An elastomer with in situ generated pure zwitterionic surfaces for fibrosis-resistant implants.

Polymeric elastomers are widely utilized in implantable biomedical devices. Nevertheless, the implantation of these elastomers can provoke a robust foreign body response (FBR), leading to the rejection of foreign implants and consequently reducing their effectiveness in vivo. Building effective anti-FBR coatings on those implants remains challenging. Herein, we introduce a coating-free elastomer with superior immunocompatibility. A super-hydrophilic anti-fouling zwitterionic layer can be generated in situ on the surface of the elastomer through a simple chemical trigger. This elastomer can repel the adsorption of proteins, as well as the adhesion of cells, platelets, and diverse microbes. The elastomer elicited negligible inflammatory responses after subcutaneous implantation in rodents for 2 weeks. No apparent fibrotic capsule formation was observed surrounding the elastomer after 6 months in rodents. Continuous subcutaneous insulin infusion (CSII) catheters constructed from the elastomer demonstrated prolonged longevity and performance compared to commercial catheters, indicating its great potential for enhancing and extending the performance of various implantable biomedical devices by effectively attenuating local immune responses. STATEMENT OF SIGNIFICANCE: The foreign body response remains a significant challenge for implants. Complicated coating procedures are usually needed to construct anti-fibrotic coatings on implantable elastomers. Herein, a coating-free elastomer with superior immunocompatibility was achieved using a zwitterionic monomer derivative. A pure zwitterionic layer can be generated on the elastomer surface through a simple chemical trigger. This elastomer significantly reduces protein adsorption, cell and bacterial adhesion, and platelet activation, leading to minimal fibrotic capsule formation even after six months of subcutaneous implantation in rodents. CSII catheters constructed from the PQCBE-H elastomer demonstrated prolonged longevity and performance compared to commercial catheters, highlighting the significant potential of PQCBE-H elastomers for enhancing and extending the performance of various implantable biomedical devices.

Modeling and admittance recursive simulation of anti-reflective coatings for photothermal conversion: synergy between subwavelength structures and gradient refractive index layers.

In the field of photothermal conversion, light-absorbing layers show limitations such as low solar energy utilization and excessive surface reflection. This paper proposes a new anti-reflective coating consisting of a gradient-doped fluorescent glass film covering a subwavelength structural layer for photothermal conversion. Its transmittance was simulated using equivalent medium theory and the admittance recursion method. The subwavelength structure provides a refractive index gradient, and its shape solves the problem of the sharp decrease in transmittance at high angles of incidence. Subsequently, we adjust the material parameters of the gradient refractive layers and control the thickness of each layer to minimize interlayer Fresnel reflections. Finally, the efficient light-trapping ability of the model was verified by calculating and comparing the transmittances of the optimized model and bare glass. Notably, within the visible spectrum, our model achieves an average transmittance of over 95% across wavelength and angle ranges, effectively suppressing surface reflections. At a larger light incident angle, the transmittance increases by 29.7%, and the minimum angle transmittance reaches 92.7%. This study proposes an innovative method to enhance the performance of transmission layers in photothermal conversion devices.

Dual Channel Emissions of Kasha and Anti-Kasha from a Single Radical Molecule.

Stable open-shell luminescent radicals have recently attracted much attention due to their unique luminescence properties. However, a radical molecule with both Kasha and anti-Kasha doublet emission properties has not been reported. Herein, we have successfully synthesized a stable chlorine-substituted Chichibabin's hydrocarbon, TTM-TTM, along with its mono-radical counterpart, TTM-HTTM. The emission of TTM-TTM follows Kasha's rule in the near infrared region. However, TTM-HTTM shows dual channel doublet emissions of Kasha and anti-Kasha. Remarkably, these two types of emission compete dynamically in both solution and condensed states. Our findings provide valuable insights into the rational design and discovery of stable radicals that possess distinctive luminescent properties, thus broadening the horizons of luminescent materials research.

A Causal Regulation Modeling Algorithm for Temporal Events with Application to Escherichia coli's Aerobic to Anaerobic Transition.

