Radiotherapy upregulated immune checkpoints contribute to the development of second primary OSCC.

OBJECTIVES: Radiation injury is common after radiotherapy for head and neck cancer. Radiotherapy can reshape the immune microenvironment and cause immunosuppression, including dysregulation of immune checkpoints (ICs). However, the relationship between oral ICs expression after radiation and the development of second primary tumors is unclear. METHODS: Clinical specimens of second primary oral squamous cell carcinoma after radiotherapy (s-OSCC) and primary OSCC (p-OSCC) were collected. The expression and prognostic value of PD-1, VISTA, and TIM-3 were analyzed using immunohistochemistry. To further clarify the relationship between radiation and ICs alteration, a rat model was constructed to explore the spatiotemporal changes of ICs in the oral mucosa after radiation. RESULTS: In carcinoma tissue, the expression of TIM-3 was higher in s-OSCC than in p-OSCC, while the expression of PD-1 and VISTA was similar between the groups. In para-carcinoma tissue, the expression of PD-1, VISTA, and TIM-3 was higher in s-OSCC. High ICs expression was associated with poor survival. In the rat model, ICs were locally upregulated in the irradiated tongue. Moreover, there was a bystander effect, in which the ICs were also upregulated in the unirradiated site. CONCLUSION: Radiation may upregulate ICs expression in oral mucosa and contribute to the development of s-OSCC.

Correlation analysis of plasma lipid profiles and the prognosis of head and neck squamous cell carcinoma.

PURPOSE: This study aims to clarify whether blood lipid profiles are indicators of prognosis in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: This retrospective study included 512 T1/2N0M0 HNSCC patients. The correlation between blood lipid profiles and progression-free survival (PFS) and disease-specific survival (DSS) was analyzed by multivariate analysis. The data from TCGA was also analyzed to investigate the expression levels and prognostic values of different lipoprotein receptors essential for specific lipid uptake. RESULTS: A high level of low-density lipoprotein cholesterol (LDL-C) indicated better PFS and DSS, and a low level of apolipoprotein A-I (Apo A-I) indicated better PFS, while a high level of apolipoprotein B (Apo B) indicated poorer PFS and DSS. The Apo A-I receptor gene SCARB1 was upregulated and associated with poor survival in HNSCC patients. Activation of SCARB1 was implicated in a series of tumor-promoting pathways. There was no significant correlation between the expression of LDL-C and Apo B-related receptors and prognosis. CONCLUSION: A high level of LDL-C and a low level of Apo A-I are protective factors for HNSCC, while a high level of Apo B is a risk factor. The upregulation of SCARB1 may participate in the progression of HNSCC.

[A New Pest of Amomum villosum in Xishuangbanna].

OBJECTIVE: To report a new pest of Amomum villosum and its distribution, occurrence regularity and damage situation, in order to provide reference for its control. METHODS: Reared the pest larvae, observed the morphological characters, and made a preliminary investigation on its distribution, occurrence regularity and damage situation. RESULTS: Through macroscopic examination, the pest was identified as Anisodera rugulosa, which distributed in the main producing areas of Amomum villosum in Xishuangbanna, the pest larvae ate the inside of Amomum villosum fruit, which made the fruit formed holes, more seriously, it made the whole fruit rot black. CONCLUSION: The pest causes the fruit yield reduction of Amomum villosum. Pest control work needs to be carry out as soon as possible.

Impact of the COVID-19 pandemic lockdown on Body Mass Index: a three-year follow up study in 6,156 Chinese college students.

