Multiple Processing Steps Research Articles

The impact of microRNAs on alterations of gene regulatory networks in allergic diseases.

Allergic diseases including asthma are worldwide on the rise and contribute significantly to health expenditures. Allergic diseases are prototypic diseases with a strong gene by environment interaction component and epigenetic mechanisms might mediate the effects of the environment on the disease phenotype. MicroRNAs, small non-coding RNAs (miRNAs), regulate gene expression post-transcriptionally. Functional single-stranded miRNAs are generated in multiple steps of enzymatic processing from their precursors and mature miRNAs are included into the RNA-induced silencing complex (RISC). They imperfectly base-pair with the 3'UTR region of targeted genes leading to translational repression or mRNA decay. The cellular context and microenvironment as well the isoform of the mRNA control the dynamics and complexity of the regulatory circuits induced by miRNAs that regulate cell fate decisions and function. MiR-21, miR-146a/b and miR-155 are among the best understood miRNAs of the immune system and implicated in different diseases including allergic diseases. MiRNAs are implicated in the induction of the allergy reinforcing the Th2 phenotype (miR-19a, miR-24, miR-27), while other miRNAs promote regulatory T cells associated with allergen tolerance or unresponsiveness. In the current chapter we describe in detail the biogenesis and regulatory function of miRNAs and summarize current knowledge on miRNAs in allergic diseases and allergy relevant cell fate decisions focusing mainly on immune cells. Furthermore, we evoke the principles of regulatory loops and feedback mechanisms involving miRNAs on examples with relevance for allergic diseases. Finally, we show the potential of miRNAs and exosomes containing miRNAs present in several biological fluids that can be exploited with non-invasive procedures for diagnostic and potentially therapeutic purposes.

New Frontier: Role of the Radiologist in Uterine Transplantation.

Uterine transplantation (UT) is a novel treatment for absolute uterine factor infertility (AUFI) that is currently being performed under experimental protocols in multiple medical centers worldwide. At the time of this publication, there have been at least 10 live births by women with a transplanted uterus. As successful outcomes from this innovative procedure increase, it is likely that more centers will perform UT. Imaging is performed in multiple steps of the UT process, including preoperative imaging of potential donors and recipients, posttransplant surveillance, and monitoring of pregnancy. Fetal imaging is performed by maternal-fetal medicine professionals, but most imaging examinations in UT are performed by radiologists. Given the significant role of imaging in this groundbreaking surgery, radiologists must be familiar with the causes of AUFI and the role of imaging in establishing this diagnosis. Radiologists working in medical centers where UT is performed should understand the role of imaging in preoperative planning and postoperative surveillance. While data regarding complications of UT are preliminary at best, radiologists must be aware of the risk of vascular compromise and graft failure and their imaging features. The authors provide a brief history of UT and define the radiologist's role in pre- and postoperative imaging assessments.©RSNA, 2019.

Rapid synthesis of dielectric tantalum-based oxynitrides

Perovskite-type oxynitride with a general formula of ATa(O,N)3 (A = Sr, Ba) is a class of promising dielectric material due to their very high permittivity. Conventional synthesis routes for these materials always require multiple processing steps, long durations and elevated temperatures. In this study, thermodynamic calculations were employed to predict the feasible synthesis reactions, possible impurities and reasonable processing parameters. Then, ceramic powders of SrTaO2N and BaTaO2N were fabricated through direct calcination of SrCO3/BaCO3 and Ta2O5 with urea as nitrogen source by using a modified pressureless spark plasma sintering set-up. High-purity oxynitrides can be obtained within 10 min. Thermal stability, corrosion resistance and dielectric property were evaluated. The results showed that SrTaO2N was thermally stable up to 475 °C in air while that temperature for BaTaO2N was 605 °C. The oxynitrides possessed a good resistance to hot water and strong acid/alkali. BaTaO2N had a very high room-temperature relative permittivity up to 9550 with a dielectric loss down to 0.001 at 100 Hz, while the values for SrTaO2N were 3141 and 0.017 respectively. The temperature dependence of permittivity for BaTaO2N was weak at −10–200 °C. The efficient synthesis method enabled the fast preparation of the tantalum-based oxynitride materials for energy storage applications.

RNASeqR: An R Package for Automated Two-Group RNA-Seq Analysis Workflow.

