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Abstract Background Cardiovascular disease (CVD) is closely associated with the triglyceride glucose (TyG) index and its related indicators, particularly its combination with obesity indices. However, there is limited research on the relationship between changes in TyG-related indices and CVD, as most studies have focused on baseline TyG-related indices. Methods The data for this prospective cohort study were obtained from the China Health and Retirement Longitudinal Study. The exposures were changes in TyG-related indices and cumulative TyG-related indices from 2012 to 2015. The K-means algorithm was used to classify changes in each TyG-related index into four classes (Class 1 to Class 4). Multivariate logistic regressions were used to evaluate the associations between the changes in TyG-related indices and the incidence of CVD. Results In total, 3243 participants were included in this study, of whom 1761 (54.4%) were female, with a mean age of 57.62 years at baseline. Over a 5-year follow-up, 637 (19.6%) participants developed CVD. Fully adjusted logistic regression analyses revealed significant positive associations between changes in TyG-related indices, cumulative TyG-related indices and the incidence of CVD. Among these changes in TyG-related indices, changes in TyG-waist circumference (WC) showed the strongest association with incident CVD. Compared to the participants in Class 1 of changes in TyG-WC, the odds ratio (OR) for participants in Class 2 was 1.41 (95% confidence interval (CI) 1.08–1.84), the OR for participants in Class 3 was 1.54 (95% CI 1.15–2.07), and the OR for participants in Class 4 was 1.94 (95% CI 1.34–2.80). Moreover, cumulative TyG-WC exhibited the strongest association with incident CVD among cumulative TyG-related indices. Compared to the participants in Quartile 1 of cumulative TyG-WC, the OR for participants in Quartile 2 was 1.33 (95% CI 1.00–1.76), the OR for participants in Quartile 3 was 1.46 (95% CI 1.09–1.96), and the OR for participants in Quartile 4 was 1.79 (95% CI 1.30–2.47). Conclusions Changes in TyG-related indices are independently associated with the risk of CVD. Changes in TyG-WC are expected to become more effective indicators for identifying individuals at a heightened risk of CVD.

The prevalent practice of substituting fishmeal with plant protein frequently leads to disturbances in bile acid metabolism, subsequently increasing the incidence of metabolic liver diseases. Bile acid nutrients such as cholesterol, taurine and glycine have been shown to enhance bile acid synthesis and confer beneficial effects on growth. Therefore, this study aimed to investigate the effects of cholesterol-taurine-glycine (Ch-Tau-Gly) supplement on bile acid metabolism and liver health in spotted seabass (Lateolabrax maculatus) fed a plant-based diet. Two isonitrogenous and isolipidic diets were formulated: (1) plant protein-based diet (PP); (2) PP supplemented 0.5% cholesterol, 0.5% taurine and 1.3% glycine (CTG). Each experimental diet was randomly fed to quadruplicate groups of 30 feed-trained spotted seabass in each tank. The results revealed that supplementing plant-based diet with Ch-Tau-Gly supplement led to an increase in carcass ratio (meat yield) in spotted seabass (P

This research explores the eco-friendly synthesis of silver nanoparticles (AgNPs) using Chrysanthemum extract, emphasizing its application in antimicrobial treatments. The study primarily focused on assessing the effect of extract concentration on nanoparticle characteristics. The synthesized AgNPs, at higher Chrysanthemum extract concentrations (up to 15%), exhibited a notable decrease in size, from 48.5 nm at 2% to 22.1 nm, and an increase in yield, achieving 2.24 mg/mL. The AgNPs showed a significant antibacterial effect, with the lowest IC50 value of 2.08 µg/mL against Vibrio cholerae, demonstrating a broad-spectrum efficacy. Advanced characterization techniques like SEM and FTIR spectroscopy confirmed the morphological integrity and phytochemical capping of the nanoparticles. The study successfully highlights the potential of Chrysanthemum extract not only as a sustainable source for nanoparticle synthesis but also in enhancing the biocompatibility and efficacy of AgNPs, paving the way for their application in medical and environmental fields.

Abstract Accumulating evidence indicates that exosomal proteins are critical in diagnosing malignant tumors. To identify novel exosomal biomarkers for lung cancer diagnosis, we isolated plasma exosomes from 517 lung cancer patients and 168 healthy controls (NLs)—186 lung adenocarcinoma (LUAD) patients (screening (SN): 20, validation (VD): 166), 159 lung squamous carcinoma (LUSC) patients (SN: 20, VD: 139), 172 benign nodules (LUBN) patients (SN: 20, VD: 152) and 168 NLs (SN: 20, VD: 148)—and randomly assigned them to the SN or VD group. Proteomic analysis by LC–MS/MS and PRM were performed on all groups. The candidate humoral markers were evaluated and screened by a machine learning method. All selected biomarkers were identified in the VD groups. For LUAD, a 7-protein panel had AUCs of 97.9% and 87.6% in the training and test sets, respectively, and 89.5% for early LUAD. For LUSC, an 8-protein panel showed AUCs of 99.1% and 87.0% in the training and test sets and 92.3% for early LUSC. For LUAD + LUSC (LC), an 8-protein panel showed AUCs of 85.9% and 80.3% in the training and test sets and 87.1% for early LC diagnosis. The characteristics of the exosomal proteome make exosomes potential diagnostic tools.

Abstract Hypervascularized glioblastoma is naturally sensitive to anti‐angiogenesis but suffers from low efficacy of transient vasculature normalization. In this study, a lipid‐polymer nanoparticle is synthesized to execute compartmentalized Cas9 and sgRNA delivery for a permanent vasculature editing strategy by knocking out the signal transducer and activator of transcription 3 (STAT3). The phenylboronic acid branched cationic polymer is designed to condense sgRNA electrostatically (inner compartment) and patch Cas9 coordinatively (outer compartment), followed by liposomal hybridization with angiopep‐2 decoration for blood–brain barrier (BBB) penetration. The lipid‐polymer nanoparticles can reach glioblastoma within 2 h post intravenous administration, and hypoxia in tumor cells triggers charge‐elimination and degradation of the cationic polymer for burst release of Cas9 and sgRNA, accompanied by instant Cas9 RNP assembly, yielding ≈50% STAT3 knockout. The downregulation of downstream vascular endothelial growth factor (VEGF) reprograms vasculature normalization to improve immune infiltration, collaborating with interleukin‐6 (IL‐6) and interleukin‐10 (IL‐10) reduction to develop anti‐glioblastoma responses. Collectively, the combinational assembly for compartmentalized Cas9/sgRNA delivery provides a potential solution in glioblastoma therapy.

AbstractHericium erinaceus (Bull.:Fr.) Pers., 1797, is an edible and medicinal fungus found in China. In this study, specimens of H. erinaceus HE0021 were collected from southeastern China (Yunhe County, Lishui City, Zhejiang Province, 28°7′12″N, 119°34′12″E). The whole mitochondrial genome of H. erinaceus HE0021 was sequenced using next-generation sequencing (NGS) technology, which comprised 15 protein-coding genes (PCGs), 27 transfer RNAs (tRNAs), two ribosomal RNAs, with a total length of 83,518 base pairs (bp). The results of the phylogenetic analysis show that H. erinaceus and H. coralloides were clustered in the same clade. The complete mitogenome sequence provides essential data for the subsequent investigation of Hericium and Russulales.

