Evaluating the Intrinsic Zinc Storage Capacity of Cation-Preintercalated Cathode with Electrochemically Active Surface Area.

The guest cation preintercalation strategy has been widely adopted to improve the performance of zinc-vanadium batteries. However, existing studies always ignore the deintercalation of guest cations. This work focuses on the severe and universal deintercalation phenomenon and confirms the unaltered capacity after deintercalation, indicating that the capacity improvement mechanism cannot be attributed to the role of guest cations. Therefore, after excluding all of the previously researched factors for capacity improvement, the decisive factor is identified as the morphology (surface area). Based on the electrochemically active surface area (ECSA), a quantitative relationship with intrinsic capacity is established for the first time. This guides us to enhance battery capacity via enhancing ECSA through liquid-phase ultrasonic crushing to achieve the highest capacity of cation-preintercalated V2O5·nH2O (333.7 mAh g-1 at 10 A g-1). We believe that the enhanced ECSA is a plausible explanation for the improved performance of hydrated vanadium oxides.

Giant Cushioning Effect in Facile Polymer/Nanoclay-Coated Flexible Polyurethane Foams.

In this work, a flexible polyurethane (PU) foam/polymer/clay (PUF/PAASep) composite is prepared via a simple dip-coating method. The composite exhibits excellent damping properties under quasi-static compression, vibration transmissibility, and impact resistance. For the composite preparation, sepiolite (Sep) dispersion in a polyacrylic acid (PAA) solution is first homogenized and evaluated using microscopy, and the obtained PAASep suspension is used to coat the PU foam uniformly for optimization of the quasi-static mechanical performance of the foam composites. The PU foam struts coated with 1 wt % PAA and 3 wt % sepiolite are strengthened, resulting in an 8-fold improvement of the stiffness and three-times increase of the impact force resistance compared to the uncoated PU foams. More importantly, the PU foam composites show a remarkable vibration damping capability, with the loss modulus 57 times that of the uncoated PU foams, enabled by micro friction and stick-slip effects mediated by the PAASep coatings. The facile prepared PAASep-coated PU foams have significant potential for cushioning, packaging, and broad engineering applications involving energy absorption.

Rapid miRNA detection enhanced by exponential hybridization chain reaction in graphene field-effect transistors.

Scalable electronic devices that can detect target biomarkers from clinical samples hold great promise for point-of-care nucleic acid testing, but still cannot achieve the detection of target molecules at an attomolar range within a short timeframe (<1 h). To tackle this daunting challenge, we integrate graphene field-effect transistors (GFETs) with exponential target recycling and hybridization chain reaction (TRHCR) to detect oligonucleotides (using miRNA as a model disease biomarker), achieving a detection limit of 100 aM and reducing the sensing time by 30-fold, from 15 h to 30 min. In contrast to traditional linear TRHCR, our exponential TRHCR enables the target miRNA to initiate an autocatalytic system with exponential kinetics, significantly accelerating the reaction speed. The resulting reaction products, long-necked double-stranded polymers with a negative charge, are effectively detected by the GFET through chemical gating, leading to a shift in the Dirac voltage. Therefore, by monitoring the magnitude of this voltage shift, the target miRNA is quantified with high sensitivity. Consequently, our approach successfully detects 22-mer miRNA at concentrations as low as 100 aM in human serum samples, achieving the desired short timeframe of 30 min, which is congruent with point-of-care testing, and demonstrates superior specificity against single-base mismatched interfering oligonucleotides.

Effect of Strain Engineering on the Spin State of the Ni-N4/C Single-Atom Catalyst and Its Consequence in Electrocatalysis.

