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Zhang, D.

Publications and source records attributed to Zhang, D..

At least 397 records · Page 22Linked to original sources
bioRxiv2020

Reproducible abnormalities of functional gradient reliably predict clinical and cognitive symptoms in schizophrenia

BackgroundSchizophrenia (SZ) typically manifests heterogeneous phenotypes involving positive, negative and cognitive symptoms. However, the underlying neural mechanisms of these symptoms keep unclear. Functional gradient is a fascinating measure to characterize continuous, hierarchical organization of brain. MethodsWe aimed to investigate whether reproducible disruptions of functional gradient existed in SZ compared to normal controls (NC), and these abnormalities were associated with severity of clinical and cognitive symptoms in SZ. All analyses were implemented in two independent large-sample multi-site datasets (discovery dataset, 400 SZ and 336 NC; replication dataset, 279 SZ and 262 NC). First, functional gradient across cerebral cortex was calculated in each subject. Second, vertex-wise comparisons of cortical gradient between SZ and NC groups were performed to identify abnormalities in SZ. Meanwhile, reproducible and robustness analyses were implemented to validate these abnormalities. Finally, regression analyses were performed using generalized additive models to link these abnormalities to severity of clinical and cognitive symptoms in SZ. ResultsWe found an abnormal gradient map in SZ in the discovery dataset, which was reproducible in the replication dataset. The abnormal gradient pattern was also robust when performing methodological alternatives and control analyses. Further, these reproducible abnormalities can reliably predict symptoms of clinical and cognitive domains across the two independent datasets. ConclusionThese findings demonstrated that alterations in functional gradient can provide a reliable signature of SZ, characterizing the heterogenous symptoms of clinical or cognitive domains, and may be further investigated to understand the neurobiological mechanisms of these symptoms. Impact StatementIn our study, using functional gradient measure and statistical learning technology and two independent multi-site case-control resting-state fMRI datasets (discovery dataset: 736 subjects; replication dataset: 541 subjects), we comprehensively investigated functional hierarchical organization in the cerebral cortex of SZ and its association with interindividual severity of symptoms. We found reproducible and robust abnormalities of functional gradient existed in SZ, which provided a reliable signature to characterize negative and general psychopathology symptoms, as well as cognitive deficits. Our findings can provide new insights to understand the neurobiological mechanisms of clinical and cognitive symptoms in SZ.

neuroscience↗
bioRxiv2020

Transcriptome analysis of Fenneropenaeus chinensis (Decapoda: Penaeidae) after low-salinity exposure identifies differentially expressed genes in pathways potentially related to osmoregulation

This study investigates the molecular responses of Chinese shrimp (Fenneropenaeus chinensis) to low salinity stress, employing RNA-seq and functional enrichment analyses. A total of 12,332 expressed genes were identified, with 227 differentially expressed genes (DEGs) detected, revealing intricate adaptive responses in gill tissues. Functional enrichment analysis highlighted DEGs associated with ion-transport regulation, bio-metabolism and detoxification (based on GO terms). The upregulation of ATP1A1, SLC26A2, and STK39 suggested a pivotal role of ion-transport regulation, emphasizing the importance of maintaining osmotic balance. In terms of bio-metabolism, ENPP6, GLS, and DMGDH exhibited significant upregulation, indicating adjustments in energy metabolism for low-salinity adaptation. Notably, the downregulation of GSTO1 and CTH raised questions about detoxification pathways, potentially reflecting adaptations or compromises in response to low salinity. Further correlation network analysis highlighted key genes like GLS, STK39, SESN1, and SARDH, revealing intricate relationships among DEGs. RT-qPCR validation confirmed the consistency of gene expression patterns with RNA-seq results. In conclusion, this study provides a comprehensive understanding of the molecular mechanisms underlying Chinese shrimp responses to low salinity stress. The identified genes lay the groundwork for targeted interventions and strategies to enhance shrimp aquaculture system resilience amid changing salinity levels.

physiology↗
bioRxiv2020

Unification of the M/ORF3-related proteins points to a diversified role for ion conductance in pathogenesis of coronaviruses and other nidoviruses

