Biofilms are ubiquitous throughout aquatic environments and they are thought to promote the acquisition and dissemination of antibiotic resistant genes (ARGs). This study focused on the occurrence ...and distribution of five types of ARG in naturally-occurring biofilms, in comparison to associated sediment and water samples, from the Yangtze Estuary, which borders the meta-city of Shanghai, China. The detection frequency and abundances of most ARGs showed the following order: biofilm > sediment > water, which can be attributed to a high level of antibiotics and metals that can accelerate the generation and propagation of ARGs in biofilms. Most of ARG abundances were contributed by extracellular DNA (eDNA) in biofilm and sediment samples. ARGs (sul1, sul2, tetA and tetW) in eDNA were significantly correlated with TOC in both biofilm and sediment samples. Furthermore, both intracellular DNA-associated ARGs per gram of microbial biomass carbon (MBC) and eDNA-associated ARGs per gram of non-MBC and were higher in biofilms than sediments, and the partitioning coefficients of ARGs in eDNA between biofilm and water were higher than those between sediment and water. Our results provide new insight for evaluating the occurrence and abundance of ARGs in aquatic environments, confirming that biofilms are a significant sink for ARGs in the estuarine environment.
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•Most of ARG abundances in the Yangtze Estuary showed: biofilm > sediment > water.•Antibiotics, metals, TOC and bacterial density may regulate ARGs in biofilms.•Most of ARGs were contributed by extracellular DNA in both biofilms and sediments.•Biofilm/water partitioning coefficients of ARGs in eDNA were higher than those of sediment/water.
The single bromodomain of the closely related transcriptional regulators CBP/EP300 is a target of much recent interest in cancer and immune system regulation. A co-crystal structure of a ...ligand-efficient screening hit and the CBP bromodomain guided initial design targeting the LPF shelf, ZA loop, and acetylated lysine binding regions. Structure–activity relationship studies allowed us to identify a more potent analogue. Optimization of permeability and microsomal stability and subsequent improvement of mouse hepatocyte stability afforded 59 (GNE-272, TR-FRET IC50 = 0.02 μM, BRET IC50 = 0.41 μM, BRD4(1) IC50 = 13 μM) that retained the best balance of cell potency, selectivity, and in vivo PK. Compound 59 showed a marked antiproliferative effect in hematologic cancer cell lines and modulates MYC expression in vivo that corresponds with antitumor activity in an AML tumor model.
We conducted a systematic review and meta-analysis to investigate whether the use of statins could be associated with the risk of all-caused dementia, Alzheimer's disease (AD), vascular dementia ...(VaD), and mild cognitive impairment (MCI). Major electronic databases were searched until December 27
, 2017 for studies investigating use of statins and incident cognitive decline in adults. Random-effects meta-analyses calculating relative risks (RRs) were conducted to synthesize effect sizes of individual studies. Twenty-five studies met eligibility criteria. Use of statins was significantly associated with a reduced risk of all-caused dementia (k = 16 studies, adjusted RR (aRR) = 0.849, 95% CI = 0.787-0.916, p = 0.000), AD (k = 14, aRR = 0.719, 95% CI = 0.576-0.899, p = 0.004), and MCI (k = 6, aRR = 0.737, 95% CI = 0.556-0.976, p = 0.033), but no meaningful effects on incident VaD (k = 3, aRR = 1.012, 95% CI = 0.620-1.652, p = 0.961). Subgroup analysis suggested that hydrophilic statins were associated with reduced risk of all-caused dementia (aRR = 0.877; CI = 0.818-0.940; p = 0.000) and possibly lower AD risk (aRR = 0.619; CI = 0.383-1.000; p = 0.050). Lipophilic statins were associated with reduced risk of AD (aRR = 0.639; CI = 0.449-0.908; p = 0.013) but not all-caused dementia (aRR = 0.738; CI = 0.475-1.146; p = 0.176). In conclusion, our meta-analysis suggests that the use of statins may reduce the risk of all-type dementia, AD, and MCI, but not of incident VaD.
In this trial, the addition of six cycles of docetaxel to androgen-deprivation therapy resulted in longer median progression-free and overall survival than that with ADT alone in patients with ...metastatic prostate cancer.
Regressions of metastatic prostate cancer were first documented in the 1940s and were achieved with surgical castration; subsequently, androgen-deprivation therapy (ADT) became the mainstay of therapy.