Strain engineering is an effective strategy to improve the activity of catalysts, especially for flexible carbon-based materials. Nitrogen-coordinated single atomic metals on a carbon skeleton (M-Nx/C) are of interest in catalytic electroreduction reactions due to their high activity and atomic utilization. However, the effect of strain on the structure-activity relationship between the electrochemical activity and the electronic and geometric structures of Ni-Nx/C remains unclear. Here, we found that by applying tensile strain on the Ni-N4/C, the spin state of the single atom can be changed from a low-spin to a high-spin state. Moreover, the energy gap between the highest occupied d orbital of Ni and the lowest unoccupied molecular orbital of the adsorbed species narrowed. With an increasing strain rate, the catalytic activity of O2 and CO2 electroreduction can be improved. Especially for the 2e- O2 reduction, the implicit solvent model, constant-potential method, and microkinetic model were used to verify the positive effect of suitable stretching on the catalytic activity from thermodynamic and kinetic viewpoints. This work can reveal the relationship between strain, spin state, and the catalytic activity of Ni-Nx/C.

A rapid-response soft end effector inspired by the hummingbird beak.

Biology is a wellspring of inspiration in engineering design. This paper delves into the application of elastic instabilities-commonly used in biological systems to facilitate swift movement-as a power-amplification mechanism for soft robots. Specifically, inspired by the nonlinear mechanics of the hummingbird beak-and shedding further light on it-we design, build and test a novel, rapid-response, soft end effector. The hummingbird beak embodies the capacity for swift movement, achieving closure in less than [Formula: see text]. Previous work demonstrated that rapid movement is achieved through snap-through deformations, induced by muscular actuation of the beak's root. Using nonlinear finite element simulations coupled with continuation algorithms, we unveil a representative portion of the equilibrium manifold of the beak-inspired structure. The exploration involves the application of a sequence of rotations as exerted by the hummingbird muscles. Specific emphasis is placed on pinpointing and tailoring the position along the manifold of the saddle-node bifurcation at which the onset of elastic instability triggers dynamic snap-through. We show the critical importance of the intermediate rotation input in the sequence, as it results in the accumulation of elastic energy that is then explosively released as kinetic energy upon snap-through. Informed by our numerical studies, we conduct experimental testing on a prototype end effector fabricated using a compliant material (thermoplastic polyurethane). The experimental results support the trends observed in the numerical simulations and demonstrate the effectiveness of the bio-inspired design. Specifically, we measure the energy transferred by the soft end effector to a pendulum, varying the input levels in the sequence of prescribed rotations. Additionally, we demonstrate a potential robotic application in scenarios demanding explosive action. From a mechanics perspective, our work sheds light on how pre-stress fields can enable swift movement in soft robotic systems with the potential to facilitate high input-to-output energy efficiency.

Isolated Octahedral Pt-Induced Electron Transfer to Ultralow-Content Ruthenium-Doped Spinel Co3O4 for Enhanced Acidic Overall Water Splitting.

The development of a highly active and stable oxygen evolution reaction (OER) electrocatalyst is desirable for sustainable and efficient hydrogen production via proton exchange membrane water electrolysis (PEMWE) powered by renewable electricity yet challenging. Herein, we report a robust Pt/Ru-codoped spinel cobalt oxide (PtRu-Co3O4) electrocatalyst with an ultralow precious metal loading for acidic overall water splitting. PtRu-Co3O4 exhibits excellent catalytic activity (1.63 V at 100 mA cm-2) and outstanding stability without significant performance degradation for 100 h operation. Experimental analysis and theoretical calculations indicate that Pt doping can induce electron transfer to Ru-doped Co3O4, optimize the absorption energy of oxygen intermediates, and stabilize metal-oxygen bonds, thus enhancing the catalytic performance through an adsorbate-evolving mechanism. As a consequence, the PEM electrolyzer featuring PtRu-Co3O4 catalyst with low precious metal mass loading of 0.23 mg cm-2 can drive a current density of 1.0 A cm-2 at 1.83 V, revealing great promise for the application of noniridium-based catalysts with low contents of precious metal for hydrogen production.

Engineering Mn Vacancies to Enhance Ion Kinetics in Layered Manganese Silicate for High-Energy and Durable Intercalation Pseudocapacitance.

