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Huang, C.

Publications and source records attributed to Huang, C..

At least 127 records · Page 7Linked to original sources
bioRxiv2023

Personal transcriptome variation is poorly explained by current genomic deep learning models

Genomic deep learning models can predict genome-wide epigenetic features and gene expression levels directly from DNA sequence. While current models perform well at predicting gene expression levels across genes in different cell types from the reference genome, their ability to explain expression variation between individuals due to cis-regulatory genetic variants remains largely unexplored. Here we evaluate four state-of-the-art models on paired personal genome and transcriptome data and find limited performance when explaining variation in expression across individuals.

genomics↗
bioRxiv2023

Reduced Reverse Replay in Anxious Individuals Impairs Reward Prediction

Understanding how we learn about the value and structure of our environment is central to neurocognitive theories of many psychiatric and neurological disorders. Learning processes have been extensively studied during performance of behavioural tasks (online learning) but less so in relation to "resting" (offline) states. A candidate mechanism for such offline learning is "replay," the sequential neural reactivation of past experiences. Notably, value-based learning is especially tied to replay unfolding in reverse order relative to the original experience ("backward replay"). Here, we demonstrate the utility of EEG-based neural decoding for investigating offline learning, and relate it to trait anxiety. Participants were first required to infer sequential relationships among task objects by using a learned rule to reorganise their visual experiences into distinct sequences. Afterwards, they observed that the final object in one of the sequences was associated with a monetary reward and then entered a post-value resting state. During this rest, we found evidence of backward replay for reward-linked object sequences. The strength of such replay was negatively associated with trait anxiety and positively predicted an increased behavioural preference for reward-predictive stimuli. We also found that high-trait-anxiety individuals showed inefficient credit assignment irrespective of reward magnitude, indicating that this effect does not merely reflect reduced reward sensitivity. Together, these findings suggest a potential aberrant replay mechanism during offline learning in individuals with high trait anxiety. More broadly, our approach illustrates the potential of EEG for measuring structured neural representations in vivo, with implications for studying cognition across a range of neuropsychiatric and neurological disorders.

neuroscience↗
bioRxiv2023

GRAS1 non-coding RNA protects against DNA damage and cell death by binding NKAP

Non-coding RNA (ncRNA) gene products are involved in diverse biological processes including splicing, epigenetic regulation, gene expression, proliferation, and metabolism. The biological mechanisms by which ncRNAs contribute to cell survival remain poorly understood. We found that the Growth Regulator Antisense 1 (GRAS1) long non-coding RNA (lncRNA) transcript promotes growth in multiple human cell types by protecting against DNA damage. Knockdown of GRAS1 induced DNA damage and cell death, along with significant expression changes in DNA damage response, intrinsic apoptotic signaling, and cellular response to environmental stimulus genes. Extensive DNA damage occurred after GRAS1 knockdown, with numerous double strand breaks occurring in each cell. The number of cells undergoing apoptosis and with fragmented nuclei increased significantly after GRAS1 knockdown. We used RNA antisense purification and mass spectrometry (RAP-MS) to identify the NF-{kappa}B activating protein (NKAP) as a direct protein interaction partner of GRAS1 lncRNA. NKAP protein was degraded after GRAS1 knockdown, in a proteasome-dependent manner. Overexpression of GRAS1 or NKAP mitigated the DNA damage effects of GRAS1 knockdown. In summary, GRAS1 and NKAP directly interact to protect against DNA damage and cell death in multiple human cell lines.

molecular biology↗
bioRxiv2023

Differential encoding of temporal context and expectation under representational drift across hierarchically connected areas

