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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is a major advance in treating NSCLC with EGFR-activating mutations. However, acquired resistance, due partially to secondary mutations limits their use. Here we report that NSCLC cells with acquired resistance to gefitinib or osimertinib (AZD9291) exhibit EMT features, with a decrease in E-cadherin, and increases in vimentin and stemness, without possessing any EGFR secondary mutations. Knockdown of E-cadherin in parental cells increased gefitinib resistance and stemness, while knockdown of vimentin in resistant cells resulted in opposite effects. Src activation and Hakai upregulation were found in gefitinib-resistant cells. Knockdown of Hakai elevated E-cadherin expression, attenuated stemness, and resensitized the cells to gefitinib. Clinical cancer specimens with acquired gefitinib resistance also showed a decrease in E-cadherin and an increase in Hakai expression. The dual HDAC and HMGR inhibitor JMF3086 inhibited the Src/Hakai and Hakai/E-cadherin interaction to reverse E-cadherin expression, and attenuated vimentin and stemness to restore gefitinib sensitivity. The EMT features of AZD9291-resistant H1975 cells were related to the upregulation of Zeb1. Both gefitinib and AZD9291 sensitivity was restored by JMF3086 through reversing EMT. Our study not only revealed a common mechanism of EMT in both gefitinib and AZD9291 resistance beyond EGFR mutations per se, but also provides a new strategy to overcome it.

Melatonin, an amine hormone highly conserved during evolution, has a wide range of physiological functions in animals and plants. It is involved in plant growth, development, maturation, and aging, and also helps ameliorate various types of abiotic and biotic stresses, including salt, drought, heavy metals, and pathogens. Melatonin-related growth and defense responses of plants are complex, and involve many signaling molecules. Among these, the most important one is nitric oxide (NO), a freely diffusing amphiphilic biomolecule that can easily cross the cell membrane, produce rapid signal responses, and participate in a wide variety of physiological reactions. NO-induced S-nitrosylation is also involved in plant defense responses. NO interacts with melatonin as a long-range signaling molecule, and helps regulate plant growth and maintain oxidative homeostasis. Exposure of plants to abiotic stresses causes the increase of endogenous melatonin levels, with the consequent up-regulation of melatonin synthesis genes, and further increase of melatonin content. The application of exogenous melatonin causes an increase in endogenous NO and up-regulation of defense-related transcription factors, resulting in enhanced stress resistance. When plants are infected by pathogenic bacteria, NO acts as a downstream signal to lead to increased melatonin levels, which in turn induces the mitogen-activated protein kinase (MAPK) cascade and associated defense responses. The application of exogenous melatonin can also promote sugar and glycerol production, leading to increased levels of salicylic acid and NO. Melatonin and NO in plants can function cooperatively to promote lateral root growth, delay aging, and ameliorate iron deficiency. Further studies are needed to clarify certain aspects of the melatonin/NO relationship in plant physiology.

Technology innovation in the tourism industry serves as a vehicle to meet the increasing need for remarkable tourist experiences. This study aims to construct a virtual reality tour-guiding platform and then establish a technology acceptance model based on the Unified Theory of Acceptance and Use of Technology (UTAUT) model. 391 students from a technological university in Taiwan participated in the study. Results indicated their learning effectiveness and technology acceptance within the education system. Interaction was an exogenous variable that has an indirect effect on technology use, implying the importance of interaction between people and devices within a digital tour environment.

This action research created an application system using robots as a tool for training English-language tour guides. It combined artificial intelligence (AI) and virtual reality (VR) technologies to develop content for tours and a 3D VR environment using the AI Unity plug-in for programming. Students learned to orally interact with the robot and act as a guide to various destinations. The qualitative methods included observation, interviews, and self-reporting of learning outcomes. Two students voluntarily participated in the study. The intervention lasted for ten weeks. The results indicated the teaching effectiveness of robot-assisted language learning (RALL). The students acknowledged the value of RALL and had positive attitudes toward it. The contextualized VR learning environment increased their motivation and engagement in learning, and students perceived that RALL could help develop autonomy, enhance interaction, and provide an active learning experience. The implications of the study are that RALL has potential and that it provides an alternative learning opportunity for students.

Instant messaging (IM) applications are ubiquitous, and while end-to-end encryption protects message content, traffic metadata remains observable. This paper proposes a traffic correlation framework for IM call services under a passive ISP-level threat model to infer communication parties from encrypted traffic. The framework extracts and matches metadata from sustained, bidirectional call flows and jointly analyzes endpoint identifiability, shared server connectivity, symmetry in call duration and traffic volume, and service type indicators to derive correlation artifacts for matching. The framework is instantiated and evaluated on WhatsApp, Facebook Messenger, and Snapchat across diverse user behavior scenarios and commonly deployed network settings. Experimental results show that the method reliably links caller and callee flows, revealing edges in users’ social graphs without decrypting any packets. Under typical data retention regimes, these findings indicate that metadata-based correlation provides a practical basis for deanonymization and represents a persistent privacy risk for users of IM calling.

