DengueSeq: a pan-serotype whole genome amplicon sequencing protocol for dengue virus.

BACKGROUND: The increasing burden of dengue virus on public health due to more explosive and frequent outbreaks highlights the need for improved surveillance and control. Genomic surveillance of dengue virus not only provides important insights into the emergence and spread of genetically diverse serotypes and genotypes, but it is also critical to monitor the effectiveness of newly implemented control strategies. Here, we present DengueSeq, an amplicon sequencing protocol, which enables whole-genome sequencing of all four dengue virus serotypes. RESULTS: We developed primer schemes for the four dengue virus serotypes, which can be combined into a pan-serotype approach. We validated both approaches using genetically diverse virus stocks and clinical specimens that contained a range of virus copies. High genome coverage (>95%) was achieved for all genotypes, except DENV2 (genotype VI) and DENV 4 (genotype IV) sylvatics, with similar performance of the serotype-specific and pan-serotype approaches. The limit of detection to reach 70% coverage was 10-100 RNA copies/µL for all four serotypes, which is similar to other commonly used primer schemes. DengueSeq facilitates the sequencing of samples without known serotypes, allows the detection of multiple serotypes in the same sample, and can be used with a variety of library prep kits and sequencing instruments. CONCLUSIONS: DengueSeq was systematically evaluated with virus stocks and clinical specimens spanning the genetic diversity within each of the four dengue virus serotypes. The primer schemes can be plugged into existing amplicon sequencing workflows to facilitate the global need for expanded dengue virus genomic surveillance.

Chip-scale integrated holographic devices based on top-emitting vertical cavity surface emitting lasers.

Holography technology is considered the ultimate three-dimensional (3D) visualization technology in the future. However, conventional methods for achieving holography generally utilize discrete optical components and off-chip laser sources, resulting in a large size and high complexity, which are undesirable for practical applications. In this Letter, chip-scale integrated holographic devices are realized by integrating top-emitting vertical cavity surface emitting lasers (VCSELs) with micro holograms printed by 3D femtosecond laser nanoprinting technology. The VCSELs are designed to operate in a single fundamental mode with a Gaussian emission profile. Then the Gaussian beams are phase-modulated by the integrated micro holograms designed by the Gerchberg-Saxton (GS) algorithm and the target holographic images can be displayed behind the holograms. Such integrated holographic devices are of micron size and can be easily scaled into arrays with arbitrary channels on-demand, which are important for achieving miniaturized and portable holographic imaging systems.

Nanoprinted Diffractive Layer Integrated Vertical-Cavity Surface-Emitting Vortex Lasers with Scalable Topological Charge.

Vertical-cavity surface-emitting lasers (VCSELs) represent an attractive light source to integrate with OAM structures to realize chip-scale vortex lasers. Although pioneering endeavors of VCSEL-based vortex lasers have been reported, they cannot achieve large topological charges (less than l = 5) due to the insufficient space-bandwidth product (SBP) caused by the inherent limited device size. Here, by integrating a nanoprinted OAM phase structure on the VCSELs, we demonstrate a vortex microlaser with a low threshold and simple structure. A monolithic microlaser array with addressable control of vortex beams with different topological charges (l = 1 to l = 5) was achieved. Nanoprinting offers high degrees of freedom for the manipulation of spatial structures. To address the challenge of insufficient SBP, two-layer cascaded spiral phase plates were designed. Thereby, a vortex beam with l = 15 and mode purity of 83.7% was obtained. Our work paves the way for future chip-scale OAM-based information multiplexing with more channels.

In Situ Growth of Graphene Catalyzed by a Phase-Change Material at 400 °C for Wafer-Scale Optoelectronic Device Application.

The use of metal foil catalysts in the chemical vapor deposition of graphene films makes graphene transfer an ineluctable part of graphene device fabrication, which greatly limits industrialization. Here, an oxide phase-change material (V2 O5 ) is found to have the same catalytic effect on graphene growth as conventional metals. A uniform large-area graphene film can be obtained on a 10 nm V2 O5 film. Density functional theory is used to quantitatively analyze the catalytic effect of V2 O5 . Due to the high resistance property of V2 O5 at room temperature, the obtained graphene can be directly used in devices with V2 O5 as an intercalation layer. A wafer-scale graphene-V2 O5 -Si (GVS) Schottky photodetector array is successfully fabricated. When illuminated by a 792 nm laser, the responsivity of the photodetector can reach 266 mA W-1 at 0 V bias and 420 mA W-1 at 2 V. The transfer-free device fabrication process enables high feasibility for industrialization.