RNA-Seq analysis has revolutionized researchers' understanding of the transcriptome in biological research. Assessing the differences in transcriptomic profiles between tissue samples or patient groups enables researchers to explore the underlying biological impact of transcription. RNA-Seq analysis requires multiple processing steps and huge computational capabilities. There are many well-developed R packages for individual steps; however, there are few R/Bioconductor packages that integrate existing software tools into a comprehensive RNA-Seq analysis and provide fundamental end-to-end results in pure R environment so that researchers can quickly and easily get fundamental information in big sequencing data. To address this need, we have developed the open source R/Bioconductor package, RNASeqR. It allows users to run an automated RNA-Seq analysis with only six steps, producing essential tabular and graphical results for further biological interpretation. The features of RNASeqR include: six-step analysis, comprehensive visualization, background execution version, and the integration of both R and command-line software. RNASeqR provides fast, light-weight, and easy-to-run RNA-Seq analysis pipeline in pure R environment. It allows users to efficiently utilize popular software tools, including both R/Bioconductor and command-line tools, without predefining the resources or environments. RNASeqR is freely available for Linux and macOS operating systems from Bioconductor (https://bioconductor.org/packages/release/bioc/html/RNASeqR.html).

One-pot fabrication of polymer micro/nano-discs via phase separation and a roll-to-roll coating process

Disc-shaped particles are one of the unique and promising shapes that can improve adhesion to interfaces and can function as the key feature in various applications; e.g. injectable drug carriers. However, most of these methods include the shape deformation process from spheres to discs using various external stimuli or require multiple processing steps, which is complicated and has limitations in terms of continuous fabrication. We herein propose a novel method combining polymer blend phase separation and a roll-to-roll coating process to continuously fabricate polymer micro/nano-discs in a one-pot manner on a large-scale. The evaporation of solvent during a roll-to-roll coating process encourages the formation of homogenous island-like domains composed of the minor component dispersed in a matrix of the major component on a water-soluble polyvinyl alcohol (PVA) film. In fact, polyvinylpyrrolidone (PVP) was chosen as the major component since it dissolves in both water and chloroform. Another polymer, polystyrene (PS), as a minor component was dissolved in chloroform with PVP. A PVP and PVA matrix film can be easily washed out by water, and micro/nano-discs of the PS minor component can be obtained in a one-pot manner. This method is shown to be capable of continuously fabricating PS micro/nano-discs at a very high rate of ∼108 particles/min. The effects of fabrication conditions, such as the blend ratio and total polymer concentration on the dimensions of the PS discs were investigated, and a maximum aspect ratio (ratio between diameter and thickness) of 6.3 (diameter ∼830 nm, thickness ∼130 nm) was demonstrated. The method proposed in this study could provide a straightforward and time-saving way to continuously fabricate micro/nano-discs via polymer phase separation and a roll-to-roll coating process.

Single-nucleotide control of tRNA folding cooperativity under near-cellular conditions

RNA folding is often studied by renaturing full-length RNA in vitro and tracking folding transitions. However, the intracellular transcript folds as it emerges from the RNA polymerase. Here, we investigate the folding pathways and stability of numerous late-transcriptional intermediates of yeast and Escherichia coli transfer RNAs (tRNAs). Transfer RNA is a highly regulated functional RNA that undergoes multiple steps of posttranscriptional processing and is found in very different lengths during its lifetime in the cell. The precursor transcript is extended on both the 5' and 3' ends of the cloverleaf core, and these extensions get trimmed before addition of the 3'-CCA and aminoacylation. We studied the thermodynamics and structures of the precursor tRNA and of late-transcriptional intermediates of the cloverleaf structure. We examined RNA folding at both the secondary and tertiary structural levels using multiple biochemical and biophysical approaches. Our findings suggest that perhaps nature has selected for a single-base addition to control folding to the functional 3D structure. In near-cellular conditions, yeast tRNAPhe and E. coli tRNAAla transcripts fold in a single, cooperative transition only when nearly all of the nucleotides in the cloverleaf are transcribed by indirectly enhancing folding cooperativity. Furthermore, native extensions on the 5' and 3' ends do not interfere with cooperative core folding. This highly controlled cooperative folding has implications for recognition of tRNA by processing and modification enzymes and quality control of tRNA in cells.

