Finotonlimab with chemotherapy in recurrent or metastatic head and neck cancer: a randomized phase 3 trial.

Immunotherapy combined with chemotherapy regimen has been shown to be effective in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, due to the small number of patients, its efficacy remains controversial in Asian populations, particularly in mainland China. Here a randomized, double-blind phase 3 trial evaluated the efficacy and safety of finotonlimab (SCT-I10A), a programmed cell death 1 (PD-1) monoclonal antibody, combined with cisplatin plus 5-fluorouracil (C5F) for the first-line treatment of R/M HNSCC. Eligible patients (n = 370) were randomly 2:1 assigned to receive finotonlimab plus C5F (n = 247) or placebo plus C5F (n = 123). The primary endpoint was overall survival (OS). In the finotonlimab plus C5F group, OS was 14.1 months (95% confidence interval (CI) 11.1-16.4), compared with 10.5 months (95% CI 8.1-11.8) in the placebo plus C5F group. The hazard ratio was 0.73 (95% CI 0.57-0.95, P = 0.0165), meeting the predefined superiority criteria for the primary endpoint. Finotonlimab plus C5F showed significant OS superiority compared with C5F alone and acceptable safety profile with R/M HNSCC, supporting its use as a first-line treatment option for R/M HNSCC. These results validate the efficacy and safety of the combination of finotonlimab and C5F in Asian patients with R/M HNSCC. ClinicalTrials.gov identifier: NCT04146402 .

Phase noise matching in resonant metasurfaces for intrinsic sensing stability.

Interferometry offers a precise means of interrogating resonances in dielectric and plasmonic metasurfaces, surpassing spectrometer-imposed resolution limits. However, interferometry implementations often face complexity or instability issues due to heightened sensitivity. Here, we address the necessity for noise compensation and tolerance by harnessing the inherent capabilities of photonic resonances. Our proposed solution, termed "resonant phase noise matching," employs optical referencing to align the phases of equally sensitive, orthogonal components of the same mode. This effectively mitigates drift and noise, facilitating the detection of subtle phase changes induced by a target analyte through spatially selective surface functionalization. Validation of this strategy using Fano resonances in a 2D photonic crystal slab showcases noteworthy phase stability (σ<10-4π). With demonstrated label-free detection of low-molecular-weight proteins at clinically relevant concentrations, resonant phase noise matching presents itself as a potentially valuable strategy for advancing scalable, high-performance sensing technology beyond traditional laboratory settings.

N4-acetylcytidine-dependent GLMP mRNA stabilization by NAT10 promotes head and neck squamous cell carcinoma metastasis and remodels tumor microenvironment through MAPK/ERK signaling pathway.

N4-acetylcytidine (ac4C) is a post-transcriptional RNA modification that regulates in various important biological processes. However, its role in human cancer, especially lymph node metastasis, remains largely unknown. Here, we demonstrated N-Acetyltransferase 10 (NAT10), as the only known "writer" of ac4C mRNA modification, was highly expressed in head and neck squamous cell carcinoma (HNSCC) patients with lymph node metastasis. High NAT10 levels in the lymph nodes of patients with HNSCC patients are a predictor of poor overall survival. Moreover, we found that high expression of NAT10 was positively upregulated by Nuclear Respiratory Factor 1 (NRF1) transcription factor. Gain- and loss-of-function experiments displayed that NAT10 promoted cell metastasis in mice. Mechanistically, NAT10 induced ac4C modification of Glycosylated Lysosomal Membrane Protein (GLMP) and stabilized its mRNA, which triggered the activation of the MAPK/ERK signaling pathway. Finally, the NAT10-specific inhibitor, remodelin, could inhibit HNSCC tumorigenesis in a 4-Nitroquinoline 1-oxide (4NQO)-induced murine tumor model and remodel the tumor microenvironment, including angiogenesis, CD8+ T cells and Treg recruitment. These results demonstrate that NAT10 promotes lymph node metastasis in HNSCC via ac4C-dependent stabilization of the GLMP transcript, providing a potential epitranscriptomic-targeted therapeutic strategy for HNSCC.

