(5S*,6R*,7R*)-6-Formyl-5-phenyl-7-propyl­perhydro­pyrazolo[1,2-a]pyrazol-1-one

The title compound, C16H20N2O2, was obtained by catalytic asymmetric cyclo­addition of trans-3-propyl­acrolein with 1-benzyl­idenepyrazolid-3-one betaine. There are two symmetry-independent mol­ecules in the asymmetric unit. In both mol­ecules, the two five-membered heterocyclic rings adopt envelope conformations

Effect of Sow Intestinal Flora on the Formation of Endometritis

Endometritis is the main cause of decreased reproductive performance of sows, while one of the most important factors in the etiology of sow endometritis is an aberration of birth canal microbiota. Therefore, people began to pay attention to the microbiota structure and composition of the birth canal of sows with endometritis. Interestingly, we found that the risk of endometritis was increased in the sows with constipation in clinical practice, which may imply that the intestinal flora is related to the occurrence of endometritis. Therefore, understanding the relationship between birth canal microbiota and intestinal microbiota of the host has become exceptionally crucial. In this study, the microbiota of birth canal secretions and fresh feces of four healthy and four endometritis sows were analyzed via sequencing the V3 + V4 region of bacterial 16S ribosomal (rDNA) gene. The results showed a significant difference between endometritis and healthy sows birth canal flora in composition and abundance. Firmicutes (74.36%) and Proteobacteria were the most dominant phyla in birth canal microbiota of healthy sows. However, the majority of beneficial bacteria that belonging to Firmicutes phylum (e.g., Lactobacillus and Enterococcus) declined in endometritis sow. The abundance of Porphyromonas, Clostridium sensu stricto 1, Streptococcus, Fusobacterium, Actinobacillus, and Bacteroides increased significantly in the birth canal microbiota of endometritis sows. Escherichia–Shigella and Bacteroides were the common genera in the birth canal and intestinal flora of endometritis sows. The abundance of Escherichia–Shigella and Bacteroides in the intestines of sows suffering from endometritis were significantly increased than the intestinal microbiota of the healthy sows. We speculated that some intestinal bacteria (such as Escherichia–Shigella and Bacteroides) might be bound up with the onset of sow endometritis based on intestinal microbiota analysis in sows with endometritis and healthy sows. The above results can supply a theoretical basis to research the pathogenesis of endometritis and help others understand the relationship with the microbiota of sow's birth canal and gut

Design, synthesis and in vitro anti-Zika virus evaluation of novel Sinefungin derivatives

We report herein the design and synthesis of a series of novel Sinefungin (SIN) derivatives, based on the structures of SIN and its analogue EPZ004777. Our results reveal that target compounds 1ad-af, 1ba-bb and 1bf-bh show better activity (IC50 = 4.56–20.16 μM) than EPZ004777 (IC50 = 35.19 μM). Surprisingly, SIN was founded to be not as active (IC50 > 50 μM) as we and other research groups predicted. Interestingly, the intermediates 9a-b and 11b display potent anti-ZIKV potency (IC50 = 6.33–29.98 μM), and compound 9a also exhibits acceptable cytotoxicity (CC50 > 200 μM), suggesting their promising potential to be leads for further development

Protective Effects of Chinese Traditional Medicine Longhu Rendan against Atherosclerosis via Negative Regulation of LOX-1

Longhu Rendan (LHRD), a Chinese traditional compound medicine, has a remarkable treatment effect on motion sickness for about half a century. However, the role of LHRD in atherosclerosis treatment is still unclear. In this study, LHRD treatment significantly diminished total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels in apolipoprotein E gene-knockout (ApoE-/-) mice fed with high fat and high cholesterol diet (western diet). Besides, LHRD treatment significantly reduced atherosclerotic lesion and plaques formation in both aortic roots and aortic trees. Furthermore, immunofluorescence staining in aortic roots demonstrated that LHRD treatment inhibited lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) expression in atherosclerotic plaques. These results indicated that LHRD ameliorated atherosclerosis via reducing serum levels of TC, TG, and LDL-C as well as LOX-1 expression, subsequently attenuating atherosclerotic lesion and lipid deposition. In conclusion, LHRD could significantly attenuate experimental atherosclerosis and might be a novel potential drug for the prevention and treatment of atherosclerosis

Molnupiravir and Its Active Form, EIDD-1931, Show Potent Antiviral Activity against Enterovirus Infections In Vitro and In Vivo

Enterovirus infections can cause hand, foot, and mouth disease (HFDM), aseptic meningitis, encephalitis, myocarditis, and acute flaccid myelitis, leading to death of infants and young children. However, no specific antiviral drug is currently available for the treatment of this type of infection. The Unites States and United Kingdom health authorities recently approved a new antiviral drug, molnupiravir, for the treatment of COVID-19. In this study, we reported that molnupiravir (EIDD-2801) and its active form, EIDD-1931, have broad-spectrum anti-enterovirus potential. Our data showed that EIDD-1931 could significantly reduce the production of EV-A71 progeny virus and the expression of EV-A71 viral protein at non-cytotoxic concentrations. The results of the time-of-addition assay suggest that EIDD-1931 acts at the post-entry step, which is in accordance with its antiviral mechanism. The intraperitoneal administration of EIDD-1931 and EIDD-2801 protected 1-day-old ICR suckling mice from lethal EV-A71 challenge by reducing the viral load in various tissues of the infected mice. The pharmacokinetics analysis indicated that the plasma drug concentration overwhelmed the EC50 for enteroviruses, suggesting the clinical potential of molnupiravir against enteroviruses. Thus, molnupiravir along with its active form, EIDD-1931, may be a promising drug candidate against enterovirus infections

Azelnidipine Exhibits In Vitro and In Vivo Antiviral Effects against Flavivirus Infections by Targeting the Viral RdRp

Flaviviruses, represented by Zika and dengue virus (ZIKV and DENV), are widely present around the world and cause various diseases with serious consequences. However, no antiviral drugs have been clinically approved for use against them. Azelnidipine (ALP) is a dihydropyridine calcium channel blocker and has been approved for use as an antihypertensive drug. In the present study, ALP was found to show potent anti-flavivirus activities in vitro and in vivo. ALP effectively prevented the cytopathic effect induced by ZIKV and DENV and inhibited the production of viral RNA and viral protein in a dose-dependent manner. Moreover, treatment with 0.3 mg/kg of ALP protected 88.89% of mice from lethal challenge. Furthermore, using the time-of-drug-addition assay, the enzymatic inhibition assay, the molecular docking, and the surface plasmon resonance assay, we revealed that ALP acted at the replication stage of the viral infection cycle by targeting the viral RNA-dependent RNA polymerase. These findings highlight the potential for the use of ALP as an antiviral agent to combat flavivirus infections