A Zinc Oxide Nanowire-Modified Mineralized Collagen Scaffold Promotes Infectious Bone Regeneration.

Bone infection poses a major clinical challenge that can hinder patient recovery and exacerbate postoperative complications. This study has developed a bioactive composite scaffold through the co-assembly and intrafibrillar mineralization of collagen fibrils and zinc oxide (ZnO) nanowires (IMC/ZnO). The IMC/ZnO exhibits bone-like hierarchical structures and enhances capabilities for osteogenesis, antibacterial activity, and bacteria-infected bone healing. During co-cultivation with human bone marrow mesenchymal stem cells (BMMSCs), the IMC/ZnO improves BMMSC adhesion, proliferation, and osteogenic differentiation even under inflammatory conditions. Moreover, it suppresses the activity of Gram-negative Porphyromonas gingivalis and Gram-positive Streptococcus mutans by releasing zinc ions within the acidic infectious microenvironment. In vivo, the IMC/ZnO enables near-complete healing of infected bone defects within the intricate oral bacterial milieu, which is attributed to IMC/ZnO orchestrating M2 macrophage polarization, and fostering an osteogenic and anti-inflammatory microenvironment. Overall, these findings demonstrate the promise of the bioactive scaffold IMC/ZnO for treating bacteria-infected bone defects.

The production of graphene using impinging jet exfoliation in a binary system of CO2 and N-methyl pyrrolidone.

High quality and high quantity few-layer graphene was successfully prepared using a new impinging jet method. Natural graphite flakes were first agitated in N-methyl pyrrolidone (NMP) with the assistance of supercritical CO2, then the half-exfoliated graphite was further stripped using the shear stress derived from the impinging jets. After the energy conversion and stress analysis of the graphite particles during the whole exfoliation process, it was revealed that the size of the target mesh, the distance between the nozzle and the target, the decompression rate, and the size of the raw materials had a significant influence on the exfoliation process. Additionally, a microscopic view of the exfoliation and dispersion mechanism of graphene in the CO2-NMP system was investigated using molecular dynamics simulation, and CO2 was found to be beneficial for the penetration of NMP into the graphite sheets. Finally, the concentration and quality characteristics of the prepared graphene were characterized using ultraviolet-visible spectroscopy, transmission electron microscopy, Raman spectroscopy, and atomic force microscopy. The maximum concentration was as high as 0.689 mg ml-1, the thickness of 68% of the product was less than 2.5 nm, and the lateral dimension was from 0.5 to 3.0 µm. These results indicate that this impinging jet method is promising for large-scale industrial production.

Suppression of OSCC malignancy by oral glands derived-PIP identified by iTRAQ combined with 2D LC-MS/MS.

Oral squamous cell carcinoma (OSCC) is the most common malignancy in head and neck cancer and a global cause of cancer-related death. Due to the poor survival rates associated with OSCC, there is a growing need to develop novel technologies and predictive biomarkers to improve disease diagnosis. The identification of new cellular targets in OSCC tumors will benefit such developments. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics analysis combined with 2-dimensional liquid chromatography and tandem mass spectrometry (2D LC-MS/MS) were used to identify differentially expressed proteins (DEPs) between tumor and normal tissues. Of the DEPs detected, the most significantly downregulated protein in OSCC tissue was prolactin-inducible protein (PIP). Clonogenic and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) experiments showed that the proliferation capacity of OSCC cells overexpressing PIP decreased due to cell cycle arrest at the G0/G1 checkpoint. Wound-healing and transwell assay further showed that PIP overexpression also reduced the migration and invasion of OSCC cells. Immunohistochemistry (IHC) was used to analyze the expression in OSCC, indicating that PIP may be secreted by glandular cells and have an inhibitory effect on OSCC cells to produce. In western blot analysis, silencing studies confirmed that PIP mediates these effects through the AKT/mitogen-activated protein kinase (MAPK) signaling axis in OSCC cells. Taken together, this study reveals PIP as a key mediator of OSCC cell growth, migration, and invasion through its effect on AKT/MAPK signaling.

circ-PKD2 inhibits carcinogenesis via the miR-204-3p/APC2 axis in oral squamous cell carcinoma.

