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Background: Microvascular invasion (MVI) is associated with an unfavorable prognosis and early recurrence of hepatocellular carcinoma (HCC), which is the crucial pathological hallmark of immunotherapy. While microvascular invasion (MVI) in hepatocellular carcinoma (HCC) currently lacks a detailed single-cell analysis of the tumor microenvironment (TME), it holds significant promise for immunotherapy using immune checkpoint inhibitors (ICI). Methods: We performed single-cell RNA sequencing (scRNA-seq) on 3 MVI positive (MVIP) and 14 MVI-negative (MVIN) tumor tissues, as well as their paired adjacent non-tumoral tissues. Results: We identified SPP1+ macrophages and CD4+ proliferative T cells as intertumoral populations critical for the formation of cold tumors and immunosuppressive environments in MVI-positive patients and verified their prognostic value in correlation with MVIP HCC patients. Additionally, we identified SPP1+ dominated interactions between SPP1+ macrophages and the immunosuppressive T population as contributors to MVI destruction and tumorigenesis. Conclusions: We provide a comprehensive single-cell atlas of HCC patients with MVI, shedding light on the immunosuppressive ecosystem and upregulated signaling associated with MVI. These findings demonstrate that intercellular mechanisms drive MVI and provide a potential immunotherapeutic target for HCC patients with HCC and underlying MVI.

Andrographolide is one of the main biologically active molecules isolated from Andrographis paniculata (A. paniculata), which is a traditional Chinese herb used extensively throughout Eastern Asia, India, and China. Pseudomonas aeruginosa, often known as P. aeruginosa, is a common clinical opportunistic pathogen with remarkable adaptability to harsh settings and resistance to antibiotics. P. aeruginosa possesses a wide array of virulence traits, one of which is biofilm formation, which contributes to its pathogenicity. One of the main modulators of the P. aeruginosa-controlled intramembrane proteolysis pathway is AlgW, a membrane-bound periplasmic serine protease. In this work, we have used a set of density functional theory (DFT) calculations to understand the variety of chemical parameters in detail between andrographolide and levofloxacin, which show strong bactericidal activity against P. aeruginosa. Additionally, the stability and interaction of andrographolide and levofloxacin with the protein AlgW have been investigated by molecular docking and molecular dynamics (MD) simulations . Moreover, the growth and inhibition of biofilm production by P. aeruginosa experiments were also investigated, providing insight that andrographolide could be a potential natural product to inhibit P. aeruginosa.

Abstract This paper presents a sequential Kalman asynchronous track fusion algorithm based on the effective sound velocity method proposed to deal with the problem of random asynchrony of multi-node measurement information in the distributed underwater multi-target detection system due to the propagation effect of the sound channel. This algorithm updates the time stamp of target information reported by each sensor by using the effective sound velocity method, so as to obtain the actual time when the target state information appears in the underwater acoustic channel. Then, according to the actual asynchronous situation of the multi-sensor, it uses the sequential filter algorithm to fuse the asynchronous sensors. The simulation results show that the algorithm can improve the positioning accuracy of the original algorithm, has a strong adaptability to sensor target loss and accuracy loss, and has a certain application value.

With modified water glass as binder and the introduction of micro silicon powders into the coremaking process, an improvement was made to the tensile strength and collapsibility of the sand core. The potassium hydroxide, sodium hexametaphosphate and white sugar were applied as the modifiers of water glass. The optimum proportion of the modifiers was determined through the combination of single factor test and orthogonal test. The optimum proportion of water glass, potassium hydroxide, sodium hexametaphosphate and white sugar is 1000: 40: 5: 5 (wt.). In terms of weight, modified binder and micro silicon powders accounted for 2% and 0.6% of sand, respectively. The sand core was hardened by going through a warm core box process, in which the temperature of core box was 150 °C, and the compressed hot air was blown at 120 °C for 40 s under a pressure of 0.2 MPa. As for the sand core bonded with modified water glass, the tensile strength is 2.46 MPa at room temperature (σ0) and 2.49 MPa at 25 °C and 40% RH for 24 h (σ24), which are 2 times more than that with unmodified binder. The bonded strengths of sand core are increased as a result of the reaction between -OH groups from addition of potassium hydroxide and SiO2 particles widely distributed in the sand core. Comparing with the sand core bonded with unmodified water glass, the high temperature residual tensile strength (σr) of sand core bonded with modified water glass under 600 °C for 5 min, is sharply reduced from 0.20 MPa to 0.01 MPa. By the comparison with unmodified water glass, the dynamic viscosity of the modified water glass and the flowability of molding sand using modified water glass are increased from 74 mPa·s and 2.15 g to 80 mPa·s and 2.21 g, respectively. As revealed by FT-IR analysis, new groups including PO3-, PO4 3-, and Si-O-C appear in the molecular structure of modified water glass, which are beneficial to the collapsibility of sand core.

