Factors Influencing Time to First Medical Contact in Patients with Acute ST-Segment Elevation Myocardial Infarction: A Retrospective Analysis.

BACKGROUND Exploring the factors that impact the time from symptom onset to first medical contact (S2FMC) is crucial for improving outcomes in elderly patients diagnosed with acute ST-segment elevation myocardial infarction (STEMI). This study conducted a retrospective analysis on 282 patients who underwent emergency percutaneous coronary intervention (PCI) or percutaneous transluminal coronary angioplasty (PTCA) in Guangzhou City District to identify significant factors affecting S2FMC. MATERIAL AND METHODS A retrospective analysis was conducted on 282 patients with STEMI who underwent emergency percutaneous coronary intervention (PCI). Descriptive statistics, univariate and multivariate Cox regression analyses were used to identify significant factors affecting S2FMC. Additionally, interactions between risk factors were examined using multivariate logistic regression and the structural equation model (SEM). RESULTS Age (HR=0.984, 95% CI: 0.975-0.993), nature of chest pain (HR=2.561, 95% CI: 1.900-3.458), admission mode (HR=1.805, 95% CI: 1.358-2.400), and vascular characteristics (HR=1.246, 95% CI: 1.069-1.451) were independent influencing factors for S2FMC. Persistent chest tightness/pain, EMS admission, and vascular characteristics (RCADL or LCADL) played a protective role in S2FMC. Among the influencing factors, vascular characteristics (OR=1.072, 95% CI: 1.008-1.141) had an independent effect on the nature of chest pain. Meanwhile, the nature of chest pain (OR=1.148, 95% CI: 1.015-1.298) was an independent influencing factor in the admission mode. CONCLUSIONS Patients with persistent chest tightness/pain, EMS admission, and vascular characteristics (RCADL or LCADL) experienced shorter S2FMC and higher compliance rate (S2FMC ≤180 min). At the same time, age and other vascular features played an inverse role. This study proposes enhancing follow-up and monitoring measures, and shows the consequences of intermittent chest pain should not be disregarded.

Comparative Genome Analyses Reveal the Genomic Traits and Host Plant Adaptations of Flavobacterium akiainvivens IK-1T.

The genus Flavobacterium contains a large group of commensal bacteria identified in diverse terrestrial and aquatic habitats. We compared the genome of a new species Flavobacterium akiainvivens IK-1T to public available genomes of Flavobacterium species to reveal the genomic traits and ecological roles of IK-1T. Principle component analysis (PCA) of carbohydrate-active enzyme classes suggests that IK-1T belongs to a terrestrial clade of Flavobacterium. In addition, type 2 and type 9 secretion systems involved in bacteria-environment interactions were identified in the IK-1T genome. The IK-1T genome encodes eukaryotic-like domain containing proteins including ankyrin repeats, von Willebrand factor type A domain, and major royal jelly proteins, suggesting that IK-1T may alter plant host physiology by secreting eukaryotic-like proteins that mimic host proteins. A novel two-component system FaRpfC-FaYpdB was identified in the IK-1T genome, which may mediate quorum sensing to regulate global gene expressions. Our findings suggest that comparative genome analyses of Flavobacterium spp. reveal that IK-1T has adapted to a terrestrial niche. Further functional characterizations of IK-1T secreted proteins and their regulation systems will shed light on molecular basis of bacteria-plant interactions in environments.

Rheinheimera salexigens sp. nov., isolated from a fishing hook, and emended description of the genus Rheinheimera.

A Gram-negative, rod-shaped bacterium, designated KH87T, was isolated from a fishing hook that had been baited and suspended in seawater off O'ahu, Hawai'i. Based on a comparison of 1524 nt of the 16S rRNA gene sequence of strain KH87T, its nearest neighbours were the GammaproteobacteriaRheinheimera nanhaiensis E407-8T (96.2 % identity), Rheinheimera chironomi K19414T (96.0 %), Rheinheimera pacifica KMM 1406T (95.8 %), Rheinheimera muenzenbergensis E49T (95.7 %), Alishewanella solinquinati KMK6T (94.9 %) and Arsukibacterium ikkense GCM72T (94.6 %). Cells of KH87T were motile by a single polar flagellum, strictly aerobic, and catalase- and oxidase-positive. Growth occurred between 4 and 39 °C, and in a circumneutral pH range. Major fatty acids in whole cells of strain KH87T were cis-9-hexadecenoic acid, hexadecanoic acid and cis-11-octadecenoic acid. The quinone system contained mostly menaquinone MK-7, and a minor amount of ubiquinone Q-8. The polar lipid profile contained the major lipids phosphatidylglycerol, phosphatidylserine, phosphatidylethanolamine, an unidentified aminolipid, and a lipid not containing phosphate, an amino group or a sugar moiety. Putrescine was the major polyamine. Physiological, biochemical and genomic data, including obligate halophily, absence of amylolytic activity, a quinone system dominated by MK-7 and DNA G+C content (42.0 mol%) distinguished KH87T from extant Rheinheimera species; strain KH87T was also distinguished by a multi-locus sequence analysis of aligned and concatenated 16S rRNA, gyrB, rpoB and rpoD gene sequences. Based on phenotypic and genotypic differences, the species Rheinheimera salexigens sp. nov. is proposed to accommodate KH87T as the type strain (=ATCC BAA-2715T=CIP 111115T). An emended description of the genus Rheinheimera is also proposed.

