Burdens and Difficulties Experienced by Parental Caregivers of Children and Adolescents with Idiopathic Nephrotic Syndrome in Mainland China: A Qualitative Study.

Purpose: To identify the difficulties and burdens related to the experience of caring for children. Methods: A phenomenological approach was used in this qualitative study. Semi-structured and adolescents with idiopathic nephrotic syndrome (INS) in mainland China. Interviews lasting 35-90 minutes were conducted with 13 parental caregivers of youth with INS. The Colaizzi's analysis was used in data analysis. Results: The mean age of parental caregivers was 40.3 ± 6.1 years, and the average caregiving year of 3.2 ± 3.3 years. Most INS patients were male (69.2%), had a mean age of 7.6 ± 4.2 years. Based on the analysis of the data, five major themes emerged. These were: persistent emotional burden; neglected physical burden; overwhelming financial burden; absence of social support system and burden related to loss of normal life. Conclusion: Health professionals must develop strategies to provide stage-by-stage, targeted health education and psychological support services to parental caregivers of INS youth in China. The government must subsidize routine medications and frequent hospitalizations to minimize the financial burden on parental caregivers of INS youth. Moreover, anti-discrimination policies must be established to protect caregivers from explicit discrimination in public places.

Transcriptome-wide map of N6-methyladenosine (m6A) profiling in coronary artery disease (CAD) with clopidogrel resistance.

BACKGROUND: Clopidogrel resistance profoundly increases the risk of major cardiovascular events in coronary artery disease (CAD) patients. Here, we comprehensively analyse global m6A modification alterations in clopidogrel-resistant (CR) and non-CR patients. METHODS: After RNA isolation, the RNA transcriptome expression (lncRNA, circRNA, and mRNA) was analysed via RNA-seq, and m6A peaks were identified by MeRIP-seq. The altered m6A methylation sites on mRNAs, lncRNAs, and circRNAs were identified, and then, GO and KEGG pathway analyses were performed. Through joint analysis with RNA-seq and MeRIP-seq data, differentially expressed mRNAs harbouring differentially methylated sites were identified. The changes in m6A regulator levels and the abundance of differentially methylated sites were measured by RT-PCR. The identification of m6A-modified RNAs was verified by m6A-IP-qPCR. RESULTS: The expression of 2919 hypermethylated and 2519 hypomethylated mRNAs, 192 hypermethylated and 391 hypomethylated lncRNAs, and 375 hypermethylated and 546 hypomethylated circRNAs was shown to be altered in CR patients. The m6A peaks related to CR indicated lower mark density at the CDS region. Functional enrichment analysis revealed that inflammatory pathways and insulin signalling pathways might be involved in the pathological processes underlying CR. The expression of mRNAs (ST5, KDM6B, GLB1L2, and LSM14B), lncRNAs (MSTRG.13776.1 and ENST00000627981.1), and circRNAs (hsa_circ_0070675_CBC1, hsa-circRNA13011-5_CBC1, and hsa-circRNA6406-3_CBC1) was upregulated in CR patients, while the expression of mRNAs (RPS16 and CREG1), lncRNAs (MSTRG.9215.1), and circRNAs (hsa_circ_0082972_CBC1) was downregulated in CR patients. Moreover, m6A regulators (FTO, YTHDF3, and WTAP) were also differentially expressed. An additional combined analysis of gene expression and m6A peaks revealed that the expression of mRNAs (such as ST5, LYPD2, and RPS16 mRNAs) was significantly altered in the CR patients. CONCLUSION: The expression of m6A regulators, the RNA transcriptome, and the m6A landscape was altered in CR patients. These findings reveal epitranscriptomic regulation in CR patients, which might be novel therapeutic targets in future.

Construction of public health core competence and the improvement of its legal guarantee in China.

Public health core capacity, first established by the 58th United Nations General Assembly in 2003 and recognized by the World Health Organization when "the International Health Regulations" were revised, refers to the basic and necessary capacity to allocate human, financial, and material resources for the prevention and control of public health events that a country or region should have. It includes national and regional levels, and its constituent elements and their basic requirements differ, but public health core capacity building at both national and regional levels requires certain legal safeguards. At present, there are still some problems, including the imperfect legal system, conflicting legal norms, the non-sufficient supply of local legislation, and the weak operability of legislation in the legal guarantee of public health core capacity building in China. China should make improvements in terms of comprehensive cleaning of existing public health laws, strengthening their post-legislative evaluation, adopting parcel legislation, strengthening legislation in key areas of public health, and promoting the supply of local legislation. The goal is to provide a perfect and comprehensive legal system to guarantee the construction of China's core capacity in public health.

