Six previously undescribed compounds, named monaxanthones A and B, monaphenol A, monathioamide A, monaprenylindole A, and monavalerolactone A, were isolated from the culture of a marine-sourced bacterium Pseudomonas sp. ZZ820R in rice medium. Their structures were elucidated based on the HRESIMS data, NMR and MS-MS spectroscopic analyses, optical rotation and ECD calculations.  https://www.selleckchem.com/products/ga-017.html  Monathioamide A is an unprecedented sulfur-contained compound and monavalerolactone A represents the first example of this type of natural products. Monaprenylindole A showed antibacterial activity against methicillin-resistant Staphylococcus aureus. Sophora flavescens Ait (Ku-Shen in Chinese) is a popular traditional Chinese herbal medicine in China for a long history. It shows significant pharmacological activities in the treatment of dysentery, eczema, fever, jaundice, vulvar swelling, gastrointestinal hemorrhage and inflammatory disorders. Alkaloids and flavonoids have been identified as virtual components, especially isoprenoid flavanonols are a class of characteristic compounds for S. flavescens. However, few studies have focused on isoprenoid flavonoids analyses and no comprehensive review has yet been published. In the current review, we systematically summarized the isoprenoid flavonoids, a total of 55 compounds have been isolated from S. flavescens, particularly an isoprenyl and a lavandulyl group in backbone structures. Further pharmacological activities, qualitative and quantitative chemical analyses research will contribute to the development of natural isoprenoid flavonoid products in S. flavescens. In a clinically-relevant model of 4 week, low-dose cisplatin-induced AKI, mice were injected subcutaneously with non small cell lung cancer (NSCLC) cells that harbor an activating Kirsten rat sarcoma viral oncogene homolog (KRAS)G12V mutation. Phospho extracellular signal-regulated kinase1/2 (pERK1/2) expression in kidney and tumors was decreased by the MEK1/2 inhibitors, U0126 and trametinib, that potently inhibit pERK1/2. U0126 resulted in a significant improvement in kidney function, acute tubular necrosis (ATN) and tubular cell apoptosis in mice with AKI. Genes that were significantly decreased by U0126 were heat shock protein 1, cyclin-dependent kinase 4 (CDK4) and stratifin (14-3-3σ). U0126 resulted in a significant decrease in tumor weight and volume and significantly increased the chemotherapeutic effect of cisplatin. Trametinib, a MEK1/2 inhibitor that is FDA-approved for the treatment of cancer, did not result in functional protection against AKI or worse AKI, but dramatically decreased tumor growth more than cisplatin. Smaller tumors in cisplatin or MEK1/2 inhibitor-treated mice were not related to changes in microtubule-associated proteins 1A/1B light chain 3B (LC3-II), p62, cleaved caspase-3, granzyme B, or programmed death-ligand 1 (PD-L1). In summary, despite ERK inhibition by both U0126 and trametinib, only U0126 protected against AKI suggesting that the protection against AKI by U0126 was due to an off-target effect independent of ERK inhibition. The effect of U0126 to decrease AKI may be mediated by inhibition of heat shock protein 1, CDK4 or stratifin (14-3-3σ). Trametinib was more effective than cisplatin in decreasing tumor growth, but unlike cisplatin, trametinib did not cause AKI. We uncover a novel non-canonical function of ATR kinase in the control of PIDDosome activation, and show that under normal cellular conditions involving no replication stress, ATR kinase controls the phosphorylation of cellular NPM via pChk1 as well as the two phosphatases, PPM1D and PP1β. We show that pNPM triggers the dissociation of NPM from PIDD, preventing the cell from undergoing caspase 2 mediated cell death via PIDDosome, thereby acting as an endogenous negative regulator of PIDDosome activation. pChk1 interaction with NPM is abrogated following ATR kinase inhibition, leading to the drop in nucleoplasmic/chromatin pNPM level, inducing PIDD. Consistent with this mechanism, the phosphomimic mutants of Chk1 and NPM become refractory to ATR/pChk1 kinase inhibition by avoiding PIDDosome signalling. INTRODUCTION Extracorporeal life support (ECLS) has shown promise in the management of cardiac arrest. The purpose of this study was to examine temporal trends and predictors of ECLS utilization and survival to discharge among inpatients with cardiac arrest in the United States. METHODS All patients admitted after out-of-hospital cardiac arrest (OHCA) and those who experienced in-hospital cardiac arrest (IHCA) from 2005 to 2014 were identified in the National Inpatient Sample. Patients carrying a pregnancy as well as those with do-not-resuscitate orders or trauma-related diagnoses were excluded. Multivariable logistic regression was used to identify predictors of ECLS utilization and survival to discharge. RESULTS An estimated 1,624,827 patients were identified. During the study period, use of ECLS increased from 77 to 564 per 100,000 arrests for OHCA, and 60 to 632 per 100,000 arrests for IHCA. Survival among patients on ECLS for OHCA and IHCA increased from 34.2% to 54.2% and from 4.7% to 19.2%, respectively. Age, year of arrest, cardiac rhythm, and the presence of a potentially reversible etiology including myocardial infarction and pulmonary embolism, were predictive of ECLS utilization. Among patients placed on ECLS, age, rhythm at arrest, and location of arrest were predictive of survival to discharge. CONCLUSIONS Mortality after cardiac arrest for those on ECLS has substantially decreased. Younger age, shockable rhythm, and out-of-hospital arrest location were predictive of survival or utilization. As ECLS use increases, it is critical to define selection criteria that maximize the benefits of ECLS. AIM In this study, we investigate the impact of bystander relation and medical training on survival to hospital discharge in out-of-hospital cardiac arrest (OHCA) patients receiving bystander cardiopulmonary resuscitation (CPR). METHODS A retrospective analysis was performed on non-traumatic OHCA patients receiving bystander CPR and Emergency Medical Service (EMS) attempted resuscitation from 2015 through 2017. Adjusted logistic regression was used to assess the association between related versus unrelated and layperson versus medically trained bystander CPR providers and survival to hospital discharge. RESULTS A total of 4464 OHCA were eligible for inclusion, of which 2385 (53.4%) received CPR from a relative, 468 (10.5%) from a work colleague or friend and 1611 (36.1%) from a stranger. Layperson's provided CPR in 3703 (83.0%) OHCA and medically trained professionals in 761 (17.0%). After adjustment for arrest characteristics, there was no difference in survival to hospital discharge between related versus unrelated CPR (adjusted odds ratio [AOR] 0.