Background: The novel coronavirus disease 2019 as the most pervasive and consequential pandemic in recent years, has exerted significant impacts on human health, including aspects related to body weight. Objectives: This study aims to assess the influence of the lockdown measures implemented during the COVID-19 pandemic on Chinese college students' Body Mass Index (BMI) through a three-year cohort study. Methods: We recruited 6156 college students (n = 4,248, 69% male, and n = 1,908, 31% female, with an average age of 18.68 ± 0.86 yr.) from a University in China to participate in this three-year cohort study. All of the subjects took the same physical fitness tests from 2019 to 2021 (pre-lockdown, during lockdown and post-lockdown). Participants' height and weight data were objectively measured by Tongfang Health Fitness Testing Products 5000 series. A paired t-test was performed in the analysis. Results: During the lockdown, there is 4.2% increase of BMI among the college student (p<0.001). Moreover, males had a greater overall mean BMI rate increase of 4.74% (p<0.001) than females (2.86%, p<0.001). After the lockdown, there is 0.94% increase of BMI among the college student (p<0.001). However, females had a greater overall mean BMI rate increase of 1.49% (p<0.001) than males (0.72%, p<0.001). During this period, the obese and overweight group's growth rate from 2019 to 2020 was smaller than the normal and underweight group, which were 2.94% (p<0.001), 3.90% (p<0.001), 4.44% (p<0.001) and 5.25% (p<0.001), respectively. Conclusion: BMI increased both during and post-lockdown periods among Chinese college students. However, during the lockdown, participants with higher BMI groups appeared to have a diminished BMI growth rate compared to those with lower BMI. After the lockdown, participants with higher BMI levels appeared to have an augmented BMI growth rate. Public policy action is needed to increase the level of physical activity of Chinese college students and take action to improve students' physical fitness performance after the lockdown.

Bridging papermaking and hydrogel production: Nanoparticle-loaded cellulosic hollow fibers with pitted walls as skeleton materials for multifunctional electromagnetic hydrogels.

Electromagnetic hydrogels have attracted significant attention due to their vast potential in soft robotics, biomedical engineering, and energy harvesting. To facilitate future commercialization via large-scale industrial processes, we present a facile concept that utilizes the specialized knowledge of papermaking to fabricate hydrogels with multifunctional electromagnetic properties. The principles of papermaking wet end chemistry, which involves the handling of interactions among cellulosic fibers, fines, polymeric additives, and other components in aqueous systems, serves as a key foundation for this concept. Notably, based on these principles, the versatile use of chemical additives in combination with cellulosic materials enables the tailored design of various products. Our methodology exploits the unique hierarchically pitted and hollow tube-like structures of papermaking grade cellulosic fibers with discernible pits, enabling the incorporation of magnetite nanoparticles through lumen loading. By combining microscale softwood-derived cellulosic fibers with additives, we achieve dynamic covalent interactions that transform the cellulosic fiber slurry into an impressive hydrogel. The cellulosic fibers act as a skeleton, providing structural support within the hydrogel framework and facilitating the dispersion of nanoparticles. In accordance with our concept, the typical hydrogel exhibits combined attributes, including electrical conductivity, self-healing properties, pH responsiveness, and dynamic rheologic behavior. Our approach not only yields hydrogels with interesting properties but also aligns with the forefront of advanced cellulosic material applications. These materials hold the promise in remote strain sensing devices, electromagnetic navigation systems, contactless toys, and flexible electronic devices. The concept and findings of the current work may shed light on materials innovation based on traditional pulp and paper processes. Furthermore, the facile processes involved in hydrogel formation can serve as valuable tools for chemistry and materials education, providing easy demonstrations of principles for university students at different levels.

Single-nucleus transcriptomics uncovers a geroprotective role of YAP in primate gingival aging.

Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis, a worldwide prevalent inflammatory disease. However, a systematic characterization and comprehensive understanding of the regulatory mechanism underlying gingival aging is still lacking. Here, we systematically dissected the phenotypic characteristics of gingiva during aging in primates and constructed the first single-nucleus transcriptomic landscape of gingival aging, by which a panel of cell type-specific signatures were elucidated. Epithelial cells were identified as the most affected cell types by aging in the gingiva. Further analyses pinpointed the crucial role of YAP in epithelial self-renew and homeostasis, which declined during aging in epithelial cells, especially in basal cells. The decline of YAP activity during aging was confirmed in the human gingival tissues, and downregulation of YAP in human primary gingival keratinocytes recapitulated the major phenotypic defects observed in the aged primate gingiva while overexpression of YAP showed rejuvenation effects. Our work provides an in-depth understanding of gingival aging and serves as a rich resource for developing novel strategies to combat aging-associated gingival diseases, with the ultimate goal of advancing periodontal health and promoting healthy aging.

The Dual Effect of Ionic Liquid Pretreatment on the Eucalyptus Kraft Pulp during Oxygen Delignification Process.

