A new capacity of gut microbiota: Fermentation of engineered inorganic carbon nanomaterials into endogenous organic metabolites.

Carbon-based nanomaterials (CNMs) have recently been found in humans raising a great concern over their adverse roles in the hosts. However, our knowledge of the in vivo behavior and fate of CNMs, especially their biological processes elicited by the gut microbiota, remains poor. Here, we uncovered the integration of CNMs (single-walled carbon nanotubes and graphene oxide) into the endogenous carbon flow through degradation and fermentation, mediated by the gut microbiota of mice using isotope tracing and gene sequencing. As a newly available carbon source for the gut microbiota, microbial fermentation leads to the incorporation of inorganic carbon from the CNMs into organic butyrate through the pyruvate pathway. Furthermore, the butyrate-producing bacteria are identified to show a preference for the CNMs as their favorable source, and excessive butyrate derived from microbial CNMs fermentation further impacts on the function (proliferation and differentiation) of intestinal stem cells in mouse and intestinal organoid models. Collectively, our results unlock the unknown fermentation processes of CNMs in the gut of hosts and underscore an urgent need for assessing the transformation of CNMs and their health risk via the gut-centric physiological and anatomical pathways.

The Exosome-Mediated Cascade Reactions for the Transfer and Inflammatory Responses of Fine Atmospheric Particulate Matter in Macrophages.

Exposure to atmospheric particulate matter (PM) is a frequent occurrence to humans, and their adverse outcomes have become a global concern. Although PM-induced inflammation is a common phenomenon, a clear picture of the mechanisms underlying exosome-mediated inflammation of PM has not yet emerged. Here, we show that exosomes can mediate the cascade reactions for the transfer of PM and inflammatory responses of macrophages. Specifically, two fine PM2.5, namely F1 (<0.49 µm) and F2 (0.95-1.5 µm), stimulated a substantial release of exosomes from macrophages (THP-1 cells) with the order of F1 > F2, via regulation of the P2X7 receptor (P2X7R). Inhibiting P2X7R with a specific inhibitor largely prevented the secretion of exosomes. In particular, we found that exosomes served as a mediator for the transfer of PM2.5 to the recipient macrophages and activated NF-κB signaling through toll-like receptor 4 (TLR-4), thereby stimulating inflammatory cytokine release and altering the inflammatory phenotype of recipients. Importantly, the exosomes derived from PM2.5-treated macrophages induced the inflammatory responses of lung in mice. Our results highlight that exosomes undergo a secretion-particle transfer-adverse outcome chain in macrophages treated with PM2.5. Given the ubiquitous atmospheric particulate matter, these new findings underscore an urgent need for assessing the secretion of exosomes and their impact on human health via exosome-centric physiological pathways.

The Nano-Intestine Interaction: Understanding the Location-Oriented Effects of Engineered Nanomaterials in the Intestine.

Engineered nanomaterials (ENMs) are used in food additives, food packages, and therapeutic purposes owing to their useful properties, Therefore, human beings are orally exposed to exogenous nanomaterials frequently, which means the intestine is one of the primary targets of nanomaterials. Consequently, it is of great importance to understand the interaction between nanomaterials and the intestine. When nanomaterials enter into gut lumen, they inevitably interact with various components and thereby display different effects on the intestine based on their locations; these are known as location-oriented effects (LOE). The intestinal LOE confer a new biological-effect profile for nanomaterials, which is dependent on the involvement of the following biological processes: nano-mucus interaction, nano-intestinal epithelial cells (IECs) interaction, nano-immune interaction, and nano-microbiota interaction. A deep understanding of NM-induced LOE will facilitate the design of safer NMs and the development of more efficient nanomedicine for intestine-related diseases. Herein, recent progress in this field is reviewed in order to better understand the LOE of nanomaterials. The distant effects of nanomaterials coupling with microbiota are also highlighted. Investigation of the interaction of nanomaterials with the intestine will stimulate other new research areas beyond intestinal nanotoxicity.

