Abstract
Objectives
To identify a novel plasmid-mediated colistin resistance gene in Klebsiella pneumoniae isolated from chickens in China.
Methods
WGS was used to identify a novel colistin ...resistance gene. The transferability of plasmids carrying mcr-7.1 was investigated by conjugation experiments. The expression of the mcr-7.1 gene was examined using an expression vector.
Results
A novel plasmid-mediated colistin resistance gene mcr-7.1, sharing 70% amino acid identity with the mcr-3 gene, was identified in three K. pneumoniae strains isolated from chickens in China. The mcr-7.1 gene was found in an IncI2-type plasmid (pSC20141012) that co-harboured the blaCTX-M-55 gene in one isolate. pSC20141012 can be transferred from K. pneumoniae SC20141012 to Escherichia coli J53Azr, exhibiting a ≥8-fold increase in colistin MIC compared with the recipient E. coli J53Azr.
Conclusions
We identified a novel plasmid-mediated colistin resistance gene named mcr-7.1 in K. pneumoniae in China. The prevalence of mcr-7.1 in various species of human and animal origin needs to be investigated immediately.
Glycosylation of immune receptors and ligands, such as T cell receptor and coinhibitory molecules, regulates immune signaling activation and immune surveillance. However, how oncogenic signaling ...initiates glycosylation of coinhibitory molecules to induce immunosuppression remains unclear. Here we show that IL-6-activated JAK1 phosphorylates programmed death-ligand 1 (PD-L1) Tyr112, which recruits the endoplasmic reticulum-associated N-glycosyltransferase STT3A to catalyze PD-L1 glycosylation and maintain PD-L1 stability. Targeting of IL-6 by IL-6 antibody induced synergistic T cell killing effects when combined with anti-T cell immunoglobulin mucin-3 (anti-Tim-3) therapy in animal models. A positive correlation between IL-6 and PD-L1 expression was also observed in hepatocellular carcinoma patient tumor tissues. These results identify a mechanism regulating PD-L1 glycosylation initiation and suggest the combination of anti-IL-6 and anti-Tim-3 as an effective marker-guided therapeutic strategy.
Long-range projections from the frontal cortex are known to modulate sensory processing in multiple modalities. Although the mouse has become an increasingly important animal model for studying the ...circuit basis of behavior, the functional organization of its frontal cortical long-range connectivity remains poorly characterized. Here we used virus-assisted circuit mapping to identify the brain networks for top-down modulation of visual, somatosensory and auditory processing. The visual cortex is reciprocally connected to the anterior cingulate area, whereas the somatosensory and auditory cortices are connected to the primary and secondary motor cortices. Anterograde and retrograde tracing identified the cortical and subcortical structures belonging to each network. Furthermore, using new viral techniques to target subpopulations of frontal neurons projecting to the visual cortex versus the superior colliculus, we identified two distinct subnetworks within the visual network. These findings provide an anatomical foundation for understanding the brain mechanisms underlying top-down control of behavior.
Direct hydrogenation of CO2 to methanol using green hydrogen has emerged as a promising method for carbon neutrality, but qualifying catalysts represent a grand challenge. In2O3/ZrO2 catalyst has ...been extensively applied in methanol synthesis due to its superior activity; however, the electronic effect by strong oxides‐support interactions between In2O3 and ZrO2 at the In2O3/ZrO2 interface is poorly understood. In this work, abundant In2O3/ZrO2 heterointerfaces are engineered in a hollow‐structured In2O3@ZrO2 heterostructure through a facile pyrolysis of a hybrid metal–organic framework precursor MIL‐68@UiO‐66. Owing to well‐defined In2O3/ZrO2 heterointerfaces, the resultant In2O3@ZrO2 exhibits superior activity and stability toward CO2 hydrogenation to methanol, which can afford a high methanol selectivity of 84.6% at a conversion of 10.4% at 290 °C, and 3.0 MPa with a methanol space‐time yield of up to 0.29 gMeOH gcat−1 h−1. Extensive characterization demonstrates that there is a strong correlation between the strong electronic In2O3–ZrO2 interaction and catalytic selectivity. At In2O3/ZrO2 heterointerfaces, the electron tends to transfer from ZrO2 to In2O3 surface, which facilitates H2 dissociation and the hydrogenation of formate (HCOO*) and methoxy (CH3O*) species to methanol. This study provides an insight into the In2O3‐based catalysts and offers appealing opportunities for developing heterostructured CO2 hydrogenation catalysts with excellent activity.
