Circumventing bottlenecks in H2O2 photosynthesis over carbon nitride with iodine redox chemistry and electric field effects.

Artificial photosynthesis using carbon nitride (g-C3N4) holds a great promise for sustainable and cost-effective H2O2 production, but the high carrier recombination rate impedes its efficiency. To tackle this challenge, we propose an innovative method involving multispecies iodine mediators (I-/I3-) intercalation through a pre-photo-oxidation process using potassium iodide (suspected deteriorated "KI") within the g-C3N4 framework. Moreover, we introduce an external electric field by incorporating cationic methyl viologen ions to establish an auxiliary electron transfer channel. Such a unique design drastically improves the separation of photo-generated carriers, achieving an impressive H2O2 production rate of 46.40 mmol g-1 h-1 under visible light irradiation, surpassing the most visible-light H2O2-producing systems. Combining various advanced characterization techniques elucidates the inner photocatalytic mechanism, and the application potential of this photocatalytic system is validated with various simulation scenarios. This work presents a significative strategy for preparing and applying highly efficient g-C3N4-based catalysts in photochemical H2O2 production.

Squamous papilloma involving the mandible: A case report and descriptive literature review.

Squamous papilloma is a benign neoplasm that originates from the stratified squamous epithelium of the mucous membrane. Its principal etiological factor is human papillomavirus infection, with a predilection for manifesting within the oral cavity. Squamous papilloma predominantly affects regions on the palate, cheeks, lips and tongue. However, to the best of our knowledge, the occurrence of squamous papilloma within the confines of the mandible remains unreported hitherto. The present report documents a case of squamous papilloma involving the mandible who was managed at the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) in January 2023. The patient underwent a series of recurrent jaw inflammations, manifesting with malignant imaging characteristics. Subsequent pathological analysis confirmed a diagnosis of papilloma in the jaw. The present report highlights the pivotal role of prolonged inflammation in the genesis of jaw squamous papilloma, prompting avenues for further investigation, including the potential of inflammation to induce aberrant cell growth, mediate cell interactions, orchestrate cytokine actions and influence stress mediators. In addition, the current study posits a plausible connection between persistent inflammation, compromised epithelial integrity and an increased likelihood of head and neck papilloma, particularly concerning human papillomavirus infection. This article delineates the clinical attributes of the uncommon manifestations of jaw papilloma and delves into the associated mechanisms, thereby contributing to an enhanced comprehension of jaw disorders. This comprehensive insight equips clinicians with a heightened knowledge base for more precise diagnosis and treatment of analogous cases.

Prevalence and influencing factors of malnutrition in stroke patients with bulbar paralysis: a cross-sectional study in China.

Background: Although malnutrition has been shown to influence the clinical outcomes of Stroke Patients with Bulbar Paralysis (SPBP), the prevalence and influencing factors have yet to be uncovered. Objective: This study aims to assess the current prevalence and factors associated with malnutrition in SPBP. Methods: A multicenter cross-sectional investigation was conducted among SPBP in China from 2019 to 2021. Information was collected on basic information, health condition, diagnosis, treatment, neurological function, activities of daily living, swallowing function, and nutritional status. A multivariable logistic regression model was used to identify the factors that influenced nutritional status. ROC analysis was used to assess the predictive value of each independent influencing factor and the logit model. Results: In total, 774 SPBP were enrolled, and the prevalence of malnutrition was 60.59%. Pulmonary infection [aOR:2.849, 95%CI: (1.426, 5.691)], hemoglobin [aOR: 0.932, 95%CI: (0.875, 0.982)], serum albumin [aOR: 0.904, 95%CI: (0.871, 0.938)], total protein [aOR: 0.891, 95%CI: (0.819, 0.969)], prealbumin [aOR: 0.962, 95%CI: (0.932, 0.993)], and National Institute of Health Stroke Scale (NIHSS) scores [aOR: 1.228, 95%CI: (1.054, 1.431)] were independent factors associated with malnutrition in SPBP. ROC analysis revealed that the logit model had the best predictive value [area under the curve: 0.874, 95% CI: (0.812, 0.936); specificity: 83.4%; sensitivity: 79.3%; p < 0.05]. Subgroup analysis showed that the nutritional status in dysphagic SPBP was additionally influenced by swallowing function and nutrition support mode. Conclusion: The prevalence of malnutrition in SPBP was 60.59%. Pulmonary infection, hemoglobin level, and NIHSS score were the independent factors associated with malnutrition. Swallowing function and nutrition support mode were the factors associated with malnutrition in dysphagic SPBP.