Safety Assessment of Nanomaterials for Antimicrobial Applications.

The interplay between nanotechnology and pathogens offers a new quest to fight against human infections. Inspiring from their unique thermal, magnetic, optical, or redox potentials, numerous nanomaterials have been employed for bacterial theranostics. The past decade has seen dramatic progress in the development of various nanoantimicrobials, which demands more focus on their safety assessment. The present review critically discusses the toxicity of nanoantimicrobials and the role of key features, including composition, size, surface charge, loading capability, hydrophobicity/philicity, precise release, and functionalization, that can contribute to modulating the effects on microbes. Moreover, how differences in microbe's structure, biofilm formation, persistence cells, and intracellular pathogens bestow resistance or sensitivity toward nanoantimicrobials is broadly investigated. In extension, the most important types of nanoantimicrobial with clinical prospective and their safety assessment are summarized, and finally, based on available evidence, an insight of the principles in designing safer nanoantimicrobials for overcoming pathogens and future challenges in the field is provided.

Mechanistic Investigation of a Self-Assembling Peptide against Escherichia coli.

Because of their distinctive mode of action in targeting bacterial cell membranes, antimicrobial peptides (AMPs) are increasingly regarded as a potential candidate for the development of novel antibiotics to combat the wide spread of bacterial resistance. To date, understanding of the exact molecular process by which AMPs act on the real bacterial envelope remains challenging. Simultaneously, the aggregated state of AMPs upon interaction with bacterial envelopes is still elusive. Previously, we have demonstrated that the potent antibacterial activity of a designed surfactant-like peptide Ac-A9K-NH2 benefited greatly from its high self-assembling ability and appropriate self-assembled morphologies and sizes. By using high-resolution atomic force microscopy, we here not only follow the variations of the Escherichia coli cell envelope in the presence of Ac-A9K-NH2 but also characterize the peptide aggregates on the bacterial surface as well as on the substrate surface. The results, together with those from fluorescence, zeta potential, circular dichroism, and scanning electron microscopy measurements, indicate that both the positively charged peptide monomers and self-assembled nanostructures can directly act on the negatively charged bacterial surface, followed by their insertion into the bacterial membrane, the formation of surface nanopores, and membrane lysis. The mechanism of Ac-A9K-NH2 against E. coli is thus consistent with the detergent-like mode of action. This work enhances our mechanistic understanding of the antibacterial behaviors of self-assembling peptides that will be valuable in exploring their biomedical applications.

Cytotoxicity and autophagy induction by graphene quantum dots with different functional groups.

Graphene quantum dots (GQDs) possess great potential in various applications due to their superior physicochemical properties and wide array of available surface modifications. However, the toxicity of GQDs has not been systematically assessed, thus hindered their further development; especially, the risk of surface modifications of GQDs is largely unknown. In this study, we employed a lung carcinoma A549 cells as the model to investigate the cytotoxicity and autophagy induction of three types GQDs, including cGQDs (COOH-GQDs), hGQDs (OH-GQDs), and aGQDs (NH2-GQDs). The results showed hGQDs was the most toxic, as significant cell death was induced at the concentration of 100 µg/mL, determining by WST-1 assay as well as Annexin-V-FITC/PI apoptosis analysis, whereas cGQDs and aGQDs were non-cytotoxic within the measured concentration. Autophagy detection was performed by TEM examination, LC3 fluorescence tracking, and Western-blot. Both aGQDs and hGQDs induced cellular autophagy to various degrees except for cGQDs. Further analysis on autophagy pathways indicated all GQDs significantly activated p-p38MAPK; p-ERK1/2 was inhibited by aGQDs and hGQDs but activated by cGQDs. p-JNK was inhibited by aGQDs and cGQDs, while activated by hGQDs. Simultaneously, Akt was activated by hGQDs but inhibited by aGQDs. Inhibition of autophagy by 3-MA significantly increased the cytotoxicity of GQDs, suggesting that autophagy played a protective role against the toxicity of GQDs. In conclusion, cGQDs showed excellent biocompatibility and may be considered for biological applications. Autophagy induction may be included in the health risk assessment of GQDs as it reflects the stress status which may eventually lead to diseases.

