Infinitely many solutions for Schrödinger–Kirchhoff-type equations involving indefinite potential

In this paper, we study the multiplicity of solutions for the following Schrödinger–Kirchhoff-type equation $$\begin{cases}-\left(a+b\int_{\mathbb{R}^N}|\nabla u|^2dx\right)\triangle u+V(x)u=f(x,u)+g(x,u), \quad x\in \mathbb{R}^N,\\ u\in H^1(\mathbb{R}^N),\end{cases}$$ where $N\geq 3$, $a,\,b>0$ are constants and the potential $V$ may be unbounded from below. Under some mild conditions on the nonlinearities $f$ and $g$, we obtain the existence of infinitely many solutions for this problem. Recent results from the literature are generalized and significantly improved

Co‐evolutionary adaptations of Acinetobacter baumannii and a clinical carbapenemase‐encoding plasmid during carbapenem exposure

Abstract: OXA‐23 is the predominant carbapenemase in carbapenem‐resistant Acinetobacter baumannii. The co‐evolutionary dynamics of A. baumannii and OXA‐23‐encoding plasmids are poorly understood. Here, we transformed A. baumannii ATCC 17978 with pAZJ221, a blaOXA−23‐containing plasmid from clinical A. baumannii isolate A221, and subjected the transformant to experimental evolution in the presence of a sub‐inhibitory concentration of imipenem for nearly 400 generations. We used population sequencing to track genetic changes at six time points and evaluated phenotypic changes. Increased fitness of evolving populations, temporary duplication of blaOXA−23 in pAZJ221, interfering allele dynamics, and chromosomal locus‐level parallelism were observed. To characterize genotype‐to‐phenotype associations, we focused on six mutations in parallel targets predicted to affect small RNAs and a cyclic dimeric (3′ → 5′) GMP‐metabolizing protein. Six isogenic mutants with or without pAZJ221 were engineered to test for the effects of these mutations on fitness costs and plasmid kinetics, and the evolved plasmid containing two copies of blaOXA−23 was transferred to ancestral ATCC 17978. Five of the six mutations contributed to improved fitness in the presence of pAZJ221 under imipenem pressure, and all but one of them impaired plasmid conjugation ability. The duplication of blaOXA−23 increased host fitness under carbapenem pressure but imposed a burden on the host in antibiotic‐free media relative to the ancestral pAZJ221. Overall, our study provides a framework for the co‐evolution of A. baumannii and a clinical blaOXA−23‐containing plasmid in the presence of imipenem, involving early blaOXA−23 duplication followed by chromosomal adaptations that improved the fitness of plasmid‐carrying cells

Contemporary survival and anticoagulation of patients with atrial fibrillation: A community based cohort study in China

BackgroundsThe understanding of death in patients with atrial fibrillation (AF) in China is limited. This study aimed to assess the contemporary survival of AF patients in China and to explore risk factors for deaths.MethodsThis was a prospective community-based cohort study including 559 AF patients, who were followed-up from July 2015 to December 2020.ResultsDuring 66-month follow-up, there were 200 deaths (56.5% cardiovascular, 40.0% non-cardiovascular, and 3.5% unknown causes) among 559 AF patients with the median age of 76 years. The top three causes of death were heart failure (33.0%), ischemic stroke (17.0%) and cancer (16.5%). Multivariate Cox regression analysis indicated baseline variables positively associated with all-cause death were age (HR: 1.10, 95% CI: 1.08–1.13), AF subtype (HR: 1.37, 95% CI: 1.08–1.73), prior myocardial infarction (HR: 3.40, 95% CI: 1.48–7.78), previous tumor (HR: 2.61, 95% CI: 1.37–4.98), hypoglycemic therapy at baseline (HR: 1.81, 95% CI: 1.13–2.91), but body weight (HR: 0.98, 95% CI: 0.97–1.00) and use of calcium channel blocker (CCB) (HR: 0.62, 95% CI: 0.41–0.95) played a protective role to all-cause death. Of patients who were alive at the end of follow-up, 24.0% were on oral anticoagulants (OAC) alone, 4.5% on dual antithrombotic therapy, 33.1% on antiplatelet agents alone and 38.4% weren't on any antithrombotic medication.ConclusionIschemic stroke still remains one of the leading causes of death and OAC is seriously underused in AF patients in China. Independent risk factors for death are age, AF subtype, previous tumor, prior myocardial infarction, hypoglycemic therapy, low body weight and no CCB use.Clinical Trial Registrationhttp://www.chictr.org.cn/ (ChiCTR-ICR-15007036)

