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Metastasis is an important cause of cancer-related death. Previous studies in our laboratory found that pregnane alkaloids from Pachysandra terminalis had antimetastatic activity against breast cancer cells. In the current study, we demonstrated that treatment with one of the alkaloid derivatives, (Z)-3β-ethylamino-pregn-17(20)-en (1), led to the downregulation of the HIF-1α/VEGF/VEGFR2 pathway, suppressed the phosphorylation of downstream molecules Akt, mTOR, FAK, and inhibited breast cancer metastasis and angiogenesis both in vitro and in vivo. Furthermore, the antimetastasis and antiangiogenesis effects of 1 treatment (40 mg/kg) were more effective than that of Sorafenib (50 mg/kg). Surface plasmon resonance (SPR) analysis was performed and the result suggested that HSP90α was a direct target of 1. Taken together, our results suggested that compound 1 might represent a candidate antitumor agent for metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Gastric cancer ranks the fifth most common and third leading cause of cancer‐related deaths worldwide. Alterations in the RTK/MAPK, WNT, cell adhesion, TP53, TGFβ, NOTCH, and NFκB signaling pathways could be identified as main oncogenic drivers. A combination of altered pathways can be associated with molecular subtypes of gastric cancer. In order to generate model systems to study the impact of different pathway alterations in a defined genetic background, we generated three murine organoid models: a RAS‐activated (KrasG12D, Tp53R172H), a WNT‐activated (Apcfl/fl, Tp53R172H), and a diffuse (Cdh1fl/fl, Apcfl/fl) model. These organoid models were morphologically and phenotypically diverse, differed in proteome expression signatures and possessed individual drug sensitivities. A differential vulnerability to RTK/MAPK pathway interference based on the different mitogenic drivers and according to the level of dependence on the pathway could be uncovered. Furthermore, an association between RTK/MAPK pathway activity and susceptibility to HDAC inhibition was observed. This finding was further validated in patient‐derived organoids from gastric adenocarcinoma, thus identifying a novel treatment approach for RTK/MAPK pathway altered gastric cancer patients. Synopsis: The analysis of murine and human gastric tumor organoids uncovered an association between RTK/MAPK pathway activity and susceptibility to HDAC inhibition, thereby identifying a potential new treatment approach for gastric cancer patients. Three murine tumor organoid models with a defined genetic background were generated by altering frequently mutated pathways in gastric cancer.The organoid models were characterized concerning their phenotype, proteome expression pattern, and therapeutic response via a drug screen.RAS activation in murine tumor organoids led to a significantly increased sensitivity to HDAC inhibition.HDAC sensitivity was confirmed in patient derived gastric cancer organoids with MAPK pathway alterations. [ABSTRACT FROM AUTHOR]

Fractal theory demonstrates significant merit in the feature expression of forms of matter in nature. This study uses fractal theory to study the backfill grouting of a shield tunnel. The seepage path was considered as a seepage mesh inserted into the rock-soil mass. For the fractal features of the seepage mesh, the formulas for the diffusion distance and the pressure contribution of grout were derived. The results showed that the diffusion equations of different grout patterns (Newtonian fluid and Bingham fluid) were of a uniform form after calculation, and the equations for the pressure distribution of grout with a change in radius were identical. The diffusion distance of grout increased with increasing grouting time, and there was no indication that the development of diffusion distance tended to be gradual; the downward tendency of the grout diffusion velocity was not moderated. The segment pressure increased with an increase in the diffusion distance. With a constant diffusion distance, a greater grouting pressure produced a greater segment pressure. The favorable performance of grout was attributed to an appropriate mixture ratio. An improper mixture ratio resulted in a smaller reinforcement area in the stratum, which impaired the stability of the shield tunnel. [ABSTRACT FROM AUTHOR]

