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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 244: 118819, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-32846303

RESUMO

Copper (Cu) plays a significant role in the process of oxygenic photosynthesis in living systems. The detection of copper ion (Cu2+) is valuable and meaningful for further investigating the functions of Cu2+ under physiological and pathological conditions. In this paper, a novel fluorescence probe DCM-Cu based on the near-infrared (NIR) fluorophore dicyanomethylene-4H-pyran (DCM) was designed for Cu2+ detection. The probe DCM-Cu possessed characteristic of "turn-on" fluorescent signal in the presence of Cu2+ through the enhanced ICT process. It exhibited satisfactory sensitivity and selectivity toward Cu2+. A good linear correlation was observed between the concentrations of Cu2+ and the fluorescence intensities at 700 nm. The detection limit (LOD) of DCM-Cu toward Cu2+ was calculated to be 2.54 × 10-8 M. Importantly, DCM-Cu was successfully applied in the detection of Cu2+ in living MCF-7 cells and tumor tissue with low cytotoxicity. Therefore, this probe would have the potential to monitor cellular Cu2+ in the living system and be applied to the diagnosis of related diseases.

2.
Chem Commun (Camb) ; 56(79): 11823-11826, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33021257

RESUMO

Epilepsy is the fourth most common neurological disorder, and aberrantly elevated sulfur dioxide derivatives (SO32-/HSO3-) are thought to underlie the hippocampal neuronal apoptosis in epilepsy. We have designed and synthesized a mitochondria-targeted polydopamine nanoprobe for visualizing endogenous SO32-/HSO3- by the nucleophilic addition reaction. The nanoprobe was used for imaging SO2 derivatives both in the mitochondria of cultured cells and zebrafish, and successfully applied in the hippocampus of a rat model of epilepsy. The PDAD nanoprobe could be of great value for the elucidation of mechanisms of abnormal SO32-/HSO3- involved in diseases such as epilepsy.

3.
MAbs ; 12(1): 1829333, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33016217

RESUMO

Disulfide bond reduction, which commonly occurs during monoclonal antibody (mAb) manufacturing processes, can result in a drug substance with high levels of low molecular weight (LMW) species that may fail release specifications because the drug's safety and the efficiency may be affected by the presence of this material. We previously studied disulfide reoxidation of mAbs and demonstrated that disulfide bonds could be reformed from the reduced antibody via redox reactions under an optimal redox condition on Protein A resin. The study here implements a redox system in a manufacturing setting to rescue the reduced mAb product and to further eliminate LMW issues in downstream processing. As such, we incorporate the optimized redox system as one of the wash buffers in Protein A chromatography to enable an on-column disulfide reoxidation to form intact antibody in vitro. Studies at laboratory scale (1 cm (ID) x 20 cm (Height), MabSelect SuRe LX) and pilot scale (30 cm (ID) x 20 cm (Height), MabSelect SuRe LX) were performed to demonstrate the effectiveness and robustness of disulfide formation with multiple mAbs using redox wash on Protein A columns. By applying this rescue strategy using ≤50 g/L-resin loading, the intact mAb purity was improved from <5% in the Protein A column load to >90% in the Protein A column elution with a product yield of >90%. Studies were also done to confirm that adding the redox wash has no negative impact on process yield or impurity removal or product quality. The rescued mAbs were confirmed to form complete interchain disulfide bonds, exhibiting comparable biophysical properties to the reference material. Furthermore, since the redox wash is followed by a bridging buffer wash before the final elution, no additional burden is involved in removing the redox components during the downstream steps. Due to its ease of implementation, significant product purity improvement, and minimal impact on other product quality attributes, we demonstrate that the on-column reoxidation using a redox system is a powerful, simple, and safe tool to recover reduced mAb during manufacturing. Moreover, the apparent benefits of using a high-pH redox wash may further drive the evolution of Protein A platform processes.