The new coronavirus, SARS-CoV-2, responsible for the COVID-19 pandemic has emphasized the need for a better understanding of the evolution of virus-host conflicts. ORF3a in both SARS-CoV-1 and SARS-CoV-2 are ion channels (viroporins) and involved in virion assembly and membrane budding. Using sensitive profile-based homology detection methods, we unify the SARS-CoV ORF3a family with several families of viral proteins, including ORF5 from MERS-CoVs, proteins from beta-CoVs (ORF3c), alpha-CoVs (ORF3b), most importantly, the Matrix (M) proteins from CoVs, and more distant homologs from other nidoviruses. By sequence analysis and structural modeling, we show that these viral families utilize specific conserved polar residues to constitute an ion-conducting pore in the membrane. We reconstruct the evolutionary history of these families, objectively establish the common origin of the M proteins of CoVs and Toroviruses. We show that the divergent ORF3a/ORF3b/ORF5 families represent a duplication stemming from the M protein in alpha- and beta-CoVs. By phyletic profiling of major structural components of primary nidoviruses, we present a model for their role in virion assembly of CoVs, ToroVs and Arteriviruses. The unification of diverse M/ORF3 ion channel families in a wide range of nidoviruses, especially the typical M protein in CoVs, reveal a conserved, previously under-appreciated role of ion channels in virion assembly, membrane fusion and budding. We show that the M and ORF3 are under differential evolutionary pressures; in contrast to the slow evolution of M as core structural component, the CoV-ORF3 clade is under selection for diversification, which indicates it is likely at the interface with host molecules and/or immune attack. IMPORTANCECoronaviruses (CoVs) have become a major threat to human welfare as the causative agents of several severe infectious diseases, namely Severe Acute Respiratory Syndrome (SARS), Middle Eastern Respiratory Syndrome (MERS), and the recently emerging human coronavirus disease 2019 (COVID-19). The rapid spread, severity of these diseases, as well as the potential re-emergence of other CoV-associated diseases have imposed a strong need for a thorough understanding of function and evolution of these CoVs. By utilizing robust domain-centric computational strategies, we have established homologous relationships between many divergent families of CoV proteins, including SARS-CoV/SARS-CoV-2 ORF3a, MERS-CoV ORF5, proteins from both beta-CoVs (ORF3c) and alpha-CoVs (ORF3b), the typical CoV Matrix proteins, and many distant homologs from other nidoviruses. We present evidence that they are active ion channel proteins, and the Cov-specific ORF3 clade proteins are under selection for rapid diversification, suggesting they might have been involved in interfering host molecules and/or immune attack.

microbiology↗
bioRxiv2020

Candidate Explorer: a tool for discovery, evaluation, and display of mutations causing significant immune phenotypes

When applied to immunity, forward genetic studies use meiotic mapping to provide strong statistical evidence that a particular mutation is causative of a particular immune phenotype. Notwithstanding this, co-segregation of multiple mutations, occasional unawareness of mutations, and paucity of homozygotes may lead to erroneous declarations of cause and effect. We sought to improve the selection of authentic causative mutations using a machine learning software tool, Candidate Explorer (CE), which integrates 65 data features into a single numeric score, mathematically convertible to the likelihood of verification of any putative mutation-phenotype association. CE has identified most genes within which mutations can be causative of flow cytometric phenovariation in Mus musculus. The majority of these genes were not previously known to support immune function or homeostasis. Mouse geneticists will find CE data informative in identifying causative mutations within quantitative trait loci, while clinical geneticists may use CE to help connect causative variants with rare heritable diseases of immunity, even in the absence of linkage information. CE displays integrated mutation, phenotype, and linkage data, and is freely available for query online.

genetics↗
bioRxiv2020

Human Identical Sequences of SARS-CoV-2 Promote Clinical Progression of COVID-19 by Upregulating Hyaluronan via NamiRNA-Enhancer Network