The high heterogeneity of lung squamous cell carcinomas (LUSC) and the complex tumor microenvironment lead to non-response to immunotherapy in many patients. Therefore, characterizing the heterogeneity of the tumor microenvironment in patients with LUSC and further exploring the immune features and molecular mechanisms that lead to immune resistance will help improve the efficacy of immunotherapy in such patients. Herein, we retrospectively analyzed the RNA sequencing (RNA-seq) data of 513 LUSC samples with other multiomics and single-cell RNA-seq data and validated key features using multiplex immunohistochemistry. We divided these samples into six subtypes (CS1–CS6) based on the RNA-seq data and found that CS3 activates the immune response with a high level of lymphocyte infiltration and gathers a large number of patients with advanced-stage disease but increases the expression of exhausted markers cytotoxic T-lymphocyte associated protein 4, lymphocyte-activation gene 3, and programmed death-1. The prediction of the response to immunotherapy showed that CS3 is potentially resistant to immune checkpoint blockade therapy, and multi-omic data analysis revealed that CS3 specifically expresses immunosuppression-related proteins B cell lymphoma 2, GRB2-associated binding protein, and dual-specificity phosphatase 4 and has a high mutation ratio of the driver gene ATP binding cassette subfamily A member 13. Furthermore, single-cell RNA-seq verified lymphocyte infiltration in the CS3 subtype and revealed a positive relationship between the expression of LAMC2-CD44 and immune resistance. LAMC2 and CD44 are epithelial-mesenchymal transition-associated genes that modulate tumor proliferation, and multicolor immunofluorescence validated the negative relationship between the expression of LAMC2-CD44 and immune infiltration. Thus, we identified a lymphocyte-infiltrated subtype (CS3) in patients with LUSC that exhibited resistance to immune checkpoint blockade therapy, and the co-hyperexpression of LAMC2-CD44 contributed to immune resistance, which could potentially improve immunological efficacy by targeting this molecule pair in combination with immunotherapy.

Abstract Extrachromosomal circular DNAs (eccDNAs) participate in tumorigenesis and tumor progression. However, the role and mechanism of eccDNAs have yet to be elucidated in non-small cell lung cancer (NSCLC). In our research, three surgically matched NSCLC tissue samples, NSCLC cell lines (H1299, A549, and H460), and a normal lung cell line (MRC-5) were used as study objects. High-throughput eccDNA sequencing and bioinformatics analysis were performed to study the distribution pattern and level of eccDNA expression. The upregulated candidate eccDNA-encoding PLCG2 was validated by routine PCR. Plasmid transfection, RNA interference, qRT‒PCR and western blotting experiments were used to verify the expression level of PLCG2. Our results showed that the chromosome distribution, length distribution, and genomic annotation of the eccDNAs were comparable between the NSCLC and normal groups. Nevertheless, there were no significant differences in eccDNAs between NSCLC tissues and matched normal lung tissues. The eccDNA derived from PLCG2 was upregulated in NSCLC cells. TCGA analysis and immunohistochemistry showed that PLCG2 was highly expressed in lung cancer tissues and tended to be associated with poor outcome. We also demonstrated that PLCG2 can promote metastasis through the regulation of mitochondrial respiration. These results suggested that PLCG2 identified by eccDNA sequencing acts as an oncogene and might be a new biomarker for NSCLC diagnosis and prognosis evaluation.

Cardiovascular diseases pose a long-term risk to human health. This study focuses on the rich-spectrum mechanical vibrations generated during cardiac activity. By combining Fourier series theory, we propose a multi-frequency vibration model for the heart, decomposing cardiac vibration into frequency bands and establishing a systematic interpretation for detecting multi-frequency cardiac vibrations. Based on this, we develop a small multi-frequency vibration sensor module based on flexible polyvinylidene fluoride (PVDF) films, which is capable of synchronously collecting ultra-low-frequency seismocardiography (ULF-SCG), seismocardiography (SCG), and phonocardiography (PCG) signals with high sensitivity. Comparative experiments validate the sensor’s performance and we further develop an algorithm framework for feature extraction based on 1D-CNN models, achieving continuous recognition of multiple vibration features. Testing shows that the recognition coefficient of determination (R2), mean absolute error (MAE), and root mean square error (RMSE) of the 8 features are 0.95, 2.18 ms, and 4.89 ms, respectively, with an average prediction speed of 60.18 us/point, meeting the re-quirements for online monitoring while ensuring accuracy in extracting multiple feature points. Finally, integrating the vibration model, sensor, and feature extraction algorithm, we propose a dynamic monitoring system for multi-frequency cardiac vibration, which can be applied to portable monitoring devices for daily dynamic cardiac monitoring, providing a new approach for the early diagnosis and prevention of cardiovascular diseases.

Chrysanthemum wilt is a plant disease that exerts a substantial influence on the cultivation of Chrysanthemum zawadskii (Herb.) for tea and beverage production. The rhizosphere microbial population exhibits a direct correlation with the overall health of plants. Therefore, studying the rhizosphere microbial community of Chrysanthemum zawadskii (Herb.) Tzvel. is of great significance for finding methods to control this disease. This study obtained rhizosphere soil samples from both diseased and healthy plant individuals and utilized high-throughput sequencing technology to analyze their microbial composition. The results showed that the rhizosphere microbial diversity decreased significantly, and the microbial community structure changed significantly. In the affected soil, the relative abundance of pathogenic microorganisms such as rhizospora and Phytophthora was greatly increased, while the relative abundance of beneficial microorganisms such as antagonistic fungi and actinomyces was greatly decreased. In addition, this study also found that soil environmental variables have an important impact on plant resistance; the environmental factors mainly include soil properties, content of major microorganisms, and resistance characteristics of samples. Redundancy analysis showed that the drug-resistant population had a greater impact on the 10 species with the highest abundance, and the environmental factors were more closely related to the sensitive population. In the fungal community, the resistant sample group was more sensitive to the influence of environmental factors and high-abundance fungi. These findings provide a theoretical basis for improving microbial community structure by optimizing fertilization structure, thus affecting the distribution of bacteria and fungi, and thus improving the disease resistance of chrysanthemum. In addition, by regulating and optimizing microbial community structure, new ideas and methods can be provided for the prevention and control of chrysanthemum wilt disease.

BackgroundDue to the lower reliability of laboratory tests, skin diseases are more suitable for diagnosis with AI models. There are limited AI dermatology diagnostic models combining images and text; few of these are for Asian populations, and few cover the most common types of diseases.MethodsLeveraging a dataset sourced from Asia comprising over 200,000 images and 220,000 medical records, we explored a deep learning-based system for Dual-channel images and extracted text for the diagnosis of skin diseases model DIET-AI to diagnose 31 skin diseases, which covers the majority of common skin diseases. From 1 September to 1 December 2021, we prospectively collected images from 6,043 cases and medical records from 15 hospitals in seven provinces in China. Then the performance of DIET-AI was compared with that of six doctors of different seniorities in the clinical dataset.ResultsThe average performance of DIET-AI in 31 diseases was not less than that of all the doctors of different seniorities. By comparing the area under the curve, sensitivity, and specificity, we demonstrate that the DIET-AI model is effective in clinical scenarios. In addition, medical records affect the performance of DIET-AI and physicians to varying degrees.ConclusionThis is the largest dermatological dataset for the Chinese demographic. For the first time, we built a Dual-channel image classification model on a non-cancer dermatitis dataset with both images and medical records and achieved comparable diagnostic performance to senior doctors about common skin diseases. It provides references for exploring the feasibility and performance evaluation of DIET-AI in clinical use afterward.

