Exposure to the World Trade Center Particulate Matter Alters the Gut-Brain Axis in Early Onset Alzheimer's Disease Mice.

Background: The September 11, 2001, catastrophe unleashed widespread destruction beyond the World Center (WTC), with fires and toxic gases leaving lasting impacts. First responders at Ground Zero faced prolonged exposure to hazardous particulate matter (PM), resulting in chronic health challenges. Among the multitude of health concerns, the potential association between the WTCPM and Alzheimer's disease (AD) has emerged as an area of intense inquiry, probing the intricate interplay between environmental factors and neurodegenerative diseases. Objective: We posit that a genetic predisposition to AD in mice results in dysregulation of the gut-brain axis following chronic exposure to WTCPM. This, in turn, may heighten the risk of AD-like symptoms in these individuals. Methods: 3xTg-AD and WT mice were intranasally administered with WTCPM collected at Ground Zero within 72 hours after the attacks. Working memory and learning and recognition memory were monitored for 4 months. Moreover, brain transcriptomic analysis and gut barrier permeability along with microbiome composition were examined. Results: Our findings underscore the deleterious effects of WTCPM on cognitive function, as well as notable alterations in brain genes associated with synaptic plasticity, pro-survival, and inflammatory signaling pathways. Complementary, chronic exposure to the WTCPM led to increased gut permeability in AD mice and altered bacteria composition and expression of functional pathways in the gut. Conclusions: Our results hint at a complex interplay between gut and brain axis, suggesting potential mechanisms through which WTCPM exposure may exacerbate cognitive decline. Identifying these pathways offers opportunities for tailored interventions to alleviate neurological effects among first responders.

2D MXene/MBene Superlattice with Narrow Bandgap as Superior Electrocatalyst for High-Performance Lithium-Oxygen Battery.

Lithium-oxygen (Li-O2) battery with large theoretical energy density (≈3500 Wh kg-1) is one of the most promising energy storage and conversion systems. However, the slow kinetics of oxygen electrode reactions inhibit the practical application of Li-O2 battery. Thus, designing efficient electrocatalysts is crucial to improve battery performance. Here, Ti3C2 MXene/Mo4/3B2-x MBene superlattice is fabricated its electrocatalytic activity toward oxygen redox reactions in Li-O2 battery is studied. It is found that the built-in electric field formed by a large work function difference between Ti3C2 and Mo4/3B2-x will power the charge transfer at the interface from titanium (Ti) site in Ti3C2 to molybdenum (Mo) site in Mo4/3B2-x. This charge transfer increases the electron density in 4d orbital of Mo site and decreases the d-band center of Mo site, thus optimizing the adsorption of intermediate product LiO2 at Mo site and accelerating the kinetics of oxygen electrode reactions. Meanwhile, the formed film-like discharge products (Li2O2) improve the contact with electrode and facilitate the decomposition of Li2O2. Based on the above advantages, the Ti3C2 MXene/Mo4/3B2-x MBene superlattice-based Li-O2 battery exhibits large discharge specific capacity (17 167 mAh g-1), low overpotential (1.16 V), and superior cycling performance (475 cycles).

The Role of the Neural Exposome as a Novel Strategy to Identify and Mitigate Health Inequities in Alzheimer's Disease and Related Dementias.

With the continuous increase of the elderly population, there is an urgency to understand and develop relevant treatments for Alzheimer's disease and related dementias (ADRD). In tandem with this, the prevalence of health inequities continues to rise as disadvantaged communities fail to be included in mainstream research. The neural exposome poses as a relevant mechanistic approach and tool for investigating ADRD onset, progression, and pathology as it accounts for several different factors: exogenous, endogenous, and behavioral. Consequently, through the neural exposome, health inequities can be addressed in ADRD research. In this paper, we address how the neural exposome relates to ADRD by contributing to the discourse through defining how the neural exposome can be developed as a tool in accordance with machine learning. Through this, machine learning can allow for developing a greater insight into the application of transferring and making sense of experimental mouse models exposed to health inequities and potentially relate it to humans. The overall goal moving beyond this paper is to define a multitude of potential factors that can increase the risk of ADRD onset and integrate them to create an interdisciplinary approach to the study of ADRD and subsequently translate the findings to clinical research.

Energy level regulation of anions via hydrogen bond effects to construct a stable solid electrolyte interface for a high-stability lithium metal anode.

An intermolecular hydrogen bond between 2,5-dihydroxyterephthalic acid and the anions in the Li+ solvation shell is constructed to promote the formation of a LiF-rich SEI on a metallic Li electrode. Li metal batteries with improved cyclability (140 cycles under an N/P ratio of 4.9) and high capacity retention (90%) are eventually obtained.

MCM8 interacts with DDX5 to promote R-loop resolution.