Recent findings have shown that dysregulation of circular RNAs (circRNAs) is implicated in various cancers. However, the contribution of circRNAs in oral squamous cell carcinoma (OSCC) remains largely unexplored. We screened circRNA expression profiles using a circRNA microarray in paired OSCC and normal tissues and explored the clinical significance of a downregulated circRNA, circ-PKD2. Moreover, the biological function of circ-PKD2 in OSCC was investigated both in vitro and in vivo. We found that downregulation of circ-PKD2 in OSCC correlated significantly with aggressive characteristics. Further analysis revealed that overexpression of circ-PKD2 inhibited OSCC cell proliferation, migration and invasion, induced apoptosis and cell cycle arrest, which were promoted by knockdown of circ-PKD2. In addition, circ-PKD2 was identified as a sponge for miR-204-3p and upregulated the expression of adenomatous polyposis coli 2 (APC2), which was the functional target of miR-204-3p. Moreover, circ-PKD2 attenuated the oncogenic effects of miR-204-3p-mediated APC2 on OSCC progression via multiple signaling pathways. These results demonstrate that the circ-PKD2/miR-204-3p/APC2 axis represents a novel pathway involved in the pathogenesis of OSCC and may serve as a novel therapeutic target of OSCC.

Decreased expression of hsa_circ_0072387 as a valuable predictor for oral squamous cell carcinoma.

OBJECTIVE: Increasing evidence points toward the key function of circular RNAs (circRNAs) in various carcinomas. This study aimed to identify aberrant expression of hsa_circ_0072387 in oral squamous cell carcinoma and probe its clinical significance. MATERIALS AND METHODS: Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to assess hsa_circ_0072387 expression levels in 63 paired OSCC tissues and three OSCC cell lines. The area under the receiver operator characteristic (ROC) curve was plotted to assess any potential clinical significance. RESULTS: Our data showed that hsa_circ_0072387 expression in OSCC was significantly downregulated compared with adjacent normal tissues (p < 0.001). Compared to human normal oral keratinocyte cell, the levels of hsa_circ_0072387 were lower in three OSCC cell lines (SCC25, SCC15, CAL27). More significantly, hsa_circ_0072387 expression was associated with the TNM stage in OSCC (p = 0.050). The area under the ROC curve reached up to 0.746. Based on bioinformatics, hsa-miR-129-3p, hsa-miR-141-3p, and hsa-miR-29-3p were predicted to be potential miRNAs binding with hsa_circ_0072387. Furthermore, hsa-miR-129-3p, hsa-miR-141-3p, and hsa-miR-29-3p were involved in multiple tumor-related signaling pathways. CONCLUSION: Our finding suggested that lower expression of has_circ_0072387 could be a key circRNA in OSCC and serve as a potential biomarker in OSCC diagnosis and therapeutic targets.

Staging of Liver Fibrosis Based on Energy Valley Optimization Multiple Stacking (EVO-MS) Model.

Currently, staging the degree of liver fibrosis predominantly relies on liver biopsy, a method fraught with potential risks, such as bleeding and infection. With the rapid development of medical imaging devices, quantification of liver fibrosis through image processing technology has become feasible. Stacking technology is one of the effective ensemble techniques for potential usage, but precise tuning to find the optimal configuration manually is challenging. Therefore, this paper proposes a novel EVO-MS model-a multiple stacking ensemble learning model optimized by the energy valley optimization (EVO) algorithm to select most informatic features for fibrosis quantification. Liver contours are profiled from 415 biopsied proven CT cases, from which 10 shape features are calculated and inputted into a Support Vector Machine (SVM) classifier to generate the accurate predictions, then the EVO algorithm is applied to find the optimal parameter combination to fuse six base models: K-Nearest Neighbors (KNNs), Decision Tree (DT), Naive Bayes (NB), Extreme Gradient Boosting (XGB), Gradient Boosting Decision Tree (GBDT), and Random Forest (RF), to create a well-performing ensemble model. Experimental results indicate that selecting 3-5 feature parameters yields satisfactory results in classification, with features such as the contour roundness non-uniformity (Rmax), maximum peak height of contour (Rp), and maximum valley depth of contour (Rm) significantly influencing classification accuracy. The improved EVO algorithm, combined with a multiple stacking model, achieves an accuracy of 0.864, a precision of 0.813, a sensitivity of 0.912, a specificity of 0.824, and an F1-score of 0.860, which demonstrates the effectiveness of our EVO-MS model in staging the degree of liver fibrosis.