Genome annotation of disease-causing microorganisms.

Humans have coexisted with pathogenic microorganisms throughout its history of evolution. We have never halted the exploration of pathogenic microorganisms. With the improvement of genome-sequencing technology and the continuous reduction of sequencing costs, an increasing number of complete genome sequences of pathogenic microorganisms have become available. Genome annotation of this massive sequence information has become a daunting task in biological research. This paper summarizes the approaches to the genome annotation of pathogenic microorganisms and the available popular genome annotation tools for prokaryotes, eukaryotes and viruses. Furthermore, real-world comparisons of different annotation tools using 12 genomes from prokaryotes, eukaryotes and viruses were conducted. Current challenges and problems were also discussed.

LegumeIP V3: from models to crops-an integrative gene discovery platform for translational genomics in legumes.

Legumes have contributed to human health, sustainable food and feed production worldwide for centuries. The study of model legumes has played vital roles in deciphering key genes, pathways, and networks regulating biological mechanisms and agronomic traits. Along with emerging breeding technology such as genome editing, translation of the knowledge gained from model plants to crops is in high demand. The updated database (V3) was redesigned for translational genomics targeting the discovery of novel key genes in less-studied non-model legume crops by referring to the knowledge gained in model legumes. The database contains genomic data for all 22 included species, and transcriptomic data covering thousands of RNA-seq samples mostly from model species. The rich biological data and analytic tools for gene expression and pathway analyses can be used to decipher critical genes, pathways, and networks in model legumes. The integrated comparative genomic functions further facilitate the translation of this knowledge to legume crops. Therefore, the database will be a valuable resource to identify important genes regulating specific biological mechanisms or agronomic traits in the non-model yet economically significant legume crops. LegumeIP V3 is available free to the public at https://plantgrn.noble.org/LegumeIP. Access to the database does not require login, registration, or password.

Oral health and 10-year cardiovascular risk in US adults: mediating role of inflammatory diet and vitamin D.

OBJECTIVE: To investigate whether E-DII or vitamin D mediates the relationship between oral health and cardiovascular disease (CVD) risk. METHODS: This study involved 6616 participants aged over 30 years old from the National Health and Nutrition Examination Survey (NHANES) in 2009-2014. Dietary inflammation and 10-year CVD risk were evaluated via the Energy-adjusted Dietary Inflammatory Index (E-DII) and the Framingham Risk Score (FRS), respectively. We used correlation analysis and mediation analysis to investigate the role of dietary inflammation and vitamin D in the relationship between oral health and CVD risk. RESULTS: Oral health indicators and CVD risk were positively correlated with E-DII (r > 0, P < 0.001) and negatively correlated with vitamin D levels (r < 0, P < 0.001). The estimated mediating role of E-DII and vitamin D in the overall association between oral health and 10-year risk of CVD ranged from 4.9 to 7.5% and 6.6 to 11.6%, respectively. Furthermore, the mediation proportion of E-DII and vitamin D levels in the total association between oral health indicators and FRS were increased in participants without periodontitis. CONCLUSION: Both E-DII and serum vitamin D were mediated the association between oral problems and 10-year CVD risk, especially in participants without periodontitis. Among them, E-DII played a positive mediating role, and serum vitamin D levels was a negative mediator. CLINICAL RELEVANCE: Anti-inflammatory diet and prevention of vitamin D deficiency might reduce the impact of oral problems on cardiovascular disease risk to some extent. The study highlights the important role of oral health and dietary inflammation and vitamin D in primary prevention of cardiovascular disease.

Modelling and Research on Intuitionistic Fuzzy Goal-Based Attack and Defence Game for Infrastructure Networks.