The direct hydrogenation of CO2 into methanol has been regarded as the one of the most economical and effective ways to reduce CO2 emissions. Here, we constructed a hollow‐structured In2O3@ZrO2 by a hybrid MOF template‐directed strategy. The resultant In2O3@ZrO2 heterostructure shows high CO2 hydrogenation activity towards CH3OH (gMeOHgcat−1) with a selectivity of 84.6%.
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► We study the corrosion performance of 2% Cr steel and compare it with other steels. ► The amorphous inner scale of 2% Cr steel mainly consists of FeCO3 and Cr(OH)3. ► Localized ...corrosion occurs if crystalline FeCO3 strips form on the corrosion scale. ► Cr content changes the crystalline state of corrosion scale by changing pH. ► The critical Cr content for general corrosion is 3%.
Scanning electron microscopy (SEM), X-ray Diffraction (XRD), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) were employed to analyze the corrosion scale formed on API X65, 1Cr, 2Cr and 3Cr steels in CO2 containing environment. The evolution of scale on 2Cr steel was characterized with electrochemical impedance spectroscopy (EIS) and in situ pH monitoring. The results show that Cr content can alter the crystalline state of corrosion scale via changing pH value. Localized corrosion occurs on 2Cr steel when FeCO3 crystal stripes form on the amorphous scale. The critical Cr content for general corrosion is 3wt.%.
Generally, glass‐ceramics have superior properties compared to their parent glasses. Here, we prepared a novel Nd3+‐doped MgO‐Al2O3‐SiO2‐based transparent glass‐ceramics with excellent fluorescence ...properties. The effects of Nd2O3 content on the structure and properties of glass‐ceramics were studied, aiming to provide a key guidance for preparing this transparent glass‐ceramics. The results revealed that the glass stability increased originally and then decreased with increasing Nd2O3 content, so did the variation of wavenumbers in infrared spectra. And these glass‐ceramics are mainly composed of cordierite with residual glassy phase. The three phenomenological intensity parameters (Ω2,4,6) and radiative properties were estimated by Judd‐Ofelt theory, and the values of Ω2 first decreased and then increased with increasing Nd2O3 content. Three main emission peaks ascribed to the transitions from 4F3/2 to 4I9/2, 4I11/2, 4I13/2 at 898, 1057, 1330 nm were observed, respectively. The branching ratios for 4F3/2→4I11/2 transition increased as the Nd2O3 content raised, and the fluorescence lifetimes of the 4F3/2 level were found to increase first and then decrease with Nd2O3 content (from 181 to 726 μs). The excellent fluorescence properties indicate that this novel glass‐ceramics can be used as a potential solid‐state optical functional material for 1.06 μm laser emission.
Background
Manual contouring is very labor‐intensive, time‐consuming, and subject to intra‐ and inter‐observer variability. An automated deep learning approach to fast and accurate contouring and ...segmentation is desirable during radiotherapy treatment planning.
Purpose
This work investigates an efficient deep‐learning‐based segmentation algorithm in abdomen computed tomography (CT) to facilitate radiation treatment planning.
Methods
In this work, we propose a novel deep‐learning model utilizing U‐shaped multi‐layer perceptron mixer (MLP‐Mixer) and convolutional neural network (CNN) for multi‐organ segmentation in abdomen CT images. The proposed model has a similar structure to V‐net, while a proposed MLP‐Convolutional block replaces each convolutional block. The MLP‐Convolutional block consists of three components: an early convolutional block for local features extraction and feature resampling, a token‐based MLP‐Mixer layer for capturing global features with high efficiency, and a token projector for pixel‐level detail recovery. We evaluate our proposed network using: (1) an institutional dataset with 60 patient cases and (2) a public dataset (BCTV) with 30 patient cases. The network performance was quantitatively evaluated in three domains: (1) volume similarity between the ground truth contours and the network predictions using the Dice score coefficient (DSC), sensitivity, and precision; (2) surface similarity using Hausdorff distance (HD), mean surface distance (MSD) and residual mean square distance (RMS); and (3) the computational complexity reported by the number of network parameters, training time, and inference time. The performance of the proposed network is compared with other state‐of‐the‐art networks.
