GCN5 regulates ZBTB16 through acetylation, mediates osteogenic differentiation, and affects orthodontic tooth movement.

In the process of orthodontic tooth movement (OTM), periodontal ligament fibroblasts (PDLFs) must undergo osteogenic differentiation. OTM increased the expression of Zinc finger and BTB domain-containing 16 (ZBTB16), which is implicated in osteogenic differentiation. Our goal was to investigate the mechanism of PDLF osteogenic differentiation mediated by ZBTB16. The OTM rat model was established, and PDLFs were isolated and exposed to mechanical force. Hematoxylin-eosin staining, Alizarin Red staining, immunofluorescence, and immunohistochemistry were carried out. The alkaline phosphatase (ALP) activity was measured. Dual-luciferase reporter gene assay and chromatin immunoprecipitation assay were conducted. In OTM models, ZBTB16 was significantly expressed. Additionally, there was an uneven distribution of PDLFs in the OTM group, as well as an increase in fibroblasts and inflammatory infiltration. ZBTB16 interference hindered PDLF osteogenic differentiation and decreased Wnt and ß-catenin levels. Meanwhile, ZBTB16 activated the Wnt/ß-catenin pathway. ZBTB16 also enhanced the expression of the osteogenic molecules osterix, osteocalcin (OCN), osteopontin (OPN), and bone sialo protein (BSP) at mRNA and protein levels. The interactions between Wnt1 and ZBTB16, as well as GCN5 and ZBTB16, were also verified. The adeno-associated virus-shZBTB16 injection also proved to inhibit osteogenic differentiation and reduce tooth movement distance in in vivo tests. ZBTB16 was up-regulated in OTM. Through acetylation modification of ZBTB16, GCN5 regulated the Wnt/ß-catenin signaling pathway and further mediated PDLF osteogenic differentiation.

Possibility of the existence of the rogue wave and the super rogue wave in granular matter.

By using the traditional perturbation technique, a focusing nonlinear Schrödinger equation (NLSE) for the one-dimensional bead chain with the initial prestress is first obtained. The Peregrine soliton, called the rogue wave in the present paper, and the super rogue wave are investigated both numerically and analytically. It is noted that both the rogue wave and the super rogue wave do exist in the one-dimensional bead chain. The solutions from the NLSE can correctly describe the real rogue wave as well as the real super rogue wave in the limiting case of small amplitude. Both the rogue wave and the super rogue wave propagate in the granular bead chain as if they are solitary waves.

Shock wave due to the short-period impact in one-dimensional plasticity bead chain.

The waves in a one-dimensional (1-D) bead chain produced by a constant velocity impact in a short period are studied numerically in the present paper. It seems that in some cases, the waves look like a shock wave, while in other cases they may be composed of several solitary waves or some oscillations. These characteristics depend on both the bead parameters and the impact parameters, such as the plasticity of the bead material, the piston velocity and the impact duration. It is found that the shock structure appears if the duration of the impact is longer, while it will evolve into several solitary waves if the duration of the impact is small enough. This indicates that the bead velocity attenuates with power function. The strength of the attenuation depends on the plasticity, the piston velocity and the bead radius.

[Study on the Influence of Mineralizer on the Preparation of Calcium Aluminates Based on Infrared Spectroscopy].

