Timmknudsen0265

Macrolide and tetracycline resistance in streptococci is mainly caused by acquisition of integrative and conjugative elements (ICEs) of the ICESa2603 family carrying erm(B) and tet(O). But the characteristics about the transferability and physiological consequences of ICEs with triplet serine integrases are still rare. This study tested the transferability of ICESsuYZDH1_SSU0877, a novel erm(B)- and tet(O)-carrying ICESa2603 family-like ICE with triplet serine integrases, and evaluated the physiological consequences after ICE transferred and integrated into recipient. The prevalence of ICESsuYZDH1-like ICEs in S. suis was analyzed based on 1334 genomic sequences available in GenBank and examined in 330 clinical isolates in China. Nonconservative transfer was observed by integrating of ICESsuYZDH1 into SSU1797 gene besides the primary SSU0877 site. Imperfect direct repeats of 2-/4-nt (5'-TC-3'/5'-TCCC-3') and (5'-GC-3'/5'-TCCC-3') were observed at SSU0877 and SSU1797 sites, respectively. The transconjugant suffered a weak fitness cost with stunted growth and less competition with recipient strain. Successive passages indicate the ICESsuYZDH1 could be persist and endued stable resistant phenotype. Comprehensive analysis of the ICESsuYZDH1-like ICEs from both public genome database and our clinical isolates revealed the widespread and diversity of the ICEs by integration at the sites of SSU0877, SSU0468, SSU1262, and SSU1797. The ICESsuYZDH1-like ICEs could stably co-exist within the host chromosome at more than one attachment sites, which is probably mediated by the triplet serine integrases. Nonconservative integration and diversity of the ICESsuYZDH1 family of ICEs might have contributed to the evolution of ICEs and the dissemination of macrolide and tetracycline resistance in S. suis.Photodynamic therapy (PDT) is an exceedingly promising cancer treatment. However, the hypoxic environment in tumor and the low penetration efficiency of short-wavelength light limit the effects of PDT. In this paper, an injectable red blood cell membrane doped hydrogel system (UCNPs/S7942/RB-RHY) containing upconversion nanoparticles (UCNPs), a photosensitizer (Rose Bengal) and a strain of cyanobacteria Synechococcus elongatus PCC 7942 (S. 7942) was developed to improve the PDT effects with a good biocompatibility and biosafety. In the system, S. 7942 was capable of inexhaustibly generating oxygen triggered by the 640 nm laser irradiation for alleviating hypoxic tumor microenvironment. In addition, UCNPs converted near-infrared light to visible light upon excitation by a 980 nm laser, which further activated the photosensitizer to release reactive singlet oxygen to eradicate tumors. Itacitinib mw In vivo experiments showed that the tumor volume in the UCNPs/S7942/RB-RHY combined 640 nm with 980 nm light group was 496.9 mm3, in compared with 955.5 mm3 of the tumor volume in the group without irradiation. The results demonstrated that UCNPs/S7942/RB-RHY was able to not only dramatically alleviate tumor hypoxia but also achieve a more efficient PDT treatment. The oxygen-generating system described here provides a new idea for hypoxia-resistant cancer therapy in the future.Exercise interventions have been shown to positively impact cognitive function in older adults, but the mechanisms underlying the neuroprotective effects of exercise on the brain are not well understood. Here, we aimed to synthesize and quantitatively analyze the current literature on exercise interventions and brain volume change in older adults and to examine the impact of key demographic and intervention features as well as study quality. This study was pre-registered with PROSPERO (CRD42018091866). EBSCOhost, Cochrane Library, Embase, and reference lists were searched to identify randomized-controlled trials (RCTs) of exercise interventions for healthy older adults and older adults (60+) with mild cognitive impairment (MCI). A total of 69 effects from 14 studies were pooled and expressed as Hedge's g using a random-effects model. Results indicated that there was no significant difference in brain volume outcomes for older adults that completed an exercise intervention compared to older adults in control groups (g = 0.012, p = 0.728, 95% CI = -0.055, .078). These results were confirmed using multilevel analysis to account for nesting of effects within studies (g = 0.009, p = 0.826, 95% CI = -0.072, 0.090) and using conservative post-hoc models to address possible non-independence of multiple outcome domains and sample nonindependence. No significant heterogeneity was detected, limiting moderator analyses. The implications for future research are discussed.Sex differences play a vital role in human brain structure and physiology. Previous reports have proposed evidence hinting at a metabolic advantage in female brains across adulthood. It remained to be determined whether this advantage would be maintained across the spectrum of cognitive impairment, up to and including dementia due to Alzheimer's disease (AD). Here, using a machine-learning algorithm, we explore sex differences in metabolic brain-age derived from fluorodeoxyglucose positron emission tomography imaging among cognitively healthy individuals and those affected by mild cognitive impairment and clinically probable AD. First, we report that cognitively healthy male participants showed a persistently "older" looking brains when compared to healthy female participants in term of metabolic brain age, confirming earlier reports. However, this distinction disappeared among MCI individuals and probable AD patients, and this loss could not be explained by an accompanying neurodegeneration. This would seem to indicate that females have a higher rate of decline in brain glucose metabolism when cognitively impaired to negate their prior advantage.Compounds incorporating guanidine moieties constitute a versatile class of biologically interesting molecules with a wide array of applications. As such, guanidines have been exploited as privileged structural motifs in designing novel drugs for the treatment of various infectious and non-infectious diseases. In designing anti-infective agents, this moiety carries great appeal by virtue of attributes such as hydrogen-bonding capability and protonatability at physiological pH in the context of interaction with biological targets. This review provides an overview of recent advances in hit-to-lead development studies of antimicrobial guanidine-containing compounds with the aim to highlight their structural diversity and the pharmacological relevance of the moiety to drug activity, insofar as possible. In so doing, emphasis is put on chemical and microbiological properties of such compounds in relation to antibacterial, antifungal and antimalarial activities.