Interaction between Genetic Risks and Socioeconomic Factors on Thyroid Cancer: Evidence from 0.5 Million UK Biobank Participants.

BACKGROUND: There is a research gap between genetic predisposition, socioeconomic factors, and their interactions on thyroid tumorigenesis. METHODS: Individual and genetic data were obtained from UK Biobank. Logistic regression models were used to evaluate the association between genetic risk, socioeconomic factors, and thyroid cancer (TCa). A stratified analysis was conducted to estimate their joint effects. A two-sample Mendelian randomization (MR) analysis was further used to examine the potential causality. RESULTS: A total of 502,394 participants were included in this study. Three index loci (rs4449583, rs7726159, and rs7725218) of telomerase reverse transcriptase (TERT) were found to be significantly related to incident TCa. Association analyses showed that high genetic risk, low household income, and high education level were independent risk factors, while unemployment and frequent social connection were suggestive risk factors for TCa. Interaction analyses showed that in participants with low genetic risk, low household income was significantly associated with TCa (odds ratio [OR] = 1.56, 95% confidence interval [CI]: 1.00-2.46). In participants with high genetic risk, those with a high education level (OR = 1.32, 95%CI: 1.06-1.65) and frequent social connection (OR = 1.36, 95%CI: 1.02-1.81) had a significantly increased risk of TCa. However, no causal relationship was observed in the MR analysis. CONCLUSION: Interactions exist between genetic risk, household income, education level, and social connection and thyroid cancer.

[Analysis of efficacy and prognosis of neoadjuvant chemotherapy and （or） surgery plus radiotherapy for hypopharyngeal squamous cell carcinoma].

Objective:To analyze the risk factors that affect the prognosis of patients with hypopharyngeal squamous cell carcinoma（HPSCC） and to compare the efficacy of surgical resection followed by adjuvant radiotherapy（SR） with that of neoadjuvant therapy consisting of platinum-based chemotherapy and fluorouracil combined with either cetuximab or nimotuzumab, followed by SR. The study also aimed to evaluate the overall survival（OS） of patients, their postoperative eating function, tracheostomy decannulation rate, and tumor response to the two neoadjuvant chemotherapies. Methods:A retrospective analysis was performed on the medical records of HPSCC patients who received SR or neoadjuvant therapy followed by SR treatment at the Shanghai General Hospital from 2012 to 2019 and had not undergone any prior treatment. The prognostic factors were analyzed, and the survival analysis of patients who underwent SR treatment with two neoadjuvant chemotherapy regimens was performed. Results:A total of 108 patients were included in the study. The results of the univariate analysis showed that gender（P=0.850） had no significant correlation with the survival rate of HPSCC patients who underwent SR. However, age, smoking history, alcohol consumption history, platelet-to-lymphocyte ratio（PLR）, neutrophil-to-lymphocyte ratio（NLR）, T stage, N stage, neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil, and histological grade were significantly associated with prognosis（P<0.05）. The multivariate analysis revealed that smoking history, histological grade, and neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil were independent risk factors affecting the prognosis of HPSCC（P<0.05）. Patients who received neoadjuvant therapy had longer OS than those who underwent SR only（P<0.001）. There was no significant difference in tumor response to the two neoadjuvant therapies and in OS（P>0.05）, and there was no significant difference in the rate of oral feeding and tracheostomy decannulation among the three treatment groups（P>0.05）. Conclusion:Univariate analysis showed that age at tumor onset, smoking history, alcohol consumption history, NLR, PLR, T stage, N stage, whether receiving neoadjuvant chemotherapy, and pathological grade were associated with the prognosis of HPSCC patients receiving SR treatment. Multivariate analysis showed that smoking history, pathological grade, and neoadjuvant chemotherapy were independent risk factors affecting the prognosis. Neoadjuvant chemotherapy with cetuximab or nimotuzumab can prolong the OS of patients, providing a certain basis and reference for the treatment of HPSCC.

Oncological and functional impact of adjuvant treatments after open partial laryngeal surgery: a systematic review of the literature and a meta-analysis.