The performance of sand core was improved by using the modified water glass as a binder and adding powder additives in the sand hardening process. The optimal proportion of the compound additives was determined by an orthogonal test, with a ratio of microsilica: polyvinyl alcohol solution: borax: B agent = 25: 20: 2: 1. The binder accounted for 2% of the sand by weight, and the compound additives accounted for 0.96%. The core box was heated to 175 °C, and the compressed hot air of 120 °C kept blowing for 40 s. Tensile strength was used as the main indicator to evaluate the humidity-resistance of the sand core. For the sand core, the instant tensile strength reached 0.73 MPa, the tensile strength at room temperature was 1.81 MPa, and that of sand core holding at the condition of 35 °C and 90% RH for 2 h and for 4 h reached 1.61 MPa and 1.19 MPa, respectively. The gas evolution was 7.5 mL·g-1 at 850 °C for 3 min. The residual tensile strength was 0 MPa at 750 °C for 5 min. Fourier-transform infrared spectroscopy analysis showed that the humidity-resistance of the core was greatly improved by the powder additives.

Knee osteoarthritis (OA) is a leading cause of late life pain and disability, and non-Hispanic black (NHB) adults experience greater OA-related pain and disability than non-Hispanic whites (NHWs). Recent evidence implicates psychosocial stress, cognitive-attentional processes, and altered central pain processing as contributors to greater OA-related pain and disability among NHBs. To address these ethnic/race disparities, this clinical trial will test whether a mindfulness intervention (Breathing and Attention Training, BAT) combined with transcranial direct current stimulation (tDCS) will enhance pain modulatory balance and pain-related brain function, reduce clinical pain, and attenuate ethnic differences therein, among NHBs and NHWs with knee OA. Participants will complete assessments of clinical pain, function, psychosocial measures, and quantitative sensory testing (QST), including mechanical temporal summation and conditioned pain modulation. Neuroimaging will be performed to examine pain-related brain structure and function. Then, participants will be randomized to one of four groups created by crossing two BAT conditions (Real vs. Sham) with two tDCS conditions (Real vs. Sham). Participants will then undergo five treatment sessions during which the assigned BAT and tDCS interventions will be delivered concurrently for 20 min over one week. After the fifth intervention session, participants will undergo assessments of clinical pain and function, QST and neuroimaging identical to the pretreatment measures, and monthly follow-up assessments of pain will be conducted for three months. This will be the first study to determine whether mindfulness and tDCS treatments will show additive or synergistic effects when combined, and whether treatment effects differ across ethnic/race groups.

Meat rabbits are a small herbivorous livestock and have been popularly raised in China for producing high-quality meat. Therefore, it is economically important to genetically improve both carcass performance and meat quality in meat rabbits. However, we still know less about the underlying candidate genes that may determine phenotypic variation on carcass and meat traits of meat rabbits. The main objective of this study was to identify candidate genes whose mRNA expression levels may be significantly involved in regulating carcass and meat traits of meat rabbits based on the transcriptome-wide association studies (TWAS). Five carcass traits of the carcass weight (CW), dressing out percentage (DP), cut weight of hind legs (LW), weight ratio of cut hind legs to carcass (RLW), and weight of visceral and interscapular fat (WF), as well as two meat traits of the drip loss (DL) and cooking loss (CL) were phenotyped in a F1 crossbred population (N = 119) between Zika rabbits and Sichuan White rabbits. The effects of mRNA expression levels of a total of 10,288 genome-wide genes on these seven traits were statistically estimated using the mixed linear model, in which the polygenic background effects were accounted for. Our results revealed two candidate genes (RDH5 and MTARC2) that were statistically significantly associated with LW trait (the adjusted p values <0.05), whereas no gene reached the statistically significant threshold for all the remaining six traits. Because of the relatively small sample size analyzed, we alternatively selected 20 candidate genes with the lowest p values for every trait and subjected them to functional enrichment analyses, which identified three Gene Ontology (GO) terms that were significantly enriched by the candidate genes of CW and RLW traits. In conclusion, this study used TWAS approach to successfully reveal several candidate genes whose mRNA expression levels may be involved in regulating carcass and meat traits in meat rabbits, which are helpful to explore the underlying molecular mechanism in the future studies. [ABSTRACT FROM AUTHOR]

Adaptive e-learning can be used to personalize learning environment for students to meet their individual demands. Individual differences depend on the students' personality traits. Numerous studies have indicated that understanding the role of personality in the learning process can facilitate learning. Hence, personality identification in e-learning is a critical issue in education. In this study, we propose the enhanced extended nearest neighbor (EENN) algorithm to automatically identify two of the Big Five personality traits from students' behavior in online learning: openness to experience and extraversion. The performance of the proposed method is evaluated using a fivefold cross-validation approach on data from 662 senior high school students. The experimental results indicate that the EENN method can automatically recognize personality at an average accuracy of 0.758. The optimized method that combines EENN with particle swarm optimization significantly improves the identification, resulting in an average accuracy of 0.976. The results can benefit students by increasing the accuracy of personalization based on their personality traits, while simultaneously allowing them to be better understood and possibly allowing their instructors to provide more appropriate learning interventions.