Validation and identification of anoikis-related lncRNA signatures for improving prognosis in clear cell renal cell carcinoma.

BACKGROUND: Clear cell carcinoma (ccRCC) usually has a high metastasis rate and high mortality rate. To enable precise risk stratification, there is a need for novel biomarkers. As one form of apoptosis, anoikis results from the disruption of cell-cell connection or cell-ECM attachment. However, the impact of anoikis-related lncRNAs on ccRCC has not yet received adequate attention. METHODS: The study utilized univariate Cox regression analysis in order to identify the overall survival (OS) associated anoikis-related lncRNAs (ARLs), followed by the LASSO algorithm for selection. On this basis, a risk model was subsequently established using five anoikis-related lncRNAs. To dig the inner molecular mechanism, KEGG, GO, and GSVA analyses were conducted. Additionally, the immune infiltration landscape was estimated using the ESTIMATE, CIBERSORT, and ssGSEA algorithms. RESULTS: The study constructed a novel risk model based on five ARLs (AC092611.2, AC027601.2, AC103809.1, AL133215.2, and AL162586.1). Patients categorized as low-risk exhibited significantly better OS. Notably, the study observed marked different immune infiltration landscapes and drug sensitivity by risk stratification. Additionally, the study preliminarily explored potential signal pathways associated with risk stratification. CONCLUSION: The study exhibited the crucial role of ARLs in the carcinogenesis of ccRCC, potentially through differential immune infiltration. Furthermore, the established risk model could serve as a valuable stratification factor for predicting OS prognosis.

The effect of sulfuration reaction rates with sulphur concentration gradient dependence on the growth pattern and morphological evolution of MoS2 in laminar flow.

Sulfuration reactions dominate the synthesis of transition-metal dichalcogenides via chemical vapor deposition. A neglected critical issue is the evolution of crystal domain morphology and growth models caused by boundary layer development. In this study, we propose two growth models within a laminar flow field to investigate the kinetic mechanism of uniformly grown MoS2. We used supercritical fluid pre-deposition to obtain a well-distributed and low-crystallinity Mo precursor on the surface of a substrate to avoid non-stoichiometric supply in sulfuration. The development of the boundary layer was suppressed through mainstream force by adjusting the substrate slope angle. For growth within the underdeveloped laminar boundary layer, monolayer MoS2 with a size of 50 µm uniformly distributed on the full substrate with R = 85% (relative change in boundary layer thickness). Moreover, the growth constrained by surface chemical reactions tended to promote spatially uniform growth. However, within the fully developed laminar flow, the crystal domains preferentially grew vertically, which was attributed to the excessive crystal growth rate (g). Our results provide new insights into the controllable preparation of two-dimensional materials.

A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models.

Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. From a screen of human airway derived cell lines that express varying levels of ACE2/TMPRSS2, we found a subset that express comparably high endogenous levels of ACE2 but surprisingly did not support SARS-CoV-2 replication. Here we report that this resistance is mediated by a basally active cGAS-STING pathway culminating in interferon (IFN)-mediated restriction of SARS-CoV-2 replication at a post-entry step. Pharmacological inhibition of JAK1/2, depletion of the IFN-α receptor and cGAS-STING pathway effectors substantially increased SARS-CoV-2 replication in these cell models. While depletion of cGAS or STING was sufficient to reduce the preexisting levels of IFN-stimulated genes (ISGs), SARS-CoV-2 infection in STING knockout cells independently induced ISG expression. Remarkably, SARS-CoV-2-induced ISG expression in STING knockout cell as well as in primary human airway cultures was limited to uninfected bystander cells, demonstrating efficient antagonism of the type I/III IFN-pathway, but not viral sensing or IFN production, in productively infected cells. Of note, SARS-CoV-2-infected primary human airway cells also displayed markedly lower levels of STING expression, raising the possibility that SARS-CoV-2 can target STING expression or preferentially infect cells that express low levels of STING. Finally, ectopic ACE2 overexpression overcame the IFN-mediated blocks, suggesting the ability of SARS-CoV-2 to overcome these possibly saturable blocks to infection. Our study highlights that in addition to viral receptors, basal activation of the cGAS-STING pathway and innate immune defenses may contribute to defining SARS-CoV-2 cellular tropism.

A Biomimetic Multifunctional Scaffold for Infectious Vertical Bone Augmentation.

The regenerative treatment of infectious vertical bone defects remains difficult and challenging today. Current clinical treatments are limited in their ability to control bacteria and infection, which is unfavorable for new bone formation and calls for a new type of material with excellent osteogenic and antibacterial properties. Here a multifunctional scaffold is synthesized that mimics natural bone nanostructures by incorporating silver nanowires into a hierarchical, intrafibrillar mineralized collagen matrix (IMC/AgNWs), to achieve the therapeutic goals of inhibiting bacterial activity and promoting infectious alveolar bone augmentation in rats and beagle dogs. An appropriate concentration of 0.5 mg mL-1 AgNWs is selected to balance biocompatibility and antibacterial properties. The achieved IMC/AgNWs exhibit a broad spectrum of antimicrobial properties against Gram-negative Porphyromonas gingivalis and Gram-positive Streptococcus mutans. When the IMC/AgNWs are cocultured with periodontal ligament stem cells, it possesses excellent osteoinductive activities under both non-inflammatory and inflammatory conditions. By constructing a rat mandibular infected periodontal defect model, the IMC/AgNWs achieve a near-complete healing through the canonical BMP/Smad signaling. Moreover, the IMC/AgNWs enhance vertical bone height and osseointegration in peri-implantitis in beagle dogs, indicating the clinical translational potential of IMC/AgNWs for infectious vertical bone augmentation.

Autophagy-related gene LAPTM4B promotes the progression of renal clear cell carcinoma and is associated with immunity.

Renal cell carcinoma (RCC) is a common urologic disease. Currently, surgery is the primary treatment for renal cancer; immunotherapy is not as effective a treatment strategy as expected. Hence, understanding the mechanism in the tumor immune microenvironment (TME) and exploring novel immunotherapeutic targets are considered important. Recent studies have demonstrated that autophagy could affect the immune environment of renal cell carcinoma and induce proliferation and apoptosis of cancer cells. By comparing lysosomal genes and regulating autophagy genes, we identified the LAPTM4B gene to be related to RCC autophagy. By analyzing the TCGA-KIRC cohort using bioinformatics, we found M2 macrophages associated with tumor metastasis to be significantly increased in the immune microenvironment of patients with high expression of LAPTM4B. GO/KEGG/GSEA/GSVA results showed significant differences in tumor autophagy- and metastasis-related pathways. Single-cell sequencing was used to compare the expression of LAPTM4B in different cell types and obtain the differences in lysosomal and autophagy pathway activities in different ccRCC cells. Subsequently, we confirmed the differential expression of LAPTM4B in renal cell carcinoma of different Fuhrman grades using western blotting. Downregulation of LAPTM4B expression significantly reduced the proliferation of renal cell carcinoma cells and promoted cell apoptosis through cell experiments. Overall, our study demonstrated that the autophagy-related gene LAPTM4B plays a critical role in the TME of RCC, and suggested that LAPTM4B is a potential therapeutic target for RCC immunotherapy.

