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The rapid, precise identification and quantification of specific biomarkers, toxins, or pathogens is currently a key strategy for achieving more efficient diagnoses. Herein a dopamine-biotin monomer was synthetized and oxidized in the presence of hexamethylenediamine, to obtain adhesive coatings based on polydopamine-biotin (PDA-BT) on different materials to be used in targeted molecular therapy. Insight into the structure of the PDA-BT coating was obtained by solid-state 13C NMR spectroscopy acquired, for the first time, directly onto the coating, deposited on alumina spheres. The receptor binding capacity of the PDA-BT coating toward 4-hydroxyazobenzene-2-carboxylic acid/Avidin complex was verified by means of UV-vis spectroscopy. Different deposition cycles of avidin onto the PDA-BT coating by layer-by-layer assembly showed that the film retains its receptor binding capacity for at least eight consecutive cycles. Finally, the feasibility of PDA-BT coating to recognize cell lines with different grade of overexpression of biotin receptors (BR) was investigated by tumor cell capture experiments by using MCF-7 (BR+) and HL-60 (BR-) cell lines. The results show that the developed system can selectively capture MCF-7 cells indicating that it could represent a first approach for the development of future more sophisticated biosensors easily accessible, low cost and recyclable with the dual and rapid detection of both proteins and cells.
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Técnicas Biossensoriais , Biotina , Dopamina , Humanos , Biotina/química , Dopamina/análise , Indóis/química , Polímeros/química , Células HL-60 , Células MCF-7 , Estrutura Molecular , Propriedades de Superfície , Avidina/química , Tamanho da PartículaRESUMO
A notch is defined as the frequency point at which hearing loss is greater than 15 dB when compared to one octave above and below. C3 dip or 1 kHz notch is rarely seen and not much information is known about the clinical profile of such condition. The aim of this case report is to highlight the audiological profile of a case with 1kHz notch and discuss the possible causes for the same. Case A (16 yrs) was referred with a complaint of hearing loss and speech understanding difficulty specially at school. The teen had taken multiple medications for several health related issues like malaria, appendicitis and the understanding difficulty was evident during this period. Detailed audiological evaluation revealed a significant C3 dip in the right ear and normal hearing sensitivity in the left ear. Evidences from literature suggests strong correlation between drugs like Cefotetan, cefotaime, piperacillin, ampicillin (appendicitis treatment) and chloroquine (malaria) and hearing loss. Hence, we concluded that the possible cause of 1khz is ototoxic medication.
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Mature neurons maintain their distinctive morphology for extended periods in adult life. Compared to developmental neurite outgrowth, axon guidance, and target selection, relatively little is known of mechanisms that maintain the morphology of mature neurons. Loss of function in C. elegans dip-2, a member of the conserved lipid metabolic regulator Dip2 family, results in progressive overgrowth of neurites in adults. We find that dip-2 mutants display specific genetic interactions with sax-2, the C. elegans ortholog of Drosophila Furry and mammalian FRY. Combined loss of dip-2 and sax-2 results in failure to maintain neuronal morphology and elevated release of neuronal extracellular vesicles (EVs). By screening for suppressors of dip-2(0) sax-2(0) double mutant defects, we identified gain-of-function (gf) mutations in the conserved Dopey family protein PAD-1 and its associated phospholipid flippase TAT-5/ATP9A that restore normal neuronal morphology and normal levels of EV release to dip-2(0) sax-2(0) double mutants. Neuron-specific knockdown suggests that PAD-1(gf) can act cell autonomously in neurons. PAD-1(gf) displays increased association with the plasma membrane in oocytes and inhibits EV release in multiple cell types. Our findings uncover a novel functional network of DIP-2, SAX-2, PAD-1, and TAT-5 that maintains neuronal morphology and modulates EV release.
