Introduction:Neoantigens from the Kirsten rat sarcoma viral oncogene homolog (KRAS) are specific cancer therapeutic targets. However, to date, no immune product targeting KRAS neoantigens has been approved for clinical use, and key challenges regarding efficacy and generalizability remain. Methods:In this study, we isolated a natural human T-cell antigen receptor (TCR) 0 that specifically recognized human leukocyte antigen (HLA)-A*11:01+ T2 cells pulsed with KRAS G12V8-16 peptides. However, TCR0 gene-transduced T cells demonstrated inadequate response to tumor cell lines. We generated T cells expressing a TCR0 mutant, being designated as TCR3. Results:TCR3-T cells showed significantly optimized avidity and response to tumor cell lines, retained specificity for the KRAS G12V8-16 peptide with no response to normal cells, killed tumor cells that highly expressed programmed cell death-ligand 1 in vitro and in vivo, proliferated without being seriously affected by indoleamine 2,3-dioxygenase, resisted transforming growth factor β, and infiltrated and recruited other immune cells to the tumor site through chemokines. Discussion:TCR3 may be useful for KRAS neoantigen-targeted clinical immunotherapy, help resolve cancer immune escape, and enhance clinical effectiveness and safety.
Engineering soft conductors that simultaneously offer high strength, extreme stretchability, and environmental stability remains a central challenge for next-generation wearable electronics. Here, we incorporate an electrospun polyurethane (PU) nanomesh rich in hydrogen bonding sites into a eutectogel matrix. Benefiting from designable interfacial interactions, the thin hybrid gel (approximate to 45 mu m) exhibits high tensile strength (12.6 MPa), remarkable stretchability (1376%) and fatigue resistance. Based on its good sensitivity, the hybrid gel can serve as a strain sensor for wide range human motion monitoring, as well as a multifunctional sensor for humidity and temperature detection. Moreover, its high water vapor transmission rate (1176 gm-2d-1) and robust anti-freezing and anti-drying properties enable reliable recording of physiological signals such as electromyography (EMG) and electrocardiography (ECG). By coupling the EMG output with a convolutional neural network (CNN), the system attains a high gesture recognition accuracy of 98.7%. This work demonstrates great potential for next-generation wearable healthcare and human-machine interfaces.
Large-area superspreading enables efficient cooling, cleaning, and liquid redistribution, yet the physical mechanisms that coordinate multi-scale surface structures with hydration conditions remain poorly defined. Here, we identify Racomitrium canescens moss leaves as a natural model that exhibits exceptional spreading performance, with fresh leaves driving water droplets to fully wet the surface in only 0.1 s, an order of magnitude faster than their dehydrated counterparts. Morphological analysis reveals a hierarchical arrangement of micrometer papillae and submicron wrinkles that suggests a multi-level wetting strategy. To elucidate this behavior, we fabricated wrinkled micropillar-arrayed surfaces (WMPS) that reproduce the essential architectural features of the moss leaves. The synthetic surfaces replicate the superspreading phenomenon, enabling a 2 & micro;L droplet to spread completely within 0.9 s and cover an area of 160 mm(2). Systematic structural decoupling demonstrates that rapid spreading arises from the synergistic action of capillary transport within the micropillar network, enhanced contact-line mobility provided by nanoscale wrinkles, and hydration-induced reduction of the surface-energy barrier. In addition, the bioinspired WMPS provides effective evaporative cooling and maintains contamination resistance, reducing steady-state temperature by 6.3 degrees C under one-sun irradiation. This work establishes a mechanistic framework for understanding hierarchical wetting and offers a scalable approach to engineering high-performance thermal-management surfaces.