Genome-wide analysis of the mulberry (Morus abla L.) GH9 gene family and the functional characterization of MaGH9B6 during the development of the abscission zone.

Plant glycoside hydrolase family 9 genes (GH9s) are widely distributed in plants and involved in a variety of cellular and physiological processes. In the current study, nine GH9 genes were identified in the mulberry and were divided into two subfamilies based on the phylogenetic analysis. Conserved motifs and gene structure analysis suggested that the evolution of the two subfamilies is relatively conserved and the glycoside hydrolase domain almost occupy the entire coding region of the GH9s gene. Only segmental duplication has played a role in the expansion of gene family. Collinearity analysis showed that mulberry GH9s had the closest relationship with poplar GH9s. MaGH9B1, MaGH9B6, MaGH9B5, and MaGH9B3 were detected to have transcript accumulation in the stalk of easy-to drop mature fruit drop, suggesting that these could play a role in mulberry fruit drop. Multiple cis-acting elements related to plant hormones and abiotic stress responses were found in the mulberry GH9 promoter regions and showed different activities under exogenous abscisic acid (ABA) and 2,4- dichlorophenoxyacetic acid (2,4-D) stresses. We found that the lignin content in the fruit stalk decreased with the formation of the abscission zone (AZ), which could indirectly reflect the formation process of the AZ. These results provide a theoretical basis for further research on the role of GH9s in mulberry abscission.

RNA modification-related genes illuminate prognostic signature and mechanism in esophageal squamous cell carcinoma.

Emerging studies have demonstrated the link between RNA modifications and various cancers, while the predictive value and functional mechanisms of RNA modification-related genes (RMGs) in esophageal squamous cell carcinoma (ESCC) remain unclear. Here we established a prognostic signature for ESCC based on five RMGs. The analysis of ESCC clinical samples further verified the prognostic power of the prognostic signature. Moreover, we found that the knockdown of NSUN6 promotes ESCC progression in vitro and in vivo, whereas the overexpression of NSUN6 inhibits the malignant phenotype of ESCC cells. Mechanically, NSUN6 mediated tRNA m5C modifications selectively enhance the translation efficiency of CDH1 mRNA in a codon dependent manner. Rescue assays revealed that E-cadherin is an essential downstream target that mediates NSUN6's function in the regulation of ESCC progression. These findings offer additional insights into the link between ESCC and RMGs, as well as provide potential strategies for ESCC management and therapy.

METTL3 inhibitor STM2457 impairs tumor progression and enhances sensitivity to anlotinib in OSCC.

OBJECTIVES: To investigate the inhibitory effects of STM2457, which is a novel METTL3 (m6 A writer) inhibitor, both as a monotherapy and in combination with anlotinib, in the treatment of oral squamous cell carcinoma (OSCC) both in vitro and in vivo. MATERIALS AND METHODS: The efficacy of STM2457 or STM2457 plus anlotinib was evaluated using two OSCC cell lines by CCK8, transwell, colony formation, would-healing, sphere formation, cell cycle, apoptosis assays, and nude mice tumor xenograft techniques. The molecular mechanism study was carried out by western blotting, qRT-PCR, MeRIP-qPCR, immunofluorescence, and immunohistochemistry. RESULTS: STM2457 combined with anlotinib enhanced inhibition of cellular survival/proliferation and promotion of apoptosis in vitro. Moreover, this combinatorial approach exerted a notable reduction in stemness properties and EMT (epithelial-mesenchymal transition) features of OSCC cells. Remarkably, in vivo studies validated the efficacy of the combination treatment. Mechanistically, our investigations revealed that the combined action of STM2457 and anlotinib exerted downregulatory effects on EGFR (epidermal growth factor receptor) expression in OSCC cells. CONCLUSIONS: The combination of STM2457 and anlotinib targeting EGFR exerted a multiple anti-tumor effect. In near future, anlotinib combined with STM2457 may provide a novel insight for the treatment of OSCC.