Transition metal silicates (TMSs) are potential electrodes for aqueous metal-ion intercalation pseudocapacitors owing to their superior theoretical capacity and high structural stability. However, the narrow interlayer spacing and intrinsic inert basal plane of TMSs lead to sluggish ions and charge transfer, causing an undesirable energy storage performance. Herein, rich Mn vacancies are introduced in layered manganous silicates (M2-xS@FA) to expedite K+ diffusion, while enhancing charge storage capacity and prolonging lifespan. In situ characterizations validate the K+ intercalation pseudocapacitance mechanism with evident crystal structure and valence state variations in M2-xS@FA. Both theoretical calculations and electrochemical experimental evaluations elucidate the imperative role of Mn vacancies in enhancing K+ diffusion kinetics and electron transfer through increased interlayer spacing and activated basal plane. Mn vacancies further boost the charge storage capacity by providing additional K+ storage sites, while simultaneously reinforcing local atomic bonding within M2-xS@FA, thereby augmenting structural stability. The assembled aqueous asymmetric solid-state cell, featuring a M2-xS@FA cathode, demonstrates exceptional power and energy densities (144.08 W h kg-1 at 375.80 W kg-1) and ultralong lifespan (100% capacity retention after 10,000 cycles). This work heralds a paradigm whereby modulating cation vacancies in layered TMSs significantly enhances K+ storage and stability for high-energy intercalation pseudocapacitance.

Prognostic Value and Immune Landscapes of Four Types of RNA Modification Writer-Related LncRNAs Signature in Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the predominant pathological subtype of non-small cell lung cancer (NSCLC). The four primary forms of RNA adenosine modifications, N6-methyladenosine (m6A), N1-methyladenosine (m1A), alternative polyadenylation (APA) and adenosine-to-inosine (A-to-I) RNA editing, play a critical role in tumor progression. However, the clinical significance of RNA modification writer-related long non-coding RNAs (lncRNAs) in LUAD remains unclear. Methods: The Cancer Genome Atlas (TCGA) database was used to obtain transcriptomic and clinicopathological data. Univariate Cox regression analysis, consensus cluster analysis, and least absolute shrinkage and selection operator (LASSO) Cox regression were used to establish the molecular subtypes and prognostic signatures of LUAD based on the expression levels of lncRNAs. ESTIMATE, CIBERSORT, ssGSEA, and TIDE algorithms were used to investigate immune cell infiltration and immunotherapy. In addition, IC50 of chemotherapeutic agents were calculated for different risk subgroups using the "pRRophetic" R package. Finally, the expression of prognosis-associated lncRNAs in lung cancer tissues was verified using qPCR. Results: A prognostic risk signature containing seven lncRNAs associated with four types of RNA modification writers was established. The high-risk group had a poorer prognosis and higher clinicopathological grade. Most immune checkpoint genes and immune cell infiltration differed significantly between the two risk groups. The high-risk group had a higher tumor mutation burden (TMB), lower TIDE score, and was more sensitive to immunotherapy. Conclusion: We developed an RNA modification writer-related seven-lncRNA signature prognostic model that was associated with prognosis, tumor microenvironment, and response to immunotherapy in LUAD patients. Among them, LINC01352, AC024075.1, AC005070.3, AL133445.2, AC005856.1, and LINC00968 were downregulated in LUAD, whereas AC092168.2 was upregulated. This model may be a valuable tool for personalized LUAD therapies.

[Role and Mechanism of Lactylation in Cancer].

Post translational modifications (PTMs) can change the properties of a protein by covalent addition of functional groups to one or more amino acids, and influence almost all aspects of normal cell biology and pathogenesis. Lactylation is a novel identified PTM, and has been found in both histone and non-histone proteins. Since associated with the end product of glycolysis-- lactate, lactylation modification could provide a new perspective for understanding the relationship between metabolic reprogramming and epigenetic modifications. Accumulated evidences suggest that lactylation play important roles in tumor progression and links to poor prognosis in clinical studies. Histone lactylation can affect gene expression in tumor cells and immunological cells, further promoting tumor progression and immune suppression. Lactylation on non-histone proteins can also regulate tumor progression and drug resistance. In this review, we aimed to summarize the roles of lactylation in cancer progression, microenvironment interactions and immune suppression, try to identify new molecular targets for cancer therapy and provide a new direction for combined targeted therapy and immunotherapy.
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Construction and Observation of Flexibly Controllable High-Dimensional Non-Hermitian Skin Effects.