Time-series experiments are crucial for understanding the transient and dynamic nature of biological phenomena. These experiments, leveraging advanced classification and clustering algorithms, allow for a deep dive into the cellular processes. However, while these approaches effectively identify patterns and trends within data, they often need to improve in elucidating the causal mechanisms behind these changes. Building on this foundation, our study introduces a novel algorithm for temporal causal signaling modeling, integrating established knowledge networks with sequential gene expression data to elucidate signal transduction pathways over time. Focusing on Escherichia coli's (E. coli) aerobic to anaerobic transition (AAT), this research marks a significant leap in understanding the organism's metabolic shifts. By applying our algorithm to a comprehensive E. coli regulatory network and a time-series microarray dataset, we constructed the cross-time point core signaling and regulatory processes of E. coli's AAT. Through gene expression analysis, we validated the primary regulatory interactions governing this process. We identified a novel regulatory scheme wherein environmentally responsive genes, soxR and oxyR, activate fur, modulating the nitrogen metabolism regulators fnr and nac. This regulatory cascade controls the stress regulators ompR and lrhA, ultimately affecting the cell motility gene flhD, unveiling a novel regulatory axis that elucidates the complex regulatory dynamics during the AAT process. Our approach, merging empirical data with prior knowledge, represents a significant advance in modeling cellular signaling processes, offering a deeper understanding of microbial physiology and its applications in biotechnology.

Multifunctional Conductive Hydrogel Composites with Nickel Nanowires and Liquid Metal Conductive Highways.

The dramatic growth of smart wearable electronics has generated a demand for conductive hydrogels due to their tunability, stimulus responsiveness, and multimodal sensing capabilities. However, the substantial trade-off between mechanical and electrical properties hinders their multifunctionality. Here, we report a double-network hydrogel composite that features a conductive "highway" constructed using magnetic-field-aligned nickel nanowires and liquid metal. The liquid metal fills the gaps between the aligned nickel nanowires. Such interconnected structures can form efficient conductive paths at low filler content, resulting in high conductivity (1.11 × 104 S/m) and mechanical compliance (Young's modulus, 89 kPa; toughness, 721 kJ/m3). When used as a wearable sensor, the hydrogel displays a high sensitivity and fast response for wireless motion detection and human-machine interaction. Furthermore, by exploiting its outstanding conductivity and electrical heating capacity, the hydrogel integrates electromagnetic shielding and thermal management functionalities. Owing to these all-around properties, our design offers a broader platform for expanding hydrogel applications.

Genome-wide characterization of Remorin gene family and their responsive expression to abiotic stresses and plant hormone in Brassica napus.

KEY MESSAGE: Remorin proteins could be positively related to salt and osmotic stress resistance in rapeseed. Remorins (REMs) play a crucial role in adaptations to adverse environments. However, their roles in abiotic stress and phytohormone responses in oil crops are still largely unknown. In this study, we identified 47 BnaREM genes in the B.napus genome. Phylogenetic relationship and synteny analysis revealed that they were categorized into 5 distinct groups and have gone through 55 segmental duplication events under purifying selection. Gene structure and conserved domains analysis demonstrated that they were highly conserved and all BnaREMs contained a conserved Remorin_C domain, with a variable N-terminal region. Promoter sequence analysis showed that BnaREM gene promoters contained various hormones and stress-related cis-acting elements. Transcriptome data from BrassicaEDB database exhibited that all BnaREMs were ubiquitously expressed in buds, stamens, inflorescences, young leaves, mature leaves, roots, stems, seeds, silique pericarps, embryos and seed coats. The qRT-PCR analysis indicated that most of them were responsive to ABA, salt and osmotic treatments. Further mutant complementary experiments revealed that the expression of BnaREM1.3-4C-1 in the Arabidopsis rem1.3 mutant restored the retarded growth phenotype and the ability to resistance to salt and osmotic stresses. Our findings provide fundamental information on the structure and evolutionary relationship of the BnaREM family genes in rapeseed, and reveal the potential function of BnaREM1.3-4C-1 in stress and hormone response.

A Guide to Quantify Arabidopsis Seedling Thermomorphogenesis at Single Timepoints and by Interval Monitoring.

Temperature-induced elongation of hypocotyls, petioles, and roots, together with hyponastic leaf responses, constitute key model phenotypes that can be used to assess a plant's capacity for thermomorphogenesis. Phenotypic responses are often quantified at a single time point during seedling development at different temperatures. However, to capture growth dynamics, several time points need to be assessed, and ideally continuous measurements are taken. Here we describe a general experimental setup and technical solutions for recording and measuring seedling phenotypes at single and multiple time points. Furthermore, we present an R-package called "rootdetectR," which allows easy processing of hypocotyl, root or petiole length, and growth rate data and provides different options of data presentation.