BackgroundThe newly discovered pan-immune-inflammation value (PIV) has been illustrated to have good prognostic value for cancer patient prognosis. However, the prognostic usefulness of PIV in breast cancer patients is unknown. As a result, to aid the clinic in providing a distinctive and trustworthy biomarker to better assess breast cancer patient’s prognosis, we conducted this meta-analysis to investigate the relationship between PIV and the survival of breast cancer patients.MethodsWe conducted a systematic search of Pubmed, Embase, the Cochrane Library, and the CNKI databases to screen for eligible studies published up to April 2023. Outcomes included overall survival (OS), progression-free survival (PFS), and pathological complete response (pCR). The hazard ratio (HR) and the corresponding 95% confidence interval (CI) were used as the indicators. STATA 15.0 software was used to perform meta-analysis, sensitivity analysis, and publication bias analysis.ResultsA total of eight articles, involving 2953 patients, met the inclusion criteria and were included in this meta-analysis. The results showed that patients with higher PIV levels had a significantly shorter OS (HR: 2.045, 95% CI: 1.355-3.086, P = 0.001) and PFS (HR: 1.466, 95% CI: 1.163-1.848, P = 0.001). Besides, the PIV value was negatively correlated with the efficacy of neoadjuvant chemotherapy. Sensitivity analysis showed that the results of this study were reliable and stable.ConclusionsPIV has a good prognostic value in breast cancer patients and is expected to be a prognostic biomarker for breast cancer.

Multi-agent reinforcement learning (MARL) for cooperative tasks has been extensively researched over the past decade. The prevalent framework for MARL algorithms is centralized training and decentralized execution. Q-learning is often employed as a centralized learner. However, it requires finding the maximum value by comparing the Q-value of each joint action a’ in the next state s’ to update the Q-value of the last visited state-action pair (s,a). When the joint action space is extensive, the maximization operation involving comparisons becomes time-consuming and becomes the dominant computational burden of the algorithm. To tackle this issue, we propose an algorithm to reduce the number of comparisons by saving the joint actions with the top 2 Q-values (T2Q). Updating the top 2 Q-values involves seven cases, and the T2Q algorithm can avoid traversing the Q-table to update the Q-value in five of these seven cases, thus alleviating the computational burden. Theoretical analysis demonstrates that the upper bound of the expected ratio of comparisons between T2Q and Q-learning decreases as the number of agents increases. Simulation results from two-stage stochastic games are consistent with the theoretical analysis. Furthermore, the effectiveness of the T2Q algorithm is validated through the distributed sensor network task and the target transportation task. The T2Q algorithm successfully completes both tasks with a 100% success rate and minimal computational overhead.

The traditional Pignistic transformation is limited in the context of “betting”, which faces information loss and is inconvenient for multi-source information fusion. To tackle this challenge, an Enhanced Pignistic transformation is proposed for the first time. New divergence and information volume measures are tailor-made for the enhanced Pignistic probability, and a novel information fusion algorithm is developed. To further prove the fusion algorithm’s advantages in conflict management, it is applied in a new semi-automatic image segmentation scheme. Two uncertain decision-support techniques named adaptive belief assignment and scalable information extraction are raised, and a fuzzy heuristic refinement algorithm is conducted, fulfilling the gap between evidential decision-making and segmentation refinement. Experimental analysis shows the proposed segmentation algorithm is superior on four metrics each and can enhance the robustness of foreground segmentation, indicating the effectiveness of the proposal in solving the decision inaccuracy of evidential segmentation schemes.

Abstract Background The cyclin-dependent kinase 7 (CDK7) inhibitor THZ1 represses multiple cancer cells. However, its tumor-repressive efficiency in wild-type p53 breast cancer cells remains controversial. Methods We conducted various assays, including CCK8, colony formation, flow cytometry, western blotting, and lactate dehydrogenase release detection, to clarify whether p53 elevation sensitizes breast cancer cells to THZ1. Results We found that upregulating functional p53 contributes to the increased sensitivity of breast cancer cells to THZ1. Increased THZ1 sensitivity requires active p53 and an intact p53 pathway, which was confirmed by introducing exogenous wild-type p53 and the subsequent elevation of THZ1-mediated tumor suppression in breast cancer cells carrying mutant p53. We confirmed that p53 accumulates in the nucleus and mitochondria during cell death. Furthermore, we identified extensive transcriptional disruption, rather than solely CDK7 inhibition, as the mechanism underlying the nutlin-3 and THZ1-induced death of breast cancer cells. Finally, we observed the combined nutlin-3 and THZ1 treatment amplified gasdermin E cleavage. Conclusion Enhanced sensitivity of breast cancer cells to THZ1 can be achieved by increasing effective p53 expression. Our approach may serve as a potential treatment for patients with breast cancer resistant to regular therapies. Video Abstract

Abstract A thorough interrogation of the immune landscape is crucial for immunotherapy strategy selection and prediction of clinical responses in non-small-cell lung cancer (NSCLC) patients. Single-cell RNA sequencing (scRNA-seq) techniques have prompted the opportunity to dissect the distinct immune signatures between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), the two major subtypes of NSCLC. Here, we performed scRNA-seq on 72,475 immune cells from 40 samples of tumor and matched adjacent normal tissues spanning 19 NSCLC patients, and drew a systematic immune cell transcriptome atlas. Joint analyses of the distinct cellular compositions, differentially expressed genes (DEGs), cell–cell interactions, pseudotime trajectory, transcriptomic factors and prognostic factors based on The Cancer Genome Atlas (TCGA), revealed the central roles of cytotoxic and effector T and NK cells and the distinct functional macrophages (Mφ) subtypes in the immune microenvironment heterogeneity between LUAD and LUSC. The dominant subtype of Mφ was FABP4-Mφ in LUAD and SPP1-Mφ in LUSC. Importantly, we identified a novel lymphocyte-related Mφ cluster, which we named SELENOP-Mφ, and further established its antitumor role in both types, especially in LUAD. Our comprehensive depiction of the immune heterogeneity and definition of Mφ clusters could help design personalized treatment for lung cancer patients in clinical practice.