Network attack and defence games are gradually becoming a new approach through which to study the protection of infrastructure networks such as power grids and transportation networks. Uncertainty factors, such as the subjective decision preferences of attackers and defenders, are not considered in existing attack and defence game studies for infrastructure networks. In this paper, we introduce, respectively, the attacker's and defender's expectation value, rejection value, and hesitation degree of the target, as well as construct an intuitionistic fuzzy goal-based attack and defence game model for infrastructure networks that are based on the maximum connectivity slice size, which is a network performance index. The intuitionistic fuzzy two-player, zero-sum game model is converted into a linear programming problem for solving, and the results are analysed to verify the applicability and feasibility of the model proposed in this paper. Furthermore, different situations, such as single-round games and multi-round repeated games, are also considered. The experimental results show that, when attacking the network, the attacker rarely attacks the nodes with higher importance in the network, but instead pays more attention to the nodes that are not prominent in the network neutrality and median; meanwhile, the defender is more inclined to protect the more important nodes in the network to ensure the normal performance of the network.

Graphene-silicon-graphene Schottky junction photodetector with field effect structure.

Graphene has unique advantages in ultrabroadband detection. However, nowadays graphene-based photodetectors cannot meet the requirements for practical applications due to their poor performance. Here, we report a graphene-silicon-graphene Schottky junction photodetector assisted by field effect. Two separate graphene sheets are located on both sides of the n-doped silicon to form two opposite lateral series heterojunctions with silicon, and a transparent top gate is designed to modulate the Schottky barrier. Low doping concentration of silicon and negative gate bias can significantly raise the barrier height. Under the combined action of these two measures, the barrier height increases from 0.39 eV to 0.77 eV. Accordingly, the performance of the photodetector has been greatly improved. The photoresponsivity of the optimized device is 2.6 A/W at 792 nm, 1.8 A/W at 1064 nm, and 0.42 A/W at 1550 nm, and the on/off photo-switching ratio reaches 104. Our work provides a feasible solution for the development of graphene-based optoelectronic devices.

Comprehensive Profiling of Paper Mulberry (Broussonetia papyrifera) Crotonylome Reveals the Significance of Lysine Crotonylation in Young Leaves.

Lysine crotonylation is a newly discovered and reversible posttranslational modification involved in various biological processes, especially metabolism regulation. A total of 5159 lysine crotonylation sites in 2272 protein groups were identified. Twenty-seven motifs were found to be the preferred amino acid sequences for crotonylation sites. Functional annotation analyses revealed that most crotonylated proteins play important roles in metabolic processes and photosynthesis. Bioinformatics analysis suggested that lysine crotonylation preferentially targets a variety of important biological processes, including ribosome, glyoxylate and dicarboxylate metabolism, carbon fixation in photosynthetic organisms, proteasome and the TCA cycle, indicating lysine crotonylation is involved in the common mechanism of metabolic regulation. A protein interaction network analysis revealed that diverse interactions are modulated by protein crotonylation. These results suggest that lysine crotonylation is involved in a variety of biological processes. HSP70 is a crucial protein involved in protecting plant cells and tissues from thermal or abiotic stress responses, and HSP70 protein was found to be crotonylated in paper mulberry. This systematic analysis provides the first comprehensive analysis of lysine crotonylation in paper mulberry and provides important resources for further study on the regulatory mechanism and function of the lysine crotonylated proteome.

First comprehensive analysis of lysine succinylation in paper mulberry (Broussonetia papyrifera).

BACKGROUND: Lysine succinylation is a naturally occurring post-translational modification (PTM) that is ubiquitous in organisms. Lysine succinylation plays important roles in regulating protein structure and function as well as cellular metabolism. Global lysine succinylation at the proteomic level has been identified in a variety of species; however, limited information on lysine succinylation in plant species, especially paper mulberry, is available. Paper mulberry is not only an important plant in traditional Chinese medicine, but it is also a tree species with significant economic value. Paper mulberry is found in the temperate and tropical zones of China. The present study analyzed the effects of lysine succinylation on the growth, development, and physiology of paper mulberry. RESULTS: A total of 2097 lysine succinylation sites were identified in 935 proteins associated with the citric acid cycle (TCA cycle), glyoxylic acid and dicarboxylic acid metabolism, ribosomes and oxidative phosphorylation; these pathways play a role in carbon fixation in photosynthetic organisms and may be regulated by lysine succinylation. The modified proteins were distributed in multiple subcellular compartments and were involved in a wide variety of biological processes, such as photosynthesis and the Calvin-Benson cycle. CONCLUSION: Lysine-succinylated proteins may play key regulatory roles in metabolism, primarily in photosynthesis and oxidative phosphorylation, as well as in many other cellular processes. In addition to the large number of succinylated proteins associated with photosynthesis and oxidative phosphorylation, some proteins associated with the TCA cycle are succinylated. Our study can serve as a reference for further proteomics studies of the downstream effects of succinylation on the physiology and biochemistry of paper mulberry.