Comprehensive analysis of the RNA transcriptome expression profiles and construction of the ceRNA network in heart failure patients with sacubitril/valsartan therapeutic heterogeneity after acute myocardial infarction.

Sacubitril/valsartan has a noteworthy advantage in improving ventricular remodelling, as well as reducing cardiovascular mortality and the rate of heart failure (HF) readmission. However, clinically, some patients with HF still have low sensitivity to sacubitril/valsartan, indicating sacubitril/valsartan resistance (SVR). A total of 46 patients with HF after AMI (23 SVR and 23 non-sacubitril/valsartan resistance (NSVR)) were selected. Five SVR and 5 matched NSVR samples were screened for differentially expressed ncRNAs along with mRNAs. A total of 124 differentially expressed miRNAs, 137 circRNAs, 237 lncRNAs and 50 mRNAs were screened by RNA sequencing technology. After quantitative real-time PCR (qRT‒PCR) verification of selected biomarkers in 18 pairs of samples, we found that for patients with SVR, hsa-miR-543, hsa-miR-642b-5p, hsa-miR-760, hsa_circ_0137499, ENST00000474394, ENST00000528337, E2F1, NEAT1, and YTHDF2 were upregulated, and hsa-miR-424-5p, hsa-miR-21-3p, hsa_circRNA_0003275, hsa_circRNA_0004494, hsa_circ_0093522, ENST00000467951, ENST00000558177, ACTA2, ANPEP, and CAMP were downregulated. Then, with the help of our constructed ceRNA network and functional annotation enrichment, we speculated that inflammatory pathways (such as the apelin signalling pathway) and lipid metabolism pathways (such as fatty acid metabolism) may be involved in the regulation of SVR. These discoveries lay a foundation for further mechanistic research and provide a direction for individualized drug administration.

DNA methylation profile in the whole blood of acute coronary syndrome patients with aspirin resistance.

BACKGROUND: Aspirin resistance (AR) results in major adverse cardiovascular events, and DNA methylation might participate in the regulation of this pathological process. METHODS: In present study, a sum of 35 patients with AR and 35 non-AR (NAR) controls were enrolled. Samples from 5 AR and 5 NAR were evaluated in an 850 BeadChip DNA methylation assay, and another 30 AR versus 30 NAR were evaluated to validate the differentially methylated CpG loci (DML). Then, qRT-PCR was used to investigate the target mRNA expression of genes at CpG loci. Finally, Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to reveal the enriched pathways. RESULTS: The AR and NAR groups displayed significant differences in DNA methylation at 7707 positions, with 270 hypermethylated sites (e.g., cg09555818 located in APOC2) and 7437 sites hypomethylated sites (e.g., cg26828689 located in SLC12A5). Six DML were validated by pyrosequencing, and it was confirmed that DNA methylation (cg16391727, cg21008208, cg21293749, and cg13945576) was related to the increasing risk of AR. The relative mRNA expression of the ROR1 gene was also associated with AR (p = 0.007), suggesting that the change of cg21293749 in DNA methylation might lead to differential ROR1 mRNA expression, ultimately resulting in AR. Furthermore, the identified differentially methylated sites were associated with the molecular pathways such as circadian rhythms and insulin secretion. CONCLUSION: Hence, the distinct DNA methylation might play a vital role in the biological regulation of AR through the pathways such as circadian rhythms.

Transfer RNA-derived small RNAs and their potential roles in the therapeutic heterogeneity of sacubitril/valsartan in heart failure patients after acute myocardial infarction.