4.
MAbs ; 12(1): 1829338, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33044887

RESUMO

Manufacturability of immunoglobulin G4 (IgG4) antibodies from the Chemistry, Manufacture, and Controls (CMC) perspective has received little attention during early drug discovery. Despite the success of protein engineering in improving antibody biophysical properties, a clear gap still exists between rational design of IgG4 candidates and their manufacturing suitability. Here, we illustrate that undesirable two-peak elution profiles in cation-exchange chromatography are attributed to the S228P mutation (in IgG4 core-hinge region) intentionally designed to prevent Fab-arm exchange. A new scaffolding platform for engineering IgG4 antibodies amenable to bioprocessing and bioanalysis is proposed by introducing an "IgG1-like" single-point mutation in the hinge or CH1 region of IgG4S228P. This work offers insight into the design, discovery, and development of innovative therapeutic antibodies that are well suited for robust biomanufacturing and quality control.

5.
Nano Lett ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33054240

RESUMO

Vertical van der Waals (vdWs) heterostructures based on layered materials are attracting interest as a new class of quantum materials, where interfacial charge-transfer coupling can give rise to fascinating strongly correlated phenomena. Transition metal chalcogenides are a particularly exciting material family, including ferromagnetic semiconductors, multiferroics, and superconductors. Here, we report the growth of an organic-inorganic heterostructure by intercalating molecular electron donating bis(ethylenedithio)tetrathiafulvalene into (Li,Fe)OHFeSe, a layered material in which the superconducting ground state results from the intercalation of hydroxide layer. Molecular intercalation in this heterostructure induces a transformation from a paramagnetic to spin-glass-like state that is sensitive to the stoichiometry of molecular donor and an applied magnetic field. Besides, electron-donating molecules reduce the electrical resistivity in the heterostructure and modify its response to laser illumination. This hybrid heterostructure provides a promising platform to study emerging magnetic and electronic behaviors in strongly correlated layered materials.

6.
eNeuro ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33055195

RESUMO

The dorsal raphe (DR) is an evolutionarily conserved brain structure that is involved in aggressive behavior. It projects onto numerous cortical and limbic areas underlying attack behavior. The specific neurocircuit through which the DR regulates aggression, however, is largely unclear. In this study we show that DR neurons expressing CaMKIIα are activated by attack behavior in mice. These neurons project to the medial aspect of the orbitofrontal cortex (OFC; MeOC) and the medial amygdala (MeA), two key regions within the neural circuit known to control aggressive behavior. Using an in vivo optogenetic approach, we show that attack bouts are shortened by inhibiting CaMKIIα+ neurons in the DR and their axons at the MeOC and prolonged by stimulating the DR-MeOC axons during an attack. By contrast, stimulating the axons of CaMKIIα+ DR neurons at the MeA shortens attack. Notably, neither the DR-MeOC or DR-MeA pathway initiates attack when stimulated. These results indicate that the DR-MeOC and DR-MeA pathways regulate the duration of attack behavior in opposite directions, revealing a circuit mechanism for the control of attack by the DR.Significance Statement The dorsal raphe (DR) is a major node in the brain circuit regulating multiple attack behaviors. The underlying neurocircuitry through which the DR acts on aggression, however, remains elusive. Here, we show that the DR regulates the duration of attack through the medial orbitofrontal cortex (OFC; MeOC) and the medial amygdala (MeA), areas known to play a key role in aggression. While neither pathway is sufficient to initiate an attack, silencing the DR-MeOC pathway or activating the DR-MeA pathway shortens an attack, and stimulation of the DR-MeOC circuit prolongs an already occurring attack. These findings identify two DR-mediated neural circuits that regulate attack behavior.

7.
Zootaxa ; 4772(2): zootaxa.4772.2.6, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33055616

RESUMO

Three species of geckos in the genus Goniurosaurus have been recorded from Hainan Island in China. We describe a new species, Goniurosaurus kwanghua sp. nov. Zhu He, bringing the number of this genus in Hainan Island to four. We conducted phylogenetic analyses with two mitochondrial genes (16S Cytb) and two nuclear genes (RAG1 C-MOS) to validate this new species. The new species is similar to G. hainanensis, but differs in the following characters: (1) middle section of the nuchal loop wide and posteriorly protracted, (2) wider body bands with dark markings, (3) yellow stripes on posterior side of humerus and femur, linked to the first and third body bands, respectively. The type specimens are deposited in the Museum of Biology, East China Normal University (ECNU).