The Time-Point Distribution Characteristics of Laryngopharyngeal Reflux in Elderly Patients.

OBJECTIVE: To identify the characteristics of the time-point distribution of the occurrence of hypopharyngeal-proximal reflux episodes (HREs) in elderly and younger patients with laryngopharyngeal reflux (LPR). STUDY DESIGN: Retrospective cohort study. SETTING: Analysis of data from patients with LPR-related symptoms and 24-hour hypopharyngeal-esophageal multichannel intraluminal impedance-pH (24-hour HEMII-pH) monitoring from February 2017 to September 2022 at Sixth Medical Center of PLA General Hospital. METHODS: Patients were divided into 2 age groups: the elderly group (>60 years) and the younger group (≤60 years). The time series of HREs and meals within 24 hours were analyzed based on HEMII-pH. RESULTS: A total of 305 patients were included (126 elderly patients). In younger patients, except for nonacid-gas HREs, the incidence of the remaining types of HREs tended to increase within 2 hours after meals, especially after dinner. The incidence of all types of HREs pre- and postmeal was not significantly different in the elderly group (χ2 = 0.080, P = .777). The incidence of nighttime HREs in elderly patients was statistically higher than in younger patients (6.23% vs 3.96%, P = .030), particularly acid-/nonacid-liquid HREs. CONCLUSION: HREs tend to increase within 2 hours after meals in younger LPR patients, except for nonacid-gas HREs. In elderly LPR patients, the incidence of all types of HREs pre- and postmeal were not significantly different, and nighttime fluid HREs was more prone to occur than in younger patients.

A Study of the Diagnostic Value of the Sign and Symptom Questionnaires for Laryngopharyngeal Reflux Disease.

OBJECTIVE: To investigate the diagnostic value of symptom questionnaires, sign questionnaires, and the combination of 2 questionnaires for laryngopharyngeal reflux disease (LPRD). STUDY DESIGN: Prospective, single-centered. SETTING: Seventy-seven patients who were hospitalized in the Department of Otolaryngology-Head and Neck Surgery from October 2022 to April 2023 were included. METHODS: Included patients completed the RSS, RSI, RSA, and RFS questionnaires and underwent 24-hour hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH). The RSS, RSI, RSA, RFS, RSS+RSA, RSS+RFS, RSI+RSA, RSI+RFS, and RSI+RFS diagnostic value were compared using Cohen's k test and receiver operating characteristic analysis. RESULTS: Based on the 24 hours HEMII-pH results, 52 patients had LPRD, and 25 patients did not have LPRD. The Kappa values of RSS, RSI, RSA, RFS, RSS+RSA,2 RSS+RFS, RSI+RSA, and RSI+RFS with the 24 hours HEMII-pH monitoring results were 0.565, 0.442, 0.318, 0.431, 0.517, 0.631, 0.451, and 0.461, respectively. The RSS+RFS questionnaire had the highest AUC of 0.836 (95% confidence interval [CI] 0.762-0.909) and the RSA questionnaire had the lowest AUC (AUC = 0.665, 95% CI 0.560-0.790). The sensitivity of RSS was the highest (98%), the specificities of RSS+RFS and RSI+RFS were the highest (96%), and the specificity of RSS was the lowest (52%). RSS+RFS had a sensitivity of 75%, second only to RSS and RFS (76%). CONCLUSION: Among the 8 methods, the RSS combined with the RFS had the highest concordance with 24 hours HEMII-pH monitoring results and AUC values when screening for LPRD.

