Performance and Morphology of Waterborne Polyurethane Asphalt in the Vicinity of Phase Inversion.

Waterborne polyurethane asphalt emulsion (WPUA) is an environmentally friendly bituminous material, whose performance is highly dependent on the phase structure of the continuous phase. In this paper, WPUAs in the vicinity of phase inversion were prepared using waterborne polyurethane (WPU) and asphalt emulsion. The chemical structures, thermal stability, dynamic mechanical properties, phase-separated morphology and mechanical performance of WPUAs were studied. Fourier-transform infrared (FTIR) spectra revealed that there are no -NCO bonds in either the pure WPU or WPUAs. Moreover, the preparation of WPUA is a physical process. The addition of WPU weakens the thermal stability of asphalt emulsion. WPU improves the storage modulus of asphalt emulsion at lower and higher temperatures. The glass transition temperatures of the WPUA films are higher than that of the pure WPU film. When the WPU concentration increases from 30 wt% to 40 wt%, phase inversion occurs; that is, the continuous phase shifts from asphalt to WPU. The WPUA films have lower tensile strength and toughness than the pure WPU film. However, the elongations at break of the WPUA films are higher than that of the pure WPU film. Both the tensile strength and toughness of the WPUA films increase with the WPU concentration. Due to the occurrence of phase inversion, the elongation at break, tensile strength and toughness of the WPUA film containing 30 wt% WPU are increased by 29%, 250% and 369%, respectively, compared to the film with 40 wt% WPU.

Leveraging Janus Substrates as a Confined "Interfacial Reactor" to Synthesize Ultrapermeable Polyamide Nanofilms.

Porous substrates act as open "interfacial reactors" during the synthesis of polyamide composite membranes via interfacial polymerization. However, achieving a thin and dense polyamide nanofilm with high permeance and selectivity is challenging when using a conventional substrate with uniform wettability. To overcome this limitation, we propose the use of Janus porous substrates as confined interfacial reactors to decouple the local monomer concentration from the total monomer amount during interfacial polymerization. By manipulating the location of the hydrophilic/hydrophobic interface in a Janus porous substrate, we can precisely control the monomer solution confined within the hydrophilic layer without compromising its concentration. The hydrophilic surface ensures the uniform distribution of monomers, preventing the formation of defects. By employing Janus substrates fabricated through single-sided deposition of polydopamine/polyethyleneimine, we significantly reduce the thickness of the polyamide nanofilms from 88.4 to 3.8 nm by decreasing the thickness of the hydrophilic layer. This reduction leads to a remarkable enhancement in water permeance from 7.2 to 52.0 l/m2·h·bar while still maintaining ~96% Na2SO4 rejection. The overall performance of this membrane surpasses that of most reported membranes, including state-of-the-art commercial products. The presented strategy is both simple and effective, bringing ultrapermeable polyamide nanofilms one step closer to practical separation applications.

Supergravity-Steered Generic Manufacturing of Nanosheets-Embedded Nanocomposite Hydrogel with Highly Oriented, Heterogeneous Architecture.

Designing nanocomposite hydrogels with oriented nanosheets has emerged as a promising toolkit to achieve preferential performances that go beyond their disordered counterparts. Although current fabrication strategies via electric/magnetic force fields have made remarkable achievements, they necessitate special properties of nanosheets and suffer from an inferior orientation degree of nanosheets. Herein, a facile and universal approach is discovered to elaborate MXene-based nanocomposite hydrogels with highly oriented, heterogeneous architecture by virtue of supergravity to replace conventional force fields. The key to such architecture is to leverage bidirectional, force-tunable attributes of supergravity containing coupled orthogonal shear and centrifugal force field for steering high-efficient movement, pre-orientation, and stacking of MXene nanosheets in the bottom. Such a synergetic effect allows for yielding heterogeneous nanocomposite hydrogels with a high-orientation MXene-rich layer (orientation degree, f = 0.83) and a polymer-rich layer. The authors demonstrate that MXene-based nanocomposite hydrogels leverage their high-orientation, heterogeneous architecture to deliver an extraordinary electromagnetic interference shielding effectiveness of 55.2 dB at 12.4 GHz yet using a super-low MXene of 0.3 wt%, surpassing most hydrogels-based electromagnetic shielding materials. This versatile supergravity-steered strategy can be further extended to arbitrary nanosheets including MoS2, GO, and C3N4, offering a paradigm in the development of oriented nanocomposites.