BACKGROUND: The oncological and functional role of postoperative radiotherapy (PORT) after open partial laryngeal surgery (OPLS) remains debatable. METHODS: A systematic review and a meta-analysis of the literature were conducted according to the PRISMA guidelines. Outcomes of patients receiving OPLS with and without PORT for laryngeal cancer were summarized. RESULTS: In the 10 studies that were included in the meta-analysis, no significant difference emerged in terms of pooled overall survival between OPLS patients who did and who did not receive PORT (- 0.3%, 95% CI - 5.4 to 4.9%, p = 0.922). Only one study showed a significantly higher incidence of complications in the PORT cohort. CONCLUSIONS: PORT may apparently be performed after OPLS in face of adverse postoperative features without an increased risk of toxicities affecting the neolarynx. Because of the limitations in the available literature, the oncological and functional effects of PORT in this setting needs to be prospectively assessed to strengthen the evidence of this treatment strategy for laryngeal cancer.

Nickel-Catalyzed Three-Component Tandem Radical Cyclization 1,5-Difunctionalization of 1,3-Enynes and Alkyl Bromide.

A nickel-catalyzed three-component tandem radical cyclization reaction of aryl bromides with 1,3-enynes and aryl boric acids to construct γ-lactam-substituted allene derivatives has been described. This protocol provides lactam alkyl radicals through the free radical cyclization process, which can be effectively used to participate in the subsequent multicomponent coupling reaction so that 1,3-enynes could directly convert into corresponding poly-substituted allene compounds. In addition, this efficient method enjoys a broad substrate scope and provides a series of 1,5-difunctionalized allenes in a one-pot reaction.

Exosomes Derived from Adipose Mesenchymal Stem Cells Carrying miRNA-22-3p Promote Schwann Cells Proliferation and Migration through Downregulation of PTEN.

Peripheral nerve injury (PNI) is often resulting from trauma, which leads to severe and permanently disability. Schwann cells are critical for facilitating the regeneration process after PNI. Adipose-derived mesenchymal stem cells (ADSCs) exosomes have been used as a novel treatment for peripheral nerve injury. However, the underlying mechanism remains unclear. In this study, we isolated ADSCs and extracted exosomes, which were verified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blot (WB). Cocultured with Dorsal Root Ganglion (DRG) and Schwann cells (SCs) to evaluate the effect of exosomes on the growth of DRG axons by immunofluorescence, and the proliferation and migration of SCs by CCK8 and Transwell assays, respectively. Through exosomal miRNA sequencing and bioinformatic analysis, the related miRNAs and target gene were predicted and identified by dual luciferase assay. Related miRNAs were overexpressed and inhibited, respectively, to clarify their effects; the downstream pathway through the target gene was determined by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and WB. Results found that ADSC-exosomes could promote the proliferation and migration of SCs and the growth of DRG axons, respectively. Exosomal miRNA-22-3p from ADSCs directly inhibited the expression of Phosphatase and Tensin Homolog deleted on Chromosome 10 (PTEN), activated phosphorylation of the AKT/mTOR axis, and enhanced SCs proliferation and migration. In conclusion, our findings suggest that ADSC-exosomes could promote SCs function through exosomal miRNA-22-3p, which could be used as a therapeutic target for peripheral nerve injury.

[Applying a rigid curved video laryngoscope in laryngeal microsurgery of patients with difficult laryngeal exposure].

Objective:To test the feasibility of a rigid curved video laryngoscope in laryngeal microsurgery of patients with difficult laryngeal exposure. Methods:Thirteen patients with difficult laryngeal exposure underwent microlayngeal surgery using a new-design rigid curved video laryngoscope. The clinical data were collected and analyzed. Results:In all of the 13 patients with difficult laryngeal exposure,the fully exposure rate of glottis was 100% using a new-design rigid curved laryngoscope.But only 7 precise surgeries using our rigid curved instruments were completed successfully. Conclusion:Rigid curved laryngoscope is a useful tool to in treating patients with difficult laryngeal exposure in microlaryngeal surgery. Satisfactory glottis exposure, magnified surgical field and precise maneuver of the lesions could be achieved. But manipulation of this tool is challenging, which warrants further investigation．.

