Pore Formation Research Articles

Preparation Method and Application of Porous Poly(lactic acid) Membranes: A Review.

Porous membrane technology has garnered significant attention in the fields of separation and biology due to its remarkable contributions to green chemistry and sustainable development. The porous membranes fabricated from polylactic acid (PLA) possess numerous advantages, including a low relative density, a high specific surface area, biodegradability, and excellent biocompatibility. As a result, they exhibit promising prospects for various applications, such as oil-water separation, tissue engineering, and drug release. This paper provides an overview of recent research advancements in the fabrication of PLA membranes using electrospinning, the breath-figure method, and the phase separation method. Firstly, the principles of each method are elucidated from the perspective of pore formation. The correlation between the relevant parameters and pore structure is discussed and summarized, subsequently followed by a comparative analysis of the advantages and limitations of each method. Subsequently, this article presents the diverse applications of porous PLA membranes in tissue engineering, oil-water separation, and other fields. The current challenges faced by these membranes, however, encompass inadequate mechanical strength, limited production efficiency, and the complexity of pore structure control. Suggestions for enhancement, as well as future prospects, are provided accordingly.

Pufferfish gasdermin Ea is a significant player in the defense against bacterial pathogens

Gasdermins (GSDMs) are proteins cleaved by caspase (CASP) to trigger pyroptosis. In teleosts, pyroptosis is mediated by gasdermin E (GSDME). The Pufferfish, Takifugu rubripes, possesses two GSDME orthologs: named TrGSDMEa and TrGSDMEb. TrGSDMEa is cleaved by CASP3/7 to liberate the N-terminal (NT) domain that can trigger pyroptosis in mammalian cells. However, the biological function of TrGSDMEa in pufferfish is unknown, and TrGSDMEb is poorly studied. We found that TrGSDMEb was cleaved by CASP1/3/6/7/8, but the resulting NT domain, despite its similarity to TrGSDMEa-NT domain in sequence and structure, failed to induce pyroptosis. TrGSDMEa and TrGSDMEb exhibited similar expression patterns in pufferfish under normal physiological conditions but were up- and downregulated, respectively, in expression during Vibrio harveyi and Edwardsiella tarda infection. Bacterial infection induced the activation of TrGSDMEa and CASP3/7 in pufferfish cells, resulting in pyroptosis accompanied with IL-1β production and maturation. Inhibition of TrGSDMEa-mediated pyroptosis via TrCASP3/7 reduced the death of pufferfish cells and augmented bacterial dissemination in fish tissues. Structure-oriented mutagenesis identified 16 conserved residues in teleost GSDMEa that were required for the pore formation or auto-inhibition of GSDMEa. This study illustrates the role of GSDMEa-mediated pyroptosis in teleost defense against bacterial pathogens and provides new insights into the structure-based function of vertebrate GSDME.

Inhibition of Clostridioides difficile toxins TcdA and TcdB by the amiodarone derivative dronedarone.

The dreaded nosocomial pathogen Clostridioides difficile causes diarrhea and severe inflammation of the colon, especially after the use of certain antibiotics. The bacterium releases two deleterious toxins, TcdA and TcdB, into the gut, which are mainly responsible for the symptoms of C.difficile-associated diseases (CDADs). Both toxins are capable of entering independently into various host cells, e.g., intestinal epithelial cells, where they mono-O-glucosylate and inactivate Rho and/or Ras GTPases, important molecular switches for various cellular functions. We have shown recently that the cellular uptake of the Clostridioides difficile toxins TcdA and TcdB (TcdA/B) is inhibited by the licensed class III antiarrhythmic drug amiodarone (Schumacher et al. in Gut Microbes 15(2):2256695, 2023). Mechanistically, amiodarone delays the cellular uptake of both toxins into target cells most likely by lowering membrane cholesterol levels and by interfering with membrane insertion and/or pore formation of TcdA/B. However, serious side effects, such as thyroid dysfunction and severe pulmonary fibrosis, limit the clinical use of amiodarone in patients with C. difficile infection (CDI). For that reason, we aimed to test whether dronedarone, an amiodarone derivative with a more favorable side effect profile, is also capable of inhibiting TcdA/B. To this end, we tested in vitro with various methods the impact of dronedarone on the intoxication of Vero and CaCo-2 cells with TcdA/B. Importantly, preincubation of both cell lines with dronedarone for 1h at concentrations in the low micromolar range rendered the cells less sensitive toward TcdA/B-induced Rac1 glucosylation, collapse of the actin cytoskeleton, cell rounding, and cytopathic effects, respectively. Our study points toward the possibility of repurposing the already approved drug dronedarone as the preferable safer-to-use alternative to amiodarone for inhibiting TcdA/B in the (supportive) therapy of CDADs.