In this study, effect of mineralizer on the structure and spectraproperties of calcium aluminates formation was extensively studied. Medium or low-grade bauxite and calcium carbonate were used as raw material and mineralizer CaF2 as additive. Calcium aluminates can be obtained after mixing fully, calcination and grinding. The prepared calcium aluminates can be directly used for the production of polyaluminiumchloride (PAC), polymeric aluminum sulfate, sodium aluminate and some other water treatment agents. The calcium aluminates preparation technology was optimized by investigating the mass ratio of raw materials (bauxiteand calcium carbonate) and mineralizer CaF2 dosage. The structure and spectra properties of bauxite and calcium aluminates were characterized by Fourier transform infrared(FTIR) spectroscopy analysis and the mineralization mechanism of the mineralizer was studied. FTIR spectra indicated that the addition of mineralizer promoted the decomposition and transformation of the diaspore, gibbsite and kaolinite, the decomposition of calcium carbonate, and more adequately reaction between bauxite and calcium carbonate. In addition, not only Ca in calcium carbonate and Si in bauxite were more readily reacted, but also Si-O, Si-O-Al and Al-Si bonds in the bauxite were more fractured which contributed to the release of Al in bauxite, and therefore, the dissolution rate of Al2O3 could be improved. The dissolution rate of Al2O3 can be promoted effectively when the mineralizer CaF2 was added in a mass ratio amount of 3%. And the mineralizer CaF2 cannot be fully functioned, when its dosage was in a mass percent of 1. 5%. Low-grade bauxite was easier to sinter for the preparation of calcium aluminates comparing with the highgrade one. The optimum material ratio for the preparation of calcium aluminates calcium at 1 250 °C was the mass ratio between bauxite and calcium carbonate of 1 : 0. 6 and mineralizer CaF2 mass ratio percent of 3%.

A multifunctional theranostics nanosystem featuring self-assembly of alcohol-abuse drug and photosensitizers for synergistic cancer therapy.

Conventional treatments for cancer, such as chemotherapy, surgical resection, and radiotherapy, have shown limited therapeutic efficacy, with severe side effects, lack of targeting and drug resistance for monotherapies, which limit their clinical application. Therefore, combinatorial strategies have been widely investigated in the battle against cancer. Herein, we fabricated a dual-targeted nanoscale drug delivery system based on EpCAM aptamer- and lactic acid-modified low-polyamidoamine dendrimers to co-deliver the FDA-approved agent disulfiram and photosensitizer indocyanine green, combining the imaging and therapeutic functions in a single platform. The multifunctional nanoparticles with uniform size had high drug-loading payload, sustained release, as well as excellent photothermal conversion. The integrated nanoplatform showed a superior synergistic effect in vitro and possessed precise spatial delivery to HepG2 cells with the dual-targeting nanocarrier. Intriguingly, a robust anticancer response of chemo-phototherapy was achieved; chemotherapy combined with the efficacy of phototherapy to cause cellular apoptosis of HepG2 cells (>35%) and inhibit the regrowth of damaged cells. Furthermore, the theranostic nanosystem displayed fluorescence imaging in vivo, attributed to its splendid accumulation in the tumor site, and it provided exceptional tumor inhibition rate against liver cancer cells (>76%). Overall, our research presents a promising multifunctional theranostic nanoplatform for the development of synergistic therapeutics for tumors in further applications.

Biomimetic nanoparticles: U937 cell membranes based core-shell nanosystems for targeted atherosclerosis therapy.

Atherosclerosis (AS), with its intricate pathogenesis, is primarily responsible for the development and progression of cardiovascular diseases. Although drug development has made some achievements in AS therapy, limited targeting ability and rapid blood clearance remain great challenges for achieving superior clinical outcomes. Herein, ginsenoside (Re)- and catalase (CAT)-coloaded porous poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs) were prepared and then surface modified with U937 cell membranes (UCMs) to yield a dual targeted model and multimechanism treatment biomimetic nanosystem (Cat/Re@PLGA@UCM). The nanoparticles consisted of a core-shell spherical morphology with a favorable size of 112.7 ± 0.4 nm. Furthermore, UCM assisted the nanosystem in escaping macrophage phagocytosis and targeting atherosclerotic plaques. Meanwhile, loading with catalase might not only exhibit favorable antioxidant effects but also enable H2O2-responsive drug release ability. The Cat/Re@PLGA@UCM NPs also exhibited outstanding ROS scavenging properties, downregulating ICAM-1, TNF-α and IL-1ß, while preventing angiogenesis to attenuate the progression of AS. Moreover, the nanodrugs displayed 2.7-fold greater efficiency in reducing the atherosclerotic area in ApoE-/- mouse models compared to free Re. Our nanoformulation also displayed excellent biosafety in response to long-term administration. Overall, our study demonstrated the superiority of UCM-coated stimuli-responsive nanodrugs for effective and safe AS therapy.

