Integrated metabolomics and metagenomics analysis of plasma and urine identified microbial metabolites associated with coronary heart disease

Coronary heart disease (CHD) is top risk factor for health in modern society, causing high mortality rate each year. However, there is no reliable way for early diagnosis and prevention of CHD so far. So study the mechanism of CHD and development of novel biomarkers is urgently needed. In this study, metabolomics and metagenomics technology are applied to discover new biomarkers from plasma and urine of 59 CHD patients and 43 healthy controls and trace their origin. We identify GlcNAc-6-P which has good diagnostic capability and can be used as potential biomarkers for CHD, together with mannitol and 15 plasma cholines. These identified metabolites show significant correlations with clinical biochemical indexes. Meanwhile, GlcNAc-6-P and mannitol are potential metabolites originated from intestinal microbiota. Association analysis on species and function levels between intestinal microbes and metabolites suggest a close correlation between Clostridium sp. HGF2 and GlcNAc-6-P, Clostridium sp. HGF2, Streptococcus sp. M143, Streptococcus sp. M334 and mannitol. These suggest the metabolic abnormality is significant and gut microbiota dysbiosis happens in CHD patients

Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome

INTRODUCTION Although much effort has been devoted to studying yeast in the past few decades, our understanding of this model organism is still limited. Rapidly developing DNA synthesis techniques have made a “build-to-understand” approach feasible to reengineer on the genome scale. Here, we report on the completion of a 770-kilobase synthetic yeast chromosome II (synII). SynII was characterized using extensive Trans-Omics tests. Despite considerable sequence alterations, synII is virtually indistinguishable from wild type. However, an up-regulation of translational machinery was observed and can be reversed by restoring the transfer RNA (tRNA) gene copy number. RATIONALE Following the “design-build-test-debug” working loop, synII was successfully designed and constructed in vivo. Extensive Trans-Omics tests were conducted, including phenomics, transcriptomics, proteomics, metabolomics, chromosome segregation, and replication analyses. By both complementation assays and SCRaMbLE (synthetic chromosome rearrangement and modification by loxP -mediated evolution), we targeted and debugged the origin of a growth defect at 37°C in glycerol medium. RESULTS To efficiently construct megabase-long chromosomes, we developed an I- Sce I–mediated strategy, which enables parallel integration of synthetic chromosome arms and reduced the overall integration time by 50% for synII. An I- Sce I site is introduced for generating a double-strand break to promote targeted homologous recombination during mitotic growth. Despite hundreds of modifications introduced, there are still regions sharing substantial sequence similarity that might lead to undesirable meiotic recombinations when intercrossing the two semisynthetic chromosome arm strains. Induction of the I- Sce I–mediated double-strand break is otherwise lethal and thus introduced a strong selective pressure for targeted homologous recombination. Since our strategy is designed to generate a markerless synII and leave the URA3 marker on the wild-type chromosome, we observed a tenfold increase in URA3 -deficient colonies upon I- Sce I induction, meaning that our strategy can greatly bias the crossover events toward the designated regions. By incorporating comprehensive phenotyping approaches at multiple levels, we demonstrated that synII was capable of powering the growth of yeast indistinguishably from wild-type cells (see the figure), showing highly consistent biological processes comparable to the native strain. Meanwhile, we also noticed modest but potentially significant up-regulation of the translational machinery. The main alteration underlying this change in expression is the deletion of 13 tRNA genes. A growth defect was observed in one very specific condition—high temperature (37°C) in medium with glycerol as a carbon source—where colony size was reduced significantly. We targeted and debugged this defect by two distinct approaches. The first approach involved phenotype screening of all intermediate strains followed by a complementation assay with wild-type sequences in the synthetic strain. By doing so, we identified a modification resulting from PCRTag recoding in TSC10 , which is involved in regulation of the yeast high-osmolarity glycerol (HOG) response pathway. After replacement with wild-type TSC10 , the defect was greatly mitigated. The other approach, debugging by SCRaMbLE, showed rearrangements in regions containing HOG regulation genes. Both approaches indicated that the defect is related to HOG response dysregulation. Thus, the phenotypic defect can be pinpointed and debugged through multiple alternative routes in the complex cellular interactome network. CONCLUSION We have demonstrated that synII segregates, replicates, and functions in a highly similar fashion compared with its wild-type counterpart. Furthermore, we believe that the iterative “design-build-test-debug” cycle methodology, established here, will facilitate progression of the Sc2.0 project in the face of the increasing synthetic genome complexity. SynII characterization. ( A ) Cell cycle comparison between synII and BY4741 revealed by the percentage of cells with separated CEN2-GFP dots, metaphase spindles, and anaphase spindles. ( B ) Replication profiling of synII (red) and BY4741 (black) expressed as relative copy number by deep sequencing. ( C ) RNA sequencing analysis revealed that the significant up-regulation of translational machinery in synII is induced by the deletion of tRNA genes in synII. </jats:sec

