Isolation of Epizootic Hemorrhagic Disease Virus Serotype 10 from Culicoides tainanus and Associated Infections in Livestock in Yunnan, China.

Two strains of viruses, JC13C644 and JC13C673, were isolated from Culicoides tainanus collected in Jiangcheng County, Yunnan Province, situated along the border area shared by China, Laos, and Vietnam. JC13C644 and JC13C673 viruses can cause cytopathic effect (CPE) in mammalian cells BHK21 and Vero cells, and cause morbidity and mortality in suckling mice 48 h after intracerebral inoculation. Whole-genome sequencing was performed, yielding complete sequences for all 10 segments from Seg-1 (3942nt) to Seg-10 (810nt). Phylogenetic analysis of the sub-core-shell (T2) showed that the JC13C644 and JC13C673 viruses clustered with the Epizootic Hemorrhagic Disease Virus (EHDV) isolated from Japan and Australia, with nucleotide and amino acid homology of 93.1% to 98.3% and 99.2% to 99.6%, respectively, suggesting that they were Eastern group EHDV. The phylogenetic analysis of outer capsid protein (OC1) and outer capsid protein (OC2) showed that the JC13C644 and JC13C673 viruses were clustered with the EHDV-10 isolated from Japan in 1998, with the nucleotide homology of 98.3% and 98.5%, and the amino acid homology of 99.6% and 99.6-99.8%, respectively, indicating that they belong to the EHDV-10. Seroepidemiological survey results demonstrated that JC13C644 virus-neutralizing antibodies were present in 29.02% (177/610) of locally collected cattle serum and 11.32% (89/786) of goat serum, implying the virus's presence in Jiangcheng, Yunnan Province. This finding suggests that EHDV-10 circulates not only among blood-sucking insects in nature but also infects local domestic animals in China. Notably, this marks the first-ever isolation of the virus in China and its discovery outside of Japan since its initial isolation from Japanese cattle. In light of these results, it is evident that EHDV Serotype 10 exists beyond Japan, notably in the natural vectors of southern Eurasia, with the capacity to infect local cattle and goats. Therefore, it is imperative to intensify the surveillance of EHDV infection in domestic animals, particularly focusing on the detection and monitoring of new virus serotypes that may emerge in the region and pose risks to animal health.

Culicoides jiangchengensis, a new species of the subgenus Sinocoides (Diptera, Ceratopogonidae) based on integrative taxonomy from China.

Biting midges of the genus Culicoides are important in both medicine and veterinary medicine because their blood-feeding regime enable them to transmit a variety of pathogens. In this study, the morphological characteristics of the new species of Culicoides (Sinocoides) jiangchengensis Wang et Liu sp. nov are described and compared with the other species of female Culicoides in the subgenus Sinocoides. Three morphological characteristics of C. jiangchengensis, such as without sensory pit in 3rd palpus segment, sensilla coeloconica on flagellomeres 1,9-13, and m1 and m2 cell of the wings with pale spots, were different from the other nine species of culicoides in subgenus Sinocoides. Genetically, C. jiangchengensis are most closely related to C. malipoensis, but they were located in different branches and the minimum interspecific distance between them was 12.6%. In addition, a checklist of 10 species in the subgenus Sinocoides Chu, 1983 (Diptera: Ceratopogonidae: Culicoides) in China, including the new species C. jiangchengensis Wang et Liu sp. nov., is provided, and an updated key to species of the subgenus Sinocoides Chu, 1983 was presented.

PGE2 protects against heart failure through inhibiting TGF-ß1 synthesis in cardiomyocytes and crosstalk between TGF-ß1 and GRK2.