Quantifying and Qualifying Alloys Based on Level of Homogenization: A U-10Mo Alloy Case Study

Abstract Homogenization heat treatment is performed to attain uniformity in microstructure which is helpful to achieve the desired workability and microstructure in final products and, eventually, to gain predictive and consistent performance. Fabrication of low-enriched uranium alloys with 10 wt% molybdenum (U-10Mo) fuel plates involves multiple thermomechanical processing steps. It is well known that the molybdenum homogeneity in the final formed product affects the performance in the nuclear reactor. To ensure uniform homogenization, a statistical method is proposed to quantify and characterize the molybdenum concentration variation in U-10Mo fuel plates by analyzing the molybdenum concentration measurement data from scanning electron microscopy energy dispersive spectroscopy line-scan. Statistical tolerance intervals (TI) are employed to determine the qualification of the U-10Mo fuel plate. We formulate an argument for the minimum number of independent samples to define fuel plate qualification if no molybdenum measurement data are available in advance and demonstrate that the given TI requirements can be equivalently reduced to a sample variance criterion in this application. The outcome of the statistical analysis can be used to optimize casting design and eventually increase productivity and reduce fabrication costs. The statistical strategy developed in this paper can be implemented for other applications especially in the field of material manufacturing to assess qualification requirements and monitor and improve the process design.

Intricate SUMO-based control of the homologous recombination machinery

The homologous recombination (HR) machinery plays multiple roles in genome maintenance. Best studied in the context of DNA double-stranded break (DSB) repair, recombination enzymes can cleave, pair, and unwind DNA molecules, and collaborate with regulatory proteins to execute multiple DNA processing steps before generating specific repair products. HR proteins also help to cope with problems arising from DNA replication, modulating impaired replication forks or filling DNA gaps. Given these important roles, it is not surprising that each HR step is subject to complex regulation to adjust repair efficiency and outcomes as well as to limit toxic intermediates. Recent studies have revealed intricate regulation of all steps of HR by the protein modifier SUMO, which has been increasingly recognized for its broad influence in nuclear functions. This review aims to connect established roles of SUMO with its newly identified effects on recombinational repair and stimulate further thought on many unanswered questions.

Evaluating the Potential of Semi-Automated Image Analysis for Delimiting Soil and Sediment Layers

ABSTRACTEstablished methods for delineating anthropogenic and natural strata during fieldwork are based on the visual and tactile perception of excavators. Modern image analysis techniques can help to ensure objectivity and reproducibility when documenting sections and plana. Within this study we examine the unsupervised classification of digital images as a technique for delimiting layers and identifying stratigraphic features. Assessing the potential of this approach, we exemplarily captured soil profiles with high-contrast stratigraphy, located in the area of a historical vineyard (Brandenburg, Germany). Reproducible analyses were carried out using open-source software, allowing for the future advancement of the methodology utilized and providing a basis for the analysis of more complex stratigraphic sequences. We compare clustering results of high-resolution RGB and hyperspectral images (470–830 nm, 37 bands). Multiple pre-processing and processing steps are carried out to evaluate their influence. Our results render the semi-automatic analysis of RGB images helpful for stratigraphic interpretation.

Applications and considerations for the use of genetically engineered mouse models in drug development.

Considering high drug attrition rates in clinical studies and the overall complexity and challenging environment of drug development, it is increasingly important to understand the therapeutic molecule and target and how they intersect with disease biology as fully as possible. This requires one to use numerous tools and investigative approaches in combination. Genetically engineered mouse models are a critical component to the drug development toolbox as they can provide key insights across multiple steps of the drug development process. While knock-out and knock-in mice can inform questions of basic biology, genetically engineered mice can also be applied to model diseases for efficacy studies, to discriminate on-target and off-target effects of novel therapeutics, and to inform an array of biologic and pharmacologic questions, including pharmacodynamics, pharmacokinetics, and biomarker discovery. However, use of these models requires not only an understanding of their strengths and limitations but also a careful consideration of the context in which they are being used and the hypotheses being addressed by them. Additionally, they should not be used in isolation, but instead in combination with other biochemical, in vitro, and clinical data to create a broad understanding of the drug, target, and disease biology.

