Unconventional superconductivity in chiral molecule-TaS2 hybrid superlattices.

Chiral superconductors, a unique class of unconventional superconductors in which the complex superconducting order parameter winds clockwise or anticlockwise in the momentum space1, represent a topologically non-trivial system with intrinsic time-reversal symmetry breaking (TRSB) and direct implications for topological quantum computing2,3. Intrinsic chiral superconductors are extremely rare, with only a few arguable examples, including UTe2, UPt3 and Sr2RuO4 (refs. 4-7). It has been suggested that chiral superconductivity may exist in non-centrosymmetric superconductors8,9, although such non-centrosymmetry is uncommon in typical solid-state superconductors. Alternatively, chiral molecules with neither mirror nor inversion symmetry have been widely investigated. We suggest that an incorporation of chiral molecules into conventional superconductor lattices could introduce non-centrosymmetry and help realize chiral superconductivity10. Here we explore unconventional superconductivity in chiral molecule intercalated TaS2 hybrid superlattices. Our studies reveal an exceptionally large in-plane upper critical field Bc2,|| well beyond the Pauli paramagnetic limit, a robust π-phase shift in Little-Parks measurements and a field-free superconducting diode effect (SDE). These experimental signatures of unconventional superconductivity suggest that the intriguing interplay between crystalline atomic layers and the self-assembled chiral molecular layers may lead to exotic topological materials. Our study highlights that the hybrid superlattices could lay a versatile path to artificial quantum materials by combining a vast library of layered crystals of rich physical properties with the nearly infinite variations of molecules of designable structural motifs and functional groups11.

Parameter-efficient fine-tuning on large protein language models improves signal peptide prediction.

Signal peptides (SP) play a crucial role in protein translocation in cells. The development of large protein language models (PLMs) and prompt-based learning provides a new opportunity for SP prediction, especially for the categories with limited annotated data. We present a parameter-efficient fine-tuning (PEFT) framework for SP prediction, PEFT-SP, to effectively utilize pretrained PLMs. We integrated low-rank adaptation (LoRA) into ESM-2 models to better leverage the protein sequence evolutionary knowledge of PLMs. Experiments show that PEFT-SP using LoRA enhances state-of-the-art results, leading to a maximum Matthews correlation coefficient (MCC) gain of 87.3% for SPs with small training samples and an overall MCC gain of 6.1%. Furthermore, we also employed two other PEFT methods, prompt tuning and adapter tuning, in ESM-2 for SP prediction. More elaborate experiments show that PEFT-SP using adapter tuning can also improve the state-of-the-art results by up to 28.1% MCC gain for SPs with small training samples and an overall MCC gain of 3.8%. LoRA requires fewer computing resources and less memory than the adapter during the training stage, making it possible to adapt larger and more powerful protein models for SP prediction.

MSI-DTI: predicting drug-target interaction based on multi-source information and multi-head self-attention.

Identifying drug-target interactions (DTIs) holds significant importance in drug discovery and development, playing a crucial role in various areas such as virtual screening, drug repurposing and identification of potential drug side effects. However, existing methods commonly exploit only a single type of feature from drugs and targets, suffering from miscellaneous challenges such as high sparsity and cold-start problems. We propose a novel framework called MSI-DTI (Multi-Source Information-based Drug-Target Interaction Prediction) to enhance prediction performance, which obtains feature representations from different views by integrating biometric features and knowledge graph representations from multi-source information. Our approach involves constructing a Drug-Target Knowledge Graph (DTKG), obtaining multiple feature representations from diverse information sources for SMILES sequences and amino acid sequences, incorporating network features from DTKG and performing an effective multi-source information fusion. Subsequently, we employ a multi-head self-attention mechanism coupled with residual connections to capture higher-order interaction information between sparse features while preserving lower-order information. Experimental results on DTKG and two benchmark datasets demonstrate that our MSI-DTI outperforms several state-of-the-art DTIs prediction methods, yielding more accurate and robust predictions. The source codes and datasets are publicly accessible at https://github.com/KEAML-JLU/MSI-DTI.

Loss of the stress sensor GADD45A promotes stem cell activity and ferroptosis resistance in LGR4/HOXA9-dependent AML.