Background: It has been reported that sacubitril/valsartan can improve cardiac function in acute myocardial infarction (AMI) patients complicated by heart failure (HF). However, a number of patients cannot be treated successfully; this phenomenon is called sacubitril/valsartan resistance (SVR), and the mechanisms remain unclear. Methods: In our present research, the expression profiles of transfer RNA (tRNA)-derived small RNAs (tsRNAs) in SVR along with no sacubitril/valsartan resistance (NSVR) patients were determined by RNA sequencing. Through bioinformatics, quantitative real-time PCR (qRT-PCR), and cell-based experiments, we identified SVR-related tsRNAs and confirmed their diagnostic value, predicted their targeted genes, and explored the enriched signal pathways as well as regulatory roles of tsRNAs in SVR. Results: Our research indicated that 36 tsRNAs were upregulated and that 21 tsRNAs were downregulated in SVR. Among these tsRNAs, the expression of tRF-59:76-Tyr-GTA-2-M3 and tRF-60:76-Val-AAC-1-M5 was upregulated, while the expression of tRF-1:29-Gly-GCC-1 was downregulated in the group of SVR. Receiver operating characteristic (ROC) curve analysis demonstrated that these three tsRNAs were potential biomarkers of the therapeutic heterogeneity of sacubitril/valsartan. Moreover, tRF-60:76-Val-AAC-1-M5 might target Tnfrsf10b and Bcl2l1 to influence the observed therapeutic heterogeneity through the lipid and atherosclerosis signaling pathways. Conclusion: Hence, tsRNA might play a vital role in SVR. These discoveries provide new insights for the mechanistic investigation of responsiveness to sacubitril/valsartan.

The DNAm levels of CREB5 (cg11301281) were associated with clopidogrel resistance.

PURPOSE: Clopidogrel resistance (CR) is mostly caused by interindividual variability of the platelet inhibition of clopidogrel, which may induce cardiovascular events. The aim of this research was to evaluate whether DNAm levels of CREB5 (cg01534253) are involved in CR among acute coronary syndrome (ACS) patients treated with clopidogrel. METHODS: 72 patients(36 CR and 36 non-CR) who underwent ACS were included in this study. The VerifyNow P2Y12 assay was selected to evaluate residual platelet reactivity, and bisulfite pyrosequencing methods was used to examine DNA methylation levels on cg01534253. Secondly, CREB5 mRNA expression was analyzed via quantitative real-time PCR. Last, we employed logistic regression to test the interaction between genetic factors of CREB5 methylation and multiple clinical variables in CR patients. RESULTS: Subunit analysis indicated that for patients whose HbA1c levels were ≥6.5% or whose GLU levels were ≥7 mmol/L, lower methylation of cg01534253 indicated a poorer clopidogrel response. In addition, CREB5 mRNA expression was increased in CR patients with GLU levels ≥7 mmol/L. Moreover, regression analysis indicated that the values of albumin and uric acid were correlated with the incidence of CR. CONCLUSIONS: Our findings were likely to provide fresh understanding for the new mechanism of platelet inhibition failure and promote individualized antiplatelet therapy.

Characterization and Performance Evaluation of Metakaolin-Based Geopolymer Foams Obtained by Adding Palm Olein as the Foam Stabilizer.

Geopolymer foams with different pore structures can be used in construction, water treatment, and heavy metal adsorption. The preparation of high porosity geopolymer foams using vegetable oil as a foam stabilizer is a feasible and cost-effective route. In this study, metakaolin-based geopolymer foams with hierarchical pore structures were fabricated by adding H2O2 as the foaming agent with palm olein as the foam stabilizer. The effects of H2O2 and palm olein content on the chemical features and pore structure of geopolymer foams were evaluated. Water absorption, thermal conductivity, and mechanical behaviors of geopolymer foams were also investigated. The results indicate that fatty acid salt surfactants were generated in situ in the geopolymer matrix due to the addition of palm olein. Geopolymer foams with H2O2 and palm olein addition possess a homogeneously concentrated macropore distribution. Palm olein exhibits a refining effect on intrinsic pores formed by geopolymerization. In addition, using appropriate amounts of palm olein and H2O2, geopolymer foams can achieve higher open porosity and better pore connectivity, resulting in the improvement of water absorption and thermal insulation capacity.

OhrR is a central transcriptional regulator of virulence in Dickeya zeae.