(Invited) Accelerating Optimization of Lithium Ion Battery Manufacturing Via Multiscale Computations

Electrochemical performance and lifetime of Lithium Ion Battery (LIB) composite electrodes strongly depend on their manufacturing parameters. Such parameters include the slurry formulation (i.e. the chemistry and amount of active material, carbon, binder and solvent), the temperature used to evaporate the solvent, the pressure applied during the electrode calendering and the time for the electrolyte impregnation. Within the perspective of developing more efficient LIBs at minimal R&D cost, it is important to develop robust tools able to predict the influence of manufacturing parameters on the electrodes mesostructure and the overall cell performance. In this keynote, i discuss the latest research progress in this sense within the ARTISTIC project, funded by the European Research Council (ERC). This project aims at developing and demonstrating a multiscale computational platform able to simulate the LIB manufacturing process and to predict optimal manufacturing parameters of LIBs responding to specific targets (energy density, etc.). Coarse Grained Molecular Dynamics, Discrete Element Method, Lattice Boltzmann and Continuum computational models are combined with deep learning algorithms to reach this objective. Examples of applications of this platform for NMC and graphite-based electrodes are discussed, in strong link with in house experimental characterizations. Physicochemical mechanisms leading to the composite electrode self-organization are discussed and guidelines towards the optimization of the multiple process steps are presented. At the end of the lecture, an experience using an in house Virtual Reality tool, to assess the manufacturing modeling results, will be proposed to the attendees. [1] ARTISTIC project (European Research Council Consolidator Grant #772873): https://www.u-picardie.fr/erc-artistic/[2] Franco, A. A., Rucci, A., Brandell, D., Frayret, C., Gaberscek, M., Jankowski, P., & Johansson, P. (2019). Boosting Rechargeable Batteries R&D by Multiscale Modeling: Myth or Reality?. Chemical Reviews. DOI: 10.1021/acs.chemrev.8b00239 [3] Rucci, A., Ngandjong, A. C., Primo, E., Maiza, M., & Franco, A.A., submitted (2019). [4] Ngandjong, A. C., Rucci, A., Maiza, M., Shukla, G., Vazquez-Arenas, J., & Franco, A. A. (2017). Multiscale Simulation Platform Linking Lithium Ion Battery Electrode Fabrication Process with Performance at the Cell Level. The journal of physical chemistry letters, 8(23), 5966-5972. Figure 1

Experimental investigations of width effects and flame splitting phenomenon in upward flame spread over advertising canvas

A series of comparative laboratory experiments were conducted to study the width effects and flame splitting phenomenon in upward flame spread. The test samples were 2.0 mm thick and 45 cm tall advertising canvas sheets with widths of 4.0–10.0 cm. The essential parameters including flame structure, flame height, flame spread rate and surface temperature were obtained by high definition video cameras and a thermal infrared imager. The major conclusions are summarized as follows: An unexpected but interesting phenomenon i.e. flame splitting, is observed in upward flame spread process, which is caused by multiple-step pyrolysis processes of the fuels. After flame splitting, the downstream flame propagates steadily to the end of the sample, while the upstream flame travels for a period time and then extinguishes. The temperature profile reveals four stages, including preheating stage, two pyrolysis stages and burnout stage, which demonstrates that the advertising canvas undergoes multiple-step pyrolysis processes in flame spreading. The maximum flame height before the flame splitting occurs, the flame heights for downstream and upstream flame after the flame splitting occurs and flame spread rate show an increase with sample width. The empirical models for flame height and flame spread rate taking sample width effects into account are established. These results in this paper are beneficial to scholars in better understanding the flame spread and fire growth of advertising canvas.

Rapid, Single-Step Protein Encapsulation via Flash NanoPrecipitation.

Flash NanoPrecipitation (FNP) is a rapid method for encapsulating hydrophobic materials in polymer nanoparticles with high loading capacity. Encapsulating biologics such as proteins remains a challenge due to their low hydrophobicity (logP < 6) and current methods require multiple processing steps. In this work, we report rapid, single-step protein encapsulation via FNP using bovine serum albumin (BSA) as a model protein. Nanoparticle formation involves complexation and precipitation of protein with tannic acid and stabilization with a cationic polyelectrolyte. Nanoparticle self-assembly is driven by hydrogen bonding and electrostatic interactions. Using this approach, high encapsulation efficiency (up to ~80%) of protein can be achieved. The resulting nanoparticles are stable at physiological pH and ionic strength. Overall, FNP is a rapid, efficient platform for encapsulating proteins for various applications.

A Comprehensive Review on the Manipulation of the Sphingolipid Pathway by Pathogenic Bacteria.