ABSTRACT: The overall prognosis of acute myeloid leukemia (AML) remains dismal, largely because of the inability of current therapies to kill leukemia stem cells (LSCs) with intrinsic resistance. Loss of the stress sensor growth arrest and DNA damage-inducible 45 alpha (GADD45A) is implicated in poor clinical outcomes, but its role in LSCs and AML pathogenesis is unknown. Here, we define GADD45A as a key downstream target of G protein-coupled receptor (LGR)4 pathway and discover a regulatory role for GADD45A loss in promoting leukemia-initiating activity and oxidative resistance in LGR4/HOXA9-dependent AML, a poor prognosis subset of leukemia. Knockout of GADD45A enhances AML progression in murine and patient-derived xenograft (PDX) mouse models. Deletion of GADD45A induces substantial mutations, increases LSC self-renewal and stemness in vivo, and reduces levels of reactive oxygen species (ROS), accompanied by a decreased response to ROS-associated genotoxic agents (eg, ferroptosis inducer RSL3) and acquisition of an increasingly aggressive phenotype on serial transplantation in mice. Our single-cell cellular indexing of transcriptomes and epitopes by sequencing analysis on patient-derived LSCs in PDX mice and subsequent functional studies in murine LSCs and primary AML patient cells show that loss of GADD45A is associated with resistance to ferroptosis (an iron-dependent oxidative cell death caused by ROS accumulation) through aberrant activation of antioxidant pathways related to iron and ROS detoxification, such as FTH1 and PRDX1, upregulation of which correlates with unfavorable outcomes in patients with AML. These results reveal a therapy resistance mechanism contributing to poor prognosis and support a role for GADD45A loss as a critical step for leukemia-initiating activity and as a target to overcome resistance in aggressive leukemia.

Monocytes Release Pro-Cathepsin D to Drive Blood-to-Brain Transcytosis in Diabetes.

BACKGROUND: Microvascular complications are the major outcome of type 2 diabetes progression, and the underlying mechanism remains to be determined. METHODS: High-throughput RNA sequencing was performed using human monocyte samples from controls and diabetes. The transgenic mice expressing human CTSD (cathepsin D) in the monocytes was constructed using CD68 promoter. In vivo 2-photon imaging, behavioral tests, immunofluorescence, transmission electron microscopy, Western blot analysis, vascular leakage assay, and single-cell RNA sequencing were performed to clarify the phenotype and elucidate the molecular mechanism. RESULTS: Monocytes expressed high-level CTSD in patients with type 2 diabetes. The transgenic mice expressing human CTSD in the monocytes showed increased brain microvascular permeability resembling the diabetic microvascular phenotype, accompanied by cognitive deficit. Mechanistically, the monocytes release nonenzymatic pro-CTSD to upregulate caveolin expression in brain endothelium triggering caveolae-mediated transcytosis, without affecting the paracellular route of brain microvasculature. The circulating pro-CTSD activated the caveolae-mediated transcytosis in brain endothelial cells via its binding with low-density LRP1 (lipoprotein receptor-related protein 1). Importantly, genetic ablation of CTSD in the monocytes exhibited a protective effect against the diabetes-enhanced brain microvascular transcytosis and the diabetes-induced cognitive impairment. CONCLUSIONS: These findings uncover the novel role of circulatory pro-CTSD from monocytes in the pathogenesis of cerebral microvascular lesions in diabetes. The circulatory pro-CTSD is a potential target for the intervention of microvascular complications in diabetes.

CSB and SMARCAL1 compete for RPA32 at stalled forks and differentially control the fate of stalled forks in BRCA2-deficient cells.

CSB (Cockayne syndrome group B) and SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent, regulator of chromatin, subfamily A-like 1) are DNA translocases that belong to the SNF2 helicase family. They both are enriched at stalled replication forks. While SMARCAL1 is recruited by RPA32 to stalled forks, little is known about whether RPA32 also regulates CSB's association with stalled forks. Here, we report that CSB directly interacts with RPA, at least in part via a RPA32C-interacting motif within the N-terminal region of CSB. Modeling of the CSB-RPA32C interaction suggests that CSB binds the RPA32C surface previously shown to be important for binding of UNG2 and SMARCAL1. We show that this interaction is necessary for promoting fork slowing and fork degradation in BRCA2-deficient cells but dispensable for mediating restart of stalled forks. CSB competes with SMARCAL1 for RPA32 at stalled forks and acts non-redundantly with SMARCAL1 to restrain fork progression in response to mild replication stress. In contrast to CSB stimulated restart of stalled forks, SMARCAL1 inhibits restart of stalled forks in BRCA2-deficient cells, likely by suppressing BIR-mediated repair of collapsed forks. Loss of CSB leads to re-sensitization of SMARCAL1-depleted BRCA2-deficient cells to chemodrugs, underscoring a role of CSB in targeted cancer therapy.

