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Highlights The acid etching Co-naphthalenedicarboxylic acid-based metal–organic frameworks (donated as AE-CoNDA) catalyst displayed an excellent oxygen evolution reaction (OER) activity for long-term stability. Integration of the AE-CoNDA cocatalyst into BiVO4 achieved a remarkable PEC-OER activity. The stretched Co-O bond length regulated the spin state transition at the Co active sites. The optimized high spin state of Co sites adjusted the orbitals hybridization of Co 3d and O 2p.

Background/purpose: Healthy states of human microbiota depend on a stable community of symbiotic microbes irrespective of external challenges from the environment. Thus, long-term stability of the oral microbiota is of importance, particularly for older patient populations. Materials and methods: We used next-generation sequencing (NGS) to examine the tongue microbiota of 18 individuals receiving long-term care over a 10-month period. Results: Beta diversity analysis demonstrated temporal stability of the tongue microbiota, as microbial compositions from all time points were indistinguishable from each other (P = 0.0887). However, significant individual variation in microbial composition (P = 0.0001) was observed, underscoring the presence of a unique microbial profile for each patient. Conclusion: The temporal dynamics of tongue microbiota exhibit long-term stability, providing diagnostic implications for oral diseases within older patient populations.

Cisplatin resistance poses a major challenge in the treatment of oral squamous cell carcinoma (OSCC). Deeper investigations into the mechanisms underlying this drug resistance is of great importance. Here, we used cellular assays and clinical immunohistochemistry to examine molecular pathways involved in both innate and acquired cisplatin resistance. We demonstrated that the p62-mTORC1 signaling complex plays a pivotal role, and is driven by the EGFR signaling network, specifically through the PI3K-Akt axis and the transcription factor C/EBP-β. Elevated p-mTOR expression was associated with cancer relapse and poor prognosis among oral cancer patients. Additionally, we illustrated that mTOR inhibitors enhance the cytotoxic effect of cisplatin, by employing cancer stem cell characteristics. Our work unveils fundamental mechanisms for cisplatin resistance, thereby presenting therapeutic implications for OSCC.

The entry of SARS-CoV-2 into host cells involves the interaction between the viral spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor. Given that the spike protein evolves rapidly to evade host immunity, therapeutics that block ACE2 accessibility, such as spike decoys, could serve as an alternative strategy for attenuating viral infection. Here, we constructed a drug screening platform based on oral epithelial cells to rapidly identify peptides or compounds capable of blocking the spike-ACE2 interaction. We engineered short decoy peptides, 8 to 14 amino acids in length, using the spike protein's receptor-binding motif (RBM) and demonstrated that these peptides can effectively inhibit virus attachment to host cells. Additionally, we discovered that diminazene aceturate (DIZE), an ACE2 activator, similarly inhibited virus binding. Our research thus validates the potential of decoy peptides as a new therapeutic strategy against SARS-CoV-2 infections, opening avenues for further development and study.

ABSTRACTBackground Dysbiosis of oral microbiome causes chronic diseases including dental caries and periodontitis, which frequently affect older patient populations. Severely disabled individuals with impaired swallowing functions may require nutritional supply via nasogastric (NG) tubes, further impacting their oral condition and possibly microbial composition. However, little is known about the effect of NG tube on oral microbes and its potential ramification.Methods By using 16S rRNA amplicon sequencing, we characterized the tongue microbiome of 27 patients fed with NG tubes and 26 others fed orally.Results The microbial compositions of NG-tube and oral-feeding patients were substantially different, with more Gram-negative aerobes enriched in the presence of NG tube. Specifically, NG-tube patients presented more opportunistic pathogens like Pseudomonas and Corynebacterium associated with pneumonia and lower levels of commensal Streptococcus and Veillonella. Co-occurrence analysis further showed an inverse relationship between commensal and pathogenic species.Conclusion We present a systematic, high-throughput profiling of oral microbiome with regard to long-term NG tube feeding among the older patient population.

