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Abstract Background Myocardial infarction (MI) is a major disease with high morbidity and mortality worldwide. However, existing treatments are far from satisfactory, making the exploration of potent molecular targets more imperative. The E3 ubiquitin ligase RING finger protein 5 (RNF5) has been previously reported to be involved in several diseases by regulating ubiquitination-mediated protein degradation. Nevertheless, few reports have focused on its function in cardiovascular diseases, including MI. Methods In this study, we established RNF5 knockout mice through precise CRISPR-mediated genome editing and utilized left anterior descending coronary artery ligation in 9-11-week-old male C57BL/6 mice. Subsequently, serum biochemical analysis and histopathological examination of heart tissues were performed. Furthermore, we engineered adenoviruses for modulating RNF5 expression and subjected neonatal rat cardiomyocytes to oxygen-glucose deprivation (OGD) to mimic ischemic conditions, demonstrating the impact of RNF5 manipulation on cellular viability. Gene and protein expression analysis provided insights into the molecular mechanisms. Statistical methods were rigorously employed to assess the significance of experimental findings. Results We found RNF5 was downregulated in infarcted heart tissue of mice and NRCMs subjected to OGD treatment. RNF5 knockout in mice resulted in exacerbated heart dysfunction, more severe inflammatory responses, and increased apoptosis after MI surgery. In vitro, RNF5 knockdown exacerbated the OGD-induced decline in cell activity, increased apoptosis, while RNF5 overexpression had the opposite effect. Mechanistically, it was proven that the kinase cascade initiated by apoptosis signal-regulating kinase 1 (ASK1) activation was closely regulated by RNF5 and mediated RNF5’s protective function during MI. Conclusions We demonstrated the protective effect of RNF5 on myocardial infarction and its function was dependent on inhibiting the activation of ASK1, which adds a new regulatory component to the myocardial infarction associated network and promises to enable new therapeutic strategy.

Information on vegetation dynamics is important for agricultural and ecological management. However, a systematic framework for the study of vegetation dynamics is still lacking. Therefore, this study developed the Vegetation Dynamic Change And Land Cover (VDCALC) framework to achieve a comprehensive analysis of vegetation dynamic change. The framework uses the Normalized Difference Vegetation Index (NDVI) data derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) and Global Inventory Modeling and Mapping Studies (GIMMS), along with land cover data as input. It combines several models, including the Theil-Sen median, Mann-Kendall test and coefficient of variation, which can qualitatively and quantitatively study the spatiotemporal dynamic change of vegetation, and Hurst exponent model, which was used to predict the future change. Meteorological and statistical data were used as auxiliary data in this framework to analyze the influencing factors of vegetation change. Results showed that the degradation area was mainly concentrated in the coastal areas of the peninsula, Rizhao, Weifang, Linyi and Zibo during the period from 2001 to 2015, accounting for 36.05%. Based on annual-scale data, the NDVI showed an overall improvement trend, with significant increases in spring and autumn. However, predictions indicated that the degraded area would account for 37.18% in the future. In addition, meteorological factors were found to influence vegetation growth differently depending on the season. This study demonstrated a complete and reliable framework for effectively reflecting regional vegetation changes. It is recommended for application in large-scale areas to guide agricultural and ecological management.

In the absence of any hazardous substances, colloidal gold nanoparticles (AuNPs) were synthesized through the reduction and stabilization of corresponding metal cations by a simple Eucommia ulmoides bark extract (EUBE). Employing these AuNPs as catalysts, at least ten distinct azo compounds were catalyzed and analyzed. The findings reveal outstanding catalytic performance across a diverse range of azo dyes, regardless of structural complexity, the count of azo bonds, the presence of various functional groups in the side chains, differences in molecular weight, degrees of water solubility, ionic characteristics of the dyes, and the particular class of dyes, whether reactive or acidic. Regardless of these varieties, azo dyes achieved over 90% degradation within 16 min, following a first-order pseudo-kinetic reaction. This report systematically explains the mechanics of AuNPs synthesis using EUBE and the step-by-step azo dye degradation. It signifies an advancement in azo-contaminated wastewater treatment, transcending the varied types and structural complexities of azo compounds.

The eco-friendly synthesis of palladium nanoparticles (PdNPs) utilizing plant phytochemicals has demonstrated its efficacy as a nano-catalyst for azo dye degradation. However, the catalytic prowess of these nanoparticles has been predominantly explored on specific model compounds. Consequently, a fundamental inquiry arises: Can these nanoparticles uniformly catalyze a spectrum of diverse azo dyes, irrespective of structural intricacies, azo bond quantity, side-chain functional groups, molecular weight (Mw) fluctuations, water solubility gradients, ionic characteristics, and dye classification (reactive or acid)? To address this comprehensively, nine azo compounds, encompassing the aforementioned criteria, were systematically chosen for catalysis utilizing the synthesized PdNPs. The synthesized particles were spherical (∼10.5 nm in diameter) with highly crystalline surfaces (d-spacing of 0.194–0.224 nm) and have a uniform size distribution. Employing green chemistry principles and Eucommia ulmoides bark extract (EUBE), this synthesis exhibits exceptional catalytic efficiency across a varied array of azo dyes, achieving degradation rates of up to 99% within 1–5 minutes. This methodical exploration offers a holistic understanding of the catalytic capabilities of PdNPs, shedding light on their potential applicability across a diverse spectrum of azo compounds, thereby propelling advancements in the field.

Biological macromolecules, encompassing plant phytochemicals, biopolymers, and polysaccharides, are validated for simultaneous metal cation reduction and their stabilization for metal nanoparticles (NPs) through green synthesis. The application of these biosynthesized NPs in azo dye catalysis is established but limited to specific model compounds. The fundamental question emerges: Do these NPs uniformly catalyze across diverse azo dyes, disregarding structural complexity, azo bond count, side chain functional groups, molecular weight (Mw) variations, water solubility levels, ionic nature, and dye class (reactive or acid)? To comprehensively investigate, nine azo compounds meeting the aforementioned criteria were chosen for catalysis using synthesized silver NPs (AgNPs). This synthesis employs Eucommia ulmoides bark extract (EUBE) within green chemistry principles. The synthesized AgNPs, predominantly spherical and nano-sized (5–14 nm) with uniform distribution and a highly crystalline surface, are securely stabilized by a thin membrane of EUBE phytochemicals, exhibiting no agglomeration. It yields outstanding catalytic performance on a diverse group of azo dyes, achieving up to 100% degradation within 1–16 min. The reaction adheres to a pseudo-kinetic first-order mechanism. This systematic approach provides a comprehensive insight into the catalytic prowess of AgNPs, elucidating their potential across a diverse range of azo compounds, thereby advancing knowledge in the field.