Double charge flips of polyamide membrane by ionic liquid-decoupled bulk and interfacial diffusion for on-demand nanofiltration.

Fine design of surface charge properties of polyamide membranes is crucial for selective ionic and molecular sieving. Traditional membranes face limitations due to their inherent negative charge and limited charge modification range. Herein, we report a facile ionic liquid-decoupled bulk/interfacial diffusion strategy to elaborate the double charge flips of polyamide membranes, enabling on-demand transformation from inherently negative to highly positive and near-neutral charges. The key to these flips lies in the meticulous utilization of ionic liquid that decouples intertwined bulk/interfacial diffusion, enhancing interfacial while inhibiting bulk diffusion. These charge-tunable polyamide membranes can be customized for impressive separation performance, for example, profound Cl-/SO42- selectivity above 470 in sulfate recovery, ultrahigh Li+/Mg2+ selectivity up to 68 in lithium extraction, and effective divalent ion removal in pharmaceutical purification, surpassing many reported polyamide nanofiltration membranes. This advancement adds a new dimension to in the design of advanced polymer membranes via interfacial polymerization.

Self-Flipping Solar Seesaw Evaporators Leverage Scaling to De-Scale.

Salt scaling poses a significant obstacle to the practical implementation of solar-driven evaporation for desalination. Attempts to mitigate scaling by enhancing mass transfer often lead to a compromise in evaporation efficiency due to associated heat loss. In the present work, a novel seesaw evaporator with a Janus structure to harness scaling for periodic self-descaling is reported. The seesaw evaporators are facilely fabricated by delignifying balsa wood and subsequently single-sided spray-coating it with soot and polydimethylsiloxane (PDMS). This unique Janus structure enables the evaporator to float on the brine while ensuring an ample supply of solution for evaporation. During evaporation, salt ions are transported directionally toward the cocked end of the evaporator to form scaling, triggering the seesaw evaporator to flip once a threshold is reached. The accumulated salts re-dissolve back into the solution. By adjusting the tilt angle, the evaporator can achieve an impressive evaporation rate of up to 2.65 kg m-2 h-1 when evaporating an 8 wt.% NaCl solution. Remarkably, these evaporators maintain a stable evaporation rate during prolonged 120 h operation and produce ≈3.93-6.35 L m⁻2·day⁻¹ of freshwater from simulated brines when assembled into an evaporation device.

Supported Ionic Liquid Membrane with Highly-permeable Polyamide Armor by In Situ Interfacial Polymerization for Durable CO2 Separation.

Supported ionic liquid membranes (SILMs), owing to their capacities in harnessing physicochemical properties of ionic liquid for exceptional CO2 solubility, have emerged as a promising platform for CO2 extraction. Despite great achievements, existing SILMs suffer from poor structural and performance stability under high-pressure or long-term operations, significantly limiting their applications. Herein, a one-step and in situ interfacial polymerization strategy is proposed to elaborate a thin, mechanically-robust, and highly-permeable polyamide armor on the SILMs to effectively protect ionic liquid within porous supports, allowing for intensifying the overall stability of SILMs without compromising CO2 separation performance. The armored SILMs have a profound increase of breakthrough pressure by 105% compared to conventional counterparts without armor, and display high and stable operating pressure exceeding that of most SILMs previously reported. It is further demonstrated that the armored SILMs exhibit ultrahigh ideal CO2/N2 selectivity of about 200 and excellent CO2 permeation of 78 barrers upon over 150 h operation, as opposed to the full failure of CO2 separation performance within 36 h using conventional SILMs. The design concept of armor provides a flexible and additional dimension in developing high-performance and durable SILMs, pushing the practical application of ionic liquids in separation processes.

