Commensal bacteria generate immensely diverse active metabolites to maintain gut homeostasis, however their fundamental role in establishing an immunotolerogenic microenvironment in the intestinal ...tract remains obscure. Here, we demonstrate that an understudied murine commensal bacterium, Dubosiella newyorkensis, and its human homologue Clostridium innocuum, have a probiotic immunomodulatory effect on dextran sulfate sodium-induced colitis using conventional, antibiotic-treated and germ-free mouse models. We identify an important role for the D. newyorkensis in rebalancing Treg/Th17 responses and ameliorating mucosal barrier injury by producing short-chain fatty acids, especially propionate and L-Lysine (Lys). We further show that Lys induces the immune tolerance ability of dendritic cells (DCs) by enhancing Trp catabolism towards the kynurenine (Kyn) pathway through activation of the metabolic enzyme indoleamine-2,3-dioxygenase 1 (IDO1) in an aryl hydrocarbon receptor (AhR)-dependent manner. This study identifies a previously unrecognized metabolic communication by which Lys-producing commensal bacteria exert their immunoregulatory capacity to establish a Treg-mediated immunosuppressive microenvironment by activating AhR-IDO1-Kyn metabolic circuitry in DCs. This metabolic circuit represents a potential therapeutic target for the treatment of inflammatory bowel diseases.
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•A novel cationic flocculant P(AM–DAC–BA) was synthesized and characterized.•P(AM–DAC–BA) was synthesized through ultraviolet (UV) initiation.•P(AM–DAC–BA) prepared in quartz reactor ...was porous structure.•Comparison between quartz reactor and glass reactor was well studied.•P(AM–DAC–BA) was efficient in the dewatering of the textile sewage sludge.
A new composite flocculant was synthesized by the copolymerization of acrylamide (AM), acryloyloxyethyltrimethyl ammonium chloride (DAC), and butylacrylate (BA) under ultraviolet (UV) radiation with 2,2′-azobis(2-methylpropionamide) dihydrochloride (V-50) as photo-initiator. This flocculant was named P(AM–DAC–BA). Nuclear magnetic resonance hydrogen spectroscopy (1H NMR), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) were used to observe the structure and morphology of P(AM–DAC–BA). Parameters affecting the intrinsic viscosity (η) and conversion of P(AM–DAC–BA), such as monomer concentration, photo-initiator concentration, pH, illumination time, and incident light intensity in a quartz or glass reactor were examined. Results showed that the optimum conditions were 30wt% total monomers, 2.0wt% hydrophobic monomer, 0.5wt‰ photo-initiator, pH 4.4, 100min of illumination time, and 1160μWcm−2 incident light intensity. To study the dewatering performance of P(AM–DAC–BA), the textile sewage sludge dewatering was evaluated by measuring both the residual turbidity and moisture content of the filter cake. At 50mgL−1 P(AM–DAC–BA) and pH 11.6, the residual turbidity of the supernatant and moisture content of the dewatered filter cake reached 5.5NTU and 73.2%, respectively. Dewatering tests demonstrated the superiority of P(AM–DAC–BA) flocculant synthesized in the quartz reactor over that synthesized in the glass reactor.
In a prototypical ferromagnet (Ga,Mn)As based on a III-V semiconductor, substitution of divalent Mn atoms into trivalent Ga sites leads to severely limited chemical solubility and metastable ...specimens available only as thin films. The doping of hole carriers via (Ga,Mn) substitution also prohibits electron doping. To overcome these difficulties, Masek et al. theoretically proposed systems based on a I-II-V semiconductor LiZnAs, where isovalent (Zn,Mn) substitution is decoupled from carrier doping with excess/deficient Li concentrations. Here we show successful synthesis of Li(1+y)(Zn(1-x)Mn(x))As in bulk materials. Ferromagnetism with a critical temperature of up to 50 K is observed in nominally Li-excess (y=0.05-0.2) compounds with Mn concentrations of x=0.02-0.15, which have p-type metallic carriers. This is presumably due to excess Li in substitutional Zn sites. Semiconducting LiZnAs, ferromagnetic Li(Zn,Mn)As, antiferromagnetic LiMnAs, and superconducting LiFeAs systems share square lattice As layers, which may enable development of novel junction devices in the future.
The articles in this special section focus on situation awareness in intelligent human-computer interaction for critical decision making (HCI). HCI is recognized as an ctive field that focuses on the ...various interactions of human with machines. The HCI has been widely applied in multiple domains, such as artificial intelligence, computer vision, image and multimedia analysis, and cognitive and behavioral sciences. The objective of the HCI is to make the computer smart via receiving enough knowledge about the environment where it is deployed and reduce the human intervention aspect toward decision making. This enables development of high-end computers that are context aware and smart in making decisions with reference to the context. Situation awareness of an intelligent HCI will decide the success and application of the solution across the real world environment. The aim of this special issue is to provide a platform on the topic of situation awareness in intelligent HCI for time critical decision making.