The COVID-19 pandemic is a widespread and deadly public health crisis. The pathogen SARS-CoV-2 replicates in the lower respiratory tract and causes fatal pneumonia. Although tremendous efforts have been put into investigating the pathogeny of SARS-CoV-2, the underlying mechanism of how SARS-CoV-2 interacts with its host is largely unexplored. Here, by comparing the genomic sequences of SARS-CoV-2 and human, we identified five fully conserved elements in SARS-CoV-2 genome, which were termed as "human identical sequences (HIS)". HIS are also recognized in both SARS-CoV and MERS-CoV genome. Meanwhile, HIS-SARS-CoV-2 are highly conserved in the primate. Mechanically, HIS-SARS-CoV-2, behaving as virus-derived miRNAs, directly target to the human genomic loci and further interact with host enhancers to activate the expression of adjacent and distant genes, including cytokines gene and angiotensin converting enzyme II (ACE2), a well-known cell entry receptor of SARS-CoV-2, and hyaluronan synthase 2 (HAS2), which further increases hyaluronan formation. Noteworthily, hyaluronan level in plasma of COVID-19 patients is tightly correlated with severity and high risk for acute respiratory distress syndrome (ARDS) and may act as a predictor for the progression of COVID-19. HIS antagomirs, which downregulate hyaluronan level effectively, and 4-Methylumbelliferone (MU), an inhibitor of hyaluronan synthesis, are potential drugs to relieve the ARDS related ground-glass pattern in lung for COVID-19 treatment. Our results revealed that unprecedented HIS elements of SARS-CoV-2 contribute to the cytokine storm and ARDS in COVID-19 patients. Thus, blocking HIS-involved activating processes or hyaluronan synthesis directly by 4-MU may be effective strategies to alleviate COVID-19 progression.

molecular biology↗
bioRxiv2020

A novel viral protein translation mechanism reveals mitochondria as a target for antiviral drug development

The ongoing Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) pandemic has acutely highlighted the need to identify new treatment strategies for viral infections. Here we present a pivotal molecular mechanism of viral protein translation that relies on the mitochondrial translation machinery. We found that rare codons such as Leu-TTA are highly enriched in many viruses, including SARS-CoV-2, and these codons are essential for the regulation of viral protein expression. SARS-CoV-2 controls the translation of its spike gene by hijacking host mitochondria through 5 leader and 3UTR sequences that contain mitochondrial localization signals and activate the EGR1 pathway. Mitochondrial-targeted drugs such as lonidamine and polydatin significantly repress rare codon-driven gene expression and viral replication. This study identifies an unreported viral protein translation mechanism and opens up a novel avenue for developing antiviral drugs. One Sentence SummaryMitochondria are a potential target for antiviral therapy

microbiology↗
bioRxiv2020

Derivation of human extended pluripotent stem cells in feeder-free condition

Human extended pluripotent stem cells (EPSCs), with bidirectional chimeric ability to contribute to both embryonic and extra-embryonic lineages, can be obtained and maintained by converting embryonic stem cells (ESCs) using chemicals. However, the transition system is based on inactivated mouse fibroblast, which greatly hinders the mechanistic studies of extended pluripotency and further applications. Here we reported a Matrigel-based feeder-free method to convert human ESCs and iPSCs into EPSCs and demonstrated the extended pluripotency in terms of molecular features, chimeric ability, and transcriptome. We further improved the protocol by applying chemicals targeting glycolysis and histone methyltransferase. Altogether, our data established a feeder-free system to generate human EPSCs and provided additional insights into the acquisition of extended pluripotency.

developmental biology↗
bioRxiv2020

Immunogenicity of novel mRNA COVID-19 vaccine MRT5500 in mice and non-human primates

An effective vaccine to address the global pandemic of coronavirus disease 2019 (COVID-19) is an urgent public health priority1. Novel synthetic mRNA and vector-based vaccine technologies offer an expeditious development path alternative to traditional vaccine approaches. Here we describe the efforts to utilize an mRNA platform for rational design and evaluations of mRNA vaccine candidates based on Spike (S) glycoprotein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus causing COVID-19. Several mRNA constructs expressing various structural conformations of S-protein, including wild type (WT), a pre-fusion stabilized mutant (2P), a furin cleavage-site mutant (GSAS) and a double mutant form (2P/GSAS), were tested in a preclinical animal model for their capacity to elicit neutralizing antibodies (nAbs). The lead 2P/GSAS candidate was further assessed in dose-ranging studies in mice and Cynomolgus macaques. The selected 2P/GSAS vaccine formulation, now designated MRT5500, elicited potent nAbs as measured in two types of neutralization assays. In addition, MRT5500 elicited TH1-biased responses in both mouse and non-human primate species, a result that helps to address a hypothetical concern regarding potential vaccine-associated enhanced respiratory diseases associated with TH2-biased responses. These data position MRT5500 as a viable vaccine candidate for clinical development against COVID-19.

