Research progress of circular RNAs in myocardial ischemia.

Circular RNAs (circRNAs) are a type of single-stranded RNA that forms a covalently closed continuous loop. Its structure, stability, properties, and cell- and tissue-specificity have gained considerable recognition in the research and clinical sectors, as its role has been observed in different diseases, such as cardiovascular diseases, cancers, and central nervous system diseases, etc. Cardiovascular disease is still named as the number one cause of death globally, with myocardial ischemia (MI) accounting for 15 % of mortality annually. A number of circRNAs have been identified and are being studied for their ability to reduce MI by inhibiting the molecular mechanisms associated with myocardial ischemia reperfusion injury, such as inflammation, oxidative stress, autophagy, apoptosis, and so on. CircRNAs play a significant role as crucial regulatory elements at transcriptional levels, regulating different proteins, and at posttranscriptional levels, having interactions with RNA-binding proteins, ribosomal proteins, micro-RNAS, and long non-coding RNAS, making it possible to exert their effects through the circRNA-miRNA-mRNA axis. CircRNAs are a potential novel biomarker and therapeutic target for myocardial ischemia and cardiovascular diseases in general. The purpose of this review is to summarize the relationship, function, and mechanism observed between circRNAs and MI injury, as well as to provide directions for future research and clinical trials.

The enhanced visible light driven photocatalytic activity of zinc porphyrin/g-C3N4 nanosheet for efficient bacterial infected wound healing.

Graphitic carbon nitride (g-C3N4) has received much attention as a metal-free polymeric two-dimensional photocatalyst for antibiotic-free antibacterial application. However, the weak photocatalytic antibacterial activity of pure g-C3N4 stimulated by visible light limits its applications. Herein, g-C3N4 is modified with Zinc (II) meso-tetrakis (4-carboxyphenyl) porphyrin (ZnTCPP) by amidation reaction to enhance the utilization of visible light and reduce the recombination of electron-hole pairs. The composite (ZP/CN) is used to treat bacterial infection under visible light irradiation with a high efficacy of 99.99% within 10 min due to the enhanced photocatalytic activity. Ultraviolet photoelectron spectroscopy and density flooding theory calculations indicate the excellent electrical conductivity between the interface of ZnTCPP and g-C3N4. The formed built-in electric field is responsible for the high visible photocatalytic performance of ZP/CN. In vitro and in vivo tests have demonstrated that ZP/CN not only possesses excellent antibacterial activity upon visible light irradiation, but also facilitates the angiogenesis. In addition, ZP/CN also suppresses the inflammatory response. Therefore, this inorganic-organic material can serve as a promising platform for effective healing of bacteria-infected wounds.

Clonal Architectures Predict Clinical Outcome in Gastric Adenocarcinoma Based on Genomic Variation, Tumor Evolution, and Heterogeneity.

Stomach adenocarcinoma (STAD) is a highly heterogeneous disease. Due to the lack of effective molecular markers and personalized treatment, the prognosis of gastric cancer patients is still very poor. The ABSOLUTE algorithm and cancer cell fraction were used to evaluate the clonal and subclonal status of 349 TCGA (The Cancer Genome Cancer Atlas)-STAD patients. Non-negative matrix factorization was used to identify the mutation characteristics of the samples. Univariate Cox regression analysis was used to determine the relationship between clonal/subclonal events and prognosis, and the Spearman correlation was used to evaluate the relationship of clonal/subclonal events to tumor mutation burden (TMB) and neoantigens. The evolution pattern of STAD demonstrated great tumor heterogeneity. TP53, USH2A, and GLI3 appeared earliest in STAD and may drive STAD. CTNNB1, LRP1B, and ERBB4 appeared the latest in STAD, and may be related to STAD's progress. Univariate Cox regression analysis identified four early genes, eight intermediate genes, and seven late genes significantly associated with overall survival. The number of subclonal events in the T stage was significantly different. The N stage, gender, and histological type were significantly different for clonal events, and there was a significant correlation between clonal/subclonal events and TMB/neoantigens. Our results highlight the importance of systematic evaluation of evolutionary models in the clinical management of STAD and personalized gastric cancer treatment.

Predictive value of H2 FPEF score in patients with heart failure with preserved ejection fraction.