BackgroundGiven the lack of research on disulfidptosis, our study aimed to dissect its role in pan-cancer and explore the crosstalk between disulfidptosis and cancer immunity.MethodsBased on TCGA, ICGC, CGGA, GSE30219, GSE31210, GSE37745, GSE50081, GSE22138, GSE41613, univariate Cox regression, LASSO regression, and multivariate Cox regression were used to construct the rough gene signature based on disulfidptosis for each type of cancer. SsGSEA and Cibersort, followed by correlation analysis, were harnessed to explore the linkage between disulfidptosis and cancer immunity. Weighted correlation network analysis (WGCNA) and Machine learning were utilized to make a refined prognosis model for pan-cancer. In particular, a customized, enhanced prognosis model was made for glioma. The siRNA transfection, FACS, ELISA, etc., were employed to validate the function of c-MET.ResultsThe expression comparison of the disulfidptosis-related genes (DRGs) between tumor and nontumor tissues implied a significant difference in most cancers. The correlation between disulfidptosis and immune cell infiltration, including T cell exhaustion (Tex), was evident, especially in glioma. The 7-gene signature was constructed as the rough model for the glioma prognosis. A pan-cancer suitable DSP clustering was made and validated to predict the prognosis. Furthermore, two DSP groups were defined by machine learning to predict the survival and immune therapy response in glioma, which was validated in CGGA. PD-L1 and other immune pathways were highly enriched in the core blue gene module from WGCNA. Among them, c-MET was validated as a tumor driver gene and JAK3-STAT3-PD-L1/PD1 regulator in glioma and T cells. Specifically, the down-regulation of c-MET decreased the proportion of PD1+ CD8+ T cells.ConclusionTo summarize, we dissected the roles of DRGs in the prognosis and their relationship with immunity in pan-cancer. A general prognosis model based on machine learning was constructed for pan-cancer and validated by external datasets with a consistent result. In particular, a survival-predicting model was made specifically for patients with glioma to predict its survival and immune response to ICIs. C-MET was screened and validated for its tumor driver gene and immune regulation function (inducing t-cell exhaustion) in glioma.

Abstract Background The lower limb mechanical axis was used to assess the severity of knee osteoarthritis (KOA) with varus/valgus deformity and the accuracy of targeted lower limb alignment correction after operation by conventional X-rays. There are lots of parameters to assess the gait in elder patients such as velocity, stride length, step width and swing/stance ratio by knee joint movement analysis system. However, the correlation between the lower limb mechanical axis and gait parameters is not clear. This study is aimed at obtaining the accuracy of the lower limb mechanical axis by the knee joint movement analysis system and the correlation between the lower limb mechanical axis and gait parameters. Methods We analysed 3D knee kinematics during ground gait of 99 patients with KOA and 80 patients 6 months after the operations with the vivo infrared navigation 3D portable knee joint movement analysis system (Opti-Knee®, Innomotion Inc, Shanghai, China). The HKA (Hip-Knee-Ankle) value was calculated and compared to X-ray findings. Results HKA absolute variation after the operation was 0.83 ± 3.76°, which is lower than that before the operation (5.41 ± 6.20°, p = 0.001) and also lower than the entire cohort (3.36 ± 5.72). Throughout the cohort, a significant correlation with low coefficients (r = -0.19, p = 0.01) between HKA value and anterior-posterior displacement was found. In comparing the HKA values measured on the full-length alignment radiographs and 3D knee joint movement analysis system (Opti-Knee), there was a significant correlation with moderate to high coefficients (r = 0.784 to 0.976). The linear correlation analysis showed that there was a significant correlation between the values of HKA measured by X-ray and movement analysis system (R2 = 0.90, p

This article focuses on two methods employed in the selection, interpretation, and representation of diverse source materials for developing alternative biographies for my ancestral landscape - Nanhai district in the Pearl River Delta in southern China. These biographies aim to approach Nanhai from a long view of continual transformation, as opposed to prevalent readings of the region that focus on the striking spatial contrasts and large-scale developments that have only come about in recent decades. The chronological reading explores a critical shift in the cosmological understanding of the landscape situated in the 19th century through a selection of historical gazetteer maps, while in the excavational reading the diffuse continuity of the lineage in the present-day landscape of Nanhai is traced. In both methods, the drawing functions as a crucial (research) tool to engage the range of source materials.

Starting from the theoretical mechanism of the impact of financial agglomeration on regional green innovation efficiency, and using panel data from 30 provinces in China from 2009 to 2017, this study calculates a financial agglomeration index and green innovation efficiency applying principal component analysis and the slacks-based measure (SBM) of super-efficiency. The study then constructs static and dynamic spatial Durbin models using two different spatial weight matrices to empirically test the spatial spillover effect of financial agglomeration on regional green innovation efficiency. The results reveal a significant positive spatial correlation between China's inter-provincial green innovation efficiency and financial agglomeration. Both static and dynamic models demonstrate that financial agglomeration has a significant spatial spillover effect on the green innovation efficiency of adjacent provinces, but the static model overestimates the impact of spatial spillover. In addition, human capital level, technology market activity, and environmental regulation all have significant positive impacts on the green innovation efficiency of provinces and adjacent provinces.

The T2/RNase gene family is widespread in eukaryotes, and particular members of this family play critical roles in the gametophytic self-incompatibility (GSI) system in plants. Wild diploid strawberry (Fragaria) species have diversified their sexual systems via self-incompatible and self-compatible traits, yet how these traits evolved in Fragaria remains elusive. By integrating the published and de novo assembled genomes and the newly generated RNA-seq data, members of the RNase T2 gene family were systematically identified in six Fragaria species, including three self-incompatible species (Fragaria nipponica, Fragaria nubicola, and Fragaria viridis) and three self-compatible species (Fragaria nilgerrensis, Fragaria vesca, and Fragaria iinumae). In total, 115 RNase T2 genes were identified in the six Fragaria genomes and can be classified into three classes (I–III) according to phylogenetic analysis. The identified RNase T2 genes could be divided into 22 homologous gene sets according to amino acid sequence similarity and phylogenetic and syntenic relationships. We found that extensive gene loss and pseudogenization coupled with small-scale duplications mainly accounted for variations in the RNase T2 gene numbers in Fragaria. Multiple copies of homologous genes were mainly generated from tandem and segmental duplication events. Furthermore, we newly identified five S-RNase genes in three self-incompatible Fragaria genomes, including two in F. nipponica, two in F. viridis, and one in F. nubicola, which fit for typical features of a pistil determinant, including highly pistil-specific expression, highly polymorphic proteins and alkaline isoelectric point (pI), while no S-RNase genes were found in all three self-compatible Fragaria species. Surprisingly, these T2/S-RNase genes contain at least one large intron (>10 kb). This study revealed that the rapid evolution of T2/S-RNase genes within the Fragaria genus could be associated with its sexual mode, and repeated evolution of the self-compatible traits in Fragaria was convergent via losses of S-RNase.