1
Attempts to improve the efficacy or decrease the treatment burden of ADT have included the use of antiandrogens alone, intermittent dosing of ADT, and the use of an antiandrogen combined with medical or surgical castration.
2
–
4
A meta-analysis revealed an increase in survival of 3 percentage points at 5 years with concurrent use of a nonsteroidal antiandrogen at the time of initiation of ADT.
2
However, resistance to ADT occurs in most patients, with the . . .
Abstract
Understanding the competition between superconductivity and other ordered states (such as antiferromagnetic or charge-density-wave (CDW) state) is a central issue in condensed matter ...physics. The recently discovered layered kagome metal
A
V
3
Sb
5
(
A
= K, Rb, and Cs) provides us a new playground to study the interplay of superconductivity and CDW state by involving nontrivial topology of band structures. Here, we conduct high-pressure electrical transport and magnetic susceptibility measurements to study CsV
3
Sb
5
with the highest
T
c
of 2.7 K in
A
V
3
Sb
5
family. While the CDW transition is monotonically suppressed by pressure, superconductivity is enhanced with increasing pressure up to P1 ≈ 0.7 GPa, then an unexpected suppression on superconductivity happens until pressure around 1.1 GPa, after that,
T
c
is enhanced with increasing pressure again. The CDW is completely suppressed at a critical pressure P2 ≈ 2 GPa together with a maximum
T
c
of about 8 K. In contrast to a common dome-like behavior, the pressure-dependent
T
c
shows an unexpected double-peak behavior. The unusual suppression of
T
c
at P1 is concomitant with the rapidly damping of quantum oscillations, sudden enhancement of the residual resistivity and rapid decrease of magnetoresistance. Our discoveries indicate an unusual competition between superconductivity and CDW state in pressurized kagome lattice.
Summary Objective Repairing articular cartilage is clinically challenging. We investigated a simple, effective and clinically feasible cell-based therapeutic approach using a ...poly(lactide-co-glycolide) (PLGA) scaffold seeded with autologous endothelial progenitor cells (EPC) to repair a full-thickness osteochondral defect in rabbits using a one-step surgery. Methods EPC obtained by purifying a small amount of peripheral blood from rabbits were seeded into a highly porous, biocompatible PLGA scaffold, namely, EPC-PLGA, and implanted into the osteochondral defect in the medial femoral condyle. Twenty two rabbits were randomized into one of three groups: the empty defect group (ED), the PLGA-only group or the EPC-PLGA group. The defect sites were evaluated 4 and 12 weeks after implantation. Results At the end of testing, only the EPC-PLGA group showed the development of new cartilage tissue with a smooth, transparent and integrated articular surface. Moreover, histological analysis showed obvious differences in cartilage regeneration. At week 4, the EPC-PLGA group showed considerably higher TGF-β2 and TGF-β3 expression, a greater amount of synthesized glycosaminoglycan (GAG) content, and a higher degree of osteochondral angiogenesis in repaired tissues. At week 12, the EPC-PLGA group showed enhanced hyaline cartilage regeneration with a normal columnar chondrocyte arrangement, higher SOX9 expression, and greater GAG and collagen type II (COLII) content. Moreover, the EPC-PLGA group showed organized osteochondral integration, the formation of vessel-rich tubercular bone and significantly higher bone volume per tissue volume and trabecular thickness (Tb.Th). Conclusion The present EPC-PLGA cell delivery system generates a suitable in situ microenvironment for osteochondral regeneration without the supplement of exogenous growth factors.
Exploratory synthesis in new chemical spaces is the essence of solid-state chemistry. However, uncharted chemical spaces can be difficult to navigate, especially when materials synthesis is ...challenging. Nitrides represent one such space, where stringent synthesis constraints have limited the exploration of this important class of functional materials. Here, we employ a suite of computational materials discovery and informatics tools to construct a large stability map of the inorganic ternary metal nitrides. Our map clusters the ternary nitrides into chemical families with distinct stability and metastability, and highlights hundreds of promising new ternary nitride spaces for experimental investigation-from which we experimentally realized seven new Zn- and Mg-based ternary nitrides. By extracting the mixed metallicity, ionicity and covalency of solid-state bonding from the density functional theory (DFT)-computed electron density, we reveal the complex interplay between chemistry, composition and electronic structure in governing large-scale stability trends in ternary nitride materials.
Context.
A link has finally been established between magnetars and fast radio burst (FRB) sources. Within this context, a major issue that remains unresolved pertains to whether sources of ...extragalactic FRBs exhibit X/
γ
-ray outbursts and whether this is correlated with radio activity. If so, the subsequent goal is to identify these sources.