Abstract Introduction Traditionally, dental students learn the skills for dentist-patient interaction and communication via on-site contact with patients, when they start clinical training. However, preclinical students (who have not started clinical practice) have fewer chances to realize the context of dentist-patient interaction. It has remained unclear if a gamification approach via digital media, i.e., a computer role-playing game, can help to learn clinical communication skills. The intervention-based study investigates the effectiveness of the clinical dentist-patient communication (CDPC) game on students’ motivation, beliefs, and self-efficacy to learn behavioral issues of clinical communication. Methods Fifty-two dental students (Preclinical group) and 18 dental interns and dentists (Clinical group) played the CDPC game, which consists of 16 scenes of clinical context about dentist-patient communication (less than 40 min for playing), via web browsers. Pre-test and post-test questionnaires were used to assess their motivation, beliefs, and self-efficacy to learn behavioral issues of clinical communication. The effectiveness was examined by comparing pre-test and post-test scores within-subject and between-group difference was compared between Preclinical and Clinical groups, via non-parametric statistical tests. Results (A) In the Preclinical group, participants showed a significant increase in motivation and self-efficacy in learning after playing the CDPC game (p

Improving fuel cell technologies based on Pt-based alloys is important for efficient fuel cells. Here, the authors report a hybrid PtCo alloy electrocatalyst for acidic oxygen reduction at high current densities and H2/air fuel cell power densities.

Background Dysbiosis of oral microbiota is the cause of many diseases related to oral and general health. However, few Asia-based studies have evaluated the role of oral microbiota in patients receiving long-term care. Thus, new indications are needed for early prevention and risk management based on information derived from the oral microbiota. Methods We used next-generation sequencing (NGS) to identify the oral bacterial composition and abundance in patients receiving long-term care: 20 from the outpatient department (OPD) and 20 home-care patients. Their microbial compositions, taxonomy, and alpha/beta diversity were characterized. Results Microbiota from the two groups showed different diversity and homogeneity, as well as distinct bacterial species. A more diverse and stable microbial population was observed among OPD patients. Our findings indicated that home-care patients had a higher risk of oral diseases due to the existence of dominant species and a less stable microbial community. Conclusion This work was the first in Taiwan to use NGS to investigate the oral microbiota of long-term care patients. Our study demonstrated the potential use of dominant bacterial species as biomarkers for the risk management of posttreatment complications.

The resection of oral cancers extending into the pterygoid region remain a challenge for head and neck surgeons. Few studies have suggested the approach methods and showed that the tumor can be resected with a clear vision. In this case series study, we advocated a surgical method for the tumor ablation surgery over this region. The study was conducted in 11 patients with tumors near or directly invading into the pterygoid regions. A cheek flap combined with ramus removal was used to approach the pterygoid plates and the associated muscles. A reciprocating saw was used subsequently for the pterygoid plate resection. In the collected 11 patients, neither serious complications occurred during the surgery nor immediate complications happened after the surgery. Four patients expired during the postoperative follow-up period. Two of them died of cancer related conditions, one for tumor recurrence and the other for distant metastasis. The reasons for non-cancer specific mortality were myocardial infraction and aspiration pneumonia Only one patient showed positive margins in the final surgical pathology.

The miR-34 family was originally found to be a direct target of p53 and is a group of putative tumor suppressors. Surprisingly, mice lacking all mir-34 genes show no increase in cancer formation by 18 months of age, hence placing the physiological relevance of previous studies in doubt. Here, we report that mice with prostate epithelium-specific inactivation of mir-34 and p53 show expansion of the prostate stem cell compartment and develop early invasive adenocarcinomas and high-grade prostatic intraepithelial neoplasia, whereas no such lesions are observed after inactivation of either the mir-34 or p53 genes alone by 15 months of age. Consistently, combined deficiency of p53 and miR-34 leads to acceleration of MET-dependent growth, self-renewal, and motility of prostate stem/progenitor cells. Our study provides direct genetic evidence that mir-34 genes are bona fide tumor suppressors and identifies joint control of MET expression by p53 and miR-34 as a key component of prostate stem cell compartment regulation, aberrations in which may lead to cancer.