Abstract Background To explore the correlation of tumor necrosis factor-α-induced protein 8-like protein 3 (TIPE3) expressions in colorectal cancer (CRC) with tumor-immune infiltration and patient prognosis. Methods Formalin-fixed paraffin-embedded tumor samples from CRC patients (n = 110) were used in this study. Immunohistochemistry staining of TIPE3 and three prognostic immune biomarkers (CD8, CD20, and CD66b) was conducted in the tumor tissues and adjacent normal tissues. A Cox regression analysis of univariate and multivariate variables was performed to assess the correlation between TIPE3 and patient prognosis. Result We found that TIPE3 was mainly expressed in the cytoplasm, with a small amount in the nucleus. The expression of TIPE3 in tumor tissues is significantly higher than in adjacent normal tissues, and it is significantly correlated with the survival rate of patients in tumor tissues (p = 0.0038) and adjacent normal tissues (p

Pigeons have natural advantages in robotics research, including a wide range of activities, low energy consumption, good concealment performance, strong long-distance weight bearing and continuous flight ability, excellent navigation, and spatial cognitive ability, etc. They are typical model animals in the field of animal robot research and have important application value. A hot interdisciplinary research topic and the core content of pigeon robot research, altering pigeon motor behavior using brain stimulation involves multiple disciplines including animal ethology, neuroscience, electronic information technology and artificial intelligence technology, etc. In this paper, we review the progress of altering pigeon motor behavior using brain stimulation from the perspectives of the neural basis and neuro-devices. The recent literature on altering pigeon motor behavior using brain stimulation was investigated first. The neural basis, structure and function of a system to alter pigeon motor behavior using brain stimulation are briefly introduced below. Furthermore, a classified review was carried out based on the representative research achievements in this field in recent years. Our summary and discussion of the related research progress cover five aspects including the control targets, control parameters, control environment, control objectives, and control system. Future directions that need to be further studied are discussed, and the development trend in altering pigeon motor behavior using brain stimulation is projected.

Learning the spatial location associated with visual cues in the environment is crucial for survival. This ability is supported by a distributed interactive network. However, it is not fully understood how the most important task-related brain areas in birds, the hippocampus (Hp) and the nidopallium caudolaterale (NCL), interact in visual–spatial associative learning. To investigate the mechanisms of such coordination, synchrony and causal analysis were applied to the local field potentials of the Hp and NCL of pigeons while performing a visual–spatial associative learning task. The results showed that, over the course of learning, theta-band (4–12 Hz) oscillations in the Hp and NCL became strongly synchronized before the pigeons entered the critical choice platform for turning, with the information flowing preferentially from the Hp to the NCL. The learning process was primarily associated with the increased Hp–NCL interaction of theta rhythm. Meanwhile, the enhanced theta-band Hp–NCL interaction predicted the correct choice, supporting the pigeons’ use of visual cues to guide navigation. These findings provide insight into the dynamics of Hp–NCL interaction during visual–spatial associative learning, serving to reveal the mechanisms of Hp and NCL coordination during the encoding and retrieval of visual–spatial associative memory.

Abstract Background The hippocampus plays an important role to support path planning and adjustment in goal-directed spatial navigation. While we still only have limited knowledge about how do the hippocampal neural activities, especially the functional connectivity patterns, change during the spatial path adjustment. In this study, we measured the behavioural indicators and local field potentials of the pigeon (Columba livia, male and female) during a goal-directed navigational task with the detour paradigm, exploring the changing patterns of the hippocampal functional network connectivity of the bird during the spatial path learning and adjustment. Results Our study demonstrates that the pigeons progressively learned to solve the path adjustment task after the preferred path is blocked suddenly. Behavioural results show that both the total duration and the path lengths pigeons completed the task during the phase of adjustment are significantly longer than those during the acquisition and recovery phases. Furthermore, neural results show that hippocampal functional connectivity selectively changed during path adjustment. Specifically, we identified depressed connectivity in lower bands (delta and theta) and elevated connectivity in higher bands (slow-gamma and fast-gamma). Conclusions These results feature both the behavioural response and neural representation of the avian spatial cognitive learning process, suggesting that the functional disarrangement and reorganization of the connectivity in the avian hippocampus during different phases may contribute to our further understanding of the potential mechanism of path learning and adjustment.

BackgroundImmunogenic cell death (ICD) is a result of immune cell infiltration (ICI)-mediated cell death, which is also a novel acknowledgment to regulate cellular stressor-mediated cell death, including drug therapy and radiotherapy.MethodsIn this study, TCGA and GEO data cohorts were put into artificial intelligence (AI) to identify ICD subtypes, and in vitro experiments were performed.ResultsGene expression, prognosis, tumor immunity, and drug sensitivity showed significance among ICD subgroups, Besides, a 14-gene-based AI model was able to represent the genome-based drug sensitivity prediction, which was further verified in clinical trials. Network analysis revealed that PTPRC was the pivotal gene in regulating drug sensitivity by regulating CD8+ T cell infiltration. Through in vitro experiments, intracellular down-regulation of PTPRC enhanced paclitaxel tolerance in triple breast cancer (TNBC) cell lines. Meanwhile, the expression level of PTPRC was positively correlated with CD8+ T cell infiltration. Furthermore, the down-regulation of PTPRC increased the level of TNBC-derived PD-L1 and IL2.DiscussionICD-based subtype clustering of pan-cancer was helpful to evaluate chemotherapy sensitivity and immune cell infiltration, and PTPRC was a potential target to against drug resistance of breast cancer.

ObjectiveThoracic aortic aneurysm and dissection (TAAD) is a cardiovascular disease with a high mortality rate. Aging is an important risk factor for TAAD. This study explored the relationship between aging and TAAD and investigated the underlying mechanisms, which may contribute to the diagnosis and treatment of TAAD.MethodsHuman aging genes were obtained from the Aging Atlas official website. Various datasets were downloaded from the GEO database:the human TAAD dataset GSE52093 were used for screening differentially expressed genes (DEGs); GSE137869, GSE102397 and GSE153434 were used as validation sets, and GSE9106 was used for diagnostic prediction of receiver operating characteristic (ROC) curves. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and protein–protein interaction (PPI) network analysis were used to screen differentially co-expressed genes from human aging genes and TAAD. Using five methods of the cytoHubba plugin in Cytoscape software (Degree, Closeness, EPC, MNC, Radiality), hub genes were identified from the differentially co-expressed genes. Single-cell RNA sequencing was used to verify the expression levels of hubgenes in different cell types of aortic tissue. ROC curves were used to further screen for diagnostic genes.ResultsA total of 70 differentially co-expressed genes were screened from human aging genes and DEGs in human TAAD dataset GSE52093. GO enrichment analysis revealed that the DEGs played a major role in regulating DNA metabolism and damaged DNA binding. KEGG enrichment analysis revealed enrichment in the longevity regulating pathway, cellular senescence, and HIF-1 signaling pathway. GSEA indicated that the DEGs were concentrated in the cell cycle and aging-related p53 signaling pathway. The five identified hubgenes were MYC, IL6, HIF1A, ESR1, and PTGS2. Single-cell sequencing of the aging rat aorta showed that hubgenes were expressed differently in different types of cells in aortic tissue. Among these five hubgenes, HIF1A and PTGS2 were validated in the aging dataset GSE102397; MYC, HIF1A and ESR1 were validated in the TAAD dataset GSE153434. The combined area under the diagnostic ROC curve (AUC) values for the five hub genes were >0.7 in the testing and training sets of the dataset GSE9106. The combined AUC values of MYC and ESR1 were equal to the combin ed AUC values of the five hub genes.ConclusionThe HIF-1 signaling pathway may play an important role in TAAD and aging. MYC and ESR1 may have diagnostic value for aging-related TAAD.