8.
Biotechnol Prog ; : e3086, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016571

RESUMO

Beta-glucans are polysaccharides of D-glucose monomers linked by (1-3) beta-glycosidic bonds, are found to have a potential immunogenicity risk in biotherapeutic products, and are labeled as process contaminants. A common source of beta-glucans is from the cellulose found in traditional depth filter media. Typically, beta-glucan impurities that leach into the product from the primary clarification depth filters can be removed by the subsequent bind-and-elute affinity chromatography capture step. Beta-glucans can also be removed by a bind-and-elute cation exchange chromatography step, which is useful for removing beta-glucans introduced by a post-Protein A depth filtration step. However, the increasing prevalence of flowthrough polishing chromatography poses a challenge for beta-glucan removal due to the lack of any bind-and-elute chromatography steps after the post-Protein A depth filter. In this work, a depth filter flush strategy was developed to control beta-glucan leaching into the product pool. Different loading conditions for the depth filtration and subsequent chromatography steps were evaluated to determine the robustness of the optimized flush strategy. Carry through runs demonstrated greater than two-fold reduction in beta-glucan levels using the optimized wash as compared to standard filter flush conditions.

9.
MAbs ; 12(1): 1829336, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33031716

RESUMO

Disulfide bonds play a crucial role in folding and structural stabilization of monoclonal antibodies (mAbs). Disulfide bond reduction may happen during the mAb manufacturing process, resulting in low molecular weight species and possible failure to meet product specifications. Although many mitigation strategies have been developed to prevent disulfide reduction, to the best of our knowledge, reforming disulfide bonds from the reduced antibody in manufacturing has not previously been reported. Here, we explored a novel rescue strategy in the downstream process to repair the broken disulfide bonds via in-vitro redox reactions on Protein A resin. Redox conditions including redox pair (cysteine/cystine ratio), pH, temperature, and reaction time were examined to achieve high antibody purity and a high reaction rate. Under the optimal redox condition, >90% reduced antibody could be reoxidized to form an intact antibody on Protein A resin in an hour. In addition, this study showed high flexibility on the range of the intact mAb fraction in the initial reduced mAb sample (the lower limit of intact mAb faction could be 14% based on the data reported in this study). Furthermore, a kinetic model based on elementary oxidative reactions was constructed to help optimize the reoxidation conditions and to predict product purity. Together, the deep understanding of interchain disulfide bond reoxidation, combined with the predictive kinetic model, provided a good foundation to implement a rescue strategy to generate high-purity antibodies with substantial cost savings in manufacturing processes.

10.
Aging (Albany NY) ; 122020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33049717

RESUMO

Accumulating evidence from epidemiological studies of humans and genetic models in rodents has shown that offspring from males of advanced paternal age (APA) are susceptible to metabolic and neurological disorders. However, knowledge of molecular mechanism(s) underlying these metabolic and behavioral changes at the intergeneration and trans-generation levels from APA is limited. Here, we characterized changes on glucose and cholesterol metabolism, and also autism spectrum disorders (ASD)-like behaviors in 1st and 2nd generations from 12- and 18-month-old male mice, respectively. Whole Genome Bisulfite Sequencing (WGBS) of sperm from APA mice identified differentially methylated regions (DMRs) within the whole genome, and DMRs within promoter regions, suggesting that specific genes and relevant pathways might be associated with autism and aberrant glucose metabolism in the offspring from APA males. These results strongly suggest that epigenetic reprogramming induced by aging in male sperm may lead to high risks of aberrant glucose metabolism and the development of ASD behaviors in intergenerational and transgenerational offspring.