Rabbits can efficiently utilize plant fibers that are indigestible to humans, and hence may contribute to the alleviation of feed–food competition. Therefore, it is economically and ecologically important to genetically improve the growth performance and feed efficiency of meat rabbits. In this study, we combined pedigree, genomic, and gut microbiota data to estimate genetic and microbial parameters for nine growth and feed efficiency traits of 739 New Zealand White rabbits, including body weight (BW) at 35 (BW35), 70 (BW70), and 84 (BW84) days of age, and average daily gain (ADG), feed conversion ratio (FCR), and residual feed intake (RFI) within two age intervals of 35–70 days (ADG70, FCR70, and RFI70) and 35–84 days (ADG84, FCR84, and RFI84). Based on single-step genomic best linear unbiased prediction, three BW traits and two ADG traits had the high estimates (±standard error, SE) of heritability, ranging from 0.44 ± 0.13 of BW35 to 0.66 ± 0.08 of BW70. Moderate heritabilities were observed for RFI70 (0.22 ± 0.07) and RFI84 (0.29 ± 0.07), whereas the estimates did not significantly deviate from zero for the two FCR traits. There was moderate positive genetic correlation (±SE) between BW70 and ADG70 (0.579 ± 0.086), but BW70 did not correlate with RFI70. Based on microbial best linear unbiased prediction, the estimates of microbiability did not significantly deviate from zero for any trait. Based on the combined use of genomic and gut microbiota data, the parameters obtained in this study could help us to implement efficient breeding schemes in meat rabbits. [ABSTRACT FROM AUTHOR]

Introduction Reactive oxygen species (ROS) are small reactive molecules that include [O.sub.2.sup.*-], [H.sub.2][O.sub.2], O[H.sup.*-], and O[C1.sup.*-], which can react actively with cellular lipids, proteins, and nucleic acids (Hafstad et al. [...], Both the Notch1 and Keap1-Nrf2 signaling pathways have cardioprotective effects, but the role of Notch1-Nrf2 crosstalk in myocardial ischemia-reperfusion injury is unclear. In this study, we established hypoxia-reoxygenation in neonate rat myocardial cells and employed [gamma]-secretase inhibitor and curcumin to inhibit and activate the Notch1 and Keap1-Nrf2 signaling pathways, respectively. We found that the combined action of the Notch1 and Keap1-Nrf2 signaling pathways significantly increased cardiomyocyte viability, inhibited cardiomyocyte apoptosis, reduced the formation of reactive oxygen species, and increased antioxidant activities. In conclusion, these findings suggest that Notch1-Nrf2 crosstalk exerts myocardial protection by reducing the formation of reactive oxygen species. Key words: Notch1 signaling, Keap1, Nrf2, ROS, myocardial protection. Les voies de signalisation Notch1 et Keap1-Nrf2 exercent toutes deux des effets cardioprotecteurs, mais le rôle de la signalisation croisée Notch1-Nrf2 dans le dommage d'ischémie--reperfusion du myocarde n'est pas clair. Dans cette étude, les auteurs ont établi une hypoxie/réoxygénation de cellules myocardiques de rats nouveau-nés et utilisé un inhibiteur de [gamma]-sécrétase et la curcumine pour inhiber et activer, respectivement, les voies de signalisation Notch1 et Keap1-Nrf2. Ils ont trouvé que l'action combinée des voies de signalisation Notch1 et Keap1-Nrf2 augmentait significativement la viabilité des cardiomyocytes, inhibait l'apoptose des cardiomyocytes, réduisait les dérivés réactifs d'oxygène et augmentait les activités antioxydantes. En conclusion, ces résultats suggèrent que la signalisation croisée Notch1-Nrf2 exerce une protection sur le myocarde en réduisant les dérivés réactifs d'oxygène. [Traduit par la Rédaction] Mots-clés : signalisation Notch1, Keap1, Nrf2, DRO, protection du myocarde.

Open, flexible and distance learning has become part of mainstream education in China. Using a blended learning program in a Chinese high school as the case, this study adopted data-mining approaches to establish predictive models using personality traits. Results showed that, for students with high OE and low extraversion, and students who are low on both of these constructs, the number of postings in digest (NPD) and average score of after-class test (SCT) were significant predictors of their achievement. For students with low OE and high extraversion, time spent on viewing course resources and number of answers provided in the format of text were significant predictors. For those with high OE and low extraversion, time spent on learning online and number of questions raised in the format of hypermedia, NPD and SCT were significant. Furthermore, deep belief networks performed best in identifying at-risk students at each stage.

Klinefelter (47,XXY) syndrome (KS), the most common form of sex-chromosomal aneuploidy, is characterized by physical, endocrinologic, and reproductive abnormalities. Individuals with KS also exhibit a cognitive/behavioral phenotype characterized by language and language-based learning disabilities and executive and attentional dysfunction in the setting of normal general intelligence. The underlying neurobiologic mechanisms are just now beginning to be elucidated through structural and functional neuroimaging. Here, we review the literature of structural and functional neural findings in KS identified by neuroimaging and present preliminary results from a functional magnetic resonance imaging study examining brain activity during a verb generation task in KS.