Arginine-Rich Cell-Penetrating Peptides Induce Lipid Rearrangements for Their Active Translocation across Laterally Heterogeneous Membranes.

Arginine-rich cell-penetrating peptides (CPPs) have emerged as valuable tools for the intracellular delivery of bioactive molecules, but their membrane perturbation during cell penetration is not fully understood. Here, nona-arginine (R9)-mediated membrane reorganization that facilitates the translocation of peptides across laterally heterogeneous membranes is directly visualized. The electrostatic binding of cationic R9 to anionic phosphatidylserine (PS)-enriched domains on a freestanding lipid bilayer induces lateral lipid rearrangements; in particular, in real-time it is observed that R9 fluidizes PS-rich liquid-ordered (Lo) domains into liquid-disordered (Ld) domains, resulting in the membrane permeabilization. The experiments with giant unilamellar vesicles (GUVs) confirm the preferential translocation of R9 through Ld domains without pore formation, even when Lo domains are more negatively charged. Indeed, whenever R9 comes into contact with negatively charged Lo domains, it dissolves the Lo domains first, promoting translocation across phase-separated membranes. Collectively, the findings imply that arginine-rich CPPs modulate lateral membrane heterogeneity, including membrane fluidization, as one of the fundamental processes for their effective cell penetration across densely packed lipid bilayers.

Mantis shrimp appendages-inspired Ag-CuO contact: Synergistically enhancing the erosion and impact resistance via gradient-layered scatter-island/chain-skeleton structure

Materials degradation induced by repeated arc erosion and impact poses a considerable challenge for Ag-based contacts. Fortunately, nature has evolved efficient strategies to construct complex gradient-layered structure that exhibit exceptional erosion and impact resistance. Drawing inspiration by the mantis shrimp appendages, a chain-like CuO nanofibre-reinforced Ag-CuO contact material with a gradient-layered scatter-island/chain-skeleton structure was designed and fabricated. Employing a combined experimental and simulation approach, the evolution of the microstructure during the erosion process was investigated. Results indicated that the interaction between the mantis shrimp appendage-like structure and the chain-like CuO nanofibres effectively suppressed the formation of cracks and pores on the contact surface. Particularly, the scatter-island layer not only played a crucial role in maintaining the viscosity of the molten pool and establishing stable electrical and thermal pathways, but also functioned as a “supplement” to continuously supply a steady source of Ag onto the molten pool surface, effectively promoting CuO skeleton restructuring. Meanwhile, the CuO skeleton diffusive-continuous restructuring of the chain-skeleton layer restricted molten pool flow, significantly enhancing contact erosion resistance. Furthermore, the strong synergistic effect between the gradient-layered structures dispersed stress and deformation concentration on the contact surface. It effectively delayed the defects formation and suppressed interfacial debonding, thereby endowing the contact with excellent impact resistance. Our work presents a fascinated route for designing novel biomimetic Ag-based contacts.

An ATP-responsive metal-organic framework against periodontitis via synergistic ion-interference-mediated pyroptosis.