11.
Sci Rep ; 10(1): 17250, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33057145

RESUMO

SQUAMOSA promoter-binding protein (SBP)-box genes encode a family of plant-specific transcription factors that play roles in plant growth and development. The characteristics of SBP-box genes in rice (Oryza sativa) and Arabidopsis have been reported, but their potential roles in wheat (Triticum aestivum) are not fully understood. In this study, 48 SBP-box genes (TaSBPs) were identified; they were located in all wheat chromosomes except for 4B and 4D. Six TaSBPs were identified as tandem duplication genes that formed three tandem duplication pairs, while 22 were segmentally duplicated genes that formed 16 segmental duplication pairs. Subcellular localization prediction showed TaSBPs were located in nucleus. Among the 48 TaSBPs, 24 were predicted to be putative targets of TamiR156. Phylogenetic analysis showed that TaSBPs, AtSBPs, and OsSBPs that shared similar functions were clustered into the same subgroups. The phylogenetic relationships between the TaSBPs were supported by the identification of highly conserved motifs and gene structures. Four types of cis-elements--transcription-related, development-related, hormone-related, and abiotic stress-related elements--were found in the TaSBP promoters. Expression profiles indicated most TaSBPs participate in flower development and abiotic stress responses. This study establishes a foundation for further investigation of TaSBP genes and provides novel insights into their biological functions.

12.
Nanoscale ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33057560

RESUMO

Na3V2(PO4)3 (NVP) is regarded as a potential cathode material that can be applied in sodium ion batteries (SIBs) owing to its NASICON structure. However, most of the reported works have focused on the synthesis of materials and the improvement of their electrochemical properties, with little research on the design and safety of pouch cells. Herein, we implemented a cost-saving route to realize the industrial-scale synthesis of NVP cathode materials. The obtained NVP samples possess an impressive Na-ion storage capability with high reversible capacity (116.3 mA h g-1 at 0.2 C), superior power capability (97.9 mA h g-1 at 30 C), and long lifespan (71.6% capacity retention after 2500 cycles at 20 C). It was remarkable that industrial-scale NVP/hard carbon (HC) sodium-ion pouch cells could be designed with an 823 mA h discharge capacity at a current of 200 mA (about 0.25 C), and which possess a long life and high rate performance (1000 cycles with a little decay at a current of 4000 mA). Besides, the pouch cells also exhibit excellent thermal stability when demonstrated for application in unmanned aerial vehicles (UAVs), and puncturing experiment results can further prove the excellent safety performance of NVP-hard carbon pouch cells.

13.
Respir Res ; 21(1): 272, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076908

RESUMO

BACKGROUND: The longer upper airway is more collapsible during sleep. This study aims to reveal relationships among upper airway length, weight, and obstructive sleep apnea (OSA), particularly to answer why the upper airway of OSA patients is longer than that of healthy people and why some obese people suffer from OSA while others do not. METHODS: We perform head and neck MRI on male patients and controls, and measure > 20 morphological parameters, including several never before investigated, to quantify the effect of weight change on upper airway length. RESULTS: The upper airway length is longer in patients and correlates strongly to body weight. Weight increase leads to significant fat infiltration in the tongue, causing the hyoid to move downward and lengthen the airway in patients. The apnea-hypopnea index (AHI) strongly correlates to airway length and tongue size. Surprisingly, a distance parameter h and angle ß near the occipital bone both show significant differences between healthy males and patients due to their different head backward tilt angle, and strongly correlates with AHI. The contributions of downward hyoid movement and head tilt on airway lengthening are 67.4-80.5% and19.5-32.6%, respectively, in patients. The parapharyngeal fat pad also correlates strongly with AHI. CONCLUSIONS: The findings in this study reveal that the amount of body weight and distribution of deposited fat both affect airway length, and therefore OSA. Fat distribution plays a larger impact than the amount of weight, and is a better predictor of who among obese people are more prone to OSA.

15.
Signal Transduct Target Ther ; 5(1): 214, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33033232

RESUMO

Epidermal growth factor receptor (EGFR) activation plays a pivotal role in EGFR-driven non-small cell lung cancer (NSCLC) and is considered as a key target of molecular targeted therapy. EGFR tyrosine kinase inhibitors (TKIs) have been canonically used in NSCLC treatment. However, prevalent innate and acquired resistances and EGFR kinase-independent pro-survival properties limit the clinical efficacy of EGFR TKIs. Therefore, the discovery of novel EGFR degraders is a promising approach towards improving therapeutic efficacy and overcoming drug resistance. Here, we identified a 23-hydroxybetulinic acid derivative, namely DPBA, as a novel EGFR small-molecule ligand. It exerted potent in vitro and in vivo anticancer activity in both EGFR wild type and mutant NSCLC by degrading EGFR. Mechanistic studies disclosed that DPBA binds to the EGFR extracellular domain at sites differing from those of EGF and EGFR. DPBA did not induce EGFR dimerization, phosphorylation, and ubiquitination, but it significantly promoted EGFR degradation and repressed downstream survival pathways. Further analyses showed that DPBA induced clathrin-independent EGFR endocytosis mediated by flotillin-dependent lipid rafts and unaffected by EGFR TKIs. Activation of the early and late endosome markers rab5 and rab7 but not the recycling endosome marker rab11 was involved in DPBA-induced EGFR lysosomal degradation. The present study offers a new EGFR ligand for EGFR pharmacological degradation and proposes it as a potential treatment for EGFR-positive NSCLC, particularly NSCLC with innate or acquired EGFR TKI resistance. DPBA can also serve as a chemical probe in the studies on EGFR trafficking and degradation.

