The hemostatic and comforting effects of oral adhesive bandages in tooth extraction: a randomized controlled clinical study.

OBJECTIVES: To compare oral adhesive bandages with the classic compression method and evaluate the clinical efficacy of this wound dressing material in improving postoperative comfort, wound healing, and hemostasis in tooth extraction. MATERIALS AND METHODS: The study was designed as a randomized controlled clinical trial. A total of 120 patients were recruited and randomly assigned to the study group and the control group. In the study group, oral adhesive bandages were used as wound dressing. In the control group, patients bit on cotton balls and gauze, as usual. Hemorrhage, comfort, and healing levels were evaluated at postoperative 1 h, 24 h, and 7 days. The adhesion time of the oral adhesive bandages was also recorded. RESULTS: The average adhesion time of the oral adhesive bandages was 26.6 h. At postoperative 1 and 24 h, the hemostatic levels of the oral adhesive bandage group were significantly higher than those of the control group. The oral adhesive bandage group also reported significantly higher comfort scores than the control group. Both groups had similar healing levels and side effects. But the mean score for wound healing was slightly higher in the oral adhesive bandage group. CONCLUSIONS: Oral adhesive bandages were more effective than cotton balls and gauze in providing hemostatic and comfort effects on extraction wounds. CLINICAL RELEVANCE: Oral adhesive bandages possess clinical value in the management of extraction wounds.

Early Predicting Osteogenic Differentiation of Mesenchymal Stem Cells Based on Deep Learning Within One Day.

Osteogenic differentiation of mesenchymal stem cells (MSCs) is proposed to be critical for bone tissue engineering and regenerative medicine. However, the current approach for evaluating osteogenic differentiation mainly involves immunohistochemical staining of specific markers which often can be detected at day 5-7 of osteogenic inducing. Deep learning (DL) is a significant technology for realizing artificial intelligence (AI). Computer vision, a branch of AI, has been proved to achieve high-precision image recognition using convolutional neural networks (CNNs). Our goal was to train CNNs to quantitatively measure the osteogenic differentiation of MSCs. To this end, bright-field images of MSCs during early osteogenic differentiation (day 0, 1, 3, 5, and 7) were captured using a simple optical phase contrast microscope to train CNNs. The results showed that the CNNs could be trained to recognize undifferentiated cells and differentiating cells with an accuracy of 0.961 on the independent test set. In addition, we found that CNNs successfully distinguished differentiated cells at a very early stage (only 1 day). Further analysis showed that overall morphological features of MSCs were the main basis for the CNN classification. In conclusion, MSCs differentiation detection can be achieved early and accurately through simple bright-field images and DL networks, which may also provide a potential and novel method for the field of cell detection in the near future.

Enhanced lipid biosynthesis in oral squamous cell carcinoma cancer-associated fibroblasts contributes to tumor progression: Role of IL8/AKT/p-ACLY axis.

Lipid metabolic reprogramming of tumor cells has been proven to play a critical role in tumor initiation and development. However, lipid metabolism in cancer-associated fibroblasts (CAFs) has rarely been studied, particularly in CAFs of oral squamous cell carcinoma (OSCC). Additionally, the molecular mechanism by which tumor cells regulate lipid metabolism in fibroblasts is unclear. In this study, we found that phosphorylated ATP citrate lyase (p-ACLY), a key lipid metabolic enzyme, was upregulated in OSCC CAFs. Compared to paracancerous normal fibroblasts, CAFs showed enhanced lipid synthesis, such as elevated cytosolic acetyl-CoA level and accumulation of lipid droplets. Conversely, reduction of p-ACLY level blocked this biological process. In addition, blocking lipid synthesis in CAFs or inhibiting fatty acid uptake by OSCC cells reduced the promotive effects of CAFs on OSCC cell proliferation, invasion, and migration. These findings suggested that CAFs are one of lipid sources required for OSCC progression. Mechanistically, AKT signaling activation was involved in the upregulation of p-ACLY level and lipid synthesis in CAFs. Interleukin-8 (IL8), an exocrine cytokine of OSCC cells, could activate AKT and then phosphorylate ACLY in fibroblasts. This study suggested that the IL8/AKT/p-ACLY axis could be considered as a potential target for OSCC treatment.