The classic view that neural populations in sensory cortices preferentially encode responses to incoming stimuli has been strongly challenged by recent experimental studies. Despite the fact that a large fraction of variance of visual responses in rodents can be attributed to behavioral state and movements, trial-history, and salience, the effects of contextual modulations and expectations on sensory-evoked responses in visual and association areas remain elusive. Here, we present a comprehensive experimental and theoretical study showing that hierarchically connected visual and association areas differentially encode the temporal context and expectation of naturalistic visual stimuli, consistent with the theory of hierarchical predictive coding. We measured neural responses to expected and unexpected sequences of natural scenes in the primary visual cortex (V1), the posterior medial higher order visual area (PM), and retrosplenial cortex (RSP) using 2-photon imaging in behaving mice collected through the Allen Institute Mindscopes OpenScope program. We found that information about image identity in neural population activity depended on the temporal context of transitions preceding each scene, and decreased along the hierarchy. Furthermore, our analyses revealed that the conjunctive encoding of temporal context and image identity was modulated by expectations of sequential events. In V1 and PM, we found enhanced and specific responses to unexpected oddball images, signaling stimulus-specific expectation violation. In contrast, in RSP the population response to oddball presentation recapitulated the missing expected image rather than the oddball image. These differential responses along the hierarchy are consistent with classic theories of hierarchical predictive coding whereby higher areas encode predictions and lower areas encode deviations from expectation. We further found evidence for drift in visual responses on the timescale of minutes. Although activity drift was present in all areas, population responses in V1 and PM, but not in RSP, maintained stable encoding of visual information and representational geometry. Instead we found that RSP drift was independent of stimulus information, suggesting a role in generating an internal model of the environment in the temporal domain. Overall, our results establish temporal context and expectation as substantial encoding dimensions in the visual cortex subject to fast representational drift and suggest that hierarchically connected areas instantiate a predictive coding mechanism.

neuroscience↗
bioRxiv2023

Three-dimensional Shear Wave Elastography Using Acoustic Radiation Force and A 2-D Row-Column Addressing (RCA) Array

Acoustic radiation force (ARF)-based shear wave elastography (SWE) is a clinically available ultrasound imaging mode that noninvasively and quantitatively measures tissue stiffness. Current implementations of ARF-SWE are largely limited to 2-D imaging, which does not provide robust estimation of heterogeneous tissue mechanical properties. Existing 3-D ARF-SWE solutions that are clinically available are based on wobbler probes, which cannot provide true 3-D shear wave motion detection. Although 3-D ARF-SWE based on 2-D matrix arrays have been previously demonstrated, they do not provide a practical solution because of the need for a high channel-count ultrasound system (e.g., 1024-channel) to provide adequate volume rates and the delicate circuitries (e.g., multiplexers) that are vulnerable to the long-duration "push" pulses. To address these issues, here we propose a new 3-D ARF-SWE method based on the 2-D row-column addressing (RCA) array which has a much lower element count (e.g., 256), provides an ultrafast imaging volume rate (e.g., 2000 Hz), and can withstand the push pulses. In this study, we combined the comb-push shear elastography (CUSE) technique with 2-D RCA for enhanced SWE imaging field-of-view. In vitro phantom studies demonstrated that the proposed method had robust 3-D SWE performance in both homogenous and inclusion phantoms. An in vivo study on a breast cancer patient showed that the proposed method could reconstruct 3-D elasticity maps of the breast lesion, which was validated using a commercial ultrasound scanner. These results demonstrate strong potential for the proposed method to provide a viable and practical solution for clinical 3-D ARF-SWE.

bioengineering↗
bioRxiv2023

Integrated Spatial Transcriptomic and Proteomic Analysis of Fresh Frozen Tissue Based on Stereo-seq

To simultaneously detect whole transcriptomes and protein markers on the same tissue section, we combined Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) and Stereo-seq to develop the Stereo-CITE-seq workflow. Here, we demonstrated that Stereo-CITE-seq can co-detect mRNAs and proteins in immune organs with high spatial resolution, reproducibility and accuracy.

molecular biology↗
bioRxiv2023

AbFold -- an AlphaFold Based Transfer Learning Model for Accurate Antibody Structure Prediction

MotivationAntibodies are a group of proteins generated by B cells, which are crucial for the immune system. The importance of antibodies is ever-growing in pharmaceutics and biotherapeutics. Despite recent advancements pioneered by AlphaFold in general protein 3D structure prediction, accurate structure prediction of antibodies still lags behind, primarily due to the difficulty in modeling the Complementarity-determining regions (CDRs), especially the most variable CDR-H3 loop. ResultsThis paper presents AbFold, a transfer learning antibody structure prediction model with 3D point cloud refinement and unsupervised learning techniques. AbFold consistently produces state-of-the-art results on the prediction accuracy of the six CDR loops. The predictions of AbFold achieve an average RMSD of 1.51 [A] for both heavy and light chains and an average RMSD of 3.04 [A] for CDR-H3, bettering current models AlphaFold and IgFold. AbFold will contribute to antibody structure prediction and design processes.

bioinformatics↗
bioRxiv2023

Lassa virus NP DEDDh 3'-5' exoribonuclease activity is required for optimal viral RNA replication.