immunology↗
bioRxiv2020

Efficient Multiplex Genome Editing Tools Identified by Protoplast Technology in Phalaenopsis

Phalaenopsis orchids are popular ornamental plants worldwide. The application of the efficient multiplex genome editing tools in Phalaenopsis, will greatly accelerate the development of orchid gene function and breeding research. In this study, we establish a fast and convenient Phalaenopsis protoplast platform for the identification of functional genome editing tools. Two multiplex genome editing tools, PTG-Cas9 (PTG, polycistronic tRNA gRNA) system and PTGm-Cas9 (PTG-Cas9 system with modified sgRNA structure) system are designed to edit PDS gene of commercial Phalaenopsis ST166 at four target sites. We find that both PTG-Cas9 and PTGm-Cas9 system are functional in Phalaenopsis, and the PTGm-Cas9 system with modified sgRNA has a higher editing efficiency than PTG-Cas9 system. Further, we design another multiplex genome editing tool, termed as DPII-Cpf1 system (dual Pol II promoter to drive the expression of Cpf1 endonuclease and crRNA), to edit PDS gene of Phalaenopsis at four target sites likewise. All the four targets are efficiently edited by DPII-Cpf1 system, and the total mutation rate is about 3 times higher than that of PTGm-Cas9 system. Taken together, using the Phalaenopsis protoplast platform, we successfully establish two efficient multiplex genome editing tools for Phalaenopsis research, PTGm-Cas9 and DPII-Cpf1. The multiplex genome editing tools established in this study have great application potentials in efficiently constructing large-scale knockout mutant libraries of orchid and speeding up orchid precise breeding.

plant biology↗
bioRxiv2020

Transcriptome analysis of potato leaves in response to infection with the necrotrophic pathogen Alternaria solani

The potato early blight was caused by Alternaria solani (Aso). At present, potato early blight resistant varieties are lacking. The experiment of Aso inoculation on a.k.a. Favorita showed that the content of chlorophyll decreased continuously within 2 days after inoculation. In addition, the contents of JA-Ile, SA, ABA and IAA were determined by LC-MS.The results of two defense-related hormones showed that jasmonic acid content decreased significantly, while jasmonic acid content did not change significantly. In order to understand the difference in gene expression of potatoes infected by Aso, the 24 hpi, 36 hpi and 48 hpi transcriptome were determined. The results showed that the gene annotation and cluster analysis of DEGs revealed a variety of defense responses to Aso infection, especially the plant hormone signal transduction pathway. The differential expression of 10 DEGs was confirmed by qPCR analysis. Finally, through weighted gene co-expression network analysis (WGCNA), "samonl" was determined as a key hormone-related network in the process of Aso infection in potatoes. This study provides an important clue for understanding the interaction between potato and Aso and for disease resistance breeding.

plant biology↗
bioRxiv2020

Activation of Notch1 drives the development of radiation-induced thymic lymphoma in p53 wild-type mice

Mouse models of radiation-induced thymic lymphoma are widely used to study the development of radiation-induced blood cancers and to gain insights into the biology of human T-lymphoblastic leukemia/lymphoma. Here, we aimed to determine key oncogenic drivers for the development of radiation-induced thymic lymphoma by performing whole-exome sequencing using tumors and paired normal tissues from mice with and without irradiation. Thymic lymphomas from irradiated wild-type (WT), p53+/- and KrasLA1 mice were not observed to harbor significantly higher numbers of non-synonymous somatic mutations compared to thymic lymphomas from unirradiated p53-/- mice. However, we observed distinct patterns of recurrent mutations in genes that control the Notch1 signaling pathway based on the mutational status of p53. Preferential activation of Notch1 signaling in p53 WT lymphomas was also observed at the RNA and protein level. Using reporter mice for activation of the Notch1 signaling we observed that TBI enriched Notch1hi CD44+ thymocytes, which are capable of self-renewal in vivo. Mechanistically, genetic inhibition of Notch1 signaling in thymocytes prevented the formation of radiation-induced thymic lymphoma in p53 WT mice. Taken together, our results demonstrate a critical role of activated Notch1 signaling in driving multi-step carcinogenesis of thymic lymphoma following total-body irradiation in p53 WT mice.