Periodontitis involves hyperactivated stromal cells that recruit immune cells, exacerbating inflammation. This study presents an ATP-responsive metal-organic framework (Mg/Zn-MOF) designed for periodontitis treatment, utilizing ion interference to modulate immune responses and prevent tissue destruction. Addressing the challenges of synergistic ion effects and targeted delivery faced by traditional immunomodulatory nanomaterials, the Mg/Zn-MOF system is activated by extracellular ATP-a pivotal molecule in periodontitis pathology-ensuring targeted ion release. Magnesium and zinc ions released from the framework synergistically inhibit membrane pore formation by attenuating Gasdermin D (GSDMD) expression and activation. This action curtails pyroptosis, lactate dehydrogenase and IL-1β release, thwarting the onset of inflammatory cascades. Mechanistically, Mg/Zn-MOF intervenes in both the NLRP3/Caspase-1/GSDMD and Caspase-11/GSDMD pathways to mitigate pyroptosis. In vivo assessments confirm its effectiveness in diminishing inflammatory cell infiltration and preserving collagen integrity, thereby safeguarding against periodontal tissue damage and bone loss. This investigation highlights the promise of ion-interference strategies in periodontitis immunotherapy, representing a significant stride in developing targeted therapeutic approaches.

Dynamics of pore formation and evolution during multi-layer directed energy deposition additive manufacturing via in-situ synchrotron X-ray imaging: A case study on high-entropy Cantor alloy

Blown-powder directed energy deposition (DED) additive manufacturing is impeded for novel alloys processing by perceivable and detrimental porosity. During multi-layer depositions, however, mechanisms of pore formation and evolution remain elusive for developing pore mitigation strategies. Here, conduction-mode multi-layer DED process of an exemplary high-entropy Cantor alloy have been investigated in-situ by high-energy high-speed synchrotron X-ray imaging. Three new pore formation mechanisms are unveiled when depositing first layer and successive layers: gas pore induced by high-velocity powder injection into melt pool, pore generated from swirl shear of turbulent melt flow, and pore trapped by surface wave. Three pore formation mechanisms are reconfirmed: pore inheritance from feedstock powder, pore generation when laser remelting defect-sensitive locations of existing pore from previous layer or unmelted powder attached on the melt pool surface, and pore formation as cooling of melt pool. A unique mechanism for pore elimination is proposed: a counter-Marangoni melt flow is experimentally found in the stable melt pool and contributes to the prolonged pore lifetime at tens of milliseconds scale; pores are prone to coalesce into larger sizes in laser interaction zone and the adjacent location with circulation zone; coalesced larger pores driven by combined effect of Marangoni and buoyant forces easily get eliminated from melt pool. The results of pore formation and evolution dynamics revealed in Cantor alloy provide quantified experimental data for high-fidelity computational modeling and in-depth insights of porosity control for high-entropy alloy printing down to melt pool scale.

The small acid-soluble proteins of Clostridioides difficile regulate sporulation in a SpoIVB2-dependent manner.

Clostridioides difficile is a pathogen whose transmission relies on the formation of dormant endospores. Spores are highly resilient forms of bacteria that resist environmental and chemical insults. In recent work, we found that C. difficile SspA and SspB, two small acid-soluble proteins (SASPs), protect spores from UV damage and, interestingly, are necessary for the formation of mature spores. Here, we build upon this finding and show that C. difficile sspA and sspB are required for the formation of the spore cortex layer. Moreover, using an EMS mutagenesis selection strategy, we identified mutations that suppressed the defect in sporulation of C. difficile SASP mutants. Many of these strains contained mutations in CDR20291_0714 (spoIVB2) revealing a connection between the SpoIVB2 protease and the SASPs in the sporulation pathway. This work builds upon the hypothesis that the small acid-soluble proteins can regulate gene expression.