Biomimetic polyphenol-coated nanoparticles by Co-assembly of mTOR inhibitor and photosensitizer for synergistic chemo-photothermal therapy.

Rapamycin (RAPA) functions as effectively clinical immunosuppressive agent, its significant tumor growth suppression effect via various pathways in diverse cancers, especially combined with photothermal therapy, is gaining a burgeoning attention. However, its critical defects, low solubility and poor stability, have severely hampered its further application. Herein, RAPA, indocyanine green (ICG) and epigallocatechin gallate (EGCG) serving as chemotherapeutic drug, photosensitizer and biomimetic coatings, respectively, were co-assembled into carrier-free, high biocompatible ICG-RAPA-EGCG nanoparticles (IRE NPs) for synergistic cancer therapy. Particularly, the bioinspired EGCG coatings not only improved the stability of IRE NPs under physiological conditions to avert NPs disassembly and drug release, but also maintained the photostability of ICG to achieve excellent photothermal response. The results indicated that the as-prepared IRE NPs displayed good monodispersity and enhanced stability at various stored media after introducing of EGCG. Compared with monotherapy of RAPA or ICG, IRE NPs showed higher dose-dependent toxicity in MCF-7 cells, HepG2 cells and HeLa cells, especially plus near-infrared laser irradiation. Furthermore, IRE NPs exhibited quicker uptake in cells, higher accumulation in tumor region (even in 48 h) than free ICG and effectively inhibited tumor growth without side effect in H22 tumor-bearing mice. Collectively, the carrier-free IRE NPs provided a simply alternative approach to fabricate RAPA/photosensitizer co-loaded nanoparticles for combinatorial tumor therapy.

[Expression and prognostic significance of EphA2 and EphrinA-1 in ovarian serous carcinomas].

OBJECTIVE: To investigate the expression and prognostic significance of EphA2 and EphrinA-1 in ovarian serous carcinomas. METHODS: Ninety five tumors from the patients with ovarian serous carcinomas and 2 ovarian cancer cell lines were recruited. The expressions of EphA2 and EphrinA-1 were examined by means of immunohistochemistry. The relationships among protein expression and clinicopathological features, survival of patients were analyzed. The mRNA and protein expressions of EphA2 and EphrinA-1 in ovarian cancer cell lines were measured with semiquantitative polymerase chain reaction and western blotting. RESULTS: The protein expressions of EphA2 and EphrinA-1 in tumor were 92.6% (88/95)and 97.9% (93/95) respectively, while were 40%(8/20) and 30% (6/20) in adjacent ovarian tissue (P = 0.000). EphA2 immunohistochemical staining could be observed in both tumour and vascular endothelial cells, and EphrinA-1 mainly localized in the tumor cells. The expression of EphA2 was significantly associated with the expression of EphrinA-1 (r = 0.98, P = 0.02). There was no significant correlation between the expressions of EphA2/EphrinA-1 and age, FIGO stage, residual tumour size and histological grade. High levels of both EphA2 and EphrinA-1 protein expression were significantly associated with a shorter overall survival in multivariate analysis (P < 0.05). High levels of EphA2 and EphrinA-1 mRNA and protein were detected in OVCAR3 and SKOV3 cell lines. CONCLUSION: There are over-expression of EphA2 and EphrinA-1 in ovarian serous carcinomas and ovarian cancer cell lines. Tumours with higher expression levels of both EphA2 and EphrinA-1 significantly associated with poorer clinical outcome.

Accelerating transdermal delivery of insulin by ginsenoside nanoparticles with unique permeability.

Diabetes is a metabolic disease caused by insufficient insulin secretion, action or resistance, in which insulin plays an irreplaceable role in the its treatment. However, traditional administration of insulin requires continuous subcutaneous injections, which is accompanied by inevitable pain, local tissue necrosis and hypoglycemia. Herein, a green and safe nanoformulation with unique permeability composed of insulin and ginsenosides is developed for transdermal delivery to reduce above-mentioned side effects. The ginsenosides are self-assembled to form shells to protect insulin from hydrolysis and improve the stability of nanoparticles. The nanoparticles can temporarily permeate into cells in 5 min and promptly excrete from the cell for deeper penetration. The insulin permeation is related to the disorder of stratum corneum lipids caused by ginsenosides. The skin acting as drug depot mantains the nanoparticles released continuously, therefore the body keeps euglycemic for 48 h. Encouraged by its long-lasting and effective transdermal therapy, ginsenosides-based nano-system is expected to deliver other less permeable drugs like proteins and peptides and benefit those who are with chronic diseases that need long-term medication.

miR-221-3p and miR-222-3p downregulation promoted osteogenic differentiation of bone marrow mesenchyme stem cells through IGF-1/ERK pathway under high glucose condition.