Genomic sequencing is required for identification of tuberculosis transmission in Hawaii.

BACKGROUND: Tuberculosis (TB) caused an estimated 1.4 million deaths and 10.4 million new cases globally in 2015. TB rates in the United States continue to steadily decline, yet rates in the State of Hawaii are perennially among the highest in the nation due to a continuous influx of immigrants from the Western Pacific and Asia. TB in Hawaii is composed of a unique distribution of genetic lineages, with the Beijing and Manila families of Mycobacterium tuberculosis (Mtb) comprising over two-thirds of TB cases. Standard fingerprinting methods (spoligotyping plus 24-loci Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats [MIRU-VNTR] fingerprinting) perform poorly when used to identify actual transmission clusters composed of isolates from these two families. Those typing methods typically group isolates from these families into large clusters of non-linked isolates with identical fingerprints. Next-generation whole-genome sequencing (WGS) provides a new tool for molecular epidemiology that can resolve clusters of isolates with identical spoligotyping and MIRU-VNTR fingerprints. METHODS: We performed WGS and SNP analysis and evaluated epidemiological data to investigate 19 apparent TB transmission clusters in Hawaii from 2003 to 2017 in order to assess WGS' ability to resolve putative Mtb clusters from the Beijing and Manila families. This project additionally investigated MIRU-VNTR allele prevalence to determine why standard Mtb fingerprinting fails to usefully distinguish actual transmission clusters from these two Mtb families. RESULTS: WGS excluded transmission events in seven of these putative clusters, confirmed transmission in eight, and identified both transmission-linked and non-linked isolates in four. For epidemiologically identified clusters, while the sensitivity of MIRU-VNTR fingerprinting for identifying actual transmission clusters was found to be 100%, its specificity was only 28.6% relative to WGS. We identified that the Beijing and Manila families' significantly lower Shannon evenness of MIRU-VNTR allele distributions than lineage 4 was the cause of standard fingerprinting's poor performance when identifying transmission in Beijing and Manila family clusters. CONCLUSIONS: This study demonstrated that WGS is necessary for epidemiological investigation of TB in Hawaii and the Pacific.

Genetic and functional characterization of multiple thermophilic organosulfur-removal systems reveals desulfurization potentials for waste residue oil cleaning.

Heavy oil and petroleum refining residues usually contain high concentrations of recalcitrant hazardous organosulfur compounds, causing long-term serious global environmental pollution during leakage and combustion. Research conducted here identified a unique thermophilic bacterium Parageobacillus thermoglucosidasius W-36 with the notable ability of waste residue oil desulfurization, utilization and tolerance of multiplex hazardous organosulfur pollutants. Genome information mining revealed multiple desulfurization systems in three organosulfur-utilizing gene clusters. Enzymatic characterization, phylogenetic relationships, transcriptional performance and structural prediction indicated four novel key monooxygenases for diverse organosulfur removal. Importantly, all monooxygenases shared obvious commonalities in the predicted tertiary structure backbone and catalytic characteristics of C-S bond cleavage, implying the potential of genetic engineering for broad-spectrum hazardous organosulfur removal. Therefore, this work demonstrated the important application potential of thermophilic bacteria as a promising alternative biodesulfurization way for waste residue oil cleaning.

Platycodin D represses ß-catenin to suppress metastasis of cetuximab-treated KRAS wild-type colorectal cancer cells.

Cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, is extensively used for clinical therapy in KRAS wild-type colorectal cancer (CRC) patients. However, some patients still cannot get benefit from the therapy, because metastasis and resistance occur frequently after cetuximab treatment. New adjunctive therapy is urgently needed to suppress metastasis of cetuximab-treated CRC cells. In this study, we used two KRAS wild-type CRC cells, HT29 and CaCo2, to investigate whether platycodin D, a triterpenoid saponin isolated from Chinese medicinal herb Platycodon grandifloras, is able to suppress the metastasis of cetuximab-treated CRC. Label-free quantitative proteomics analyses showed that platycodin D but not cetuximab significantly inhibited expression of ß-catenin in both CRC cells, and suggested that platycodin D counteracted the inhibition effect of cetuximab on cell adherence and functioned in repressing cell migration and invasion. Western blot results showed that single platycodin D treatment or combined platycodin D and cetuximab enhanced inhibition effects on expressions of key genes in Wnt/ß-catenin signaling pathway, including ß-catenin, c-Myc, Cyclin D1 and MMP-7, compared to single cetuximab treatment. Scratch wound-healing and transwell assays showed that platycodin D combined with cetuximab suppressed migration and invasion of CRC cells, respectively. Pulmonary metastasis model of HT29 and CaCo2 in nu/nu nude mice consistently showed that combined treatment using platycodin D and cetuximab inhibited metastasis significantly in vivo. Our findings provide a potential strategy to inhibit CRC metastasis during cetuximab therapy by addition of platycodin D.

