Search

Traumatic brain injury (TBI) and spinal cord injury (SCI) are capable of causing severe sensory, motor and autonomic nervous system dysfunctions. However, effective treatments for TBI and SCI are still unavailable, mainly because the death of nerve cells is uncontrollable. Necroptosis is a type of programmed cell death and a critical mechanism in the process of neuronal cell death. However, the role of necroptosis has not been comprehensively defined in TBI and SCI.This review aimed to summarize the role of necroptosis in central nervous system (CNS) trauma and its therapeutic implications and present important suggestions for researchers conducting in-depth research.Necroptosis is orchestrated by a complex comprising the receptor-interacting protein kinase (RIPK)1, RIPK3 and mixed lineage kinase domain-like protein (MLKL) proteins. Mechanistically, RIPK1 and RIPK3 form a necrosome with MLKL. After MLKL dissociates from the necrosome, it translocates to the plasma membrane to induce pore formation in the membrane and then induces necroptosis. In this review, the necroptosis signalling pathway and the execution of necroptosis are briefly discussed. In addition, we focus on the existing information on the mechanism by which necroptosis participates in CNS trauma, particularly in the temporal pattern of RIPKs and in different cell types. Furthermore, we describe the association of miRNAs and necroptosis and the relationship between different types of CNS trauma cell death. Finally, this study highlights agents likely capable of curtailing such a type of cell death according to results optimization and CNS trauma and presents important suggestions for researchers conducting in-depth research.

Gut microbes are closely associated with most human health. When ingested orally, probiotics can effectively regulate the composition and quantity of human intestinal microorganisms, which is beneficial to human health. However, probiotics will be affected by the harsh environment of the digestive tract during the in vivo transportation process, and ensuring the viability of probiotics is a great challenge. Probiotic encapsulating technology provides an effective solution to this problem. The introduction of extreme temperatures, large probiotic microcapsule sizes and the difficulty in controlling probiotic microcapsule particle sizes mean that traditional microcapsule encapsulation methods have some limitations. From traditional microcapsule technology to the bulk encapsulation of probiotics with nanofibers and nanoparticles to the recent ability to wear nano "armor" for a single probiotic through biofilm, biological membrane and nanocoating. Emerging probiotic nanoagents provides a new conceptual and development direction for the field of probiotic encapsulation. In this review, we presented the characteristics of encapsulated probiotic carrier materials and digestive tract transport systems, we focused on the encapsulation systems of probiotic nanoagents, we analyzed the shortcomings and advantages of the current agent encapsulation systems, and we stated the developmental direction and challenges for these agents for the future.

In this work, a full circuit of memristor-based neural network with weighted sum simultaneous perturbation training is proposed. Firstly, a synaptic circuit is designed by using a pair of memristors, which can represent negative, zero, and positive synaptic weights. Secondly, a full circuit of the neural network is designed, with all operations being completed on the circuit without any computer aid. The neural network is trained with the weighted sum simultaneous perturbation algorithm. The algorithm does not involve complex derivative calculation and error back propagation, and it only applies perturbations to weighted sum, so the circuit implementation is more simple. Finally, application simulations of the proposed neural network circuit are performed via PSpice. The results of simulation indicate that the memristor-based neural network is practical and effective.

Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with poor prognosis due to early metastasis. The aberrant N6-methyladenosine (m6A) RNA modification has emerged as an important mechanism in cancer progression and metastasis, but its role in PDAC remained largely unknown. Here, we demonstrated that an m6A regulator, heterogeneous nuclear ribonucleoprotein C (HNRNPC), modulated alternative splicing events to promote PDAC metastasis. In clinical PDAC tissues, high expression of HNRNPC was correlated with metastasis, resulting in poor prognosis in PDAC patients. Knockdown of HNRNPC significantly reduced PDAC cell invasion in vitro and metastasis in vivo. In contrast, overexpression of HNRNPC provoked malignant phenotypes of PDAC cells. Mechanistically, HNRNPC antagonized the anti-metastatic isoform of TAF8 (TAF8L) but increased the pro-metastatic alternative splicing isoform of TAF8 (TAF8S). Mutation of the m6A-site of TAF8 attenuated the interaction between HNRNPC and TAF8 transcript, leading to the decrease of TAF8S. Furthermore, experimental manipulation of the anti-metastasis splicing isoform TAF8L revealed that splice isoform switching of TAF8 is crucial for PDAC metastasis. In conclusion, our findings demonstrate the essentiality of HNRNPC-mediated alternative splicing events that impinges on metastatic PDAC.