cancer biology↗
bioRxiv2020

An effective, safe and cost-effective cell-based chimeric vaccine against SARS-CoV2

More than one hundred vaccines against SARS-CoV-2 have been developed and some of them have entered clinical trials, but the latest results revealed that these vaccines still face great challenges. Here, we developed a novel cell-based gp96-Ig-secreting chimeric vaccine which is composed of two viral antigens, the RBD of spike protein, and a truncated nucleocapsid protein that could induce epitope-specific cytotoxic T lymphocytes but low antibody response. Syrian hamsters immunized with the cell-based vaccine produced high level of SARS-CoV-2 specific NAbs and specific T cell immunity which could eliminate RBD-truncated N-expressing cells, without the induction of antibody against N protein and other observed toxicity. This study provides a proof of concept for clinical testing of this safe, effective and cost-effective vaccine against SARS-CoV2 infection.

immunology↗
bioRxiv2020

Eurycomanone regulates lipid metabolism by activating the cAMP/PKA pathway

Eurycoma longifolia Jack (ELJ) contains mainly alkaloids, and quassinoids, which are the main active ingredients. Eurycomanone (EN), one of the most common quassinoids, is said to have beneficial effects on lipid and glucose metabolism. In this study, we investigated the effects of EN on lipolysis by establishing a high-fat animal model in vivo and evaluated its efficacy as a lipolytic and anti-fatty liver agent. Oil red O staining showed morphological changes of 3T3-L1 preadipocytes after EN treatment and confirmed the inhibitory effects of EN on adipocyte differentiation. The mechanism of EN promotes lipolysis in 3T3-L1 cells was analyzed by immunofluorescence, Western blotting, quantitative real-time PCR and siRNA transfection. In C57BL/6J mice fed a high-fat diet, intragastric administration of EN (5 mg/kg and 10 mg/kg) for two weeks, decreased fat droplet mass and size, and reduced fat accumulation in the liver. Furthermore, EN activated PKA and promoted the PKA/hormone sensitive lipase lipolysis signaling pathway, thereby increasing the release of glycerol and free fatty acids from adipocytes. Our findings indicate the potential of EN as a promising alternative pharmacologic agent for the prevention of obesity.

pharmacology and toxicology↗
bioRxiv2020

Sodium leak channel as a therapeutic target for neuronal sensitization in neuropathic pain

Neuropathic pain affects up to 10% of the total population and no specific target is ideal for therapeutic need. The sodium leak channel (NALCN), a voltage-independent cation channel, mediates the background Na+ leak conductance and controls neuronal excitability and rhythmic behaviors. Here, we show that increases of NALCN expression and function in dorsal root ganglion (DRG) and dorsal spinal cord contribute to chronic constriction injury (CCI)-induced neuropathic pain in rodents. NALCN current and neuronal excitability in acutely isolated DRG neurons and spinal cord slices of rats were increased after CCI which were decreased to normal levels by NALCN-siRNA. Accordingly, pain-related symptoms were significantly alleviated by NALCN-siRNA-mediated NALCN knockdown and completely reversed by NALCN-shRNA-mediated NALCN knockdown in rats or by conditional NALCN knockout in mice. Our results indicate that increases in NALCN expression and function contribute to CCI-induced neuronal sensitization; therefore, NALCN may be a novel therapeutic target for neuropathic pain.

neuroscience↗
bioRxiv2020

In Silico Design of siRNAs Targeting Existing and Future Respiratory Viruses with VirusSi

The COVID-19 pandemic has exposed global inadequacies in therapeutic options against both the COVID-19-causing SARS-CoV-2 virus and other newly emerged respiratory viruses. In this study, we present the VirusSi computational pipeline, which facilitates the rational design of siRNAs to target existing and future respiratory viruses. Mode A of VirusSi designs siRNAs against an existing virus, incorporating considerations on siRNA properties, off-target effects, viral RNA structure and viral mutations. It designs multiple siRNAs out of which the top candidate targets >99% of SARS-CoV-2 strains, and the combination of the top four siRNAs is predicted to target all SARS-CoV-2 strains. Additionally, we develop Greedy Algorithm with Redundancy (GAR) and Similarity-weighted Greedy Algorithm with Redundancy (SGAR) to support the Mode B of VirusSi, which pre-designs siRNAs against future emerging viruses based on existing viral sequences. Time-simulations using known coronavirus genomes as early as 10 years prior to the COVID-19 outbreak show that at least three SARS-CoV-2-targeting siRNAs are among the top 30 pre-designed siRNAs. Before-the-outbreak pre-design is also possible against the MERS-CoV virus and the 2009-H1N1 swine flu virus. Our data support the feasibility of pre-designing anti-viral siRNA therapeutics prior to viral outbreaks. We propose the development of a collection of pre-designed, safety-tested, and off-the-shelf siRNAs that could accelerate responses toward future viral diseases.