AIMS: The H2 FPEF score is a convenient risk stratification tool for diagnosing heart failure with preserved ejection fraction (HFpEF). This study examined the value of the H2 FPEF score for predicting all-cause mortality and rehospitalization in HFpEF patients. METHODS AND RESULTS: This was a retrospective cohort study of patients diagnosed with HFpEF by echocardiography at a single tertiary centre between 1 January 2015 and 30 April 2018. According to the H2 FPEF score, the subjects were divided into low (0-1 points), intermediate (2-5 points), and high (6-9 points) score groups. The primary outcomes were all-cause mortality and rehospitalization. A total of 476 patients (mean age: 70.5 ± 8.4 years, 60.7% female) were included. Of these, 47 (9.9%), 262 (55.0%), and 167 (35.1%) were classified into the low, intermediate, and high score groups, respectively. Over a mean follow-up of 27.5 months, 63 patients (13.2%) died, and 311 patients (65.3%) were rehospitalized. The mortality rates were 3 (6.4%), 29 (11.1%), and 31 (18.6%), and the number of patients with rehospitalization was 28 (59.6%), 159 (60.7%), and 124 (74.3%) for the low, intermediate, and high score groups, respectively. Multivariate Cox regression identified H2 FPEF score as an independent predictor of all-cause mortality (hazard ratio [HR]: 1.46, 95% CI: 1.23-1.73, P < 0.0001) and rehospitalization (HR: 1.15, 95% CI: 1.08-1.22, P < 0.0001). Receiver operating characteristic (ROC) analysis demonstrated the H2 FPEF score can effectively predict all-cause mortality (AUC 0.67, 95% CI: 0.60-0.73, P < 0.0001) and rehospitalization (AUC 0.59, 95% CI: 0.54-0.65, P = 0.001) after adjusting for age and NYHA class. With a cut-off value of 5.5, the sensitivity and specificity were 68.3% and 55.4% for all-cause mortality and 50.5% and 66.7% for rehospitalization. CONCLUSIONS: The H2 FPEF score can be used to predict prognosis in HFpEF patients. Higher scores are associated with higher all-cause mortality and rehospitalization.

Population Genetics of Hirsutella rhossiliensis, a Dominant Parasite of Cyst Nematode Juveniles on a Continental Scale.

Hirsutella rhossiliensis is a parasite of juvenile nematodes, effective against a diversity of plant-parasitic nematodes. Its global distribution on various nematode hosts and its genetic variation for several geographic regions have been reported, while the global population genetic structure and factors underlying patterns of genetic variation of H. rhossiliensis are unclear. In this study, 87 H. rhossiliensis strains from five nematode species (Globodera sp., Criconemella xenoplax, Rotylenchus robustus, Heterodera schachtii, and Heterodera glycines) in Europe, the United States, and China were investigated by multilocus sequence analyses. A total of 280 variable sites (frequency, 0.6%) at eight loci and six clustering in high accordance with geographic populations or host nematode-associated populations were identified. Although H. rhossiliensis is currently recognized as an asexual fungus, recombination events were frequently detected. In addition, significant genetic isolation by geography and nematode hosts was revealed. Overall, our analyses showed that recombination, geographic isolation, and nematode host adaptation have played significant roles in the evolutionary history of H. rhossiliensis IMPORTANCE: H. rhossiliensis has great potential for use as a biocontrol agent to control nematodes in a sustainable manner as an endoparasitic fungus. Therefore, this study has important implications for the use of H. rhossiliensis as a biocontrol agent and provides interesting insights into the biology of this species.

The transcription factor SKN7 regulates conidiation, thermotolerance, apoptotic-like cell death and parasitism in the nematode endoparasitic fungus Hirsutella minnesotensis.

The transcription factor SKN7 is a highly conserved protein among fungi and was initially recognized as a response regulator that protects cells from oxidative stress and maintains cell wall integrity in yeast. Orthologs of SKN7 are extensively present in biocontrol agents of plant pathogens, but they had not been functionally characterized. Here, we identified and characterized the transcription factor SKN7 in the nematode endoparasitic fungus Hirsutella minnesotensis. Null mutant lacking HIM-SKN7 (HIM_03620), which was generated by a gene disruption strategy, demonstrated reduced conidiation, increased sensitivity to high temperature, hydrogen peroxide, mannitol and ethanol, and reduced fungal resistance to farnesol. However, over-expression mutant showed increased conidial production, thermotolerance and resistance to farnesol, suggesting that HIM-SKN7 regulates antiapoptotic-like cell death in H. minnesotensis. Moreover, the results showed that in null mutant, H. minnesotensis had decreased endoparasitic ability as compared to wild type and over-expression strain. During the infection process, the relative expression of the HIM-SKN7 gene was significantly induced in the wild type and over-expression strain. The results of the present study advance our understanding of the functions of the SKN7 gene in biocontrol agents, in particular, nematode endoparasitic fungi.

The mitochondrial genome of the nematode endoparasitic fungus Hirsutella rhossiliensis.