SIRT5 exacerbates eosinophilic chronic rhinosinusitis by promoting polarization of M2 macrophage.

BACKGROUND: Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated TH2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.

Design of Antiferromagnetic Second-Order Band Topology with Rotation Topological Invariants in Two Dimensions.

The existence of fractionally quantized topological corner charge serves as a key indicator for two-dimensional (2D) second-order topological insulators (SOTIs), yet it has not been experimentally observed in realistic materials. Here, based on effective model analysis and symmetry arguments, we propose a strategy for achieving SOTI phases with in-gap corner states in 2D systems with antiferromagnetic (AFM) order. We discover that the band topology originates from the interplay between intrinsic spin-orbital coupling and interlayer AFM exchange interactions. Using first-principles calculations, we show that the 2D AFM SOTI phase can be realized in (MnBi2Te4)(Bi2Te3)m films. Moreover, we demonstrate that the SOTI states are linked to rotation topological invariants under 3-fold rotation symmetry C3, resulting in fractionally quantized corner charge, i.e., n3|e| (mod e). Due to the great achievements in (MnBi2Te4)(Bi2Te3)m systems, our results providing reliable material candidates for experimentally accessible AFM SOTIs should draw intense attention.

Structural Insights of a cis-Epoxysuccinate Hydrolase Facilitate the Development of Robust Biocatalysts for the Production of l-(+)-Tartrate.

l-(+)-Tartaric acid plays important roles in various industries, including pharmaceuticals, foods, and chemicals. cis-Epoxysuccinate hydrolases (CESHs) are crucial for converting cis-epoxysuccinate to l-(+)-tartrate in the industrial production process. There is, however, a lack of detailed structural and mechanistic information on CESHs, limiting the discovery and engineering of these industrially relevant enzymes. In this study, we report the crystal structures of RoCESH and KoCESH-l-(+)-tartrate complex. These structures reveal the key amino acids of the active pocket and the catalytic triad residues and elucidate a dynamic catalytic process involving conformational changes of the active site. Leveraging the structural insights, we identified a robust BmCESH (550 ± 20 U·mg-1) with sustained catalytic activity even at a 3 M substrate concentration. After six batches of transformation, immobilized cells with overexpressed BmCESH maintained 69% of their initial activity, affording an overall productivity of 200 g/L/h. These results provide valuable insights into the development of high-efficiency CESHs and the optimization of biotransformation processes for industrial uses.

Electron Divergence of Cuδ- and Pdδ+ in Cu3Pd Alloy-Based Heterojunctions Boosts Concerted C≡C Bond Binding and the Volmer Step for Alkynol Semihydrogenation.

Electrocatalytic semihydrogenation of alkynols presents a sustainable alternative to conventional thermal methodologies for the high-value production of alkenols. The design of efficient catalysts with superior catalytic and energy efficiency for semihydrogenation poses a significant challenge. Here, we present the application of an electron-divergent Cu3Pd alloy-based heterojunction in promoting the electrocatalytic semihydrogenation of alkynols to alkenols using water as the proton source. The tunable electron divergence of Cuδ- and Pdδ+, modulated by rectifying contact with nitrogen-rich carbons, enables the concerted binding of active H species from the Volmer step of water dissociation and the C≡C bond of alkynols on Pdδ+ sites. Simultaneously, the pronounced electron divergence of Cu3Pd facilitates the universal adsorption of OH species from the Volmer step and alkynols on the Cuδ- sites. The electron-divergent dual-center substantially boosts water dissociation and inhibition of completing hydrogen evolution to give a turnover frequency of 2412 h-1, outperforming the reported electrocatalysts' value of 7.3. Moreover, the continuous production of alkenols at industrial-related current density (-200 mA cm-2) over the efficient and durable Cu3Pd-based electrolyzer could achieve a cathodic energy efficiency of 45 mol kW·h-1, 1.7 times the bench-marked reactors, promising great potential for sustainable industrial synthesis.