OBJECTIVE: This study aims to investigate the roles of miR-221-3p and miR-222-3p in the regulation of osteogenic differentiation of bone marrow mesenchyme stem cells (BMSCs) under high glucose condition. MATERIALS AND METHODS: The expreesions of miR-221-3p, miR-222-3p and insulin-like growth factor 1 (IGF-1) were detected by qRT-PCR. The protein levels of osteoblast-related proteins (Osterix, Runx-2 and Osteopontin) were detected by western blot. Whether miR-221-3p and miR-222-3p can target IGF-1 was assessed by dual luciferase reporter gene assay. RESULTS: miR-221-3p and miR-222-3p were up-regulated in the mandibles of diabetic rats and BMSCs cultured in high glucose condition. Silencing miR-221-3p or/ and miR-222-3p increased ALP activity and up-regulated osteoblast-related protein levels, and the simultaneous silence the two miRNAs showed stronger effects on ALP activity and osteoblast-related protein levels. Next, we confirmed that miR-221-3p and miR-222-3p both targeted IGF-1 and cooperatively regulated its expression. Besides, miR-221-3p and miR-222-3p regulated ERK activation through IGF-1. Silencing miR-221-3p and miR-222-3p promoted osteogenic differentiation of BMSCs through IGF-1 under high glucose condition. CONCLUSION: miR-221-3p and miR-222-3p inhibited osteogenic differentiation of BMSCs via IGF-1/ERK pathway under high glucose condition.

Improving the Stability of Liposomal Curcumin by Adjusting the Inner Aqueous Chamber pH of Liposomes.

Curcumin (CURC) is a hydrophobic molecule and its water solubility can be greatly improved by liposome encapsulation. However, investigations on the stability of pH-sensitive molecules incorporated into liposomal membranes are limited. In this study, CURC-loaded liposomes with varied internal pH values (pH 2.5, 5.0, or 7.4) were prepared and designated as CURC-LP (pH 2.5), CURC-LP (pH 5.0), and CURC-LP (pH 7.4). Physical properties including particle size, ζ-potential, morphology, entrapment efficiency, and physical stabilities of these CURC-LPs were assessed. In addition, the chemical stability of liposomal CURC to different external physiological environments and internal microenvironmental pH levels were investigated. We found that among these CURC-LPs, CURU-LP (pH 2.5) has the highest entrapment efficiency (73.7%), the best physical stabilities, and the slowest release rate in vitro. Liposomal CURC remains more stable in an acid external environment. In the physiological environment, the chemical stability of liposomal CURC is microenvironmental pH-dependent. In conclusion, we prove that the stability of liposomal CURC is external physiological environment- and internal microenvironmental pH-dependent. These findings suggest that creating an acidic microenvironment in the internal chamber of liposomes is beneficial to the stability of liposomal CURC, as well as for other pH-sensitive molecules.

[Effect of anatomical parameters of maxillary sinus on the outcomes of transcrestal sinus lift].