Dickeya zeae is the causal agent of rice foot rot disease. The pathogen is known to rely on a range of virulence factors, including phytotoxin zeamines, extracellular enzymes, cell motility, and biofilm, which collectively contribute to the establishment of infections. Phytotoxin zeamines play a critical role in bacterial virulence; signalling pathways and regulatory mechanisms that govern bacterial virulence remain unclear. In this study, we identified a transcriptional regulator OhrR (organic hydroperoxide reductase regulator) that is involved in the regulation of zeamine production in D. zeae EC1. The OhrR null mutant was significantly attenuated in its virulence against rice seed, potato tubers and radish roots. Phenotype analysis showed that OhrR was also involved in the regulation of other virulence traits, including the production of extracellular cellulase, biofilm formation, and swimming/swarming motility. DNA electrophoretic mobility shift assay showed that OhrR directly regulates the transcription of key virulence genes and genes encoding bis-(3'-5')-cyclic dimeric guanosine monophosphate synthetases. Furthermore, OhrR positively regulates the transcription of regulatory genes slyA and fis through binding to their promoter regions. Our findings identify a key regulator of the virulence of D. zeae and add new insights into the complex regulatory network that modulates the physiology and virulence of D. zeae.

Antioxidant effect of yeast on lipid oxidation in salami sausage.

Salami is a kind of fermented meat product with rich nutrition and unique flavor. Because it is rich in fat, it is easy to oxidize to produce bad flavor. Compared with the way of adding artificial or natural antioxidants to reduce the degree of sausage oxidation, the antioxidant characteristics of developing the starter itself deserve more attention. In this study, firstly the antioxidant activities of 5 strains of yeast were measured in vitro, and then the mixture of yeast and Lactobacillus rhamnosus YL-1 was applied to fermented sausage model. The effect of the starter in the sausage model was investigated through physicochemical parameters, degree of fat oxidation, free fatty acid content, and though volatile flavor compound analysis, sensory evaluation and various indexes after storage were observed. Metagenomics was used to explore metabolic pathways, functional genes and key enzymes related to lipid oxidizing substances in sausage in yeast. The results showed that Wickerhamomyces anomalus Y12-3 and Y12-4 had strong tolerance to H2O2, and had higher SOD and CAT enzyme activities. The addition of yeast effectively reduced the material value of peroxidation value and active thiobarbiturate in salami. In flavor analysis, the content of flavor compounds associated with lipid oxidation, such as hexanal, heptanal, nonanal and (E)-2-decenal were significantly lower with the use of Debaryomyces hansenii Y4-1 and Y12-3. Meanwhile, the possible pathways of yeast metabolism of flavor substances related to lipid oxidation (mainly aldehydes) were discussed with the help of metagenomic techniques. According to the results of metagenomics, fatty acid degradation (ko00071) metabolic pathway was related to the degradation of aldehydes through aldehyde dehydrogenase, which was the potential key enzyme.

Gene polymorphisms of insulin secretion signaling pathway associated with clopidogrel resistance in Han Chinese population.

BACKGROUND: Due to the loss of responsiveness to insulin, diabetes mellitus (DM) patients develop increased platelet reactivity and reduced response to antiplatelet agents. Nevertheless, the relationship between the single-nucleotide polymorphisms (SNP) of the signal pathway gene of insulin secretion and the effect of clopidogrel is elusive. METHODS: Blood samples were collected from patients administered with dual-antiplatelet therapy (clopidogrel, 75 mg, once daily and aspirin, 100 mg, once daily) after 5 days and completed test within 4 h. The VerifyNow P2Y12 assay was used to measure the platelet functions, and the results were expressed as a P2Y12 reaction unit (PRU). Notably, the selected SNPs were analyzed to demonstrate the functionality of genetic variants. RESULTS: Analysis of the study population showed that old age, lower plasma albumin (ALB) level, higher creatinine (CREA) level, higher uric acid (UA) level, lower platelet (PLT) count, and lower plateletcrit (PCT) potentially increased the risk of clopidogrel resistance. In a single-nucleotide polymorphism rs6056209 of the PCLB1 gene, the AG genotype was a risk factor for clopidogrel resistance (p < 0.05, OR = 1.574). Similarly, the CC and AG genotype in GNAS rs7121 and CCKAR rs1800857 were protective factors (p < 0.05, OR = 0.094; p <0.05, OR = 0.491). TT was a protective factor in rs10814274 of the CREB3 gene (p < 0.05, OR = 0.444). In the RAPGEF4 gene polymorphism rs17746510, TG was the protective genotype, and the TT genotype was a risk factor for clopidogrel resistance. GCG rs5645 was confirmed; there was a relationship between genotypes containing A or G and clopidogrel resistance. CONCLUSION: Single-nucleotide polymorphisms of insulin secretion signaling pathway genes trigger clopidogrel resistance.