Silk fibroin/methacrylated gelatine/hydroxyapatite biomimetic nanofibrous membranes for guided bone regeneration.

By mimicking in vivo bionic microenvironment and promoting osteogenic differentiation, the hybrid organic-inorganic nanofibrous membranes provide promising potential for guided bone regeneration (GBR) in the treatment of clinical bone defects. To develop a degradable and osteogenic membrane for GBR by combining the natural biomacromolecule silk fibroin (SF) and gelatine with the bioactive nano hydroxyapatite (nHA), the anhydride-modified gelatine-nano hydroxyapatite (GelMA-nHA) composites were synthesized in situ and introduced into silk fibroin to prepare nanofibrous membranes with different ratios using electrospinning and photocrosslinking. The nanofibrous membranes, particularly those with a mass ratio of 7:2:1, were found to exhibit satisfactory elongation at break up to 110 %, maintain the nanofibrous structure for up to 28 days, and rapidly form bone-like apatite within 3 days, thus offering advantages when it comes to guided bone regeneration. In vitro cell results showed that the SF/GelMA/nHA membranes had excellent biocompatibility and enhanced osteogenic differentiation of hBMSCs. In vivo studies revealed that the hybrid composite membranes can improve bone regeneration of critical-sized calvarial defects in rat model. Therefore, the novel hybrid nanofibrous membrane is proposed to be a alternative candidate for creating a bionic microenvironment that promotes bone regeneration, indicating their potential application to bone injury treatment.

Harmonic amide bond density as a game-changer for deciphering the crosslinking puzzle of polyamide.

It is particularly essential to analyze the complex crosslinked networks within polyamide membranes and their correlation with separation efficiency for the insightful tailoring of desalination membranes. However, using the degree of network crosslinking as a descriptor yields abnormal analytical outcomes and limited correlation with desalination performance due to imperfections in segmentation and calculation methods. Herein, we introduce a more rational parameter, denoted as harmonic amide bond density (HABD), to unravel the relationship between the crosslinked networks of polyamide membranes and their desalination performance. HABD quantifies the number of distinct amide bonds per unit mass of polyamide, based on a comprehensive segmentation of polyamide structure and consistent computational protocols derived from X-ray photoelectron spectroscopy data. Compared to its counterpart, HABD overcomes the limitations and offers a more accurate depiction of the crosslinked networks. Empirical data validate that HABD exhibits the expected correlation with the salt rejection and water permeance of reverse osmosis and nanofiltration polyamide membranes. Notably, HABD is applicable for analyzing complex crosslinked polyamide networks formed by highly functional monomers. By offering a powerful toolbox for systematic analysis of crosslinked polyamide networks, HABD facilitates the development of permselective membranes with enhanced performance in desalination applications.

Solid-state, liquid-free ion-conducting elastomers: rising-star platforms for flexible intelligent devices.

Soft ionic conductors have emerged as a powerful toolkit to engineer transparent flexible intelligent devices that go beyond their conventional counterparts. Particularly, due to their superior capacities of eliminating the evaporation, freezing and leakage issues of the liquid phase encountered with hydrogels, organohydrogels and ionogels, the emerging solid-state, liquid-free ion-conducting elastomers have been largely recognized as ideal candidates for intelligent flexible devices. However, despite their extensive development, a comprehensive and timely review in this emerging field is lacking, particularly from the perspective of design principles, advanced manufacturing, and distinctive applications. Herein, we present (1) the design principles and intriguing merits of solid-state, liquid-free ion-conducting elastomers; (2) the methods to manufacture solid-state, liquid-free ion-conducting elastomers with preferential architectures and functions using advanced technologies such as 3D printing; (3) how to leverage solid-state, liquid-free ion-conducting elastomers in exploiting advanced applications, especially in the fields of flexible wearable sensors, bioelectronics and energy harvesting; (4) what are the unsolved scientific and technical challenges and future opportunities in this multidisciplinary field. We envision that this review will provide a paradigm shift to trigger insightful thinking and innovation in the development of intelligent flexible devices and beyond.