A Novel Induction-Type Pressure Sensor based on Magneto-Stress Impedance and Magnetoelastic Coupling Effect for Monitoring Hand Rehabilitation.

Visualization of training effectiveness is critical to patients' confidence and eventual rehabilitation. Here, an innovative magnetoinductive pressure sensor is proposed for monitoring hand rehabilitation in stroke hemiplegic patients. It couples the giant magneto and stress-impedance effects of a square spiral amorphous wire with the giant magnetoelastic effect of a polymer magnet (NdFeB@PDMS). The addition of the magnetoelastic layer results in a sensitivity improvement of 178%, a wide sensing range (up to 1 MPa), fast response/recovery times (40 ms), and excellent mechanical robustness (over 15 000 cycles). Further integration with an LC oscillation circuit enables frequency adjustment into the MHz range resulting in a sensitivity of 6.6% kPa-1 and outstanding linearity (R2 =  0.99717) over a stress range of up to 100 kPa. When attached to a commercial split-fingerboard, the sensor is capable of dynamically monitoring the force in each finger, providing a reading of the rehabilitation process. Unlike conventional inductive sensors, the sensor is based on an inductive force-responsive material (amorphous wire), which significantly boosts the sensitivity. The approach also demonstrates the potential of magnetoelasticity in static pressure sensing, which is highly sensitive to dynamic pressure only through electromagnetic induction. This makes it more suitable for long-term and continuous human health monitoring.

Poly(Glutamic Acid-Lysine) Hydrogels with Alternating Sequence Resist the Foreign Body Response in Rodents and Non-Human Primates.

The foreign body response (FBR) to implanted biomaterials and biomedical devices can severely impede their functionality and even lead to failure. The discovery of effective anti-FBR materials remains a formidable challenge. Inspire by the enrichment of glutamic acid (E) and lysine (K) residues on human protein surfaces, a class of zwitterionic polypeptide (ZIP) hydrogels with alternating E and K sequences to mitigate the FBR is prepared. When subcutaneously implanted, the ZIP hydrogels caused minimal inflammation after 2 weeks and no obvious collagen capsulation after 6 months in mice. Importantly, these hydrogels effectively resisted the FBR in non-human primate models for at least 2 months. In addition, the enzymatic degradability of the gel can be controlled by adjusting the crosslinking degree or the optical isomerism of amino acid monomers. The long-term FBR resistance and controlled degradability of ZIP hydrogels open up new possibilities for a broad range of biomedical applications.

A wireless fluorescent sensing device for on-site closed-loop detection of hydrazine levels in the environment.

Given the extensive need for the detection of hydrazine (N2H4) in the biomedical and chemical-pharmaceutical sectors, there is a necessity to devise a fast, sensitive, specific, and portable technique for precisely quantifying hydrazine at environmental levels. In our work, an "OFF-ON" type fluorescent probe namely 2-(4-(10-(naphthalen-2-yl)anthracen-9-yl)phenyl)isoindole-1,3-dione (NAP), which was inspired by the "Gabriel" reaction, was synthesized. The NAP fluorescent cellulose film successfully achieved the detection of hydrazine vapor with a LOD = 0.658 ppm. Compared to previous qualitative methods for detecting hydrazine, this study successfully achieved quantitative identification of hydrazine at low concentrations. In addition, a portable sensor device based on NAP cellulose film was successfully integrated, enabling ultra-sensitive, wireless, remote, and real-time detection of N2H4 vapor. It was determined that the probe (NAP) exhibited excellent detection performance when applied to various environmental samples including distilled water, tap water, creek water, soil and plants. This study introduces a potentially effective approach for detecting hydrazine in real-world settings.

Bioinspired Solar-Driven Osmosis for Stable High Flux Desalination.