Polymorphisms in the GCK gene increase the risk of clopidogrel resistance in stable coronary artery disease (SCAD) patients.

BACKGROUND: Diabetes mellitus is a major factor in clopidogrel resistance (CR), and the glucokinase (GCK) gene plays a pivotal role in glucose homeostasis. This study investigated the contribution of GCK polymorphisms to CR risk. METHODS: Two hundred SCAD patients were recruited, and their platelet functions were detected by the Verify-Now P2Y12 assay. The polymorphisms of GCK were tested based on the methods of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We investigated the associations of GCK polymorphisms and CR. Multivariate logistic regression was performed to analyse the correlations between GCK polymorphisms and clinical values. RESULTS: Our study found that the SNPs rs4607517 and rs6975024 were associated with CR. Additionally, patients with the G allele of rs4607517had a greater CR risk, but the C allele of rs6975024 might be a protective factor. Finally, logistic regression revealed that CC + TC (rs6975024) as well as the values of albumin were correlated with a decreased risk of CR, and higher levels of uric acid (UA) may be positively associated with CR. CONCLUSION: The GCK gene polymorphisms might increase the CR risk in SCAD patients. Meanwhile, higher albumin levels and lower UA values might decrease the risk.

The association of polymorphisms in related circadian rhythm genes and clopidogrel resistance susceptibility.

Previous studies have confirmed that a dynamic change in circadian rhythm will affect platelet activity, resulting in clopidogrel resistance (CR). We attempted to evaluate whether polymorphisms of related circadian rhythm genes are involved in CR in stable coronary artery disease (SCAD) patients. A sum of 204 SCAD patients met our requirements and were recruited, and 96 patients were considered to have CR. After clinical data collection and platelet function evaluation, genomic DNA was isolated from human peripheral blood, and 23 tagSNPs from related circadian rhythm genes were genotyped by GenomeLab SNPstream Genotyping System. After RNA isolation, relative expression of related gene mRNAs (CLOCK, CRY1, CACNA1C and PRKCG) was measured by real-time PCR. The results showed that polymorphisms in CRY1, CACNA1C and PRKCG changed the response to clopidogrel. And then, the rs1801260 polymorphism might lead to higher mRNA expression in CLOCK and potentially induce the occurrence of CR. Additionally, the TC genotype of rs3745406 might lower mRNA expression of PRKCG, resulting in CR. These findings support the hypothesized role of circadian rhythm genes in CR and indicate probable biomarkers for CR susceptibility, providing new insight into individualized medicine for coronary heart disease.

Associations of PER3 polymorphisms with clopidogrel resistance among Chinese Han people treated with clopidogrel.

BACKGROUND: Changes in circadian rhythm are related to various diseases, such as immune system diseases and cardiovascular diseases. The PERIOD3 (PER3) clock gene is one of the most important genes in the rhythm regulation system. Our goal was to evaluate the possible association between the PER3 rs228729 (T/C) polymorphism or PER3 rs2797685(T/C) polymorphism and clopidogrel resistance (CR) and to study the impact of clinical baseline data on clopidogrel resistance. METHODS: PER3 polymorphisms rs2797685 (T/C) and rs228729 (T/C) were assessed in 156 patients with (72) and without (84) CR. Blood samples were collected and analyzed after the application of clopidogrel for interventional therapy. RESULTS: Age, albumin, PLT, and PCT levels influenced the risk of CR (p < 0.05). For rs2797685, when the PCT value was greater than 0.19, patients with the TT + TC genotype had an increased risk of clopidogrel resistance compared with those with the CC genotype (PCT ≥ 0.19, p = 0.014; PCT p = 0.004). In patients with albumin values greater than 40 or PCT greater than 0.19, those with the rs228729 TT + TC genotype had an increased risk of clopidogrel resistance compared with those with the CC genotype (albumin≥40, TT+TC:CC, p = 0.01, albumin p = 0.005; PCT ≥ 0.19, TT+TC:CC, p < 0.001, PCT p = 0.004). Logistic regression analysis of clinical baseline data and genotype showed that high albumin is a protective factor against clopidogrel resistance. The PER3 gene polymorphism has no clear correlation with clopidogrel resistance. CONCLUSION: In summary, our research shows that PER3 SNPs may be helpful to assess the pathogenesis of CR.