Economic evaluation of stent retrievers in basilar artery occlusion: An analysis from Chinese healthcare system perspective.

PURPOSE: This study aimed to investigate the cost-effectiveness of stent retriever (SR) versus best medical management (BMM) in patients with basilar artery occlusion (BAO) in China. METHODS: We used a two-step approach to compare the cost-effectiveness of SR plus BMM with that of BMM alone over 20 years. A decision tree was initially constructed for the first 3 months, followed by a Markov model for the subsequent period. Collected data on clinical aspects were extracted from the BAOCHE investigation, while costs-related information was sourced from previously published research. The key metric for evaluating the primary outcome was the incremental cost-effectiveness ratio (ICER), achieved $/QALY. The threshold for identifying SR as highly cost-effective was set at an ICER below $12,551/QALY, SR was deemed cost-effective if the ICER ranged from $12,551 to $37,654 per QALY. Uncertainty was addressed using scenario, one-way sensitivity, and probabilistic sensitivity analyses (PSA). FINDINGS: For Chinese patients with BAO, the 20-year cost per patient was $8678 with BMM alone and $21,988 for SR plus BMM. Effectiveness was 1.45 QALY for BMM alone, and 2.77 QALY for SR plus BMM. The ICER of SR + BMM versus BMM alone was $10,050 per QALY. The scenario and one-way sensitivity analyses revealed that in certain situations the ICER could exceed $12,551 per QALY, but remain below $37,654 per QALY. Results from the PSA suggested that SR was likely to be cost-effective for Chinese patients with BAO, with a probability exceeding 98% when considering a willingness-to-pay (WTP) threshold of $12,551 per QALY. IMPLICATIONS: Our study indicates that SR is an intervention option that is highly likely to be cost-effective for Chinese patients with BAO, with a probability of over 98% under the current WTP threshold of $12,551 per QALY.

PIK3C2A is a prognostic biomarker that is linked to immune infiltrates in kidney renal clear cell carcinoma.

Background: Phosphoinositide 3-kinases (PI3Ks) are lipid enzymes that regulate a wide range of intracellular functions. In contrast to Class I and Class III PI3K, which have more detailed descriptions, Class II PI3K has only recently become the focus of functional research. PIK3C2A is a classical member of the PI3Ks class II. However, the role of PIK3C2A in cancer prognosis and progression remains unknown. Methods: The expression pattern and prognostic significance of PIK3C2A in human malignancies were investigated using multiple datasets and scRNA-seq data. The PIK3C2A expression in renal clear cell carcinoma (KIRC) was then validated utilizing Western blot. The functional role of PIK3C2A in KIRC was assessed using combined function loss experiments with in vitro experiments. Furthermore, the correlation of PIK3C2A expression with tumor immunity was investigated in KIRC. The TCGA database was employed to investigate PIK3C2A functional networks. Results: Significant decrease in PIK3C2A expression in KIRC, demonstrated that it potentially influences the prognosis of diverse tumors, particularly KIRC. In addition, PIK3C2A was significantly correlated with the T stage, M stage, pathologic stage, and histologic grade of KIRC. Nomogram models were constructed and used to predict patient survival based on the results of multivariate Cox regression analysis. PIK3C2A knockdown resulted in significantly increased KIRC cell proliferation. Of note, PIK3C2A expression demonstrated a significant correlation with the infiltrating levels of primary immune cells in KIRC. Conclusion: These findings support the hypothesis that PIK3C2A is a novel biomarker for tumor progression and indicates dynamic shifts in immune infiltration in KIRC. Furthermore, aberrant PIK3C2A expression can influence the biological activity of cancer cells.

Vapor-Liquid-Solid Growth of Site-Controlled Monolayer MoS2 Films Via Pressure-Induc ed Supercritical Phase Nucleation.