Aims.
We aim to constrain possible X/
γ
-ray burst activity from one of the nearest extragalactic FRB sources currently known. This is to be done over a broad energy range by looking for bursts over a range of timescales and energies that are compatible with those of powerful flares from extragalactic magnetars.
Methods.
We followed up on the observation of the as-yet nearest extragalactic FRB source, located at a mere 149 Mpc distance, namely, the periodic repeater
FRB 180916.J0158+65
. This took place during the active phase between 4 and 7 February 2020, using the Insight–Hard X-ray Modulation Telescope (Insight–HXMT). By taking advantage of the combination of broad-band wavelengths, a large effective area, and several independent detectors at our disposal, we searched for bursts over a set of timescales from 1 ms to 1.024 s with a sensitive algorithm that had been previously characterised and optimised. Moreover, through simulations, we studied the sensitivity of our technique in the released energy-duration phase space for a set of synthetic flares and assuming a range of different energy spectra.
Results.
We constrain the possible occurrence of flares in the 1−100 keV energy band to
E
< 10
46
erg for durations Δ
t
< 0.1 s over several tens of ks exposure.
Conclusions.
We can rule out the occurrence of giant flares similar to the ones that were observed in the few cases of Galactic magnetars. The absence of reported radio activity during our observations prevents us from making any determinations regarding the possibility of simultaneous high-energy emission.
This study examined the prevalence of major depressive disorder (MDD), and the correlations and co-morbid conditions associated with MDD, in the adult Taiwanese population, which a previous estimate ...in the 1980s had found to be at the lower end of the spectrum worldwide. Possible explanations for the reported low prevalence of MDD were evaluated.
As part of a survey of common psychiatric disorders in a nationally representative sample of individuals aged ≥ 18 years who were non-institutionalized civilians in Taiwan, a face-to-face interview using the paper version of the World Mental Health Survey of the World Health Organization (WHO) Composite International Diagnostic Interview (WMH-CIDI) was conducted between 2003 and 2005. Functional impairment and help-seeking behaviors were compared between Taiwanese subjects with MDD and their counterparts in the USA.
Among the 10 135 respondents, the lifetime prevalence of MDD was 1.20% standard error (S.E.)=0.2%. Individuals who were divorced or widowed, aged ≤ 40 years, and female were at increased risk, whereas rural residents were at lower risk for MDD. The proportion of MDD cases co-morbid with other psychiatric disorders in this study was much lower than in the US study. Only one-third of Taiwanese individuals with MDD sought help despite having twice the number of lost workdays compared with the US sample.
Despite the low prevalence of MDD in Taiwanese adults, the pattern of low help-seeking behavior and profound functional impairment indicates much room for improvement in the early detection of and intervention in major depression in this population.
Across a variety of adverse life circumstances, such as social isolation and low socioeconomic status, mammalian immune cells have been found to show a conserved transcriptional response to adversity ...(CTRA) involving increased expression of proinflammatory genes. The present study examines whether such effects might stem in part from the selective up-regulation of a subpopulation of immature proinflammatory monocytes (Ly-6c ʰⁱᵍʰ in mice, CD16 ⁻ in humans) within the circulating leukocyte pool. Transcriptome representation analyses showed relative expansion of the immature proinflammatory monocyte transcriptome in peripheral blood mononuclear cells from people subject to chronic social stress (low socioeconomic status) and mice subject to repeated social defeat. Cellular dissection of the mouse peripheral blood mononuclear cell transcriptome confirmed these results, and promoter-based bioinformatic analyses indicated increased activity of transcription factors involved in early myeloid lineage differentiation and proinflammatory effector function (PU.1, NF-κB, EGR1, MZF1, NRF2). Analysis of bone marrow hematopoiesis confirmed increased myelopoietic output of Ly-6c ʰⁱᵍʰ monocytes and Ly-6c ⁱⁿᵗᵉʳᵐᵉᵈⁱᵃᵗᵉ granulocytes in mice subject to repeated social defeat, and these effects were blocked by pharmacologic antagonists of β-adrenoreceptors and the myelopoietic growth factor GM-CSF. These results suggest that sympathetic nervous system-induced up-regulation of myelopoiesis mediates the proinflammatory component of the leukocyte CTRA dynamic and may contribute to the increased risk of inflammation-related disease associated with adverse social conditions.
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