Bacterial pathogens have developed many different strategies to hijack host cell responses to promote their own survival. The manipulation of lipid biogenesis and cell membrane stability is emerging as a key player in bacterial host cell control. Indeed, many bacterial pathogens such as Legionella, Pseudomonas, Neisseria, Staphylococci, Mycobacteria, Helicobacter, or Clostridia are able to manipulate and use host sphingolipids during multiple steps of the infectious process. Sphingolipids have long been considered only as structural components of cell membranes, however, it is now well known that they are also intracellular and intercellular signaling molecules that play important roles in many eukaryotic cell functions as well as in orchestrating immune responses. Furthermore, they are important to eliminate invading pathogens and play a crucial role in infectious diseases. In this review, we focus on the different strategies employed by pathogenic bacteria to hijack the sphingolipid balance in the host cell to promote cellular colonization.

Electromechanical characterization of a 3D printed dielectric material for dielectric electroactive polymer actuators

Dielectric electroactive polymers (DEAPs) represent a subclass of smart materials that are capable of converting between electrical and mechanical energy. These materials can be used as energy harvesters, sensors, and actuators. However, current production and testing of these devices is limited and requires multiple step processes for fabrication. This paper presents an alternate production method via 3D printing using Thermoplastic Polyurethane (TPU) as a dielectric elastomer. This study provides electromechanical characterization of flexible dielectric films produced by additive manufacturing and demonstrates their use as DEAP actuators. The dielectric material characterization of TPU includes: measurement of the dielectric constant, percentage radial elongation, tensile properties, pre-strain effects on actuation, surface topography, and measured actuation under high voltage. The results demonstrated a high dielectric constant and ideal elongation performance for this material, making the material suitable for use as a DEAP actuator. In addition, it was experimentally determined that the tensile properties of the material depend on the printing angle and thickness of the samples thereby making these properties controllable using 3D printing. Using surface topography, it was possible to analyze how the printing path affects the roughness of the films and consequently affects the voltage breakdown of the structure and creates preferential deformation directions. Actuators produced with concentric circle paths produced an area expansion of 4.73% uniformly in all directions. Actuators produced with line paths produced an area expansion of 5.71% in the direction where the printed lines are parallel to the deformation direction, and 4.91% in the direction where the printed lines are perpendicular to the deformation direction.

Portable sensing system based on electrochemical impedance spectroscopy for the simultaneous quantification of free and total microcystin-LR in freshwaters

Microcystins are the most worldwide extended and common toxins produced by cyanobacteria in freshwater. Microcystin-leucine arginine (MC-LR), associated with the most toxic incidents involving microcystins, are within the cyanobacteria (intracellular) until released into the surrounding waters (extracellular) during cell lysis. Therefore, the relationship between intracellular and extracellular cyanotoxins will allow a comprehensive risk of cyanobacteria-containing waters, preventing disease and improving human safety. In this work, we present the development of a novel portable microfluidic sensing platform for the simultaneous detection of free (extracellular) and total MC-LR (intracellular and extracellular). The integrated system contains the sample processing and detection modules capable of performing the chemical lysis, filtration, sample mixing with antibodies, and electrochemical detection of MC-LR based on an indirect strategy. The performance of the immunosensors was evaluated by electrochemical impedance spectroscopy, showing a linear dynamic range between 3.3 × 10−4 and 10−7 g L−1 and a limit of detection of 5.7 × 10−10 g L−1. The results demonstrate the potential of the developed portable biosensor platform and its suitable application for the analysis of MC-LR at regulated levels for drinking water. Finally, the integrated system was able to simultaneously detect the free and total MC-LR on a Microcystis aeruginosa culture. To the best of our knowledge this is the first described system that can differentiate between intracellular and extracellular concentration of MC-LR. This novel electrochemical sensing platform avoids the multiple processing steps typically needed for standard MC-LR analysis in the laboratory and provides an early warning system for MC-LR remote monitoring in water.

Controllable Synthesis of Mesoporous TiO2 Polymorphs with Tunable Crystal Structure for Enhanced Photocatalytic H2 Production