bioinformatics↗
bioRxiv2020

Repopulating Kupffer Cells Originate Directly from Hematopoietic Stem Cells

Kupffer cells (KCs) originate from yolk sac progenitors before birth. Throughout adulthood, they self-maintain independently from the input of circulating monocytes (MOs) at stead state, and are replenished within 2 weeks after having been depleted, but the origin of repopulating KCs in adult remains unclear. The current paradigm dictates that repopulating KCs originate from preexisting KCs or monocytes, but there remains a lack of fate-mapping evidence. In current study, we firstly traced the fate of preexisting KCs and that of monocytic cells with tissue-resident macrophage-specific and monocytic cell-specific fate mapping mouse models, respectively, and found no evidences that repopulating KCs originate from preexisting KCs or MOs. Secondly, we performed genetic lineage tracing to determine the type of progenitor cells involved in response to KC depletion in mice, and found that in response to KC depletion, hematopoietic stem cells (HSCs) proliferated in the bone marrow, mobilized into the blood, adoptively transferred into the liver and differentiated into KCs. Finally, we traced the fate of HSCs in a HSC-specific fate-mapping mouse model, in context of chronic liver inflammation induced by repeated carbon tetrachloride treatment, and confirmed that repopulating KCs originated directly from HSCs. Taken together, these findings provided strong in vivo fate-mapping evidences that repopulating KCs originate directly from Hematopoietic stem cells not from preexisting KCs or from MOs. SignificanceThere is a standing controversy in the field regarding the cellular origin of repopulating macrophages. This paper provides strong in vivo fate-mapping evidences that repopulating KCs originate directly from hematopoietic stem cells not from preexisting KCs or from MOs, which presenting a completely novel understanding of the cellular origin of repopulating Kupffer Cells and shedding light on the divergent roles of KCs in liver homeostasis and diseases.

cell biology↗
bioRxiv2020

Cyclin G2 inhibits oral squamous cell carcinoma growth and metastasis by binding to insulin-like growth factor binding protein 3 and regulating the FAK-SRC-STAT signaling pathway

The cell cycle protein cyclin G2 is considered a tumor suppressor. However, its regulatory effects and potential mechanisms in oral cancers are not well understood. This study aimed to investigate the effect of cyclin G2 on oral squamous cell carcinoma (OSCC). The data from 80 patients with OSCC were utilized to predict the abnormal expression of cyclin G2. The proliferation and metastasis were determined by a cell counting Kit-8 assay, flow cytometry, a wound-healing assay and a cell invasion assay. The expression of key proteins and genes associated with the cyclin G2 signaling pathways was determined by western blotting and real-time PCR, respectively. The orthotopic nude mice model was established by a mouth injection of SCC9 cells overexpressing cyclin G2. We showed that the low level of cyclin G2 in OSCC, which is negatively correlated with clinical staging, was a negative prognostic factor for the disease. We also found that cyclin G2 inhibited the proliferation, metastasis and blocked the cell cycle at G1/S of OSCC cells, suggesting that cyclin G2 has an inhibitory effect in OSCC. Mechanistically, cyclin G2 inhibited the growth and metastasis of OSCC by binding to insulin-like growth factor binding protein 3 (IGFBP3) and regulating the focal adhesion kinase (FAK) -SRC-STAT signal transduction pathway. Cyclin G2 competed with integrin to bind to IGFBP3; the binding between integrin and IGFBP3 was reduced after cyclin G2 overexpression, thereby inhibiting the phosphorylation of FAK and SRC. These results showed that cyclin G2 inhibited the progression of OSCC by interacting with IGFBP3 and that it may be a new target for OSCC treatment.

cancer biology↗