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The Youjiang Basin is the main area of the Middle Devonian shale gas resources in southern China, with complex geological conditions, diverse stratigraphic structures, low level of exploration and limited hydrocarbon geological data. In this study, a method is proposed for evaluating the regional shale gas preservation conditions, by which it is easy to obtain information (using available data from regional geological maps) and to process data (processed by computer software). This method was applied to the evaluation of the preservation conditions of the Middle Devonian shale gas in the Youjiang Basin. Information extracted from geologic maps includes exposed stratum, magmatic rock distribution, stratigraphic occurrence and surface fracture distribution. Evaluation criteria for three indexes (stratigraphy index, dip angle index and fracture index) were established to classify the preservation conditions into five types from good to bad. Based on the calculated values of comprehensive index (CI), the comprehensive evaluation each area: 11621.23 km2 for CI of 0.7-1.0, 37162.67 km2 for CI of 0.5-0.7, 57784.43 km2 for CI of 0.3-0.5, 69303.77 km2 for CI of 0.1-0.3, and 69303.77 km2 for CI of 0.0-0.1, accounting for 3.19%, 10.19%, 15.84%, 18.99% and 51.80% of the whole area, respectively. These results are highly consistent with the actual exploration discoveries, showing that in the northern and central parts of the Guizhong Basin, the southern part of the Xidamingshan Uplift, and the northern part of the Qiannan Basin, there are large areas with good shale gas preservation conditions.
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Layered rocks are prevalent in the Earth's crust and are frequently encountered in underground engineering construction. Due to their pronounced anisotropy, the deformation and failure mechanism of layered rock are complex. Laboratory tests are an effective way to study these mechanisms. However, natural layered rocks present challenges, such as difficult sampling and large discreteness. Additionally, current methods for creating layered rock models are often costly or lack precision, limiting research into their mechanical properties. In this study, a 3D printing process using wet material extrusion was adopted, with a wide range of material options and low production costs. Five layered model samples with bedding dip angles of 0°, 30°, 45°, 60° and 90° were printed using this method. Uniaxial compression tests were conducted, supplemented by digital image correlation (DIC) to capture detailed stress-strain data and failure patterns. The results demonstrate that the mechanical properties of the 3D-printed samples closely resemble those of natural layered rocks and exhibit significant anisotropy. This approach presents a new cost-effective method for studying the mechanical behavior of layered rock.
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Descurainia sophia L. Webb ex Prantl is used in traditional medicine globally. However, the lack of an efficient and reliable genetic transformation system has seriously limited the investigation of gene function and further utilization of D. sophia. In this study, a highly efficient, time-saving, and cost-effective Agrobacterium tumefaciens-mediated genetic transformation system has been developed in D. sophia. In this method, the transformation was accomplished by simply dipping developing D. sophia inflorescences for 45 s into an Agrobacterium suspension (OD600 = 0.6) containing 5% sucrose and 0.03% (v/v) Silwet L-77. Treated plants were allowed to set seeds which were then plated on a selective medium with hygromycin B (HygB) to screen transformants. Additionally, the CRISPR/Cas9 genomic editing system was validated by targeting phytoene desaturase (PDS) gene using this floral dip method, and mutant plants with the expected albino phenotype could be obtained in 2.5 months. This genetic transformation and targeted editing system will be a valuable tool for routine investigation of gene function and further exploitation in D. sophia.
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Study of the interaction between fault activation and mining stress evolution in the longwall working face is helpful to provide a targeted area for fault type heavy mine pressure disaster control. Combining theoretical analysis, physical and numerical simulation, the mechanical mechanism of fault activation is analyzed, the interaction law between mining stress and fault activation is studied, and the influence of fault dip angle on the evolution of fault activation and mining stress is discussed. The minimum critical dip angles α of normal and reverse fault activation are π/4 + φ/2 and π/4-φ/2, respectively. During the mining process, the activation position of the fault surface, the peak values of stress and displacement gradually increase and transfer from the high position of the fault to the low position, and the peak value of the advance abutment pressure reaches the maximum at the fault. The advancing distance of the working face required for fault activation gradually decreases with the decrease of the fault dip angle, and the peak elevation area of the working face gradually increases with the decrease of the fault dip angle. Combined with the on-site microseismic monitoring results, it can be seen that when the working face is about 20 m away from the fault, the stress and energy increase sharply, which is the main control area of the impact disaster.