In this study, a novel pressure-induced supercritical phase nucleation method is proposed to synthesize monolayer MoS2 films, which is promoter free and can avoid contamination of films derived from these heterogeneous promoters in most of the existing techniques. The low-crystallinity and size-controlled MoO2(acac)2 particles are recrystallized on the substrate via the pressure-sensitive solvent capacity of supercritical CO2 and these particles are used as growth sites. The size of single-crystal MoS2 on the substrate is found to be dependent on the wetting area of the pyrolyzed precursor droplets (MoO2) on the surface, and the formation of continuous films with high coverage is mainly controlled by the coalescence of MoO2 droplets. It is enhanced by the increase of the nucleation site density, which can be adjusted by the supersaturation of the supercritical fluid solution. Our findings pave a new way for the controllable growth of MoS2 and other two-dimensional materials and provide sufficient and valuable evidence for vapor-liquid-solid growth.

Effect of tea polyphenol on oxidative injury in S180 cells induced hepatocarcinoma mice.

The purpose of this study was to evaluate the antioxidant nature of tea polyphenol on S180 cells induced liver cancer in mice. In the present study, hepatocellular carcinoma was induced by tumor transplantation of liver in situ. The antitumor activity of tea polyphenol has been determined in vivo in hepatocellular carcinoma mice after treatment of drug (50, 100, 150 mg/kg body weight) by gavage for 20 days. Results showed that a significant increase in serum aspartate transaminase (AST), alkaline phosphatase (ALP), alanine aminotransfere (ALT), malondialdehyde (MDA) level, decrease in serum white blood cells (WBC), serum total protein (TP), albumin (ALB), A/G, tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ), liver reduced glutathione (GSH) levels were observed. In addition, the levels of enzymic and non-enzymic antioxidants were decreased when subjected to S180 cells induction. These altered enzyme levels were ameliorated significantly by administration of tea polyphenol at the concentration of 50, 100, 150 mg/kg body weight in drug-treated animals. These results indicate that the protective effect of tea polyphenol was associated with inhibition of MDA induced by S180 cells and to maintain the antioxidant enzyme levels.

Effect of ß-carotene on immunity function and tumour growth in hepatocellular carcinoma rats.

The aim of the present study was to investigate the anticancer and immunity activity of ß-carotene in hepatocellular carcinoma (HCC) rats. Three days after transplantation, forty Wistar rats were randomly divided into four groups, each group consisting of 10 animals. These groups were control group (untreated), low-dose ß-carotene-treated group (20 mg/kg), middle-dose group (40 mg/kg) and high-dose (60 mg/kg) group. ß-Carotene-treated groups were fed with ß-carotene (20, 40, 60 mg/kg b.w.) orally for 30 days. Control group was treated with the same volume of physiological saline. Another ten rats were served as the normal group. Results showed that 30 days of ß-carotene treatment could significantly inhibit tumour growth, enhance blood NK, IL-2, TNF-α, WBC, TP, ALB and A/G levels, and decrease blood ALT, AST and ALP activities in HCC rats. Pathological analysis of liver tissue showed that ß-carotene treatment may decrease damage of liver tissue in HCC rats. It can be concluded that ß-carotene may improve the immunity function and inhibit tumour growth in HCC rats.

Effects of Lycium barbarum aqueous and ethanol extracts on high-fat-diet induced oxidative stress in rat liver tissue.

This study evaluated the protective effects of aqueous extract of Lycium barbarum (LBAE) and ethanol extract of Lycium barbarum (LBEE) on blood lipid levels, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities and liver tissue antioxidant enzyme activities in rats fed a high fat diet (HF). The rats were randomly divided into seven groups of ten rats each and fed a different diet for eight weeks as follows: One group (NC group) was fed a standard diet, one group was fed a high-fat diet (HF group), one group was fed a high-fat diet and orally fed with 20 mg/kg b.w. simvastatin (HF + simvastatin group), and the other group was fed the high fat diet and orally fed with 50 mg/kg b.w. or 100 mg/kg b.w. LBAE (HF + LBAE), or 50 mg/kg b.w. or 100 mg/kg b.w. LBEE (HF + LBEE), respectively. After eight weeks, the HF diet caused deleterious metabolic effects. Rats fed the HF diet alone showed increased hepatocellular enzyme activities in plasma, a significant decline in antioxidant enzyme activities, and elevated liver lipid peroxidation indices. LBAE and LBEE administration significantly reduced liver damage and oxidative changes, and brought back the antioxidants and lipids towards normal levels. These data suggest that these antioxidants protect against toxicity parameters in HF rats.