Melatonin inhibits the stemness of head and neck squamous cell carcinoma by modulating HA synthesis via the FOSL1/HAS3 axis.

Hyaluronic acid (HA) is a glycosaminoglycan and the main component of the extracellular matrix (ECM), which has been reported to interact with its receptor CD44 to play critical roles in the self-renewal and maintenance of cancer stem cells (CSCs) of multiple malignancies. Melatonin is a neuroendocrine hormone with pleiotropic antitumor properties. However, whether melatonin could regulate HA accumulation in the ECM to modulate the stemness of head and neck squamous cell carcinoma (HNSCC) remains unknown. In this study, we found that melatonin suppressed CSC-related markers, such as CD44, of HNSCC cells and decreased the tumor-initiating frequency of CSCs in vivo. In addition, melatonin modulated HA synthesis of HNSCC cells by downregulating the expression of hyaluronan synthase 3 (HAS3). Further study showed that the Fos-like 1 (FOSL1)/HAS3 axis mediated the inhibitory effects of melatonin on HA accumulation and stemness of HNSCC in a receptor-independent manner. Taken together, melatonin modulated HA synthesis through the FOSL1/HAS3 axis to inhibit the stemness of HNSCC cells, which elucidates the effect of melatonin on the ECM and provides a novel perspective on melatonin in HNSCC treatment.

Accessible Tetrathiafulvalene Moieties in a 3D Covalent Organic Framework for Enhanced Near-Infrared Photo-Thermal Conversion and Photo-Electrical Response.

Redox-active tetrathiafulvalene (TTF)-based covalent organic frameworks (COFs) exhibit distinctive electrochemical and photoelectrical properties, but their prevalent two-dimensional (2D) structure with densely packed TTF moieties limits the accessibility of redox center and constrains their potential applications. To overcome this challenge, an 8-connected TTF linker (TTF-8CHO) is designed as a new building block for the construction of three-dimensional (3D) COFs. This approach led to the successful synthesis of a 3D COF with the bcu topology, designated as TTF-8CHO-COF. In comparison to its 2D counterpart employing a 4-connected TTF linker, the 3D COF design enhances access to redox sites, facilitating controlled oxidation by I2 or Au3+ to tune physical properties. When irradiated with a 0.7 W cm-2 808 nm laser, the oxidized 3D COF samples ( I X - ${\mathrm{I}}_{\mathrm{X}}^{-}$ @TTF-8CHO-COF and Au NPs@TTF-8CHO-COF) demonstrated rapid temperature increases of 239.3 and 146.1 °C, respectively, which surpassed those of pristine 3D COF (65.6 °C) and the 2D COF counterpart (6.4 °C increment after I2 treatment). Furthermore, the oxidation of the 3D COF heightened its photoelectrical responsiveness under 808 nm laser irradiation. This augmentation in photothermal and photoelectrical response can be attributed to the higher concentration of TTF·+ radicals generated through the oxidation of well-exposed TTF moieties.

ROCK2-RNA interaction map reveals multiple biological mechanisms underlying tumor progression in renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common form of kidney cancer in adults. Despite new therapeutic modalities, the outcomes for RCC patients remain unsatisfactory. Rho-associated coiled-coil forming protein kinase 2 (ROCK2) has previously been shown to be upregulated in RCC, and its expression was negatively correlated with patient survival. However, the precise molecular function of ROCK2 has remained unclear. Herein, using RNA-seq analysis of ROCK2 knockdown and control cells, we identified 464 differentially expressed genes, and 1287 alternative splicing events in 786-O RCC cells. Furthermore, mapping of iRIP-seq reads in 786-O cells showed a biased distribution at 5' UTR, intronic and intergenic regions. By comparing ROCK2-regulated alternative splicing and iRIP-seq data, we found 292 overlapping genes that are enriched in multiple tumorigenic pathways. Taken together, our work defined a complex ROCK2-RNA interaction map on a genomic scale in a human RCC cell line, which deepens our understanding of the molecular function of ROCK2 in cancer development.