History of Previous Surgical Resection Promotes the Sclerosis of the Arytenoid Cartilage in Patients With Laryngeal Contact Granuloma.

OBJECTIVES: To explore the relationship between arytenoid cartilage sclerosis and a history of previous surgical resection in patients with laryngeal contact granuloma. METHODS: 167 patients with laryngeal contact granuloma treated from March 2016 to December 2018 were studied. The high-resolution computed tomography (HRCT) data of the sclerosis of arytenoid cartilage is divided into asymmetric sclerosis, bilateral sclerosis, and no sclerosis according to the range of sclerosis. The proportions of various ranges of sclerosis in two subgroups of patients were compared to patients with and without a history of previous surgical resection. RESULTS: The arytenoid cartilage sclerosis rate of 167 patients was 69.46%. The exact probability method showed that P < 0.001, suggesting that the distribution of arytenoid cartilage sclerosis was different in patients with and without a history of previous surgical resection, and there was a moderate correlation between the extent of arytenoid sclerosis and history of previous surgical resection (Cramer's V = 0.436, P < 0.001). There were 18 cases of bilateral sclerosis in patients with a history of previous surgical resection, of which 50% had contralateral recurrence after combined therapy (proton pump inhibitor (PPI) and glucocorticoid injection into granuloma via the thyrohyoid membrane approach), accounting for 75% of recurrence after combined therapy. CONCLUSION: Surgery promotes the expansion of arytenoid sclerosis, Patients with bilateral arytenoid sclerosis are prone to recurrence of contralateral laryngeal contact granuloma.

Relationship Between Laryngopharyngeal Reflux and Obstructive Sleep Apnea in Adult Males.

OBJECTIVE: To investigate the relationship between laryngopharyngeal reflux (LPR) and obstructive sleep apnea (OSA). METHODS: Patients diagnosed with OSA who were hospitalized in the Department of Otolaryngology-Head and Neck Surgery from November 2021 to April 2022 were selected, and male patients with non-OSA during the same period were selected as the control group. Patients who participated in the study completed the Reflux Symptom Index (RSI), the Reflux Finding Sign (RFS), and 24-hour multichannel intraluminal impedance-pH (MII-pH) monitoring. RSI, RFS, and outcomes of 24 hour-MII-pH monitoring were compared between the OSA group and the control group. RESULTS: A total of 86 patients were enrolled, of whom 49 were OSA patients and 37 were non-OSA patients. The positive rate of LPR (97.96% vs 75.68%) and the median number of LPR episodes (9 vs 5) were significantly higher in OSA patients than in non-OSA patients (P < 0.01, P < 0.05, respectively). A logistic regression model including body mass index, alcohol consumption, and the presence of OSA showed that having OSA was a risk factor for the occurrence of LPR (P < 0.05, OR [odds ratio] = 9.995, 95% CI [confidence interval] 1.084-92.181). There were correlations between Apnea-Hypopnea Index and the number of non-acid LPR episodes and the number of alkaline LPR episodes (r = 0.243, P < 0.05, r = 0.274, P < 0.05, respectively). CONCLUSIONS: Having OSA is a risk factor for LPR, and LPR episodes occur more frequently in patients with OSA compared to those without OSA. When OSA is comorbid with LPR, the occurrence of alkaline LPR, such as bile reflux, should be a concurrent concern.

Exploring the Molecular Mechanism of Niuxi-Mugua Formula in Treating Coronavirus Disease 2019 via Network Pharmacology, Computational Biology, and Surface Plasmon Resonance Verification.