Results
In the institutional dataset, the proposed network achieved the following volume similarity measures when averaged over all organs: DSC = 0.912, sensitivity = 0.917, precision = 0.917, average surface similarities were HD = 11.95 mm, MSD = 1.90 mm, RMS = 3.86 mm. The proposed network achieved DSC = 0.786 and HD = 9.04 mm on the public dataset. The network also shows statistically significant improvement, which is evaluated by a two‐tailed Wilcoxon Mann–Whitney U test, on right lung (MSD where the maximum p‐value is 0.001), spinal cord (sensitivity, precision, HD, RMSD where p‐value ranges from 0.001 to 0.039), and stomach (DSC where the maximum p‐value is 0.01) over all other competing networks. On the public dataset, the network report statistically significant improvement, which is shown by the Wilcoxon Mann–Whitney test, on pancreas (HD where the maximum p‐value is 0.006), left (HD where the maximum p‐value is 0.022) and right adrenal glands (DSC where the maximum p‐value is 0.026). In both datasets, the proposed method can generate contours in less than 5 s. Overall, the proposed MLP‐Vnet demonstrates comparable or better performance than competing methods with much lower memory complexity and higher speed.
Conclusions
The proposed MLP‐Vnet demonstrates superior segmentation performance, in terms of accuracy and efficiency, relative to state‐of‐the‐art methods. This reliable and efficient method demonstrates potential to streamline clinical workflows in abdominal radiotherapy, which may be especially important for online adaptive treatments.
CYP19A1/aromatase (Ar) is a prognostic biomarker of gastric cancer (GCa). Ar is a critical enzyme for converting androstenedione to oestradiol in the steroidogenesis cascade. For decades, Ar has been ...targeted with Ar inhibitors (ARIs) in gynaecologic malignancies; however, it is unexplored in GCa. A single‐cohort tissue microarray examination was conducted to study the association between Ar expression and disease outcome in Asian patients with GCa. The results revealed that Ar was a prognostic promoter. Bioinformatics analyses conducted on a Caucasian‐based cDNA microarray databank showed Ar to be positively associated with GCa prognosis for multiple clinical modalities, including surgery, 5‐Fluorouracil (5‐FU) for adjuvant chemotherapy, or HER2 positivity. These findings imply that targeting Ar expression exhibits a potential for fulfilling unmet medical needs. Hence, Ar‐targeting compounds were tested, and the results showed that exemestane exhibited superior cancer‐suppressing efficacy to other ARIs. In addition, exemestane down‐regulated Ar expression. Ablating Ar abundance with short hairpin (sh)Ar could also suppress GCa cell growth, and adding 5‐FU could facilitate this effect. Notably, adding oestradiol could not prevent exemestane or shAr effects, implicating a nonenzymatic mechanism of Ar in cancer growth. Regarding translational research, treatment with exemestane alone exhibited tumour suppression efficacy in a dose‐dependent manner. Combining subminimal doses of 5‐FU and exemestane exerted an excellent tumour suppression effect without influencing bodyweight. This study validated the therapeutic potentials of exemestane in GCa. Combination of metronomic 5‐FU and exemestane for GCa therapy is recommended.
infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for ...population-wide and family-based
infection control and management to reduce the related disease burden.
Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements.
Experts discussed and modified the original 23 statements on family-based
infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1)
infection and transmission among family members, (2) prevention and management of
infection in children and elderly people within households, and (3) strategies for prevention and management of
infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based
infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases.
is transmissible from person to person, and among family members. A family-based
prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.
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