Protection of laryngeal mucosa and function in laryngeal burns by heat absorption of perilaryngeal tissue.

OBJECTIVE: The laryngeal tissue carries most of the heat during inhalation injury. This study aims to explore the heat transfer process and the severity of injury inside laryngeal tissue by horizontally studying the temperature rise process at various anatomical layers of the larynx and observing the thermal damage in various parts of the upper respiratory tract. METHODS: The 12 healthy adult beagles were randomly divided into four groups, and inhaled room temperature air (control group), dry hot air of 80 °C (group I), 160 °C (group II), and 320 °C (group III) for 20 min, respectively. The temperature changes of the glottic mucosal surface, the inner surface of the thyroid cartilage, the external surface of the thyroid cartilage, and subcutaneous tissue were measured every minute. All animals were immediately sacrificed after injury, and pathological changes in various parts of laryngeal tissue were observed and evaluated under a microscope. RESULTS: After inhaling hot air of 80 °C, 160 °C and 320 °C, the increase of laryngeal temperature in each group was ΔT = 3.57 ± 0.25 °C, 7.83 ± 0.15 °C, 11.93 ± 0.21 °C. The tissue temperature was approximately uniformly distributed, and the difference was not statistically significant. The average laryngeal temperature-time curve showed that the laryngeal tissue temperature in group I and group II showed a trend of "first decrease and then increase", except that the temperature of group III directly increased with time. The prominent pathological changes after thermal burns mainly concluded necrosis of epithelial cells, loss of the mucosal layer, atrophy of submucosal glands, vasodilatation, erythrocytes exudation, and degeneration of chondrocytes. Mild degeneration of cartilage and muscle layers was also observed in mild thermal injury. Pathological scores indicated that the pathological severity of laryngeal burns increased significantly with the increase of temperature, and all layers of laryngeal tissue were seriously damaged by 320 °C hot air. CONCLUSIONS: The high efficiency of tissue heat conduction enabled the larynx to quickly transfer heat to the laryngeal periphery, and the heat-bearing capacity of perilaryngeal tissue has a certain degree of protective effect on laryngeal mucosa and function in mild to moderate inhalation injury. The laryngeal temperature distribution was in accordance with the pathological severity, and the pathological changes of laryngeal burns provided a theoretical basis for the early clinical manifestations and treatment of inhalation injury.

N-Doped Carbon Nanotubes Supported Fe-Mn Dual-Single-Atoms Nanozyme with Synergistically Enhanced Peroxidase Activity for Sensitive Colorimetric Detection of Acetylcholinesterase and Its Inhibitor.

Monitoring acetylcholinesterase (AChE) and its inhibitors is of importance for early diagnosis and therapy of neurological diseases. Herein, N-doped carbon nanotubes supported Fe-Mn dual-single-atoms (FeMn DSAs/N-CNTs) were fabricated by a simple pyrolysis, as thoroughly figured out by a series of the characterization techniques. The peroxidase-like activity of FeMn DSAs/N-CNTs was investigated by catalytic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to generate rich hydroxyl radicals (·OH) in the H2O2 system, which effectively catalyzed colorless TMB oxidation to blue oxidized TMB (ox-TMB). Besides, the peroxidase-like activity was greatly weakened by thiocholine (derived from AChE), accompanied by making blue ox-TMB fade. Impressively, the highly improved peroxidase-like property is further evidenced by density functional theory (DFT) calculations, where the dual-single atoms show a lower energy barrier (0.079 eV) and their interactions with the N-CNTs played critical roles for producing the oxygen radicals. By virtue of the nanozyme, a low-cost, specific, and sensitive colorimetric sensor was built for detection of AChE with a broader linear range of 0.1-30 U L-1 and a lower limit of detection (LOD, 0.066 U L-1), combined with its feasible analysis in human serum samples. Also, this platform was applied for measuring huperzine A inhibitor with a wide linear scope of 5-500 nM and a LOD down to 4.17 nM. This strategy provides a low-cost and convenient approach for early clinical diagnosis and drug development.