The growing global water crisis necessitates sustainable desalination solutions. Conventional desalination technologies predominantly confront environmental issues such as high emissions from fossil-fuel-driven processes and challenges in managing brine disposal during the operational stages, emphasizing the need for renewable and environmentally friendly alternatives. This study introduces and assesses a bioinspired, solar-driven osmosis desalination device emulating the natural processes of mangroves with effective contaminant rejection and notable productivity. The bioinspired solar-driven osmosis (BISO) device, integrating osmosis membranes, microporous absorbent paper, and nanoporous ceramic membranes, was evaluated under different conditions. We conducted experiments in both controlled and outdoor settings, simulating seawater with a 3.5 wt % NaCl solution. With a water yield of 1.51 kg m-2 h-1 under standard solar conditions (one sun), the BISO system maintained excellent salt removal and accumulation resistance after up to 8 h of experiments and demonstrated great cavitation resistance even at 58.14 °C. The outdoor test recorded a peak rate of 1.22 kg m-2 h-1 and collected 16.5 mL in 8 h, showing its practical application potential. These results highlight the BISO device's capability to address water scarcity using a sustainable approach, combining bioinspired design with solar power, presenting a viable pathway in renewable-energy-driven desalination technology.

Covalently grafted human serum albumin coating mitigates the foreign body response against silicone implants in mice.

Implantable biomaterials and biosensors are integral components of modern medical systems but often encounter hindrances due to the foreign body response (FBR). Herein, we report an albumin coating strategy aimed at addressing this challenge. Using a facile and scalable silane coupling strategy, human serum albumin (HSA) is covalently grafted to the surface of polydimethylsiloxane (PDMS) implants. This covalently grafted albumin coating remains stable and resistant to displacement by other proteins. Notably, the PDMS with covalently grafted HSA strongly resists the fibrotic capsule formation following a 180-day subcutaneous implantation in C57BL/6 mice. Furthermore, the albumin coating led to reduced recruitment of macrophages and triggered a mild immune activation pattern. Exploration of albumin coatings sourced from various mammalian species has shown that only HSA exhibited a promising anti-FBR effect. The albumin coating method reported here holds the potential to improve and extend the function of silicone-based implants by mitigating the host responses to subcutaneously implanted biomaterials.

Fibrous capsule-resistant, controllably degradable and functionalizable zwitterion-albumin hybrid hydrogels.

Foreign body response (FBR) represents an immune-mediated cascade reaction capable of inducing the rejection of foreign implants, thereby compromising their in vivo performance. Pure zwitterionic hydrogels have demonstrated the ability to resist long-term FBR, owing to their outstanding antifouling capabilities. However, achieving such a robust anti-FBR effect necessitates stringent requirements concerning the purity of zwitterionic materials, which constrains their broader functional applications. Herein, we present a biocompatible, controllably degradable, and functionalizable zwitterion-albumin hybrid hydrogel. The zwitterionic hydrogel crosslinked with serum albumin exhibits controllable degradation and excels in preventing the adsorption of various proteins and adhesion of cells and bacteria. Moreover, the hydrogel significantly alleviates the host's FBR compared with PEG hydrogels and particularly outperforms PEG-based cross-linker crosslinked zwitterionic hydrogels in reducing collagen encapsulation when subcutaneously implanted into mice. The zwitterion-albumin hybrid hydrogel shows potential as a functionalizable anti-FBR material in the context of implantable materials and biomedical devices.

Complex epistatic interactions between ELF3, PRR9, and PRR7 regulate the circadian clock and plant physiology.

Circadian clocks are endogenous timekeeping mechanisms that coordinate internal physiological responses with the external environment. EARLY FLOWERING3 (ELF3), PSEUDO RESPONSE REGULATOR (PRR9), and PRR7 are essential components of the plant circadian clock and facilitate entrainment of the clock to internal and external stimuli. Previous studies have highlighted a critical role for ELF3 in repressing the expression of PRR9 and PRR7. However, the functional significance of activity in regulating circadian clock dynamics and plant development is unknown. To explore this regulatory dynamic further, we first employed mathematical modeling to simulate the effect of the prr9/prr7 mutation on the elf3 circadian phenotype. These simulations suggested that simultaneous mutations in prr9/prr7 could rescue the elf3 circadian arrhythmia. Following these simulations, we generated all Arabidopsis elf3/prr9/prr7 mutant combinations and investigated their circadian and developmental phenotypes. Although these assays could not replicate the results from the mathematical modeling, our results have revealed a complex epistatic relationship between ELF3 and PRR9/7 in regulating different aspects of plant development. ELF3 was essential for hypocotyl development under ambient and warm temperatures, while PRR9 was critical for root thermomorphogenesis. Finally, mutations in prr9 and prr7 rescued the photoperiod-insensitive flowering phenotype of the elf3 mutant. Together, our results highlight the importance of investigating the genetic relationship among plant circadian genes.

A Conjugated Microporous Polymer/Wood Aerogel with Physical Adsorption, Chemical Degradation and Antibacterial Self-Cleaning Triple Sewage Treatment Functions.