In recent decades, the application of GIS and RS in archaeological and cultural heritage (ACH) has witnessed a notable surge both in terms of quantity and scope. During the initial implementation period (2016–2021) of the Digital Belt and Road Heritage (DBAR-Heritage) working group, several instances of GIS-RS-based applications in support of cultural heritage conservation have merged. In this paper, in order to discuss the great potential of GIS and RS on the Silk Road, an overview of GIS- and RS-based applications in ACH is first presented. In a substantial portion of the published scientific literature, the identification and comprehension of archaeological sites, the monitoring and risk assessment of cultural heritage, and the management and visualization of cultural heritage data are highlighted. Following this, five illustrative case studies from the DBAR-Heritage working group are presented to exemplify how the integration of GIS and RS serves as key approaches in recognizing and appreciating cultural heritage. These selected case studies showcase the utilization of multi-source data for the identification of linear sites; detailed, refined monitoring and assessment of the Angkor Wat heritage; and the reconstruction of the Silk Road routes. These instances serve as the cornerstone for highlighting current trends in GIS and RS applications in ACH along the Silk Road. These methodologies efficiently integrate multi-source geospatial data and employ multidisciplinary approaches, ultimately furnishing sophisticated and intelligent tools for the exploration and management of archaeological and cultural heritage in the era of Big Earth Data. Subsequently, a comprehensive discussion on the merits and challenges of GIS and RS applications in ACH is presented, followed by an exploration of the current application trends. Finally, the prospects for the widespread application of GIS and RS in ACH along the Silk Road are outlined in accordance with the operational plan of DBAR-Heritage during its second implementation phase.

The role of desmoglein-3 (DSG3) in oncogenesis is unclear. This study aimed to uncover molecular mechanisms through comparative transcriptome analysis in oral cancer cells, defining potential key genes and associated biological processes related to DSG3 expression. Four mRNA libraries of oral squamous carcinoma H413 cell lines were sequenced, and 599 candidate genes exhibited differential expression between DSG3-overexpressing and matched control lines, with 12 genes highly significantly differentially expressed, including 9 upregulated and 3 downregulated. Genes with known implications in cancer, such as MMP-13, KRT84, OLFM4, GJA1, AMOT and ADAMTS1, were strongly linked to DSG3 overexpression. Gene ontology analysis indicated that the DSG3-associated candidate gene products participate in crucial cellular processes such as junction assembly, focal adhesion, extracellular matrix formation, intermediate filament organisation and keratinocyte differentiation. Validation of RNA-Seq was performed through RT-qPCR, Western blotting and immunofluorescence analyses. Furthermore, using transmission electron microscopy, we meticulously examined desmosome morphology and revealed a slightly immature desmosome structure in DSG3-overexpressing cells compared to controls. No changes in desmosome frequency and diameter were observed between the two conditions. This study underscores intricate and multifaceted alterations associated with DSG3 in oral squamous carcinoma cells, implying a potential oncogenic role of this gene in biological processes that enable cell communication, motility and survival.

Hydrogen is considered a future energy carrier for clean and sustainable technology. Photocatalytic reforming of methanol produced hydrogen using water and energy from sunlight. This study reported enhanced activity of TiO2 without metal co-catalyst for hydrogen production following H2O2 exfoliation. TiO2 was transformed into peroxo-titania species on the outer layer of the particles, resulting in surface exfoliation. The exfoliation reduced TiO2 crystallite sizes enhanced the surface hydroxyl group and reduced the band gap to 3.0 eV. Hydrogen production from methanol-water mixtures on the TiO2 after four consecutive exfoliations was measured at 300 µmol, significantly higher than the fresh TiO2 (50 µmol). H2O2 exfoliated TiO2 reduced the pathway for charge migration to the surface. A high concentration of surface hydroxyl group trapped the charge carriers for efficient hydrogen production. Copyright © 2022 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).

Alterations of the Hippo–YAP pathway are potential targets for oral squamous cell carcinoma (OSCC) therapy, but heterogeneity in this pathway could be responsible for therapeutic resistance. We analysed the Hippo–YAP signatures in a cohort of characterised keratinocyte cell lines derived from the mouth floor and buccal mucosa from different stages of OSCC tumour progression and focused on the specific role of YAP on invasive and metastatic potential. We confirmed heterogeneity in the Hippo–YAP pathway in OSCC lines, including overexpression of YAP1, WWTR1 (often referred to as TAZ) and the major Hippo signalling components, as well as the variations in the genes encoding the intercellular anchoring junctional proteins, which could potentially regulate the Hippo pathway. Specifically, desmoglein‐3 (DSG3) exhibited a unique and mutually exclusive regulation of YAP via YAP phosphorylation during the collective migration of OSCC cells. Mechanistically, such regulation was associated with inhibition of phosphorylation of epidermal growth factor receptor (EGFR) (S695/Y1086) and its downstream effectors heat shock protein beta‐1 (Hsp27) (S78/S82) and transcription factor AP‐1 (c‐Jun) (S63), leading to YAP phosphorylation coupled with its cytoplasmic translocation and inactivation. Additionally, OSCC lines displayed distinct phenotypes of YAP dependency or a mixed YAP and TAZ dependency for cell migration and present distinct patterns in YAP abundance and activity, with the latter being associated with YAP nuclear localisation. In conclusion, this study provides evidence for a newly identified paradigm in the Hippo–YAP pathway and suggests a new regulation mechanism involved in the control of collective migration in OSCC cells.

Explosive emission cathodes are extensively used in high power microwave sources. Growing requirements are highlighted in the performance of the explosive emission cathode with the development of the high power microwave technology. In order to improve the emission properties of the graphite cathode, modifications using SiC particles or whiskers are carried out by the in situ chemical vapor reaction method. The experiments demonstrate that SiC whiskers accelerate the explosive emission turn-on speed of the graphite cathode for large field enhancement factors and improve the emission uniformity due to the surface flashover plasma generation mechanism. SiC particles increase the emission capability of the graphite cathode, possibly corresponding to the dielectric properties of SiC particles. These results suggest that the SiC whiskers modified graphite cathode is suitable for applications under low magnetic field and large emission area conditions, while the SiC particles modified graphite cathode has a brighter application prospect in the long-time stable operation.

Abstract. Background:. Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia. Methods:. This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high- risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years. Results:. A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group. Conclusions:. In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.

ObjectiveStudies have shown that carbon dioxide (CO2) insufflation during endoscopic thyroidectomy is associated with many risks. Recently, we have designed a simple lifting tool using Kirschner wire. We aimed to use this tool for flap-lifting in modified areola approach endoscopic thyroidectomy and compare it with conventional CO2 insufflation.MethodsIn a prospective study, patients who underwent endoscopic thyroidectomy via modified areola approach were randomly assigned into gasless (n = 20) or CO2 groups (n = 22). Pre-operative variables included age, gender, tumor diameter, and clinical diagnosis. Intra-operative hemodynamic monitoring included mean arterial pressure, heart rate, pulse oximetry, end-tidal carbon dioxide (ET-CO2) and arterial pH. Other intra-operative details included total operative time, operative blood loss, conversion from endoscopic surgery to open surgery, intra-operative events, and endoscope video score. Postoperatively, the hospital stay, drainage volume, and complications were recoded.ResultsPatient characteristics were not different between the two groups. During the operation, ET-CO2 levels were significantly higher in the CO2 group (P < 0.05), whereas arterial pH levels were significantly lower (P < 0.05). The CO2 group had longer operation time and higher endoscope clarity VAS score than gasless group. Hospital stay, drainage volume, and postoperative complications did not differ significantly between the two groups (P > 0.05).ConclusionsThe gasless endoscopic thyroidectomy we performed via our Kirschner wire hook was safe, feasible, and yielded good results.