AbstractMultiphasic titanium dioxide (TiO2) possessing abundant heterophase junctions have been widely used for various photocatalytic applications. Current synthesis of multiphasic TiO2 mainly involves the process of thermal treatment and multiple steps of rigorous reactions, which is adverse to controlling the crystal phases and phase ratios of multiphasic TiO2. Meanwhile, the resulting products have relatively low surface area and nonporous structure. Here, a facile polymer‐assisted coordination‐mediated self‐assembly method to synthesize mesoporous TiO2 polymorphs with controllable heterophase junctions and large surface area by using polyethylenimine as the porogen in an acidic aqueous synthesis system is reported. Using this approach, the crystal phases (triphase, biphase, and monophase) and phase compositions (0–100%) are easily tailored by selecting the suitable acidic media. Furthermore, the specific surface areas (77–228 m2 g−1) and pore sizes (2.9–10.1 nm) are readily tailored by changing the reaction temperature. The photocatalytic activity of mesoporous TiO2 polymorphs is evaluated by photocatalytic hydrogen evolution. The triphasic TiO2 exhibits an excellent photocatalytic H2 generation rate of 3.57 mmol h−1 g−1 as compared to other polymorphs, which is attributed to the synergistic effects of heterophase junctions and mesostructure. The band diagram of possible electron transfer pathway for triphasic TiO2 is also elucidated.

"Sculptural Processing of Dramatic Character Make-up"

For thousands of years, primitive man has painted on his face and body. Colors were a very clear symbol of love, sex, death, eternity, joy and sorrow. This man, without knowing, was writing the history of make-up and its future today, which became a science.Man has always tried to draw some expressions on his face before putting masks on them, and perhaps he started with making masks then moved to painting on his face, and then switched to the carving of external parts and installed them on the human body in complicated and multiple steps process. The relationship between the mask, the make-up and the art of sculpture appear in all cases.The clothes, makeup and masks are among the oldest elements in the art of drama. Since ancient times, make-up was used for decoration and to represent the various characters on the stage. The main purpose of makeup and masks was to disguise.In different make-up process, materials and techniques varied, which clearly show the close connection between the designer sculptor and the make-up artist. In which, some special roles require more complex means than makeup based on colors such as man in aging, or enlargement of any part of the face or body in general, or making burns effect on the skin or wounds or deep scars.

Intensifying ethanol production from brewer’s spent grain waste: Use of whole slurry at high solid loadings

This work targets the valorization of brewer’s spent grain (BSG) waste by ethanol production, providing strategies for increasing titers in the multiple process steps involved. High solid loadings and use of whole slurry from the pretreatment were evaluated, aiming to achieve high ethanol concentration and yield. As variability in BSG chemical composition presents a challenge for their valorization, six different BSGs were chemically characterized, which allowed the selection of two with high polysaccharide content. High solid loadings (up to 25%) were employed for the pretreatment of selected BSGs by autohydrolysis, an environmentally friendly process, to improve enzymatic saccharification and extract fermentable sugars as oligosaccharides and monosaccharides. As a result, high glucose concentrations (43.7 and 57.7 g L−1) and glucose yield (85.9 and 70.6%) were obtained from the saccharification of the pretreated BSG whole slurry at 20 and 25% solid loading, respectively. Whole slurries from autohydrolysis were used as substrate for ethanol production by hybrid saccharification and fermentation. Two different Saccharomyces cerevisiae strains were evaluated and high ethanol concentration (42.27 g L−1) at a high yield (94.0%) was achieved. The results attained by the combined intensification approaches qualify BSG waste as a valuable renewable resource for cost-effective ethanol production.

Targeting neddylation inhibits intravascular survival and extravasation of cancer cells to prevent lung-cancer metastasis.

Metastasis is the leading cause of tumor-related death from lung cancer. However, limited success has been achieved in the treatment of lung cancer metastasis due to the lack of understanding of the mechanisms that underlie the metastatic process. In this study, Lewis lung carcinoma (LLC) cells which expressed green fluorescent protein in the nucleus and red fluorescent protein in the cytoplasm were used to record metastatic process in real-time via a whole-mouse imaging system. Using this system, we show the neddylation inhibitor MLN4924 inhibits multiple steps of the metastatic process, including intravascular survival, extravasation, and formation of metastatic colonies, thus finally suppressing tumor metastasis. Mechanistically, MLN4924 efficiently inhibits the expression of MMP2, MMP9, and vimentin and disrupts the actin cytoskeleton at an early stage to impair invasive potential and subsequently causes a DNA damage response, cell cycle arrest, and apoptosis upon long exposure to MLN4924. Furthermore, MMP2 and MMP9 are overexpressed in patient lung adenocarcinoma, which conferred a worse overall survival. Together, targeting the neddylation pathway via MLN4924 suppresses multiple steps of the metastatic process, highlighting the potential therapeutic value of MLN4924 for the treatment of metastatic lung cancer.