We extend the definition of Bowen topological entropy of subsets to continuous action of amenable groups on a compact metrizable space. We investigate how Bowen topological entropy behaves for ...restricted actions of finite-index subgroups and verify the validity of the subgroup formula. We also show that the Bowen topological entropy of subsets for amenable group actions can be determined via the local entropies of measures. As applications, we compute the Bowen topological entropy of a subset for Bernoulli shift over amenable groups.
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•There are significant regional differences in the development level of UGI in the YREB.•Cities with high UGI development are mostly concentrated in economically developed areas.•The ...level of UGI development in the YREB region has been shown to be influenced by a combination of diverse conditions.•The high level UGI groupings of cities are more consistent, and the development paths of non-high level UGI are more diverse.
In cities, green infrastructure (GI) is a vital natural life support system that is intimately linked to the daily lives of citizens. High levels of Urban Green Infrastructure (UGI) can help mitigate a series of ecological problems faced by cities, which is extremely important for preserving the stability of urban ecosystems and promoting sustainable urban development. However, current research has not fully explored the influencing factors of UGI and the interaction effect between them. Therefore, in order to better explore the results of China’s proposed policy to promote GI development, data from 110 cities in China’s Yangtze River Economic Belt (YREB) region during the 12th Five-Year Plan and 13th Five-Year Plan periods were measured separately, and natural and geographic environmental conditions, quality of urban construction, level of economic development, socio-cultural development, and eco-environmental quality were selected as the influencing factors. The entropy TOPSIS was used to evaluate the development trend of UGI in the two periods of the region, and the relationship between influencing factors and UGI development was investigated through the use of fs/QCA, and the high-level development path of each city to achieve GI was explained. The results show that (1) Cities with high UGI development are mostly concentrated in economically developed areas, while cities in the YREB’s central and western regions have relatively low levels of UGI development. (2) According to the spatial and temporal differences, the factors driving the high level and non-high level of UGI development in prefecture-level cities in the YREB showed several different configurations, confirming that the development level of UGI was affected by a variety of conditions. (3) During the 12th Five-Year Plan to 13th Five-Year Plan periods, the configuration of urban high-level UGI was found to be more consistent, while the development path of non-high-level UGI is more diversified. The study explores the overall development level and trend of green infrastructure in different cities, and the citation of fs/QCA provides a better understanding of the complex mechanisms of the interactions between these variables, with a view to providing some guidance and enlightenment for enhancing the future urban UGI development and urban high-quality development in the Yangtze River Economic Belt.
Application of nitrogen (N) fertilizer increases grain yield and soil organic carbon (SOC) sequestration, but accompanied by the emission of greenhouse gas (GHG) especially nitrous oxide (N2O). To ...spatial-temporally analyze the trade-off between yield and GHG emissions under different N fertilization levels at regional scale, this study integrated geographic information system (GIS) and the DeNitrification-DeComposition (DNDC, Version 9.5) model to define the impacts of different N fertilization levels on rice production, SOC sequestration, and GHG emission in Fuyang District, a county-scale region in Eastern China. The whole region was divided into 28825 polygon-based modeling units based on heterogeneity of soil property, climate and agricultural management conditions. After validating the DNDC model by field observation data of the year 1979 and 2015, five N fertilization levels (0, 140, 210, 280 and 350 kg N ha−1) from the year 2016–2035 were designed for simulating the rice yield, SOC sequestration, N2O and methane (CH4) emissions. Validation results showed a good performance of the refined DNDC model. Simulation results indicated that yield and GHG emission increased with the growth of N fertilization rate, but the SOC sequestration change was not noticeable. Around 210 kg N ha−1 was recommended as optimal N fertilization level in Fuyang District, because its global warming potential intensity (GWPI) was the lowest among all the N fertilization levels. As excessive N input is a common problem across China, our results provide a case for a win-win scenario for both food security and environmental friendliness.
•Increasing N fertilization level makes the growth of yield as well as GHG emission.•The reduction of yield can be compensated by the decline of N2O emission.•Yield growth and carbon sequestration potential are influenced by the soil type.•25 percent reduction of N fertilization is suggested in the study area.
Autophagy, a highly conserved self-digesting process, has been deeply involved in the development and progression of oral squamous cell carcinoma (OSCC). However, the prognostic value of ...autophagy-related genes (ARGs) for OSCC still remains unclear. Our study set out to develop a multigene expression signature based on ARGs for individualized prognosis assessment in OSCC patients.
Based on The Cancer Genome Atlas (TCGA) database, we identified prognosis-related ARGs through univariate COX regression analysis. Then we performed the least absolute shrinkage and selection operator (LASSO) regression analysis to identify an optimal autophagy-related multigene signature with the subsequent validation in testing set, GSE41613 and GSE42743 datasets.