In this study, we report the complete mitochondrial genome of Hirsutella rhossiliensis (Ophiocordycipitaceae, Hypocreales, Ascomycota). We construct the mitochondrial DNA genome organization of 62 483 bp in length of H. rhossiliensis by using the whole-genome resequencing method. Conserved genes including the large and small rRNA subunits, 26 tRNA and 14 protein-coding genes are identified. These protein-coding genes utilize ATG, GTG or TTG as initiation codons and TAA or TAG as termination codons. Moreover, we detect 10 group I introns and one unclassified intron in six genes (rnl, cob, cox1, cox3, nad1 and nad5) encoding ORFs of ribosomal protein S3 and GIY-YIG/LAGLIDADG endonucleases or hypothetical proteins. This mitochondrial genome will be useful in understanding the distribution and genetic diversity of this species.

Genetic structure and parasitization-related ability divergence of a nematode fungal pathogen Hirsutella minnesotensis following founder effect in China.

The fungal parasitoid, Hirsutella minnesotensis, is a dominant parasitoid of the soybean cyst nematode, which is a destruction pest of soybean crops. We investigated population structure and parasitism pattern in samples of H. minnesotensis in China to reveal the spreading pattern of this fungal species and the underlying mechanism generating the parasitization-related ability variability in Chinese population. In cross-inoculation experiments using different combinations of H. minnesotensis and soybean cyst nematode samples from China, most H. minnesotensis isolates fitted the criterion for "local versus foreign" parasitism profile, exhibiting local adaptation pattern to the SCN host. However, the genetic analysis of the single nucleotide polymorphisms with clone-corrected samples based on ten DNA fragments in 56 isolates of H. minnesotensis from China revealed that the Chinese H. minnesotensis population was a clonal lineage that underwent a founder event. The results demonstrated that the Chinese H. minnesotensis population had generated parasitization-related ability diversity after a founder event through individual variation or phenotypic plasticity other than local adaptation. The rapid divergence of parasitization-related abilities with simple genetic structure in Chinese H. minnesotensis population indicates a fundamental potential for the establishment of invasive fungal species, which is a prerequisite for biological control agents.

Comparative genomics and transcriptomics analyses reveal divergent lifestyle features of nematode endoparasitic fungus Hirsutella minnesotensis.

Hirsutella minnesotensis [Ophiocordycipitaceae (Hypocreales, Ascomycota)] is a dominant endoparasitic fungus by using conidia that adhere to and penetrate the secondary stage juveniles of soybean cyst nematode. Its genome was de novo sequenced and compared with five entomopathogenic fungi in the Hypocreales and three nematode-trapping fungi in the Orbiliales (Ascomycota). The genome of H. minnesotensis is 51.4 Mb and encodes 12,702 genes enriched with transposable elements up to 32%. Phylogenomic analysis revealed that H. minnesotensis was diverged from entomopathogenic fungi in Hypocreales. Genome of H. minnesotensis is similar to those of entomopathogenic fungi to have fewer genes encoding lectins for adhesion and glycoside hydrolases for cellulose degradation, but is different from those of nematode-trapping fungi to possess more genes for protein degradation, signal transduction, and secondary metabolism. Those results indicate that H. minnesotensis has evolved different mechanism for nematode endoparasitism compared with nematode-trapping fungi. Transcriptomics analyses for the time-scale parasitism revealed the upregulations of lectins, secreted proteases and the genes for biosynthesis of secondary metabolites that could be putatively involved in host surface adhesion, cuticle degradation, and host manipulation. Genome and transcriptome analyses provided comprehensive understanding of the evolution and lifestyle of nematode endoparasitism.

[Diversity of bacteria isolated from cysts Heterodera glycines in Heilongjiang].

OBJECTIVE: To understand the bacterial diversity isolated from the cysts of Heterodera glycines in the soybean field in Heilongjiang Province. METHODS: Bacteria were isolated from cysts on nutrient agar plates using dilution plate method and further identified by phylogenetic analysis based on 16S rDNA gene sequences. RESULTS: Totally 90 bacteria strains with different colony morphology were selected on nutrient agar plate and their phylogenetic features were analyzed based on the partial 16S rDNA sequences. In total 7 genera and 22 species were identified, including 46 strains in Gammaproteobacteria (51.1%), 32 in Firmicutes (35.6%), 10 in Betaproteobacteria (11.1%), and 2 in Alphaproteobacteria (2.2%). The dominant bacteria species were Pseudomonas and Bacillus. CONCLUSION: There was abundant species diversity of bacteria isolated from cysts Heterodera glycines in Heilongjiang, and these bacteria may play a physical and ecological roles in nematodes.