Study on Temperature-Dependent Uniaxial Tensile Tests and Constitutive Relationship of Modified Polyurethane Concrete

Modified polyurethane concrete (MPUC) is a new material for steel deck pavements. In service, the pavement is often cracked due to excessive tensile stress caused by temperature changes. In order to study the tensile properties of MPUC in the diurnal temperature range of steel decks, uniaxial tensile tests of MPUC were carried out at five temperatures. Three kinds of specimens and a novel fixture were designed and fabricated to compare the results of four different tensile test methods. The deformation of the specimen was collected synchronously by two methods: pasting strain gauge and digital image correlation (DIC) technique. Based on the experiment, the tensile mechanical properties, failure modes, and constitutive relations of MPUC were studied under the effect of temperature. The research results show that the novel fixture can avoid stress concentration. By observing the fracture surface of the specimens, the bonding performance is great between the binder and the aggregate at different temperatures. The tensile strength and elastic modulus of MPUC decrease with increasing temperatures, while the fracture strain, and fracture energy increase with increasing temperatures. The formulas of temperature-dependent tensile strength, fracture strain, and elastic modulus of MPUC were established, and the constitutive relationship of MPUC is further constructed in the rising stage under uniaxial tension. The calculation results show good agreement with experimental ones

External quality assessment for the molecular detection of microsatellite instability in China, 2021-2022

Microsatellite instability (MSI) analysis of tumors informs Lynch syndrome testing, therapeutic choice, and prognosis. The status of MSI is mainly detected by polymerase chain reaction coupled with capillary electrophoresis. However, there are various assays with different detection loci and the obtained results may vary. The objective of this study was to evaluate the concordance among different assays and the performance among different laboratories. External quality assessment (EQA) for the detection of MSI was performed in 2021 and 2022. Each sample panel consisted of five samples, including microsatellite-stable and MSI tumor tissues. The sample panels were coded at random, and the returned results were compared and scored. The fully validated sample panels showed appropriate applicability with commercially available assays. There were eight false-negative results in 2021 and five false results (two false-positives and three false-negatives) in 2022. Among the participating laboratories, in 2021, 20 (74.07%) provided completely correct results; in 2022, 38 (92.68%) obtained an optimal score. The molecular detection of MSI in China exhibited an improvement in a 2-year EQA study. Participation in EQA program is an efficient way of assessing the performance of laboratories and improving their ability.</p

Effects of the Framework and Mesoporosity on the Catalytic Activity of Hierarchical Zeolite Catalysts in Benzyl Alcohol Conversion