Oxygen delignification presents high efficiency but causes damage to cellulose, therefore leading to an undesired loss in pulp strength. The effect of ionic liquid pretreatment of [BMIM][HSO4] and [TEA][HSO4] on oxygen delignification of the eucalyptus kraft pulp was investigated at 10% IL loading and 10% pulp consistency, after which composition analysis, pulp and fiber characterizations, and the mechanism of lignin degradation were carried out. A possible dual effect of enhancing delignification and protecting fibers from oxidation damage occurred simultaneously. The proposed [TEA][HSO4] pretreatment facilitated lignin removal in oxygen delignification and provided fibers with improved DP, fiber length and width, and curl index, resulting in the enhanced physical strength of pulp. Particularly, its folding endurance improved by 110%. An unusual brightness reduction was identified, followed by detailed characterization on the pulps and extracted lignin with FTIR, UV, XPS, and HSQC. It was proposed that [TEA][HSO4] catalyzed the cleavage of ß-O-4 bonds in lignin during the oxygen delignification, with the formation of Hibbert's ketones and quinonoid compounds. The decomposed lignin dissolved and migrated to the fiber surface, where they facilitated the access of the oxidation agent and protected the fiber framework from oxidation damage. Therefore, it was concluded that ionic liquid pretreatment has a dual effect on oxygen delignification.

Diet-induced obesity accelerates oral carcinogenesis by recruitment and functional enhancement of myeloid-derived suppressor cells.

Although obesity has been associated with an increased risk and aggressiveness of many types of carcinoma, whether it promotes squamous cell carcinoma remains unclear. To reveal the role of obesity in oral squamous cell carcinoma (OSCC) initiation and development, we used 4NQO-induced OSCC model mice to examine the impact of dietary obesity on carcinogenesis. The results showed that high-fat diet (HFD)-induced obesity significantly promoted the incidence of OSCC and altered the local immune microenvironment with the expansion of CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs). The underlying mechanism that induced an immunosuppressive local microenvironment in obesity was the recruitment of MDSCs through the CCL9/CCR1 axis and enhancement of MDSC immunosuppressive function via intracellular fatty acid uptake. Furthermore, clinical samples verified the increase in infiltrated CD33+ (a marker of human MDSCs) cells in obese OSCC patients, and data from the TCGA dataset confirmed that CD33 expression was positively correlated with local adipocytes in OSCC. Survival analysis showed that enrichment of adipocytes and high expression of CD33 were associated with poor prognosis in OSCC patients. Strikingly, depletion of MDSCs significantly ameliorated HFD-promoted carcinogenesis in 4NQO-induced model mice. These findings indicate that obesity is also an important risk factor for OSCC, and cancer immunotherapy, especially targeting MDSCs, may exhibit greater antitumor efficacy in obese patients.

Antibacterial and mechanical properties of reduced graphene-silver nanoparticle nanocomposite modified glass ionomer cements.

OBJECTIVES: Glass ionomer cements (GIC) are widely recognized as important dental restorative materials whilst they often suffer from restoration failures due to the poor mechanical properties and secondary caries. Reduced graphene-silver nanoparticle (R-GNs/Ag) nanocomposite exhibits excellent antibacterial activities. This study aimed to evaluate the antibacterial and mechanical properties of GIC modified by incorporation of different proportion of R-GNs/Ag. METHODS: R-GNs/Ag nanoparticles were incorporated into conventional glass ionomer powder at 0-2.00 wt.% concentration and cement specimen were prepared. The antibacterial properties of R-GNs/Ag modified GIC materials were investigated by direct contact test (DCT), scanning electron microscopy (SEM) observation, XTT assay and bacteria live/dead assay. Flexural strength and surface microhardness were measured by a universal testing machine and a microhardness tester, respectively. RESULTS: The DCT demonstrated an obvious decrease of S. mutans quantity with incorporation of 2.00 wt.% nanoparticles (p < 0.05). SEM images showed fewer bacteria and smaller stacks on the surface of modified specimens. No significant difference was found in the metabolic activity of S. mutans according to the XTT assay (p < 0.05). The addition of 1.00 and 2.00 wt.% R-GNs/Ag significantly decreased the percentage of viable bacteria (p < 0.05). There was no significant decrease of flexural strength and surface microhardness with incorporation of up to 2.00 wt.% nanocomposite (p < 0.05). CONCLUSIONS: R-GNs/Ag nanocomposite might be a promising agent to improve the antibacterial activity of dental restorative GIC without compromising its mechanical properties. CLINICAL SIGNIFICANCE: R-GNs/Ag nanocomposite can serve as a potential modifier for dental restorative materials.