The growth in oil demand has driven technological innovation in enhanced oil recovery (EOR). Chemical flooding, widely adopted for its effectiveness in improving oil recovery, enhances the macroscopic sweep efficiency by altering interfacial properties. However, strong oil-solid adhesion leads to residual oil, posing a key technical challenge. Although low-salinity water flooding can disrupt the hydrated ion bridge structure, its efficacy is limited, and it fails to fully resolve residual oil issues. To tackle this residual oil challenge, we developed traditional Chinese medicine (TCM) composite agents based on polyphenol-silicon complexation with dual EOR functions: in situ oil displacement and long-term oil isolation. Under weak alkaline conditions, the TCM composite agent continuously reacts with silicon, overcoming van der Waals forces between crude oil and silicate, thereby effectively displacing oil in micron-scale grooves. The polyphenol-silicon complexes, along with polyphenol, form a hydrophilic coating with micro/nanostructures via π-π interactions, maintaining superoleophobic and nonadhesive properties against crude oil even after 1 week. Additionally, the TCM agents altered the wettability of shale from oil-wet to water-wet and achieved an 88.24% recovery rate in core flooding tests. This breakthrough offers a solution for crude oil recovery, promoting efficient and environmentally sustainable development in the industry.
Overheating is a major cause of device failure. Thin-film evaporative cooling leverages the latent heat of liquid phase change, but its performance is often governed by the balance between interfacial liquid supply and interfacial mass-transfer kinetics. The canine tongue maintains a continuously wetted surface through rapid saliva replenishment and evaporation during thermoregulation. Here, previously unreported nanocilia on the tongue surface of the Beagle (Canis lupus familiaris) are identified. These nanocilia coat microscale papillae, revealing a naturally evolved micro-nano hierarchical architecture. Inspired by this architecture, a bioinspired cross-scale continuous surface (BioCCS) integrating microgrooves and nanowires is developed. Microgrooves promote stable liquid spreading, while nanoscale confinement modulates interfacial water interactions and weakens interfacial hydrogen bonding, together establishing a cross-scale coupled evaporation mechanism (CCEM) bridging micro-nano-molecular scales. Tested at 80 °C, a temperature relevant to device reliability, BioCCS achieves an evaporation rate of 31.36 kg h-1 m-2, enabling a self-sustained passive cooling system with a 150% enhancement in heat dissipation compared with an unmodified surface. These results provide a concept for autonomously sustained phase change cooling under subboiling conditions.
Biological fluid stability plays an irreplaceable role in maintaining physiological functions, and compromised stability can lead to health issues. Even tear instability can lead to vision impairment or dry eye disease (DED). Artificial tears (ATs) are a popular treatment; however, the comprehensive molecular mechanism by which ATs stabilize tears remains obscure. This study explores the effects of water structure rearrangement by electrolyte ions on the ATs stability. Through in situ observation and analysis of evaporation thermodynamics and hydration states, it is demonstrated that anions induce an ordered and strong hydration arrangement that significantly contributes to ATs film stability. Additionally, magnesium induces water molecule rearrangements that influence evaporation characteristics and overall stability. Notably, in vivo experiments underscore the efficacy of strong hydration anion buffers in mitigating dryness and inflammation associated with tear film instability. These insights provide personalized formulations for DED and establish a foundation for exploring biological fluid stability across various applications.
Cu-TiO2 composite coatings have attracted extensive attention due to their combination of the excellent electrical conductivity and ductility of metals with the unique properties of the reinforcing phases, etc. However, the improvement of wear resistance, interfacial solid content, and photocatalytic activity of composite coatings are remaining challenges. In this work, a Cu-TiO2 composite coating with enhanced wear resistance by electroplating of Cu2+ and electrophoresis of TiO2 nanoparticles is prepared. It is intriguing to find that there is an optimal interfacial solid content of TiO2 for Cu-TiO2 composite coating with low surface roughness at the electroplating voltage of 2.6 V, the pH of 4, the duration of 10 min, and the TiO2 nanoparticle concentration of 1 g L-1. A balance mechanism for electroplating and electrophoresis is proposed indicating the deposition of TiO2 nanoparticles and the reduction of copper ions on the substrate is competitive. Based on the Cu-TiO2 composite coating, the photocatalytic degradation performance of various organic compounds under UV light is studied, indicating increased hardness and significantly enhanced photocatalytic degradation performance. The degradation efficiency and universality of the Cu-TiO2 composite coatings are further explored, revealing that various organic dyes can be effectively degraded to below 5% within 24 h.