Non-Hermitian skin effect (NHSE) is one of the most fundamental phenomena in non-Hermitian physics. It is established that 1D NHSE originates from the nontrivial spectral winding topology. However, the topological origin behind the higher-dimensional NHSE remains unclear, which poses a substantial challenge in constructing and manipulating high-dimensional NHSEs. Here, an intuitive bottom-to-top scheme to construct high-dimensional NHSEs is proposed, through assembling multiple independent 1D NHSEs. Not only the elusive high-dimensional NHSEs can be effectively predicted from the well-defined 1D spectral winding topologies, but also the high-dimensional generalized Brillouin zones can be directly synthesized from the 1D counterparts. As examples, two 2D nonreciprocal acoustic metamaterials are experimentally implemented to demonstrate highly controllable multi-polar NHSEs and hybrid skin-topological effects, where the sound fields can be frequency-selectively localized at any desired corners and boundaries. These results offer a practicable strategy for engineering high-dimensional NHSEs, which can boost advanced applications such as selective filters and directional amplifiers.

Discovery of Higher-Order Nodal Surface Semimetals.

The emergent higher-order topological insulators significantly deepen our understanding of topological physics. Recently, the study has been extended to topological semimetals featuring gapless bulk band nodes. To date, higher-order nodal point and line semimetals have been successfully realized in different physical platforms. However, for the conceptually expected higher-order nodal surface semimetals, a concrete model has yet to be proposed, let alone experimentally observed. Here, we report an ingenious design route for constructing this unprecedented higher-order topological phase. The three-dimensional model, layer-stacked with a two-dimensional anisotropic Su-Schrieffer-Heeger lattice, exhibits appealing hinge arcs connecting the projected nodal surfaces. Experimentally, we realize this new topological phase in an acoustic metamaterial, and present unambiguous evidence for both the bulk nodal structure and hinge arc states, the two key manifestations of the higher-order nodal surface semimetal. Our findings can be extended to other classical systems such as photonic, elastic, and electric circuit systems, and open new possibilities for controlling waves.

High LGALS3 expression induced by HCP5/hsa-miR-27b-3p correlates with poor prognosis and tumor immune infiltration in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is widely recognized for its unfavorable prognosis. Increasing evidence has revealed that LGALS3 has an essential function in initiating and developing several malignancies in humans. Nevertheless, thorough analysis of the expression profile, clinical prognosis, pathway prediction, and immune infiltration of LGALS3 has not been fully explored in HCC. METHODS: In this study, an initial pan-cancer analysis was conducted to investigate the expression and prognosis of LGALS3. Following a comprehensive analysis, which included expression analysis and correlation analysis, noncoding RNAs that contribute to the overexpression of LGALS3 were subsequently identified. This identification was further validated using HCC clinical tissue samples. TIMER2 and GEPIA2 were employed to examine the correlation between LGALS3 and HCP5 with immunological checkpoints, cell chemotaxis, and immune infiltration in HCC. The R program was applied to analyze the expression distribution of immune score in in HCC patients with high and low LGALS3 expression. The expression profiles of immune checkpoints were also analyzed. Use R to perform GSVA analysis in order to explore potential signaling pathways. RESULTS: First, we conducted pan-cancer analysis for LGALS3 expression level through an in-depth analysis of public databases and found that HCC has a high LGALS3 gene and protein expression level, which were then verified in clinical HCC specimens. Meanwhile, high LGALS3 gene expression is related to malignant progression and poor prognosis of HCC. Univariate and multivariate analyses confirmed that LGALS3 could serve as an independent prognostic marker for HCC. Next, by combining comprehensive analysis and validation on HCC clinical tissue samples, we hypothesize that the HCP5/hsa-miR-27b-3p axis could serve as the most promising LGALS3 regulation mechanism in HCC. KEGG and GO analyses highlighted that the LGALS3-related genes were involved in tumor immunity. Furthermore, we detected a significant positive association between LGALS3 and HCP5 with immunological checkpoints, cell chemotaxis, and immune infiltration. In addition, high LGALS3 expression groups had significantly higher immune cell scores and immune checkpoint expression levels. Finally, GSVA analysis was performed to predict potential signaling pathways linked to LGALS3 and HCP5 in immune evasion and metabolic reprogramming of HCC. CONCLUSIONS: Our findings indicated that the upregulation of LGALS3 via the HCP5/hsa-miR-27b-3p axis is associated with unfavorable prognosis and increased tumor immune infiltration in HCC.