Characterization of drying-induced changes in moduli and internal stresses in a constrained gel using laser vibrometry.

Hydrogels, water-saturated polymer networks find widespread use in soft robotics, biomedical, pharmaceutical and food industries. Both solid and water constituents of hydrogels are sensitive to external stimuli such as temperature, humidity, osmolarity, and light. For instance, common hydrogels swell or shrink in the presence of chemical potential gradient between the sample and surrounding environment. Corresponding changes in internal water content lead to significant changes in mechanical properties of hydrogels. Besides, internal stresses build up if the gel samples are constrained during swelling or dehydration. In the present research, we utilize modal analyses technique on drying hydrogels to identify dehydration-induced changes in elastic moduli and internal stresses. In particular, natural frequencies and damping ratios of the first two axisymmetric transverse vibration modes are measured on clamped gelatin disks using non-contact laser vibrometry at various water loss states. Experimental modal frequencies are then compared to the predictions of a pre-stressed thick plate model. The evolutions of elastic moduli and internal stresses for water losses up to 80% are identified. The broadband loss capacity of gelatin is also determined from the measured modal damping ratios. Highly transient mechanical response observed on the gelatin disks further demonstrates the need for non-contact and rapid mechanical characterization of hydrogels. As illustrated in this work, vibration and wave-based techniques are promising candidates to fulfill that need.

Design of Photothermal "Ion Pumps" for Achieving Energy-Efficient, Augmented, and Durable Lithium Extraction from Seawater.

Extracting lithium from seawater has emerged as a disruptive platform to resolve the issue of an ever-growing lithium shortage. However, achieving highly efficient and durable lithium extraction from seawater in an energy-efficient manner is challenging, as imposed by the low concentration of lithium ions (Li+) and high concentration of interfering ions in seawater. Here, we report a facile and universal strategy to develop photothermal "ion pumps" (PIPs) that allow achieving energy-efficient, augmented, and durable lithium extraction from seawater under sunlight. The key design of PIPs lies in the function fusion and spatial configuration manipulation of a hydrophilic Li+-trapping nanofibrous core and a hydrophobic photothermal shell for governing gravity-driven water flow and solar-driven water evaporation. Such a synergetic effect allows PIPs to achieve spontaneous, continuous, and augmented Li+ replenishment-diffusion-enrichment, as well as circumvent the impact of concentration polarization and scaling of interfering ions. We demonstrate that our PIPs exhibit dramatic enhancement in Li+ trapping rate and outstanding Li+ separation factor yet have ultralow energy consumption. Moreover, our PIPs deliver ultrastable Li+ trapping performance without scaling even under high-concentration interfering ions for 140 h operation, as opposed to the significant decrease of nearly 55.6% in conventional photothermal configuration. The design concept and material toolkit developed in this work can also find applications in extracting high-value-added resources from seawater and beyond.

Room-temperature endogenous lubricant-infused slippery surfaces by evaporation induced phase separation.

We present a novel approach to fabricate endogenous slippery lubricant-infused porous surfaces (eSLIPS) at room temperature using an evaporation-induced phase separation process. The ternary coating system, comprising ethylene-propylene copolymer, caprylyl methicone, and n-hexane, forms a porous structure in situ infiltrated with lubricant, resulting in surfaces with remarkable anti-fouling and anti-icing properties.