CSMD1 suppresses cancer progression by inhibiting proliferation, epithelial-mesenchymal transition, chemotherapy-resistance and inducing immunosuppression in esophageal squamous cell carcinoma.

Human CUB and Sushi multiple domains (CSMD1) is considered a crucial role in cancer progression, but the specific function in esophageal squamous cell carcinoma (ESCC) is not clear. Understanding the role of CSMD1 in ESCC progression may lead to a novel strategy for ESCC treatment. Here, we found that both CSMD1 mRNA and protein levels were downregulated in ESCC tissues. Reduced CSMD1 expression was correlated with a poor prognosis in ESCC patients. CSMD1 expression inhibited proliferation, migration and invasion in ESCC cell lines in vitro. CSMD1 deficiency in established xenografted tumors increases tumor size and weight. We further found that CSMD1-overexpression cells are more sensitive to chemotherapy. Moreover, we addressed the role of CSMD1 in the CD8+ T cell immune response. An in vitro killing assay showed that the cytotoxicity of CD8+ T cells was inhibited in CSMD1-overexpression tumor cells. In vivo, in CSMD1 deficiency tumor-bearing mice activation and expansion of CD8+ T cells were increased. Further investigation showed that CSMD1 expression on tumor cells was positively correlated with CD8+ T cells infiltration and cytokines secretion. These findings highlight that CSMD1 is a tumor suppressor gene in ESCC patients and a positive regulator of CD8+ T cells expansion and activation, and could increase cytokines secretion, indicating that tumor cell-associated CSMD1 might be a target for ESCC.

Extensive hearing loss induced by low-frequency noise exposure.

Background: With little attention given to low-frequency traffic noise and our understanding that cochlear function may be highly susceptible to low-frequency noise, there is an urgent need to determine traffic noise-induced hearing loss (NIHL), not only the hearing loss at low frequency but also the possible high-frequency hearing loss. Methods: The current study aims to investigate the potential for extensive hearing loss induced by exposure to 0.063 kHz octave band noise (OBN), which is an important component of low-frequency traffic noise. The threshold of auditory brainstem response (ABR) was used to evaluate hearing function before and after noise exposure. Chinchillas were randomly assigned into seven different groups. Group 63-3 h/6 h, Group 2 k-3 h/6 h, and group 4 k-3 h/6 h were exposed for either 3 or 6 h to 0.063, 2, and 4 kHz OBN at 90 dB SPL, respectively. The control group was not exposed to noise. Results: Significant ABR threshold-shifts (TS) were observed at 0.88, 2, 4, and 5.7 kHz in Group 63-6 h, and at 2.8 and 4 kHz in Group 2 k-6 h, and at 5.7 kHz in Group 4 k-6 h. ABR-TS were consistent with outer hair cell (OHC) losses, exposure to 0.063 kHz OBN at 90 dB SPL for 6 h induced large-scale losses of OHC both in low- and high-frequency region. Conclusions: Exposure to 0.063 kHz low-frequency OBN at 90 dB SPL for 6 h leads to significant hearing loss over an extensive range from low to high frequencies.

Prevalence and Characteristics of Erectile Dysfunction in Obstructive Sleep Apnea Patients.

BACKGROUND: Obstructive sleep apnea (OSA) is a common and severe social problem. Erectile dysfunction (ED) is an important health concern. The prevalence of OSA with ED is increasing, which significantly affects the quality of life and work efficiency of patients. However, the mechanism underlying the comorbidity of these two diseases remains unclear. OBJECTIVES: (1) Investigate the prevalence of OSA with ED; (2) analyze the correlation between OSA and ED; and (3) explore the treatment response to and possible mechanism of uvulapalatopharyngoplasty (UPPP) in patients with OSA and ED. This study aims to provide a theoretical basis for the clinical diagnosis and comprehensive treatment of OSA with ED and improve prevention and treatment strategies. MATERIALS AND METHODS: In total, 135 subjects were enrolled in the study. Clinical data, polysomnography, the ESS score, Beck anxiety score, Beck depression score, IIEF-5 score and ASEX score were recorded before UPPP and 6 months after UPPP. Sex hormones were measured for all subjects using a Roche electrochemiluminescence analyzer. RESULT: The prevalence of OSA with ED was 64.52%, and the prevalence of severe OSA with ED was 73.02%. The prevalence of OSA with ED increased with age, BMI and apnea-hypopnea index (AHI) value. Among polysomnography indicators, minimum oxygen saturation and average oxygen saturation may predict the occurrence of OSA with ED. Improving the patient's anxiety and depression is very important for treating OSA with ED. Sex hormone levels were not significantly correlated with the occurrence of OSA with ED. CONCLUSION: ED is a common symptom of OSA patients. This study showed that sex hormone levels in OSA patients with ED were not significantly correlated with the condition, but further investigation of this relationship is worthwhile. It is recommended that the free and combined types of sex hormones be further distinguished during testing because the free type is the active form. UPPP surgical treatment is effective for OSA with ED, and its possible mechanism is protection of the peripheral nerves of the sex organs by improving nighttime hypoxia and arousal.