Metformin as a senostatic drug enhances the anticancer efficacy of CDK4/6 inhibitor in head and neck squamous cell carcinoma.

CDK4/6 inhibitors show promising antitumor activity in a variety of solid tumors; however, their role in head and neck squamous cell carcinoma (HNSCC) requires further investigation. The senescence-associated secretory phenotype (SASP) induced by CDK4/6 inhibitors has dual effects on cancer treatment. The need to address the SASP is a serious challenge in the clinical application of CDK4/6 inhibitors. We investigated whether metformin can act as a senostatic drug to modulate the SASP and enhance the anticancer efficacy of CDK4/6 inhibitors in HNSCC. In this study, the efficacy of a combination of the CDK4/6 inhibitor LY2835219 and metformin in HNSCC was investigated in in vitro assays, an HSC6 xenograft model, and a patient-derived xenograft model. Senescence-associated ß-galactosidase staining, antibody array, sphere-forming assay, and in vivo tumorigenesis assay were used to detect the impacts of metformin on the senescence and SASP induced by LY2835219. We found that LY2835219 combined with metformin synergistically inhibited HNSCC by inducing cell cycle arrest in vitro and in vivo. Metformin significantly modulated the profiles of the SASP elicited by LY2835219 by inhibiting the mTOR and stat3 pathways. The LY2835219-induced SASP resulted in upregulation of cancer stemness, while this phenomenon can be attenuated when combined with metformin. Furthermore, results showed that the stemness inhibition by metformin was associated with blockade of the IL6-stat3 axis. Survival analysis demonstrated that overexpression of IL6 and stemness markers was associated with poor survival in HNSCC patients, indicating that including metformin to target these proteins might improve patient prognosis. Collectively, our data suggest that metformin can act as a senostatic drug to enhance the anticancer efficacy of CDK4/6 inhibitors by reprogramming the profiles of the SASP.

Obesity and genes related to lipid metabolism predict poor survival in oral squamous cell carcinoma.

OBJECTIVES: Obesity is an important risk factor for several malignancies, but its effect on oral squamous cell carcinoma (OSCC) prognosis is controversial. We aimed to disclose the association between obesity and the OSCC outcome, and explore the potential of some lipid metabolism-related genes as biomarkers for prognostic prediction. MATERIALS AND METHODS: A total of 576 patients diagnosed as T1/2N0M0 OSCC without prediagnosis weight loss was included in this retrospective study. These patients were grouped according to body mass index (BMI). The univariate and multivariate analysis were used to compare the progression-free survival (PFS) and disease specific survival (DSS) between groups. Propensity score matching (PSM) was adopted to minimize confounders. Data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were employed to analyze the potential of some lipid metabolism-related genes for OSCC prognosis prediction. RESULTS: The PFS (P = 0.023) and DSS (P = 0.047) were poorer in obese patients than in normal weight ones. Obesity was an independent risk factor for PFS (Hazard Ratio = 2.016, 95% Confidence Interval 1.101-3.693, P = 0.023) and DSS (Hazard Ratio = 2.022, 95% Confidence Interval 1.040-3.932, P = 0.038). Furthermore, the PSM matched cohort analysis revealed that obesity was associated with poor prognosis of OSCC patients. Finally, 72 dysregulated lipid metabolism-related genes were identified in OSCC, and a combining signature of TGFB1, SPP1, and SERPINE1 was defined as a biomarker for prognostic prediction. CONCLUSIONS: Obesity is an independent risk factor for T1/2N0M0 OSCC, and a combining signature of TGFB1, SPP1, and SERPINE1 may be applied to predict prognosis of OSCC patients.

The poor outcome of second primary oral squamous cell carcinoma is attributed to Bmi1 upregulation.