Perfluoroalkyl acid exposure induces protective mitochondrial and endoplasmic reticulum autophagy in lung cells.

Wide application of perfluoroalkyl acids (PFAAs) has raised great concerns on their side-effects on human health. PFAAs have been shown to accumulate mainly in the liver and cause hepatotoxicity. However, PFAAs can also deposit in lung tissues through air-borne particles and cause serious pulmonary toxicity. But the underlying mechanisms are still largely unknown. Autophagy is a type of programmed cell death parallel to necrosis and apoptosis, and may be involved in the lung toxicity of PFAAs. In this study, lung cancer cells, A549, were employed as the model to investigate the effects of three PFAAs with different carbon chain lengths on cell autophagy. Through Western blot analysis on LC3-I/II ratio of cells exposed to non-cytotoxic concentration (200 µM) and cytotoxic concentration (350 µM), we found concentration-dependent increase of autophagosomes in cells, which was further confirmed by TEM examination on ultra-thin section of cells and fluorescence imaging on autophagosomes in live cells. The abundance of p62 increased with the PFAAs concentration indicating the blockage of autophagy flux. Furthermore, we identified the mitochondrial autophagy (mitophagy) and endoplasmic reticulum autophagy (ER-phagy) morphologically as the major types of autophagy, suggesting the disruption on mitochondria and ERs. These organelle damages were confirmed by the overgeneration of ROS, hyperpolarization of mitochondrial membrane potential, as well as the up-regulation of ER-stress-related proteins, ATF4 and p-IRE1. Further analysis on the signaling pathways showed that PFAAs activated the MAPK pathways and inhibited the PI3K/Akt pathway, with potencies following the order of PFDA > PFNA > PFOA. Anti-oxidant (NAC) treatment did not rescue cells from death, indicating that oxidative stress is not the reason of cytotoxicity. Inhibition of autophagy by Atg5 siRNA and chloroquine even increased the toxicity of PFAAs, suggesting that PFAAs-autophagy was induced as the secondary effects of organelle damages and played a protective role during cell death.

Rational Design of Short Peptide-Based Hydrogels with MMP-2 Responsiveness for Controlled Anticancer Peptide Delivery.

Molecular self-assembly makes it feasible to harness the structures and properties of advanced materials via initial molecular design. To develop short peptide-based hydrogels with stimuli responsiveness, we designed here short amphiphilic peptides by engineering protease cleavage site motifs into self-assembling peptide sequences. We demonstrated that the designed Ac-I3SLKG-NH2 and Ac-I3SLGK-NH2 self-assembled into fibrillar hydrogels and that the Ac-I3SLKG-NH2 hydrogel showed degradation in response to MMP-2 but the Ac-I3SLGK-NH2 hydrogel did not. The cleavage of Ac-I3SLKG-NH2 into Ac-I3S and LKG-NH2 was found to be mechanistically responsible for the enzymatic degradation. Finally, when an anticancer peptide G(IIKK)3I-NH2 (G3) was entrapped into Ac-I3SLKG-NH2 hydrogels, its release was revealed to occur in a "cell-demanded" way in the presence of HeLa cells that overexpress MMP-2, therefore leading to a marked inhibitory effect on their growth on the gels.

Crucial Role of P2X7 Receptor in Regulating Exocytosis of Single-Walled Carbon Nanotubes in Macrophages.