Cys-tathionine-β-synthase (CBS) domain-containing proteins (CDCPs) are essential for regulating plant responses to various biotic and abiotic stressors. This study describes the systematic identification and characterization of CDCP family genes in Saccharum spontaneum. A total of 95 SsCDCP genes and eight phylogenetic groups were identified that were distributed over 29 chromosomes of the AP85-441 genome. Most (78/95) SsCDCPs underwent fragment duplication events, and 64 gene pairs were located in synteny blocks. Expression profiling of nine ShCDCPs was also carried out in the Saccharum spp. cultivars ROC22 and MT11-611 that are resistant and susceptible to red stripe, respectively, in response to: (i) Infection by the bacterial pathogen Acidovorax avenue subsp. avenae (Aaa); (ii) abiotic stressors (drought and salinity); and (iii) exogenous salicylic acid (SA) treatment. Members of one gene pair (ShCBSD-PB1-5A and ShCBSD-PB1-7A-1) with a fragment duplication event acted as negative regulators in sugarcane under four stresses, as supported by the significantly decreased expression levels of ShCBSD-PB1-5A (23-83%) and ShCBSD-PB1-7A-1 (15-75%) at all-time points, suggesting that they have functional redundancy. Genes in another pair, ShCBS-4C and ShCBS-4D-1, which have a fragment duplication event, play opposing regulatory roles in sugarcane exposed to multiple stresses, particularly Aaa and NaCl treatments. ShCBS-4C expression was significantly decreased by 32-77%, but ShCBS-4D-1 expression was dramatically upregulated by 1.2-6.2-fold in response to Aaa treatment of both cultivars across all-time points. This result suggested that both genes exhibited functional divergence. Meanwhile, the expression of SsCBSDCBS-5A was significantly upregulated in ROC22 by 1.4-4.6-fold in response to the four stressors. These findings provide important clues for further elucidating the function of ShCDCP genes in sugarcane responding to a diverse range of stresses. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The cholinesterases are essential targets implicated in the pathogenesis of Alzheimer's disease (AD). We have identified tryptophan‐tetrahydroisoquinoline derivatives as selective micro‐nanomolar butyrylcholinesterase (BChE) inhibitors. Molecular docking was applied for the rational design and binding mode analysis. They were defined according to their target inhibitory activity, low cytotoxicity, predicted permeability through the blood‐brain barrier (BBB), and in vivo cognitive improvement. Additionally, the preferred compound showed ability to decrease self‐induced Aβ1‐42 aggregation and Aβ1‐42 induced SH‐SY5Y cell injury. Altogether, these factors indicated their potential as unique lead compounds for AD treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: The malignant growth and therapy resistance of isocitrate dehydrogenase (IDH)-wildtype glioblastoma is thought to be driven by a subpopulation of tumor cells with cancer stem-like cell (CSC) properties. Employing a high-throughput in vitro drug screen, we identified LGK974 and berberine as drugs that impair wingless (WNT) signaling and can thereby sensitize glioblastoma stem-like cells (GSCs) to glucose starvation-induced cell death. The main goal of this study was to characterize the role of the WNT pathway in mediating the survival and metabolic plasticity of GSCs under nutrient-restricted growth conditions. Gas chromatography mass spectrometry (GC-MS) was used to determine WNT-specific alterations of intracellular metabolites in GSCs grown under nutrient restriction, i.e., glucose depletion, or under standard conditions. Metabolic fingerprints hold the promise to complement classic biomarkers, thus potentially aiding the prediction of tumor behavior and patient prognosis. Isocitrate dehydrogenase (IDH)-wildtype glioblastoma is the most common primary malignant brain tumor. It is associated with a particularly poor prognosis, as reflected by an overall median survival of only 15 months in patients who undergo a supramarginal surgical reduction of the tumor mass followed by combined chemoradiotherapy. The highly malignant nature of IDH-wildtype glioblastoma is thought to be driven by glioblastoma stem-like cells (GSCs) that harbor the ability of self-renewal, survival, and adaptability to challenging environmental conditions. The wingless (WNT) signaling pathway is a phylogenetically highly conserved stemness pathway, which promotes metabolic plasticity and adaptation to a nutrient-limited tumor microenvironment. To unravel the reciprocal regulation of the WNT pathway and the nutrient-limited microenvironment, glioblastoma cancer stem-like cells were cultured in a medium with either standard or reduced glucose concentrations for various time points (24, 48, and 72 h). Glucose depletion reduced cell viability and facilitated the survival of a small population of starvation-resistant tumor cells. The surviving cells demonstrated increased clonogenic and invasive properties as well as enhanced chemosensitivity to pharmacological inhibitors of the WNT pathway (LGK974, berberine). Glucose depletion partially led to the upregulation of WNT target genes such as CTNNB1, ZEB1, and AXIN2 at the mRNA and corresponding protein levels. LGK974 treatment alone or in combination with glucose depletion also altered the metabolite concentration in intracellular compartments, suggesting WNT-mediated metabolic regulation. Taken together, our findings suggest that WNT-mediated metabolic plasticity modulates the survival of GSCs under nutrient-restricted environmental conditions. [ABSTRACT FROM AUTHOR]