A theoretical study of the NbS2 monolayer as a promising anchoring material for lithium-sulfur batteries.

Developing efficient cathode materials with good conductivity to restrain the shuttle effect and promote the reaction kinetics has been a key scientific issue for the development of lithium-sulfur (Li-S) batteries. Here, by means of first-principles computations, we demonstrate that the NbS2 monolayer is a promising cathode anchoring material for Li-S batteries. It has a metallic feature that improves the conductivity of sulfur and lithium polysulfides (LiPSs) and promotes the electron transfer ability. The discharge products LiPSs are strongly anchored on the NbS2 monolayer without structural distortion, which effectively alleviates the shuttle effect. Remarkably, the reductions of sulfur to soluble LiPSs are spontaneous exothermic reactions while the subsequent reductions to insoluble LiPSs are endothermic reactions with low Gibbs free energy barriers (0.09-0.18 eV) and reaction activation barriers (0.83-0.93 eV), ensuring the rapid discharge process. In addition, the barriers of Li2S decomposition and Li atom diffusion are only 0.64 and 0.18 eV, respectively, which improve the reaction kinetics in the charging process and the cycling life of batteries. These results suggest that the NbS2 monolayer can be utilized as a promising anchoring material for Li-S batteries to achieve high reversible capacity and conversion efficiency.

Multiple measurement analysis of resting-state fMRI for ADHD classification in adolescent brain from the ABCD study.

Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in school-aged children. Its accurate diagnosis looks after patients' interests well with effective treatment, which is important to them and their family. Resting-state functional magnetic resonance imaging (rsfMRI) has been widely used to characterize the abnormal brain function by computing the voxel-wise measures and Pearson's correlation (PC)-based functional connectivity (FC) for ADHD diagnosis. However, exploring the powerful measures of rsfMRI to improve ADHD diagnosis remains a particular challenge. To this end, this paper proposes an automated ADHD classification framework by fusion of multiple measures of rsfMRI in adolescent brain. First, we extract the voxel-wise measures and ROI-wise time series from the brain regions of rsfMRI after preprocessing. Then, to extract the multiple functional connectivities, we compute the PC-derived FCs including the topographical information-based high-order FC (tHOFC) and dynamics-based high-order FC (dHOFC), the sparse representation (SR)-derived FCs including the group SR (GSR), the strength and similarity guided GSR (SSGSR), and sparse low-rank (SLR). Finally, these measures are combined with multiple kernel learning (MKL) model for ADHD classification. The proposed method is applied to the Adolescent Brain and Cognitive Development (ABCD) dataset. The results show that the FCs of dHOFC and SLR perform better than the others. Fusing multiple measures achieves the best classification performance (AUC = 0.740, accuracy = 0.6916), superior to those from the single measure and the previous studies. We have identified the most discriminative FCs and brain regions for ADHD diagnosis, which are consistent with those of published literature.

Redox-Active Mixed-Linker Metal-Organic Frameworks with Switchable Semiconductive Characteristics for Tailorable Chemiresistive Sensing.

Metal-organic frameworks (MOFs), with diverse metal nodes and designable organic linkers, offer unique opportunities for the rational engineering of semiconducting properties. In this work, we report a mixed-linker conductive MOF system with both tetrathiafulvalene and Ni-bis(dithiolene) moieties, which allows the fine-tuning of electronic structures and semiconductive characteristics. By continuously increasing the molar ratio between tetrathiafulvalene and Ni-bis(dithiolene), the switching of the semiconducting behaviors from n-type to p-type was observed along with an increase in electrical conductivity by 3 orders of magnitude (from 2.88×10-7  S m-1 to 9.26×10-5  S m-1 ). Furthermore, mixed-linker MOFs were applied for the chemiresistive detection of volatile organic compounds (VOCs), where the sensing performance was modulated by the corresponding linker ratios, showing synergistic and nonlinear modulation effects.