Superspreading occurs when the liquid-surface interaction becomes sufficiently strong to overcome the liquid's surface tension, as evidenced by a contact angle approaching 0 degrees. Conventional superspreading relies on complex designed artificial or biological surfaces, or external stimuli, which renders it challenging to exert its efficacy in common scenarios. Herein, inspired by mussel adhesion to rocks, we introduced a strategy utilizing catecholbased compounds that demonstrate strong silicate binding in saline environments, effectively modulating liquid-liquid-solid wettability at the molecular scale. Under mildly basic conditions, catechol induces a stable hydrated layer on the silicate surface, increasing the surface charge and facilitating the dewetting of oil during spreading. The strong interaction between catechol and silicon overcomes the van der Waals forces between silicate and crude oil, enabling efficient oil displacement. Moreover, we demonstrate that polyphenol-treated surfaces perform better in high-salinity environments, where surfactants lose effectiveness due to agglomeration caused by calcium ion. In contrast, polyphenol-based composite agents achieve a 70 % crude oil recovery in oil sand separation and a 90 % recovery in core flooding tests. The study demonstrates the potential of polyphenol-silicon complexation for cost-effective, scalable superspreading applications in oil recovery and contamination management, highlighting its robust salt tolerance and promising industrial relevance.
Solid-state nanochannels with probe modification demonstrate effective spontaneous charge modulation and selective ionic current regulation. Outer-surface functionalization of these nanochannels enables tunable ionic current signals before and after analyte detection. To modulate local charge distributions, we designed sensing nanochannels with significant ion rectification properties for protein detection. In this work, we utilized asymmetrically charged sensing nanochannels with DNA probe modifications to generate abundant ionic current information for multianalyte recognition. During protein detection, DNA probes on the outer surfaces of the nanochannels were competitively replaced by proteins, thereby modulating the local charge distribution. This modulation influences the ionic current through ion rectification, generating cross-reactive and differentiated signals for each target. As a result, the sensing nanochannels with asymmetry of the surface charge effectively discriminate 6 proteins using only one kind of probe. Furthermore, this system successfully distinguished proteins across various concentrations and within complex environments. This work represents a significant advancement in the development of differential sensors based on outer-surface-functionalized nanochannels for multianalyte discrimination.
Antireflective (AR) coatings are indispensable for optimizing light energy capture in transparent materials and mitigating glare-induced hazards. However, current nanoporous coatings suffer from small pore sizes (2-10 nm) that are prone to blockage by atmospheric moisture and organic pollutants, limiting their practical performance. Herein, we report a scalable, low-cost fabrication method for robust meso-macroporous (similar to 46 nm) SiO2 coatings with transmittance as high as 99.3% on glass, featuring superhydrophilicity for effective antifogging. By utilizing a sol-gel phase separation approach, polyacrylic acid acts as a dynamic template in an ethanol-water cosolvent system to enable precise size control. The resulting coatings exhibit remarkable adhesion (grade 5B), exceptional scratch resistance (over 100 cycles), and stable performance under humid heat treatment for 15 days. When applied to transparent conductive glass and solar cells, these coatings improve light transmittance by over 8.7% and solar cell relative efficiency by similar to 7.7%. Moreover, a simple dip-coating technique exhibits exceptional scalability for fabricating relatively large-area (75 cm2) AR coatings. This approach offers a versatile platform for designing durable, high-performance porous AR coatings, with transformative potential in solar energy, optical devices, and architectural applications.
Gating, a fundamental feature of biological nanochannels, enables the intelligent regulation of ion and molecule transport in response to specific requirements. Inspired by nature, numerous artificial gating systems have been researched through the functionalization of solid-state nanochannels. However, these gating systems typically allow only two transitions: “open” and “closed”, which makes it challenging to achieve multi-state transport. Herein, we construct dynamic liquid film nanochannels (DLFNs) by inserting an oil droplet into a capillary with gradient wettability that is filled with ionic solutions. The liquid film, formed between the oil and the capillary, functions as a nanochannel for ion and molecule transport, with its height dynamically adjusted through the capillary's gradient wettability. At a deeper level, the variations in liquid film thickness are driven by the interfacial water structure, which is mediated by hydrogen bonding interactions. Furthermore, unlike traditional solid-state nanochannels, which involve two phases (liquid/solid), the properties of DLFNs are influenced by three phases (oil/water/solid), resulting in distinct performance characteristics, such as reconfigurability, low cost, and ease of fabrication. This work provides an avenue for designing dynamic nanofluids and may spark promising applications of DLFNs with multiscale gating properties in drug delivery, microreactors, sieving, biosensing, and other related fields.