Stiffness promotes cell migration, invasion, and invadopodia in nasopharyngeal carcinoma by regulating the WT-CTTN level.

Matrix stiffness potently promotes the malignant phenotype in various biological contexts. Therefore, identification of gene expression to participate in mechanical force signals transduced into downstream biochemical signaling will contribute substantially to the advances in nasopharyngeal carcinoma (NPC) treatment. In the present study, we detected that cortactin (CTTN) played an indispensable role in matrix stiffness-induced cell migration, invasion, and invadopodia formation. Advances in cancer research have highlighted that dysregulated alternative splicing contributes to cancer progression as an oncogenic driver. However, whether WT-CTTN or splice variants (SV1-CTTN or SV2-CTTN) regulate matrix stiffness-induced malignant phenotype is largely unknown. We proved that alteration of WT-CTTN expression modulated matrix stiffness-induced cell migration, invasion, and invadopodia formation. Considering that splicing factors might drive cancer progression through positive feedback loops, we analyzed and showed how the splicing factor PTBP2 and TIA1 modulated the production of WT-CTTN. Moreover, we determined that high stiffness activated PTBP2 expression. Taken together, our findings showed that the PTBP2-WT-CTTN level increases upon stiffening and then promotes cell migration, invasion, and invadopodia formation in NPC.

FGF19 promotes nasopharyngeal carcinoma progression by inducing angiogenesis via inhibiting TRIM21-mediated ANXA2 ubiquitination.

PURPOSE: Nasopharyngeal carcinoma (NPC) has characteristics of high invasion and early metastasis. Most NPC patients present with locoregionally advanced illness when first diagnosed. Therefore, it is urgent to discover NPC biomarkers. Fibroblast growth Factor 19 (FGF19) plays a role in various physiological or pathological processes, including cancer. In this research, we discovered the importance of FGF19 in NPC, and clarified its role in tumour angiogenesis. METHODS: Western blotting, immunohistochemistry and ELISA were used to investigate FGF19 expression in NPC. Then we took CCK8, colony formation, Transwell and wound healing assays to identify the influence of FGF19 on NPC malignant behaviours. The proliferative and metastatic capacity of FGF19 were evaluated in nude mice and zebrafish. The role of FGF19 in angiogenesis was investigated by tube formation and Matrigel plug angiogenesis assays. We then evaluated the variation in Annexin A2(ANXA2) levels with the treatment of FGF19. Lastly, co-immunoprecipitation and ubiquitination assays were performed to identify the mechanisms involved. RESULTS: FGF19 levels were elevated in tissues and serum of NPC patients and were associated with poor clinical stages. High expression of FGF19 promoted NPC malignant behaviours. In particular, FGF19 expression was correlated with microvessel density in tissues and NPC-derived FGF19 could accelerate angiogenesis in vitro and in vivo. Mechanistically, FGF19 influenced ANXA2 expression to promote angiogenesis. Moreover, tripartite motif-containing 21(TRIM21) interacted with ANXA2 and was responsible for ANXA2 ubiquitination. CONCLUSION: FGF19 promoted NPC angiogenesis by inhibiting TRIM21-mediated ANXA2 ubiquitination. It may serve as a noninvasive biomarker for NPC and provides new insights for therapy.