16.
Zootaxa ; 4852(2): zootaxa.4852.2.6, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33056426

RESUMO

Five species of geckos in the genus Goniurosaurus had been recorded from Guangxi, China. Here we describe a new species, Goniurosaurus gezhi sp. nov. Zhu, He Li. The new species is similar to those found in Guangxi and Guizhou provinces of China and Northern Vietnam, but unique in a combination of the following characters: (1) three body bands between limb insertions; (2) precloacal pores 18-20; (3) body small (SVL=70.6-83.8 mm); (4) body color orange to yellow. We evaluated the phylogenetic position of this new species based on the 16S mitochondrial gene. Molecular phylogenies validate this new species as distinct to currently described lineages within Goniurosaurus. The type specimens are deposited in the Museum of Biology, East China Normal University (ECNU).


Assuntos
Lagartos , Animais , China , Genes Mitocondriais , Masculino , Filogenia
17.
J Chromatogr A ; 1631: 461573, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-33010710

RESUMO

High molecular weight (HMW) aggregate formation of therapeutic monoclonal antibodies (mAbs) during cation-exchange chromatography (CEX) has been frequently observed, and can be a challenge for downstream purification. To gain mechanistic understanding of this phenomenon, aggregate formation in bind-elute CEX for two therapeutic mAbs (IgG1 and IgG4) was examined on three CEX resins (Capto SP ImpRes, Fractogel EMD SE Hicap, and POROS XS). First, mAb structural stability was studied in solutions under CEX load conditions. Using differential scanning fluorimetry (DSF), the measured melting temperature (Tm DSF (Unbound)) decreased from 60.7 to 52.4°C for mAb1 and 51.5 to 45.2°C for mAb2 when lowering pH from 6.0 to 4.5. Then, mAb structural stability was further investigated in the bound state on CEX surfaces. Using differential scanning calorimetry (DSC), the measured melting temperature of the bound mAbs (Tm DSC (Bound)) was 4.5 - 6.5°C lower than that for the unbound mAbs (Tm DSC (Unbound)) in the same solutions. The Tm differences (∆Tm DSC (Unbound minus Bound)) between the two states correlated with the severity of mAb aggregation in CEX operations, indicating the importance of both intrinsic mAb stability and resin properties. In particular, resin hydrophobicity was shown to have a critical impact. The interplay among these protein- and resin-related factors, together with solution conditions, ultimately dictates the aggregate formation observed. Finally, the hydrophobicity of the CEX resins (Capto SP ImpRes < Fractogel EMD SE Hicap < POROS XS) was measured using a fluorescence-based method to quantitatively characterize this resin property. Results suggest that the mAb-accessible hydrophobic regions of the CEX resins affect the structural stability of the bound mAbs to various degrees, leading to differences in aggregate formation upon mAb elution. In summary, this study offers insight into the mechanism of mAb aggregation in bind-elute CEX operations, and the in-depth understanding facilitates the development of robust CEX conditions for mAb purification.

