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In this study, we built and tested a theoretical model to determine how ethical leadership affects team creativity among teams composed of different characteristics. Following social learning theory and an antecedentbenefit—cost framework, we conducted analyses of multisource data from 50 team supervisors and 186 employees, which revealed an inverted U-shaped relationship between ethical leadership and team creativity. The teams exhibited more creativity when there was a moderate level of ethical leadership than when there were very low or very high levels. Moreover, from an interactional perspective, we found that team faultlines significantly moderated the curvilinear relationship between ethical leadership and team creativity such that the inverted U-shaped relationship was more significant among teams with weak team faultlines. The theoretical and practical implications of these findings are discussed.

Autonomous vehicles (AVs) are entering the market, which will have a great impact on future decision making on mode choice in transportation systems. The aim of this study is to explore the determinants which influence travelers’ intentions to use AVs based on structural equation modelling (SEM). 310 valid sets of data from an online survey were collected to analyze factors which influence travelers’ intentions. Data analyses were conducted using IBM SPSS Statistics 23 and AMOS 23. The results showed that personality and preferences in relation to AVs are the main potential factors that cause travelers’ AVs use. Attitudes to modal services also affect intentions to use AVs. Personality has a significant positive effect on both attitude and preferences. The results provide exploratory empirical support for all hypotheses. The research results will help understand travelers’ choice motivation from psychological and service perspectives, and provide support for governments and enterprises to improve the management and services of autonomous vehicles.

Autophagy is an evolutionarily conserved catabolic cellular process that exerts antiviral functions during a viral invasion. However, co-evolution and co-adaptation between viruses and autophagy have armed viruses with multiple strategies to subvert the autophagic machinery and counteract cellular antiviral responses. Specifically, the host cell quickly initiates the autophagy to degrade virus particles or virus components upon a viral infection, while cooperating with anti-viral interferon response to inhibit the virus replication. Degraded virus-derived antigens can be presented to T lymphocytes to orchestrate the adaptive immune response. Nevertheless, some viruses have evolved the ability to inhibit autophagy in order to evade degradation and immune responses. Others induce autophagy, but then hijack autophagosomes as a replication site, or hijack the secretion autophagy pathway to promote maturation and egress of virus particles, thereby increasing replication and transmission efficiency. Interestingly, different viruses have unique strategies to counteract different types of selective autophagy, such as exploiting autophagy to regulate organelle degradation, metabolic processes, and immune responses. In short, this review focuses on the interaction between autophagy and viruses, explaining how autophagy serves multiple roles in viral infection, with either proviral or antiviral functions. Highlights This review focuses on the interaction between autophagy and viruses, explaining how autophagy serves multiple roles in viral infection, with either proviral or antiviral functions. Based on different steps of autophagy and the regulation of immune responses by autophagy, this review oversees the role of autophagy in viral replication, maturation, egress and cell–cell spreading. This review provides an important foundation for the development of broad-spectrum antiviral treatment strategies and drugs based on the regulation of autophagy.

Squamous cell carcinomas (SCCs) are aggressive malignancies. Previous report demonstrated that master transcription factors (TFs) TP63 and SOX2 exhibited overlapping genomic occupancy in SCCs. However, functional consequence of their frequent co-localization at super-enhancers remains incompletely understood. Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter. Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR , thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways. These results together identify a SCC-specific DNA/RNA/protein complex which activates TP63/SOX2-CCAT1-EGFR cascade and promotes SCC tumorigenesis, advancing our understanding of transcription dysregulation in cancer biology mediated by master TFs and super-enhancers. Master regulator transcription factors TP63 and SOX2 have been reported to overlap in genomic occupancy in squamous cell carcinomas (SCCs). Here, the authors demonstrate that TP63 and SOX2 promote co-operatively long non-coding RNA CCAT1 expression through activating its super-enhancer, and CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR super-enhancers and enhances both the MEK/ERK1/2 and PI3K/AKT signaling pathways in SCC.