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Malaria remains a global health issue, especially in resource-limited regions. Artemisinin, a key antimalarial compound from Artemisia annua, is crucial for treatment, but low natural yields hinder large-scale production. In this study, we employed advanced transgenic technology to co-overexpress six key biosynthetic enzymes-Isopentenyl Diphosphate Isomerase (IDI), Farnesyl Pyrophosphate Synthase (FPS), Amorpha 4,11-diene Synthase (ADS), cytochrome P450 monooxygenase (CYP71AV1), cytochrome P450 oxidoreductase (AACPR) and artemisinic aldehyde D11 reductase (DBR2)-in A. annua to significantly enhance artemisinin production. Our innovative approach utilized a co-expression strategy to optimize the artemisinin biosynthetic pathway, leading to a remarkable up to 200 % increase in artemisinin content in T1 transgenic plants compared to non-transgenic controls. The stability and efficacy of this transformation were confirmed in subsequent generations (T2), achieving a potential 232 % increase in artemisinin levels. Additionally, we optimized transgene expression to maintain plant growth and development, and performed untargeted metabolite analysis using GC-MS, which revealed significant changes in metabolite composition among T2 lines, indicating effective diversion of farnesyl diphosphate into the artemisinin pathway. This metabolic engineering breakthrough offers a promising and scalable solution for enhancing artemisinin production, representing a major advancement in the field of plant biotechnology and a potential strategy for more cost-effective malaria treatment.
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Insertion/deletion polymorphisms, or InDels, are widely present in the human genome. They have been considered as potential markers for forensic analysis because they can be genotyped using the CE platform and compatible typing techniques used in forensic laboratories. Additionally, InDels have lower mutation rates and often short amplicon sizes, making them ideal for detecting degraded samples. However, most InDels are bi-allelic; therefore, their discrimination power is relatively low. A new set of genetic marker called multi-InDels was reported to improve InDel's informativeness. Multi-InDel markers are generally designated as microhaplotypes encompassing two or more InDels within a short distance, usually less than 200â¯bp. In this study, we evaluated the applicability of three previously proposed panels of multi-InDel markers, designed for Asian populations, for human identification in Brazil. We assessed all the multi-InDel markers using high-coverage whole-genome sequencing data from a census-based cohort of 1171 Brazilians residing in São Paulo, the largest Brazilian capital. The results showed that most markers are informative for Brazilian individuals since they present more than three frequent haplotypes with different sizes. However, most markers are prone to amplification/sequencing errors due to repetitive or low-complexity regions. Among the tested panels, the one from Huang et al. (2014) is the most promising for forensic use in Brazil, with a combined match probability and cumulative power of exclusion of 4.92 ×10-14 and 0.9991, respectively. Nevertheless, these values are low compared to the ones obtained with CODIS STRs (short tandem repeats) and larger SNP (single nucleotide polymorphisms) panels. Therefore, new attempts to scan the human genome for highly polymorphic multi-InDel markers are still necessary to obtain a suitable panel of multi-InDels for worldwide populations.
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Launched in 2022 at the Policlinique d'hématologie et d'immunologie (PHI) of the Centre hospitalier (CH) Saint-Louis, the therapeutic patient education (TPE) program for patients suffering from rare hematology pathologies is continuing to develop. It has led to the creation of an TPE team. To date, two workshops are up and running, and a third is nearing completion.
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Doenças Hematológicas , Educação de Pacientes como Assunto , Doenças Raras , Humanos , Doenças Raras/terapia , Doenças Hematológicas/terapia , França , HematologiaRESUMO
The removal of zinc dross, which continuously generates and partially floats on a molten zinc surface, has been a persistent challenge during hot-dip galvanizing. Herein, a three-dimensional mathematical model coupled with the electromagnetic field, flow field and air-knife jet flow was established to investigate the flow and zinc dross removal in a zinc pot. Two types of traveling magnetic field combined modes (Mode 1 and Mode 2) were compared. The surface dross removal efficiency was introduced to evaluate the ability of the zinc flow field to compel the movement of zinc dross. The research findings indicate that, in comparison to the influence of strip steel line speed, both the electromagnetic field and air-knife jet have a more pronounced effect on altering the flow characteristics of a molten zinc at surface. The dross removal efficiency for Mode 1 is much far superior to that of Mode 2. With an increase in the driving current, the dross removal efficiency increases while the excessive driving current cannot promote the dross removal efficiency significantly.