MCM8 has emerged as a core gene in reproductive aging and is crucial for meiotic homologous recombination repair. It also safeguards genome stability by coordinating the replication stress response during mitosis, but its function in mitotic germ cells remains elusive. Here we found that disabling MCM8 in mice resulted in proliferation defects of primordial germ cells (PGCs) and ultimately impaired fertility. We further demonstrated that MCM8 interacted with two known helicases DDX5 and DHX9, and loss of MCM8 led to R-loop accumulation by reducing the retention of these helicases at R-loops, thus inducing genome instability. Cells expressing premature ovarian insufficiency-causative mutants of MCM8 with decreased interaction with DDX5 displayed increased R-loop levels. These results show MCM8 interacts with R-loop-resolving factors to prevent R-loop-induced DNA damage, which may contribute to the maintenance of genome integrity of PGCs and reproductive reserve establishment. Our findings thus reveal an essential role for MCM8 in PGC development and improve our understanding of reproductive aging caused by genome instability in mitotic germ cells.

Controllable Regulation of the Oxygen Redox Process in Lithium-Oxygen Batteries by High-Configuration-Entropy Spinel with an Asymmetric Octahedral Structure.

Designing bifunctional electrocatalysts to boost oxygen redox reactions is critical for high-performance lithium-oxygen batteries (LOBs). In this work, high-entropy spinel (Co0.2Mn0.2Ni0.2Fe0.2Cr0.2)3O4 (HEOS) is fabricated by modulating the internal configuration entropy of spinel and studied as the oxygen electrode catalyst in LOBs. Under the high-entropy atomic environment, the Co-O octahedron in spinel undergoes asymmetric deformation, and the reconfiguration of the electron structure around the Co sites leads to the upward shift of the d-orbital centers of the Co sites toward the Fermi level, which is conducive to the strong adsorption of redox intermediate LiO2 on the surface of the HEOS, ultimately forming a layer of a highly dispersed Li2O2 thin film. Thin-film Li2O2 is beneficial for ion diffusion and electron transfer at the electrode-electrolyte interface, which makes the product easy to decompose during the charge process, ultimately accelerating the kinetics of oxygen redox reactions in LOBs. Based on the above advantages, HEOS-based LOBs deliver high discharge/charge capacity (12.61/11.72 mAh cm-2) and excellent cyclability (424 cycles). This work broadens the way for the design of cathode catalysts to improve oxygen redox kinetics in LOBs.

Applications of Life Cycle Assessment in the Chocolate Industry: A State-of-the-Art Analysis Based on Systematic Review.

Chocolate is a popular food for its unique flavor and taste, rich nutritional value, and the psychological values brought to people. The raw material production of chocolate, product manufacturing, sales and transportation have different degrees of environmental impact. This review explores the environmental hot spots in the life cycle of chocolate and puts forward corresponding suggestions for the improvement. By applying a systematic review method, this paper collected 25 articles on life cycle assessment (LCA) of the environmental impact of the chocolate industry. It is found that the life cycle of chocolate has the highest environmental impact in the raw material production and chocolate manufacturing stages (accounting for 77-97% of total impacts), among which milk powder, sugar and cocoa derivatives are the important contributors to significant environmental burden. Dark chocolate generates the lowest carbon emissions (1.67 kg CO2 eq/kg product) among existing chocolate categories, while the chocolate confectionery products release the highest carbon emissions (6.76 kg CO2 eq/kg product) among chocolate-containing products. Improvement measures are proposed for reducing environmental impacts and for selecting environmentally friendly product formulae. This study can provide benchmarking for the chocolate industry and improves the understanding of life cycle environmental impacts of chocolate products.

Optimized Lithium Ion Coordination via Chlorine Substitution to Enhance Ionic Conductivity of Garnet-Based Solid Electrolytes.

Garnet-type solid-state electrolytes attract abundant attentions due to the broad electrochemical window and remarkable thermal stability while their poor ionic conductivity obstructs their widespread application in all-solid-state batteries. Herein, the enhanced ionic conductivity of garnet-type solid electrolytes is achieved by partially substituting O2- sites with Cl- anions, which effectively reduce Li+ migration barriers while preserving the highly conductive cubic phase of garnet-type solid-state electrolytes. This substitution not only weakens the anchoring effect of anions on Li+ to widen the size of Li+ diffusion channel but also optimizes the occupancy of Li+ at different sites, resulting in a substantial reduction of the Li+ migration barrier and a notable improvement in ionic conductivity. Leveraging these advantageous properties, the developed Li6.35La3Zr1.4Ta0.6O11.85-Cl0.15 (LLZTO-0.15Cl) electrolyte demonstrates high Li+ conductivity of 4.21×10-6 S cm-1. When integrated with LiFePO4 (LFP) cathode and metallic lithium anode, the LLZTO-0.15Cl electrolyte enables the solid-state battery to operate for more than 100 cycles with a high capacity retention of 76.61% and superior Coulombic efficiency of 99.48%. This work shows a new strategy for modulating anionic framework to enhance the conductivity of garnet-type solid-state electrolytes.