Malignant meningiomas have a high mortality rate and short survival time and currently have no effective treatment. In our study, proteomics analysis was performed to identify highly expressed proteins as therapeutic targets in malignant meningiomas. Cell Counting Kit-8 (CCK-8) assays were performed to verify the effect of LB-100 on the growth of malignant meningiomas. In addition, immunoblotting was used to verify the expression of B7-H3 and phosphorylation of STAT1 (Tyr701) in tissues and cells. Our results show that STAT1 and CD276 (B7-H3) regulated by PP2A were enriched in GO_IMMUNE_EFFECTOR_PROCESS and GO_REGULATION_OF_IMMUNE_SYSTEM_PROCESS. The immunotherapy target protein B7-H3 was confirmed to be upregulated in malignant meningiomas compared with meningothelial (p = 0.0001) and fibroblastic (p = 0.0046) meningiomas. In vitro, the PP2A inhibitor LB-100 suppressed the growth and invasion of malignant meningioma cells. Notably, the PP2A inhibitor LB-100 increased the phosphorylation of STAT1, thereby increasing the expression of the immune checkpoint protein B7-H3 in malignant meningioma cells in vitro. In conclusion, B7-H3 was found to be upregulated in malignant meningiomas. The PP2A inhibitor LB-100 increased the phosphorylation of STAT1 and B7-H3 expression, which could increase the sensitivity of malignant meningiomas to B7-H3 targeted immunotherapy.

Objective: Phase transfer entropy (TEθ) methods perform well in animal sensory–spatial associative learning. However, their advantages and disadvantages remain unclear, constraining their usage. Method: This paper proposes the performance baseline of the TEθ methods. Specifically, four TEθ methods are applied to the simulated signals generated by a neural mass model and the actual neural data from ferrets with known interaction properties to investigate the accuracy, stability, and computational complexity of the TEθ methods in identifying the directional coupling. Then, the most suitable method is selected based on the performance baseline and used on the local field potential recorded from pigeons to detect the interaction between the hippocampus (Hp) and nidopallium caudolaterale (NCL) in visual–spatial associative learning. Results: (1) This paper obtains a performance baseline table that contains the most suitable method for different scenarios. (2) The TEθ method identifies an information flow preferentially from Hp to NCL of pigeons at the θ band (4–12 Hz) in visual–spatial associative learning. Significance: These outcomes provide a reference for the TEθ methods in detecting the interactions between brain areas.

Abstract Clinical success of IL-17/IL-23 pathway biologics for the treatment of moderate to severe psoriasis suggests that targeting RORγt, a master regulator for the proliferation and function of Th17 cells, could be an effective alternative. However, oral RORγ antagonists (VTP43742, TAK828) with high systemic exposure showed toxicity in phase I/II clinical trials and terminated development. To alleviate the potential safety concerns, identifying compounds with skin-restricted exposure amenable for topical use is of great interest. Systematic structure activity relationship study and multi-parameter optimization led to the discovery of a novel RORγ antagonist (SHR168442) with desired properties for a topical drug. It suppressed the transcription of IL-17 gene, leading to reduction of IL-17 cytokine secretion. It showed high exposure in skin, but low in plasma. Topical application of SHR168442 in Vaseline exhibited excellent efficacy in the imiquimod-induced and IL-23-induced psoriasis-like skin inflammation mouse models and correlated with the reduction of Th17 pathway cytokines, IL-6, TNFα and IL-17A. This work demonstrated restricted skin exposure of RORγ antagonist may provide a new topical treatment option as targeted therapeutics for mild to moderate psoriasis patients and may be suitable for the treatment of any other inflammatory disorders that are accessible locally.

Anaplastic meningioma is classified as a World Health Organization (WHO) grade III tumor and shows a strong tendency to recur. Although the incidence of anaplastic meningioma is low, the high rate of recurrence and death still makes treatment a challenge. A proteomics analysis was performed to investigate the differentially expressed proteins between anaplastic meningiomas and fibrous meningiomas by micro-LC-MS/MS. The key metabolic enzyme nicotinamide phosphoribosyltransferase (NAMPT) showed upregulated expression in anaplastic meningiomas. However, targeting NAMPT to treat anaplastic meningiomas has not been reported. In vitro, NAMPT inhibitor -FK866 reduced the viability of anaplastic meningiomas by inducing cell cycle arrest at the G2/M phase. Intriguingly, the NAMPT inhibitor -FK866 decreased the protein expression of immune checkpoints PD-L1 and B7-H3 by down-regulating the STAT1 and p-STAT1 expression in vitro. Furthermore, FK866 suppressed the growth of anaplastic meningiomas in an in vivo xenograft model. The expression of Ki-67 and immune checkpoint proteins (PD-L1 and B7-H3) showed significant differences between the group treated with FK866 and the control group treated with DMSO. In conclusion, the expression of NAMPT, which plays a crucial role in energy metabolism, was upregulated in anaplastic meningiomas. The NAMPT inhibitor -FK866 significantly suppressed the growth of anaplastic meningiomas in vitro and in vivo. More strikingly, FK866 potently inhibited immune checkpoint protein (PD-L1 and B7-H3) expression by regulating STAT1 in vitro and in vivo. Our results demonstrated that NAMPT inhibitors could potentially be an effective treatment method for patients suffering from anaplastic meningiomas.

Abstract Objective This study aimed to explore the effects of activating GABAB1 receptor by baclofen on proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of ovarian cancer cells. Results One hundred μmol/L, 200 μmol/L and 300 μmol/L were selected as low, medium and high baclofen concentrations respectively. Cells were divided into four groups: Control, 100 μmol/L, 200 μmol/L and 300 μmol/L. Compared with the control group, the viability, colony formation, migration and invasion of SKOV3 cells were inhibited, and the apoptosis of SKOV3 cells were enhanced significantly at 200 μmol/L and 300 μmol/L baclofen. Moreover, they changed significantly with the increase of baclofen concentration. Compared with the control group, the expression of E-cadherin and GABAB1 increased and the N-cadherin expression decreased significantly in 200 μmol/L and 300 μmol/L groups. Higher concentration of baclofen induced higher expression of E-cadherin and lower expression of N-cadherin. Conclusion Baclofen inhibited the proliferation, cloning, migration, invasion and EMT of ovarian cancer cells by activating GABAB1 receptor. These results might contribute a lot to clarify the role and possible mechanism of GABAB1 receptor in ovarian cancer.