Squamous cell carcinomas (SCCs) comprise one of the most common histologic types of human cancer. Transcriptional dysregulation of SCC cells is orchestrated by tumor protein p63 (TP63) , a master transcription factor (TF) and a well-researched SCC-specific oncogene. In the present study, both Gene Set Enrichment Analysis (GSEA) of SCC patient samples and in vitro loss-of-function assays establish fatty-acid metabolism as a key pathway downstream of TP63. Further studies identify sterol regulatory element binding transcription factor 1 (SREBF1) as a central mediator linking TP63 with fatty-acid metabolism, which regulates the biosynthesis of fatty-acids, sphingolipids (SL), and glycerophospholipids (GPL), as revealed by liquid chromatography tandem mass spectrometry (LC-MS/MS)-based lipidomics. Moreover, a feedback co-regulatory loop consisting of SREBF1/TP63/ Kruppel like factor 5 (KLF5) is identified, which promotes overexpression of all three TFs in SCCs. Downstream of SREBF1, a non-canonical, SCC-specific function is elucidated: SREBF1 cooperates with TP63/KLF5 to regulate hundreds of cis-regulatory elements across the SCC epigenome, which converge on activating cancer-promoting pathways. Indeed, SREBF1 is essential for SCC viability and migration, and its overexpression is associated with poor survival in SCC patients. Taken together, these data shed light on mechanisms of transcriptional dysregulation in cancer, identify specific epigenetic regulators of lipid metabolism, and uncover SREBF1 as a potential therapeutic target and prognostic marker in SCC. The relevance and underlying molecular mechanisms of epigenetic regulation in squamous cell carcinomas (SCC) await further characterization. Here, the authors show a transcriptional regulatory loop involving SREBF1, TP63 and KLF5 driving tumourigenesis in SCC through fatty acid, ERBB and mTOR pathway regulation.

ObjectivesOesophageal squamous cell carcinoma (OSCC) and adenocarcinoma (OAC) are distinct cancers in terms of a number of clinical and epidemiological characteristics, complicating the design of clinical trials and biomarker developments. We analysed 1048 oesophageal tumour-germline pairs from both subtypes, to characterise their genomic features, and biological and clinical significance.DesignPreviously exome-sequenced samples were re-analysed to identify significantly mutated genes (SMGs) and mutational signatures. The biological functions of novel SMGs were investigated using cell line and xenograft models. We further performed whole-genome bisulfite sequencing and chromatin immunoprecipitation (ChIP)-seq to characterise epigenetic alterations.ResultsOSCC and OAC displayed nearly mutually exclusive sets of driver genes, indicating that they follow independent developmental paths. The combined sample size allowed the statistical identification of a number of novel subtype-specific SMGs, mutational signatures and prognostic biomarkers. Particularly, we identified a novel mutational signature similar to Catalogue Of Somatic Mutations In Cancer (COSMIC)signature 16, which has prognostic value in OSCC. Two newly discovered SMGs, CUL3 and ZFP36L2, were validated as important tumour-suppressors specific to the OSCC subtype. We further identified their additional loss-of-function mechanisms. CUL3 was homozygously deleted specifically in OSCC and other squamous cell cancers (SCCs). Notably, ZFP36L2 is associated with super-enhancer in healthy oesophageal mucosa; DNA hypermethylation in its super-enhancer reduced active histone markers in squamous cancer cells, suggesting an epigenetic inactivation of a super-enhancer-associated SCC suppressor.ConclusionsThese data comprehensively contrast differences between OSCC and OAC at both genomic and epigenomic levels, and reveal novel molecular features for further delineating the pathophysiological mechanisms and treatment strategies for these cancers.

To explore the effect of different stress environments on fault-slip rockbursts. Bidirectional shear friction experiments with different lateral pressures were conducted on precracked syenogranites buried at 800 m. The macroscopic statistical parameters (cumulative number of AE events, magnitude and b value ) and local characteristic parameters (amplitude and dominant frequency) of acoustic emission during the stick-slip process under different lateral pressures were investigated. In addition, based on fractal theory, the nonlinear characteristics of AE spectrum were analyzed. On this basis, the microscopic mechanism of fault stick-slip was discussed. The results show that the lateral pressure influences the friction strength of the fault and stick-slip motion characteristics. With increasing lateral pressure, the proportion of transgranular shear fractures increases, which leads to an increase of cumulative number of AE events and magnitude. The periodic decrease in the b value is more significant at high lateral pressure. There is a good correlation between a high-magnitude AE event and a stress drop. The AE frequency with phased response characteristics can be used to effectively identify the evolution of fault stick-slip instability at the laboratory scale. A sharp increase in the amplitude of the dominant frequency can be regarded as one of the precursory features of fault stick-slip instability. The AE frequency spectra have multifractal characteristics, that differ among the different stages. The maximum multifractal dimension and spectral width can reflect the difference in energy released during fault stick-slip motion.