Lassa virus (LASV), a mammarenavirus from Arenaviridae, is the causative agent of Lassa fever (LF) endemic in West Africa. Currently, there are no vaccines or antivirals approved for LF. The RNA-dependent RNA polymerases (RdRp) of RNA viruses are error-prone. As a negative-sense RNA virus, how LASV copes with errors in RNA synthesis and ensures optimal RNA replication are not well elucidated. LASV nucleoprotein (NP) contains a DEDDH 3'-to-5' exoribonuclease motif (ExoN), which is known to be essential for LASV evasion of the interferon response via its ability to degrade virus-derived double-stranded RNA. Herein, we present evidence that LASV NP ExoN has an additional function important for viral RNA replication. We rescued an ExoN-deficient LASV mutant (ExoN- rLASV) by using a reverse genetics system. Our data indicated that abrogation of NP ExoN led to impaired LASV growth and RNA replication in interferon-deficient cells as compared with wild-type rLASV. By utilizing PacBio Single Molecule, Real-Time (SMRT) long-read sequencing technology, we found that rLASV lacking ExoN activity was prone to producing aberrant viral genomic RNA with structural variations. In addition, NP ExoN deficiency enhanced LASV sensitivity to mutagenic nucleoside analogues in virus titration assay. Next-generation deep sequencing analysis showed increased single nucleotide substitution in ExoN- LASV RNA following mutagenic 5-flurouracil treatment. In conclusion, our study revealed that LASV NP ExoN is required for efficient viral RNA replication and mutation control. Among negative-sense RNA viruses, LASV NP is the first example that a viral protein, other than the RdRp, contributes to reduce errors in RNA replication and maintain genomic RNA integrity. These new findings promote our understanding of the basics of LASV infection and inform antiviral and vaccine development. Authors SummaryLassa fever (LF) is a severe and often fatal disease endemic in West Africa. There is no vaccines or antivirals approved for LF. The disease is caused by Lassa virus (LASV), a member of the arenavirus family. LASV nucleoprotein (NP) contains a DEDDh exoribonuclease (ExoN) motif, through which NP degrades virus-derived, immunostimulatory double-stranded RNA and inhibit host innate immune response. Thus, it is well known that NP ExoN is important for LASV pathogenicity. Intriguingly, the NP ExoN motif is highly conserved among arenaviruses, regardless of pathogenicity and viral ability to evade innate immune response, suggesting arenavirus NP ExoN may have additional function(s) in virus infection. In this study, we found that loss of ExoN activity affected LASV multiplication and RNA replication in interferon-deficient Vero cells. The ExoN-deficient rLASV exhibited reduced level of viral RNA, increased frequency of structural variation in virus genomic RNA, and higher mutation rate following mutagenic nucleoside analogue treatment. In conclusion, LASV NP ExoN plays an important role in viral RNA replication and fitness. Our new findings may inform antiviral and vaccine development and have broader implication on the function of NP ExoN of other arenaviruses.

microbiology↗
bioRxiv2023

High Volume Rate 3-D Ultrasound Imaging Using Fast-Tilting and Redirecting Reflectors