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The application of environmentally friendly and sustainable catalysts requires efficient and safe preparation methods using cheap and renewable materials. Although many metal nanoparticles (NPs) have low colloidal stability, they are still very effective as catalysts. Using a straightforward method, we developed a bacterial cellulose-glycol chitosan-silver (BC-GCS-Ag) nanocomposite, by introducing both AgNPs and self-crosslinked GCS within the BC network. Self-crosslinking of GCS occurred during the formation of AgNPs by employing the glycol moieties for reduction to produce aldehyde functionalities, thereby forming Schiff's base bonds within the GCS structure. Using GCS, well-defined AgNPs within the BC matrix. The formation of AgNPs and the self-crosslinking of GCS were characterized using UV-visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The results showed that spherical AgNPs with a mean diameter of 10 nm exhibited a well-organized structure within the BC-GCS matrix. The BC-GCS-Ag nanocomposite was applied as dip catalyst for the reduction of 4-nitrophenol (4NP) to 4-aminophenol (4AP), chosen as a model reaction. The results showed that the catalytic reaction was completed within 4 min, with high reusability (10 times) and without loss of catalyst. The reaction followed pseudo-first-order kinetics with a high rate constant of 0.582 min-1. Therefore, the BC-GCS-Ag dip catalyst is an attractive alternative for environmentally friendly and sustainable catalysis, owing to its exceptional catalytic performance, high recyclability, and stability, as well as the minimal environmental footprint of the supporting materials.
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One of the latest trends in sustainable agriculture is the use of beneficial microorganisms to stimulate plant growth and biologically control phytopathogens. Bacillus subtilis, a Gram-positive soil bacterium, is recognized for its valuable properties in various biotechnological and agricultural applications. This study presents, for the first time, the successful encapsulation of B. subtilis within electrospun poly(3-hydroxybutyrate) (PHB) fibers, which are dip-coated with cellulose derivatives. In that way, the obtained fibrous biohybrid materials actively ensure the viability of the encapsulated biocontrol agent during storage and promote its normal growth when exposed to moisture. Aqueous solutions of the cellulose derivatives-sodium carboxymethyl cellulose and 2-hydroxyethyl cellulose, were used to dip-coat the electrospun PHB fibers. The study examined the effects of the type and molecular weight of these cellulose derivatives on film formation, mechanical properties, bacterial encapsulation, and growth. Scanning electron microscopy (SEM) was utilized to observe the morphology of the biohybrid materials and the encapsulated B. subtilis. Additionally, ATR-FTIR spectroscopy confirmed the surface chemical composition of the biohybrid materials and verified the successful coating of PHB fibers. Mechanical testing revealed that the coating enhanced the mechanical properties of the fibrous materials and depends on the molecular weight of the used cellulose derivatives. Viability tests demonstrated that the encapsulated B. subtilis exhibited normal growth from the prepared materials. These findings suggest that the developed fibrous biohybrid materials hold significant promise as biocontrol formulations for plant protection and growth promotion in sustainable agriculture.
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BACKGROUND: Circadian heart rate (HR) fluctuations are associated with cardiovascular health. We examined their relationship with microvascular disease and long-term survival in patients with diabetes. METHODS: In this secondary analysis from the CHAMP1ON cohort of 497 adults with metabolic disease, 349 participants who had type 1 or type 2 diabetes, baseline 24h ambulatory blood pressure and HR monitoring (ABPM), and survival data over a 21-year observational follow-up were included. Clinical features, microvascular complications, and mortality rates were examined in participants with low circadian HR fluctuations (24h-HR SD below the median of 30.4) and blunted nocturnal HR dip (<10%). RESULTS: Low 24h-HR SD and blunted nocturnal HR dip were associated with an adverse cardiometabolic risk profile and 12-23% higher prevalence of cardiac autonomic neuropathy and nephropathy. After 6,251 person-years follow-up (21.0 [14.0-21.0] years), a total of 136 (39%) deaths occurred, of which 100 (68%) of cardiovascular cause. The low 24h-HR SD group had a higher risk for both cardiovascular (adjusted hazard ratio [aHR] 2.00, 95%CI 1.30-3.08, p=0.002) and all-cause mortality (aHR 1.61, 95%CI 1.13-2.29, p=0.009), compared with high 24h-HR SD. Similarly, patients with blunted nocturnal HR dip had a higher risk for cardiovascular (aHR 1.63, 95%CI 1.08-2.46, p=0.019) and all-cause mortality (aHR 1.69, 95%CI 1.20-2.38, p=0.003), compared with those with preserved nocturnal HR dip. CONCLUSIONS: Impaired circadian HR fluctuations are associated with microvascular disease and long-term cardiovascular and all-cause mortality in diabetes. ABPM-derived HR measures may provide a widely available and inexpensive risk stratification tool in this high-risk population.