18.
J Pharm Sci ; 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32946897

RESUMO

In this study, three different chitosan, namely carboxymethyl chitosan (CMC), hydroxypropyl chitosan (HPC) and trimethyl chitosan (TMC) were used as cationic materials to prepare tetrandrine lipid nanoparticles (TET-LNPs) for the treatment of glaucoma. In vitro drug release and pre-corneal retention were used to select the optimal chitosan. In vitro drug release curves of three kinds of LNPs showed a sustained release and TMC-TET-LNPs were the slowest. Moreover, compared with CMC-TET-LNPs and HPC-TET-LNPs, TMC-TET-LNPs had longer corneal retention time. Afterwards, the characteristics of TMC-TET-LNPs were investigated. The ocular irritation study revealed no sign of irritation in rabbit eyes. The pharmacokinetic studies showed that the area under the curve of TMC-TET-LNPs was increased by 2.03 times than TET solution (p < 0.01). Furthermore, the drug biofilm interactions were evaluated by molecular dynamics (MD) simulation. In MD simulation, the strong hydrophobic group of TET interacted with the tail of POPC, making it hard to enter the hydrophobic region of the membrane, thereby restricting TET ocular bioavailability. The experiments and MD simulation indicated that TMC-TET-LNPs had great potential for ocular administration and MD simulation could predict transmembrane transport of drugs.

19.
Stem Cell Res Ther ; 11(1): 408, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32967715

RESUMO

OBJECTIVES: This study is designed to generate and propagate human spermatogonial stem cells (SSCs) derived from human pluripotent stem cells (hPSCs). METHODS: hPSCs were differentiated into SSC-like cells (SSCLCs) by a three-step strategy. The biological characteristics of SSCLCs were detected by immunostaining with antibodies against SSC markers. The ability of self-renewal was measured by propagating for a long time and still maintaining SSCs morphological property. The differentiation potential of SSCLCs was determined by the generation of spermatocytes and haploid cells, which were identified by immunostaining and flow cytometry. The transcriptome analysis of SSCLCs was performed by RNA sequencing. The biological function of SSCLCs was assessed by xeno-transplantation into busulfan-treated mouse testes. RESULTS: SSCLCs were efficiently generated by a 3-step strategy. The SSCLCs displayed a grape-like morphology and expressed SSC markers. Moreover, SSCLCs could be propagated for approximately 4 months and still maintained their morphological properties. Furthermore, SSCLCs could differentiate into spermatocytes and haploid cells. In addition, SSCLCs displayed a similar gene expression pattern as human GPR125+ spermatogonia derived from human testicular tissues. And more, SSCLCs could survive and home at the base membrane of seminiferous tubules. CONCLUSION: SSCLCs were successfully derived from hPSCs and propagated for a long time. The SSCLCs resembled their counterpart human GPR125+ spermatogonia, as evidenced by the grape-like morphology, transcriptome, homing, and functional characteristics. Therefore, hPSC-derived SSCLCs may provide a reliable cell source for studying human SSCs biological properties, disease modeling, and drug toxicity screening.

20.
BMC Cancer ; 20(1): 917, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32972383

RESUMO

BACKGROUND: Identification of effective diagnostic and prognostic biomarkers of cancer is necessary for improving precision medicine. Long non-coding RNAs (lncRNAs) play an important regulatory role in tumor initiation and progression. The lncRNA LOC284454 is distinctly expressed in various head and neck cancers (HNCs), as demonstrated by our previous bioinformatics analysis. However, the expression levels and functions of LOC284454 in cancer are still unclear. METHODS: We investigated the dysregulation of lncRNAs in HNCs using the GEO database and found that LOC284454 was highly expressed in HNCs. Serum samples from 212 patients with HNCs and 121 normal controls were included in this biomarker study. We measured the expression of LOC284454 in the sera of HNC patients and normal controls using RT-qPCR. Receiver operating characteristics (ROC) analysis is an important statistical method that is widely used in clinical diagnosis and disease screening. ROC was used to analyze the clinical value of LOC284454 in the early diagnosis of HNCs. RESULTS: LOC284454 was significantly upregulated in the sera of patients with nasopharyngeal carcinoma, oral cancer, and thyroid cancer. LOC284454 upregulation had good clinical diagnostic value in these cancers, as evaluated by area under the ROC curve values of 0.931, 0.698, and 0.834, respectively. CONCLUSIONS: LOC284454 may be a valuable serum biomarker for HNCs facilitating the early diagnosis of malignant cancers. Further studies are needed to elucidate the mechanisms underlying the involvement of LOC284454 in HNCs. This study provides the first evidence that LOC284454 may be a serum biomarker for HNCs.

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