BACKGROUND: In China, Niuxi-Mugua formula (NMF) has been widely used to prevent and treat coronavirus disease 2019 (COVID-19). However, the mechanism of NMF for treating COVID-19 is not yet fully understood. OBJECTIVE: This study aimed to explore the potential mechanism of NMF for treating COVID-19 by network pharmacology, computational biology, and surface plasmon resonance (SPR) verification. METHODS: The NMF-compound-target network was constructed to screen the key compounds, and the Molecular Complex Detection (MCODE) tool was used to screen the preliminary key genes. The overlapped genes (OGEs) and the preliminary key genes were further analyzed by enrichment analysis. Then, the correlation analysis of immune signatures and the preliminary key genes was performed. Molecular docking and molecular dynamic (MD) simulation assays were applied to clarify the interactions between key compounds and key genes. Moreover, the SPR interaction experiment was used for further affinity kinetic verification. RESULTS: Lipid and atherosclerosis, TNF, IL-17, and NF-kappa B signaling pathways were the main pathways of NMF in the treatment of COVID-19. There was a positive correlation between almost the majority of immune signatures and all preliminary key genes. The key compounds and the key genes were screened out, and they were involved in the main pathways of NMF for treating COVID-19. Moreover, the binding affinities of most key compounds binding to key genes were good, and IL1B-Quercetin had the best binding stability. SPR analysis further demonstrated that IL1B-Quercetin showed good binding affinity. CONCLUSION: Our findings provided theoretical grounds for NMF in the treatment of COVID19.

MaABI5 and MaABF1 transcription factors regulate the expression of MaJOINTLESS during fruit abscission in mulberry (Morus alba L.).

Mulberry holds significant economic value. However, during the ripening stage of its fruit, the phenomenon of abscission, resulting in heavy fruit drop, can severely impact the yield. The formation of off-zone structures is a critical factor in the fruit abscission process, and this process is regulated by multiple transcription factors. One such key gene that plays a significant role in the development of the off-zone in the model plant tomato is JOINTLESS, which promotes the expression of abscission-related genes and regulates the differentiation of abscission zone tissue cells. However, there is a lack of information about fruit abscission mechanism in mulberry. Here, we analyzed the MaJOINTLESS promoter and identified the upstream regulators MaABF1 and MaABI5. These two regulators showed binding with MaJOINTLESS promoter MaABF1 (the ABA Binding Factor/ABA-Responsive Element Binding Proteins) activated the expression of MaJOINTLESS, while MaABI5 (ABSCISIC ACID-INSENSITIVE 5) inhibited the expression of MaJOINTLESS. Finally, the differentially expressed genes (DEGs) were analyzed by transcriptome sequencing to investigate the expression and synergistic relationship of endogenous genes in mulberry during abscission. GO classification and KEGG pathway enrichment analysis showed that most of the DEGs were concentrated in MAPK signaling pathway, flavonoid biosynthesis, citric acid cycle, phytohormone signaling, amino acid biosynthesis, and glycolysis. These results provide a theoretical basis for subsequent in-depth study of physiological fruit abscission in mulberry.

NAT10-mediated ac4C tRNA modification promotes EGFR mRNA translation and gefitinib resistance in cancer.

Aberrant RNA modifications are frequently associated with cancers, while the underlying mechanisms and clinical significance remain poorly understood. Here, we find that the ac4C RNA acetyltransferase NAT10 is significantly upregulated in esophageal cancers (ESCAs) and associated with poor ESCA prognosis. In addition, using ESCA cell lines and mouse models, we confirm the critical functions of NAT10 in promoting ESCA tumorigenesis and progression in vitro and in vivo. Mechanistically, NAT10 depletion reduces the abundance of ac4C-modified tRNAs and decreases the translation efficiencies of mRNAs enriched for ac4C-modified tRNA-decoded codons. We further identify EGFR as a key downstream target that facilitates NAT10's oncogenic functions. In terms of clinical significance, we demonstrate that NAT10 depletion and gefitinib treatment synergistically inhibit ESCA progression in vitro and in vivo. Our data indicate the mechanisms underlying ESCA progression at the layer of mRNA translation control and provide molecular insights for the development of effective cancer therapeutic strategies.