Recently, object detection has become a research hotspot in computer vision, which often detects regular images with small viewing angles. In order to obtain a field of view without blind spots, fisheye cameras, which have distortions and discontinuities, have come into use. The fisheye camera, which has a wide viewing angle, and an unmanned aerial vehicle equipped with a fisheye camera are used to obtain a field of view without blind spots. However, distorted and discontinuous objects appear in the captured fisheye images due to the unique viewing angle of fisheye cameras. It poses a significant challenge to some existing object detectors. To solve this problem, this paper proposes a PGDS-YOLOv8s model to solve the issue of detecting distorted and discontinuous objects in fisheye images. First, two novel downsampling modules are proposed. Among them, the Max Pooling and Ghost’s Downsampling (MPGD) module effectively extracts the essential feature information of distorted and discontinuous objects. The Average Pooling and Ghost’s Downsampling (APGD) module acquires rich global features and reduces the feature loss of distorted and discontinuous objects. In addition, the proposed C2fs module uses Squeeze-and-Excitation (SE) blocks to model the interdependence of the channels to acquire richer gradient flow information about the features. The C2fs module provides a better understanding of the contextual information in fisheye images. Subsequently, an SE block is added after the Spatial Pyramid Pooling Fast (SPPF), thus improving the model’s ability to capture features of distorted, discontinuous objects. Moreover, the UAV-360 dataset is created for object detection in fisheye images. Finally, experiments show that the proposed PGDS-YOLOv8s model on the VOC-360 dataset improves mAP@0.5 by 19.8% and mAP@0.5:0.95 by 27.5% compared to the original YOLOv8s model. In addition, the improved model on the UAV-360 dataset achieves 89.0% for mAP@0.5 and 60.5% for mAP@0.5:0.95. Furthermore, on the MS-COCO 2017 dataset, the PGDS-YOLOv8s model improved AP by 1.4%, AP50 by 1.7%, and AP75 by 1.2% compared with the original YOLOv8s model.

Background: There is increasing evidence that long non-coding RNAs (lncRNAs) can be used as potential prognostic factors for cancer. This study aimed to develop a prognostic model for lung adenocarcinoma (LUAD) using angiogenesis-related long non-coding RNAs (lncRNAs) as potential prognostic factors.Methods: Transcriptome data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify aberrantly expressed angiogenesis-related lncRNAs in LUAD. A prognostic signature was constructed using differential expression analysis, overlap analysis, Pearson correlation analysis, and Cox regression analysis. The model’s validity was assessed using K-M and ROC curves, and independent external validation was performed in the GSE30219 dataset. Prognostic lncRNA-microRNA (miRNA)-messenger RNA (mRNA) competing endogenous RNA (ceRNA) networks were identified. Immune cell infiltration and mutational characteristics were also analyzed. The expression of four human angiogenesis-associated lncRNAs was quantified using quantitative real-time PCR (qRT-PCR) gene arrays.Results: A total of 26 aberrantly expressed angiogenesis-related lncRNAs in LUAD were identified, and a Cox risk model based on LINC00857, RBPMS-AS1, SYNPR-AS1, and LINC00460 was constructed, which may be an independent prognostic predictor for LUAD. The low-risk group had a significant better prognosis and was associated with a higher abundance of resting immune cells and a lower expression of immune checkpoint molecules. Moreover, 105 ceRNA mechanisms were predicted based on the four prognostic lncRNAs. qRT-PCR results showed that LINC00857, SYNPR-AS1, and LINC00460 were significantly highly expressed in tumor tissues, while RBPMS-AS1 was highly expressed in paracancerous tissues.Conclusion: The four angiogenesis-related lncRNAs identified in this study could serve as a promising prognostic biomarker for LUAD patients.

Microorganisms are found in diverse communities whose structure and function are determined by interspecific interactions. Just as single species seldom exist in isolation, communities as a whole are also constantly challenged and affected by external species. Though much work has been done on characterizing how individual species affect each other through pairwise interactions, the joint effects of multiple species on a single (focal) species remain underexplored. As such, it is still unclear how single-species effects combine to a community-level effect on a species of interest. To explore this relationship, we assayed thousands of communities of two, three, and four bacterial species, measuring the effect of single, pairs of, and trios of 61 affecting species on six different focal species. We found that when multiple species each have a negative effect on a focal species, their joint effect is typically not given by the sum of the effects of individual affecting species. Rather, they are dominated by the strongest individual-species effect. Therefore, while joint effects of multiple species are often non-additive, they can still be derived from the effects of individual species, making it plausible to map complex interaction networks based on pairwise measurements. This finding is important for understanding the fate of species introduced into an occupied environment and is relevant for applications in medicine and agriculture, such as probiotics and biocontrol agents, as well as for ecological questions surrounding migrating and invasive species.

Head pose estimation (HPE) is a key step in computation and quantification of 3D facial features and has a significant impact on the precision and accuracy of measurements. High-precision HPE is the basis for standardized facial data collection and analysis. The Camper’s plane is the standard (baseline) plane commonly used by anthropologists for head and face research, but there is no research on automatic positioning of the Camper’s plane using color and depth cameras. This paper presents a high-accuracy method for Camper’s plane localization and HPE based on multi-view RGBD depth sensors. The 3D facial point clouds acquired by the multi-view RGBD depth sensors are aligned to obtain a complete 3D face. Keypoint RCNN is used for facial keypoint detection to obtain facial landmarks. A method is proposed to build a general face datum model based on a self-built dataset. The head pose is estimated by applying rigid body transformation to an individual 3D face and the general 3D face model. In order to verify the accuracy of Camper’s plane localization and HPE, 102 cases of 3D facial data and experiments were collected and conducted. The tragus and nasal alar points are localized to within 7 pixels (about 0.83 cm) and the average accuracy of the three dimensions of Camper’s plane identified is 0.87°, 0.64° and 0.47° respectively. The average accuracies of the three dimensions of HPE were 1.17°, 0.90° and 0.97. The experiment results demonstrate the effectiveness of the method for Camper’s plane localization and HPE.

Anthocyanins, a class of flavonoid compounds that provide pigmentation to plant organs, are beneficial components of the human diet and there is an interest in understanding the regulation of their formation in crop plants. The apple cultivar ‘May’ represents an excellent model for the study of anthocyanin metabolism due to the spatial color pattern of its flesh, which transitions sequentially from red to white to red again, from the outside to the inside of the apple fruit. To screen the transcription factors involved in the anthocyanin pathway, transcriptomes from differently colored sections of ‘May’ fruits were analyzed by RNA sequencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to analyse the gene expression data. The results suggested differentially expressed genes (DEGs) that are related to phytohormones are involved in regulating anthocyanin biosynthesis. K-means clustering analysis revealed 167 common DEGs between different sections of fruit with the same expression pattern as candidates for regulating anthocyanin synthesis. Further analysis showed that nine of the 167 DEGs were annotated as transcription factors and quantitative real time PCR (qRT-PCR) confirmed that their expression was obviously higher in red regions of the fruit, consistent with their roles as hub genes that regulate anthocyanin synthesis. This study provides valuable results for future studies of anthocyanin synthesis in apple fruit.

Abstract Lung adenocarcinoma (LUAD) and squamous carcinoma (LUSC) are two major subtypes of non-small cell lung cancer with distinct pathologic features and treatment paradigms. The heterogeneity can be attributed to genetic, transcriptional, and epigenetic parameters. Here, we established a multi-omics atlas, integrating 52 single-cell RNA sequencing and 2342 public bulk RNA sequencing. We investigated their differences in genetic amplification, cellular compositions, and expression modules. We revealed that LUAD and LUSC contained amplifications occurring selectively in subclusters of AT2 and basal cells, and had distinct cellular composition modules associated with poor survival of lung cancer. Malignant and stage-specific gene analyses further uncovered critical transcription factors and genes in tumor progression. Moreover, we identified subclusters with proliferating and differentiating properties in AT2 and basal cells. Overexpression assays of ten genes, including sub-cluster markers AQP5 and KPNA2, further indicated their functional roles, providing potential targets for early diagnosis and treatment in lung cancer.