WRKY transcription factors (TFs) are essential players in different signaling cascades and regulatory networks involved in defense responses to various stressors. This study systematically analyzed and characterized WRKY family genes in the Saccharum spp. hybrid R570 and their expression in two sugarcane cultivars LCP85-384 (resistant to leaf scald) and ROC20 (susceptible to leaf scald) in response to bacterial pathogen infection and nitrogen implantation dosage. A total of 53 ShWRKY genes with 66 alleles were systematically identified in R570 based on the query sequence SsWRKY in S. spontaneum AP85-441. All ShRWKY alleles were further classified into four groups with 11 (16.7%) genes in group I, 36 (54.5%) genes in group II, 18 (27.3%) genes in group III, and 1 (1.5%) gene in group IV. Among them, 4 and 11 ShWRKY gene pairs displayed tandem and segmental duplication events, respectively. The ShWRKY genes exhibited conserved DNA-binding domains, which were accompanied by variations in introns, exons, and motifs. RT-qPCR analysis of two sugarcane cultivars triggered by Xanthomonas albilineans (Xa) revealed that four genes, ShWRKY13-2/39-1/49-3/125-3 , exhibited significant upregulation in leaf scald-resistant LCP85-384. These WRKY genes were downregulated or unchanged in ROC20 at 24–72 h post-inoculation, suggesting that they play an important role in defense responses to Xa infection. Most of the 12 tested ShWRKY s, ShWRKY22-1/49-3/52-1 in particular, functioned as negative regulators in the two cultivars in response to a range of nitrogen (N) implantation doses. A total of 11 ShWRKY proteins were predicted to interact with each other. ShWRKY43 and ShWRKY49-3 are predicted to play core roles in the interaction network, as indicated by their interaction with six other ShWRKY proteins. Our results provide important candidate gene resources for the genetic improvement of sugarcane and lay the foundation for further functional characterization of ShWRKY genes in response to coupling effects of Xa infection and different N levels. [ABSTRACT FROM AUTHOR]

In stability analysis of rock soil engineering, before establishing similar physical simulation model, many match experiments on similar material are required, the current standard sample forming processes are difficult to satisfy the uniformity and compactness in the same sample set often, and have obvious defects in the molding process, molding efficiency and bedding processing. A pressing mechanism consists of adjustable concave-convex composite mould, multi-function trough, drive screw and framework is designed, the mould is pressed nto material to fill directly. Each layered material, dip angle, thickness and position can be controlled, forming number for each lot is adjustable, uniform of the same lot is good, all parts are detachable, operation is also simple. This mechanism is suitable for small batch forming, and has obvious advantages in bedding controlling, forming efficiency, forming quality and operation convenience, which can work well for match experiments before large-scale physical similar simulation experiment, geotechnical experiment, composite rock mass experiment, also can be used to make micro physical model with engineering structure.

The Vibrio fischeri quorum-sensing signal N-3-oxohexanoyI-L-homoserine lactone (3OC6-HSL) activates expression of the seven-gene luminescence operon. We used mieroarrays to unveil 18 additional 3OC6-HSLcontrolled genes, 3 of which had been identified by other means previously. We show most of these genes are regulated by the 3OC6-HSL-responsive transcriptional regulator LuxR directly. This demonstrates that V. fischeri quorum sensing regulates a substantial number of genes other than those involved in light production.