Upregulated expression of immune checkpoint molecules correlates with exhausted phenotype and impaired function of cytotoxic T cells to evade host immunity. By disrupting the interaction of PD-L1 and PD1, immune checkpoint inhibitors can restore immune system function against cancer cells. Growing evidence have demonstrated apigenin and luteolin, which are flavonoids abundant in common fruits and vegetables, can suppress growth and induce apoptosis of multiple types of cancer cells with their potent anti-inflammatory, antioxidant and anticancer properties. In this study, the effects and underlying mechanisms of luteolin, apigenin, and anti-PD-1 antibody combined with luteolin or apigenin on the PD-L1 expression and anti-tumorigenesis in KRAS-mutant lung cancer were investigated. Luteolin and apigenin significantly inhibited lung cancer cell growth, induced cell apoptosis, and down-regulated the IFN-γ-induced PD-L1 expression by suppressing the phosphorylation of STAT3. Both luteolin and apigenin showed potent anti-cancer activities in the H358 xenograft and Lewis lung carcinoma model in vivo, and the treatment with monoclonal PD1 antibody enhanced the infiltration of T cells into tumor tissues. Apigenin exhibited anti-tumor activity in Genetically engineered KRASLA2 mice. In conclusion, both apigenin and luteolin significantly suppressed lung cancer with KRAS mutant proliferation, and down-regulated the IFN-γ induced PD-L1 expression. Treatment with the combination of PD-1 blockade and apigenin/luteolin has a synergistic effect and might be a prospective therapeutic strategy for NSCLC with KRAS-mutant.

The aluminum-steel hybrid assemblies would simultaneously reach the engineering aim to reduce weight and improve fuel efficiency. However, it is of great challenge to join aluminum to steel due to the great difference in thermal properties and the formation of IMC. In this work, a better joint between aluminum and Al-Si coated boron steel was successfully achieved using laser/DP-MIG hybrid welding-brazing. The examinations of welding appearance, macrostructure, interface microstructure, and tensile tests were carried out. The laser/DP-MIG hybrid welding-brazing could simultaneously strengthen metallurgic bonding and wettability compared to conventional MIG joint. The plasma characteristics of laser/DP-MIG hybrid source contributes to suppress the formation and growth of IMC. Three phases and its formation mechanism were demonstrated in detail: τ5-Fe2Al8Si, θ-Fe(Al,Si)3, and η-Fe2(Al,Si)5. The average joint strength of laser/DP-MIG was 271.8 N/mm whereas that of conventional MIG was 138.4 N/mm. The substantial adhesion area at the brazing interface and the brittle IMC is the two main factors in determining the tensile strength.

In this study, shell-core fibers were successfully prepared by using Eudragit S100 (ES100) and poly(vinyl alcohol) (PVA)/pectin (PEC) through coaxial electrospinning technology. The electrospun fiber was characterized by attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray diffraction (XRD). Thermo-gravimetric analysis (TGA) showed that the coaxial electrospun fiber encapsulated with Lactobacillus rhamnosus 1.0320 (L. rhamnosus) had higher thermal stability than the electrospun fiber prepared by uniaxial electrospinning. L. rhamnosus encapsulated by coaxial electrospun fiber maintained 90.07% and 91.96% survivability in simulated gastric and intestinal fluids. After continuous simulated gastrointestinal fluid treatment, the survival rate of L. rhamnosus encapsulated by coaxial electrospun fiber was 81.40%. The results indicate that shell-core fiber-encapsulated probiotics can improve the tolerance of probiotics to the harsh environment of gastrointestinal tract. The fiber prepared in this study can be applied to the preparation of functional fermented food such as probiotic yogurt fermentation in the future.