Construction of Dimeric Drug-Loaded Polymeric Micelles with High Loading Efficiency for Cancer Therapy

Polymeric micelles (PMs) have been applied widely to transport hydrophobic drugs to tumor sites for cancer treatment. However, the low load efficiency of the drug in the PMs significantly reduces the therapeutic efficiency. We report here that disulfide-linked camptothecin (CPT) as a kind of dimeric drug can be effectively embedded in the core of poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL) PMs for improving drug-loading efficiency, and PEG can be used as a hydrophilic shell. Moreover, the dimeric CPT-loaded PCL–PEG–PCL PMs exhibited excellent solubility in phosphate-buffered saline (PBS) media and significant cytotoxicity to cancer cells

A time-dependent density functional theory investigation of the spectroscopic properties of the beta-subunit in C-phycocyanin

By using time-dependent density functional theory combined with the polarizable continuum model, a satisfactory assignment of the absorption and circular dichroism spectra and energy transfer flow of the beta-subunit in C-phycocyanin (C-PC) was achieved when the protonation of beta-84 and beta-155 phycocyanobilin (PCB) and their interaction with the protein moiety in C-PC have been taken into account. We attribute the main peak for both beta-84 and beta-155 as arising from the pi electron excitation of the pyrrole rings and the shoulder peak as arising from the charge transfer from the asparate residue to PCBH+. The satisfactory agreement between theory and experiment suggests that Forster resonance theory prevails such that energy transfer occurs from beta(s)(beta-155) to beta(f)(beta-84)

Evolution of Acinetobacter baumannii In Vivo: International Clone II, More Resistance to Ceftazidime, Mutation in ptk

Acinetobacter baumannii is an important nosocomial pathogen worldwide. A more comprehensive understanding of the within-host genomic evolution of A. baumannii would provide a molecule basis for improving treatment of A. baumannii infection. To understand the evolutionary mechanism facilitating A. baumannii survived in human body, we here reported the genomic analysis of A. baumannii isolated sampled from Chinese patients. We used whole-genome sequence of A. baumannii isolates from the same patient to determine single-nucleotide variants, insertion sequence mapping, and gene change. The MICs for 10 antimicrobial agents were determined. Motility assay and microscopy were performed on the isolated pairs harboring ptk mutations. The gene ptk encoded a putative protein tyrosine kinase involved in the production of capsular polysaccharide. Approximately half (39/86) of the strains isolated from the same patient harbored the same MLST patterns, and during the replacement of international clonal lineage II (ICL-II) and non-ICL-II strains, most of the alteration was that non-ICL-II strain was replaced by ICL-II strain (10/12). A. baumannii was resistant to major antimicrobial agents, whereas the strains were more resistant to ceftazidime, azithromycin, and sulfonamides after within-host evolution. Isolates from the ICL-II lineage displayed greater resistance to antimicrobial agents than non-ICL-II isolates. Isolates from ICL-II harbored more resistance genes and mobile elements than non-ICL-II strains. Several lineages evolved a more mucoid phenotype. Genome sequencing revealed that the phenotype was achieved by genetic changes in the ptk gene. ICL-II (especially ST195 and ST208) was the terminal destination for bacteria after within-host evolution. These results indicate that the molecular basis and the treatment for ICL-II strains needed further investigation