OBJECTIVE: To investigate the effect of three anatomical parameters (maxillary sinus width, maxillary sinus angle, and residual bone height) on the outcomes of transcrestal sinus lift with simultaneous implant placement. METHODS: A total of 60 maxillary sinuses in 42 patients were included in this study. All patients were treated with transcrestal sinus lift procedure associated with simultaneous implant placement using a composite graft material of autogenous bone and Bio-Oss. For each patient, beam computed tomography (CBCT) scans were performed preoperatively, immediately after surgery, and 6 months after surgery. The parameters were measured on the preoperative and postoperative CBCT images. The correlation of three anatomical parameters with graft resorption was analyzed using Pearson's correlation test. RESULTS: The average residual bone height was (4.46±1.55) mm. The average width of maxillary sinus was (13.86±2.71) mm. The average sinus angle was 78.09°±10.27°. A significant positive correlation was observed between maxillary sinus width and graft resorption (P<0.01). A positive association was also found between sinus angle and graft resorption (P<0.01). CONCLUSIONS: The findings show that graft bone resorption in elevated sinus has a positive correlation with the sinus width and sinus angle.

A study to evaluate herb-drug interaction underlying mechanisms: An investigation of ginsenosides attenuating the effect of warfarin on cardiovascular diseases.

Warfarin and ginseng have been widely used in the treatment of cardiovascular diseases. However, the clinical safety and effectiveness of herb-drug combination treatment are still controversial. Therefore, it is very essential to probe the interaction between warfarin and ginseng. In this study, in vitro and in vivo study was carried out to demonstrate that whether there is an interaction between warfarin and ginsenosides (GS), which is the main component of ginseng. In vitro study showed that the adhesion ability between endothelial cells and matrigel/platelets was enhanced due to the up-regulating expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) proteins by treatment of warfarin+GS combination compared to warfarin/GS treatment alone. Moreover, GS could weaken the anticoagulation effect of warfarin in hyperlipemia rats owning to the increased expression levels of coagulation factors and hepatic cytochrome P450 enzymes in plasma after long-term co-administration of warfarin with GS. The results of both in vitro and in vivo study demonstrated that there is a serious interaction between warfarin and ginseng, which may deteriorate atherosclerosis and thrombosis after combined use of warfarin and GS.

Conversion of puerarin into its 7-O-glycoside derivatives by Microbacterium oxydans (CGMCC 1788) to improve its water solubility and pharmacokinetic properties.

Microbacterium oxydans strain NJ 6 isolated from soil samples converted puerarin into two novel compounds, puerarin-7-O-glucoside and puerarin-7-O-isomaltoside, via an unreported O-glycosylation of the phenolic hydroxyl group at the 7-position of puerarin. Sucrose, maltotriose, and maltose could be used as glucosyl donors for glycosylation of puerarin, but uridine-diphosphate glucose, glucose, fructose, lactose, cyclodextrin, and starch could not. Regardless of the position of B-ring in the (iso)flavonoids core structure, the glycosylation of the phenolic hydroxyl group at the 7-position of (iso)flavonoids was governed by the presence or absence of a glucosyl residue at 8-C. The apparent solubility of puerarin-7-O-glucoside and puerarin-7-O-isomaltoside was approximately 18 and 100 times that of natural puerarin, respectively. Like parent puerarin, puerarin-7-O-glucoside maintained its physiological ability to relax the contractions of isolated rat thoracic aortic rings in vitro induced by phenylephrine. However, puerarin-7-O-glucoside was able to maintain higher plasma concentrations and have a longer mean residence time in the blood than the parent puerarin.

Research progress of improving demyelination in treatment of spinal cord injury / 中国药理学通报

Axonal demyelination is an important factor causing neurological dysfunction after spinal cord injury. Retaining the integrity of myelin sheath and promoting remyelination play an important role in the functional recovery of spinal cord injury. The bottleneck of the failure of remyelination is the inability of myelin-forming cells (oligodendrocytes and Schwann cells) to differentiate and mature. In recent years related research on spinal cord injury demyelination has found that cell transplantation, neuregulin-1 and hydrogel can effectively enhance remyelination, and identified aquaporin-4 (aquaporin-4, AQP4), metal-loproteinase (Matrix metailoproteinase, MMP) may be a potential therapeutic target to promote myelin recovery after spinal cord injury. This review discusses the research progress of enhancing remyelination after spinal cord injury, providing ideas for the further development of new methods for the treatment of spinal cord injury.

Percutaneous bone biopsy using a flat-panel cone beam computed tomography virtual navigation system.