This study constructs a two-echelon low-carbon supply chain consisting of a single manufacturer and a retailer. The manufacturer’s initial capital is zero. The study analyzes three financing modes of the manufacturer by using the Stackelberg game model: external financing (the EF mode), internal financing (the IF mode), and trade credit financing (the TC mode). We found that the IF mode is superior to the EF mode while inferior to the TC mode regarding carbon emission reduction (CER), market demand, and the manufacturer’s profit. Additionally, the IF mode is superior to the EF mode regarding the retailer and supply chain’s profits and special to the TC mode only when the loan and deposit interest rate meet the specific conditions. The best financing mode for the manufacturer is the TC mode, but he needs to give some compensation to the retailer in order to make the retailer cooperate with him. The impact of carbon tax rate changes on the equilibrium solutions in the three financing modes is not only related to the change range of the carbon tax rate itself but also closely related to the initial carbon emissions. A high carbon tax rate can help stimulate the cleaner manufacturer to reduce carbon emissions, but a moderate carbon tax rate is more applicable to the polluting manufacturer. A numerical example is given to demonstrate some of the conclusions. Finally, the study provides managerial insights based on the analytical results.

Different biochars have diverse properties, with ambiguous effects on soil nematodes. This study investigated how aspen sawdust (ABC), bamboo powder (BBC), maize straw (MBC) and peanut-shell biochars (PBC) affected Caenorhabditis elegans via culture assays and RNA-seq analysis. The results showed that biochars derived from different agricultural materials varied significantly in physicochemical properties, and PBC produced more volatile organic compounds (VOCs) to attract C. elegans than ABC, BBC and MBC. Moreover, worms in ABC experienced the worst outcomes, while worms in PBC experienced milder impacts. Nematode body length decreased to 724.6 μm, 784.0 μm and 799.7 μm on average in ABC, BBC and MBC, respectively, compared to the control (1052 μm) and PBC treatments (960 μm). The brood size in ABC, MBC, BBC and PBC decreased 41.1%, 39.4%, 39.2% and 19.1% compared to the control, respectively. Furthermore, the molecular mechanisms of biochar-induced developmental effects on C. elegans were explored. Although several differentially expressed genes (DEGs) were different among the four biochars, worm phenotypic changes were mainly related to col genes (col-129; col-140; col-40; col-184), bli-6, sqt-3, perm-2/4, cdk-8, daf-16 and sod-1/2/5, which are associated with cuticle collagen synthesis, eggshell formation in postembryonic growth and rhythmic processes. Our study suggests that different properties of biochars could be crucial to soil nematodes, as well as the worms' biochemical changes are important for the health in agriculture soil.

Agaricus bisporus growth alters the lignocellulosic composition and structure of compost. However, it is difficult to differentiate the enzyme activities of A. bisporus mycelia from the wider microbial community owing to the complication of completely speareting the mycelia from compost cultures. Macrogenomics analysis was employed in this study to examine the fermentation substrate of A. bisporus before and after mycelial growth, and the molecular mechanism of substrate utilization by A. bisporus mycelia was elucidated from the perspective of microbial communities and CAZymes in the substrate. The results showed that the relative abundance of A. bisporus mycelia increased by 77.57-fold after mycelial colonization, the laccase content was significantly increased and the lignin content was significantly decreased. Analysis of the CAZymes showed that AA10 family was extremely differentiated. Laccase-producing strains associated with AA10 family were mostly bacteria belonging to Thermobifida and Thermostaphylospora, suggesting that these bacteria may play a synergistic role in lignin decomposition along with A. bisporus mycelia. These findings provide preliminary evidence for the molecular mechanism of compost utilization by A. bisporus mycelia and offer a reference for the development and utilization of strains related to lignocellulose degradation.

Classroom teaching is a kind of social activity system. Thus, as a form of classroom learning, collaborative problem solving has a strong social attribute. It is extremely common to choose the conflict discourse in the context of cooperation. The verbal characteristics of the conflicting discourse level in cooperative mathematics problem solving directly affects the cooperative learning between students and the classroom teaching of teachers. This article focuses on the overall linguistic characteristics of conflict discourse in solving cooperative problems and the discourse style and language characteristics of the three stages of conflict discourse. The main research conclusions are as follows: (1) The classification of language features of conflict discourse includes extreme summaries, negation, discourse markers, and so on. Among them, the frequency of Indexical 2nd-person pronouns is the highest. (2) The language expressions at the “initial stage of conflict” include Explanatory statement Negative response, instruct refuse and Seditious inquiry Confrontational answer. The language shows the characteristics of using emphatic words or phrases, negative words, imperative sentences and so on. Meanwhile, rebuttal questions, direct responses, explanations, and negative avoidance are the main forms language expressions at the “conflict stage.” It also exhibits the verbal characteristics of rhetorical questions, negative comments, and direct negation. Lastly, topic-shifting, compromise, third-party intervention, and one-sided wins are the linguistic expressions at the “end of conflict.” The language features are the appearance of tone relaxation and language easing, and the conflict ending utterances reflect cooperation.

Alkaline stress severely limits plant growth and yield worldwide. NF-YC transcription factors (TFs) respond to abiotic stress by activating gene expression. However, the biological function of NF-YC TFs in alfalfa (Medicago sativa L.) is not clear. In our study, an NF-YC2 gene was identified and transgenic plants were obtained by constructing overexpression vector and cotyledon node transformation system in alfalfa. The open reading frame of MsNF-YC2 is 879 bp with 32.4 kDa molecular mass. MsNF-YC2 showed tissue expression specificity and was induced by a variety of abiotic stresses including drought, salt, and alkali stress in alfalfa. Under alkali stress treatment, transgenic plants exhibited higher levels of antioxidant enzyme activities and proline (Pro), correlating with a lower levels of hydrogen peroxide (H2O2), superoxide anion (O2–) compared with wild-type (WT) plants. Transcriptomic results showed that overexpression of MsNF-YC2 regulated the expression of phytohormone signal transduction and photosynthesis-related genes under normal and alkaline stress treatments. These results suggest that the MsNF-YC2 gene plays crucial role enhance alkali adaptation abilities in alfalfa.

In this paper, a novel plasmonic all-optical half-subtractor and full-subtractor are designed for optical computing. The structure of plasmonic subtractors consists of a metal–insulator–metal (MIM) waveguide and rectangular ring resonators covered by a graphene layer. Due to the nonlinear optical properties of graphene, the states of the plasmonic resonators can be controlled by the pump intensity of a pump beam focused on the graphene layer. The resonators can work as all-optical switches with an ultra-fast response time to constitute optical logic devices according to the directed logic mechanism. A finite-difference time-domain method is utilized to numerically investigate the transmission of the output signals which represent the results of subtraction operations. Simulation results obtained indicate that the proposed plasmonic devices have the ability to implement half-subtraction and full-subtraction with a small feature size and fast response time, and provide a new concept and method for the design and realization of optical computing devices.