Pleomorphic adenomas (PAs) are the most common benign salivary neoplasms. PAs are generally slow-growing but may sometimes become aggressive and grow rapidly within a short period of time. Here, we report the case of an 83-year-old Chinese woman with an anterior neck mass that had been growing over the past 30 years. She felt uncomfortable because the mass had grown quite rapidly in the past year. The final diagnosis of a PA of the left submandibular gland was confirmed by histopathological and immunohistochemical examinations after surgical resection. Our patient recalled a history of an excision of a neck mass 40 years prior to presentation at another hospital. Based on our imaging findings and surgical findings, we speculate that the neck mass 40 years prior may also have been a PA. Our case reminds us the rare recurrence possibility of PAs, and early and thorough resection may have a good prognosis. In addition, to the best of our knowledge, this is the largest PA of the submandibular gland reported to date.

In this paper, a discrete element method (DEM) is used to simulate the suction process of fresh concrete in the pumping system, and the influence of the stirring blade on the suction is explored. The Hertz-Mindlin with JKR Cohesion contact model is used to establish the DEM model of fresh concrete, and the suction work is realized by an API function of DEM, and the movement of particles in the suction cylinder can be completed smoothly. The changes of the concrete flow field during the suction process are further studied, and the influence mechanism of the stirring blade on the suction process is explained. A numerical simulation scheme is designed to explore the influence of the rotation speed, installation angle, and edges distance of the stirring blade on the suction efficiency and the stirring resistance torque, and the structure of the stirring blade is optimized according to the influence law. The simulation results show that the stirring resistance torque of the optimized stirring blade is reduced without the suction efficiency of the pumping system reduced, and the stirring energy consumption of the pump suction is reduced.

Obesity is a foremost health issue that affects about 1.6 million people out of which 400 million worldwide. Epidemiological evidences prove obesity is the primary cause for various metabolic ailments e.g. diabetes. Poria cocos possess extensive biological actions, for instance, antioxidant, anti-inflammatory, antitumor, immunomodulatory actions. The primary limitation of all phytomedicine was their poor bioavailability hence in this investigation, we bio-fabricated the gold nanoparticles from Poria cocos aqueous extract and inspected their potency to treat obesity. Obese rat model were produced via fed the young female rats with high fat food for 8 weeks regimen. Further to confirm the potency of Poria cocos gold nanoparticles against obesity induced metabolic disorders we treated obese rats with low dose streptozotocin in the conclusion of the investigational time. The synthesis of Poria cocos gold-nanoparticles was evidenced via the UV-Spectroscopic study and characterized with SEM, TEM and EDAX studies. The anti-obesity actions of Poria cocos gold-nanoparticles were investigated by estimating the glucose profile, kidney markers, lipid profile, inflammatory cytokines, adipocyte markers, antioxidants in the Poria cocos gold nanoparticles treated obese rats. To confirm the Poria cocos gold nanoparticles role on inhibiting the obesity induced metabolic disorders we analyzed the histopathological changes in cardiac tissues. Our physical characterization confirms the synthesized Poria cocos gold nanoparticles assure the distinctions of influential nanoparticles to be utilized for the treatment. The results from biochemical and histopathological analysis confirms Poria cocos gold nanoparticles is a persuasive antidiabetic, anti-inflammatory, antioxidant, anti-obesity drug. Overall our results authentically confirm Poria cocos gold nanoparticles is a potent anti-obesity drug and it also protects from obesity induced metabolic disorders.

Qinzhou Port is one of the most important ports in the “Beibu Gulf” of China. It is also the main hub port of the "21st century maritime silk road" strategy. Based on a basic collision risk assessment approach, an Event Sequence Diagram (ESD) model that explains the four-stage collision avoidance decision-making procedure is proposed from the perspectives of perception, cognition, decision, and execution. Using the historical data derived from collision accident reports from the Qinzhou Port waters from 2013 to 2017, as well as the data elicited from expert knowledge, a quantitative evaluation of probability distributions of different collision failure modes is performed. The results are also compared with relevant results from other types of navigation waters to analyse collision risk level of Qinzhou waters. At the same time, the main failures paths of collision avoidance decision making are identified. The proposed model can provide with an overall collision risk picture from a macro perspective.

Nonlinear mapping is an essential and common demand in online systems, such as sensor systems and mobile phones. Accelerating nonlinear mapping will directly speed up online systems. Previously the authors of this paper proposed a Dendrite Net (DD) with enormously lower time complexity than the existing nonlinear mapping algorithms; however, there still are redundant calculations in DD. This paper presents a DD with an acceleration module (AC) to accelerate nonlinear mapping further. We conduct three experiments to verify whether DD with AC has lower time complexity while retaining DD’s nonlinear mapping properties and system identification properties: The first experiment is the precision and identification of unary nonlinear mapping, reflecting the calculation performance using DD with AC for basic functions in online systems. The second experiment is the mapping precision and identification of the multi-input nonlinear system, reflecting the performance for designing online systems via DD with AC. Finally, this paper compares the time complexity of DD and DD with AC and analyzes the theoretical reasons through repeated experiments. Results: DD with AC retains DD’s excellent mapping and identification properties and has lower time complexity. Significance: DD with AC can be used for most engineering systems, such as sensor systems, and will speed up computation in these online systems.

The Hippo pathway is an evolutionarily conserved pathway that serves to promote cell death and differentiation while inhibiting cellular proliferation across species. The downstream effectors of this pathway, yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), are considered vital in promoting the output of the Hippo pathway, with activation of upstream kinases negatively regulating YAP/TAZ activity. The upstream regulation of the Hippo pathway is not entirely understood on a molecular level. However, several studies have shown that numerous cellular and non-cellular mechanisms such as cell polarity, contact inhibition, soluble factors, mechanical forces, and metabolism can convey external stimuli to the intracellular kinase cascade, promoting the activation of key components of the Hippo pathway and therefore regulating the subcellular localisation and protein activity of YAP/TAZ. This review will summarise what we have learnt about the role of intercellular junction-associated proteins in the activation of this pathway, including adherens junctions and tight junctions, and in particular our latest findings about the desmosomal components, including desmoglein-3 (DSG3), in the regulation of YAP signalling, phosphorylation, and subcellular translocation.

Shiyiwei Shenqi Tablet (SSTs) has been widely used for treatment of different types of cancer including breast cancer. SST has drawn more and more interest due to the low rate of side effects. The aim of this study was to investigate the metabolites in serums of breast cancer patients who received base-line chemotherapy only or combination treatment with SST. An untargeted metabolomics method was developed to investigate the alteration of metabolism in patients’ serums using ultra-high-performance liquid chromatography/Q-exactive Orbitrap mass spectrometry. The patients were separated based on the metabolomics data, and further analyses showed that SST treatment can affect the metabolism of glucose, fatty acid, bile acid and amino acid. In particular, SST treatment significantly reduced some short peptides which are potential tumor neoantigens. This study may provide novel insights into the mechanism underlying interaction between SST and base-line chemotherapy in terms of affecting metabolic pathways and thereby changing metabolic products, which might shed new light for clinical medication.