Despite recent advances in diagnosis and therapeutic strategies, treatment of non-small-cell lung cancer (NSCLC) remains unsatisfactory in terms of prognosis. Andrographolide (AD), a principal active component of Andrographis paniculata (Burm.f.) Nees, exerts anti-cancer therapeutic properties. AD has been used for centuries in China for clinical treatment of viral infections. However, the pharmacological biology of AD in NSCLC remains unknown. In this study, AD regulated autophagy and PD-L1 expression in NSCLC. Molecular dynamics simulations indicated that AD bound directly to signal transducer and activator of transcription-3 (STAT3) with high affinity. Proteomics analysis indicated that AD reduced the expression of tumour PD-L1 in NSCLC by suppressing JAK2/STAT3 signalling. AD modulated the P62-dependent selective autophagic degradation of PD-L1 by inhibiting STAT3 phosphorylation. In vivo study revealed that AD suppressed tumour growth in H1975 xenograft mice and Lewis lung carcinoma cell models, and better efficacy was obtained at higher concentrations. AD prolonged the survival time of the mice and enhanced the treatment efficacy of anti-PD-1 mAb immunotherapy by stimulating CD8

In this paper we present an approach to training neural network to generate sequences using successor feature learning from reinforcement learning. The model can be thought as two components, an MLE-based token generator and an estimator that predicts the future value of whole sentence. As we know, reinforcement learning has been applied to dealing with the exposure bias problem of generating sequences. Compared with other RL algorithm, successor feature(SF) can learn robust value function provided observations and reward by decomposing the value function into two components - a reward predictor and a successor map. The encoder-decoder framework with SF enables the decoder to generate outputs that receive more future reward, which means that the model pays attention on not only the current word but also the rest words. We demonstrate that the approach improves performance on two translation tasks.

The influence of cooling rates (using different immersion temperatures of –35 °C, –45 °C, and –55 °C) and super-chilling temperatures (–1.5 °C and –3.0 °C) on the ice crystal state, cell structure, and physicochemical quality of super-chilled fresh-cut celery was investigated. Results showed that the average freezing temperature of celery was –0.48 ± 0.08 °C. Tissues super-chilled to –1.5 °C at –55 °C presented numerous tiny ice crystals with a uniform distribution outside and inside cells and well-maintained structures. The retention of texture attributes, the contents of total polyphenols, total flavonoids, and soluble solid, and the scavenging ability of DPPH· were significantly (P

Despite the high response rate after surgery and platinum-combination chemotherapy, treatment of ovarian cancer remains challenging due to tumor recurrence and metastasis. Tumor-associated macrophages (TAMs) have been linked to cancer progression and metastasis. However, the impact of the crosstalk between chemotherapy and TAMs on ovarian cancer progression remains unclear. Here, we demonstrated that cisplatin-stimulated classically activated macrophages (CAMs) promote ovarian cancer cell migration by increasing CCL20 production, which activates its receptor CCR6 on ovarian cancer cells, triggering epithelial-to-mesenchymal transition. In clinical ovarian cancer samples, high CCR6 expression on ovarian cancer cells positively correlates with cancer metastasis, leading to poor prognosis. Pharmacological blockage of CCL20 on cisplatin-stimulated CAMs and siRNA-mediated inactivation of CCR6 on cancer cells effectively abrogated ovarian cancer cell migration induced by cisplatin-stimulated CAMs. Collectively, our results reveal a novel pro-migration mechanism driven by the crosstalk between cisplatin and CAMs, and implicate the CCL20-CCR6 axis as a potential therapeutic target to reduce chemotherapy-induced metastasis in advanced stage ovarian cancer.

This paper discusses the sliding mode control (SMC) problem for nonlinear systems (NSs) with time-varying delays and external disturbances. Different from some existing results, the derivative of the time-varying delay is allowed to be bounded by an arbitrary bounded real number rather than by one. On this basis, an integral sliding mode surface (SMS) with time-varying delays is introduced. By exploiting the Lyapunov stability theory and the improved reciprocally convex inequality, several conditions of globally asymptotically stable are obtained for the sliding mode motion dynamics. Moreover, some results of globally exponentially stable are also established by resorting to double-integral calculations, the integral mean-value theorem and the zero-point existence theorem. Then, the normal/adaptive SMC laws are provided to ensure the reachability of the specified SMS. Finally, the validity and the application of the proposed SMC method are illustrated by two practical examples.