Solitary hyoid plasmacytoma with unicentric Castleman disease: A case report and review of literature.

BACKGROUND: Solitary plasmacytoma and unicentric Castleman disease (UCD) are rare lymphoproliferative disorders characterized by monoclonal plasma cells and a single set of locally enlarged lymph nodes, respectively. CASE SUMMARY: A 48-year-old Han Chinese man presented to our department with a neck mass and progressive foreign body sensation in his throat. 18F-FDG positron emission tomography revealed focally increased radioactivity centered around the hyoid, and computed tomography (CT) revealed osteolytic lesions. Histopathology revealed Castleman-like features and CD138/CD38-positive mature plasma cells. Systemic work-up ruled out the possibility of POEMS syndrome, lymphoma, and multiple myeloma, leading to a final diagnosis of solitary hyoid plasmacytoma with UCD. The patient underwent partial hyoid resection and selective neck dissection, followed by intensity-modulated radiotherapy. 99mTc-MDP single-photon emission computed tomography/CT reevaluation showed neither local recurrence nor distant bone metastasis at the 40-mo follow-up. CONCLUSION: The diagnostic process and differential diagnosis of this rare case provided valuable educational information to clinicians.

The RNA N6-Methyladenosine Demethylase FTO Promotes Head and Neck Squamous Cell Carcinoma Proliferation and Migration by Increasing CTNNB1.

OBJECTIVE: In this study, we aimed to investigate the role of RNA N6-methyladenosine demethylase fat mass and obesity-associated protein (FTO) in head and neck squamous cell carcinoma (HNSCC). METHODS: Clinical data downloaded from The Cancer Genome Atlas (TCGA) database were used to analyze the relationship between mRNA levels of FTO, METTL3, METTL14, and ALKBH5, and the overall survival in cancer and para-cancer datasets. FTO expression in tumor and normal tissues was compared using immunohistochemistry, and its relationship with overall survival was analyzed based on the Kaplan-Meier method. The FaDu cell line with high FTO levels was chosen from five HNSCC cell lines for further experiments. FTO was verified as an oncogene in HNSCC by in vitro loss-of-function and overexpression studies, cell proliferation assay, wound healing assay, and identification of expression changes of epithelial-mesenchymal transition (EMT)-related markers. Catenin beta 1 (CTNNB1) was confirmed as a downstream target gene of FTO with additional methods like the GEPIA online tool, qRT-PCR, Western blotting, and dot blot assay. RESULTS: We found that FTO expression was significantly upregulated in HNSCC datasets and tissues. Increased FTO expression indicated a trend towards poor prognosis and was found to promote disease proliferation and migration. Mechanistically, cell proliferation assay, wound healing assay, and identification of expression changes of EMT-related markers demonstrated that FTO could act as an oncogene in HNSCC. FTO expression was significantly correlated with CTNNB1 expression. Moreover, it exerted a tumorigenic effect by increasing CTNNB1 expression in an m6A-dependent manner. CONCLUSION: FTO promotes head and neck squamous cell carcinoma proliferation and migration by increasing CTNNB1 in an m6A-dependent manner.

MiR-224 ameliorates inflammation and symptoms in mouse model of allergic rhinitis by targeting CDK9.