Background: Visual oral examination (VOE) is a conventional oral cancer screening method. This study aimed to evaluate the value of methylation marker to assist VOE in identifying oral epithelial dysplasia and oral squamous cell carcinoma (OED/OSCC) from non-cancerous lesions in a real-world situation. Methods: 201 patients with high-risk personal habits who self-perceived oral anomaly were VOE examined, ZNF582 methylation (ZNF582m) tested, and histologically diagnosed. Results: Among them, 132 patients (65.7%) were histologically diagnosed OED/OSCC. Using VOE, 56.1% OED/OSCC patients had possible oral cancer, whereas 37.7% non-OED/OSCC patients had leukoplakia. ZNF582m-positive was detected in 90.2% OED/OSCC patients and 44.9% non-OED/OSCC patients. Various logistic regression models were postulated to evaluate the diagnostic performance of conventional VOE and new strategies using ZNF582m. ROC analysis and its corresponding C-index demonstrated that either triage or co-testing models of VOE and ZNF582m could improve diagnostic performance and discriminative abilities compared with the VOE only approach. Conclusions: In conclusion, methylation marker test shows equivalent performance to an experienced judgment by oral maxillofacial surgeons and plays a significantly supplementary role in increasing the efficacy in identifying oral malignant lesions. ZNF582m may be an especially important tool for family physicians or general dentists to properly diagnose suspicious oral lesions.

miR-372 has been shown a potent oncogenic miRNA in the pathogenesis of oral squamous cell carcinoma (OSCC). The zinc finger and BTB domain containing 7A protein (ZBTB7A) is a transcriptional regulator that is involved in a great diversity of physiological and oncogenic regulation. However, the modulation of ZBTB7A in OSCC remains unclear. Tissue analysis identifies a reverse correlation in expression between miR-372 and ZBTB7A in OSCC tumors. When OSCC cells have stable knockdown of ZBTB7A, their oncogenic potential and drug resistance is increased. By way of contrast, such an increase is attenuated by expression of ZBTB7A. Screening and validation confirms that ZBTB7A is able to modulate expression of the death receptors TRAIL-R1, TRAIL-R2, Fas and p53 phosphorylated at serine-15. In addition, ZBTB7A transactivates TRAIL-R2, which sensitizes cells to cisplatin-induced apoptosis. The ZBTB7A-TRAIL-R2 cascade is involved in both the extrinsic and intrinsic cisplatin-induced pathways of apoptosis. Database analysis indicates that the expression level of and the copy status of ZBTB7A and TRAIL-R2 are important survival predictors for head and neck cancers. Collectively, this study indicates the importance of the miR-372-ZBTB7A-TRAIL-R2 axis in mediating OSCC pathogenesis and in controlling OSCC drug resistance. Therefore, silencing miR-372 and/or upregulating ZBTB7A would seem to be promising strategies for enhancing the sensitivity of OSCC to cisplatin therapy.

Oral squamous cell carcinoma (OSCC) is among the leading causes of cancer-associated death worldwide. miR-31 is an oncogenic miRNA in OSCC. NUMB is an adaptor protein capable of suppressing malignant transformation. Disruption of the miR-31-NUMB regulatory axis has been demonstrated in malignancies. Mitochondrial dysfunction and adaptation to glycolytic respiration are frequent events in malignancies. Monocarboxylate transporters (MCTs) function to facilitate lactate flux in highly glycolytic cells. Upregulation of MCT1 and MCT4 has been shown to be a prognostic factor of OSCC. Here, we reported that miR-31-NUMB can modulate glycolysis in OSCC. Using the CRISPR/Cas9 gene editing strategy, we identified increases in oncogenic phenotypes, MCT1 and MCT4 expression, lactate production, and glycolytic respiration in NUMB-deleted OSCC subclones. Transfection of the Numb1 or Numb4 isoform reversed the oncogenic induction elicited by NUMB deletion. This study also showed, for the first time, that NUMB4 binds MCT1 and MCT4 and that this binding increases their ubiquitination, which may decrease their abundance in cell lysates. The disruptions in oncogenicity and metabolism associated with miR-31 deletion and NUMB deletion were partially rescued by MCT1/MCT4 expression or knockdown. This study demonstrated that NUMB is a novel binding partner of MCT1 and MCT4 and that the miR-31-NUMB-MCT1/MCT4 regulatory cascade is present in oral carcinoma.