3-D ultrasound imaging has many advantages over 2-D imaging such as more comprehensive tissue evaluation and less operator dependence. Although many 3-D ultrasound imaging techniques have been developed in the last several decades, a low-cost and accessible solution with high imaging volume rate and imaging quality remains elusive. Recently we proposed a new, high volume rate 3-D ultrasound imaging technique: Fast Acoustic Steering via Tilting Electromechanical Reflectors (FASTER), which uses a water-immersible and fast-tilting acoustic reflector to steer ultrafast plane waves in the elevational direction to achieve high volume rate 3-D ultrasound imaging with conventional 1-D array transducers. However, the initial implementation of FASTER imaging only involves a single fast-tilting acoustic reflector, which is inconvenient to use because the probe cannot be held in the regular upright position. Also, conventional FASTER imaging can only be performed inside a water tank because of the necessity of using water for acoustic conduction. To address these limitations of conventional FASTER, here we developed a novel ultrasound probe clip-on device that encloses a fast-tilting reflector, a redirecting reflector, and an acoustic wave conduction medium. The new FASTER 3-D imaging device can be easily attached to or removed from clinical ultrasound transducers, allowing rapid transformation from 2-D to 3-D ultrasound imaging. In vitro B-mode imaging studies demonstrated that the proposed method provided comparable imaging quality (e.g., spatial resolution and contrast-to-noise ratio) to conventional, mechanical-translation-based 3-D imaging while providing a much faster 3-D volume rate (e.g., 300 Hz vs [~]10 Hz). In addition to B-mode imaging, we also demonstrated 3-D power Doppler imaging and 3-D super-resolution ultrasound localization microscopy with the newly developed FASTER device. An in vivo imaging study showed that the FASTER device could clearly visualize the 3-D anatomy of the basilic vein of a healthy volunteer, and customized beamforming was implemented to accommodate the speed of sound difference between the acoustic medium and the imaging object (e.g., soft tissue). These results suggest that the newly developed redirecting reflector and the clip-on device could overcome key hurdles for future clinical translation of the FASTER 3-D imaging technology.

bioengineering↗
bioRxiv2023

Genome mining unveils a class of ribosomal peptides with two amino termini

The era of inexpensive genome sequencing and improved bioinformatics tools has reenergized the study of natural products, including the ribosomally synthesized and post-translationally modified peptides (RiPPs). In recent years, RiPP discovery has challenged preconceptions about the scope of post-translational modification chemistry, but genome mining of new RiPP classes remains an unsolved challenge. Here, we report a RiPP class defined by an unusual (S)-N2,N2-dimethyl-1,2-propanediamine (Dmp)-modified C-terminus, which we term the daptides. Nearly 500 daptide biosynthetic gene clusters (BGCs) were identified by analyzing the RiPP Recognition Element (RRE), a common substrate-binding domain found in half of prokaryotic RiPP classes. A representative daptide BGC from Microbacterium paraoxydans DSM 15019 was selected for experimental characterization. Derived from a C-terminal threonine residue, the class-defining Dmp is installed over three steps by an oxidative decarboxylase, aminotransferase, and methyltransferase. Daptides uniquely harbor two positively charged termini, and thus we suspect this modification could aid in membrane targeting, as corroborated by hemolysis assays. Our studies further show that the oxidative decarboxylation step requires a functionally unannotated accessory protein. Fused to the C-terminus of the accessory protein is an RRE domain, which delivers the unmodified substrate peptide to the oxidative decarboxylase. This discovery of a class-defining post-translational modification in RiPPs may serve as a prototype for unveiling additional RiPP classes through genome mining.

biochemistry↗
bioRxiv2023

SUMOylation of PTEN promotes DNA end resection through directly dephosphorylating 53BP1 in homologous recombination repair

Homologous recombination (HR) repair for DNA double-strand breaks (DSBs) is critical for maintaining genome stability and cell survival. Nuclear PTEN plays a key role in HR repair, but the underlying mechanism remains largely elusive. We find that SUMOylated PTEN promotes HR repair but represses non-homologous end joining (NHEJ) repair by directly dephosphorylating 53BP1. During DNA damage responses (DDR), p14ARF was phosphorylated and then interacted efficiently with PTEN, thus promoting PTEN SUMOylation as an atypical SUMO E3 ligase. Interestingly, SUMOylated PTEN was subsequently recruited to the chromatin at DNA-break sites. This was because that SUMO1 conjugated to PTEN was recognized and bound by the SUMO-interacting motif (SIM) of BRCA1, which has been located to the core of 53BP1 foci on the chromatin during S/G2 stage. Further, these chromatin-loaded PTEN directly and specifically dephosphorylated pT543 of 53BP1, resulting in the dissociation of 53BP1-complex, which facilitated DNA end resection and ongoing HR repair. The SUMOylation-deficient PTENK254R mice also showed decreased DNA damage repair in vivo. Blocking PTEN SUMOylation pathway with either an SUMOylation inhibitor or a p14ARF(2-13) peptide sensitized tumor cells to chemotherapy. Our study therefore provides the new mechanistic understanding of PTEN in HR repair and clinical intervention of chemo-resistant tumors.

cell biology↗
bioRxiv2023

Loss of the endocytic tumor suppressor HD-PTP phenocopies LKB1 and promotes RAS-driven oncogenesis.