OBJECTIVES: To explore the regulatory effects of microRNA (miRNA)-224 and its potential target gene, cyclin dependent kinase 9 (CDK9), in the pathological process of allergic rhinitis (AR). METHODS: To investigate the role of miR-224 and CDK9, it was screened by bioinformatics prediction software and verified by dual-luciferase reporter assay. The mouse model of AR was established by ovalbumin (OVA).The animal models were intervened with miR-224 agomir, negative control agomir, and saline respectively. The symptoms of sneezing and nasal rubbing were recorded. The expressions of miR224, CDK9, and cytokines in the nasal mucosa of different groups were analyzed by rt-PCR or western blotting. Enzyme-linked immunoassay (ELISA) was used to evaluate the levels of IgE and Histamine (HA) in the serum. The infiltration of inflammatory cells in the nasal mucosa was studied by immunohistochemistry. The expression and distribution of CDK9 in the nasal mucosa of mice were revealed by immunofluorescence. RESULTS: In the nasal mucosa of the animal models, the level of miR-224 was downregulated, while that of CDK9 was upregulated. The upregulation of miR-224 by miR-224 agomir reduced the frequencies of nasal rubbing and sneezing, the expression of CDK9, the levels of cytokines, and the concentrations of IgE and HA. Moreover, miR-224 appeared to attenuate the infiltration of inflammatory cells and hypersecretion of glands in the nasal mucosa. The expression of CDK9, which was distributed under the mucosa, especially in the submucosa interstitial tissue, was significantly reduced. CONCLUSION: MiR-224 affected the pathogenesis of AR by targeting CDK9. It proves that miR-224 could be a novel potential therapeutic target for AR.

Identification of a prognostic 4-mRNA signature in laryngeal squamous cell carcinoma.

Background: Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignancy in the respiratory tract and could reduce the quality of life seriously like dyspnea, dysphonia and dysphagia. Moreover, 5-year survival rate has decreased over the past 40 years. This study was designed to identify mRNAs that related to prognosis in LSCC to enable early detection and outcome improvement. Methods: Gene expression profiles from Gene Expression Omnibus (GEO) (GSE59102, GSE84957) and The Cancer Genome Atlas (TCGA) were analyzed to identify differentially expressed genes (DEGs) with the help of bioinformatics tools. Functional enrichment analyses including Gene Ontology (GO) and pathway analysis were carried out to investigate the role of those genes and underlying molecular mechanisms in LSCC. Cox's regression analyses (univariate, LASSO and multivariate in order) were utilized to identify DEGs related with patients' overall survival and a 4-mRNA-based prognostic risk score model was established. Univariate and multivariate Cox's regression analyses were then performed on LSCC data (90 patients left) to identify independent predictors of OS, including the signature and clinicopathologic variables. The prognostic value of the gene signature was further validated and the genes were analyzed by GEPIA to get pan-cancer expression profiles. Results: 444 differentially expressed mRNAs (250 up-regulated, 194 down-regulated) were identified based on the threshold of fold change > 2 and adjusted p value < 0.05. Univariate Cox's regression analysis showed that high risk score (HR: 3.056, 95% confidence interval [CI]: 0.135-0.649, p<0.001) and female (HR: 0.296, 95% CI: 2.020-4.624, p=0.002) were associated with relatively poor prognosis. Further multivariate Cox's regression analysis indicated that risk score and gender were independent prognostic factors (p<0.05). The risk score model could stratify patients into high- and low­risk groups, which presents significantly differential overall survival (p= 8.252e-04). The AUCs of 1-, 3- and 5-year OS were 0.724, 0.783 and 0.818, respectively. Conclusions: Our study provides evidence that the four-mRNA signature could serve as a biomarker to predict prognosis in LSCC, especially in long-term.

Defective Indium Tin Oxide Forms an Ohmic Back Contact to an n-Type Cu2O Photoanode to Accelerate Charge-Transfer Kinetics for Enhanced Low-Bias Photoelectrochemical Water Splitting.