The regulation of the lux operon (luxICDABEG) of Vibrio fischeri has been intensively studied as a model for quorum sensing in proteobacteria. Two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis previously identified several non-Lux proteins in V. fischeri MJ-100 whose expression was dependent on LuxR and 3-oxo-hexanoyl-L-homoserine lactone (3-oxo-C6-HSL). To determine if the LuxR-dependent regulation of the genes encoding these proteins was due to direct transcriptional control by LuxR and 3-oxo-C6-HSL or instead was due to indirect control via an unidentified regulatory element, promoters of interest were cloned into a lacZ reporter and tested for their LuxR and 3-oxo-C6-HSL dependence in recombinant Escherichia coli. The promoters for qsrP, acfA, and ribB were found to be directly activated via LuxR-3-oxo-C6-HSL. The sites of transcription initiation were established via primer extension analysis. Based on this information and the position of the lux box-binding site near position -40, all three promoters appear to have a class II-type promoter structure. In order to more fully characterize the LuxR regulon in V. fischeri MJ-100, real-time reverse transcription-PCR was used to study the temporal expression of qsrP, acfA, and ribB during the exponential and stationary phases of growth, and electrophoretic mobility shift assays were used to compare the binding affinities of LuxR to the promoters under investigation. Taken together, the results demonstrate that regulation of the production of QsrP, RibB, and AcfA is controlled directly by LuxR at the level of transcription, thereby establishing that there is a LuxR reguion in V. fischeri MJ-100 whose genes are coordinately expressed during mid-exponential growth.

A stable solid electrolyte interphase (SEI) is highly desired to prevent parasitic reactions during normal operation of lithium‐ion batteries (LIBs). Lithium carbonate (Li2CO3) is one of the most significant components for smooth SEI passivation layers; while the formation mechanism and special distribution of the Li2CO3 layer has not yet been illustrated. Here, an over‐potential tailored Li2CO3 growth mechanism based on the typical hard carbon anode is demonstrated. With an increase in the over‐potential, the size of Li2CO3 decreases gradually as the amount increases. When the over‐potential is large (potential at 0.01 V), a Li2CO3‐rich thin and dense inorganic layer with the average thickness of 4.4 nm in the SEI is constructed. The special SEI the completely wraps the boundaries of the anode enables a larger Li‐ion de‐solvation energy barrier and a lower Li‐ion diffusion energy barrier, which supports low self‐discharge behavior and a fast kinetic rate at the anode. More generally, this Li2CO3 growth mechanism is also applicable to commercialized graphite anodes and similar results are also obtained. Therefore, this work provides a new insight into the Li2CO3 growth mechanism in SEIs, as well as a guideline for the design of stable artificial SEIs. [ABSTRACT FROM AUTHOR]

Shield tunnel is widely adopted in the metro construction, and backfill grouting is the significant part. With power-law fluid grouts as the study object, a cylindrical infiltration diffusion model and spherical infiltration diffusion model are developed by applying the generalized Darcy law and theories of seepage mechanics based on the displacement effect of grout on groundwater. Through examples, the impact of factors including grouting pressure and formation permeability coefficient in the spherical displacement infiltration diffusion model on diffusion radius, flow rate, total pressure of grout in segments, and uniform equivalent pressure in grout diffusion area (grout pressure per unit area in a segment) is analyzed. The result shows that, the diffusion speed, injection flow rate and the pressure received in segments increase with an increase of the grouting pressure. Meanwhile, as the injection time increases, the flow rate of grout under conditions of different grouting pressure all decreases, and a sharp decrease exists. The diffusion speed and grouting pressure are positively correlated to the permeability coefficient, and with the increasement of the injection time, the diffusion displacement of grout in different permeability coefficient varies increasingly, the increase amplitude of the pressure acting on the segment by grout increases gradually. [ABSTRACT FROM AUTHOR]