Interfacial polymerization at unconventional interfaces: an emerging strategy to tailor thin-film composite membranes.

Interfacial polymerization is a well-known process to synthesize separation layers for thin film composite membranes at an immiscible organic liquid-aqueous liquid interface. The organic-aqueous interface determines the diffusion dynamics of monomers and the chemical environment for polymerization, exerting a critical influence on the formation of polymer thin films. This review summarizes recent advances in tailoring interfacial polymerization using interfaces beyond the conventional alkane-water interface to achieve high-performance separation films with designed structures. Diverse liquid-liquid interfaces are introduced for synthesizing separation films by adding co-solvents into the organic phase and/or the aqueous phase, respectively, or by replacing one of the liquid phases with other solvents. Innovative liquid-gel and liquid-gas interfaces are then summarized for the synthesis of polymer thin films for separation. Novel strategies to form reaction interfaces, such as spray-coating, are also presented and discussed. In addition, we discuss the details of how a physically or chemically patterned substrate affects interfacial polymerization. Finally, the potential of unconventional interfaces in interfacial polymerization is forecast with both challenges and opportunities.

Photothermal Janus fabrics enabling persistent directional sweat-wicking in personal wet-thermal management.

Directional sweat-wicking by Janus fabrics has gained substantial attention in promoting personal wet-thermal management for optimal human comfort. During intense physical exercise, excessive sweating can cause the flooding of fabrics and weaken their wicking capabilities once the inner capillary channels are saturated. To address this issue, we develop a photothermal Janus fabric through a facile polydopamine (PDA) deposition followed by single-sided spray-coating of hydrophobic polydimethylsiloxane (PDMS). Such innovative fabrics enable directional sweat-wicking through a Janus structure and persistent removal of excessive sweat by solar-powered evaporation. Under sunlight, our photothermal Janus fabrics exhibit an enhanced evaporation rate, approximately twice compared with that of conventional Janus fabrics (∼1.143 ± 0.027 kg m-2h-1), making them suitable for high sweating rates during vigorous exercise. Furthermore, these fabrics help to maintain the skin temperature within the normal range, preventing hypothermia caused by profuse sweating. In addition, our photothermal Janus fabrics exhibit excellent washing durability even after multiple washing cycles, ensuring prolonged performance and safety.

Development of magnetic poly(L-lactic Acid) nanofibrous microspheres for transporting and delivering targeted cells.

To avoid infection and other risks caused by large open-surgery incisions using scaffold transplants, it is very important to study injectable microcarrier-loaded cells for targeted therapy and tissue regeneration. In this study, on the one hand, to simulate the hierarchical structure of the extracellular matrix and carry cells, poly(L-lactic acid) (PLLA) nanofibrous microspheres (large microspheres) were initially fabricated as cell carriers. On the other hand, to precisely deliver cells through a magnetic field and promote stem cell differentiation, drug-loaded mesoporous Fe3O4@SiO2 microspheres (small microspheres) were prepared and coated on the surface PLLA nanofibrous microspheres. The coating conditions were systematically studied and optimized. The results showed that planetary-satellite-like cell carriers were successfully prepared and the carriers were capable of freely translocating under the influence of a magnetic field. It has been demonstrated in vitro experiments that the carriers are biocompatible and are capable of acting as drug carriers. Specifically, they were able to load and release cells in response to magnetic fields. In vivo experiments indicated that the carriers could successfully load and release GFP-labelled cells in nude mice. The study presented in this paper provides a versatile and promising platform for the cell-based therapy in tissue engineering and regenerative medicine.

Stainless Steel Screen Modified with Renatured Xerogel for Efficient and Highly Stable Oil/Water Separation via Gravity.