Identification of important genes associated with acute myocardial infarction using multiple cell death patterns.

Acute myocardial infarction (AMI) is a global health threat, and programmed cell death (PCD) plays a crucial role in its occurrence and development. In this study, integrated bioinformatics tools were used to explore new biomarkers and therapeutic targets in AMI. Thirteen types of PCD-related genes were identified through literature review, KEGG, and GSEA pathways. Gene expression matrices and clinical data from AMI patients and healthy controls were obtained from the GEO database. Statistical analysis in R identified 377 differentially expressed genes in AMI patients. Intersection analysis between the differentially expressed genes and PCD-related genes revealed 24 genes positively correlated with immune cells such as Neutrophils and Monocytes, while negatively correlated with T cells CD4 memory resting and Plasma cells. Unsupervised clustering analysis divided patients into two groups (C1 and C2) based on the expression levels of these 24 genes. GSVA analysis showed that C2 patients were more active in pathways related to maintaining normal cell morphology and promoting phagocytosis, suggesting a lower programmed cell death rate and a higher tendency to maintain cell survival. Two hub genes, TNFAIP3 and TP53INP2, were identified through LASSO regression analysis and SVM-RFE, and were validated using an external dataset and RT-qPCR、Western blot and ELISA analysis. These hub genes showed significantly higher expression and protein secretion levels in AMI patients compared to healthy individuals. Overall, regulating and controlling PCD, particularly through the identified hub genes, TNFAIP3 and TP53INP2, may provide new therapeutic strategies for improving the prognosis of AMI patients and preventing heart failure.

Complete genome sequence of Salmonella enterica subsp. enterica serovar Typhi P-stx-12.

We report here the complete genome sequence of Salmonella enterica subsp. enterica serovar Typhi P-stx-12, a clinical isolate obtained from a typhoid carrier in India.

Tools to kill: genome of one of the most destructive plant pathogenic fungi Macrophomina phaseolina.

BACKGROUND: Macrophomina phaseolina is one of the most destructive necrotrophic fungal pathogens that infect more than 500 plant species throughout the world. It can grow rapidly in infected plants and subsequently produces a large amount of sclerotia that plugs the vessels, resulting in wilting of the plant. RESULTS: We sequenced and assembled ~49 Mb into 15 super-scaffolds covering 92.83% of the M. phaseolina genome. We predict 14,249 open reading frames (ORFs) of which 9,934 are validated by the transcriptome. This phytopathogen has an abundance of secreted oxidases, peroxidases, and hydrolytic enzymes for degrading cell wall polysaccharides and lignocelluloses to penetrate into the host tissue. To overcome the host plant defense response, M. phaseolina encodes a significant number of P450s, MFS type membrane transporters, glycosidases, transposases, and secondary metabolites in comparison to all sequenced ascomycete species. A strikingly distinct set of carbohydrate esterases (CE) are present in M. phaseolina, with the CE9 and CE10 families remarkably higher than any other fungi. The phenotypic microarray data indicates that M. phaseolina can adapt to a wide range of osmotic and pH environments. As a broad host range pathogen, M. phaseolina possesses a large number of pathogen-host interaction genes including those for adhesion, signal transduction, cell wall breakdown, purine biosynthesis, and potent mycotoxin patulin. CONCLUSIONS: The M. phaseolina genome provides a framework of the infection process at the cytological and molecular level which uses a diverse arsenal of enzymatic and toxin tools to destroy the host plants. Further understanding of the M. phaseolina genome-based plant-pathogen interactions will be instrumental in designing rational strategies for disease control, essential to ensuring global agricultural crop production and security.

Multi-parameter optimization maximizes the performance of genetically engineered Geobacillus for degradation of high-concentration nitroalkanes in wastewater.

Nitroalkanes are important toxic pollutants for which there is no effective removal method at present. Although genetic engineering bacteria have been developed as a promising bioremediation strategy for years, their actual performance is far lower than expected. In this study, important factors affecting the application of engineered Geobacillus for nitroalkanes degradation were comprehensively optimized. The deep-reconstructed engineered strains significantly raised the expression and activity level of catalytic enzymes, but failed to fully enhance the degradation efficiency. However, further debugging of a variety of key parameters effectively improved the performance of the engineering strains. The increased cell membrane permeability, trace supplementation of vital nutritional factors, synergy of multifunctional enzyme engineered bacteria, switch of oxygen-supply mode, and moderate initial biomass all effectively boosted the degradation efficiency. Finally, a low-cost and highly effective bioreactor test for high-concentration nitroalkanes degradation proved the multi-parameter optimization mode helps to maximize the performance of genetically engineered bacteria.