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.
Aqueous Zn-ion batteries (ZIBs) are a potential electrochemical energy storage device because of their highly intrinsic safety, low cost, and large capacity. However, it is still in the primary stage ...because of the limited selection of cathode materials with high rate and long-life cycling stability. In addition, the energy storage mechanisms of ZIBs have not been well established. In this work, we report the synthesis of porous V2O3@C materials with high conductivity and further illustrate its application as the intercalation cathode for aqueous zinc-ion batteries. The unique channel and appropriate pore size distribution of corundum-type V2O3 are beneficial to the rapid zinc ion intercalation and removal, leading to a high rate capability. Also, the carbon framework structure achieves a high cyclic stability. The porous V2O3@C cathode delivers high capacities of 350 mA h g–1 at 100 mA g–1, an excellent rate capability (250 mA h g–1 at 2 A g–1), and an impressive long-life cycling stability with 90% capacity retention over 4000 cycles at 5 A g–1. The storage mechanism of zinc ions in the Zn/V2O3 system was studied by various analytical methods and first-principles calculation.
Carriers of BRCA1 germline mutations are predisposed to breast and ovarian cancers. Accumulated evidence shows that BRCA1 is quickly recruited to DNA lesions and plays an important role in the DNA ...damage response. However, the mechanism by which BRCA1 is recruited to DNA damage sites remains elusive. BRCA1 forms a Ring-domain heterodimer with BARD1, a major partner of BRCA1 that contains tandem BRCA1 C-terminus (BRCT) motifs. Here, we identify the BRCTs of BARD1 as a poly(ADP-ribose) (PAR)-binding module. The binding of the BARD1 BRCTs to PAR targets the BRCA1/BARD1 heterodimer to DNA damage sites. Thus, our study uncovers a PAR-dependent mechanism of rapid recruitment of BRCA1/BARD1 to DNA damage sites.
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•The BARD1 BRCT domain targets BRCA1 to DNA lesions during early DNA damage response•The BARD1 BRCT domain is a PAR-binding domain•PARP inhibitors suppress the fast recruitment of BRCA1 to DNA lesions•PARP inhibition sensitizes the cells bearing mutations in the BRCA1 BRCT domain to IR
Light-sound interactions have long been exploited in various acousto-optic devices based on bulk crystalline materials. Conventionally, these devices operate in megahertz frequency range where the ...acoustic wavelength is much longer than the optical wavelength and a long interaction length is required to attain significant coupling. With nanoscale transducers, acoustic waves with sub-optical wavelengths can now be excited to induce strong acousto-optic coupling in nanophotonic devices. Here we demonstrate microwave frequency surface acoustic wave transducers co-integrated with nanophotonic resonators on piezoelectric aluminum nitride substrates. Acousto-optic modulation of the resonance modes at above 10 GHz with the acoustic wavelength significantly below the optical wavelength is achieved. The phase and modal matching conditions in this scheme are investigated for efficient modulation. The new acousto-optic platform can lead to novel optical devices based on nonlinear Brillouin processes and provides a direct, wideband link between optical and microwave photons for microwave photonics and quantum optomechanics.
NK-lysin is an antimicrobial protein produced by cytotoxic T lymphocytes and natural killer cells. In this study, we examined the biological property of a peptide, NKLP27, derived from tongue sole ...(Cynoglossus semilaevis) NK-lysin. NKLP27 is composed of 27 amino acids and shares little sequence identity with known NK-lysin peptides. NKLP27 possesses bactericidal activity against both Gram-negative and Gram-positive bacteria including common aquaculture pathogens. The bactericidal activity of NKLP27 was dependent on the C-terminal five residues, deletion of which dramatically reduced the activity of NKLP27. During its interaction with the target bacterial cells, NKLP27 destroyed cell membrane integrity, penetrated into the cytoplasm, and induced degradation of genomic DNA. In vivo study showed that administration of tongue sole with NKLP27 before bacterial and viral infection significantly reduced pathogen dissemination and replication in tissues. Further study revealed that fish administered with NKLP27 exhibited significantly upregulated expression of the immune genes including those that are known to be involved in antibacterial and antiviral defense. These results indicate that NKLP27 is a novel antimicrobial against bacterial and viral pathogens, and that the observed effect of NKLP27 on bacterial DNA and host gene expression adds new insights to the action mechanism of fish antimicrobial peptides.