The application of hydrogel coatings to surface-modified metallic materials has gained considerable attention in engineering practice such as water-oil separation. However, the low coating adhesion and poor coating stability restrict its application. In this study, to obtain special wettability and durable filter materials, polyacrylamide (PAM)/sodium alginate (SA) xerogel particles were first prepared and adhered to a stainless steel screen by using an epoxy resin as a linker. Subsequently, the xerogel particles of the screen rehydrates in water to form a PAM-SA double-network hydrogel. The results show that the screen modified by PAM-SA xerogel of 20-30 µm particle size and a linker concentration of 0.1 g/mL resulted in a chimeric structure and subsequently transformed a uniform double-network hydrogel coating in water. According to the experimental results, the rough hydrogel coating exhibits superhydrophilicity and superoleophobicity under water; in particular, it has excellent wear resistance as well as physical and chemical stability. Under gravity-driven action, the PAM-SA-modified screen demonstrates high separation efficiency values of up to 99% in separating a wide range of oil/water mixtures and maintaining a water flux of (2-6) × 104 L·m-2·h-1. There was no significant reduction in efficiency of separation and water flux after 10 cycles, indicating that the PAM-SA-modified screen is capable of offering outstanding separation performance and durability. Moreover, the hydrogel-modified screen demonstrated corrosion and swelling resistance in some extreme environments, paving a way for practical applications in water treatment. The novel hydrogel-coating-modified screen with ease of preparation holds great promise for oil/water separation and other engineering applications.

A miRNA-based gene therapy nanodrug synergistically enhances pro-inflammatory antitumor immunity against melanoma.

MicroRNA (miRNA)-based gene therapy is a robust approach to treating human cancers. However, the low target specificity and safety issues associated with viral vectors have limited the clinical use of miRNA therapeutics. In the present study, we aimed to develop a biocompatible nanocarrier to deliver the tumor suppressor miR-30a-5p for gene therapy of ocular melanoma. The quasi-mesoporous magnetic nanospheres (MMNs) were prepared by polyelectrolytes-mediated self-assembling Fe3O4 nanocrystals; the cationic polymer capped quasi-mesoporous inner tunnels of the MMNs facilitate high miRNA loading and protect from nuclease degradation. Then, the outer layer of the MMNs was modified with a disulfide bond bridged very low molecular weight polyethyleneimine (PEI) network to form redox-responsive nanospheres (rMMNs) that enhance the miRNA payload and enable miRNA release under glutathione-dominant tumor microenvironment. The miR-30a-5p loaded rMMNs nanodrug (miR-30a-5p@rMMNs) upregulated miR-30a-5p level and inhibited malignant phenotypes of ocular melanoma by targeting the transcription factor E2F7 both in vitro and in vivo. Additionally, rMMNs act as an enhancer to increase cancer cell apoptosis by modulating M1-like macrophage polarization and activating Fenton reaction. Thus, the rMMNs is a promising miRNA carrier for gene therapy and could enhance pro-inflammatory immunity in melanoma and other cancers. STATEMENT OF SIGNIFICANCE: • miR-30a-5p@rMMNs inhibited malignant phenotypes of ocular melanoma both in vitro and in vivo. • The rMMNs promoted M1 macrophage polarization thus synergistically enhancing pro-inflammatory anti-tumor immunity against melanoma. • The rMMNs showed no obvious toxicity under the injection dose.

Solar-Driven Evaporators with Thin-Film-Composite Architecture Inspired by Plant Roots for Treating Concentrated Nano-/Submicrometer Emulsions.

Oil/water separation by porous materials has received growing interest over the past years since the ever-increasing oily wastewater discharges seriously threaten our living environment. Purification of nano-sized and concentrated emulsions remains a big challenge because of the sharp flux decline by blocking the pores and fouling the surfaces of those porous materials. Herein, we propose a solar-driven evaporator possessing thin-film-composite architecture to deal with these two bottlenecks. Inspired by plant roots, our evaporator composes of a large-pore sponge wrapped by a thin hydrogel film, which is constructed by the contra-diffusion and cross-linking of alginate and calcium ions at the sponge surface. The dense superoleophobic hydrogel layer serves as a selective barrier that prevents oil emulsions but allows water permeation, while the inner sponge with large pores facilitates water transport within the evaporator, ensuring sufficient water supply for evaporation. By splitting the single evaporator into an array, the evaporator performs a high evaporation rate of ∼3.10 kg·m-2·h-1 and oil removal efficiency above 99.9% for a variety of oil emulsions. Moreover, it displays a negligible decline in the evaporation rate when treating concentrated emulsions for 8 h.