Psychometric properties of the 'Self-Management and Transition to Adulthood with Rx = Treatment Questionnaire' in Chinese children and young people with chronic diseases.

AIMS: The aims of this work were to translate, culturally adapt and evaluate the reliability and validity of the Chinese version of the Self-Management and Transition to Adulthood with Rx = Treatment Questionnaire. BACKGROUND: Children and young people with chronic diseases are expected to start self-managing their diseases and have a smooth and coordinated transition from paediatric- to adult-oriented care. DESIGN: This study involved the cultural adaptation of a questionnaire into Chinese and examined its factor structure. METHODS: This was a multicentre cross-sectional study of children and young people/adolescents (8-18 years) who were diagnosed with chronic diseases in China from June 2016 to December 2018. Exploratory and confirmatory factor analyses were performed to analyse the questionnaire's validity. RESULTS: Four major factors were identified in the Chinese version of the questionnaire, and it had a good fit to the target population. The internal reliability was good. All factors were positively and strongly correlated with the total score. The t test revealed that the Medication Management score was not significantly different between two age groups (8-11 and 12-18 years), but the scores of the other factors and overall scale were lower in the 8-11 years age group. CONCLUSION: The Chinese version of the questionnaire has good reliability and validity in the Chinese context.

Prebiotic, Probiotic, Antimicrobial, and Functional Food Applications of Bacillus amyloliquefaciens.

Bacillus amyloliquefaciens belongs to the genus Bacillus and family Baciliaceae. It is ubiquitously found in food, plants, animals, soil, and in different environments. In this review, the application of B. amyloliquefaciens in probiotic and prebiotic microbes in fermentation, synthesis, and hydrolysis of food compounds is discussed as well as further insights into its potential application and gaps. B. amyloliquefaciens is also a potential microbe in the synthesis of bioactive compounds including peptides and exopolysaccharides. In addition, it can synthesize antimicrobial compounds (e.g., Fengycin, and Bacillomycin Lb), which makes its novelty in the food sector greater. Moreover, it imparts and improves the functional, sensory, and shelf life of the end products. The hydrolysis of complex compounds including insoluble proteins, carbohydrates, fibers, hemicellulose, and lignans also shows that B. amyloliquefaciens is a multifunctional and potential microbe which can be applied in the food industry and in functional food processing.

Chinese family care patterns of childhood rheumatic diseases: A cluster analysis.

OBJECTIVES: The purpose is to distinguish family care (FC) patterns of childhood rheumatic diseases in Chinese families and to determine the predictors of FC patterns. METHODS: This secondary analysis contained two cross-section surveys with a convenient sample of totally 398 caregivers who have a child with rheumatic diseases from four pediatric hospitals. Caregivers were required to completed Family Management Measure questionnaire. Cluster analysis was used to distinguish patterns and multinomial logistic regression analysis was used to find predictors. RESULTS: Four patterns were identified: the normal-perspective and collaborative (28.4%), the effortless and contradictory (24.6%), the chaotic and strenuous (18.3%), and the confident and concerning (28.7%). Disease category (χ 2 = 21.23, P = 0.002), geographic location (χ 2 = 8.41, P = 0.038), maternal educational level (χ 2 = 12.69, P = 0.048) and family monthly income (χ 2 = 33.21, P < 0.001) predicted different patterns. CONCLUSIONS: FC patterns were different among families. Disease-related and family-related factors were vital predictors to distinguish patterns consistent with the Family Management Style Framework. The result assisted that clinicians recognize FC patterns and predictors effectively to provide tailored advice in time.

Functional Characteristics of Lactobacillus and Yeast Single Starter Cultures in the Ripening Process of Dry Fermented Sausage.