The ensemble transfer entropy (TEensemble) refers to the transfer entropy estimated from an ensemble of realizations. Due to its time-resolved analysis, it is adapted to analyze the dynamic interaction between brain regions. However, in the traditional TEensemble, multiple sets of surrogate data should be used to construct the null hypothesis distribution, which dramatically increases the computational complexity. To reduce the computational cost, a fast, efficient TEensemble with a simple statistical test method is proposed here, in which just one set of surrogate data is involved. To validate the improved efficiency, the simulated neural signals are used to compare the characteristics of the novel TEensemble with those of the traditional TEensemble. The results show that the time consumption is reduced by two or three magnitudes in the novel TEensemble. Importantly, the proposed TEensemble could accurately track the dynamic interaction process and detect the strength and the direction of interaction robustly even in the presence of moderate noises. The novel TEensemble reaches its steady state with the increased samples, which is slower than the traditional method. Furthermore, the effectiveness of the novel TEensemble was verified in the actual neural signals. Accordingly, the TEensemble proposed in this work may provide a suitable way to investigate the dynamic interactions between brain regions.

Pemphigus Vulgaris (PV) is a life-threatening autoimmune disease manifested with blisters in the skin and mucosa and caused by autoantibodies against adhesion protein desmoglein-3 (Dsg3) expressed in epithelial membrane linings of these tissues. Despite many studies, the pathogenesis of PV remains incompletely understood. Recently we have shown Dsg3 plays a role in regulating the yes-associated protein (YAP), a co-transcription factor and mechanical sensor, and constraining reactive oxygen species (ROS). This study investigated the effect of PV sera as well as the anti-Dsg3 antibody AK23 on these molecules. We detected elevated YAP steady-state protein levels in PV cells surrounding blisters and perilesional regions and in keratinocytes treated with PV sera and AK23 with concomitant transient ROS overproduction. Cells treated with hydrogen peroxide also exhibited augmented nuclear YAP accompanied by reduction of Dsg3 and α-catenin, a negative regulator of YAP. As expected, transfection of α-catenin-GFP plasmid rendered YAP export from the nucleus evoked by hydrogen peroxide. In addition, suppression of total YAP was observed in hydrogen peroxide treated cells exposed to antioxidants with enhanced cell-cell adhesion being confirmed by decreased fragmentation in the dispase assay compared to hydrogen peroxide treatment alone. On the other hand, the expression of exogenous YAP disrupted intercellular junction assembly. In contrast, YAP depletion resulted in an inverse effect with augmented expression of junction assembly proteins, including Dsg3 and α-catenin capable of abolishing the effect of AK23 on Dsg3 expression. Finally, inhibition of other kinase pathways, including p38MAPK, also demonstrated suppression of YAP induced by hydrogen peroxide. Furthermore, antioxidant treatment of keratinocytes suppressed PV sera-induced total YAP accumulation. In conclusion, this study suggests that oxidative stress coupled with YAP dysregulation attributes to PV blistering, implying antioxidants may be beneficial in the treatment of PV.

Although teacher feedback and teacher support are believed as important predictors of student resilience, few studies have compared their effects on student resilience and explored how such effects are mediated by students' achievement goals. To address this gap, this study analysed the PISA 2018 student survey data on the four variables (i.e., student resilience, teacher feedback, teacher support and achievement goals) obtained from 41,872 participants (girls = 20,527; boys = 21,345) in six academically high-performing East Asian countries/economies. The findings showed that (i) mastery and performance-approach goals significantly and positively predicted student resilience while the impacts of performance-avoidance goals on student resilience were negative; (ii) teacher feedback exerted a significant positive influence on student resilience both directly and indirectly, and the indirect influence was mediated by students' achievement goals; and (iii) teacher support had only an indirect significant positive effect on student resilience mediated by achievement goals. This study establishes a mediation model to associate teacher feedback and support with student resilience via students' achievement goals. It also reveals the cultural relevance of student resilience. The findings have implications for East Asian teachers to cultivate resilient students in changing times.

Potentially pre-malignant oral lesions (PPOLs) are composed of keratinocytes that are either mortal (MPPOL) or immortal (IPPOL) in vitro. We report here that MPPOL, but not generally IPPOL, keratinocytes upregulate various extracellular tumor-promoting cytokines (interleukins 6 and 8) and prostaglandins E1 (ePGE1) and E2 (ePGE2) relative to normal oral keratinocytes (NOKs). ePGE upregulation in MPPOL was independent of PGE receptor status and was associated with some but not all markers of cellular senescence. Nevertheless, ePGE upregulation was dependent on the senescence program, cyclo-oxygenase 2 (COX2) and p38 mitogen-activated protein kinase and was partially regulated by hydrocortisone. Following senescence in the absence of p16INK4A, ePGEs accumulated in parallel with a subset of tumor promoting cytokine and metalloproteinase (MMP) transcripts, all of which were ablated by ectopic telomerase. Surprisingly, ataxia telangiectasia mutated (ATM) function was not required for ePGE upregulation and was increased in expression in IPPOL keratinocytes in line with its recently reported role in telomerase function. Only ePGE1 was dependent on p53 function, suggesting that ePGEs 1 and 2 are regulated differently in oral keratinocytes. We show here that ePGE2 stimulates IPPOL keratinocyte proliferation in vitro. Therefore, we propose that MPPOL keratinocytes promote the progression of IPPOL to oral SCC in a pre-cancerous field by supplying PGEs, interleukins and MMPs in a paracrine manner. Our results suggest that the therapeutic targeting of COX-2 might be enhanced by strategies that target keratinocyte senescence.

The Hippo-YAP pathway serves as a central signalling hub in epithelial tissue generation and homeostasis. Yes-associated protein (YAP) is an essential downstream transcription cofactor of this pathway, with its activity being negatively regulated by Hippo kinase-mediated phosphorylation, leading to its cytoplasmic translocation or degradation. Our recent study showed phospho-YAP complexes with Desmoglein-3 (Dsg3), the desmosomal cadherin known to be required for junction assembly and cell–cell adhesion. In this study, we show that YAP inhibition by Verteporfin (VP) caused a significant downregulation of desmosomal genes and a remarkable reduction in desmosomal proteins, including the Dsg3/phospho-YAP complex, resulting in attenuation of cell cohesion. We also found the desmosomal genes, along with E-cadherin, were the YAP-TEAD transcriptional targets and Dsg3 regulated key Hippo components, including WWTR1/TAZ, LATS2 and the key desmosomal molecules. Furthermore, Dsg3 and phospho-YAP exhibited coordinated regulation in response to varied cell densities and culture durations. Overexpression of Dsg3 could compensate for VP mediated loss of adhesion components and proper architecture of cell junctions. Thus, our findings suggest that Dsg3 plays a crucial role in the Hippo network and regulates junction configuration via complexing with phospho-YAP.

Previous studies showed that spatial navigation depends on a local network including multiple brain regions with strong interactions. However, it is still not fully understood whether and how the neural patterns in avian nidopallium caudolaterale (NCL), which is suggested to play a key role in navigation as a higher cognitive structure, are modulated by the behaviors during spatial navigation, especially involved path adjustment needs. Hence, we examined neural activity in the NCL of pigeons and explored the local field potentials’ (LFPs) spectral and functional connectivity patterns in a goal-directed spatial cognitive task with the detour paradigm. We found the pigeons progressively learned to solve the path adjustment task when the learned path was blocked suddenly. Importantly, the behavioral changes during the adjustment were accompanied by the modifications in neural patterns in the NCL. Specifically, the spectral power in lower bands (1–4 Hz and 5–12 Hz) decreased as the pigeons were tested during the adjustment. Meanwhile, an elevated gamma (31–45 Hz and 55–80 Hz) connectivity in the NCL was also detected. These results and the partial least square discriminant analysis (PLS-DA) modeling analysis provide insights into the neural activities in the avian NCL during the spatial path adjustment, contributing to understanding the potential mechanism of avian spatial encoding. This study suggests the important role of the NCL in spatial learning, especially path adjustment in avian navigation.