Este ensayo examina la interacción entre la ley, la tecnología y la cultura en la distribución y el consumo de películas censuradas en China. Comienza analizando las leyes y regulaciones relevantes ...en la industria y explorando las diversas formas en que el cine clandestino evade las restricciones gubernamentales. Destaca el uso de nuevas tecnologías y medios alternativos por parte de cineastas independientes como estrategia para publicar sus obras censuradas. Durante la pandemia, el director Jiang Nengjie difundió su documental Miners, Groom, and Pneumoconiosis (2019) a través de enlaces privados en servicios de almacenamiento en la nube, lo que generó una gran repercusión en la red y le valió el apodo de “director de la nube”. La transmisión a través de aplicaciones de videoconferencia también ha creado nuevas oportunidades para que las películas independientes prosperen en China. El surgimiento del cine clandestino en la red ha creado un movimiento social en curso, brindando a las películas independientes la oportunidad de prosperar fuera de los medios tradicionales.
This essay examines the interplay between law, technology, and culture in the distribution and consumption of censored films in China. It begins by analyzing the relevant laws and regulations in the industry and explores the various ways that underground cinema circumvents government restrictions. It highlights the independent filmmakers' use of new technologies and alternative media as strategies to publish their censored works. During the pandemic, director Jiang Nengjie shared his documentary Miners, Groom, and Pneumoconiosis (2019) via private links on cloud services, leading to its online virality and earning him the nickname “cloud drive director”. Streaming via video conferencing apps has also created new opportunities for independent films to thrive in China. The emergence of underground cinema online has created an ongoing social movement, providing independent films with the chance to prosper outside of mainstream media.
Este ensaio examina a interação entre a lei, a tecnologia e a cultura na distribuição e consumo de filmes censurados na China. Começa com uma análise das leis e regulamentações relevantes na indústria, explorando as diversas maneiras pelas quais o cinema clandestino contorna as restrições governamentais. Destaca o uso de novas tecnologias e mídias alternativas pelos cineastas independentes como estratégia para publicar seus trabalhos censurados. Durante a pandemia, o diretor Jiang Nengjie difundiu seu documentário Miners, Groom, and Pneumoconiosis (2019) por meio de links privados em serviços de armazenamento em nuvem, o que gerou uma grande repercussão nas redes e lhe proporcionou o apelido de “diretor da nuvem”. A transmissão por meio de aplicativos de videoconferência também criou novas oportunidades para filmes independentes prosperarem na China. O surgimento do cinema clandestino na rede criou um movimento social contínuo, proporcionando aos filmes independentes a chance de prosperar fora das mídias tradicionais.
Traffic information is of great importance for urban cities, and accurate prediction of urban traffics has been pursued for many years. Urban traffic prediction aims to exploit sophisticated models ...to capture hidden traffic characteristics from substantial historical mobility data and then makes use of trained models to predict traffic conditions in the future. Due to the powerful capabilities of representation learning and feature extraction, emerging deep learning becomes a potent alternative for such traffic modeling. In this article, we envision the potential and broard usage of deep learning in predictions of various traffic indicators, for example, traffic speed, traffic flow, and accident risk. In addition, we summarize and analyze some early attempts that have achieved notable performance. By discussing these existing advances, we propose two future research directions to improve the accuracy and efficiency of urban traffic prediction on a large scale.
This paper presents an experimental investigation on the stability of bound chlorides in chloride-contaminated cement pastes with and without FA/GGBS when subjected to Na2SO4 and MgSO4 attack. It is ...shown that bound chlorides were released in the chloride-contaminated pastes when exposed to Na2SO4 or MgSO4 solution. This is mainly attributed to the decomposition of Friedel's salt (FS), where Cl− bound in FS is replaced by SO42−. However there were fewer released chlorides found in the pastes exposed to MgSO4 solution than in those exposed to Na2SO4 solution. This is partly due to the low pH in the pore solution and partly due to the blocking effect of brucite on ionic transport caused by MgSO4. The inclusion of FA/GGBS in concrete can increase the decomposition of FS and thus the release of bound chlorides. However, it also resists the penetration of Na2SO4 and thus reduces the attack of Na2SO4.
Abstract
Optical computing with integrated photonics brings a pivotal paradigm shift to data-intensive computing technologies. However, the scaling of on-chip photonic architectures using spatially ...distributed schemes faces the challenge imposed by the fundamental limit of integration density. Synthetic dimensions of light offer the opportunity to extend the length of operand vectors within a single photonic component. Here, we show that large-scale, complex-valued matrix-vector multiplications on synthetic frequency lattices can be performed using an ultra-efficient, silicon-based nanophotonic cavity acousto-optic modulator. By harnessing the resonantly enhanced strong electro-optomechanical coupling, we achieve, in a single such modulator, the full-range phase-coherent frequency conversions across the entire synthetic lattice, which constitute a fully connected linear computing layer. Our demonstrations open up the route toward the experimental realizations of frequency-domain integrated optical computing systems simultaneously featuring very large-scale data processing and small device footprints.
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