Background： This study was to establish a disease differentiation model for ST-segment elevation myocardial infarction （STEMI） youth patients experiencing ischemia and reperfusion via ...ultra-performance liquid chromatography and mass spectrometry （UPLC/MS） platform, which searches for closely related characteristic metabolites and metabolic pathways to evaluate their predictive value in the prognosis after discharge. Methods： Forty-seven consecutive STEMI patients （23 patients under 45 years of age, referred to here as ＂youth,＂ and 24 elderly patients） and 48 healthy control group members （24 youth, 24 elderly） were registered prospectively. The youth patients were required to provide a second blood draw during a follow-up visit one year after morbidity （n - 22, one lost）. Characteristic metabolites and relative metabolic pathways were screened via UPLC/MS platform base on the Kyoto encyclopedia of genes and genomes （KEGG） and Human Metabolome Database. Receiver operating characteristic （ROC） curves were drawn to evaluate the predictive value of characteristic metabolites in the prognosis after discharge. Results： We successfully established an orthogonal partial least squares discriminated analysis model （R2X = 71.2%, R2Y = 79.6%, and Q2 55.9%） and screened out 24 ions; the sphingolipid metabolism pathway showed the most drastic change. The ROC curve analysis showed that ceramide Cer（dl 8：0/16：0）, Cer（t 18：0/12：0） and sphinganine in the sphingolipid pathway have high sensitivity and specificity on the prognosis related to major adverse cardiovascular events after youth patients were discharged. The area under curve （AUC） was 0.67 1, 0.750, and 0.711, respectively. A follow-up validation one year after morbidity showed corresponding AUC of 0.778, 0.833, and 0.806. Conclusions： By analyzing the plasma metabolism of myocardial infarction patients, we successfully established a model that can distinguish two different factors simultaneously： pathological conditions and age. Sphingolipid metabolism is the top most altered pathway in young STEMI patients and as such may represent a valuable prognostic factor and potential therapeutic target.
•We conducted the first investigation of personal black carbon (BC) exposure among elderly adults in urban China.•The personal BC exposure level in our study is higher than those in developed ...countries or regions.•Temperature could significantly affect personal BC exposure by affecting individual activity patterns.•Individuals’ education level may be a potential determinant of personal BC exposure among elderly adults.
Personal exposure to air pollution is affected by its concentration in the microenvironment and individual time-activity patterns. To investigate personal black carbon (BC) exposure levels and identify their potential determinants, we conducted a panel study among 67 elderly residents aged 60–69 years in Jinan, China. Personal BC exposure was measured using portable real-time monitors, while corresponding ambient BC concentrations and meteorological conditions were also collected from the local central site. Time-activity and household characteristics were recorded. A linear mixed-effects model was used to identify potential determinants of personal BC exposure. The daily average personal BC exposure concentration was 4.1 ± 2.0 μg/m3 (±standard deviation, SD), which was significantly lower than the ambient concentration (4.6 ± 2.5 μg/m3) (p < 0.001). Strong correlation (Spearman’s r = 0.63, p < 0.001) was found between personal and ambient BC concentrations. The fixed-site monitoring ambient concentration cannot fully reflect the actual personal exposure concentration. Ambient BC concentration, ambient temperature, relative humidity, education level and air purifier use were significant determinants of personal BC exposure. Our findings highlight the need for detailed assessment of personal exposure on health risk assessment of BC and also help develop strategies for targeted risk reduction.
Tropaeolum majus (nasturtium) is an important ornamental and medicinal plant due to its colorful flowers, shield-shaped leaves, and richness in mineral elements and bioactive compounds. However, the ...key genes related to these important biological traits, as well as their expression patterns and functions, remain obscure. In this study, to choose appropriate reference genes for quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis, we screened 14 candidate genes from the transcriptome of T. majus and evaluated their expression stability. Through evaluation with four commonly used algorithms (geNorm, NormFinder, BestKeeper, and RefFinder), EXP1, EXP2, and TUB6 were found to be the most stably expressed genes among different organs, while EXP1 combined with CYP2 was identified as the optimal reference gene combination for seeds at different development stages. For all the tested samples, EXP1, EXP2, CYP2, and ACT2 were the most suitable reference genes. Moreover, the target gene KCS11 involved in very-long-chain fatty acid biosynthesis was employed to confirm the most and least stable reference genes in different organs, seeds at different development stages, and all the tested samples. The expression profiles of KCS11 were similar, with minor differences based on the analysis of different stable reference genes (either alone or in combination), while the expression profiles were diverse and the relative expression level was overestimated when using the least stable ones. These results suggest that the appropriate selection of reference genes is critical for the normalization of gene expression. Furthermore, the reference genes screened in this study will greatly improve the accuracy of the qRT-PCR quantification of candidate genes involved in the many biological characteristics of nasturtium.