Previous studies have explored the impact of the cost ratio of individual solutions versus collective solutions on people's cooperation tendency in the presence of individual solutions. This study further explored the impact of team credibility on people's propensity to cooperate in the presence of individual solutions. Study 1 investigated the influence of different level of altruistic tendencies or the self-interest tendencies of teammates on participants' decision-making. Study 2 explored the influence of the distribution of altruistic tendencies or self-interest tendencies on participants' decision-making. The results of Study 1 showed that the proportion of participants who chose the collective solution increased with an increase in the altruistic tendencies of the team. When the altruistic tendencies of the teammates reached a certain value, the proportion of participants taking the collective solution showed a trend to stabilize. Furthermore, the proportion of participants who chose the individual solution increased with the increase in the self-interest tendencies of the team. When the self-interest tendencies of the teammates reached a certain value, the individual solution was stably adopted. The results of Study 2 showed that with the total altruistic tendency remaining unchanged, the more altruistic group members that altruistic tendencies were allocated to, the higher a participant's level of trust in the team would be, which showed the decentralized effect of altruistic tendencies. In the case that the total self-interest tendency was unchanged, the fewer self-interest group members the self-interest tendencies were allocated to, the higher a participant's level of trust in the team would be, which showed the convergent effect of self-interest tendencies. [ABSTRACT FROM AUTHOR]

There is a growing consensus that plant‐derived antimicrobials may be a safe and effective alternative to synthetic chemical preservatives against foodborne pathogens. This study aims to investigate the potential application of the stems and leaves of Astragalus membranaceus (AMSL) in food preservation. Antibacterial activity of AMSL was evaluated by the disk diffusion method and the minimum inhibitory concentration (MIC) assay, and then the activity stability at different conditions (temperatures, pHs and ultraviolet irradiations) was analyzed and the antibacterial mechanism was revealed. Chemical composition of the active substances was also identified by UPLC–MS/MS. The results showed that the extracts from AMSL had low activities against Geotrichum candidum and Escherichia coli, while good action on Staphylococcus aureus, Bacillus subtilis, Aspergillus flavus, and Candida albicans. In contrast, the ethyl acetate fraction (EAF) of AMSL was the most active against Bacillus subtilis with a diameter of inhibition zone of 15.75 mm and the MIC value of 12.5 mg/mL. EAF exhibited good stability against heating at 80°C for 30 min, 60 min exposure to UV light, and it was effective in pH range of 2.0–6.0. After treating by EAF, the growth of the Bacillus subtilis was inhibited with delayed logarithmic phase, and the cell wall and the cell membrane of the bacteria were damaged deduced from the increased extracellular activity of alkaline phosphatase, the leakage of nucleic acids, and the increase of extracellular conductivity. Further SEM and TEM analysis confirmed the destroying of the cell wall integrity and cell membrane permeability with visually wrinkled even empty cells caused by EAF. Subsequent analysis revealed that flavonoids were the predominant components of EAF, followed by organic acids. Our findings provided a theoretical possibility that the AMSL could be used as a natural food preservative in the food industry. [ABSTRACT FROM AUTHOR]

Quinoa panicle rot (QPR) is a novel disease that poses a significant threat to quinoa production in China. Typical symptoms on panicles include a film of pale pink, grey‐white, or dark brown mould on the grains during the grain‐filling stage. Furthermore, QPR causes quinoa grain discolouration, unfilling, and malformation. In total, 37 isolates were identified as belonging to three species: Trichothecium roseum (nine isolates), Alternaria alternata (12), and Fusarium citri (16) based on morphology, and phylogenetic and pathogenicity characterization. The present study shows for the first time that T. roseum, A. alternata, and F. citri are the pathogens responsible for QPR. An evaluation of the growth and germination rates revealed a significant difference among the three species, with T. roseum and F. citri isolates having higher fitness in warmer (25–30℃) and humid conditions (water activity ≥0.98). However, A. alternata preferred cooler (20–25℃) and more arid conditions, and germinated in a wide range of water activities (water activity of 0.90–1.00). Among the three species, T. roseum and F. citri are probably responsible for the pink and grey diseased grains in humid regions, and A. alternata for the black‐brown diseased grains in arid regions. Pathogenicity tests showed that all three species could infect the quinoa panicles. The results of this study provide a basis for the recognition and management of QPR. [ABSTRACT FROM AUTHOR]