In significant contrast to the tremendous research efforts mostly geared to addressing the severe hole accumulation at the back contact of a p-type Cu2O photocathode with a fluorine-doped tin oxide (FTO) substrate, sluggish electron transfer from an n-type Cu2O photoanode to a tin-doped indium oxide (ITO) substrate has been largely overlooked. To tackle this issue that has been reported to largely limit the photoelectrochemical performance of n-type Cu2O photoanodes at a low bias, the present contribution puts forward a strategy to introduce oxygen vacancies into the ITO substrate via an unprecedented yet facile electrochemical approach. Such defect engineering turns out to decrease the work function of the ITO substrate, which in turn approaches the conduction band extremum of n-Cu2O to highly efficiently extract the photoexcited electrons therein. Moreover, the dendritic growth of n-Cu2O is, in the meantime, interfered by the oxygen vacancy manifested as pinholes distributed over the ITO substrate, which is thereby crystallized into several small grains with augmented surface roughness that is in favor of the injection of the photoexcited hole into the electrolyte. Such facile interfacial charge-transfer kinetics leads to a significant cathodic shift amounting to 200 mV of the onset potential to 0 VAg/AgCl, whereat the n-Cu2O photoanode deposited on the defective ITO substrate delivers the maximum photocurrent density reaching 2 mA cm-2 and, more significantly, its applied bias photon-to-current efficiency (ABPE) reaches 1.1%, which is among the highest performance reported to date for a variety of state-of-the-art metal oxide-based photoanodes in the literature.

RNA methyltransferase NSUN2 promotes hypopharyngeal squamous cell carcinoma proliferation and migration by enhancing TEAD1 expression in an m5C-dependent manner.

RNA methyltransferase NSUN2 is involved in cell proliferation and invasion in a variety of tumors. However, the expression, function, and mechanism of NSUN2 in hypopharyngeal squamous cell carcinoma (HPSCC) remains unknown. We used a bioinformatics database, polymerase chain reaction, cell culture and transfection, immunohistochemistry, cell proliferation assay, wound healing experiments, transwell assays, western blotting, RNA-seq detection, dual-luciferase reporter assay, in vivo experiments, and a dot blot assay to evaluate the role of NSUN2 in HPSCC. NSUN2 mRNA and protein were highly expressed in HPSCC; NSUN2 knockdown in vitro and in vivo decreased cell proliferation and invasion. Studies have shown that TEAD1, a transcription factor, may act downstream of NSUN2 in HPSCC. NSUN2 was found to promote the proliferation and invasion of HPSCC by upregulating TEAD1 in an 5-methylcytosine-dependent manner, thereby representing an oncogene and potential new target for treating HPSCC.

Socioeconomic factors are associated with the prognosis of Thyroid Cancer.

Background: Thyroid adenomas/adenocarcinomas are the most common type of thyroid cancer. The impact of socioeconomic factors on the prognosis of thyroid cancer is unclear. Methods: Clinical information and socioeconomic factors were obtained from the Surveillance, Epidemiology, and End Results Database (SEER) 18 Registries Custom Database. The association between thyroid adenomas/adenocarcinomas and socioeconomic factors including gender, race/ethnicity, insurance status, marital status, living area, and Yost index (including education, income, working, etc.) were fully evaluated. Results: A total of 136,313 patients between 2010 and 2016 were finally included in the present study. Among them, 126,160 patients were diagnosed with the single malignancy. Median follow-up time was 64 months. In general, non-Hispanic Asian or Pacific Islander and Hispanic patients had significantly better survival than non-Hispanic White patients (All P <0.05). Patients insured by Medicaid had significantly poorer cancer-specific survival (CSS, hazard ratio, HR=2.15, P <0.001) and overall survival (OS, HR=2.42, P <0.001) than those insured by commercial insurance or Medicare. In addition, divorced or widowed status, rural living location and low Yost index were significantly associated with poor CSS and OS of thyroid adenomas/adenocarcinomas (All P <0.05). Subgroup analyses showed similar results in patients who received surgical procedure, as well as in patients who received both surgical and radiation therapy. Multivariate analyses suggested that insurance status, marital status and Yost index remained significantly associated with CSS and OS (all P <0.05). Conclusions: Socioeconomic factors, including insurance status, marital status, living area, and Yost index, were significant predictors for the survival of thyroid adenomas/adenocarcinomas.