDP‐d‐glucose or dTDP‐d‐glucose were measured and demonstrated that L136 is efficient with both substrates. This is in sharp contrast to the structurally related DesI from Streptomyces venezuelae, whose three‐dimensional architecture was previously reported by this laboratory. As determined in this investigation,DesI shows a profound preference in its catalytic efficiency for the dTDP‐linked sugar substrate. This difference can be explained in part by a hydrophobic patch in DesI that is missing in L136. Notably, the structure of L136 reported here represents the first three‐dimensional model for a virally encoded PLP‐dependent enzyme and thus provides new information on sugar aminotransferases in general.  相似文献   

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Fecal microbial biomarkers represent a less invasive alternative for acquiring information on wildlife populations than many traditional sampling methodologies. Our goal was to evaluate linkages between fecal microbiome communities in Rocky Mountain elk (Cervus canadensis) and four host factors including sex, age, population, and physical condition (body‐fat). We paired a feature‐selection algorithm with an LDA‐classifier trained on elk differential bacterial abundance (16S‐rRNA amplicon survey) to predict host health factors from 104 elk microbiomes across four elk populations. We validated the accuracy of the various classifier predictions with leave‐one‐out cross‐validation using known measurements. We demonstrate that the elk fecal microbiome can predict the four host factors tested. Our results show that elk microbiomes respond to both the strong extrinsic factor of biogeography and simultaneously occurring, but more subtle, intrinsic forces of individual body‐fat, sex, and age‐class. Thus, we have developed and described herein a generalizable approach to disentangle microbiome responses attributed to multiple host factors of varying strength from the same bacterial sequence data set. Wildlife conservation and management presents many challenges, but we demonstrate that non‐invasive microbiome surveys from scat samples can provide alternative options for wildlife population monitoring. We believe that, with further validation, this method could be broadly applicable in other species and potentially predict other measurements. Our study can help guide the future development of microbiome‐based monitoring of wildlife populations and supports hypothetical expectations found in host‐microbiome theory.  相似文献   

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