Increasing amounts of tailings and waste rubber tires have caused threats to the environment. In order to reuse these solid wastes, this study proposed a cemented tailings material containing crumb rubber recovered from waste tires. Unconfined compression tests and thermal conductivity measurements were conducted to evaluate the feasibility and performance of the proposed cemented tailings. Results revealed that the stress-strain behavior of the cemented tailings changed by the inclusion of crumb rubber. The unconfined compressive strength of cemented tailings decreased with increasing crumb rubber content. The inclusion of crumb rubber increased the failure strain and nonlinearity index of the cemented tailings. It was found that the addition of 4% crumb rubber provided the greatest improvement in ductility. The increase of the rubber content further increased the thermal insulation capacity of the cemented tailings. The low stiffness and the dimpled surface of the crumb rubber were responsible for the reduced compressive strength and thermal conductivity of the cemented tailings. In conclusion, the crumb rubber had both positive and negative effects on the cemented tailings. In practical application, the rubber admixture amount should be flexibly adjusted for different use case to make the cemented tailings material show the most suitable performance characteristic. [ABSTRACT FROM AUTHOR]

Progress toward intelligent human–robotic interactions requires monitoring sensors that are mechanically flexible, facile to implement, and able to harness recognition capability under harsh environments. Conventional sensing methods have been divided for human‐side collection or robot‐side feedback and are not designed with these criteria in mind. However, the iontronic polymer is an example of a general method that operates properly on both human skin (commonly known as skin electronics or iontronics) and the machine/robotic surface. Here, a unique iontronic composite (silk protein/glycerol/Ca(II) ion) and supportive molecular mechanism are developed to simultaneously achieve high conductivity (around 6 kΩ at 50 kHz), self‐healing (within minutes), strong stretchability (around 1000%), high strain sensitivity and transparency, and universal adhesiveness across a broad working temperature range (−40–120 °C). Those merits facilitate the development of iontronic sensing and the implementation of damage‐resilient robotic manipulation. Combined with a machine learning algorithm and specified data collection methods, the system is able to classify 1024 types of human and robot hand gestures under challenging scenarios and to offer excellent object recognition with an accuracy of 99.7%. [ABSTRACT FROM AUTHOR]

Aesculetin, a coumarin compound present in the sancho tree and chicory, exhibits excellent antioxidant and anti‐inflammatory activities in the vascular and immune system. In this study, a rapid and sensitive ultra‐high performance liquid chromatography electrospray ionization–tandem mass spectrometry (UHPLC–ESI–MS/MS) method was established and validated for the determination of aesculetin in rat plasma. Plasma samples were prepared by protein precipitation with acetonitrile. Chromatographic separation was performed on an Acquity UPLC HSS T3 C18 column (2.1 × 100 mm, 1.8 μm) with gradient elution at a flow rate of 0.3 ml/min, using mobile phase consisting of 0.1% formic acid (A) and acetonitrile (B). Aesculetin and puerarin (internal standard) were detected by multiple reaction monitoring in negative ion mode. The method was fully validated according to the US Food and Drug Administration guidelines. The calibration curve was linear over the range of 2–1,000 ng/ml with correlation coefficient >0.9980. The carry‐over, matrix effect, extraction recovery, dilution effect, intra‐ and inter‐day precision and the accuracy were within acceptable limits. The method was then applied to a pharmacokinetic study of aesculetin in rats. After oral administration at doses of 5, 10 and 20 mg/kg, the plasma concentration reached peaks of 95.7, 219.9, 388.6 ng/ml at times of 1.22–1.78 h. The oral bioavailability was calculated as 15.6–20.3% in rat plasma. The result provided pre‐clinical information for further application of aesculetin. [ABSTRACT FROM AUTHOR]