Oral cancer is one of the most common head and neck malignancies and has an overall 5-year survival rate that remains below 50%. Oral cancer is generally preceded by oral potentially malignant disorders (OPMDs) but determining the risk of OPMD progressing to cancer remains a difficult task. Several diagnostic technologies have been developed to facilitate the detection of OPMD and oral cancer, and some of these have been translated into regulatory-approved in vitro diagnostic systems or medical devices. Furthermore, the rapid development of novel biomarkers, electronic systems, and artificial intelligence may help to develop a new era where OPMD and oral cancer are detected at an early stage. To date, a visual oral examination remains the routine first-line method of identifying oral lesions; however, this method has certain limitations and as a result, patients are either diagnosed when their cancer reaches a severe stage or a high-risk patient with OPMD is misdiagnosed and left untreated. The purpose of this article is to review the currently available diagnostic methods for oral cancer as well as possible future applications of novel promising technologies to oral cancer diagnosis. This will potentially increase diagnostic options and improve our ability to effectively diagnose and treat oral cancerous-related lesions.

Oral squamous cell carcinoma (OSCC) is a globally prevalent malignancy. The molecular mechanisms of this cancer are not well understood and acquire elucidation. Peroxiredoxin like 2A (PRXL2A) has been reported to be an antioxidant protein that protects cells from oxidative stress. Our previous study identified an association between PRXL2A upregulation in OSCC and a worse patient prognosis. MicroRNAs (miRNAs) are small non-coding RNAs that are involved in the modulation of biological/pathological properties. The miR-125 family of genes drive pluripotent regulation across a wide variety of cancers. In this study, we identify the oncogenic eligibility of PRXL2A and clarify miR-125b as its upstream regulator. Downregulation of miR-125b can be observed in OSCC tumors. Lower miR-125b expression in tumors results in a worse patient prognosis at the relatively early stage. Reporter assays are able to validate that PRXL2A is a direct target of miR-125b. Exogenous miR-125b expression in OSCC cells results in increased oxidative stress, increased drug sensitivity, and suppressor activity that is paralleled by the knockout of PRXL2A gene. The suppressor activity of miR-125b is able to be rescued by PRXL2A, which suggests the existence of a miR-125b-PRXL2A regulatory axis that is part of OSCC pathogenesis. Nuclear factor-erythroid 2-related factor 2 (NRF2) was found to be a downstream effector of the miR-125b-PRXL2A cascade. As a whole, this study has pinpointed novel clues demonstrating that downregulation of miR-125b suppressor underlies upregulation of PRXL2A in OSCC, and this then protects the affected tumor cells from oxidative stress. Keywords: HNSCC, miR-125, NRF2, Oxidation, Peroxiredoxin like 2A

Oral squamous cell carcinoma (OSCC) is among the leading causes of cancer-associated deaths worldwide. Family members in miR-371/372/373 miRNA cluster, which is localized at human chromosome 19q13.4, are co-expressed in both human stem cells and malignancies. The individual miRNA in this cluster are also involved in modulating the pathogenesis of malignancies as either oncogenes or suppressors. The 19q13 region is frequently gained in head and neck cancers. High expression of miR-372 and miR-373 are survival predictors for OSCC. However, the role of the miR-371/372/373 cluster in oral carcinogenesis remains to be fully investigated. We use the clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 system to establish OSCC cell subclones that had the miR-371/372/373 cluster deleted. In addition, further subclones were established that had the promoter of this cluster deleted. Concordant silencing in SAS cells of miR-371/372/373 decreased oncogenic potential, increased cisplatin sensitivity, activated p53, and upregulated the expression of Bad and DKK1. We also employed the CRISPR/dCas9 synergistic activation mediator system, which allowed robust transcriptional activation of the whole miR-371/372/373 cistron. Upregulation of endogenous miR-371/372/372 expression increased both oncogenicity and drug resistance. These were accompanied by a slight activation of AKT, β-catenin, and Src. This study identifies the oncogenic role of the miR-371/372/373 cluster in OSCC. Using CRISPR based strategy can be a powerful paradigm that will provide mechanistic insights into miRNA cluster functionality, which will also likely help the development of targeting options for malignancies.