Surface fogging affects the light transmittance of various transparent materials and poses potential safety hazards. Superhydrophilic TiO2 surfaces can effectively prevent fogging by promoting continuous water film formation; however, they often struggle to maintain stable hydrophilicity and adhesion on plastic films. Self-cleaning and antifogging coatings on plastic substrates are crucial for applications requiring long-term clarity and minimal maintenance costs. Herein, we present a nanostructured SiO2-TiO2 coating, developed using sol-gel and spray coating methods, specifically designed for plastic films. The coated plastic films exhibit a high optical transmittance of 89.8% and superhydrophilicity with an optimal thickness of 70 nm. Notably, these coated films maintain their superhydrophilicity without the need for ultraviolet irradiation, providing continuous fogging prevention and effective degradation of adsorbed organic matter for self-cleaning. Furthermore, the SiO2-TiO2 coating can adhere stably to substrates and resist solution soaking, showing great mechanical stability. This straightforward method of creating self-cleaning superhydrophilic coatings on plastic substrates underscores its critical role in large-scale applications, where maintaining clarity and cleanliness is paramount. These applications span packaging films, greenhouse covers, and resin lenses, where durability and ease of upkeep are of the utmost importance.
Flexible electronic skin has experienced rapid development in health monitoring, human-machine interfaces, and medical diagnostics. However, improving the microenvironment of the human skin surface without affecting electrical signals remains a significant challenge. Herein, polyurethane nanofiber membranes produced via electrospinning are treated with plasma and stable superhydrophilic SiO2-TiO2 coating. A second layer of hydrophobic nanofibers is then spun on its surface, forming Janus membranes. Silver nanowires are incorporated into these Janus membranes through vacuum filtration, creating a breathable flexible electrode. Residual solvents promote fiber bonding at interfaces, preventing layer separation and ensuring electrode stability. The flexible Janus electrode demonstrates a combination of functional properties, providing stretchability, breathability, conductivity, and antibacterial effects simultaneously. Compared to the commercial gel electrode, it also demonstrates stable directional water transport and resistance to mechanical stress, efficiently channeling sweat to the surface for rapid evaporation. This capability helps regulate skin temperature and humidity, thereby enhancing comfort during wear. Additionally, the electrode supports the accurate monitoring of human electrocardiographic and electromyographic signals, offering a promising tool for health monitoring and personal protection.
Calcium-gated nanochannels in vivo play an important role in many life activities. Inspired by biological ion channels, artificial ion gating has been extensively studied. However, conventional ion gating relies on asymmetric charge structures and fixed nanochannel sizes, resulting in difficult channel blocking and low gating ratios. Herein, a dynamic liquid film nanochannel is constructed by inserting an oil droplet into a carboxylated glass capillary filled with ion solution. The liquid film between the oil and capillary is used as a nanochannel to transport ions and molecules, and the height of the nanochannel can be flexibly controlled by the electrostatic force between the oil–water and water–solid interfaces. The switching of the liquid film nanochannel depends on the ion valence. Compared to monovalent ions, the introduction of multivalent ions yields less negative zeta potential at both the oil–water and water–solid interfaces, which in turn reduces the electrostatic repulsion force between the oil–water and water–solid interfaces, resulting in the nanochannel changing from the “ON” state to the “OFF” state. The system shows good cyclic gating performance and high gating ratios up to ∼1000. Moreover, this cation-gated liquid film nanochannel enables controlled transport of molecules such as rhodamine 6G. In this paper, we present a convenient intelligent nanochannel capable of regulating the transport of ions and molecules within the liquid film simply by adjusting the electrostatic force between the oil–water and water–solid interfaces. This research holds promise for applications in drug delivery, biosensing, species separation, and beyond.