Accurate and up-to-date land cover maps inform and support effective management and policy decisions. Describing phenological changes in spectral response using time-series data may help to distinguish vegetation types, thereby allowing for more specificity within vegetation classification. In this research, we test this by classifying indigenous forest vegetation in New Zealand, using PlanetScope (PS) and Sentinel-2 (S-2) satellite time-series data. The study was undertaken in a podocarp forest in New Zealand's central north island, which was classified into nine land cover classes. Phenological features, based on S-2 imagery, were extracted, including the enhanced vegetation index (EVI), enhanced vegetation index 2 (EVI2) and normalised difference vegetation index (NDVI). Google Earth Engine (GEE) harmonic analysis and TIMESAT double logistic fitting function were used to extract phenological features. Pixel-based classifications were performed using a Neural Network on six different scenarios. The accuracy of the classification scenarios was determined and the importance score for each feature was evaluated. Using only the fused PS and S-2 bands, the land cover in the study area was classified with 90.1% accuracy. Adding phenological features increased the classification accuracy to 93.1%. When combined with VIs, texture features, and a digital terrain model, the addition of phenological features increased the classification accuracy to 96.6%. Including GEE-generated phenological features resulted in better classification accuracies than TIMESAT features. In terms of feature importance evaluation, EVI2- and NDVI-generated phenological features all had high scores; the effectiveness of EVI features could potentially have been limited by the quality of the blue band. The results demonstrate that it is possible to produce a more accurate classification of New Zealand's native vegetation by using phenological features. This method offers important cost-savings as the platforms for phenological analysis are free to use.

Intervertebral disc degeneration (IVDD) is a highly prevalent musculoskeletal disorder characterized by a local inflammatory response associated with the IL-1β/NLRP3 inflammasome positive feedback loop. Rice bran-derived gamma-oryzanol (Ory) as a sterol ferulate has attracted much attention due to its powerful anti-inflammatory, hypoglycemic and hypolipidemic health effects. As a clinical pharmaceutical for autonomic disorders, Ory's role in musculoskeletal degenerative disease remains unknown.This study aims to validate the role of Ory in IVDD and explore the potential mechanism.Establishing the in vitro and in vivo IVDD models to detect the protective effect and molecular mechanism of Ory.The anti-ECM degradation, antioxidant and anti-NLRP3 inflammasome activation effects of Ory on IL-1β-stimulated nucleus pulposus (NP) cells were assessed by immunoblotting and immunofluorescence, etc. MRI, S-O staining and immunohistochemistry were performed to estimate the effects of Ory administration on acupuncture-mediated IVDD in rats at imaging and histological levels.Ory treatment inhibited IL-1β-mediated ECM degradation, oxidative stress and NLRP3 inflammasome activation in NP cells. By interfering with NF-κB signaling and ROS overproduction, Ory interrupted IL-1β/NLRP3-inflammasome positive cycle. In vivo experiments showed that Ory delayed acupuncture-mediated IVDD development.Our results support the potential application of Ory as a therapeutic compound for IVDD.

The aim of this study was to evaluate the effects of geographic location (i.e., latitude, longitude, altitude) and soil fertility (i.e., nitrogen, phosphorus) on main phenolic compounds and fatty acids in VOO nearby the Bailong River in Longnan city, a representative planting-region in China. The geographical distribution analysis showed that the sampling-points from the middle reaches of Bailong River had higher secondary metabolites, such as oleacein and oleocanthal. Correlation analysis revealed that the contents of ligustroside, vanillic acid and rutin were negatively correlated with altitude while the contents of heptadecenoic acid, oleic acid and eicosenoic were positively related to the altitude. Moreover, the excessive available nitrogen had an adverse effect on the content of phenolic compounds and fatty acids in virgin olive oil. It was helpful for the accumulation of phenolic compounds and fatty acids in virgin olive oil when the level of available nitrogen ranged from 51 to 100 mg/kg. These findings are helpful for the geographic-location selection and fertilization management of olive orchard.