Oral squamous cell carcinoma (OSCC) is a cancerous disease with poor prognosis. According to the statistics, the 5-year survival rate has not improved significantly over the past 20 years. The platelet-derived growth factor (PDGF) and its signaling pathway is a key regulator of angiogenesis and tumorigenesis. High level of PDGF and its receptor (PDGFR) have been reported in several types of malignancies. In this study, we investigated the relationship of the molecular expression levels of PDGF and PDGFR with clinicopathological parameters in OSCC. To this end, we measured the mRNA and protein levels of PDGF and PDGFR by real-time quantitative PCR (qRT-PCR), immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA), respectively. We found positive correlations of the mRNA levels of PDGFA, PDGFB, and PDGFRB with lymph node metastasis and poor overall survival (OS). High expression of PDGF, PDGFRA, and PDGFRB were remarkably associated with lymph node metastasis and poor OS, as determined by immunohistochemistry. Preoperative serum levels of PDGF-AA and PDGF-BB had a positive correlation with preoperative platelet count. Elevated serum levels of PDGF-AA. PDGF-BB, and platelet count correlated with lymph node metastasis and an unfavorable outcome. In multivariate Cox regression analysis, PDGFA mRNA, PDGFB mRNA, PDGFRB mRNA, PDGF immunoexpression, PDGFRB immunoexpression, serum PDGF-AA, serum PDGF-BB, and platelet count emerged as significant independent prognostic factors for OS. In vitro, we found that elevated PDGF promotes colony formation, migration, and invasiveness of SAS and OECM-1 cancer cell lines. Our results suggest that the expression level of serum PDGF has the potential to become a useful diagnostic marker for the prognosis of OSCC. In addition, PDGFR should be considered as a potential therapeutic target for OSCC. Furthermore, research should be undertaken to elucidate the role of PDGF and PDGFR regarding the behavior of tumor cells in OSCC.

Background/purpose: The purposes of this study were to report the suitability, alternate-forms reliability, and the concurrent validity of the analysis of diadochokinesis (DDK) samples in normal speech using the Diadochokinetic Rate Analysis (DRA) program. Methods: Fifteen healthy participants were recorded as they repeated various syllables as quickly and steadily as possible. When the lowest peak intensity during consonant-vowel syllables is lower than the highest peak intensity during intersyllable pauses, the DRA output is incorrect and the DDK sample is defined as nonexecutable. The executable DDK samples were hand measured and executed by the DRA program to generate outputs at different thresholds. Analyses were based on the percentage of nonexecutable DDK samples and the comparisons of the results between repeated analyses at different thresholds and between automatic and manual measuring methods. Results: One-ninth of the DDK samples could not be accurately executed. When the protocol could be accurately executed, the reliability at different thresholds and the validity between different measuring methods were both satisfactory. Conclusion: Although inadvertent articulatory breakdown or the incoordination of intrasyllabic movements were major limiting factors to the suitability, the alternate-forms reliability and concurrent validity of the analysis of DDK in adults with normal speech using the DRA program were both satisfactory if the DDK train was executable by DRA.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent carcinomas worldwide. MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression and modulate physiological or pathological processes including OSCC carcinogenesis. miR-31 has been found to be up-regulated in OSCC and to act as an oncogenic miRNA. However, the molecular mechanism underlying miR-31 up-regulation in OSCC is still obscure. The activation of epidermal growth factor receptor (EGFR) signaling axis plays key roles in driving oral carcinogenesis. Our screening identified that there is up-regulation of miR-31, miR-181b and miR-222 in OSCC cells following EGF treatment. Subsequent analysis showed that EGF treatment led to AKT activation, which then resulted in miR-31 up-regulation. Moreover, EGF treatment and the AKT activation induced by exogenous expression up-regulated C/EBPβ expression. The miR-31 up-regulation induced by EGF was abrogated by AKT inhibition or by the knockdown of C/EBPβ expression. In OSCC cell subclones stably overexpressing the functional isoform of C/EBPβ, miR-31 expression was up-regulated. Curcumin is a natural ingredient exhibiting anti-cancer potential. It was found that curcumin attenuated AKT activation and the up-regulation of C/EBPβ and miR-31 caused by EGF stimulation in OSCC cells. Lastly, concordance across the expression of EGFR, the expression of C/EBPβ and the expression of miR-31 in OSCC tissues was found. This study describes a novel scenario where the up-regulation of miR-31 expression in OSCC is, at least in part, a consequence of EGFR oncogenic activation. Although the AKT activation and C/EBPβ expression after EGF treatment might not be directly linked, both events are the crucial mediators underlying miR-31 up-regulation in the EGFR signaling axis.