Carbon reserves in rice straw (stem and sheath) before flowering contribute to a significant portion of grain filling. However, the molecular mechanism of carbon reserve remobilization from straw to ...grains remains unclear. In this study, super rice LYP9 and conventional rice 9311 showed different carbon reserve remobilization behaviors. The transcriptomic profiles of straws of LYP9 and 9311 were analyzed at three stages of grain filling. Among the differentially expressed genes (DGs), 5,733 genes were uniquely up- or down-regulated at 30 days after anthesis (DAA) between LYP9 and 9311 in comparison with 681 at 10 DAA and 495 at 20 DAA, suggesting that the gene expression profile of LYP9 was very different from that of 9311 at the late stage of grain filling. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Ontology (GO) classification of DGs both showed that the carbohydrate catabolic pathway, plant hormone signal transduction and photosynthesis pathway were enriched in DGs, suggesting their roles in carbon reserve remobilization, which explains to a certain extent the difference in non-structural carbohydrate content, photosynthesis and ABA content between the two cultivars during grain filling. Further comparative analysis and confirmation by quantitative real-time PCR and enzyme assays suggest that genes involved in trehalose synthesis (trehalose-phosphate phosphatase and trehalose 6-phosphate synthase/phosphatase), starch degradation (β-amylase) and sucrose synthesis (sucrose-phosphate synthase and sucrose synthase) were important for carbon reserve remobilization, whereas ABA content was determined by the counteraction of NCED1 and ABA8ox1 genes. The higher expression level of all these genes and ABA content in 9311 resulted in better efficiency of carbon reserve remobilization in 9311 than in LYP9.
The experiments of high-strength steel-fiber-reinforced concrete (SFRC) beams subjected to fatigue bend loading were conducted in this work. A total of 12 beams were tested to failure, including 2 ...under static loading and 10 under fatigue loading. The main varying parameters of the tested beams included the stress level, fiber volume fraction, and strength of the steel reinforcement. The fatigue life, mid-span deflection, residual deflection, and crack width were measured and evaluated. The stiffness degradation of high-strength SFRC beams was analyzed. The results indicated that both the stress level and fiber volume fraction have significant influences on the fatigue life of the tested beam. The fatigue life of the beams decreased with increasing stress level and increased with fiber volume fraction. With added steel fibers, the stiffness of the beam improved significantly, which leads to the reduced deflection and narrower average crack width during the fatigue loading. The total deflection of high-strength SFRC beam subjected to fatigue loading can be divided into two parts: residual deflections and instantaneous deflections. Both of them were fitted based on the experimental results. Finally, an analytical method which considers the influences of steel fibers was proposed to predict the mid-span deflections of high-strength SFRC beam at different cycles, which agrees well with the experimental results.
The biological functions of coiled coils generally depend on efficient folding and perfect pairing of their α-helices. Dynamic changes in the helical registry that lead to staggered helices have only ...been proposed for a few special systems and not found in generic coiled coils. Here, we report our observations of multiple staggered helical structures of two canonical coiled coils. The partially folded structures are formed predominantly by coiled coil misfolding and occasionally by helix sliding. Using high-resolution optical tweezers, we characterized their energies and transition kinetics at a single-molecule level. The staggered states occur less than 2% of the time and about 0.1% of the time at zero force. We conclude that dynamic changes in helical registry may be a general property of coiled coils. Our findings should have broad and unique implications in functions and dysfunctions of proteins containing coiled coils.
•The genome was sequenced for a monokaryon strain of Pleurotus eryngii.•Combined Illumina and long-reads Pacbio datasets analyses gave an improved genome assembly.•The number of CAZymes determined in ...the genome of P. eryngii 183 was the highest than that in other fungi.•The number of oxidoreductases for lignin degradation was much higher (41 copies) than other saprophytic fungi.•The CAZymes and oxidoreductases in P. eryngii 183 brightened the mechanisms of bioconversion of cellulose and lignin in this fungus and increased the diversity of the enzymes related to degradation of lignocellulose.