Dehydration of goethite during vacuum step-heating and implications for he retentivity characterization

Uncertainty exists over what environmental conditions and mineralogical/chemical properties are required to ensure retention of helium such that (UTh)/He dates record the time of goethite crystallization. We undertook vacuum step heating experiments to determine He diffusion parameters for extrapolation to Earth surface conditions on 10 goethite specimens in which we had created a uniform distribution of 3He. Arrhenius plots of apparent diffusion coefficients on all samples follow the same pattern. At temperatures <200 °C the data define arrays consistent with progressive degassing of increasingly large crystallites. However, above 200 °C the computed diffusivities increase dramatically until about 80% of the helium is extracted, after which they suddenly decline. The sudden increase in diffusivity at 200 °C coincides with the onset of dehydration of the goethite structure, a process which continues throughout the remainder of the step heat. There is a strong correlation between evolved water and 3He amounts. These observations likely reflect previously reported processes of formation, growth, and coalescence of pores as the phase transition to hematite proceeds. While significantly higher dehydration temperatures of ∼270 °C are observed using techniques such as thermogravimetric analysis in air, the long step durations, and vacuum conditions of our experiments destabilize goethite. Orders of magnitude differences in the computed diffusivities among our samples may reflect crystallite-size-distribution control on dehydration kinetics, and the qualitative size distributions we infer from the step heats are consistent with SEM observations of crystallite lengths. Vacuum step-heating experiments in which goethite is decomposing cannot be used to determine He diffusion behavior in nature, but the inferred crystallite size distribution provides some useful indirect evidence. A strong relationship exists between metrics of the crystallite size distribution from step heating results and the degree of He retention in nature inferred from the 4He/3He method. This observation provides evidence supporting the validity of the 4He/3He technique for estimating retention, and further suggests that the dominant control on He retention in nature is the crystallite size distribution. Experiments under hydrothermal conditions in which goethite remains stable may be an alternative approach to address the question of He diffusion behavior in nature.

Stretch-Induced Spin-Cast Membranes Based on Semi-Crystalline Polymers for Efficient Microfiltration.

Microfiltration membranes derived from semi-crystalline polymers face various challenges when synthesized through the extrusion-casting technique, including the use of large quantities of polymer, long casting times, and the generation of substantial waste. This study focuses on synthesizing these membranes using spin-casting, followed by stretch-induced pore formation. Recycled high-density polyethylene (HDPE) and virgin polyethylene powder, combined with a calcium carbonate filler, were used as the source materials for the membranes. The influence of the polymer-filler ratio with and without stretching on the morphology, tensile strength, and water flow rate was investigated. Optimal conditions were determined, emphasizing a balance between pore structure and mechanical integrity. The permeable membrane exhibited a water flow rate of 19 mL/min, a tensile strength of 32 MPa, and a water contact angle of 126°. These membranes effectively eliminated suspended particles from water, with their performance evaluated against that of commercially available membranes. This research, carried out utilizing the spin-casting technique, outlines a synthesis route for microfiltration membranes tailored to semi-crystalline polymers and their plastic forms.

The effects of graphene intrinsic defects on the formation of extrinsic defects by plasma treatment

Two-dimensional materials, like graphene, are expected to make highly efficient permeation membranes for separation and sensing applications; however, defects of a specific size and location must be added to the film to make them selectively permeable. Though techniques like TEM drilling give precise information on size and location, this method is not scalable for eventual commercial use. Plasma treatments are a scalable alternative, but there is less information on where the defect formation begins and how intrinsic defects affect pore formation. This work seeks to understand these effects by using Raman spectroscopy at the same location before and after plasma treatments to map how the intrinsic defects affect the formation of extrinsic defects to create nanopores. Defect density increases with increasing RF power, independent of the gas used during the plasma treatment, suggesting that the mechanism is due to ion bombardment. Coalesced and arrested graphene syntheses are used to study the relative trends of defect formation and map existing graphene grain boundary locations. The results show that regions starting with high densities of intrinsic defects, potentially due to strain, were found to degrade into nanocrystalline graphene first on the amorphization trajectory, even before grain boundaries.