Circadian heart rate (HR) fluctuations are associated with cardiovascular health. We examined their relationship with microvascular disease and long-term survival in patients with diabetes. Impaired HR fluctuations measured by 24h ambulatory blood pressure and HR monitoring (ABPM) were associated with an adverse cardiometabolic risk profile, higher prevalence of cardiac autonomic neuropathy and nephropathy, and higher risk for cardiovascular and all-cause mortality over a 21-year follow-up. ABPM-derived HR measures may provide a cost-effective risk stratification tool in this high-risk population.
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Combined distal interphalangeal joint (DIP) arthrodesis with proximal interphalangeal joint (PIP) arthroplasty or arthrodesis presents unique challenges. Although less common than isolated surgery for the DIP and PIP joints, with an aging population, combined DIP and PIP procedures are an increasingly encountered occurrence. Anatomical and morphological studies have provided length and width measurement standards for the middle and distal phalanges, allowing for planning to assess the compatibility of strategies. Besides reviewing anatomical studies to provide length and width guidelines for hardware placement, we will also discuss optimal hardware combinations for combined surgical intervention in the DIP and PIP joints. Conflict may exist between hardware used for the DIP arthrodesis and implants used for the PIP arthroplasty. As an example, if K-wires are used for DIP arthrodesis, any intervention in the PIP joint will be compatible. However, if headless screws are used for DIP arthrodesis, these should ideally not reach proximal to the midpoint of the middle phalanx. Other techniques, such as single or multiple oblique screws, and tension bands are compatible with PIP arthroplasty. Hence, options for management of the PIP joint are dependent on the technique used for DIP arthrodesis.
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Purpose: To control medical costs and regulate the behavior of providers, China has formed an original widely piloted case-based payment under the regional global budget, called the Diagnosis-Intervention Packet (DIP). This study aimed to evaluated the impact of the DIP payment reform on medical costs, quality of care, and medical service capacity in a less-developed pilot city in Northwest China. Patients and Methods: We used the de-identified case-level discharge data of hospitalized patients from January 2021 to June 2022 in pilot and control cities located in the same province. We performed difference-in-differences (DID) analysis to examine the differential impact of the DIP reform for the entire sample and between secondary and tertiary hospitals. Results: The DIP payment reform resulted in a significant decrease of total expenditure per case in the entire sample (5.5%, P < 0.01) and tertiary hospitals (9.3%, P < 0.01). In-hospital mortality rate decreased significantly in tertiary hospitals (negligible in size, P < 0.05), as did all-cause readmission rate within 30 days in the entire sample (1.1 percentage points, P < 0.01) and secondary hospitals (1.4 percentage points, P < 0.01). Proportion of severe patients increased significantly in the entire sample (1.2 percentage points, P < 0.05) and tertiary hospitals (2.5 percentage points, P < 0.01). We did not find the DIP reform was associated with a significant change in relative weight per case. Conclusion: The DIP payment reform in the less-developed pilot city achieved short-term success in controlling medical costs without sacrificing the quality of care for the entire sample. Compared with secondary hospitals, tertiary hospitals experienced a greater decline in medical costs and received more severe patients. These findings hold lessons for less developed countries or areas to implement case-based payments and remind them of the variations between different levels of hospitals.
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In this study, severe cracking occurred during an investigation of the direct hot rolling of industrial electrolytic nickel plates. To determine the cause of hot-rolling cracking, the microstructure phase composition was analyzed through the utilization of various techniques, including optical microscopy, scanning electron microscopy, electron backscattering diffraction, transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS) and electron probe micro-analysis. The comparative microstructural analysis took place between specimens heat treated in atmospheric and vacuum environments. The characterization and analysis of the hot-rolled plates considered the crack microstructure and fracture morphology. It was shown that holes appeared along the large angular grain boundaries after annealing at 1100 °C for 8 h. Possible reason: In a high-temperature environment, the decomposition of residual additives in the electrolytic nickel releases oxidizing gases, which oxidizes the grain boundaries. The reaction with carbon diffused into the grain boundaries and produced carbon monoxide gas, which induced holes and severely reduced the grain boundary plasticity. The heat treatment time did not need to be very long for severe grain boundary degradation to occur. After severe cavitation, the electrolytic nickel was severely cracked at grain boundaries cracks due to a shear force, and brittle fractures occurred along grains with very low plasticity.