Metal-Polyphenol Coordination at the Aqueous Contra-diffusion "Interface": A Green Way to High-Performance Iron(III)/Tannic Acid Thin-Film-Composite Nanofiltration Membranes.

Thin-film-composite (TFC) nanofiltration membranes have found wide uses in environment remediation and industrial separation. There is a growing trend to avoid the use of organic solvents and toxic chemicals during membrane fabrication. Therefore, the aqueous fabrication of TFC membranes receives considerable interest as a green and sustainable process. However, it remains challenging to construct a defect-free and ultrathin film in a homogeneous aqueous phase without the assistance of an interface. The contra-diffusion process provides a special "interface" to confine the film formation within a narrow space by regulating the competition between precursor diffusion and interfacial reactions. Herein, Fe3+/tannic acid (TA) TFC membranes were fabricated by a contra-diffusion process. The effects of fabrication parameters on the Fe3+/TA TFC membrane microstructure and performance were also investigated. The negatively charged membrane performs a competitive Na2SO4 rejection of 95.6% with a permeation flux of 44.3 L m-2 h-1 under 0.6 MPa as well as more than 99.5% rejection to several anionic dyes. The as-prepared membranes perform superior nanofiltration performance compared to other reported Fe3+/TA-based membranes, owing to the thin and defect-free selective layers by self-regulation. Moreover, the membranes exhibit stable rejection during a long-term nanofiltration test.

Ganciclovir-induced mutations are present in a diverse spectrum of post-transplant malignancies.

BACKGROUND: Ganciclovir (GCV) is widely used in solid organ and haematopoietic stem cell transplant patients for prophylaxis and treatment of cytomegalovirus. It has long been considered a mutagen and carcinogen. However, the contribution of GCV to cancer incidence and other factors that influence its mutagenicity remains unknown. METHODS: This retrospective cohort study analysed genomics data for 121,771 patients who had undergone targeted sequencing compiled by the Genomics Evidence Neoplasia Information Exchange (GENIE) or Foundation Medicine (FM). A statistical approach was developed to identify patients with GCV-associated mutational signature (GCVsig) from targeted sequenced data of tumour samples. Cell line exposure models were further used to quantify mutation burden and DNA damage caused by GCV and other antiviral and immunosuppressive drugs. RESULTS: Mutational profiles from 22 of 121,771 patient samples in the GENIE and FM cohorts showed evidence of GCVsig. A diverse range of cancers was represented. All patients with detailed clinical history available had previously undergone solid organ transplantation and received GCV and mycophenolate treatment. RAS hotspot mutations associated with GCVsig were present in 9 of the 22 samples, with all samples harbouring multiple GCV-associated protein-altering mutations in cancer driver genes. In vitro testing in cell lines showed that elevated DNA damage response and GCVsig are uniquely associated with GCV but not acyclovir, a structurally similar antiviral. Combination treatment of GCV with the immunosuppressant, mycophenolate mofetil (MMF), increased the misincorporation of GCV in genomic DNA and mutations attributed to GCVsig in cell lines and organoids. CONCLUSIONS: In summary, GCV can cause a diverse range of cancers. Its mutagenicity may be potentiated by other therapies, such as mycophenolate, commonly co-prescribed with GCV for post-transplant patients. Further investigation of the optimal use of these drugs could help reduce GCV-associated mutagenesis in post-transplant patients.