Palmitoylation promotes pores.

Palmitoylation of intact or cleaved gasdermin D causes plasma membrane pore formation.

Corrosion behavior of new nuclear shielding Ni–Cr–W–Gd alloys in simulated spent nuclear fuel pool water

The novel Ni–Cr–W–Gd alloy have the gadolinium neutron absorption unit and the tungsten gamma ray shielding unit, which can be used for thermal neutron and gamma ray co-shielding. This Ni–Cr–W–Gd alloy have good strength and fracture elongation, however, its corrosion performance has not been reported yet. In this work, the corrosion behavior for Ni–Cr–W–Gd alloys was studied in the boric acid solution at 40 °C. Electrochemical measurement techniques, long-term immersion tests, corrosion morphology and composition analysis, and first principles calculation have been used. After 4000 h immersing, the maximum steady state corrosion rate among all alloys is only 0.3221 μm/yr. The increasing Gd promotes the increase in corrosion current density and make the weight loss of alloys more serve. Both the results of relative potential test and first principles calculation demonstrate the NiCrW matrix is the anode and Ni5Gd is the cathode in micro galvanic corrosion. The matrix around the interface of matrix/Ni5Gd suffer preferential anodic dissolution, resulting in the detachment of the Ni5Gd phase and formation of pores on the surfaces. The passive films are composed of Cr2O3 and WO3, moreover, the intensity of Gd2O3 increases with Gd content. This work contributes to the promotion of the novel alloys in spent fuel storage environments.

Rhein Inhibits Cell Development and Aflatoxin Biosynthesis via Energy Supply Disruption and ROS Accumulation in Aspergillus flavus.

Aspergillus flavus and its carcinogenic secondary metabolites, aflatoxins, not only cause serious losses in the agricultural economy, but also endanger human health. Rhein, a compound extracted from the Chinese herbal medicine Rheum palmatum L. (Dahuang), exhibits good anti-inflammatory, anti-tumor, and anti-oxidative effects. However, its effect and underlying mechanisms against Aspergillus flavus have not yet been fully illustrated. In this study, we characterized the inhibition effect of rhein on A. flavus mycelial growth, sporulation, and aflatoxin B1 (AFB1) biosynthesis and the potential mechanism using RNA-seq analysis. The results indicate that A. flavus mycelial growth and AFB1 biosynthesis were significantly inhibited by 50 μM rhein, with a 43.83% reduction in colony diameter and 87.2% reduction in AFB1 production. The RNA-seq findings demonstrated that the differentially expressed genes primarily participated in processes such as spore formation and development, the maintenance of cell wall and membrane integrity, management of oxidative stress, the regulation of the citric acid cycle, and the biosynthesis of aflatoxin. Biochemical verification experiments further confirmed that 50 μM rhein effectively disrupted cell wall and membrane integrity and caused mitochondrial dysfunction through disrupting energy metabolism pathways, leading to decreased ATP synthesis and ROS accumulation, resulting in impaired aflatoxin biosynthesis. In addition, a pathogenicity test showed that 50 μM rhein inhibited A. flavus spore growth in peanut and maize seeds by 34.1% and 90.4%, while AFB1 biosynthesis was inhibited by 60.52% and 99.43%, respectively. In conclusion, this research expands the knowledge regarding the antifungal activity of rhein and provides a new strategy to mitigate A. flavus contamination.