Dry fermented sausage is popular among the world because of its rich nutrition and unique flavor. Starter cultures play an important role in the quality of dry fermented sausage. In this study, probiotics lactic acid bacteria Lactobacillus delbrueckii N102, Latilactobacillus sakei H1-5, Debaryomyces hansenii Y4-1, and Wickerhamomyces anomalus Y12-3 were isolated from food-borne materials. The physicochemical properties, microbial populations, TBARS, lipolysis, proteolysis, and volatile flavor compounds of dry fermented sausages with different starter cultures were evaluated comparatively during the ripening process. The results showed that both L. delbrueckii N102 and L. sakei H1-5 grow well and could rapidly reduce the pH value of the products. At the same time, they could significantly reduce the number of Enterobacter putrefaciens, so as to ensure the safety of the products. In addition, the strains N102 promoted the formation of flavor compounds 2,3-butanedione, 3-hydroxy-2-butanone, and carnosine, whereas taurine content of batch H1-5 was significantly increased, while yeast y4-1 and y12-3 could also grow faster in sausage and promoted the esters and alcohols formation such as ethyl acetate and linalool, with the formation of γ-aminobutyric acid by y4-1. Compared with lactic acid bacteria, yeasts showed to contribute more in flavor formation and effective inhibition of lipid oxidation. The starter cultures played different roles in flavor contribution and had obvious differentiation in the ripening process of dry fermented sausage.

Clopidogrel Resistance Is Associated With DNA Methylation of Genes From Whole Blood of Humans.

Antiplatelet therapy has become a cornerstone in the treatment of coronary heart disease (CHD). However, due to high-residual-platelet-reactivity, clopidogrel resistance (CR) is a common phenomenon, and it is rarely known about the relationship between CR and epigenetic changes. This study compared the whole genomic methylation patterns of blood samples from patients with CR (n = 6) and non-CR (n = 6) with the Human Methylation 850K BeadChip assay. We explored differentially methylated CpG sites, genes, and pathways using bioinformatics profiling. The CR and control groups showed significantly different DNA methylation at 7,098 sites, with 979 sites showing hypermethylation and 6,119 sites showing hypomethylation. The pyrosequencing method was used to validate four differentially methylated CpG loci (cg23371584, cg15971518, cg04481923, cg22507406), confirming that DNA methylation was associated with the risk of CR (30 CR vs. 30 non-CR). The relative mRNA expression of the four genes (BTG2, PRG2, VTRNA2-1, PER3) corresponding to the loci above was also associated with CR, suggesting that alterations in DNA methylation may affect the expression of these four genes, eventually resulting in CR. Additionally, differentially methylated sites are partially related to genes and pathways that play key roles in process of circadian entrainment, insulin secretion, and so on. Hence, the mechanism and biological regulation of CR might be reflected through these epigenetic alterations, but future research will need to address the causal relationships.

Exosomal miRNAs as potential biomarkers for acute myocardial infarction.

microRNAs (miRNAs) can be used as biomarkers for acute myocardial infarction (AMI). However, few reports have focused on the value of exosomal miRNAs in the mechanism of the pathophysiological process from stable coronary artery disease (SCAD) to AMI. Exosomes were isolated via ultracentrifugation after serum samples were collected. The exosomes were then identified by transmission electron microscopy, western blotting, and nanoparticle tracking analysis. The differential expression of miRNAs in exosomes from six AMI and six matching SCAD patients was screened using the Agilent Human miRNA Microarray Kit. Target genes of the candidate miRNAs were predicted via an online miRNA database, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. Further validation was conducted through quantitative real-time polymerase chain reaction with 60 exosome samples. The expression of 13 miRNAs was significantly downregulated in the AMI samples compared with the SCAD samples. In addition, we identified various target genes that are mainly involved in the pathways of cardiac rehabilitation and remodelling. Validation of the expression of candidate miRNAs indicated that exosomal miR-1915-3p, miR-4,507, and miR-3,656 were significantly less expressed in AMI samples than in SCAD samples, and area under the receiver-operating-characteristic curve (AUC) analysis showed that the expression of these miRNAs resulted in good predictive accuracy [miR-1915-3p (AUC: 0.772); miR-4,507 (AUC: 0.684); and miR-3,656 (AUC: 0.771)], suggesting that these serum exosomal miRNAs might be predictive for AMI at an early stage. Hence, exosomal miRNAs might play an important role in the pathophysiology of AMI and could serve as diagnostic biomarkers.