ZC3H13 Inhibits the Progression of Hepatocellular Carcinoma through m6A-PKM2-Mediated Glycolysis and Enhances Chemosensitivity.

OBJECTIVE: N6-Methyladenosine (m6A) is the most prevalent RNA epigenetic modulation in eukaryotic cells, which serves a critical role in diverse physiological processes. Emerging evidences indicate the prognostic significance of m6A regulator ZC3H13 in hepatocellular carcinoma (HCC). Herein, this study was conducted for revealing biological functions and mechanisms of ZC3H13 in HCC. METHODS: Expression of ZC3H13 was examined in collected HCC and normal tissues, and its prognostic significance was investigated in a public database. Gain/loss of functional assays were presented for defining the roles of ZC3H13 in HCC progression. The specific interactions of ZC3H13 with PKM2 were validated in HCC cells via mRNA stability, RNA immunoprecipitation, and luciferase reporter and MeRIP-qPCR assays. Moreover, rescue experiments were carried out for uncovering the mechanisms. RESULTS: ZC3H13 expression was downregulated in HCC, and its loss was in relation to dismal survival outcomes. Functionally, overexpressed ZC3H13 suppressed proliferation, migration, and invasion and elevated apoptotic levels of HCC cells. Moreover, ZC3H13 overexpression sensitized to cisplatin and weakened metabolism reprogramming of HCC cells. Mechanically, ZC3H13-induced m6A modified patterns substantially abolished PKM2 mRNA stability. ZC3H13 facilitated malignant behaviors of HCC cells through PKM2-dependent glycolytic signaling. CONCLUSION: Collectively, ZC3H13 suppressed the progression of HCC through m6A-PKM2-mediated glycolysis and sensitized HCC cells to cisplatin, which offered a fresh insight into HCC therapy.

Design and Performance Study for Electrothermally Deep-Sea Drive Microunits Using a Paraffin Phase Change Material.

Considering the further exploration of the ocean, the requirements for deep-sea operation equipment have increased. Many problems existing in the widely used deep-sea hydraulic system have become increasingly prominent. Compared with the traditional deep-sea hydraulic system, actuators using a paraffin phase change material (PCM) have incomparable advantages, including lightweight structure, low energy consumption, high adaptability to the deep sea, and good biocompatibility. Thus, a deep-sea drive microunit (DDM) based on paraffin PCM is proposed in this paper. The device adopts a flexible shell, adapting to the high-pressure environment of the deep-sea based on the principle of pressure compensation. The device realizes the output of displacement and force through the electrothermal drive, which can be used as actuator or power source of other underwater operation equipment. The microunit successfully completes the functional verification experiments in air, shallow water, and hydrostatic pressure of 110 MPa. In accordance with experimental results, a reasonable control curve is fitted, highlighting its potential application in deep-sea micro electro mechanical systems, especially in underwater soft robot.

Experimental Study on the Coating Removing Characteristics of High-Pressure Water Jet by Micro Jet Flow.

In this paper, coating removal characteristics of water jet by micro jet flow affected by cleaning parameters is analyzed. Numerical simulation of fluid field calculates the velocity and pressure distribution of a water jet impinging on a rigid wall, which is used for design experiments of coating removal affected by jet pressure, traversal speed, and repeated impacting times. The removal width is used as a measure of water jet coating removal capability. Experiment results show that the coating removal width is constant, independent with traversal speed or repeated times when total exposure time of waterjet impingement is fixed. According to results of coating removal by a linear moving water jet, this study also analyzes characteristics of coating removal by rotating jet disc, especially residual coating affected by rotational and moving speed of the cleaning disc. The research is helpful to improve the coating removal efficiency of cleaning disc devices.