Exocytosis of single-walled carbon nanotubes (SWCNTs) determines therapeutic efficiency and toxicity of nanoproducts but its underlying mechanism remains elusive. In this study, it is found that the exocytosis mechanism of SWCNTs is mediated mainly through the activation of P2X7 receptor (P2X7 R), an ATP-gated membrane receptor highly expressed in macrophages. Inhibition of P2X7 R signaling by either a specific inhibitor (oxidized ATP) or small interfering RNA targeting P2X7 R largely prevents the exocytosis of SWCNTs from Raw264.7 cells, resulting in significant accumulation of SWCNTs within cells. In contrast, activation of P2X7 R with ATP promotes exocytosis of SWCNTs. Specifically, it is elucidated that internalized SWCNTs are accumulated in lysosomes and induce transitional release of ATP into extracellular space, which further activates P2X7 R, leading to the influx of calcium ions, phosphorylation of protein kinase C, ERK1/2, p38, and JNK, as well as alkalization of lysosomes. SWCNTs exposure also induces microtubules reorganization that facilitates the secretion of SWCNTs-containing lysosomes. It is also found that P2X7 R simultaneously mediates secretion of IL-1ß from Raw264.7 cells during the process of SWCNTs exocytosis. The combined data reveals that P2X7 R-mediated pathway is the predominant molecular mechanism for exocytosis of SWCNTs in Raw264.7 cells. Moreover, SWCNT-induced inflammation is closely coupled with the exocytosis of SWCNTs through P2X7 R.

Insight into the Mechanisms of Combined Toxicity of Single-Walled Carbon Nanotubes and Nickel Ions in Macrophages: Role of P2X7 Receptor.

Coexistence of nanomaterials and environmental pollutants requires in-depth understanding of combined toxicity and underlying mechanism. In this work, we found that coexposure to the mixture of noncytotoxic level of single-walled carbon nanotubes (SWCNTs) (10 µg/mL) and Ni2+ (20 µM) induced significant cytotoxicity in macrophages. However, almost equal amount of intracellular Ni2+ was detected after Ni2+/SWCNT coexposure or Ni2+ single exposure, indicating no enhanced cellular uptake of Ni2+ occurred. SDS-PAGE analysis revealed 50% more SWCNTs retained in Ni2+/SWCNT exposed cells than that with SWCNT exposure alone, regardless of the exposure sequence (coexposure, Ni2+ pre- or post-treatment), suggesting inhibited SWCNT exocytosis by Ni2+. The increased cellular dose of SWCNTs could quantitatively account for the elevated toxicity of Ni2+/SWCNT mixture to cells. It was then found that agonist (ATP) and antagonist (o-ATP) of P2X7R could regulate intracellular SWCNT amount and the cytotoxicity accordingly. In addition, inhibition of P2X7R by P2X7-targeting siRNA diminished the inhibitory effect of Ni2+. It was therefore concluded that Ni2+ impeded SWCNT exocytosis by inhibiting P2X7R, leading to higher intracellular retention of SWCNTs and elevated cytotoxicity. Our work identified exocytosis inhibition as an important mechanism for SWCNT/Ni2+ toxicity, and revealed the crucial role of P2X7R in mediating such inhibitory effect.

Regulation of hydrogen binding energy via oxygen vacancy enables an efficient trifunctional Rh-Rh2O3 electrocatalyst for fuel cells and water splitting.

Developing multi-functional electrocatalysts is of great practical significance for fuel cells and water splitting. Herein, Rh-Rh2O3 nanoclusters are prepared and the surface oxygen vacancy content is regulated elaborately by post-treatment. The optimized Rh-Rh2O3/C-400 exhibits superior trifunctional catalytic activity for hydrogen oxidation reaction (HOR), hydrogen evolution reaction (HER) and hydrazine oxidation reaction (HzOR), i.e., the mass activity for HOR is 2.29 mA µgRh-1, and the overpotential for HER and HzOR at 10 mA cm-2 is as low as 12 mV and 31 mV, respectively, superior to the benchmark Pt/C. Rh-Rh2O3/C-400 also displays promising performance in practical devices, with the H2-O2 anion-exchange-membrane fuel cell delivering a peak power density of 0.66 W cm-2, and the hydrazine-assisted water splitting electrolyzer requiring a low electrolysis voltage of 0.161 V at 0.1 A cm-2. The experimental and theoretical investigations discover that the hydrogen binding energy (HBE) is linearly depended on surface oxygen vacancy contents, and the HBE directly determines the catalytic activity for HOR, HER and HzOR. This work not only innovates an efficient Rh-based nanocluster tri-functional electrocatalyst, but also eludicates the intrinsic relationship of surface structure-intermediate adsorption-catalytic activity.