ObjectivesOesophageal squamous cell carcinoma (OSCC) is an aggressive malignancy and the major histological subtype of oesophageal cancer. Although recent large-scale genomic analysis has improved the description of the genetic abnormalities of OSCC, few targetable genomic lesions have been identified, and no molecular therapy is available. This study aims to identify druggable candidates in this tumour.DesignHigh-throughput small-molecule inhibitor screening was performed to identify potent anti-OSCC compounds. Whole-transcriptome sequencing (RNA-Seq) and chromatin immunoprecipitation sequencing (ChIP-Seq) were conducted to decipher the mechanisms of action of CDK7 inhibition in OSCC. A variety of in vitro and in vivo cellular assays were performed to determine the effects of candidate genes on OSCC malignant phenotypes.ResultsThe unbiased high-throughput small-molecule inhibitor screening led us to discover a highly potent anti-OSCC compound, THZ1, a specific CDK7 inhibitor. RNA-Seq revealed that low-dose THZ1 treatment caused selective inhibition of a number of oncogenic transcripts. Notably, further characterisation of the genomic features of these THZ1-sensitive transcripts demonstrated that they were frequently associated with super-enhancer (SE). Moreover, SE analysis alone uncovered many OSCC lineage-specific master regulators. Finally, integrative analysis of both THZ1-sensitive and SE-associated transcripts identified a number of novel OSCC oncogenes, including PAK4, RUNX1, DNAJB1, SREBF2 and YAP1, with PAK4 being a potential druggable kinase.ConclusionsOur integrative approaches led to a catalogue of SE-associated master regulators and oncogenic transcripts, which may significantly promote both the understanding of OSCC biology and the development of more innovative therapies.

De-Chen Lin, Ming-Rong Wang and colleagues report exome sequencing, RNA sequencing, and copy number analyses of esophageal squamous cell carcinoma. They identified recurrent mutations in FAT1 , FAT2 , ZNF750 , EP300 and KMT2D . Esophageal squamous cell carcinoma (ESCC) is prevalent worldwide and particularly common in certain regions of Asia. Here we report the whole-exome or targeted deep sequencing of 139 paired ESCC cases, and analysis of somatic copy number variations (SCNV) of over 180 ESCCs. We identified previously uncharacterized mutated genes such as FAT1 , FAT2 , ZNF750 and KMT2D, in addition to those already known ( TP53, PIK3CA and NOTCH1 ). Further SCNV evaluation, immunohistochemistry and biological analysis suggested their functional relevance in ESCC. Notably, RTK-MAPK-PI3K pathways, cell cycle and epigenetic regulation are frequently dysregulated by multiple molecular mechanisms in this cancer. Our approaches also uncovered many druggable candidates, and XPO1 was further explored as a therapeutic target because it showed both gene mutation and protein overexpression. Our integrated study unmasks a number of novel genetic lesions in ESCC and provides an important molecular foundation for understanding esophageal tumors and developing therapeutic targets.

This paper addresses the challenges of equipment inspection in complex substation environments by proposing a lightweight small object detection algorithm, YOLOv8-MCDE, specifically designed for instrument recognition and suitable for deployment on inspection robots. Through model structure optimization, the proposed method significantly enhances both the small object detection performance and real-time efficiency of instrument detection on edge computing devices. YOLOv8-MCDE adopts the lightweight MobileNetV3 architecture as its backbone, effectively reducing model complexity and improving operational efficiency. The neck integrates a CNN-based Cross-scale Feature Fusion (CCFF) algorithm, which further lowers computational overhead while enhancing detection capability for small objects. In addition, a Deformable Large Kernel Attention (D-LKA) mechanism is integrated to increase the model’s sensitivity to small objects within complex backgrounds. The conventional CIOU loss function is also replaced with the more efficient EIOU loss function, significantly improving bounding box localization accuracy and accelerating model convergence. Experimental results demonstrate that YOLOv8-MCDE achieves a Precision of 92.80% and an mAP50 of 91.36%, representing improvements of 2.38% and 1.27%, respectively, compared to the original YOLOv8. Furthermore, the proposed algorithm reduces FLOPs by 37.68% and model size by 36%. These enhancements substantially reduce computational resource demands while significantly improving the real-time detection capabilities and small object recognition performance of inspection robots operating in complex environments.