We identified 36 prognosis-related ARGs for OSCC. Subsequently, the multigene signature based on 13 prognostic ARGs was constructed and successfully divided OSCC patients into low and high-risk groups with significantly different overall survival in TCGA training set (
< 0.0001). The autophagy signature remained as an independent prognostic factor for OSCC in univariate and multivariate Cox regression analyses. The area under the curve (AUC) values of the receiver operating characteristic (ROC) curves for 1, 3, and 5-year survival were 0.758, 0.810, 0.798, respectively. Then the gene signature was validated in TCGA testing set, GSE41613 and GSE42743 datasets. Moreover, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and single-sample gene set enrichment analysis (ssGSEA) revealed the underlying biological characteristics and signaling pathways associated with this signature in OSCC. Finally, we constructed a nomogram by combining the gene signature with multiple clinical parameters (age, gender, TNM-stage, tobacco, and alcohol history). The concordance index (C-index) and calibration plots demonstrated favorable predictive performance of our nomogram.
In summary, we identified and verified a 13-ARGs prognostic signature and nomogram, which provide individualized prognosis evaluation and show insight for potential therapeutic targets for OSCC.
Despite therapeutic advances in HER2-positive metastatic breast cancer, resistance to trastuzumab inevitably develops. In the PHOEBE study, we aimed to assess the efficacy and safety of pyrotinib (an ...irreversible pan-HER inhibitor) plus capecitabine after previous trastuzumab.
This is an open-label, randomised, controlled, phase 3 trial done at 29 hospitals in China. Patients with pathologically confirmed HER2-positive metastatic breast cancer, aged 18–70 years, who had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had been previously treated with trastuzumab and taxanes were randomly assigned (1:1) to receive oral pyrotinib 400 mg or lapatinib 1250 mg once daily plus oral capecitabine 1000 mg/m2 twice daily on days 1–14 of each 21-day cycle. Randomisation was done via a centralised interactive web-response system with a block size of four or six and stratified by hormone receptor status and previous lines of chemotherapy for metastatic disease. The primary endpoint was progression-free survival according to masked independent central review. Efficacy and safety were assessed in all patients who received at least one dose of the study drugs. Results presented here are from a prespecified interim analysis. This study is registered with ClinicalTrials.gov, NCT03080805.
Between July 31, 2017, and Oct 30, 2018, 267 patients were enrolled and randomly assigned. 134 patients received pyrotinib plus capecitabine and 132 received lapatinib plus capecitabine. At data cutoff of the interim analysis on March 31, 2019, median progression-free survival was significantly longer with pyrotinib plus capecitabine (12·5 months 95% CI 9·7–not reached) than with lapatinib plus capecitabine (6·8 months 5·4–8·1; hazard ratio 0·39 95% CI 0·27–0·56; one-sided p<0·0001). The most common grade 3 or worse adverse events were diarrhoea (41 31% in the pyrotinib group vs 11 8% in the lapatinib group) and hand–foot syndrome (22 16% vs 20 15%). Serious adverse events were reported for 14 (10%) patients in the pyrotinib group and 11 (8%) patients in the lapatinib group. No treatment-related deaths were reported in the pyrotinib group and one sudden death in the lapatinib group was considered treatment related.
Pyrotinib plus capecitabine significantly improved progression-free survival compared with that for lapatinib plus capecitabine, with manageable toxicity, and can be considered an alternative treatment option for patients with HER2-positive metastatic breast cancer after trastuzumab and chemotherapy.
Jiangsu Hengrui Medicine and National Key R&D Program of China.
For the Chinese translation of the abstract see Supplementary Materials section.
We report the discovery of a strong and tunable spin-lifetime anisotropy with excellent out-of-plane spin lifetimes up to 7.8 ns at 100 K in dual-gated bilayer graphene. Remarkably, this realizes the ...manipulation of spins in graphene by electrically controlled spin-orbit fields, which is unexpected due to graphene's weak intrinsic spin-orbit coupling (∼12 μeV). We utilize both the in-plane magnetic field Hanle precession and oblique Hanle precession measurements to directly compare the lifetimes of out-of-plane vs in-plane spins. We find that near the charge neutrality point, the application of a perpendicular electric field opens a band gap and generates an out-of-plane spin-orbit field that stabilizes out-of-plane spins against spin relaxation, leading to a large spin-lifetime anisotropy (defined as the ratio between out-of-plane and in-plane spin lifetime) up to ∼12 at 100 K. This intriguing behavior occurs because of the unique spin-valley coupled band structure of bilayer graphene. Our results demonstrate the potential for highly tunable spintronic devices based on dual-gated 2D materials.
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