Radiotherapy for nasopharyngeal carcinoma has been reported to cause second primary oral squamous cell carcinoma (s-OSCC). The prognosis and pathologic characteristic of s-OSCC are largely unknown. Bmi1 was associated with the repair of radiation-induced DNA damage, suggesting its possible involvement in the pathologic process of s-OSCC. Herein, we compared the prognosis between s-OSCC and primary OSCC (p-OSCC) and explored the involvement of Bmi1 in s-OSCC development. In this retrospective study, s-OSCC and p-OSCC patients were matched by propensity scores. Their outcomes were compared by univariate and multivariate analyses. The expression of Bmi1 in s-OSCC and p-OSCC was detected by immunohistochemistry (IHC). Radiation-induced Bmi1 alteration in early-stage was explored in a rat model and HaCaT cells. After matching, 116 pairs of patients with highly balanced characteristics were included. In univariate analysis, the overall survival (OS), disease-specific survival (DSS), and local recurrence-free survival (LRFS) were poorer in s-OSCC than in p-OSCC (P < 0.05), while their regional metastasis-free survival (RMFS) was parallel (P = 0.112). Multivariate analysis further revealed that radiotherapy history was an independent risk factor for OS, DSS, and LRFS (P < 0.05). IHC results showed that the positive rate of Bmi1 was higher in s-OSCC (P = 0.0027). In a rat model of radiotherapy-induced mucositis, Bmi1 upregulation was observed 8 days after irradiation. Consistently, Bmi1 was upregulated in HaCaT cells 1 h after irradiation, and its upregulation was in accord with X-ray exposure duration. In conclusion, the prognosis of s-OSCC is poorer as compared to p-OSCC, which may be attributed to Bmi1 upregulation.

Enhanced antimicrobial activities of silver-nanoparticle-decorated reduced graphene nanocomposites against oral pathogens.

As a means of capitalizing on the synergistic properties between reduced graphene nanosheets (R-GNs) and silver nanoparticles (AgNPs), an efficient and convenient chemical reduction method was used to prepare silver-nanoparticle-decorated reduced graphene nanocomposites (R-GNs/Ag). The products were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Raman spectroscopy, which confirmed the loading of well-dispersed silver nanoparticles on reduced graphene sheets. Their antimicrobial activities against oral pathogens such as Candida albicans, Lactobacillus acidophilus, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans were investigated by MIC determination, the counting of colony-forming units (CFU), agar diffusion tests, and growth curve observation. Compared with pure R-GNs and AgNPs, R-GNs/Ag composites exhibited enhanced antimicrobial properties owing to highly dispersed AgNPs on R-GNs.

Quercetin ameliorates senescence and promotes osteogenesis of BMSCs by suppressing the repetitive element­triggered RNA sensing pathway.

Cell senescence impedes the self­renewal and osteogenic capacity of bone marrow mesenchymal stem cells (BMSCs), thus limiting their application in tissue regeneration. The present study aimed to elucidate the role and mechanism of repetitive element (RE) activation in BMSC senescence and osteogenesis, as well as the intervention effect of quercetin. In an H2O2­induced BMSC senescence model, quercetin treatment alleviated senescence as shown by a decrease in senescence­associated ß­galactosidase (SA­ß­gal)­positive cell ratio, increased colony formation ability and decreased mRNA expression of p21 and senescence­associated secretory phenotype genes. DNA damage response marker γ­H2AX increased in senescent BMSCs, while expression of epigenetic markers methylation histone H3 Lys9, heterochromatin protein 1α and heterochromatin­related nuclear membrane protein lamina­associated polypeptide 2 decreased. Quercetin rescued these alterations, indicating its ability to ameliorate senescence by stabilizing heterochromatin structure where REs are primarily suppressed. Transcriptional activation of REs accompanied by accumulation of cytoplasmic double­stranded (ds)RNA, as well as triggering of the RNA sensor retinoic acid­inducible gene I (RIG­I) receptor pathway in H2O2­induced senescent BMSCs were shown. Similarly, quercetin treatment inhibited these responses. Additionally, RIG­I knockdown led to a decreased number of SA­ß­gal­positive cells, confirming its functional impact on senescence. Induction of senescence or administration of dsRNA analogue significantly hindered the osteogenic capacity of BMSCs, while quercetin treatment or RIG­I knockdown reversed the decline in osteogenic function. The findings of the current study demonstrated that quercetin inhibited the activation of REs and the RIG­I RNA sensing pathway via epigenetic regulation, thereby alleviating the senescence of BMSCs and promoting osteogenesis.