The novel coronavirus disease 2019 , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic, but the factors influencing viral RNA shedding, which would help inform optimal control strategies, remain unclear. Methods: The clinical course and viral RNA shedding pattern of 267 consecutive symptomatic COVID-19 patients admitted to the hospital from January 20, 2020 to March 15, 2020 were evaluated retrospectively. Results: The median duration of viral RNA shedding was 12 days (interquartile range 8-16 days) after the onset of illness. Of the 267 patients included in this study, 65.2% had viral RNA clearance within 14 days, 88.8% within 21 days, and 94.4% within 28 days. Older age (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.98-1.00; p = 0.04), time lag from illness onset to hospital admission (HR 0.91, 95% CI 0.88-0.94; p < 0.001), diarrhea (HR 0.59, 95% CI 0.36-0.96; p = 0.036), corticosteroid treatment (HR 0.60, 95% CI 0.39-0.94; p = 0.024), and lopinavir/ritonavir use (HR 0.70, 95% CI 0.52-0.94; p = 0.014) were significantly and independently associated with prolonged viral RNA shedding. Conclusions: Early detection and timely hospital admission may be warranted for symptomatic COVID-19 patients, especially for older patients and patients with diarrhea. Corticosteroid treatment is associated with prolonged viral RNA shedding and should be used with caution. Lopinavir/ritonavir use may be associated with prolonged viral RNA shedding in non-severe patients; further randomized controlled trials are needed to confirm this finding.

Compelling evidence indicates that stress in utero, as manifested by low birth weight (LBW), increases the risk of metabolic syndrome in adulthood. Singletons conceived by assisted reproductive technology (ART) display a significant increase in LBW risk and ART offspring have a different metabolic profile starting at birth. Here, used mouse as a model, we found that ART resulted in reduced fetal weight and placental overgrowth at embryonic day 18.5 (E18.5). The ART placentae exhibited histomorphological alterations with defects in placental layer segregation and glycogen cells migration at E18.5. Further, ART treatments resulted in downregulation of a majority of placental nutrient transporters and reduction in placental efficiency. Moreover, the ART placentae were associated with increased methylation levels at imprinting control regions of H19, KvDMR1 and disrupted expression of a majority of imprinted genes important for placental development and function at E18.5. Our results from the mouse model show the first piece of evidence that ART treatment could affect fetal growth by disrupting placental development and function, suggests that perturbation of genomic imprinting resulted from embryo manipulation may contribute to these problems.

Background:The novel coronavirus disease 2019 characterized by respiratory symptoms has become a global pandemic although factors influencing viral RNA clearance remained unclear to inform optimal isolation period and treatment strategies. Methods:In this retrospective study, we included patients with confirmed COVID-19The associations of clinical characteristics and treatment regimens on time to viral RNA clearance were analyzed. Results:We examined 284 consecutive COVID-19 cases, accounting for 82% of confirmed cases in Guangzhou during this period. At the time of reporting (20 th March 2020), 276 (97.2%) had recovered and were discharged from hospital with a median hospital stay of 18 days (interquartile range [IQR]:13-24). Overall, 280 patients achieved viral RNA clearance with a median length of 12 days (IQR: 8-16) after onset of illness. Amongst them, 66.1% had viral RNA cleared within 14 days, and 89.3% within 21 days. Older age, severity of disease, time lag from illness onset to hospital admission, high body temperature, and corticosteroid use were associated with delayed clearance of viral RNA. None of the antiviral regimens (chloroquine, oseltamivir, arbidol, and lopinavir/ritonavir) improved viral RNA clearance.The use of lopinavir/ritonavir was associated with delayed clearance of viral RNA after adjusting for confounders. Conclusion:In patients with COVID-19, isolation for a minimum of 21 days after onset of illness may be warranted, while the use of antiviral drugs does not enhance viral RNA clearance.

Hypertension is a dominating risk factor for cardiovascular disease. To characterize the genomic response to hypertension, we administered vehicle or angiotensin II to mice and performed gene expression analyses. AngII treatment resulted in a robust increase in blood pressure and altered expression of 235 genes in the aorta, including Gucy1a3 and Gucy1b3 which encode subunits of soluble guanylyl cyclase (sGC). Western blotting and immunohistochemistry confirmed repression of sGC associated with curtailed relaxation via sGC activation. Analysis of transcription factor binding motifs in promoters of differentially expressed genes identified enrichment of motifs for RBPJ, a component of the Notch signaling pathway, and the Notch coactivators FRYL and MAML2 were reduced. Gain and loss of function experiments demonstrated that JAG/NOTCH signaling controls sGC expression together with MAML2 and FRYL. Reduced expression of sGC, correlating with differential expression of MAML2, in stroke prone and spontaneously hypertensive rats was also seen, and RNA-Seq data demonstrated correlations between JAG1, NOTCH3, MAML2 and FRYL and the sGC subunits GUCY1A3 and GUCY1B3 in human coronary artery. Notch signaling thus provides a constitutive drive on expression of the major nitric oxide receptor (GUCY1A3/GUCY1B3) in arteries from mice, rats, and humans, and this control mechanism is disturbed in hypertension.

MicroRNAs (miRNAs) are closely associated with cell proliferation, invasion and metastasis in various types of cancer, including prostate cancer. In this study, the role of miR-429 in the regulation of cell proliferation was investigated in prostate cancer cells. miR-429 expression levels were measured in the IF11 and IA8 prostate cancer cell lines and normal prostate epithelial tissues by quantitative polymerase chain reaction. miR-429 mimics or an miR-429 inhibitor were then transfected into the human prostate cancer cell lines. MTT and fluorescence-activated cell sorting were used to detect the effect of miR-429 on cell proliferation. A luciferase reporter system was employed to verify the potential target of miR-429. The results revealed that miR-429 was significantly upregulated in the human prostate cancer cell lines, compared with the normal prostate epithelial tissue. Downregulation of miR-429 expression in IF11 and IA8 cells inhibited cell proliferation and arrested the cells in the G1 phase of the cell cycle. The luciferase assay demonstrated that p27Kip1 was a direct target of miR-429. Furthermore, overexpression of p27Kip1 was observed to partially rescue the proliferation‑promoting effect of miR-429 on IA8 cells. In conclusion, to the best of our knowledge this study was the first to show that miR-429 is involved in the oncogenesis of prostate cancer and thus may be a novel prognostic biomarker in prostate cancer.