Penta-BCN monolayer: a metal-free photocatalyst with a high carrier mobility for water splitting.

Photocatalytic water splitting has been regarded as a promising strategy to provide clean energy and solve the energy crisis; thus, extensive efforts have been devoted to developing highly efficient photocatalysts. Herein, based on density functional theory computations, we demonstrated that the penta-BCN monolayer is a promising photocatalyst for water splitting. The penta-BCN monolayer is semiconducting with a moderate direct band gap of 2.87 eV, and its band edge positions straddle the redox potentials of water. Remarkably, the penta-BCN monolayer also has a pronounced optical absorption in the ultraviolet and visible light regions and exhibits an ultrahigh hole mobility (∼2 × 105 cm2 V-1 s-1). These desirable properties render the penta-BCN monolayer a promising candidate for photocatalytic water splitting.

miR-5590-3p inhibits the proliferation and metastasis of renal cancer cells by targeting ROCK2 to inhibit proliferation, migration and invasion.

The present study aimed to clarify the role of microRNA (miR)-5590-3p in the progression of renal cell carcinoma (RCC) and investigate the underlying mechanisms. The expression levels of miR-5590-3p, Rho-associated protein kinase (ROCK)2 and ß-catenin in RCC cells were measured by reverse transcription-quantitative PCR and western blot analysis. Following overexpression of miR-5590-3p and ROCK2 by transfection of miR-5590-3p mimics and GV367-ROCK2, respectively, changes in the proliferation, migration and invasion of RCC cells were determined through colony-formation, wound-healing and Transwell assays, respectively. The direct binding interaction between miR-5590-3p and ROCK2, initially predicted using Targetscan, was validated by a dual-luciferase reporter assay. The results indicated that miR-5590-3p was downregulated in RCC. Overexpression of miR-5590-3p led to downregulation of ROCK2 and ß-catenin and inhibited the proliferation, migration and invasion of RCC cells. The dual-luciferase reporter assay confirmed the binding relationship between miR-5590-3p and ROCK2. Of note, overexpression of ROCK2 effectively reversed the regulatory effects of miR-5590-3p on RCC cells. In conclusion, miR-5590-3p inhibits the proliferation, migration and invasion of RCC cells by targeting ROCK2, which is a potential molecular biomarker and therapeutic target for RCC.

FVC as an adaptive and accurate method for filtering variants from popular NGS analysis pipelines.

The quality control of variants from whole-genome sequencing data is vital in clinical diagnosis and human genetics research. However, current filtering methods (Frequency, Hard-Filter, VQSR, GARFIELD, and VEF) were developed to be utilized on particular variant callers and have certain limitations. Especially, the number of eliminated true variants far exceeds the number of removed false variants using these methods. Here, we present an adaptive method for quality control on genetic variants from different analysis pipelines, and validate it on the variants generated from four popular variant callers (GATK HaplotypeCaller, Mutect2, Varscan2, and DeepVariant). FVC consistently exhibited the best performance. It removed far more false variants than the current state-of-the-art filtering methods and recalled ~51-99% true variants filtered out by the other methods. Once trained, FVC can be conveniently integrated into a user-specific variant calling pipeline.

Unveiling the Degradation Mechanism of High-Temperature Superconductor Bi2Sr2CaCu2O8+δ in Water-Bearing Environments.