Objective Zearalenone (ZEA) has estrogen-like effects. Our previous study has shown that ZEA (0.5 to 1.5 mg/kg) could induce abnormal uterine proliferation through transforming growth factor signaling pathway. To further study the other regulatory networks of uterine hypertrophy caused by ZEA, the potential mechanism of ZEA on porcine endometrial epithelial cells (PECs) was explored by the Illumina Hiseq 2000 sequencing system. Methods The PECs were treated with ZEA at 0 (ZEA0), 5 (ZEA5), 20 (ZEA20), and 80 (ZEA80) μmol/L for 24 h. The collected cells were subjected to cell cycle, RNA-seq, real-time quantitative polymerase chain reaction, immunofluorescence, and western blot analysis. Results The proportion of cells in the S and G2 phases decreased (p

ObjectiveTo observe the clinical effect and adverse reactions of perampanel in the treatment of epilepsy in children.MethodsA retrospective analysis was performed on 83 children with epilepsy who were treated with perampanel in the Department of Pediatric Neurology, Second Affiliated Hospital of Xi'an Jiaotong University from April to August 2021. The treatment status, prognosis and adverse reactions were followed up. The effective rates of different age groups, different seizure types and epilepsy syndromes, and different treatment methods were statistically analyzed. The effective rate and adverse reactions of all patients were statistically analyzed.ResultsThe overall effective rate of perampanel in the treatment of epilepsy was 62.03%, and there was no significant difference in the effective rate of perampanel in the treatment of epilepsy in patients of different ages (P > 0.05). The effective rates of perampanel in the treatment of focal seizures and generalized seizures were 60.38% and 65.38%, and the effective rates of benign childhood epilepsy with centrotemporal spikes (BECT), BECT combined with electrical status epilepticus during sleep (ESES) and frontal lobe epilepsy (FLE) were 88.89, 72.73, and 66.67%. The effective rates of monotherapy and combination therapy were 88.88 and 58.57%, respectively. The above statistical differences were not statistically significant (P > 0.05). In addition, the adverse reaction rate of perampanel treatment was 16.45%, including irritability, drowsiness, dizziness, nausea, vomiting and abnormal liver function.ConclusionPerampanel has a high efficiency and controllable adverse reactions in the treatment of childhood epilepsy. This drug can be used as a reliable choice for long-term use in the treatment of epilepsy in children.

Biomacromolecule drugs of nucleic acids and proteins/peptides have occupied growing share of global pharmaceutical market, but their biomedical application faces substantial challenges in lacking of safe and effective delivery vehicles due to the high molecular weight and the sensitive structure. Because of the unique physicochemical and biological properties of hydrophobicity and lipophobicity, superior assembly performance, desirable chemical stability, and biological inertness, fluoropolymers are a modular solution to these problems as an ideal delivery vehicle of biomacromolecules. In the review, we discuss how to endow the polymer with “fluorine magic” as fluoropolymers and summarized the recent advances of fluoropolymers specifically tailored to the delivery challenges of biomacromolecule drugs, including stability, serum tolerance, membrane permeability, endosomal escape of nucleic acids and intercellular delivery of proteins/peptides. Moreover, this work concludes the application of fluoropolymers-mediated biomacromolecule drug delivery in cancer therapy. Finally, we discuss the opportunities, challenges and further perspectives of fluoropolymers for the delivery of biomacromolecule drugs, aiming to facilitate further development of fluoropolymers in biomedical application.

In this work, a series of chitosan (CS)-grafted carbon oxynitride (OCN) nanoparticles (denoted as CS-OCN) were successfully synthesized for the first time by thermal polycondensation and subsequent esterification. The structure and photocatalytic performance of CS-OCN nanoparticles were investigated. The XPS spectra of CS-OCN-3 showed the presence of amino bonds. The optimal photocatalytic degradation efficiency of the synthesized CS-OCN-3 could reach 94.3% within 390 min, while the photocurrent response intensity was about 150% more than that of pure OCN. The improved photocatalytic performance may be mainly attributed to the enhanced photogenerated carrier’s separation and transportation and stronger visible light response after CS grafting. In addition, the inhibition diameter of CS-OCN-3 reached 23 mm against E. coli within 24 h under visible light irradiation, exhibiting excellent photocatalytic bactericidal ability. The results of bacterial inhibition were supported by absorbance measurements (OD600) studies of E. coli. In a word, this work provided a rational design of an efficient novel metal-free photocatalyst to remove bacterial contamination and accelerate the degradation of organic dyes.

Abstract Background The present study aimed to assess the correlation of fibroblast growth factor (FGF)-23 expression with clinical characteristics, then further explore its value in predicting 2-year in-stent restenosis (ISR) risk in coronary heart disease (CHD) patients underwent percutaneous coronary intervention (PCI) with drug-eluting stent (DES). Methods In this prospective, single-center, observational study, totally 214 CHD patients treated by PCI with DES were consecutively recruited, and peripheral blood samples were collected prior to PCI with DES for serum samples isolation. Following, FGF-23 level in the serum samples was detected via enzyme linked-immuno-sorbent Assay. The follow-up coronary angiography was performed at 1 year and 2 years after PCI or if suspected ISR symptoms occurred. Results FGF-23 was positively correlated with fasting blood-glucose, insulin resistance, serum creatinine, serum uric acid, LDL-C, high-sensitivity C-reactive protein, cardiac troponin I and N-terminal-proB-type natriuretic peptide, while was negatively associated with HDL-C and left ventricular ejection fraction (all P 0.05). Moreover, FGF-23 level was higher in 2-year ISR patients (n = 38) compared to 2-year non-ISR patients (n = 176) (P

Optical networks-on-chips (ONoCs) are the key technology for the sustainable development of multiprocessors system-on-chip (MPSoC) in the future. Micro-ring resonators (MRs) are widely used in ONoCs as key device to select and redirect optical signals. However, MRs have the inherent property of being sensitive to environmental temperature. With the fluctuation of environmental temperature, its resonance wavelength drifts, which can introduce more loss and crosstalk noise to ONoCs and make the network performance decline sharply. Therefore, it is very important to analyze the influence of thermal effect in ONoCs to solve this problem. In this paper, the theoretical models of loss and crosstalk noise changing with temperature are established from device level to network level, respectively. And a series of network performances of mesh-based ONoCs caused by thermal effect are systematically modeled and analyzed employing formal methods. Finally, we conduct case studies for mesh-based ONoCs using optimized crossbar optical router and crux optical router to evaluate the proposed method. The simulation results show that the performance of mesh-based ONoCs declines with the increase of temperature, such as the decrease of optical signal-to-noise ratio (OSNR) and the increase of bit error rate (BER), which severely limits the network scalability. The formal analytical models provide a criterion for the performance analysis of thermal effect in ONoCs. In addition, the formal methods have high portability and scalability, and can provide technical support for future research work.

Abstract Background Increasing evidence has revealed the close link between mitochondrial dynamic dysfunction and cancer. MIEF2 (mitochondrial elongation factor 2) is mitochondrial outer membrane protein that functions in the regulation of mitochondrial fission. However, the expression, clinical significance and biological functions of MIEF2 are still largely unclear in human cancers, especially in ovarian cancer (OC). Methods The expression and clinical significance of MIEF2 were determined by qRT-PCR, western blot and immunohistochemistry analyses in tissues and cell lines of OC. The biological functions of MIEF2 in OC were determined by in vitro and in vivo cell growth and metastasis assays. Furthermore, the effect of MIEF2 on metabolic reprogramming of OC was determined by metabolomics and glucose metabolism analyses. Results MIEF2 expression was significantly increased in OC mainly due to the down-regulation of miR-424-5p, which predicts poor survival for patients with OC. Knockdown of MIEF2 significantly suppressed OC cell growth and metastasis both in vitro and in vivo by inhibiting G1-S cell transition, epithelial-to-mesenchymal transition (EMT) and inducing cell apoptosis, while forced expression of MIEF2 had the opposite effects. Mechanistically, mitochondrial fragmentation-suppressed cristae formation and thus glucose metabolism switch from oxidative phosphorylation to glycolysis was found to be involved in the promotion of growth and metastasis by MIEF2 in OC cells. Conclusions MIEF2 plays a critical role in the progression of OC and may serve as a valuable prognostic biomarker and therapeutic target in the treatment of this malignancy.