Abstract/SummaryOncogenic RAS mutations drive aggressive cancers that are difficult to treat in the clinic, and while direct inhibition of the most common KRAS variant in lung adenocarcinoma (G12C) is undergoing clinical evaluation, a wide spectrum of oncogenic RAS variants together make up a large percentage of untargetable lung and GI cancers. Here we report that loss-of-function alterations (mutations and deep deletions) in the gene that encodes HD-PTP (PTPN23) occur in up to 14% of lung cancers in the ORIEN Avatar lung cancer cohort, associate with adenosquamous histology, and occur alongside an altered spectrum of KRAS alleles. Furthermore, we show that in publicly available early-stage NSCLC studies loss of HD-PTP is mutually exclusive with loss of LKB1, which suggests they restrict a common oncogenic pathway in early lung tumorigenesis. In support of this, knockdown of HD-PTP in RAS-transformed lung cancer cells is sufficient to promote FAK-dependent invasion. Lastly, knockdown of the Drosophila homolog of HD-PTP (dHD-PTP/Myopic) synergizes to promote RAS-dependent neoplastic progression. Our findings highlight a novel tumor suppressor that can restrict RAS-driven lung cancer oncogenesis and identify a targetable pathway for personalized therapeutic approaches for adenosquamous lung cancer.

cancer biology↗
bioRxiv2023

Acetylated dietary protein contributes to the acetylome in cells via KARS-mediated intra-translational deposition of acetyl-lysine in nascent protein

N6-acetyl-L-lysine residue is abundant in dietary protein but less is known about its potential influences on the diet-consumers. We herein report that KARS mediates intra- translational deposition of diet-derived N6-acetyl-L-lysine in nascent proteins to contribute the acetylome in cells. Acetylated dietary protein is a direct source of N6-acetyl-L-lysine that can widely and substantially contribute the acetylome in multiple organs of mice. By analyzing the co-crystal structure of Lysyl-tRNA synthetase (KARS) in complex with N6- acetyl-L-lysyl-AMP and pyrophosphate, together with in vitro biochemical assays, we learned that KARS can utilize N6-acetyl-L-lysine to produce N6-acetyl-L-lysyl-AMP and transfers the N6-acetyl-L-lysyl-moiety to lysine cognate tRNA to generate N6-acetyl-L- lysyl-tRNA, which introduces N6-acetyl-L-lysine into growing nascent polypeptide and intra-translationally results in protein acetylation. This undocumented protein modification mechanism is inherently different from post-translational modification (PTM) and termed as intra-translational modification (ITM). ITM can functionally mimic PTM mechanisms to deposit acetylation in histones to decondense chromatin. It can also modify PTM- inaccessible regions that are buried inside and functionally important to proteins. ITM is expected to extend the repertoire of acetylome and improve our understandings in protein modification modes in cells.

biochemistry↗
bioRxiv2022

StereoSiTE: A framework to spatially and quantitatively profile the cellular neighborhood organized iTME

With emerging of Spatial Transcriptomics (ST) technology, a powerful algorithmic framework to quantitatively evaluate the active cell-cell interactions in the bio-function associated iTME unit will pave the ways to understand the mechanism underlying tumor biology. This study provides the StereoSiTE incorporating open source bioinformatics tools with the self-developed algorithm, SCII, to dissect a cellular neighborhood (CN) organized iTME based on cellular compositions, and to accurately infer the functional cell-cell communications with quantitatively defined interaction intensity in ST data. We applied StereoSiTE to deeply decode ST data of the xenograft models receiving immunoagonist. Results demonstrated that the neutrophils dominated CN5 might attribute to iTME remodeling after treatment. To be noted, SCII analyzed the spatially resolved interaction intensity inferring a neutrophil leading communication network which was proved to actively function by analysis of Transcriptional Factor Regulon and Protein-Protein Interaction. Altogether, StereoSiTE is a promising framework for ST data to spatially reveal tumoribiology mechanisms.

cancer biology↗
bioRxiv2022

Nicotiana benthamiana XYLEM CYSTEINE PROTEASE genes facilitate tracheary element formation in interfamily grafting