Interface residues at sites of protein-protein interaction (PPI) are the focus for affinity optimisation. However, protein hydrophobic cores (HCs) play critical roles and shape the protein surface. We hypothesise that manipulating protein HCs can enhance PPI interaction affinities. A cell stress molecule, major histocompatibility complex class I chain-related protein A (MICA), binds to the natural killer group 2D (NKG2D) homodimer to form three molecule interactions. MICA was used as a study subject to support our hypothesis. We redesigned MICA HCs by directed mutagenesis and isolated high-affinity variants through a newly designed partial-denature panning (PDP) method. A few mutations in MICA HCs increased the NKG2D-MICA interaction affinity by 325-5613-fold. Crystal structures of the NKG2D-MICA variant complexes indicated that mutagenesis of MICA HCs stabilised helical elements for decreasing intermolecular interactive free energy (ΔG) of the NKG2D-MICA heterotrimer. The repacking of MICA HC mutants maintained overall surface residues and the authentic binding specificity of MICA. In conclusion, this study provides a new method for MICA redesign and affinity optimisation through HC manipulation without mutating PPI interface residues. Our study introduces a novel approach to protein manipulation, potentially expanding the toolkit for protein affinity optimisation.
The phenotype of tumor-associated macrophages plays an important role in their function of regulating the tumor immune microenvironment. The M1-phenotype macrophages display tumor-killing and immune activating functions. Here we show that the tobacco mosaic virus (TMV), a rod-like plant virus, can polarize macrophages to an M1 phenotype and shape a tumor-suppressive microenvironment. RAW 264.7 cells and bone marrow derived-macrophages (BMDMs) can recognize TMV via Toll-like receptor-4, and then the MAPK and NF-κB signaling pathways are activated, leading to the production of pro-inflammatory factors. Furthermore, the in vivo assessments on a subcutaneous co-injection tumor model show that the TMV-polarized BMDMs shape a tumor-suppressive microenvironment, resulting in remarkable delay of 4T1 tumor growth. Another in vivo assessment on an established tumor model indicates the high tumor-metastasis-inhibiting capacity of TMV-polarized BMDMs. This work suggests a role for this plant virus in macrophage-mediated therapeutic approaches and provides a strategy for tumor immunotherapy.
Ultra-long organic room temperature phosphorescent materials (UORTP) have attracted more and more attention in the fields of imaging, anti-counterfeiting and information encryption due to their unique long life and abundant excited state characteristics. Polymer materials with UORTP are gradually coming into people's eyes because of their machinability, transparency and flexibility. In this work, a series of polymers with UORTP phosphorescent properties were synthesized by modifying phthalic acid molecules on polyethylenimide (PEI) molecular chains through amide bonds using phthalic acid derivatives (isophthalic acid, IPA/terephthalic acid, TPA/phthalic acid, PA) as phosphorescent units. Fourier transform infrared spectrum and X-ray photoelectron spectroscopy demonstrated that the phthalic acid molecules were successfully modified on polyethylenimide. C-13 Nuclear magnetic resonance illustrates the structure of the phthalic acid remained. Density functional theory (DFT) calculation proved the existence of energy transfer effect between phthalic acid and polyethylenimide, which explained the mechanism of long life phosphorescence. By changing the content of phthalic acid molecules, these polymers can achieve a long-lived lifetime of 1.51 s and an afterglow of 6 s. This is because the rigid environment constructed by the increasing intramolecular hydrogen bond limits the non-radiative transition with the increase of phosphor molecule content. The maximum lifetimes of IPA-PEI, TPA-PEI and PA-PEI were 1.51 s, 0.27 s and 0.03 s, which were 1.5 times, 13.8 times and 47.6 times longer than those of IPA (1 s), TPA (19.6 ms) and PA (0.63 ms), respectively. Thermogravimetry confirmed that the polymers have good thermal stability and the cyclic variable-temperature curves of phosphorescence intensity and cyclic variable-temperature curves of phosphorescent lifetime also illustrate the polymers' thermal stability. In addition, we further developed application of these polymers in the field of temperature sensing based on the change of phosphorescence intensity with temperature, which the relative sensitivity is up to 1.5%.K-1. This work provides a novel way for designing smart luminescent polymers with long-lived room temperature phosphorescence and adjustable afterglow.