Pleurotus eryngii (DC.) Quél. is widely used for bioconverting lignocellulosic byproducts into biofuel and value added products. Sequencing and annotating the genome of a monokaryon strain P. eryngii 183 allows us to gain a better understanding of carbohydrate-active enzymes (CAZymes) and oxidoreductases for degradation of lignocellulose in white-rot fungi. The genomic data provides insights into genomic basis of degradation mechanisms of lignin and cellulose and may pave new avenues for lignocellulose bioconversion.
CD1d-restricted natural killer T (NKT) cells are innate-like lymphocytes that express a conserved T-cell receptor and contribute to host defence against various microbial pathogens. However, their ...target lipid antigens have remained elusive. Here we report evidence for microbial, antigen-specific activation of NKT cells against Gram-negative, lipopolysaccharide (LPS)-negative alpha-Proteobacteria such as Ehrlichia muris and Sphingomonas capsulata. We have identified glycosylceramides from the cell wall of Sphingomonas that serve as direct targets for mouse and human NKT cells, controlling both septic shock reaction and bacterial clearance in infected mice. In contrast, Gram-negative, LPS-positive Salmonella typhimurium activates NKT cells through the recognition of an endogenous lysosomal glycosphingolipid, iGb3, presented by LPS-activated dendritic cells. These findings identify two novel antigenic targets of NKT cells in antimicrobial defence, and show that glycosylceramides are an alternative to LPS for innate recognition of the Gram-negative, LPS-negative bacterial cell wall.
Abstract Background and aims Patients with familial hypercholesterolemia (FH) are often characterized by premature coronary artery disease (CAD) with heterogeneity at onset. The aim of the present ...study was to investigate the associations of lipoprotein (a) Lp(a) with the FH phenotype, genotype and roles of Lp(a) in determining CAD risk among patients with and without FH. Methods We enrolled 8050 patients undergoing coronary angiography, from our Lipid clinic. Clinical FH was diagnosed using the Dutch Lipid Clinic Network criteria. Mutational analysis ( LDLR , APOB , PCSK9 ) in definite/probable FH was performed by target exome sequencing. Results Lp(a) levels were increased, with a clinical FH diagnosis (unlikely, possible, definite/probable FH) independent of the patients status, with Lp(a)- hyperlipoproteinemia Lp(a)-HLP (median 517.70 vs. 570.98 vs. 604.65 mg/L, p < 0.001) or without (median 89.20 vs. 99.20 vs. 133.67 mg/L, p < 0.001). Patients with Lp(a)-HLP had a higher prevalence of definite/probable FH than those without (6.1% vs. 2.4%, p < 0.05). However, no significant difference in Lp(a) was observed in patients with definite/probable FH phenotype carrying LDLR or LDLR-independent ( APOB , PCSK9 ) or neither mutations ( p > 0.05). Multivariate analysis showed that Lp(a) and FH phenotype were both significant determinants in predicting the early onset and severity of CAD. Subsequently, patients with Lp(a)-HLP in definite/probable FH increased significantly the CAD risk (all p < 0.05). Conclusions Lp(a) levels were higher in patients with FH phenotype than in those without, but no difference were found in FH patients of different mutated backgrounds. Moreover, Lp(a) and FH played a synergistic role in predicting the early onset and severity of CAD.
The establishment and rapid progress in sensitive biosensing using immunogold silver enhancement has occurred in the past 30 years. Its high sensitivity and simplicity have made immunogold silver ...enhancement a revolutionary technique for signal amplification in biosensing. This review focuses on the major applications of immunogold silver enhancement, with special emphasis on quantitative biosensing. In this review, the combinations of immunogold silver enhancement with a series of quantitative techniques, such as colorimetry, electrical and electrochemical methods, gravimetry, chemiluminescence, Raman spectroscopy, and inductively coupled plasma-mass spectrometry (ICP-MS), are discussed in detail. Immunogold silver enhancement has become one of the most useful methods in highly sensitive quantitative bioanalysis. The recent development of ICP-MS detection shows great potential in combination with immunogold silver enhancement.
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