Mild-Temperature Supercritical Water Confined in Hydrophobic Metal-Organic Frameworks.

Fluids under extreme confinement show characteristics significantly different from those of their bulk counterpart. This work focuses on water confined within the complex cavities of highly hydrophobic metal-organic frameworks (MOFs) at high pressures. A combination of high-pressure intrusion-extrusion experiments with molecular dynamic simulations and synchrotron data reveals that supercritical transition for MOF-confined water takes place at a much lower temperature than in bulk water, ∼250 K below the reference values. This large shifting of the critical temperature (Tc) is attributed to the very large density of confined water vapor in the peculiar geometry and chemistry of the cavities of Cu2tebpz (tebpz = 3,3',5,5'-tetraethyl-4,4'-bipyrazolate) hydrophobic MOF. This is the first time the shift of Tc is investigated for water confined within highly hydrophobic nanoporous materials, which explains why such a large reduction of the critical temperature was never reported before, neither experimentally nor computationally.

User-Friendly Multifunctional Red-Emissive Carbon Dots for Rapid Cell Nucleus Staining via Targeting Nuclear Proteins.

Cytoarchitectural staining is of great importance in disease diagnosis and cell biology research. This study developed user-friendly multifunctional red-emissive carbon dots (R-CDs) for rapid cell nucleus staining via targeting nuclear proteins. R-CDs, simply prepared by electrochemical treatment of 1,2,4-benzenetriamine, exhibit strong emission at 635 nm when excited at 507 nm. The R-CDs can rapidly stain the nucleus of human SH-SY5Y, HepG2, and HUH-7 cells with a high signal-to-noise ratio owing to fluorescence enhancement after entering the nucleus. Compared to conventional cytosolic dyes such as Hoechst and DAPI, R-CDs are cheaper, more highly dispersed in water, and more stable (requiring no stringent storage conditions). The R-CDs show stable optical properties with insignificant photobleaching over 7 days and salt resistance up to 2 M of NaCl. More importantly, R-CDs, possessing a positive charge, allow rapid staining of live cells (3 min) and dead cells (10 s) in saline. According to kinetic variation, R-CDs can distinguish live cells from dead cells. Staining exhibits high efficiency in onion epidermal cells, Aspergillus niger, Caenorhabditis elegans, and human spermatozoa. The mechanism for efficient staining is based on their fast accumulation in the nucleus due to their small size and positive charge and strong interaction with nuclear proteins at amino acid residues of histidine and arginine, resulting in fluorescence enhancement by dozens of times. The developed R-CDs do not bind to DNA and would not cause genetic damage and will find various safe applications in biological and medical fields.

Ultraphotostable Phosphorescent Nanosensors for Sensing the Lysosomal pH at the Single-Cell Level over Long Durations.

Ultraphotostable phosphorescent nanosensors have been designed for continuously sensing the lysosome pH over a long duration. The nanosensors exhibited excellent photostability, high accuracy, and capability to measure pH values during cell proliferation for up to 7 days. By arranging a metal-ligand complex of long phosphorescence lifetime and pH indicator in silica nanoparticles, we discover efficient Förster resonance energy transfer, which converts the pH-responsive UV-vis absorption signal of the pH indicator into a phosphorescent signal. Both the phosphorescent intensity and lifetime change at different pH values, and intracellular pH values can be accurately measured by our custom-built rapid phosphorescent lifetime imaging microscopy. The excellent photostability, high accuracy, and good biocompatibility prove that these nanosensors are a useful tool for tracing the fluctuation of pH values during endocytosis. The methodology can be easily adapted to design new nanosensors with different pKa or for different kinds of intracellular ions, as there are hundreds of pH and ion indicators readily available.

The clinical value of artificial intelligence in assisting junior radiologists in thyroid ultrasound: a multicenter prospective study from real clinical practice.