The catalytic performance of three‐dimensionally ordered mesoporous imprinted (3DOm‐i) zeolite catalysts with different frameworks (3DOm‐i MFI, 3DOm‐i BEA, and 3DOm‐i LTA) were investigated by the liquid‐phase catalytic conversion of benzyl alcohol in mesitylene and compared to that of other microporous and mesoporous catalysts with a high external surface area, which included MCM‐22, 300 nm MFI, ITQ‐2, and Al‐MCM‐41. The mesoporosity in MFI and BEA zeolites can effectively enhance the catalytic performance of the zeolite catalysts for benzyl alcohol self‐etherification catalyzed by both the acid sites on the external and internal surface and the alkylation of mesitylene with benzyl alcohol catalyzed exclusively by the acid sites on the external surface. For 3DOm‐i LTA, MCM‐22, and Al‐MCM‐41, only the acid sites on the external surface can be utilized in the catalytic reactions. A distinct difference in the product selectivity was also observed for the microporous and mesoporous catalysts.Inside out: The effects of the framework and mesoporosity on the catalytic activity of hierarchical zeolite catalysts are investigated by studying the catalytic performance of three‐dimensionally ordered mesoporous imprinted zeolites and comparing them to other microporous and mesoporous catalysts with a high external surface area. The mesoporosity in MFI and BEA zeolites can enhance the catalytic performance of the zeolite catalysts for the self‐etherification of benzyl alcohol.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137338/1/cctc201600322.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137338/2/cctc201600322-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137338/3/cctc201600322_am.pd

Digital Quantitative Study on Fracture Gas Storage Space for a Three-Layer Composite Residual Mining Area

Quantifying the fracture gas storage space is the key to improving the coalbed methane (CBM) extraction efficiency in residual mining areas (RMAs). In this paper, a new digital quantitative description method of fractures is proposed when using a digital image correlation (DIC) system to monitor strata displacement, which improves the accuracy of fracture statistical data. The results show that with the evolution of RMA from single to three layers, the rock strata area with displacement greater than 3.5 mm increases radially and the maximum fracture rate of the uppermost RMA increases by 64.26%. The fracture rate increases exponentially from top to bottom in a long-distance composite RMA and distributes parabolically in the horizontal partition. The area with the highest average fracture rate (12.65%) in the close-distance composite RMA is defined as the concentrated growth area. The longitudinal fracture rate of a cross-layer fracture area in the three-layer RMA exceeds 60%. The cross-layer fracture area connecting the composite RMA at the open-cut side is a favorable extraction location for surface drilling. The research results will provide theoretical support for the safe and sustainable exploitation of CBM and residual coal in composite RMA

Association between gut microbiota and its functional metabolites with prenatal depression in women

Background: The gut microbiota may affect mood through the microbiota-gut-brain axis. The purpose of this study was to examine the effect of the gut microbiota and its metabolites, such as short-chain fatty acids (SCFAs), on prenatal depression and to determine the role of 5-hydroxytryptamine (5-HT) on prenatal depression in association with the gut microbiota and its metabolites (i.e. SCFAs). Methods: Eighty-six pregnant women in the third trimester were recruited. Prenatal depression was determined by a score of 10 via the Edinburgh Postpartum Depression Scale. Demographic data, stool, and blood samples were collected. The gut microbiota and its metabolites SCFAs were determined by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry analysis. Plasma 5-HT was determined by gas chromatography-mass spectrometry analysis. Results: After controlling relevant covariates, our results found the higher the abundance of Candidatus_Soleaferrea, the lower the risk of prenatal depression; the higher the concentration of propanoic acid, the higher risk of prenatal depression. Our results also found the lower the plasma 5-HT, the higher the risk of prenatal depression, and 5-HT was related to unclassified_c_Clostridia and NK4A214_group. However, results of this study did not support the moderating effect of plasma 5-HT on the association of Candidatus_Soleaferrea or propionic acid with prenatal depression. Conclusions: Results of this study supported that changes in certain gut microbiota, SCFAs, and plasma 5-HT during pregnancy were associated with prenatal depression. This finding provides new ideas for interventions based on diet or probiotics to regulate mood during pregnancy