Loneliness is a growing public health problem that threatens physical and mental health to a large extent. Compelling evidence has shown that premature parental death is strongly associated with many mental health disorders in adulthood, but whether it increases the risk of loneliness remains unclear. In this large community-based study, we included 32,682 adult participants (20–93 years old) from Southwest China and used the three-item short version of University of California, Los Angeles, Loneliness Scale to identify participants with loneliness. A total of 1,975 participants reported loneliness, which resulted in a loneliness prevalence of 6.0% in Southwest China. Logistic regression was used to evaluate the association between early parental death and loneliness after adjusting for age, gender, education level, marital status, smoking and drinking status, living status, and chronic diseases. We found that early parental death was significantly associated with loneliness [odds ratio (OR) = 1.21, 95% confidence interval (CI), 1.03–1.42]. A Sensitivity analysis excluding those with mental health disorders (796 participants) yielded similar results (OR = 1.26, 95% CI = 1.06–1.49). We also found that being younger, single, divorced, or widowed, and more educated; living alone; and having chronic disorders were associated with loneliness. We conclude that childhood parental death is associated with loneliness in adulthood, suggesting the need for early intervention in affected children to prevent long-term adverse neuropsychiatric effects.

Objectives To assess the influence of patent foramen ovale (PFO) on the prevalence of migraine without aura based on propensity score-matched samples in Southwest China.Design Propensity-matched cross-sectional study.Participants Residents over 20 years of age were recruited from 15 communities of Western China from July 2020 to October 2020. A total of 3741 residents having accepted to undergo contrast-transthoracic echocardiography and a standard structured questionnaire was assessed for the relationship between PFO and migraine without aura.Primary and secondary outcome measures The primary outcome measures were the prevalence of migraine without aura across different degrees of right–left shunts.Results A total of 3741 participants were included. Among them, 881 participants were diagnosed with PFO. The prevalence of migraine without aura in the PFO group was 12.83%, significantly higher than the other group (7.83%, p

This article reports on an online collaboration among creative arts therapists (CATs) from the West and East during the emerging worldwide health crisis related to coronavirus. Four women were from China and were in a restrictive quarantine as the crisis was emerging in that country. Three CATs were from Guam, a Pacific island territory of the United States. The other CAT was from New York City. This group met once across several time zones in a ZOOM room. The goal was to develop arts-based communication about their personal subjective experience of the health crisis. Most of the members of the group were new to each other, each other’s languages and culture, and to using the Internet as an avenue for spontaneous expressive communication. The overall purpose of the meeting was to reach out to each other during this unusual and tragic time to develop collaborative metaphor making as a way to understand each other’s experiences. The group used improvised dance, art, poetry, and fairy tale making. The resulting metaphors suggested a complex combination of the feelings related to both the destructiveness of the health crisis as well as the positive feeling of creative connections among those from different countries and cultures in this dramatic time.

Background and objective Thyroid transcription factor-1 (TTF-1) has been widely studied in non-small cell lung cancer, which is considered as an independent prognostic factor in patiens with non-small cell lung cancer. However, there are few studies on the prognostic value of TTF-1 in small cell lung cancer (SCLC). The purpose of this study was to explore the relationship between the expression state of TTF-1 and the sensitivity to first-line chemotherapy and prognosis in patients with SCLC. Methods A retrospective analysis was made on 234 patients with SCLC who were diagnosed and treated in The Affiliated Hospital of Qingdao University and received platinum-based chemotherapy. The clinical characteristics, treatment and survival of the patients were followed up. Chi χ² test and Logistic regression model were used to analyze the relationship between TTF-1 expression and chemotherapy response rate. Kaplan-Meier method and Cox proportional hazard regression model were used to analyze the effect of TTF-1 expression on survival time of patients. Results Among the 234 patients, the positive expression of TTF-1 was 188 cases (80.3%), and the negative expression of TTF-1 was 46 cases (19.7%). The objective response rate (ORR) of first-line chemotherapy in patients with positive expression of TTF-1 was higher than that in patients with negative expression of TTF-1 (70.7% vs 47.8%) (χ²=8.681, P=0.003). Logistic regression multivariate analysis showed that the expression state of TTF-1 was an independent predictor of ORR in first-line chemotherapy (OR=0.216, 95%CI: 0.076-0.615, P=0.004), however this difference was only reflected in LS-SCLC. The median progression free survival (PFS) of patients with negative expression of TTF-1 was shorter than that of patients with positive expression (6.9 months vs 9.0 months) (χ²=9.357, P=0.002). The median OS in TTF-1 negative group was shorter than that in TTF-1 positive group (13.3 months vs 20.1 months)(χ²=12.082, P=0.001). Conclusion TTF-1 expression is an independent predictor of first-line chemotherapy response rate and survival in patients with SCLC, and may become a biomarker to predict the efficacy and prognosis of SCLC.

Abstract Background Non-small cell lung cancer (NSCLC) patients with activating EGFR mutations initially respond to first-generation EGFR inhibitors; however, the efficacy of these drugs is limited by acquired resistance driven by the EGFR T790M mutation. The discovery of third-generation EGFR inhibitors overcoming EGFR T790M and their new resistance mechanisms have attracted much attention. Methods We examined the antitumor activities and potential resistance mechanism of a novel EGFR third-generation inhibitor in vitro and in vivo using ELISA, SRB assay, immunoblotting, flow cytometric analysis, kinase array, qRT-PCR and tumor xenograft models. The clinical effect on a patient was evaluated by computed tomography scan. Results We identified compound ASK120067 as a novel inhibitor of EGFR T790M , with selectivity over EGFR W T . ASK120067 exhibited potent anti-proliferation activity in tumor cells harboring EGFR T790M (NCI-H1975) and sensitizing mutations (PC-9 and HCC827) while showed moderate or weak inhibition in cells expressing EGFR W T . Oral administration of ASK120067 induced tumor regression in NSCLC xenograft models and in a PDX model harboring EGFR T790M . The treatment of one patient with advanced EGFR T790M-positive NSCLC was described as proof of principle. Moreover, we found that hyperphosphorylation of Ack1 and the subsequent activation of antiapoptotic signaling via the AKT pathway contributed to ASK120067 resistance. Concomitant targeting of EGFR and Ack1 effectively overrode the acquired resistance of ASK120067 both in vitro and in vivo. Conclusions Our results idenfity ASK120067 as a promising third-generation EGFR inhibitor and reveal for the first time that Ack1 activation as a novel resistance mechanism to EGFR inhibitors that guide to potential combination strategy.