The physical properties of copper oxide high-temperature superconductors have been studied extensively, such as the band structure and doping effects of Bi2Sr2CaCu2O8+δ (Bi-2212). However, some chemical-related properties of these superconductors are rarely reported, such as their stability in water-bearing environments. Herein, we report experiments combined with ab initio calculations that address the effects of water in contact with Bi-2212. The evolution of Bi-2212 flakes with exposure to water for different time intervals was tested and characterized by optical microscopy (OM), atomic force microscopy (AFM), Raman spectroscopy, transmission electron microscopy (TEM), and electrical measurements. The thickness of Bi-2212 flakes is gradually decreased in water, and some thin flakes can be completely etched away after a few days. The stability of Bi-2212 in other solvents is also evaluated, including alcohol, acetone, HCl, and KOH. The morphology of Bi-2212 flakes is relatively stable in organic solvents. However, the flakes are etched relatively quick in HCl and KOH, especially in an acidic environment. Our results imply that hydrogen ions are primarily responsible for the deterioration of their properties. Both TEM and calculation results demonstrate that the atoms in the Bi-O plane are relatively stable when compared to the inner atoms in Sr-O, Ca-O, and Cu-O planes. This work contributes toward understanding the chemical stability of a Bi-2212 superconducting device in environmental medium, which is important for both fundamental studies and practical applications of copper oxide high-temperature superconductors.

Sex-specific genetic association between psychiatric disorders and cognition, behavior and brain imaging in children and adults.

Although there are pronounced sex differences for psychiatric disorders, relatively little has been published on the heterogeneity of sex-specific genetic effects for these traits until very recently for adults. Much less is known about children because most psychiatric disorders will not manifest until later in life and existing studies for children on psychiatric traits such as cognitive functions are underpowered. We used results from publicly available genome-wide association studies for six psychiatric disorders and individual-level data from the Adolescent Brain Cognitive Development (ABCD) study and the UK Biobank (UKB) study to evaluate the associations between the predicted polygenic risk scores (PRS) of these six disorders and observed cognitive functions, behavioral and brain imaging traits. We further investigated the mediation effects of the brain structure and function, which showed heterogeneity between males and females on the correlation between genetic risk of schizophrenia and fluid intelligence. There was significant heterogeneity in genetic associations between the cognitive traits and psychiatric disorders between sexes. Specifically, the PRSs of schizophrenia of boys showed stronger correlation with eight of the ten cognitive functions in the ABCD data set; whereas the PRSs of autism of females showed a stronger correlation with fluid intelligence in the UKB data set. Besides cognitive traits, we also found significant sexual heterogeneity in genetic associations between psychiatric disorders and behavior and brain imaging. These results demonstrate the underlying early etiology of psychiatric disease and reveal a shared and unique genetic basis between the disorders and cognition traits involved in brain functions between the sexes.

Efficient and Selective Electroreduction of CO2 to HCOOH over Bismuth-Based Bromide Perovskites in Acidic Electrolytes.

Metal halide perovskites, primarily used as optoelectronic devices, have not been applied for electrochemical conversion due to their insufficient stability in moisture. Herein, two bismuth-based perovskites are introduced as novel electrocatalysts to convert CO2 into HCOOH in aqueous acidic media (pH 2.5), exhibiting a high Faradaic efficiency for HCOOH of >80 % in a wide potential range from -0.75 to -1.25 V. Their structural evolution against water was dynamically monitored by in situ spectra. Theoretical calculations further reveal that the formation of intermediate OCHO* on bismuth sites of Cs3 Bi2 Br9 (111) play a pivotal role toward HCOOH production, which has a lower energy barrier than that on Cs2 AgBiBr6 (001) surfaces. Significantly, CO2 reacts with protons instead of water which can enhance CO2 reduction rate and suppress hydrogen evolution by avoiding carbonate formation in acidic electrolytes. This work paves the way for the extensive investigation of halide perovskites in aqueous systems.

Temperature processing and distribution in larynx thermal inhalation injury with analogy to human airway cells: a mechanism of protection.