OBJECTIVES: To assess the clinical role of flat-panel cone beam CT (CBCT) in performing percutaneous needle biopsy (PNB) of bone lesions. Flat-panel cone beam CT systems have been used as a guidance tool for performing percutaneous biopsy. Real-time fluoroscopy and virtual navigation systems help simplify needle path planning and shorten procedure times. METHODS: From March 2012 to March 2016, 80 patients with 80 bone lesions were retrospectively enrolled in the study in Zhengzhou city of China. Technical success, diagnostic accuracy, puncture performance, procedure time, complications, and effective radiation exposure were calculated. RESULTS: All biopsies were technically successful (100%). Sufficient tissue for histopathological analysis was obtained in 75 of 80 cases. The sensitivity of PNB of bone lesions was 95.5%, the specificity was 83.3%, and accuracy was 93.7%. The mean scoring of puncture performance was 3.9 ± 1.3. The mean total procedure time was 13.20 ± 4.4 min, resulting in a mean exposure dose of 11.3 ± 5.1 mSv. The complication rate was 8.7%. CONCLUSION: Percutaneous bone biopsy using CBCT is a safe and effective method that simplifies needle path planning and shortens procedure times.

Comparison of the predictive value of Padua and the IMPEDE assessment scores for venous thromboembolism in patients with newly diagnosed multiple myeloma: A single institution experience / 中华血液学杂志

Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.

Status quo of frailty and its influential factors among the community-dwelling elderly / 中华健康管理学杂志

Objective:To investigate and analyze the status quo and influential factors of the elderly in the community.Methods:From July to September 2021, 543 elderly people were investigated in 9 community healthcare service centers in Hangzhou by using the Comprehensive Frailty Assessment Instrument (including four dimensions: physical, psychological, social, and environmental frailty) and the Social Support Rating Scale (including three dimensions: subjective support, objective support, and support availability). Independent sample t-test, analysis of variance, correlation analysis, and multiple linear regression were conducted to examine key determinants of frailty. Results:The total score of frailty among older adults in the community was (43.1±12.0). The results showed that the total score of social support was negatively associated with frailty of community-dwelling older adults ( r=-0.449, P<0.01); age ≥80 years old ( β=0.229, P<0.001) was positively associated with frailty; not living alone, children′s household support, children′s spiritual support, the accessibility of elderly care facilities within a 15-minute walk, and social support score were negatively associated with frailty ( β=-0.118, -0.081, -0.260, -0.155, -0.250,all P<0.05). Conclusion:The elderly in the community have a moderate degree of frailty, which affected by age, living condition, children′s support, the accessibility of elderly care facilities, and social support.

A comprehensive profile of TCF1+ progenitor and TCF1- terminally exhausted PD-1+CD8+ T cells in head and neck squamous cell carcinoma: implications for prognosis and immunotherapy / 国际口腔科学杂志·英文版

The heterogeneity of exhausted T cells (Tex) is a critical determinant of immune checkpoint blockade therapy efficacy. However, few studies have explored exhausted T cell subpopulations in human cancers. In the present study, we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer (HNSCC) by multiplex immunohistochemistry (mIHC) to investigate two subsets of Tex, CD8+PD1+TCF1+ progenitor exhausted T cells (TCF1+Texprog) and CD8+PD1+TCF1- terminally exhausted T cells (TCF1-Texterm). Moreover, fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells (Tregs) in the tumor immune microenvironment (TIME). mIHC and flow cytometry analysis showed that TCF1-Texterm represented a greater proportion of CD8+PD1+Tex than TCF1+Texprog in most patients. TCF1+Texprog produced abundant TNFα, while TCF1-Texterm expressed higher levels of CD103, TIM-3, CTLA-4, and TIGIT. TCF1-Texterm exhibited a polyfunctional TNFα+GZMB+IFNγ+ phenotype; and were associated with better overall survival and recurrence-free survival. The results also indicated that larger proportions of TCF1-Texterm were accompanied by an increase in the proportion of Tregs. Therefore, it was concluded that TCF1-Texterm was the major CD8+PD1+Tex subset in the HNSCC TIME and that these cells favor patient survival. A high proportion of TCF1-Texterm was associated with greater Treg abundance.