BACKGROUND: This study is to propose a clinically applicable 2-echelon (2e) diagnostic criteria for the analysis of thyroid nodules such that low-risk nodules are screened off while only suspicious or indeterminate ones are further examined by histopathology, and to explore whether artificial intelligence (AI) can provide precise assistance for clinical decision-making in the real-world prospective scenario. METHODS: In this prospective study, we enrolled 1036 patients with a total of 2296 thyroid nodules from three medical centers. The diagnostic performance of the AI system, radiologists with different levels of experience, and AI-assisted radiologists with different levels of experience in diagnosing thyroid nodules were evaluated against our proposed 2e diagnostic criteria, with the first being an arbitration committee consisting of 3 senior specialists and the second being cyto- or histopathology. RESULTS: According to the 2e diagnostic criteria, 1543 nodules were classified by the arbitration committee, and the benign and malignant nature of 753 nodules was determined by pathological examinations. Taking pathological results as the evaluation standard, the sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) of the AI systems were 0.826, 0.815, 0.821, and 0.821. For those cases where diagnosis by the Arbitration Committee were taken as the evaluation standard, the sensitivity, specificity, accuracy, and AUC of the AI system were 0.946, 0.966, 0.964, and 0.956. Taking the global 2e diagnostic criteria as the gold standard, the sensitivity, specificity, accuracy, and AUC of the AI system were 0.868, 0.934, 0.917, and 0.901, respectively. Under different criteria, AI was comparable to the diagnostic performance of senior radiologists and outperformed junior radiologists (all P < 0.05). Furthermore, AI assistance significantly improved the performance of junior radiologists in the diagnosis of thyroid nodules, and their diagnostic performance was comparable to that of senior radiologists when pathological results were taken as the gold standard (all p > 0.05). CONCLUSIONS: The proposed 2e diagnostic criteria are consistent with real-world clinical evaluations and affirm the applicability of the AI system. Under the 2e criteria, the diagnostic performance of the AI system is comparable to that of senior radiologists and significantly improves the diagnostic capabilities of junior radiologists. This has the potential to reduce unnecessary invasive diagnostic procedures in real-world clinical practice.

Counterintuitive Trend of Intrusion Pressure with Temperature in the Hydrophobic Cu2(tebpz) MOF.

Liquid porosimetry experiments reveal a peculiar trend of the intrusion pressure of water in hydrophobic Cu2(3,3',5,5'-tetraethyl-4,4'-bipyrazolate) MOF. At lower temperature (T) range, the intrusion pressure (Pi) increases with T. For higher T values, Pi first reaches a maximum and then decreases. This is at odds with the Young-Laplace law, which for systems showing a continuous decrease of contact angle with T predicts a corresponding reduction of the intrusion pressure. Though the Young-Laplace law is not expected to provide quantitative predictions at the subnanoscale of Cu2(tebpz) pores, the physical intuition suggests that to a reduction of their hydrophobicity corresponds a reduction of the Pi. Molecular dynamics simulations and sychrothron experiments allowed to clarify the mechanism of the peculiar trend of Pi with T. At increasing temperatures the vapor density within the MOF' pores grows significantly, bringing the corresponding partial pressure to ≈5 MPa. This pressure, which is consistent with the shift of Pi observed in liquid porosimetry, represents a threshold to be overcame before intrusion takes place. Beyond some value of temperature, the phenomenon of reduction of hydrophobicity (and water surface tension) dominated over the opposite effect of increase of vapor pressure and Pi inverts its trend with T.

Telitacicept in patients with active systemic lupus erythematosus: results of a phase 2b, randomised, double-blind, placebo-controlled trial.