N-Terminalized Ti3 C2 Tx MXene for Supercapacitor with Extraordinary Pseudocapacitance Performance.

MXenes have demonstrated significant potential in electrochemical energy storage, particularly in supercapacitors, owing to their exceptional properties. The surface terminal groups of MXene play a pivotal role in pseudocapacitive mechanism. Considering the hindered electrolyte ion transport caused by -F terminal groups and the limited ion binding sites associated with -O terminal groups, this study proposes a novel strategy of replacing -F with -N terminal groups. The modulated MXene-N electrode, featuring a substantial number of -N terminal groups, demonstrates an exceptionally high gravimetric capacitance of 566 F g-1 (at a scan rate of 2 mV s-1 ) or 588 F g-1 (at a discharge rate of 1 A g-1 ) in 1 м H2 SO4 electrolyte, and the potential window is significantly increased. Furthermore, subsequent spectra analysis and density functional theory calculations are employed to investigate the mechanism associated with -N terminal groups. This work exemplifies the significance of terminal modulation in the context of electrochemical energy storage.

Phenethyl isothiocyanate inhibits metastasis potential of non-small cell lung cancer cells through FTO mediated TLE1 m6A modification.

N6-methyladenosine (m6A) modification is a prevalent RNA epigenetic modification, which plays a crucial role in tumor progression including metastasis. Isothiocyanates (ITCs) are natural compounds and inhibit the tumorigenesis of various cancers. Our previous studies show that ITCs inhibit the proliferation and metastasis of non-small cell lung cancer (NSCLC) cells, and have synergistic effects with chemotherapy drugs. In this study, we investigated the molecular mechanisms underlying the inhibitory effects of ITCs on cancer cell metastasis. We showed that phenethyl isothiocyanate (PEITC) dose-dependently inhibited the cell viability of both NSCLC cell lines H1299 and H226 with IC50 values of 17.6 and 15.2 µM, respectively. Furthermore, PEITC dose-dependently inhibited the invasion and migration of H1299 and H226 cells. We demonstrated that PEITC treatment dose-dependently increased m6A methylation levels and inhibited the expression of the m6A demethylase fat mass and obesity-associated protein (FTO) in H1299 and H226 cells. Knockdown of FTO significantly increased m6A methylation in H1299 and H226 cells, impaired their abilities of invasion and migration in vitro, and enhanced the inhibition of PEITC on tumor growth in vivo. Overexpression of FTO promoted the migration of NSCLC cells, and also mitigated the inhibitory effect of PEITC on migration of NSCLC cells. Furthermore, we found that FTO regulated the mRNA m6A modification of a transcriptional co-repressor Transducin-Like Enhancer of split-1 (TLE1) and further affected its stability and expression. TCGA database analysis revealed TLE1 was upregulated in NSCLC tissues compared to normal tissues, which might be correlated with the metastasis status. Moreover, we showed that PEITC suppressed the migration of NSCLC cells by inhibiting TLE1 expression and downstream Akt/NF-κB pathway. This study reveals a novel mechanism underlying ITC's inhibitory effect on metastasis of lung cancer cells, and provided valuable information for developing new therapeutics for lung cancer by targeting m6A methylation.

Effects of adding steel slag on humification and characteristics of bacterial community during phosphate-amended composting of municipal sludge.