Conjugated microporous polymers (CMPs) have important applications in the fields of optoelectronics and sewage treatment due to their high specific surface area, broad visible absorption, processability and simple synthesis process. Biocompatibility, recycling, mass production and solar photodegradation are particularly important in wastewater treatment. Here, A CMP with a high specific surface area and a hierarchical pore structure (CPOP) was constructed based on 4,4',4″-Tris(carbazol-9-yl)-triphenylamine (3CZ-TPA). Furthermore, a CMP-loaded wood aerogel (CPOP/wood aerogel) with physical adsorption, chemical degradation, bacterial inhibition and self-cleaning properties was prepared by in situ polymerization and used for wastewater treatment. The obtained CPOP/wood aerogel is highly biocompatible and easy to recycle. In addition, the inherent broad visible light absorption property of CPOP endows it with promising photocatalytic properties. Subsequently, we investigated the photocatalytic mechanism of CPOP, and the results showed that it was mainly affected by peroxyl radicals, which implied and confirmed its microbial self-cleaning for secondary cleaning of water pollutants. The reported studies on CPOP/wood aerogel provide a new direction for water purification materials with excellent adsorption, degradation and antibacterial properties.

Discovery of isatin-ß-methyldithiocarbazate derivatives as New Delhi metallo- ß-lactamase-1 (NDM-1) inhibitors against NDM-1 producing clinical isolates.

New Delhi metallo-ß-lactamase-1 (NDM-1) poses a threat to public health due to its capability to hydrolyze nearly all ß-lactam antibiotics, leaving limited treatment options for NDM-1 positive pathogens. Regrettably, there are presently no effective NDM-1 inhibitors in clinical use. This compels us to seek new compounds to combat multi-drug resistant bacterial infections (MDR). In our study, Zndm19 was identified as a new NDM-1 inhibitor through virtual screening and an NDM-1 enzyme activity inhibition assay. Subsequently, we employed the checkerboard method, time-killing assay, and combined disk test to investigate the synergistic bactericidal efficacy of Zndm19 in combination with meropenem (MEM). Meanwhile, molecular docking and site-directed mutagenesis were conducted to uncover the crucial amino acid residues engaged in Zndm19 binding. Finally, we established a mice peritonitis infection model to assess the synergistic effect of Zndm19 and MEM in vivo. Our findings demonstrated that 16 µg/mL of Zndm19 inhibited NDM-1 activity without affecting NDM-1 expression, restoring the bactericidal activity of MEM against NDM-1-positive Escherichia coli in vitro. Furthermore, MET-67, ASP-124, HIS-189, and HIS-250 amino acid residues constituted the active site of Zndm19 in NDM-1. Importantly, this combination therapy exhibited synergistic anti-infection activity in the mice peritonitis infection model, leading to an approximate 60% increase in survival rates and reduction of tissue bacterial load, effectively combating bacterial infection in vivo. In summary, our research validates that the synthetic novel NDM-1 inhibitor Zndm19 holds promise as a drug to treat drug-resistant bacterial infections, especially those harboring NDM-1.

Exploration and Biological Evaluation of 1,3-Diamino-7H-pyrrol[3,2-f]quinazoline Derivatives as Dihydrofolate Reductase Inhibitors.

Dihydrofolate reductase (DHFR), a core enzyme of folate metabolism, plays a crucial role in the biosynthesis of purines and thymidylate for cell proliferation and growth in both prokaryotic and eukaryotic cells. However, the development of new DHFR inhibitors is challenging due to the limited number of scaffolds available for drug development. Hence, we designed and synthesized a new class of DHFR inhibitors with a 1,3-diamino-7H-pyrrol[3,2-f]quinazoline derivative (PQD) structure bearing condensed rings. Compound 6r exhibited therapeutic effects on mouse models of systemic infection and thigh infection caused by methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300. Moreover, methyl-modified PQD compound 8a showed a strong efficacy in a murine model of breast cancer, which was better than the effects of taxol. The findings showcased in this study highlight the promising capabilities of novel DHFR inhibitors in addressing bacterial infections as well as breast cancer.

A Robust Drug-Target Interaction Prediction Framework with Capsule Network and Transfer Learning.