OBJECTIVES: This phase 2b, randomised, double-blind, placebo-controlled trial evaluated the efficacy and safety of telitacicept, a novel fusion protein that neutralises signals of B lymphocyte stimulator and a proliferation-inducing ligand, in active systemic lupus erythematosus (SLE). METHODS: Adult patients with active SLE (n=249) were recruited from 29 hospitals in China and randomised 1:1:1:1 to receive subcutaneous telitacicept at 80 mg (n=62), 160 mg (n=63), 240 mg (n=62) or placebo (n=62) once weekly in addition to standard therapy. The primary endpoint was the proportion of patients achieving an SLE Responder Index 4 (SRI-4) response at week 48. Missing data were imputed using the last observation carried forward method. RESULTS: At week 48, the proportion of patients achieving an SRI-4 response was 75.8% in the 240 mg telitacicept group, 68.3% in the 160 mg group, 71.0% in the 80 mg group and 33.9% in the placebo group (all p<0.001). Significant treatment responses were observed in secondary endpoints, including a ≥4-point reduction on the Systemic Lupus Erythematosus Disease Activity Index, a lack of Physician's Global Assessment score worsening and a glucocorticoid dose reduction in the 240 mg group. Telitacicept was well tolerated, and the incidence of adverse events and serious adverse events was similar between the telitacicept and placebo groups. CONCLUSIONS: This phase 2b clinical trial met the primary endpoint. All telitacicept groups showed a significantly higher proportion of patients achieving an SRI-4 response than the placebo group at week 48, and all doses were well tolerated. These results support further investigations of telitacicept in clinical trials involving more diverse populations and larger sample sizes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT02885610).

Changes of cerebral structure and perfusion in subtypes of systemic sclerosis: a brain magnetic resonance imaging study.

OBJECTIVES: The characteristics of brain impairment in different subtypes of systemic sclerosis (SSc) (dcSSc, diffuse cutaneous SSc; lcSSc, limited cutaneous SSc) remain unclear. This study aimed to characterize cerebral structure and perfusion changes in different subtype of SSc patients using magnetic resonance (MR) imaging. METHODS: Seventy SSc patients (46.0 ± 11.7 years, 62 females) and 30 healthy volunteers (44.8 ± 13.7 years, 24 females) were recruited and underwent brain MR imaging and Montreal Cognitive Assessment (MoCA) test. Gray matter (GM) volumes were measured using voxel-based morphometry analysis on T1-weighted images. Voxel-based and regional cerebral blood flow (CBF) was calculated on arterial spin labelling images. The cerebral structural and perfusion measurements by MR imaging were compared among dcSSc, lcSSc and healthy subjects using one-way ANOVA. The correlations between clinical characteristics and MR imaging measurements were also analyzed. RESULTS: The dcSSc patients exhibited a significant reduction in GM volume in the para-hippocampal region (cluster p < 0.01, FWE corrected) compared with healthy volunteers. Whereas, SSc patients, particularly lcSSc patients, showed elevated CBF in cerebellum, insula, cerebral cortex, and subcortical structures (regional analyses: all p < 0.05; voxel-based analyses: cluster p < 0.01, FWE corrected). Furthermore, clinical characteristics of modified Rodnan skin score (mRSS) (r value ranged from -0.29 to -0.45), MoCA scores (r = 0.40) and antinuclear antibody (ANA) positivity (r=-0.33) were significantly associated with CBF in some regions (all p < 0.05). CONCLUSION: The manifestations of brain involvement vary among different subtypes of SSc. In addition, severe skin sclerosis may indicate higher risk of brain involvement in SSc patients.

Ethylene-mediated stomatal responses to dehydration and rehydration in seed plants.

Ethylene, a plant hormone that significantly influences both plant growth and response to stress, plays a well-established role in stress signaling. However, its impact on stomatal opening and closure during dehydration and rehydration remains relatively unexplored and is still debated. Exogenous ethylene has been proven to induce stomatal closure through a series of signaling pathways, including the accumulation of reactive oxygen species (ROS), subsequent synthesis of nitric oxide (NO) and hydrogen sulfide (H2S), and SLOW ANION CHANNEL-ASSOCIATED 1 (SLAC1) activation. Thus, it has been suggested that ethylene might function to induce stomatal closure synergistically with abscisic acid (ABA). Furthermore, it has also been shown that increased ethylene can inhibit ABA- and jasmonic acid (JA)-induced stomatal closure, thus hindering drought-induced closure during dehydration. Simultaneously, other stresses, such as chilling, ozone pollution and K+ deficiency, inhibit drought and ABA-induced stomatal closure through an ethylene synthesis dependent way. However, ethylene has been shown to take on an opposing role during rehydration, preventing stomatal opening in the absence of ABA through its own signaling pathway. These findings offer novel insights into the function of ethylene in stomatal regulation during dehydration and rehydration, gaining a better understanding of the mechanisms underlying ethylene-induced stomatal movement in seed plants.