Different eukaryotic cell organelles (e.g., mitochondria, endoplasmic reticulum, lysosome) are involved in various cancer processes, by dominating specific cellular activities. Organelles cooperate, such as through contact points, in complex biological activities that help the cell regulate energy metabolism, signal transduction, and membrane dynamics, which influence survival process. Herein, we review the current studies of mechanisms by which mitochondria, endoplasmic reticulum, and lysosome are related to the three major malignant gynecological cancers, and their possible therapeutic interventions and drug targets. We also discuss the similarities and differences of independent organelle and organelle–organelle interactions, and their applications to the respective gynecological cancers; mitochondrial dynamics and energy metabolism, endoplasmic reticulum dysfunction, lysosomal regulation and autophagy, organelle interactions, and organelle regulatory mechanisms of cell death play crucial roles in cancer tumorigenesis, progression, and response to therapy. Finally, we discuss the value of organelle research, its current problems, and its future directions.

Touch displays are ubiquitous in modern technologies. However, current protective methods for emerging flexible displays against static, scratches, bending, and smudge rely on multilayer materials that impede progress towards flexible, lightweight, and multifunctional designs. Developing a single coating layer integrating all these functions remains challenging yet highly anticipated. Herein, we introduce an organic–inorganic covalent–ionic hybrid network that leverages the reorganizing interaction between siloxanes (i.e., trifluoropropyl–funtionalized polyhedral oligomeric silsesquioxane and cyclotrisiloxane) and fluoride ions. This nanoscale organic–inorganic covalent–ionic hybridized crosslinked network, combined with a low surface energy trifluoropropyl group, offers a monolithic layer coating with excellent optical, antistatic, anti–smudge properties, flexibility, scratch resistance, and recyclability. Compared with existing protective materials, this all–in–one coating demonstrates comprehensive multifunctionality and closed–loop recyclability, making it ideal for future flexible displays and contributing to ecological sustainability in consumer electronics. Lin et al. report a nanoscale organic-inorganic covalent-ionic hybrid network leveraging the reorganising interaction between siloxanes and fluoride ions, enabling a single layer coating with excellent optical, antistatic, anti-smudge, anti-scratch, and mechanical properties for touch displays.

Mimicking enzyme function and increasing performance of naturally evolved proteins is one of the most challenging and intriguing aims of nanoscience. Here, we employ DNA nanotechnology to design a synthetic enzyme that substantially outperforms its biological archetypes. Consisting of only eight strands, our DNA nanostructure spontaneously inserts into biological membranes by forming a toroidal pore that connects the membrane’s inner and outer leaflets. The membrane insertion catalyzes spontaneous transport of lipid molecules between the bilayer leaflets, rapidly equilibrating the lipid composition. Through a combination of microscopic simulations and fluorescence microscopy we find the lipid transport rate catalyzed by the DNA nanostructure exceeds 10 7 molecules per second, which is three orders of magnitude higher than the rate of lipid transport catalyzed by biological enzymes. Furthermore, we show that our DNA-based enzyme can control the composition of human cell membranes, which opens new avenues for applications of membrane-interacting DNA systems in medicine. Mimicking enzyme function and improving upon it is a challenge facing nanotechnology. Here the authors design a DNA nanostructure that catalyzes the transport of lipids between bilayers at a rate three orders of magnitude higher than biological enzymes.

In non-cleistogamous plants, the male gametophyte, the pollen grain is immotile and exploits various agents, such as pollinators, wind, and even water, to arrive to a receptive stigma. The complex process of pollination involves a tubular structure, i.e., the pollen tube, which delivers the two sperm cells to the female gametophyte to enable double fertilization. The pollen tube has to penetrate the stigma, grow in the style tissues, pass through the septum, grow along the funiculus, and navigate to the micropyle of the ovule. It is a long journey for the pollen tube and its two sperm cells before they meet the female gametophyte, and it requires very accurate regulation to perform successful fertilization. In this review, we update the knowledge of molecular dialogues of pollen-pistil interaction, especially the progress of pollen tube activation and guidance, and give perspectives for future research.

Electrostatic charge accumulation via contact electrification poses significant challenges in natural and engineered systems, such as displays. Existing anti-static coatings, while promising, are limited by trade-offs between optical transparency, mechanical robustness, and anti-static behavior. Here we report a molecularly tailored strategy to fabricate highly durable, transparent anti-triboelectric material by chemically crosslinking two heterogeneous components: aminopropyl oligomeric silsesquioxane (electron-donating) and trifluoropropyl-rich (electron-withdrawing) counterpart containing minor epoxy groups. By precise molecular engineering, we construct a highly crosslinked organic-inorganic hybrid network with tunable surface potential, enabling suppression of contact electrification. When applied to diverse substrates, this coating inhibits charge generation and withstands over 16,000 steel wool abrasion cycles (~25 kPa) without visible scratches while retaining anti-triboelectric properties. It also exhibits high transparency (>91%), anti-smudge performance, and foldability (down to 1 mm bending radius of curvature). This work contributes to overcoming the trade-off between optical clarity, wear resistance, and static suppression, establishing a versatile coating platform for diverse applications. Li et al. report a molecularly tailored strategy to fabricate durable, transparent anti-triboelectric coating by chemically crosslinking electron-donating and electron-withdrawing components.