Analysis of two pheromone-responsive conjugative multiresistance plasmids carrying the novel mobile optrA locus from Enterococcus faecalis

Background: The acquired optrA gene, which encodes a ribosomal protection protein of the ABC-F family, can confer cross-resistance to linezolid and florfenicol, posing a serious therapeutic challenge to both human and veterinary medicine. Purpose: The objective of this study was to investigate the two Enterococcus faecalis (E. faecalis) plasmids for their fine structure, their transferability and the presence of mobile antimicrobial resistance loci. Methods: To elucidate their fine structure, the two plasmids were completely sequenced and the sequences analysed. Besides conjugation experiments, inverse PCR assays were conducted to see whether minicircles are produced from the mobile antimicrobial resistance loci. Results: Two pheromone-responsive conjugative optrA-carrying plasmids from E. faecalis, pE211 and pE508 were identified, which can transfer with frequencies of 2.6 ×10−2 and 3.7 ×10−2 (transconjugant per donor), respectively. In both plasmids, optrA was located on the novel mobile optrA locus with different sizes (12,834 bp in pE211 and 7,561 bp in pE508, respectively), flanked by two copies of IS1216 genes in the same orientation. Inverse PCR revealed that circular forms can be generated, consisting of optrA and one copy of IS1216, indicating they are all active. The 77,562 bp plasmid pE211 also carried Tn558 and a mobile bcrABDR locus, and the 84,468 bp plasmid pE508 also harbored the genes fexA, tet(L), tet(O/W/32/O) and a mobile aac(A)-aph(D) locus. Conclusion: The presence of mobile genetic elements in these plasmids renders them flexible and these elements will aid to the persistence and dissemination of these plasmids among enterococci and potentially also other gram-positive bacteria

Deciphering the Structural Evolution and Electronic Properties of Magnesium Clusters: An Aromatic Homonuclear Metal Mg17 Cluster

The structures and electronic properties of low-energy neutral and anionic Mg_<i>n</i> (<i>n</i> = 3–20) clusters have been studied by utilizing a widely adopted CALYPSO structure searching method coupled with density functional theory calculations. A large number of low-energy isomers are optimized at the B3PW91 functional with the 6-311+G­(d) basis set. The optimized geometries clearly indicate that a structural transition from hollow three-dimensional configurations to filled-cage-like structures occurs at <i>n</i> = 16 for both neutral and anionic clusters. Based on the anionic ground state structures, photoelectron spectra are simulated using time-dependent density functional theory (TD-DFT) and compared with experimental results. The good agreement validates that the current ground state structures, obtained from the symmetry-unconstrained searches, are true global minima. A detailed chemical bonding analysis distinctly indicates that the Mg₁₇ cluster is the first neutral locally π-aromatic homonuclear all-metal cluster, which perfectly satisfies Hückel’s well-known 4<i>N</i> + 2 rule

Effect of angiotensin receptor neprilysin inhibitors on left atrial remodeling and prognosis in heart failure

Aims The angiotensin receptor–neprilysin inhibitor (ARNI), sacubitril/valsartan, confers additional protective effects compared with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs) in terms of reversed left ventricular (LV) remodelling and improves the prognosis of patients with heart failure (HF). However, few studies have examined the effects of ARNI on the left atrium. Accordingly, this study compared the effects of ARNI and ACEI/ARB on left atrial (LA) remodelling in heart failure with reduced ejection fraction (HFrEF). Methods and results This was a single-centre retrospective study of patients with HFrEF hospitalized at the First Affiliated Hospital of Dalian Medical University between 26 February 2016 and 8 July 2020. Patients were classified into ARNI and ACEI/ARB groups and further subgroups based on the left atrial volume index (LAVI): mildly abnormal (29 mL/m2 ≤ LAVI < 34 mL/m2), moderately abnormal (34 mL/m2 ≤ LAVI < 40 mL/m2), and severely abnormal (LAVI ≥ 40 mL/m2). The primary endpoint was changes in LA parameters by echocardiography. The secondary endpoint was all-cause mortality. A total of 336 patients (mean age: 64.11 ± 12.86, 30.06% female) were included. Except those lost to follow-up, 274 HFrEF patients remained, with 144 cases in the ARNI group and 130 cases in the ACEI/ARB group. Greater reductions from baseline were seen with ARNI in LA diameter (LAD) (P = 0.013, t-test), superior and LA superior–inferior diameter (LASID) (P < 0.0001), LA transverse diameter (LATD) (P < 0.0001), LA volume (LAV) (P < 0.0001), LAVI (P < 0.0001), and LA sphericity index (LASI) (P < 0.0001). Over a mean follow-up of 19.40 months, 97 patients (67.3%) in the ARNI group and 29 patients (22.3%) in the ACEI/ARB group showed LA reverse remodelling (LARR). Kaplan–Meier analysis showed significantly lower overall mortality in the ARNI group compared with the ACEI/ARB group (P = 0.048, log-rank test). The mildly abnormal LAVI group of ARNI patients showed a reduction in mortality compared with ACEI/ARB patients (P = 0.044). However, no significant difference was observed for the moderately abnormal (P = 0.571) or severely abnormal LAVI groups (P = 0.609), suggesting that early initiation of ARNI was associated with a better prognosis. Conclusions In this proof-of-concept study, ARNI use showed greater effects on LARR and was associated with a better prognosis compared with ACEI/ARB use in HFrEF. Early initiation of ARNI in the HF disease process may produce greater benefit, but this needs to be confirmed in future studies