Abstract Background Retinoblastoma (RB) is the most common intraocular malignancy in children. Long non-coding RNA X-inactive specific transcript (lncRNA XIST) has been reported to be associated with RB, but research on the mechanism of XIST is not well studied. Methods Expressions of XIST, microRNA-140-5p (miR-140-5p), and sex-determining region Y-related high-mobility group box 4 (SOX4) were analyzed by qRT-PCR or Western blot. Relationships of XIST, SOX4, and miR-140-5p were evaluated by dual-luciferase reporter assay and Spearman’s analysis. Cell Counting Kit-8 (CCK-8) and Transwell assay were performed to assess the function of XIST on RB cell proliferation and invasion. Results In RB tissues, XIST and SOX4 expressions were obviously increased, but the miR-140-5p expression was markedly reduced. XIST expression was positively related to SOX4 expression while negatively correlated with miR-140-5p expression, and negative correlation was exhibited between miR-140-5p and SOX4 expression in RB tissues. XIST was confirmed to directly bind to miR-140-5p, and SOX4 was one target of miR-140-5p. XIST knockdown could impede RB cell proliferation and invasion, while miR-140-5p inhibition reversed the effects. In addition, XIST overexpression or miR-140-5p inhibition could abrogate the inhibition of SOX4 silencing on cell proliferation and invasion of RB cells. Conclusions XIST was obviously increased in RB tissues and cells, and XIST inhibition repressed the proliferation and invasion of RB cells by miR-140-5p/SOX4 axis, which may provide new understandings of the XIST molecular mechanism in RB.

Abstract Background Abdominal surgery is common and is associated with severe postoperative pain. The transverse abdominal plane (TAP) block is considered an effective means for pain control in such cases. The quadratus lumborum (QL) block is another option for the management of postoperative pain. The aim of this study was to conduct a meta-analysis and thereby evaluate the efficacy and safety of QL blocks and TAP blocks for pain management after abdominal surgery. Methods We comprehensively searched PubMed, EMBASE, EBSCO, the Cochrane Library, Web of Science and CNKI for randomized controlled trials (RCTs) that compared QL blocks and TAP blocks for pain management in patients undergoing abdominal surgery. All of the data were screened and evaluated by two researchers. RevMan5.3 was adopted for the meta-analysis. Results A total of 8 RCTs involving 564 patients were included. The meta-analysis showed statistically significant differences between the two groups with respect to postoperative pain scores at 2 h (standardized mean difference [Std.MD] = − 1.76; 95% confidence interval [CI] = − 2.63 to − 0.89; p

Named Data Networking (NDN) is a new clean-slate architecture for the future Internet. Efficient content retrieval is the original intention of NDN design. The content retrieval process driven by content consumers in NDN includes the following challenges, consumers do not know whether the content exists and whether the content producer is reliable. Invalid interest packets could cause the occupation of limited network resources and DoS attack problem. To ensure the authenticity and integrity of the data packets, consumers need to pre-configure the trust schema, which is centralized and prone to the single point of failure problem. Blockchain has widespread attention to build trust in a distributed way, and Ethereum is a programmable blockchain, a decentralized smart contract platform. To lighten the burden of consumers, we proposed a Smart Contract-based Trusted Content Retrieval Mechanism (SCTCRM) for NDN in this paper. The mechanism contains a trustworthy information base for content and producers based on smart contracts, and provides content retrieval and name resolution services for content consumers. The purpose of this mechanism is to improve the efficiency and security of content retrieval process. We described the framework and the workflow of SCTCRM, and used Colored Petri Nets to create a formal mathematical model and analyze the security of the mechanism. Finally, the cost of storage and Gas in smart contracts are evaluated through the prototype deployment. From the results, we can see that the proposed mechanism is security and practicality.

BackgroundThe volume of epicardial adipose tissue (EAT) is associated with an increased incidence of cardiovascular disease (CVD); however, only a few studies have examined its effect on the myocardial function of endurance in athletes. The association between the EAT and the variation of myocardial function is still unclear in amateur marathoners. Consequently, by using some sedentary individuals as the control, this study aims to evaluate the correlation between the EAT volume and the myocardial strain in the left and right ventricles of Chinese amateur marathoners by cardiac magnetic resonance (CMR).MethodsA total of 30 amateur marathoners were included as the exercise group and 20 sedentary people as a control group. All participants received the cardiac magnetic resonance (CMR) to measure the left and right ventricular end-diastolic volume, end-systolic volume and volume index, stroke volume and index, cardiac output index, ejection fraction and myocardial mass, the EAT volume, global radial, circumferential, and longi-tudinal strains, and the strain rates of left and right ventricular myocardium.ResultsThere was a significant difference in the EAT volume (EATV) index between the exercise group and the control group (26.82±11.76ml/m2 vs 37.82±17.15ml/m2, P = 0.01). Results from the multivariate linear regression analysis showed that BMI (standardized β = 0.458; P < 0.001) had an independent positive correlation with the EATV index. The EATV index was negatively correlated with the left ventricular global radial strain (GRS) (r = -0.505; P = 0.004) in the exercise group, while it is negatively correlated with right ventricular GRS (r = -0.492; P = 0.027) and positively correlated with global longitudinal strain (GLS) (r = 0.601; P = 0.005) in the control group. In the exercise group, the multivariate linear regression analysis showed that the EATV index (standardized β = -0.429; P = 0.021) was an independent determinant of the left ventricular GRS, and being a male (standardized β = 0.396; P = 0.029) was an independent determinant of the right ventricular GLS.ConclusionThe EATV index is independently correlated with the left ventricular GRS in the amateur Chinese marathoners, also, the amateur marathon reduces the EATV index and increases the left ventricular myocardial mass, which consequently reduces the adverse effects on myocardial function.

Alfalfa is widely grown worldwide as a perennial high-quality legume forage and as a good ecological landcover. The cysteine synthase (CSase) gene family is actively involved in plant growth and development and abiotic stress resistance but has not been systematically investigated in alfalfa. We identified 39 MsCSase genes on 4 chromosomes of the alfalfa genome. Phylogenetic analysis demonstrated that these genes were clustered into six subfamilies, and members of the same subfamily had similar physicochemical properties and sequence structures. Overexpression of the CSase gene in alfalfa increased alkali tolerance. Compared with control plants, the overexpression lines presented higher proline, soluble sugars, and cysteine and reduced glutathione contents and superoxide dismutase and peroxidase activities as well as lower hydrogen peroxide and superoxide anion contents after alkali stress. The relative expression of γ-glutamyl cysteine synthetase gene (a downstream gene of CSase) in the overexpression lines was much higher than that in the control line. The CSase gene enhanced alkalinity tolerance by regulating osmoregulatory substances and improving antioxidant capacity. These results provide a reference for studying the CSase gene family in alfalfa and expanding the alkali tolerance gene resources of forage plants.

First-principles calculations were used to simulate the aggregation of the peroxy chain defect POL and the oxygen vacancy defect ODC(I). Defect aggregation’s electronic structure and optical properties were investigated. The two defects were most likely to accumulate on a 6-membered ring in ortho-position. When the two defects are aggregated, it is discovered that 0.75 ev absorption peaks appear in the near-infrared band, which may be brought on by the addition of oxygen vacancy defect ODC(I). We can draw the conclusion that the absorption peak of the aggregation defect of ODC(I) defect and POL is more prominent in the near infrared region and visible light area than ODC(I) defect and POL defect.