Dynamic phase manipulation of vertical-cavity surface-emitting lasers via on-chip integration of microfluidic channels.

Vertical-cavity surface-emitting lasers (VCSELs) play a key role in the development of the next generation of optoelectronic technologies, thanks to their unique characteristics, such as low-power consumption, circular beam profile, high modulation speed, and large-scale two-dimensional array. Dynamic phase manipulation of VCSELs within a compact system is highly desired for a large variety of applications. In this work, we incorporate the emerging microfluidic technologies into the conventional VCSELs through a monolithic integration approach, enabling dynamic phase control of lasing emissions with low power consumption and low thermal generation. As a proof of concept, a beam steering device is experimentally demonstrated by integrating microfluidic channel on a coherently coupled VCSELs array. Experimental results show that the deflection angles of the laser beam from the chip can be tuned from 0° to 2.41° under the injection of liquids with different refractive index into the microchannel. This work opens an entirely new solution to implement a compact laser system with real-time wavefront controllability. It holds great potentials in various applications, including optical fiber communications, laser printing, optical sensing, directional displays, ultra-compact light detection and ranging (LiDAR).

High responsivity graphene-InGaAs near-infrared photodetector realized by hole trapping and its response saturation mechanism.

Graphene is an ideal material for wide spectrum detector owing to its special band structure, but its low light absorption and fast composite of photogenerated carriers lead to a weak response performance. In this paper, we designed a unique photoconductive graphene-InGaAs photodetector. The built-in electric field was formed between graphene and InGaAs, which can prolong the lifetime of photogenerated carriers and improve the response of devices by confining the holes. Compared with graphene-Si structure, a higher built-in electric field and reach to 0.54 eV is formed. It enables the device to achieve a responsivity of 60 AW-1 and a photoconductive gain of 79.4 at 792 nm. In the 1550 nm communication band, the responsivity of the device is also greater than 10 AW-1 and response speed is less than 2 ms. Meanwhile, the saturation phenomenon of light response was also found in this photoconductive graphene heterojunction detector during the experiment, we have explained the phenomenon by the capacitance theory of the built-in electric field, and the maximum optical responsivity of the detector is calculated theoretically, which is in good agreement with the measurement result.

Comprehending Cornales: phylogenetic reconstruction of the order using the Angiosperms353 probe set.

PREMISE: Cornales is an order of flowering plants containing ecologically and horticulturally important families, including Cornaceae (dogwoods) and Hydrangeaceae (hydrangeas), among others. While many relationships in Cornales are strongly supported by previous studies, some uncertainty remains with regards to the placement of Hydrostachyaceae and to relationships among families in Cornales and within Cornaceae. Here we analyzed hundreds of nuclear loci to test published phylogenetic hypotheses and estimated a robust species tree for Cornales. METHODS: Using the Angiosperms353 probe set and existing data sets, we generated phylogenomic data for 158 samples, representing all families in the Cornales, with intensive sampling in the Cornaceae. RESULTS: We curated an average of 312 genes per sample, constructed maximum likelihood gene trees, and inferred a species tree using the summary approach implemented in ASTRAL-III, a method statistically consistent with the multispecies coalescent model. CONCLUSIONS: The species tree we constructed generally shows high support values and a high degree of concordance among individual nuclear gene trees. Relationships among families are largely congruent with previous molecular studies, except for the placement of the nyssoids and the Grubbiaceae-Curtisiaceae clades. Furthermore, we were able to place Hydrostachyaceae within Cornales, and within Cornaceae, the monophyly of known morphogroups was well supported. However, patterns of gene tree discordance suggest potential ancient reticulation, gene flow, and/or ILS in the Hydrostachyaceae lineage and the early diversification of Cornus. Our findings reveal new insights into the diversification process across Cornales and demonstrate the utility of the Angiosperms353 probe set.

Graphene-assisted preparation of large-scale single-crystal Ag(111) nanoparticle arrays for surface-enhanced Raman scattering.