OBJECTIVE: Inhalation injuries, especially laryngeal injuries, threaten the lives of burn patients. Unlike studies on temperature distribution in the upper airway, studies on temperature development in different laryngeal layers, including the mucosa, lamina propria, cartilage, muscle, and subcutaneous layer, are lacking. METHOD: For the in-vivo study, 16 healthy adult male beagles were divided into four groups: control, low-, medium-, and high-heat groups, inhaling dry air at 26, 80, 160, and 320°C for 20 min, with temperature probes punctured through skin into layers as mentioned, and heat energy was calculated. For the in-vitro study, we heated human lung fibroblasts and bronchial epithelial cells using a similar heating profile with heat energy of 15-90 J/g to investigate cell survival and viability for clinical comparison. RESULTS: No statistical difference emerged between the temperatures of different laryngeal layers at each timepoint. The temperatures decreased significantly and shortly before increasing unevenly in the low- and medium-heat groups. The survival rates and viability of the two cell lines correlated negatively with heat energy. The heat energy absorbed in the low-, medium-, and high-heat groups of beagles were 12, 29, and 44 J/g, with calculated in-vitro human cell survival rates of 114%, 90%, and 69%, respectively, for the corresponding energy levels. CONCLUSIONS: The abnormal temperature processing and lack of a difference between layers indicate an effective self-protective mechanism of heat conduction in larynx. The in-vitro results demonstrate a high survival rate of lung cells at comparable heat energy levels to those measured in the larynx.

miR-1307-5p suppresses proliferation and tumorigenesis of bladder cancer via targeting MDM4 and the Hippo signaling pathway.

BACKGROUND: Emerging evidence has shown that miR-1307-5p is involved in tumorigenesis of various types of cancer. This study aims to assess the role and mechanism of miR-1307-5p in bladder cancer. METHODS: Bioinformatics analyses were carried out with clinical datasets in the public domains. To investigate the cellular functions of miR-1307-5p, assays of cell proliferation, cell cycle and cell apoptosis were conducted in bladder cancer cell lines and xenografts. The molecular mechanisms of miR-1307-5p were studied using luciferase reporter, RT-qPCR, and western blotting analyses. RESULTS: We found that miR-1307-5p expression was significantly decreased in bladder cancer tissues, and its lower level was associated with poor prognosis. Cellular assays indicated the tumor-suppressor roles of miR-1307-5p were linked to cell proliferation, cell cycle inhibition, and cell apoptosis promotion. Conversely, anti-miR-1307-5p facilitated cell proliferation and cell cycle and antagonized cell apoptosis. In the in vivo setting, tumor growth was suppressed by miR-1307-5p overexpression. We found by bioinformatic and luciferase reporter assays that miR-1307-5p targets the 3'-UTR of MDM4, a well-known Inhibitor of TP53-mediated transactivation, cell cycle arrest and apoptosis. Specifically, miR-1307-5p markedly reduced MDM4 proteins expression, decreased the expression of Ki-67 and PCNA, and increased the expression of cleaved-caspase 3 and caspase 9. While in parallel assays, anti-miR-1307-5p had opposite effects. In addition, we found that miR-1307-5p overexpression would suppress bladder cancer cell growth by inhibiting MDM4 and its downstream Hippo pathway. CONCLUSION: In bladder cancer, miR-1307-5p functions as a tumor suppressor and has the potentials as biomarker and therapeutical agent.

Cancer cells corrupt normal epithelial cells through miR-let-7c-rich small extracellular vesicle-mediated downregulation of p53/PTEN.

Tumor volume increases continuously in the advanced stage, and aside from the self-renewal of tumor cells, whether the oncogenic transformation of surrounding normal cells is involved in this process is currently unclear. Here, we show that oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) promote the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of normal epithelial cells but delay their apoptosis. In addition, nuclear-cytoplasmic invaginations and multiple nucleoli are observed in sEV-treated normal cells, both of which are typical characteristics of premalignant lesions of OSCC. Mechanistically, miR-let-7c in OSCC-derived sEVs is transferred to normal epithelial cells, leading to the transcriptional inhibition of p53 and inactivation of the p53/PTEN pathway. In summary, we demonstrate that OSCC-derived sEVs promote the precancerous transformation of normal epithelial cells, in which the miR-let-7c/p53/PTEN pathway plays an important role. Our findings reveal that cancer cells can corrupt normal epithelial cells through sEVs, which provides new insight into the progression of OSCC.