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer deaths among women in the United States, but its pathogenesis is poorly understood (1-3). Some epithelial cancers are known to occur in transitional zones between two types of epithelium, whereas others have been shown to originate in epithelial tissue stem cells (4-6). The stem cell niche of the ovarian surface epithelium (OSE), which is ruptured and regenerates during ovulation, has not yet been defined unequivocally. Here we identify the hilum region of the mouse ovary, the transitional (or junction) area between the OSE, mesothelium and tubal (oviductal) epithelium, as a previously unrecognized stem cell niche of the OSE. We find that cells of the hilum OSE are cycling slowly and express stem and/or progenitor cell markers ALDH1, LGR5, LEF1, CD133 and CK6B. These cells display longterm stem cell properties ex vivo and in vivo, as shown by our serial sphere generation and long-term lineage-tracing assays. Importantly, the hilum cells show increased transformation potential after inactivation of tumour suppressor genes Trp53 and Rbl, whose pathways are altered frequently in the most aggressive and common type of human EOC, high-grade serous adenocarcinoma (7,8). Our study supports experimentally the idea that susceptibility of transitional zones to malignant transformation may be explained by the presence of stem cell niches in those areas. Identification of a stem cell niche for the OSE may have important implications for understanding EOC pathogenesis., An extensive integrated genomic analysis of 489 high-grade serous ovarian adenocarcinomas has provided important insights into the repertoire of molecular aberrations that are characteristic for this most common and deadly [...]

MicroRNAs are short non-coding RNAs that regulate gene expression and are crucial to tumorigenesis. Oral squamous cell carcinoma (OSCC) is a prevalent malignancy worldwide. Up-regulation of miR-146 has been identified in OSCC tissues. However, the roles of miR-146 in carcinogenesis are controversial as it is suppressive in many other malignancies. The present study investigated the pathogenic implications of miR-146a in oral carcinogenesis. Microdissected OSCC exhibits higher levels of miR-146a expression than matched adjacent mucosal cells. The plasma miR-146a levels of patients are significantly higher than those of control subjects; these levels decrease drastically after tumor resection. miR-146a levels in tumors and in patients' plasma can be used to classify OSCC and non-disease status (sensitivity: >0.72). Exogenous miR-146a expression is significantly increased in vitro oncogenic phenotypes as well as during xenograft tumorigenesis and OSCC metastasis. The plasma miR-146a levels of these mice parallel the xenograft tumor burdens of the mice. A miR-146a blocker abrogates the growth of xenograft tumors. miR-146a oncogenic activity is associated with down-regulation of IRAK1, TRAF6 and NUMB expression. Furthermore, miR-146a directly targets the 3'UTR of NUMB and a region within the NUMB coding sequence when suppressing NUMB expression. Exogenous NUMB expression attenuates OSCC oncogenicity. Double knockdown of IRAK1 and TRAF6, and of TRAF6 and NUMB, enhance the oncogenic phenotypes of OSCC cells. Oncogenic enhancement modulated by miR-146a expression is attenuated by exogenous IRAK1 or NUMB expression. This study shows that miR-146a expression contributes to oral carcinogenesis by targeting the IRAK1, TRAF6 and NUMB genes.