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This study focuses on the development of nanofiltration (NF) membranes with enhanced antifouling properties, high flux, and low molecular weight cut-off (MWCO) for the separation of lignin from paper mill wastewater. Using a sol-gel method by dip-coating, alumina hollow fiber membranes were fabricated with an interlayer to reduce surface roughness. The interlayer improved mechanical properties, effectively covering the surface irregularities and allowing for the subsequent application of a thinner functional layer. This approach significantly reduced surface roughness, from 112.6 nm to 62.9 nm, enhancing contamination resistance and lifetime. Characterization techniques, including X-ray diffraction (XRD), scanning electron microscope (SEM), atomic force microscopy (AFM), and water contact angle measurements, confirmed the successful fabrication and enhanced properties of the membranes. The C2T6T3 membrane demonstrated the smallest roughness and the highest flux recovery rate (FRR) of 82.39% after cleaning with a 0.1 M NaOH solution. Performance evaluations showed that the developed membranes maintained high permeability (initial flux of 25.58 L·m⻲·h⻹, decreasing to 14.06 L·m⻲·h⻹ over time), achieved effective lignin rejection (consistently above 80%), and exhibited excellent long-term operational stability over 144 h of operation.
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Two-photon lithography has revolutionized multi-photon 3D laser printing, enabling precise fabrication of micro- and nanoscale structures. Despite many advancements, challenges still persist, particularly in biofunctionalization of 3D microstructures. This study introduces a novel approach combining two-photon lithography with scanning probe lithography for post-functionalization of 3D microstructures overcoming limitations in achieving spatially controlled biomolecule distribution. The method utilizes a diverse range of biomolecule inks, including phospholipids, and two different proteins, introducing high spatial resolution and distinct functionalization on separate areas of the same microstructure. The surfaces of 3D microstructures are treated using bovine serum albumin and/or 3-(Glycidyloxypropyl)trimethoxysilane (GPTMS) to enhance ink retention. The study further demonstrates different strategies to create binding sites for cells by integrating different biomolecules, showcasing the potential for customized 3D cell microenvironments. Specific cell adhesion onto functionalized 3D microscaffolds is demonstrated, which paves the way for diverse applications in tissue engineering, biointerfacing with electronic devices and biomimetic modeling.
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In tongue cancer, many patients already have metastasis at the time of diagnosis, and such cases are usually unresponsive to treatment, resulting in a poor prognosis. Therefore, there is an urgent need to develop more effective diagnostic and therapeutic methods to cure tongue cancer at the earliest possible stage in clinical practice. Follistatin-like 1 (FSTL1) is known as a negative effector molecule that induces and enhances the refractoriness of cancer cells directly and indirectly via suppressing anti-tumor immunity in various types of cancer. However, the molecular expression, functions, and clinical significance of FSTL1 and its receptor DIP2A in tongue cancer remains to be elucidated. In this study, we revealed that FSTL1, which is highly expressed in tongue cancer cells, plays a key role in its malignancy and is a significant risk factor for recurrence of early-stage tongue cancer. Basic study shows that FSTL1 is abundantly produced from human tongue cancer cell lines, and blocking FSTL1 with specific siRNAs or mAb significantly suppresses cellular functions. Clinical study shows that both FSTL1 and its receptor DIP2A are highly and correlatively expressed in tumor tissues of tongue cancer patients, and high expression levels of both in stage I tumors are significantly associated with shorter relapse-free survival. These suggest that targeting the FSTL1-DIP2A axis may be useful as a biomarker for early prediction of prognosis in tongue cancer patients, and as a therapeutic target for developing new drugs to treat tongue cancer more effectively. This strategy will contribute to improving clinical outcomes in tongue cancer.