Drug-target interactions (DTIs) are considered a crucial component of drug design and drug discovery. To date, many computational methods were developed for drug-target interactions, but they are insufficiently informative for accurately predicting DTIs due to the lack of experimentally verified negative datasets, inaccurate molecular feature representation, and ineffective DTI classifiers. Therefore, we address the limitations of randomly selecting negative DTI data from unknown drug-target pairs by establishing two experimentally validated datasets and propose a capsule network-based framework called CapBM-DTI to capture hierarchical relationships of drugs and targets, which adopts pre-trained bidirectional encoder representations from transformers (BERT) for contextual sequence feature extraction from target proteins through transfer learning and the message-passing neural network (MPNN) for the 2-D graph feature extraction of compounds to accurately and robustly identify drug-target interactions. We compared the performance of CapBM-DTI with state-of-the-art methods using four experimentally validated DTI datasets of different sizes, including human (Homo sapiens) and worm (Caenorhabditis elegans) species datasets, as well as three subsets (new compounds, new proteins, and new pairs). Our results demonstrate that the proposed model achieved robust performance and powerful generalization ability in all experiments. The case study on treating COVID-19 demonstrates the applicability of the model in virtual screening.

Astragaloside IV protects LO2 cells from oxidative damage caused by radiation-induced bystander effect through Akt/Nrf2 pathway.

Background: The protective effects of astragaloside IV (ASIV) on various diseases are well known, but its potential impact on radiation-induced bystander effect (RIBE) has remained unclear. Objective: This study aimed to explore the protective mechanism of ASIV against oxidative damage caused by RIBE in LO2 cells. Methods: To construct the RIBE model, the conditioned medium from HepG2 cells irradiated with radiation was transferred to nonirradiated LO2 cells. LY294002, a commonly used phosphatidylinositol 3-kinase/Akt pathway inhibitor, was added to LO2 cells 1 h before exposing HepG2 cells to radiation. LO2 cells were then collected for analyses after RIBE exposure. Results: The study found that ASIV significantly improved cell proliferation and promoted the recovery of mitochondrial membrane potential while reducing the rate of apoptosis. Western blot analyses demonstrated that ASIV upregulated B-cell lymphoma 2 and downregulated B-cell lymphoma 2-related X protein and cleaved-caspase 3. Measurement of reactive oxygen species, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels showed that ASIV effectively restored the oxidative stress state induced by RIBE. Additionally, immunofluorescence and western blots analyses confirmed that ASIV enhanced the translocation of Nrf2 to the nucleus and activated downstream nicotinamide adenine dinucleotide phosphate: quinine oxidoreductase 1 and heme oxygenase 1. Importantly, Akt pathway inhibitor repressed ASIV-induced activation of Nrf2 and its protective effect against RIBE. Conclusion: This study demonstrates that ASIV protects LO2 cells against oxidative damage caused by RIBE through activation of the Akt/Nrf2 pathway.

Transcription factors MdMYC2 and MdMYB85 interact with ester aroma synthesis gene MdAAT1 in apple.

Volatile esters in apple (Malus domestica) fruit are the critical aroma components determining apple flavor quality. While the exact molecular regulatory mechanism remains unknown, jasmonic acid (JA) plays a crucial role in stimulating the synthesis of ester aromas in apples. In our study, we investigated the effects of methyl jasmonate (MeJA) on the production of ester aroma in apples. MeJA treatment significantly increased ester aroma synthesis, accompanied by the upregulation of several genes involved in the jasmonate pathway transduction. Specifically, expression of the gene MdMYC2, which encodes a transcription factor associated with the jasmonate pathway, and the R2R3-MYB transcription factor gene MdMYB85 increased upon MeJA treatment. Furthermore, the essential gene ALCOHOL ACYLTRANSFERASE 1 (MdAAT1), encoding an enzyme responsible for ester aroma synthesis, showed increased expression levels as well. Our investigation revealed that MdMYC2 and MdMYB85 directly interacted with the promoter region of MdAAT1, thereby enhancing its transcriptional activity. In addition, MdMYC2 and MdMYB85 directly bind their promoters and activate transcription. Notably, the interaction between MdMYC2 and MdMYB85 proteins further amplified the regulatory effect of MdMYB85 on MdMYC2 and MdAAT1, as well as that of MdMYC2 on MdMYB85 and MdAAT1. Collectively, our findings elucidate the role of the gene module consisting of MdMYC2, MdMYB85, and MdAAT1 in mediating the effects of JA and promoting ester aroma synthesis in apples.