Selective attention is essential when we face sensory inputs with distractions. In the past decades, Lavie's load theory of selective attention delineates a complete picture of distractor suppression under different attentional control load. The present study was originally designed to explore how reward modulates the load effect of attentional selection. Unexpectedly, it revealed new findings under extended attentional load that was not involved in previous work. Participants were asked to complete a rewarded attentive visual tracking task while presented with irrelevant auditory oddball stimuli, with their behavioral performance, event‐related potentials and pupillary responses recorded. We found that although the behavioral performance and pupil sizes varied unidirectionally with the attentional load, the processing of distractors as reflected by the mismatch negativity (MMN) increased first and then decreased. In contrast to the prediction of Lavie's theory that attentional control fails to effectively suppress distractor processing under high attentional control load, our finding suggests that extremely high attentional control load may instead require suppression of distractor processing at a stage as early as possible. Besides, P3a, a positive‐polarity response sometimes following the MMN, was not affected by the attentional load, but both N1 (a negative‐polarity component peaking ~100 ms from sound onset) and P3a were weakened at higher reward, indicating that reward leads to attenuated early processing of distractor and thus suppresses the attentional orienting towards distractors. These findings altogether complement Lavie's load theory of selective attention, presenting a more complex picture of how attentional load and reward affects selective attention. In a rewarded attentive tracking task with auditory distractors, the processing of distractors was found to increase first and then decrease with attentional load, and also weakened with higher reward. This contradicts the prediction of previous theory that attentional control fails to suppress distractor processing under high attentional control load. Instead, it suggests that extremely high attentional control load may require suppression of distractor processing at an early stage, presenting a more complex picture of how attentional load and reward affect selective attention. [ABSTRACT FROM AUTHOR]

In this work, NH2-substituted oxazoles and NO2/NF2/NHNO2-substituted ethylenes/acetylenes were designed and used as dienes and dienophiles, respectively, in order to develop new bridge-ring insensitive high energy compounds through the Diels-Alder reaction between them. The reaction type, reaction feasibility and performance of reaction products were investigated in detail theoretically. The results showed that dienes most possibly react with dienophiles through the HOMO-diene controlled normal Diels-Alder reaction at relatively low energy barrier. Tetranitroethylene could react with the designed dienes much more easily than other dienophiles, and was employed to further design 29 new bridge-ring energetic compounds. Due to high heat of formation, density and oxygen balance, all designed bridge-ring energetic compounds have outstanding detonation performance, 16 of them have higher energy than HMX (1,3,5,7-tetranitro-1,3,5,7-tetrazocine) and 2 others even possess comparative energy with the representative of high energy compounds CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12- hexaazaisowurtzitane). The predicted average h50 value of these bridge-ring energetic compounds is 83 cm, showing their low impact sensitivity. The NH2 groups could obviously impel the proceeding of Diels-Alder reactions, but would slightly decrease the energy and sensitivity performance. In all, the new designed bridge-ring compounds have both high energy and low sensitivity, and may be produced through Diels-Alder reactions at relatively low energy barrier. This paper may be helpful for the theoretical design and experiment synthesis of new advanced insensitive high energy compounds. [ABSTRACT FROM AUTHOR]