Surface plasmon resonance (SPR) of metal nanostructures has broad application prospects in the fields of sensing, energy, catalysis and optics. This paper reports a graphene-assisted method for preparing large-scale single-crystal Ag(111) nanoparticle (NP) arrays based on the ion implantation technique. By surface periodic patterning treatment and annealing of the implanted sample, regularly arranged Ag NPs can be prepared on the sample surface. A new application for graphene is proposed, that is, as a perfect barrier layer to prevent metal atoms from evaporating or diffusing. All the Ag NPs show (111) crystal orientation. Besides, the Ag atoms are covered by graphene immediately when they precipitate from the substrate, which can prevent them from being oxidized. On the basis of this structure, as one of the applications of the metal SPR, we have measured the surface-enhanced Raman scattering effect and found that the G peak of the Raman spectrum of the graphene achieved about 20 times enhancement.

A Cu2O/TBAB-promoted approach to synthesize heteroaromatic 2-amines via one-pot cyclization of aryl isothiocyanates with ortho-substituted amines in water.

An efficient approach to synthesize heteroaromatic 2-amines from one-pot desulfurization/dehydrogenative cyclization of aryl isothiocyanates with ortho-substituted amines in water was developed. This approach tolerated a wide range of functional groups on the aromatic ring, providing a practical and environment-friendly process to synthesize heteroaromatic 2-amines in moderate to excellent yields. A plausible mechanism was proposed and the role of TBAB and Cu2O in the present strategy was suggested with the help of ESI mass spectrometry.

Membrane-tethered Notch1 exhibits oncogenic property via activation of EGFR-PI3K-AKT pathway in oral squamous cell carcinoma.

Notch proteins are highly conserved cell surface receptors which play essential roles in cellular differentiation, proliferation, and apoptotic events at all stages of development. Recently, NOTCH1 mutations have been extensively observed in oral squamous cell carcinoma (OSCC) and are hinted to be Notch1-inactivating mutations. However, little is known about the biological effect of these reported mutations in OSCC. To mimic the inactivation of Notch1 due to inappropriate mutations and to determine the potential mechanisms, we utilized wild-type Notch1 vectors (Notch1WT ) or mutant Notch1 vectors (Notch1V1754L ) to transfect into OSCC cell lines. Membrane-tethered Notch1 induced by mutation was analyzed by immunofluorescence staining. γ-Secretase inhibitor PF-03084014 was utilized to determine the phenotype in the absence of endogenous Notch1 activation. Here we demonstrated that membrane-tethered Notch1 inactivated the canonical Notch1 signaling and oncogenic phenotypes were identified by promoting cell proliferation and invasion and by inducing epithelial-to-mesenchymal transition in cells. The γ-secretase inhibitor PF-03084014 also showed distinct oncogenic property after treatment. Importantly, both membrane-tethered Notch1 and PF-03084014 inhibitor activated the epidermal growth factor receptor (EGFR)-phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway, which has been confirmed as an overwhelming modulator in OSCC. This was the first time that we clearly simulated the mutated Notch1 activities and determined the oncogenic phenotypes of membrane-tethered Notch1. Compared with wild-type Notch1, membrane-tethered Notch1 was strongly associated with activated EGFR-PI3K-AKT signaling pathway.

Ultra-compact electrically controlled beam steering chip based on coherently coupled VCSEL array directly integrated with optical phased array.

Beam steering devices have wide applications in both military and civil fields. The ultimate goal for such devices is to reduce their size, weight, and power consumption. However, the laser source in these devices is spatially separate from the phase shifter, resulting in large size, complex packaging, and low coupling efficiency. To solve these problems, a novel electrically controlled beam steering chip based on coherently coupled vertical cavity surface emitting laser (VCSEL) array directly integrated with liquid crystal optical phased array (LCOPA) is proposed in this paper. Implant-defined in-phase coherently coupled VCSEL arrays (CCVAs) with uniform near-field are designed and fabricated first to act as the coherent laser source for the chip. Then, taking advantage of the CCVA planar structure, the LCOPA is integrated directly on the CCVA by conventional process. The coherent light generated by the in-phase CCVA is uniformly and normally incident into the LCOPA and is electrically steered by the LCOPA. One-dimensional beam steering is achieved by two proof-of-concept integrated chips. The chips based on a 4 × 4 square CCVA and a 16-element hexagonal CCVA offer a field of view of 2.21° and 6.06°, respectively. Independent control of the CCVA and LCOPA guarantees a relatively high wavelength stability and power stability. Theoretical calculations are also performed, which are consistent with the experiments.