Grafting is a plant propagation technique widely used in agriculture. A recent discovery of the capability of interfamily grafting in Nicotiana has expanded the potential combinations of grafting. In this study, we showed that xylem connection is essential for the achievement of interfamily grafting and investigated the molecular basis of xylem formation at the graft junction. Transcriptome and gene network analyses revealed gene modules for tracheary element (TE) formation during grafting that include genes associated with xylem cell differentiation and immune response. The reliability of the drawn network was validated by examining the role of the Nicotiana benthamiana XYLEM CYSTEINE PROTEASE (NbXCP) genes in TE formation during interfamily grafting. Promoter activities of NbXCP1 and NbXCP2 genes were found in differentiating TE cells in the stem and callus tissues at the graft junction. Analysis of a Nbxcp1;Nbxcp2 loss-of-function mutant indicated that NbXCPs control the timing of de novo TE formation at the graft junction. Moreover, grafts of the NbXCP1 overexpressor increased the scion growth rate as well as the fruit size. Thus, we identified gene modules for TE formation at the graft boundary and demonstrated potential ways to enhance Nicotiana interfamily grafting.

plant biology↗
bioRxiv2022

Electrophysiological indices of distractor processing in visual search are shaped by target expectations.

Although in many cases salient stimuli capture attention involuntarily, it has been proposed recently that under certain conditions the bottom-up signal generated by such stimuli can be proactively suppressed. In support of this signal suppression hypothesis, ERP studies have demonstrated that salient stimuli that do not capture attention elicit a distractor positivity (PD), a putative neural index of suppression. At the same time, it is becoming increasingly clear that regularities across preceding search episodes have a large influence on attentional selection. Yet to date, studies in support of the signal suppression hypothesis have largely ignored the role of selection history on the processing of distractors. The current study addressed this issue by examining how electrophysiological markers of attentional selection (N2pc) and suppression (PD) elicited by targets and distractors respectively were modulated when the search target randomly varied instead of being fixed across trials. Results showed that while target selection was unaffected by this manipulation, both in terms of manual response times, as well as in terms of the N2pc component, the PD component was reliably attenuated when the target features varied randomly across trials. This result demonstrates that the distractor PD, which is typically considered the marker of selective distractor processing cannot unequivocally be attributed to suppression only, as it also, at least in part, reflects the upweighting of target features.

neuroscience↗
bioRxiv2022

Identification of S1PR4 as an immune modulator for favorable prognosis in HNSCC through unbiased machine learning

As the largest family of membrane proteins, G protein-coupled receptors (GPCRs) are the most prominent family of pharmacological targets. However, only a few GPCRs have been well-defined in terms of their physiological and pathological functions. Thus, an efficient way to identify key GPCRs involved in tumour formation is urgently needed. In this study, patients with head and neck squamous cell carcinoma (HNSCC) were classified into two different subtypes based on the characteristics of GPCRs using an unbiased machine learning method. Notably, these two subtypes showed significant differences in prognosis, gene expression, and immune microenvironment, especially in the infiltration of CD8+ T cells. Based on these differences, we screened three potential key regulators (S1PR4, S1PR5, and GPR87) from all GPCRs and constructed a prognostic nomogram for patients with HNSCC. We identified S1PR4 as the key GPCR in determining the two subtypes for positive correlation with the proportion and cytotoxicity of CD8+ T cells in HNSCC and was mainly expressed in a subset of CX3CR1+CD8+ T cells. We also demonstrated that S1PR4 is an immune modulator for the favourable prognosis of HNSCC patients. We found that S1PR4 was highly expressed in CD8+ T cells from the tumours of HNSCC patients, which was significantly associated with better prognosis, and S1PR4 expression was accompanied by higher T cell cytotoxic marker expression (IFNG and GZMB). Notably, S1PR4 co-localised with CX3CR1, which has been identified as the most cytotoxic marker of CD8+ T cells. Furthermore, S1PR4 upregulation could significantly increase T cell function in CAR-T cell therapy, indicating its great potential in cancer immunotherapy. Therefore, these results identified S1PR4 as a key indicator of cytotoxicity and the proportion of tumour-infiltrating CD8+ T cells and confirmed the prognostic value of S1PR4 in HNSCC. Our findings contribute to the knowledge of S1PR4 in anti-tumour immunity, providing a potential GPCR-targeted therapeutic option for future HNSCC treatment.

cancer biology↗