Identification and Functional Evaluation of Alternative Splice Variants of Dax1 in Mouse Embryonic Stem Cells.

Dax1 (Nr0b1; Dosage-sensitive sex reversal-adrenal hypoplasia congenital on the X-chromosome gene-1) is an important component of the transcription factor network that governs pluripotency in mouse embryonic stem cells (ESCs). Functional evaluation of alternative splice variants of pluripotent transcription factors has shed additional insight on the maintenance of ESC pluripotency and self-renewal. Dax1 splice variants have not been identified and characterized in mouse ESCs. We identified 18 new transcripts of Dax1 with putative protein-coding properties and compared their protein structures with known Dax1 protein (Dax1-472). The expression pattern analysis showed that the novel isoforms were cotranscribed with Dax1-472 in mouse ESCs, but they had transcriptional heterogeneity among single cells and the subcellular localization of the encoded proteins differed. Cell function experiments indicated that Dax1-404 repressed Gata6 transcription and functionally replaced Dax1-472, while Dax1-38 and Dax1-225 partially antagonized Dax1-472 transcriptional repression. This study provided a comprehensive characterization of the Dax1 splice variants in mouse ESCs and suggested complex effects of Dax1 variants in a self-renewal regulatory network.

Specific Expression of Antimicrobial Peptides from the Black Soldier Fly in the Midgut of Silkworms (Bombyx mori) Regulates Silkworm Immunity.

Antimicrobial peptides are molecules with strong antimicrobial activity and are of substantial interest for the immunization of insects. As a type of dipteran insect that can turn organic waste into animal feed, the black soldier fly (BSF) can "turn waste into treasure". In this study, we investigated the antimicrobial activity of the antimicrobial peptide genes, HiCG13551 and Hidiptericin-1, of BSF in silkworms, by overexpressing the genes specifically in the midgut. Changes in the mRNA levels of the transgenic silkworms after infection with Staphylococcus aureus were evaluated using transcriptome sequencing. The results showed that Hidiptericin-1 had stronger antimicrobial activity than HiCG13551. KEGG enrichment analysis showed that the differentially expressed genes in the transgenic overexpressed Hidiptericin-1 silkworm lines from the D9L strain were mainly enriched in the starch and sucrose metabolism, pantothenate and CoA biosynthesis, drug metabolism (other enzymes), biotin metabolism, platinum drug resistance, galactose metabolism, and pancreatic secretion pathways. In addition, immune-related genes were up-regulated in this transgenic silkworm strain. Our study may provide new insights for future immune studies on insects.

METTL3-mediated ALDH m6 A methylation regulates the malignant behavior of BMI1+ HNSCC stem cells.

OBJECTIVES: To reveal the effect and mechanism of methyltransferase-like 3 (METTL3) on cancer stem cells (CSCs) of head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: First, we analyzed 14-HNSCC-patients' scRNA-seq dataset and TCGA dataset of HNSCC. Then, Mettl3 knockout or overexpression mice models were studied via tracing and staining technologies. In addition, we took flow cytometry sorting and sphere formation assays to observe tumorigenicity and used cell transfection and western blotting to verify target protein expression levels. Furthermore, methylated RNA immunoprecipitation sequencing (MeRIP-seq) and MeRIP-quantitative real-time PCR (MeRIP-qPCR) were taken to identify the mechanism of Mettl3 regulating Bmi1+ CSCs in HNSCC. RESULTS: Due to SOX4 transcriptional regulation, METTL3 regulated the malignant behavior of BMI1+ HNSCC stem cells through cell division pathway. The progression and malignancy of HNSCC were decreased after Mettl3 knocked-out, while increased after Mettl3 knocked-in in Bmi1+ CSCs in vivo. Knockdown of Mettl3 inhibited stemness properties of CSCs in vitro. Mechanically, Mettl3 mediated the m6 A modification of ALDH1A3 and ALDH7A1 mRNA in Bmi1+ HNSCC CSCs. CONCLUSION: Regulated by SOX4, METTL3-mediated ALDH m6 A methylation regulates the malignant behavior of BMI1+ HNSCC CSCs through cell division pathway.