Resolving relationships and phylogeographic history of the Nyssa sylvatica complex using data from RAD-seq and species distribution modeling.

Nyssa sylvatica complex consists of several woody taxa occurring in eastern North America. These taxa were recognized as two or three species including three or four varieties by different authors. Due to high morphological similarities and complexity of morphological variation, classification and delineation of taxa in the group have been difficult and controversial. Here we employ data from RAD-seq to elucidate the genetic structure and phylogenetic relationships within the group. Using the genetic evidence, we evaluate previous classifications and delineate species. We also employ Species Distribution Modeling (SDM) to evaluate impacts of climatic changes on the ranges of the taxa and to gain insights into the relevant refugia in eastern North America. Results from Molecular Variance Analysis (AMOVA), STRUCTURE, phylogenetic analyses using Maximum likelihood, Bayesian Inference, and Splittree methods of RAD-seq data strongly support a two-clade pattern, largely separating samples of N. sylvatica from those of N. biflora-N. ursina mix. Divergence time analysis with BEAST suggests the two clades diverged in the mid Miocene. The ancestor of the present trees of N. sylvatica was suggested to be in the Pliocene and that of N. biflora-N. ursina mix in the end of the Miocene. Results from SDM predicted a smaller range in the southern part of the species present range of each clade during the Last Glacial Maximum (LGM). A northward expansion of the ranges during interglacial period and a northward shift of the ranges in the future under a model of global warming were also predicted. Our results support the recognition of two species in the complex, N. sylvatica and N. biflora, following the phylogenetic species concept. We found no genetic evidence supporting recognitions of intraspecific taxa. However, we propose subsp. ursina and subsp. biflora within N. biflora due to their distinction in habits, distributions, and habitats. Our results further support movements of trees in eastern North America in response to climatic changes. Finally, our study demonstrates that RAD-seq data and a combination of population genomics and SDM are valuable in resolving relationship and biogeographic history of closely related species that are taxonomically difficult.

MiR-876-5p modulates head and neck squamous cell carcinoma metastasis and invasion by targeting vimentin.

BACKGROUND: Local or distant metastasis remains the main course of death in head and neck squamous cell carcinoma (HNSCC) patients. MicroRNAs (miRNAs) have been implicated in metastasis of HNSCC, but the mechanisms of their action are mainly undocumented. Through public head and neck cancer miRNA expression datasets, we found that miR-876-5p was a novel potential tumor suppressor targeting HNSCC metastasis. METHODS: Clinical significance and mechanism of miR-876-5P was systematically analyzed in HNSCC. Quantitative RT-PCR was used to evaluate miR-876-5p levels in HNSCC cell lines and in 20 pairs of HNSCC with associated regional nodal metastases and HNSCC without metastatic primary tumors. Scratch and invasion assays were evaluated to determine the role of miR-876-5p in the regulation of HNSCC cell migration and invasion, respectively. Western blotting was used to investigate the mechanism by which miR-876-5p suppresses HNSCC cell invasion and migration. Luciferase assays were performed to assess miR-876-5p binding to the vimentin gene. The animal model was used to support the in vitro experimental findings. RESULTS: MiR-876-5p mimics inhibited HNSCC cell migration and invasion. Vimentin protein and mRNA levels were decreased in the miR-876-5p mimics group but increased in the miR-876-5p inhibitors group, which demonstrated that miR-876-5p inhibits vimentin expression in HNSCC cells. By directly targeting the vimentin 3'-UTR, we used dual-luciferase reporter assays to verify that vimentin is a functional downstream target of miR-876-5p. Importantly, increased vimentin expression promoted cell migration and invasion, and co-transfection with miR-876-5p mimics and vimentin restored cell aggressiveness to the original level. Moreover, miR-876-5p overexpression significantly downregulated vimentin expression level and inhibited the distal metastasis of HNSCC cells in vivo. CONCLUSIONS: miR-876-5p, which functions as a tumor suppressor in HNSCC, inhibits metastasis by targeting vimentin and provides a novel therapeutic target for HNSCC treatment.