Advancing intestinal organoid technology to decipher nano-intestine interactions and treat intestinal disease.

With research burgeoning in nanoscience and nanotechnology, there is an urgent need to develop new biological models that can simulate native structure, function, and genetic properties of tissues to evaluate the adverse or beneficial effects of nanomaterials on a host. Among the current biological models, three-dimensional (3D) organoids have developed as powerful tools in the study of nanomaterial-biology (nano-bio) interactions, since these models can overcome many of the limitations of cell and animal models. A deep understanding of organoid techniques will facilitate the development of more efficient nanomedicines and further the fields of tissue engineering and personalized medicine. Herein, we summarize the recent progress in intestinal organoids culture systems with a focus on our understanding of the nature and influencing factors of intestinal organoid growth. We also discuss biomimetic extracellular matrices (ECMs) coupled with nanotechnology. In particular, we analyze the application prospects for intestinal organoids in investigating nano-intestine interactions. By integrating nanotechnology and organoid technology, this recently developed model will fill the gaps left due to the deficiencies of traditional cell and animal models, thus accelerating both our understanding of intestine-related nanotoxicity and the development of nanomedicines.

Oral administration of silver nanomaterials affects the gut microbiota and metabolic profile altering the secretion of 5-HT in mice.

Due to their excellent antibacterial ability, silver nanomaterials (Ag NMs) are the most frequently used nanomaterials. Their widespread use introduces the risk of human ingestion. However, the potential toxicity of Ag NMs to the gut microbiota and their metabolic profile are yet to be fully explored. In this study, we examined the effects of Ag NMs after oral administration (0.5 mg kg-1 and 2.5 mg kg-1, 14 and 28 days) on gut homeostasis by integrating tissue imaging, 16s rRNA gene sequencing and metabolomics techniques. We uncovered that silver nanoparticles (Ag NPs) and silver nanowires (Ag NWs) altered the structure (inhibiting the proliferation of Gram-negative bacteria) and decreased the diversity of gut microbiota in mice after short-term (14 days) exposure, while the microbial community tended to recover after long-term exposure (28 days), indicating that the resistance and resilience of the gut microbiome may pose a defense against the interference by reactive, exogenous nanomaterials. Interestingly, even though the gut microbiota structure recovered after 28 days of exposure, the gut metabolites significantly changed, showing increased 1H-indole-3-carboxylic acid and elevated levels of 5-HT in the gut and blood. Collectively, our results provide a piece of evidence on the association between the ingestion of exogenous nanoparticles and gut homeostasis, especially the metabolic profile of the host. This work thus provides additional insights for the continued investigation of the adverse effects of silver nanomaterials on biological hosts.

The implication of mesenteric functions and the biological effects of nanomaterials on the mesentery.

A growing number of nanomaterials are being broadly used in food-related fields as well as therapeutics. Oral exposure to these widespread nanomaterials is inevitable, with the intestine being a major target organ. Upon encountering the intestine, these nanoparticles can cross the intestinal barrier, either bypassing cells or via endocytosis pathways to enter the adjacent mesentery. The intricate structure of the mesentery and its entanglement with the abdominal digestive organs determine the final fate of nanomaterials in the human body. Importantly, mesentery-governed dynamic processes determine the distribution and subsequent biological effects of nanomaterials that cross the intestine, thus there is a need to understand how nanomaterials interact with the mesentery. This review presents the recent progress in understanding the mesenteric structure and function and highlights the importance of the mesentery in health and disease, with a focus on providing new insights and research directions around the biological effects of nanomaterials on the mesentery. A thorough comprehension of the interactions between nanomaterials and the mesentery will facilitate the design of safer nanomaterial-containing products and the development of more effective nanomedicines to combat intestinal disorders.