Parallel Genome-Wide CRISPR Screens to Identify State-Dependent Self-Renewal Regulators of Mouse Embryonic Stem Cells.

The pluripotency of embryonic stem cells (ESCs) is more accurately viewed as a continuous developmental process rather than a fixed state. However, the factors that play general or state-specific roles in regulating self-renewal in different pluripotency states remain poorly defined. In this study, parallel genome-wide CRISPR/Cas9 knockout (KO) screens were applied in ESCs cultured in the serum plus LIF (SL) and in the 2i plus LIF (2iL) conditions. The candidate genes were classified into seven groups based on their positive or negative effects on self-renewal, and whether this effect was general or state-specific for ESCs under SL and 2iL culture conditions. We characterized the expression and function of genes in these seven groups. The loss of function of novel pluripotent candidate genes Usp28, Zfp598, and Zfp296 was further evaluated in mouse ESCs. Consistent with our screen, the knockout of Usp28 promotes the proliferation of SL-ESCs and 2iL-ESCs, whereas Zfp598 is indispensable for the self-renewal of ESCs under both culture conditions. The cell phenotypes of Zfp296 KO ESCs under SL and 2iL culture conditions were different. Our work provided a valuable resource for dissecting the molecular regulation of ESC self-renewal in different pluripotency states.

METTL1/WDR4-mediated tRNA m7G modification and mRNA translation control promote oncogenesis and doxorubicin resistance.

Osteosarcoma is the most common bone tumor that leads to high mortality in adolescents and children. The tRNA N7-methylguanosine methyltransferase METTL1 is located in chromosome 12q14.1, a region that is frequently amplified in osteosarcoma patients, while its functions and underlying mechanisms in regulation of osteosarcoma remain unknown. Herein we show that METTL1 and WDR4 are overexpressed in osteosarcoma and associated with poor patient prognosis. Knockdown of METTL1 or WDR4 causes decreased tRNA m7G modification level and impairs osteosarcoma progression in vitro and in vivo. Conversely, METTL1/WDR4 overexpression promotes osteosarcoma proliferation, migration and invasion capacities. tRNA methylation and mRNA translation profiling indicate that METTL1/WDR4 modified tRNAs enhance translation of mRNAs with more m7G tRNA-decoded codons, including extracellular matrix (ECM) remodeling effectors, which facilitates osteosarcoma progression and chemoresistance to doxorubicin. Our study demonstrates METTL1/WDR4 mediated tRNA m7G modification plays crucial oncogenic functions to enhance osteosarcoma progression and chemoresistance to doxorubicin via alteration of oncogenic mRNA translation, suggesting METTL1 inhibition combined with chemotherapy is a promising strategy for treatment of osteosarcoma patients.

Identification and functional comparison of novel alternatively spliced isoforms of human YAP.

As a key effector of the Hippo pathway, yes-associated protein (YAP) is a major regulator of cell proliferation and apoptosis. In this study, 23 hYAP isoforms were identified in HEK293 cells, with 14 isoforms being reported for the first time. These isoforms were classified into hYAP-a and hYAP-b isoforms based on the variation in exon 1. The two groups of isoforms showed distinctly different subcellular localizations. hYAP-a isoforms could activate TEAD- or P73-mediated transcription, affect the proliferation rate, and enhance the cellular chemosensitivity of HEK293 cells. Moreover, different activation abilities and pro-cytotoxic effects were observed among hYAP-a isoforms. However, hYAP-b isoforms were not found to exert any significant biological effects. Our findings add to the knowledge of YAP gene structure and protein-coding capacity and will help in the elucidation of the function and related molecular mechanisms of the Hippo-YAP signaling pathway.