Environmental-Friendly Catalytic Oxidation Processes Based on Hierarchical Titanium Silicate Zeolites at SINOPEC

Since it was claimed by EniChem in 1983 for the first time, titanium silicate‐1 (TS‐1) zeolite presented the most delightful catalytic performance in the area of selective organic oxidation reactions. To enhance the mass diffusion property, hierarchical titanium silicate with hollow cavities within crystal was prepared by using a post‐synthesis treatment in the presence of organic template, and then, it was commercially produced and employed in many industrial catalytic oxidation processes, such as propylene epoxidation, phenol hydroxylation, and cyclohexanone ammoximation. Moreover, we also developed several totally novel oxidation reactions on hollow titanium silicate (HTS) zeolite, i.e., Baeyer‐Villiger oxidation of cyclohexanone and chlorohydrination of allyl chloride with HCl and H2O2. In all cases, HTS shows much better catalytic performance than TS‐1, attributing to the mass diffusion intensification by introducing hollow cavities. On the other hand, enormous works on synthesizing hierarchical TS‐1 zeolites with open intracrystalline mesopores have been done via silanization treatment and recrystallization. Based on them, several bulk molecule oxidation processes with tert‐butyl hydroperoxide, such as epoxidation of fatty acid methyl ester (FAME) and large olefins, have been carried out. As a consequence, hierarchical TS‐1 zeolites supply a platform for developing environmental‐friendly catalytic oxidation processes to remarkably overcome the drawbacks of traditional routes

Reverse atrial remodeling in heart failure with recovered ejection fraction

Background Heart failure with recovered ejection fraction (HFrecEF) has been a newly recognized entity since 2020. However, the concept has primarily focused on left ventricular ejection fraction improvement, with less focus on the recovery of the left atrium. In this study, we investigated changes in left atrial (LA) echocardiographic indices in HFrecEF. Methods and Results An inpatient cohort with heart failure with reduced ejection fraction (HFrEF) was identified retrospectively and followed up prospectively in a single tertiary hospital. The enrolled patients were classified into HFrecEF and persistent HFrEF groups. Alternations in LA parameters by echocardiography were calculated. The primary outcome was a composite of cardiovascular death or heart failure rehospitalization. A total of 699 patients were included (HFrecEF: n=228; persistent HFrEF: n=471). Compared with persistent HFrEF, the HFrecEF group had greater reductions in LA diameter, LA transverse diameter, LA superior–inferior diameter, LA volume, and LA volume index but not in LA sphericity index. Cox regression analysis showed that the HFrecEF group experienced lower risks of prespecified end points than the persistent HFrEF group after adjusting for confounders. Additionally, 136 (59.6%) and 62 (13.0%) patients showed LA reverse remodeling (LARR) for the HFrecEF and persistent HFrEF groups, respectively. Among the HFrecEF subgroup, patients with LARR had better prognosis compared with those without LARR. Multivariate logistic analysis demonstrated that age and coronary heart disease were 2 independent negative predictors for LARR. Conclusions In HFrecEF, both left ventricular systolic function and LA structure remodeling were improved. Patients with HFrecEF with LARR had improved clinical outcomes, indicating that the evaluation of LA size provides a useful biomarker for risk stratification of heart failure

Predictive value of HFA-PEFF score in patients with heart failure with preserved ejection fraction

HFA-PEFF score has been proposed for diagnosing heart failure with preserved ejection fraction (HFpEF). Currently, there are only a limited number of tools for predicting the prognosis. In this study, we evaluated whether the HFA-PEFF score can predict mortality in patients with HFpEF. This single-center, retrospective observational study enrolled patients diagnosed with HFpEF at the First Affiliated Hospital of Dalian Medical University between January 1, 2015, and April 30, 2018. The subjects were divided according to their HFA-PEFF score into low (0-2 points), intermediate (3-4 points), and high (5-6 points) score groups. The primary outcome was all-cause mortality. A total of 358 patients (mean age: 70.21 ± 8.64 years, 58.1% female) were included. Of these, 63 (17.6%), 156 (43.6%), and 139 (38.8%) were classified into the low, intermediate, and high score groups, respectively. Over a mean follow-up of 26.9 months, 46 patients (12.8%) died. The percentage of patients who died in the low, intermediate, and high score groups were 1 (1.6%), 18 (11.5%), and 27 (19.4%), respectively. A multivariate Cox regression identified HFA-PEFF score as an independent predictor of all-cause mortality [hazard ratio ( ):1.314, 95% : 1.013-1.705, = 0.039]. A Cox analysis demonstrated a significantly higher rate of mortality in the intermediate ( : 4.912, 95% 1.154-20.907, = 0.031) and high score groups ( : 5.291, 95% : 1.239-22.593, = 0.024) than the low score group. A receiver operating characteristic (ROC) analysis indicated that the HFA-PEFF score can effectively predict all-cause mortality after adjusting for age and New York Heart Association (NYHA) class [area under the curve (AUC) 0.726, 95% 0.651-0.800, = 0.000]. With an HFA-PEFF score cut-off value of 3.5, the sensitivity and specificity were 78.3 and 54.8%, respectively. The AUC on ROC analysis for the biomarker component of the score was similar to that of the total score. The HFA-PEFF score can be used both to diagnose HFpEF and predict the prognosis. The higher scores are associated with higher all-cause mortality. [Abstract copyright: Copyright © 2021 Sun, Si, Li, Dai, King, Zhang, Zhang, Xia, Tse and Liu.