Inflammation plays a central role in the development of heart failure. Prostaglandin E2 (PGE2) is a key mediator of the inflammatory process in the cardiovascular system. However, the role of PGE2 in heart failure is complex and controversial. A recent report suggested that PGE2 inhibits acute ß adrenergic receptor (ß-AR) stimulation-enhanced cardiac contractility. The aim of this study was to characterize the influence of PGE2 on chronic ß-AR stimulation-induced heart failure. Male C57BL/6 J mice received isoproterenol (ISO) or vehicle for 4 weeks. PGE2 significantly reversed ISO-induced cardiac contractile dysfunction and remodeling. Mechanically, ventricular myocytes were found to be an important source of TGF-ß1 in ISO-model and PGE2 ablated TGF-ß1 synthesis in cardiomyocytes through inhibition of ß-AR activated PKA-CREB signaling. Furthermore, PGE2 significantly suppressed TGF-ß1-GRK2 crosstalk-induced pro-hypertrophy and pro-fibrotic signaling in cardiomyocytes and cardiac fibroblasts, respectively. Pharmacological inhibition of GRK2 also attenuated contractile dysfunction and cardiac hypertrophy and fibrosis in ISO-model. These studies elucidate a novel mechanism by which PGE2 reduces TGF-ß1 synthesis and its downstream signaling in heart failure and identify PGE2 or TGF-ß1-GRK2 crosstalk as plausible therapeutic targets for preventing or treating heart failure induced by chronic ß-AR stimulation.

3.0 T Magnetic Resonance Functional Imaging Quantitative Parameters for Differential Diagnosis of Benign and Malignant Lesions of the Breast.

Objective: To investigate value of quantitative dynamic contrast-enhanced magnetic resonance imaging (MRI) parameters and apparent diffusion coefficient (ADC) value in differential diagnosis of breast benign and malignant lesions, and their correlation with prognostic factors of breast cancer. Methods: The study collected MRI images and clinical data from 232 female patients suspected of breast cancer. Philips INGENIA 3.0T superconducting magnetic resonance scanner was used for imaging examination. Complete pathological data of patients were collected, and the expression of ER, PR, HER-2, and Ki-67 were further investigated. Results: Kep was higher in malignant breast lesion group than that in benign breast lesion group, and ADC value was lower in the former group than that in the latter group (both p < 0.05). The areas under the receiver operating characteristic curves for Kep, ADC, and extravascular volume fraction (Ve) were 0.904 (95% confidence interval [CI]: 0.863-0.945), 0.813 (95% CI: 0.752-0.875), and 0.774 (95% CI: 0.707-0.841), respectively. Furthermore, according to the maximum Youden index, the specificity of Kep and the sensitivity of ADC were high, which were 97.20% and 96.00%, respectively, with a cutoff value of 0.314 and 0.151, respectively. Kep value in ER-positive expression group was significantly higher than that in ER-negative expression group (p < 0.05). Kep value in PR-positive expression group was significantly higher than that in PR-negative expression group (p < 0.05). There was positive correlation between Kep and expression of Ki-67 (p < 0.05). ADC value was negatively correlated with Ki-67 expression (p < 0.05). Conclusion: Quantitative parameters Kep and ADC of 3.0 T MR functional imaging can be used as reference indexes for differential diagnosis of benign and malignant breast lesions and for biological behavior evaluation, indicating potential clinical value for noninvasive preoperative evaluation of breast cancer.

SIRT1-mediated ERß suppression in the endothelium contributes to vascular aging.

SIRT1 has many important molecular functions in aging, and the estrogen receptors (ERs) have a vasculoprotective effect, although the detailed mechanism for the roles of SIRT1 and ERs in vascular aging remains unclear. We found that ERß expression in the endothelium was reduced in aging mice, and the expression of ERα and SIRT1 did not change, while SIRT1 activity declined. Further investigation showed that the ERß expression was regulated by SIRT1 through complexes of SIRT1-PPARγ/RXR-p300 that bind to a PPRE (PPAR response element) site on the ERß promoter, and the declined SIRT1 function in aging mice was due to compromised phosphorylation at S154. A single-mutant SIRT1-C152(D) restored the reduced ERß expression in the endothelium with minimized reactive oxygen species generation and DNA damage and increased mitochondrial function and fatty acid metabolism. In high-fat diet aging mice, the endothelium-specific delivery of ERß or SIRT1-C152(D) on the vascular wall reduced the circulating lipids with ameliorated vascular damage, including the restored vessel tension and blood pressure. We conclude that SIRT1-mediated ERß suppression in the endothelium contributes to vascular aging, and the modulation of SIRT1 phosphorylation through a single-mutant SIRT1-C152(D) restores this effect.

ERß expression in the endothelium ameliorates ischemia/reperfusion-mediated oxidative burst and vascular injury.