IntroductionThe presence of soluble human programmed cell death-ligand 1 (shPD-L1) in the blood of patients with cancer has been reported to be negatively correlated with disease prognosis. However, little information exists about the mechanisms underlying high levels of shPD-L1 for promoting disease progression. MethodsIn this study, we first analyzed the correlations between shPD-L1 and apoptosis of T cells in patients with cancer, then tested the effect of shPD-L1 on T-cell functions and the production of regulatory T cells. ResultsWe found that the apoptosis of human peripheral PD-1+CD4+ T cells was significantly elevated in patients with cancer compared with healthy donors and was positively correlated with circulating PD-L1 levels in patients with cancer. In vitro, monomeric shPD-L1 significantly inhibited the proliferation, cytokine secretion, and cancer cell-killing activity of peripheral blood mononuclear cells (PBMCs) activated by either agonist antibodies or HATac (high-affinity T cell activation core)-NYE (NY-ESO-1 antigen). It also promoted CD4+ T cells to express forkhead family transcription factor 3 (FoxP3) for the conversion of induced T regulatory cells, which was more significant than that mediated by soluble human PD-L1 fusion protein (shPD-L1-Fc). DiscussionThese results confirm that soluble PD-L1 could be a candidate for inhibiting the functions of activated T cells, promoting peripheral tolerance to tumor cells, and implicating in system tumor immune escape in addition to the tumor microenvironment. This is an important mechanism explaining the negative correlation between peripheral blood PD-L1 levels and cancer prognosis. Therefore, understanding the roles of hPD-L1 in peripheral blood will be helpful for the development of precision immunotherapy programs in treating various tumors.
Antiadhesive surfaces have been gaining continuous attention, because of the scientific and industrial significance. Slippery surfaces and antismudge coatings with antiadhesive behavior have been readily designed and prepared. However, improving robustness of the surfaces, especially the simultaneous demonstration of features of high hardness, excellent adhesion to different substrates, and high thermal stability, is constantly challenging. Herein, we present a silica/polydimethylsiloxane (PDMS) nanocomposite coating (SPNC), wherein silica acts as a consecutive phase and nanophased PDMS is covalently embedded. The nanoconfined PDMS phase exhibits enhanced thermal stability and endows SPNC with slippery behavior; meanwhile, enrichment of PDMS on the surface renders a gradient composition of the coating. Accordingly, the inorganic-organic SPNC simultaneously displays a high nanoindentation hardness of 3.07 GPa and a pencil hardness over 9H, outstanding thermal stability of the slippery performance up to 400 °C, and excellent adhesion strength to different substrates. Additionally, SPNC exhibits high optical transparency, flexibility, resistance to bacterial clone, and chemical corrosion. With the scalable fabrication process, it can be envisioned that the antiadhesive coating with unprecedented comprehensive merits in this work has significant potentials for large-area applications, especially under severe service environments.
Conventional methods used during nuclear facility decommissioning to remove radioactive contamination from equipment surfaces produced a lot of trash and could result in secondary contamination. Peelable coatings, on the other hand, have been frequently employed for surface decontamination because of their great efficacy, peelability, flexibility, and compatibility with various substrates. Herein, we developed a novel efficient magnetic cesium ion adsorbent (Qmax = 249 mg/g) and combined it with polymers such as polyvinyl alcohol (PVA) to design a peelable composite coating. The composite coating can be used to decontaminate a variety of surfaces, including aluminum, plexiglas, marble, and stainless steel, with a combined decontamination efficiency of more than 95%, especially when applied to stainless steel surfaces with a decontamination rate of 98.69%. The coating also possesses excellent mechanical properties and recyclability, allowing easy recovery of the film-forming material and magnetic adsorbent recovery at the end of the decontamination process. (c) 2023 Elsevier B.V. All rights reserved.