Facile construction of porous epoxy resin/geopolymer composites using red mud and slag by well‐distributed dual‐blending

AbstractPorous geopolymer composite (E51) reinforced by E51 epoxy resin was prepared by well‐distributed dual‐blending using red mud, metakaolin, and slag as raw materials. The effects of E51 content on microstructure, porosity, mechanical properties, and thermal insulation properties of the porous composites were investigated. The addition of E51 changed the setting time and viscosity of the slurry with high content of solid wastes (80%), which play an important role in the formation of pores during the direct foaming process. The addition of E51 had great influence on the porous properties of geopolymer composites, which in turn affected their compressive strength (0.19–1.44 MPa) and thermal conductivity (0.09–0.12 W/mK). The addition of E51 enabled the production of geopolymer composites in a rather large range of total porosity (67.3–81.1 vol%), with an optimal sample possessing a total porosity of up to 78.7 vol%, a thermal conductivity of 0.086 W/mK, and a compression strength of 0.47 MPa.

Separation of Damage Mechanisms in Full Forward Rod Extruded Case-Hardening Steel 16MnCrS5 Using 3D Image Segmentation.

In general, formed components are lightweight as well as highly economic and resource efficient. However, forming-induced ductile damage, which particularly affects the formation and growth of pores, has not been considered in the design of components so far. Therefore, an evaluation of forming-induced ductile damage would enable an improved design and take better advantage of the lightweight nature as it affects the static and dynamic mechanical material properties. To quantify the amount, morphology and distribution of the pores, advanced scanning electron microscopy (SEM) methods such as scanning transmission electron microscopy (STEM) and electron channeling contrast imaging (ECCI) were used. Image segmentation using a deep learning algorithm was applied to reproducibly separate the pores from inclusions such as manganese sulfide inclusions. This was achieved via layer-by-layer ablation of the case-hardened steel 16MnCrS5 (DIN 1.7139, AISI/SAE 5115) with a focused ion beam (FIB). The resulting images were reconstructed in a 3D model to gain a mechanism-based understanding beyond the previous 2D investigations.

The combined application of ultrasound and UVC have the potential to control mature Listeria monocytogenes and Bacillus subtilis biofilms

The present study aims to determine the bactericidal and disintegrating effect of ultraviolet type C treatments combined with ultrasound against biofilms of Listeria monocytogenes and Bacillus subtilis formed at different incubation periods (i.e. 24, 48, and 72 h). Treatments applied are UVC doses ranging from 60 to 360 mJ/cm2 (5–30 s) and US doses of 5–15 min, depending on the maturity of biofilms and the microorganism. Initially, we investigated the effects of UVC on planktonic cells, revealing a significantly higher lethality in L. monocytogenes compared to B. subtilis (P < 0.05). Moreover, B. subtilis demonstrated greater resistance in both its spore and vegetative forms (P < 0.05). The application of UVC on biofilms demonstrates that, as the more structured and robust the biofilm is, the more difficult it is for UVC to penetrate the biofilm structure and reach the cells that conform them, which is why higher lethality is observed in the shortest formation period (i.e. 24 h). In addition, as the UVC dose increases, microorganisms show a higher resistance to the treatment, thus showing a greater reduction in the microbial population at lower doses. The single application of ultrasound (US) manages to reduce the cell load between 1 and 4 log CFU/cm2, depending on the microorganism and exposure time. The results obtained after the combination of both technologies achieve higher lethality, 5.2 log reductions at the lowest doses (i.e. applying 5 min of US and 5 s of UVC). Furthermore, the maximum reduction possible for these experiments (≥5.6 log) is achieved in any treatment applying a 15-s UVC exposure time. Significant differences are observed (P < 0.05) as the maturity stage increases ([+Let] 24a > 48b > 72c hours). The combination of these two technologies demonstrates highly promising outcomes across all examined bacterial structures, including spores and vegetative biofilms.

Rapid, Point-of-Care Microwave Lysis and Electrochemical Detection of Clostridioides difficile Directly from Stool Samples.