Estrogen and estrogen receptors (ERs) have been reported to play protective roles in ischemia/reperfusion (I/R)-mediated injury, but the detailed mechanism remains to be fully understood. Nitric oxide (NO) and reactive oxygen species (ROS) also play important roles in the I/R process; however, due to the lack of sensitive and reproducible in vivo monitoring systems, we still do not have direct evidence for the effect of NO and ROS in vivo. In this study, we have established reliable in vivo monitoring systems to measure the variations in circulating ROS and NO during the I/R. We found that during the first few minutes of post-ischemia reperfusion, an oxidative burst occurred concurrent with a rapid loss of NO. Expression of ERß in the endothelium reduced these effects that accompanied an attenuation in myocardial infarction and vascular damage. Further investigation showed that Tie2-driven lentivirus delivery of ERß to the vascular wall in rats increased the expression of its target genes in the endothelium, including ERRα, SOD2 and eNOS. These changes modulate ROS generation, DNA damage, and mitochondrial function in rat endothelial cells. We also found that ERß expression in the endothelium reduced ROS generation and restored mitochondrial function in cardiomyocytes; this may be due to ERß-mediated NO formation and its high diffusibility to cardiomyocytes. We conclude that ERß expression in the endothelium ameliorates ischemia/reperfusion-mediated oxidative burst and vascular injury.

An aqueous extract of Yunnan Baiyao inhibits the quorum-sensing-related virulence of Pseudomonas aeruginosa.

Yunnan Baiyao is a famous Chinese medicine that has long been directly applied to wounds to reduce bleeding, pain, and swelling without causing infection. However, little is known about its ability to prevent infection. The present study aimed to assess in vitro the anti-virulence activity of an aqueous extract of Yunnan Baiyao (YBX) using Pseudomonas aeruginosa as a pathogenic model. We found that a sub-MIC (2.5 mg/ml) of YBX can efficiently interfere with the quorum-sensing (QS) signaling circuit. Real-time polymerase chain reaction analysis showed that a sub-MIC of YBX down-regulated the transcriptions of lasR, lasI, rhlR, and rhlI, which resulted in global attenuation of QS-regulated virulence activities, such as biofilm formation, and secretion of LasA protease, LasB elastase and pyocyanin. Further, YBX reduced the motility of P. aeruginosa related to QS, and impaired the formation of biofilms. These results suggest that YBX may possess global inhibitory activity against the virulence of P. aeruginosa and that YBX may also exhibit antimicrobial activity in vivo. The present study suggests that Yunnan Baiyao represents a potential source for isolating novel, safe, and efficacious antimicrobial agents.

Genetic variation in cytochrome P450 2J2 and soluble epoxide hydrolase and risk of ischemic stroke in a Chinese population.

OBJECTIVE: Epoxyeicosatrienoic acids have been recognized for their protective effects on the cardiovascular system. This study investigated whether two common polymorphisms in genes believed to be influential in regulating circulating levels of epoxyeicosatrienoic acids, namely cytochrome P450 2J2 (CYP2J2) G-50T and soluble epoxide hydrolase (EPHX2) G860A, were associated with ischemic stroke risk in a Chinese population. METHODS AND RESULTS: Screening of 200 patients with ischemic stroke and 350 control participants revealed that CYP2J2-50T allele frequency was not significantly different in ischemic stroke cases versus controls. In contrast, EPHX2 860A allele frequency was 16.8% in ischemic stroke cases versus 21.7% in controls (P=0.047), and the presence of this variant allele was associated with a significantly lower risk of ischemic stroke after adjustment for sex, age and multiple cardiovascular risk factors (adjusted odds ratio=0.50, 95% confidence interval 0.29-0.86). Moreover, there was a significant interaction between the EPHX2 G860A polymorphism, smoking and ischemic stroke risk such that nonsmokers carrying the EPHX2 G860A variant allele were at the lowest risk of ischemic stroke (odds ratio=0.33, 95% confidence interval, 0.17-0.67, P=0.002), whereas no significant association was observed in smokers. CONCLUSIONS: Collectively, these data indicate a protective influence of the G860A polymorphism of EPHX2 on ischemic stroke in Chinese nonsmokers.