Objective: The prognosis of mild and severe patients has prominent differences during the prevalence of COVID-19, and it will be significant to identify patients' potential risk of progressing to severe cases according to their first clinical presentations. Therefore, we aim to review the clinical symptoms of the COVID-19 epidemic systematically.Methods:We searched PubMed, Embase, Web of Science, and CNKI (Chinese Database) for studies about the clinical features of COVID-19 in China from March 18 to April 18. Then we used REVMAN to conduct a meta-analysis.Results: After screening, 20 articles including 3,326 COVID-19 confirmed cases were selected from 142 articles we retrieved at the beginning of our research. We divided all the cases into a severe group (including severe and critically severe patients) and a mild group according to the “Diagnosis and Treatment Protocol for Novel Coronavirus Infection-Induced Pneumonia” version 4 (trial). Of all the initial symptoms (including fever, cough, abdominal pain, anorexia, chest tightness, diarrhea, dyspnea, expectoration, fatigue, headache, hemoptysis, myalgia, nausea or vomiting, and pharyngalgia) we studied, we found that cough (odds ratio [OR] = 1.4, 95% confidence interval [CI]: 1.2–1.7; p < 0.001), fever (OR = 1.5, 95% CI: 1.2–1.9; p < 0.001), dyspnea (OR = 6.2, 95% CI: 3.6–10.6; p < 0.001), diarrhea (OR = 2.6, 95% CI: 1.3–4.9; p < 0.001), fatigue (OR = 2.1, 95% CI: 1.3–3.3; p < 0.01), expectoration (OR = 1.7, 95% CI: 1.2–2.6; p < 0.01), myalgia (OR = 1.6, 95% CI: 0.8–3.1; p < 0.001), hemoptysis (OR = 4.0, 95% CI: 1.5–11.3; p < 0.001), abdominal pain (OR = 7.5, 95% CI: 2.4–23.4; p < 0.001), and anorexia (OR = 2.8, 95% CI: 1.5–5.1; p < 0.001) had a different distribution in two groups and were statistically significant (p < 0.05).Conclusion:COVID-19 patients whose initial manifestation is dyspnea, hemoptysis, anorexia, diarrhea, or fatigue, especially abdominal pain should be closely monitored to prevent disease deterioration.

Objective: Functional deficits induced by nerve injuries can be restored by achieving effective reinnervation of the denervated targets and functional reorganization of the central nervous system after nerve reconstruction. In this study, we investigated the effect and extent of cortical functional reorganization related to the ability of transferred hypoglossal neurons to restore facial function in facial paralysis patients after a surgical bridge of neurorrhaphy ectopically between the ipsilateral hypoglossal nerve and injured facial nerve. Methods: We treated 23 patients (35.4 ± 10.3 years, 10 males) and followed them up for 2.9 ± 0.61 years. We used motor-task-related functional magnetic resonance imaging to map activation change at multiple time points before and after neurorrhaphy; 20 normal subjects were included as control. Results: All patients regained facial function to some extent after neurorrhaphy. Enhanced activation in motor-related cortices gradually returned to normal levels and was positively correlated with regained facial function. The related cortical functional areas included the left middle temporal gyrus, left inferior frontal gyrus, insula, bilateral motor cortex and the supplementary motor area extending to the paracingulate involved in intensive eye closing, as well as the left superior temporal gyrus, right putamen and the bilateral motor cortex involved in lip pursing. Intriguingly, significant correlations were found between the pre-surgery activation while intensive eye closing in bilateral motor cortex and recovery of facial nerve function induced by the neurorrhaphy treatment. Conclusion: This is the first study mapping activation change in motor cortices at multiple time points before and after repair of the facial nerve. The cortex functional reorganization found may suggest potential treatment targets in the central nervous system for adjuvant therapies such as repetitive transcranial magnetic stimulation to further improve functional recovery.

Background: The incidence of incomplete facial paralysis is now relatively higher in clinical practice, and surgical intervention is still desirable for patients with significant facial paralysis. However, the importance and usefulness of the remaining and/or spontaneously regenerated facial axons for regaining facial function when using hypoglossal–facial nerve (HN-FN) neurorrhaphy or other nerve-transferring methods to treat facial paralysis remain controversial.Objective: We designed a rat FN injury model with preservation of the anatomical structure followed by HN-FN side-to-side neurorrhaphy to investigate the effects of the remaining and/or spontaneously regenerated FN axons on restoration of facial function.Methods: After the evident return of facial function in 3 months following FN injury and HN-FN side-to-side neurorrhaphy, the FN was cross-sectioned again according to different ratios (0, 30, 70, and 100%) at the site rostral to the initial FN injury to retain, partially abolish, or completely abolish the spontaneously regenerated FN axons that had successfully reinnervated the paralyzed facial muscles. Then, FN function was assessed using clinical evaluation methods and electrophysiological examinations, as well as retrograde labeling and axonal counting assessments of the reconstructed nerve pathways.Results: The evaluations show that the remaining facial axons not only influenced the extent of regained function, such as facial symmetry, eye blinking activity, and vibrissae motion, but also had an impact on regeneration and innervation of hypoglossal motoneurons.Conclusion: Participation of remaining or spontaneously regenerated facial axons plays an important role in innervating paralyzed facial muscles by both facial and hypoglossal motoneurons, thus, reestablishing facial function.

There is no previous study on the effect of pinocembrin on ovarian cancer to the best of our knowledge. Moreover, the effects of pinocembrin on the expression of GABAB1 and GABAB2 genes are not studied before. Therefore, this study aimed to investigate effects of pinocembrin on the growth of ovarian cancer cells and the expression of cadherin and GABAB receptor to explore whether pinocembrin was helpful in the treatment of epithelial ovarian cancer. SKOV3 cells were divided into six groups: Control (blank control), DDP (cisplatin as positive control; cells were incubated with 15 μg/ml DDP), 25 μM (cells were incubated with 25 μM pinocembrin), 50 μM (cells were incubated with 50 μM pinocembrin), 100 μM (cells were incubated with 100 μM pinocembrin), and 200 μM (cells were incubated with 200 μM pinocembrin). CCK8 assay, cell scratch assay and Annexin V-FITC/PI staining found that when pinocembrin concentration reached 100 μM and the treatment time reached 48 h, pinocembrin could inhibit the cell proliferation and migration and promote the cell apoptosis, and this effect was enhanced with the increase of pinocembrin concentration. Western blotting found that the protein expression of E-cadherin, N-cadherin, GABAB1 and GABAB2 was not significantly affected by pinocembrin. RT-PCR found that pinocembrin also had no significant influence on the E-cadherin mRNA level, but it could reduce the mRNA levels of N-cadherin, GABAB1 and GABAB2. In conclusion, pinocembrin inhibited the proliferation and migration and promoted the apoptosis of ovarian cancer cells through down-regulating the mRNA levels of N-cadherin and GABAB receptor.