The rapid detection of the spore form of Clostridioides difficile has remained a challenge for clinicians. To address this, we have developed a novel, precise, microwave-enhanced approach for near-spontaneous release of DNA from C. difficile spores via a bespoke microwave lysis platform. C. difficile spores were microwave-irradiated for 5 s in a pulsed microwave electric field at 2.45 GHz to lyse the spore and bacteria in each sample, which was then added to a screen-printed electrode and electrochemical DNA biosensor assay system to identify presence of the pathogen's two toxin genes. The microwave lysis method released both single-stranded and double-stranded genome DNA from the bacterium at quantifiable concentrations between 0.02 μg/mL to 250 μg/mL allowing for subsequent downstream detection in the biosensor. The electrochemical bench-top system comprises of oligonucleotide probes specific to conserved regions within tcdA and tcdB toxin genes of C. difficile and was able to detect 800 spores of C. difficile within 300 µL of unprocessed human stool samples in under 10 min. These results demonstrate the feasibility of using a solid-state power generated, pulsed microwave electric field to lyse and release DNA from human stool infected with C. difficile spores. This rapid microwave lysis method enhanced the rapidity of subsequent electrochemical detection in the development of a rapid point-of-care biosensor platform for C. difficile.

Parametric Control via the Algebraic Expression of Lotus-Type Pore Shapes in Metals

Lotus-type porous metals, characterized by low densities, large surface areas, and directional properties, are contemporarily utilized as lightweight, catalytic, and energy-damping materials; heat sinks; etc. In this study, the effects of dimensionless working parameters on the morphology of lotus-type pores in metals during unidirectional solidification were extensively investigated via general algebraic expressions. The independent dimensionless parameters include metallurgical, transport, and geometrical parameters such as Sieverts’ law constant, a partition coefficient, the solidification rate, a mass transfer coefficient, the imposed mole fraction of a solute gas, the total pressure at the top free surface, hydrostatic pressure, a solute transport parameter, inter-pore spacing, and initial contact angle. This model accounts for transient gas pressure in the pore, affected by the solute transfer, gas, capillary, and hydrostatic pressures, and Sieverts’ laws at the bubble cap and top free surface. Solute transport across the cap accounts for solute convection at the cap and the amount of solute rejected by the solidification front into the pore. The shape of lotus-type pores can be described using a proposed fifth-degree polynomial approximation, which captures the major portions between the initial contact angle and the maximum radius at a contact angle of 90 degrees, obtained by conserving the total solute content in the system. The proposed polynomial approximation, along with its working parameters, offers profound insights into the formation and shape of lotus-type pores in metals. It systematically provides deep insights into mechanisms that may not be easily revealed with experimental studies. The prediction of a lotus-type pore shape is thus algebraically achieved in good agreement with the available experimental data and previous analytical results.

Gut microbiota-mediated activation of GSDMD ignites colorectal tumorigenesis

Activation of Gasdermin D (GSDMD) results in its cleavage, oligomerization, and subsequent formation of plasma membrane pores, leading to a form of inflammatory cell death denoted as pyroptosis. The roles of GSDMD in inflammation and immune responses to infection are well documented. However, whether GSDMD also plays a role in sporadic cancer development, especially that in the gut epithelium, remains unknown. Here, we show that GSDMD is activated in colorectal tumors of both human and mouse origins. Ablation of GSDMD in a mouse model of sporadic colorectal cancer resulted in reduced tumor formation in the colon and rectum, suggesting a tumor-promoting role of the protein in the gut. Both antibiotic-mediated depletion of gut microbiota and pharmacological inhibition of NLRP3 inflammasome reduced the activation of GSDMD. Loss of GSDMD resulted in reduced infiltration of immature myeloid cells, and increased numbers of macrophages in colorectal tumors. Activation of GSDMD is also accompanied by the aggregation of the endosomal sorting complex required for transport (ESCRT) membrane repair proteins on the membrane of colorectal tumor cells, suggesting that active membrane repairment may prevent pyroptosis induced by the formation of GSDMD pore in tumor cells. Our results show that gut microbiota/NLRP3-mediated activation of GSDMD promotes the development of colorectal tumors, and supports the use of NLRP3 inhibitors to treat colon cancer.