This study aimed to investigate the effects of different proportions (0%, 5%, 7.5%, and 10%) of steel slag (SS) on humification and bacterial community characteristics during phosphate-amended composting of municipal sludge. Compared with adding KH2PO4 alone, co-adding SS significantly promoted the temperature, pH, nitrification, and critical enzyme activities (polyphenol oxidase, cellulase, laccase); especially organic matter (OM) degradation rate (25.5%) and humification degree (1.8) were highest in the 5%-SS treatment. Excitation-emission matrix-parallel factor confirmed that co-adding SS could promote the conversion of protein-like substances or microbial by-products into humic-like substances. Furthermore, adding 5%-SS significantly improved the relative abundances of Actinobacteria, Firmicutes and the genes related to carbohydrate and amino acid metabolism, and enhanced the interactions of bacterial community in stability and complexity. The partial least squares path model indicated that OM was the primary factor affecting humification. These results provided a promising strategy to optimize composting of municipal sludge via SS.

Experimental Investigation of Wave Propagation Characteristics in Entangled Metallic Wire Materials by Acoustic Emission.

In this paper, the response characteristics of wave propagation in entangled metallic wire materials (EMWMs) are investigated by acoustic emission. The frequency, amplitude of wave emission, and the pre-compression force of the specimen can be adjusted in the experimental setup. EMWM specimens fabricated from stainless steel wires and with different design parameters are tested in this work. The results show that waves of different amplitudes propagate in EMWMs with approximate linear characteristics and the fluctuation coefficient of wave passing ratios is calculated below 15%. The response spectrum of passing waves shows a distinct single-peak characteristic, with the peak response at approximately 14 kHz. The parameters of pre-compression force, porosity, wire diameter, helix diameter, specimen height, and the layered structure of specimens have no significant effect on the frequency characteristics but moderately affect the wave passing ratios. Notably, EMWMs exhibit a lower wave passing ratio (ranging from 0.01 to 0.18) compared to aluminum alloy and natural rubber. The characteristics of response spectrums can be successfully reproduced by the finite element simulation. This work demonstrates EMWMs' potential as an acoustic frequency vibration isolation material, offering excellent performance and engineering design convenience.

The role of regulators of RNA m6A methylation in lung cancer.

N6-methyladenosine (m6A) modification is found the most prevalent and abundant post-transcriptional mRNA modification in eukaryotic cells. It regulates almost all stages of RNA life cycle including splicing, translocation, stability, decay and translation. As a dynamic and reversible process, m6A modification is catalyzed by the RNA methyltransferases ('writers'), removed by the demethylases ('erasers'), and interacts with m6A-binding proteins ('readers'). Recent studies have revealed that these m6A modification regulators are frequently expressed aberrantly in various types of cancer, and involved in cell proliferation, differentiation, metabolism, particularly, in tumorigenesis and tumor progression through diverse mechanisms. In this review, the m6A modification process and its regulatory functions in lung cancer are summarized. Furthermore, the research progress in the inhibitor development of m6A modification, and the potential of targeting m6A modifying proteins for clinical application are discussed.

Cancer-associated fibroblasts promote migration and invasion of non-small cell lung cancer cells via METTL3-mediated RAC3 m6A modification.

Cancer progression depends on the communication between tumor cells and tumor microenvironment. Cancer-associated fibroblasts (CAFs) are a major component of stromal cells. CAFs promote cancer metastasis; however, it has not been evaluated whether N6-methyladenosine (m6A) modification is responsible for CAFs' role in metastasis. In the present study, we found that CAFs promoted migration and invasion of non-small cell lung cancer (NSCLC) cells by elevating m6A modification in NSCLC cells. Methyltransferase-like 3 (METTL3) in NSCLC cells mediated CAFs' effect on m6A modification, and was regulated by CAFs-secreted vascular endothelial growth factor A (VEGFA). METTL3 knockdown in NSCLC cells dramatically inhibited cell migration and invasion, and suppressed tumor growth in vivo. Database analysis revealed that METTL3 was associated with poor prognosis of lung cancer. The mechanism study showed that METTL3 increased m6A level of RAC3 mRNA, resulting in increased stability and translation of RAC3 mRNA. RAC3 was responsible for the CAFs' promoting effect on cell migration via the AKT/NF-κB pathway. This study established a CAF-METTL3-RAC3 m6A modification-dependent regulation system in NSCLC metastasis, suggesting potential candidates for metastasis treatment.