Peripheral nerves directly mediate the transneuronal translocation of silver nanomaterials from the gut to central nervous system.

The blood circulation is considered the only way for the orally administered nanoparticles to enter the central nervous systems (CNS), whereas non-blood route-mediated nanoparticle translocation between organs is poorly understood. Here, we show that peripheral nerve fibers act as direct conduits for silver nanomaterials (Ag NMs) translocation from the gut to the CNS in both mice and rhesus monkeys. After oral gavage, Ag NMs are significantly enriched in the brain and spinal cord of mice with particle state however do not efficiently enter the blood. Using truncal vagotomy and selective posterior rhizotomy, we unravel that the vagus and spinal nerves mediate the transneuronal translocation of Ag NMs from the gut to the brain and spinal cord, respectively. Single-cell mass cytometry analysis revealed that enterocytes and enteric nerve cells take up significant levels of Ag NMs for subsequent transfer to the connected peripheral nerves. Our findings demonstrate nanoparticle transfer along a previously undocumented gut-CNS axis mediated by peripheral nerves.

Laser nanoprinting of 3D nonlinear holograms beyond 25000 pixels-per-inch for inter-wavelength-band information processing.

Nonlinear optics provides a means to bridge between different electromagnetic frequencies, enabling communication between visible, infrared, and terahertz bands through χ(2) and higher-order nonlinear optical processes. However, precisely modulating nonlinear optical waves in 3D space remains a significant challenge, severely limiting the ability to directly manipulate optical information across different wavelength bands. Here, we propose and experimentally demonstrate a three-dimensional (3D) χ(2)-super-pixel hologram with nanometer resolution in lithium niobate crystals, capable of performing advanced processing tasks. In our design, each pixel consists of properly arranged nanodomain structures capable of completely and dynamically manipulating the complex-amplitude of nonlinear waves. Fabricated by femtosecond laser writing, the nonlinear hologram features a pixel diameter of 500 nm and a pixel density of approximately 25000 pixels-per-inch (PPI), reaching far beyond the state of the art. In our experiments, we successfully demonstrate the novel functions of the hologram to process near-infrared (NIR) information at visible wavelengths, including dynamic 3D nonlinear holographic imaging and frequency-up-converted image recognition. Our scheme provides a promising nano-optic platform for high-capacity optical storage and multi-functional information processing across different wavelength ranges.

An interconnected-graphene enveloped titanium dioxide flower as a robust support for proton exchange membrane fuel cells.

Support corrosion is a traditional intractable problem for oxygen electrodes of fuel cells, so developing anti-corrosion supports is highly desirable. Herein, we fabricate a three-dimensional (3D) interconnected-graphene enveloped titanium dioxide flower (TiO2@RGO) as a robust support for the oxygen reduction reaction (ORR). Benefiting from the unique 3D architecture, the TiO2@RGO composite possesses both a large surface area of 174 m2 g-1 and a superior electrical conductivity of 0.19 S cm-1, enabling an electron highway for efficient simultaneous mass transfer of reactants. After loading Pt nanoparticles, the Pt-TiO2@RGO catalyst exhibits a similar catalytic activity to the commercial Pt/C catalyst, while superior stability under the accelerated degradation protocols for both catalysts (0.6-1.0VRHE) and supports (1.0-1.5VRHE), due to the strong metal-support interaction (SMSI) of Pt nanoparticles and the TiO2@RGO composite support. The PEMFC with the Pt-TiO2@RGO cathode delivers a peak power density of 901 mW cm-2, which is comparable to that with a Pt/C cathode. This work proposes a new strategy for designing robust catalyst supports for PEMFCs.

Anderson-Type Polyoxometalate-Assisted Synthesis of Defect-Rich Doped 1T/2H-MoSe2 Nanosheets for Efficient Seawater Splitting and Mg/Seawater Batteries.