Objectives: Immunoglobulin A vasculitis (IgAV), previously known as Henoch–Schönlein purpura, is the most common vasculitis that has a classical skin manifestation of palpable purpuric rash. Factors pertinent to IgAV remain inadequately understood. Here, we aimed to examine the gut microbiome shifts associated with IgAV and its recovery. Methods: Stool samples were collected from 10 children with IgAV (6–14 years old) before and after a multi‐drug therapy, along with 9 age‐matched healthy children. The samples were subjected to metagenomic analyses to investigate the taxonomic and functional shifts of the gut microbiome. Results: The analyses revealed that compared with healthy controls, treatment‐naïve patients exhibited substantial taxonomic and functional alterations of gut microbiota, including 104 IgAV‐depleted species and 7 IgAV‐elevated species (FDR < 0.05). After treatment, the IgAV patients displayed a partial restoration of the microbiota shifts, as the relative abundances of some biomarkers (e.g. 9 genera and 22 species) became comparable (FDR > 0.1) between the patients and healthy controls. The treatment‐responsive features included Weissella, Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum and three components of a putative glutamine transport system. Importantly, gram‐positive bacteria accounted for over 85% of the numbers and total relative abundance of the species that were associated with IgAV and responsive to the treatment. In addition, of the 122 IgAV‐depleted bacterial genes, 82 were mainly contributed by gram‐positive bacteria and 12 by gram‐negative bacteria. Conclusions: Gram‐positive bacteria are the main drivers underlying the gut microbiome shifts of IgAV, which may assist rational management of the disease. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prevalence and clinical characteristics of myelinated retinal nerve fibre (MRNF) in a large teleophthalmology system. Methods: All records between January 2015 and December 2015 from Daheng Prust teleophthalmology system were reviewed by 2 ophthalmologists independently. MRNF was classified into continuous group and discontinuous group according to the relationship between MRNF patches and optic disc. The number, total area and location of MRNF patches were analysed. Concomitant ocular diseases were documented. Results: Out of 51469 subjects, MRNF was detected in 304 eyes of 263 subjects with a prevalence rate of 0.51 ± 7.1% per subject and 0.30 ± 5.4% per eye. Among 304 eyes with MRNF, 239 (78.6%) eyes were in continuous group and 65 (21.4%) eyes were in discontinuous group. Single MRNF patch was found in 249 (81.9%) eyes and multiple MRNF patches were found in 55 (18.1%) eyes. MRNF of small size was found in 150 (49.3%) eyes. The ratios of multiple MRNF patches and small-sized MRNF in the continuous group were significantly higher than those in the discontinuous group (P =.014 and P <.001). In continuous group, the MRNF patches were located most frequently in the superior region (68.6%) of the optic disc; In discontinuous group, the MRNF patches were located most frequently in the inferotemporal region (38.5%) of the retina. Epiretinal membrane (12 eyes, 3.9%) was the most common concomitant ocular disease. Conclusion: MRNF is uncommon in China. MRNF usually presents unilaterally and as a single small whitish patch that is connected with optic disc. [ABSTRACT FROM AUTHOR]

Gut microbiome alteration was closely associated with colorectal cancer (CRC). Previous studies had demonstrated the bacteria composition changes but lacked virome profiles, trans-kindom interactions, and reliable diagnostic model explorations in CRC. Hence, we performed metagenomic sequencing to investigate the gut microbiome and microbial interactions in adenoma and CRC patients. We found the decreased microbial diversity in CRC and revealed the taxonomic alterations of bacteria and viruses were highly associated with CRC at the species level. The relative abundance of oral-derived species, such as Fusobacterium nucleatum , Fusobacterium hwasookii , Porphyromonas gingivalis , and Bacteroides fragilis , increased. At the same time, butyrate-producing and anti-inflammatory microbes decreased in adenoma and CRC by non-parametric Kruskal-Wallis test. Despite that, the relative abundance of Escherichia viruses and Salmonella viruses increased, whereas some phages, including Enterobacteria phages and Uncultured crAssphage , decreased along with CRC development. Gut bacteria was negatively associated with viruses in CRC and healthy control by correlation analysis (P=0.017 and 0.002, respectively). Viruses were much more dynamic than the bacteria as the disease progressed, and the altered microbial interactions were distinctively stage-dependent. The degree centrality of microbial interactions decreased while closeness centrality increased along with the adenoma to cancer development. Uncultured crAssphage was the key bacteriophage that enriched in healthy controls and positively associated with butyrate-producing bacteria. Diagnostic tests based on bacteria by random forest confirmed in independent cohorts showed better performance than viruses for CRC. In conclusion, our study revealed the novel CRC-associated bacteria and viruses that exhibited specific differences and intensive microbial correlations, which provided a reliable diagnostic panel for CRC. [ABSTRACT FROM AUTHOR]