Designing high-performance hydrogen evolution reaction (HER) catalysts is crucial for seawater splitting. Herein, we demonstrate a facile Anderson-type polyoxometalate-assisted synthesis route to prepare defect-rich doped 1T/2H-MoSe2 nanosheets. As demonstrated, the optimized defect-rich doped 1T/2H-MoSe2 nanosheets display low overpotentials of 116 and 274 mV to gain 10 mA cm-2 in acidic and simulated seawater for the HER, respectively. A magnesium (Mg)/seawater battery was fabricated with the defect-rich doped 1T/2H-MoSe2 nanosheet cathode, displaying the highest power density of up to 7.69 mW cm-2 and stable galvanostatic discharging over 24 h. The theoretical and experimental investigations show that the superior HER and battery performances of the heteroatom-doped MoSe2 nanosheets are attributed to both the improved intrinsic catalytic activity (effective activation of water and favorable subsequent hydrogen desorption) and the abundant active sites, benefiting from the favorable catalytic factors of the doped heteroatom, 1T phase, and defects. Our work presents an intriguing structural modulation strategy to design high-performance catalysts toward both HER and Mg/seawater batteries.

Carbon Nanotubes Promote the Development of Intestinal Organoids through Regulating Extracellular Matrix Viscoelasticity and Intracellular Energy Metabolism.

The biological effect of engineered carbon nanotubes (CNTs) as beneficial biomaterials on the intestine, especially on its development, remains unclear. Here, we investigated the profitable effect of CNTs with a different graphene layer and surface modification on the 3D model of intestinal organoids and demonstrated that CNTs (50 µg/mL) promoted the development of intestinal organoids over time (0-5 days). The mechanisms involve the modulation of extracellular matrix (ECM) viscoelasticity and intracellular energy metabolism. In particular, CNTs reduced the hardness of the extracellular matrix through decreasing the elasticity and increasing the viscosity as a result of elevated metalloproteinase and binding to a protein scaffold, which activated the mechanical membrane sensors of cells, Piezo, and downstream P-p38-yes-associated protein (YAP) pathway. Moreover, CNTs altered the metabolic profile of intestinal organoids and induced increased mitochondria activity, respiration, and nutrient absorption. These mechanisms cooperated with each other to promote the proliferation and differentiation of intestinal organoids. In addition, the promoted effect of CNTs is highly dependent on the number of graphene layers, manifested as multiwalled CNTs > single-walled CNTs. Our findings highlight the CNT-intestine interaction and imply the potential of CNTs as biomaterials for intestine-associated tissue engineering.

Perturbation of gut microbiota plays an important role in micro/nanoplastics-induced gut barrier dysfunction.

The widespread occurrence of microplastics (MPLs) and nanoplastics (NPLs), collectively abbreviated as M/NPLs, has markedly affected the ecosystem and has become a global threat to human health. Multiple investigations have shown that the chronic ingestion of M/NPLs negatively affects gut barrier function but the mechanism remains unclear. Herein, this research has investigated the toxic effects of pristine polystyrene (PS) M/NPLs, negatively charged carboxylated polystyrene M/NPLs (PS-COOH) and positively charged aminated polystyrene M/NPLs (PS-NH2) of two sizes (70 nm and 5 µm in diameter) in mice. Gavage of these PS M/NPLs for 28 days caused obvious injuries to the gut tract, leading to the decreased expression of tight junction proteins. The toxicity of the M/NPLs was ranked as PS-NH2 > PS-COOH > pristine PS. Oral administration of these M/NPLs resulted in marked gut microbiota dysbiosis. The M/NPLs-enriched genera generally contained opportunistic pathogens which are accompanied by a deteriorated intestinal barrier function, while most M/NPLs-decreased bacteria were beneficial microbes with known tight junction-promoting functions, implicating an important indirect toxic effect of gut microbiota dysbiosis in M/NPLs-induced gut barrier dysfunction. In conclusion, this research highlights the importance of gut microbiota in the toxicity of M/NPLs exposure on gut barrier function, providing novel insights into the adverse effects of M/NPLs exposure on human health.