Toward the Improvement of the Mechanical and Tribological Properties of Braided Ligament for ACL Reconstruction: A "Carrot and Stick" Strategy.

Bone tunnel enlargement has been troubling the clinical adoption of braided artificial ligaments for decades, to which mechanical and tribological performance promotion shall be an effective and promising approach. Herein, a "carrot and stick" strategy has been introduced with two types of polyethylene terephthalate (PET) fibers to fabricate hybrid textures, which is expected to advance fatigue and tribological performance without yielding essential mechanical strength and biocompatibility. Owing to advancements in such a "carrot and stick" strategy, the obtained grafts present three promising properties: i) enhancement of mechanical strength; ii) coefficient of friction (COF) reduction of 25% at the greatest extent, thus lowering the risk of bone tunnel enlargement; iii) final displacement shrinkage of graft length after cyclic loadings, favored in the clinic for isometric reconstruction. The results obtained in this study show that the "carrot and stick" strategy can be a creative and convenient method to optimize the service life, saving the complication rate of artificial ligaments for clinical applications.

Structure and Charge Regulation Strategy Enabling Superior Cycling Stability of Ni-Rich Cathode Materials.

Ni-rich layered oxides LiNixCoyMn1-x-yO2 (NCMs, x > 0.8) are the most promising cathode candidates for Li-ion batteries because of their superior specific capacity and cost affordability. Unfortunately, NCMs suffer from a series of formidable challenges such as structural instability and incompatibility with commonly used electrolytes, which seriously hamper their practical applications on a large scale. Herein, the Al/Ta codoping modification strategy is proposed to improve the performance of the LiNi0.83Co0.1Mn0.07O2 cathode, and the as-prepared Al/Ta-modified LiNi0.83Co0.1Mn0.07O2 delivers exceptional cycling stability with a capacity retention of 97.4% after 150 cycles at 1C and an excellent rate performance with a high capacity of 143.2 mAh g-1 even at 3C. Based on the experimental study, it is found that the structural stability of NCM is strengthened due to the regulated coordination of oxygen by introducing a robust Ta-O covalent bond, which prevents the layered structure from collapsing. Moreover, the reconstructed rock-salt-like surface is capable of effectively inhibiting interfacial side reactions as well as the overgrowth of the cathode-electrolyte interface. Theoretically, the energy of Li/Ni mixing is significantly increased with the introduction of Al and Ta elements in Al/Ta codoped NCM, leading to inhibited adverse phase transition during cycling. A feasible pathway for designing and developing advanced Ni-rich cathode materials for Li-ion batteries is provided in this work.

Role of Artificial Intelligence in Multinomial Decisions and Preventative Nutrition in Alzheimer's Disease.

Alzheimer's disease (AD) affects 50 million people worldwide, an increase of 35 million since 2015, and it is known for memory loss and cognitive decline. Considering the morbidity associated with AD, it is important to explore lifestyle elements influencing the chances of developing AD, with special emphasis on nutritional aspects. This review will first discuss how dietary factors have an impact in AD development and the possible role of Artificial Intelligence (AI) and Machine Learning (ML) in preventative care of AD patients through nutrition. The Mediterranean-DASH diets provide individuals with many nutrient benefits which assists the prevention of neurodegeneration by having neuroprotective roles. Lack of micronutrients, protein-energy, and polyunsaturated fatty acids increase the chance of cognitive decline, loss of memory, and synaptic dysfunction among others. ML software has the ability to design models of algorithms from data introduced to present practical solutions that are accessible and easy to use. It can give predictions for a precise medicine approach to evaluate individuals as a whole. There is no doubt the future of nutritional science lies on customizing diets for individuals to reduce dementia risk factors, maintain overall health and brain function.

Adjusting Li+ Solvation Structures via Dipole-Dipole Interaction to Construct Inorganic-Rich Interphase for High-Performance Li Metal Batteries.

Practical applications of lithium metal batteries are limited by unstable solid electrolyte interphase (SEI) and uncontrollable dendrite Li deposition. Regulating the solvation structure of Li+ via modifying electrolyte components enables optimizing the structure of the SEI and realizing dendrite-free Li deposition. In this work, it is found that the ionic-dipole interactions between the electron-deficient B atoms in lithium oxalyldifluoro borate (LiDFOB) and the O atoms in the DME solvent molecule can weaken the interaction between the DME molecule and Li+, accelerating the desolvation of Li+. On this basis, the ionic-dipole interactions facilitate the entry of abundant anions into the inner solvation sheath of Li+, which promotes the formation of inorganic-rich SEI. In addition, the interaction between DFOB- and DME molecules reduces the highest occupied molecular orbital energy level of DME molecules in electrolytes, which improves the oxidative stability of the electrolytes system. As a result, the Li||Li cells in LiDFOB-containing electrolytes exhibit an excellent cyclability of over 1800 h with a low overpotential of 18.2 mV, and the Li||LiFePO4 full cells display a high-capacity retention of 93.4% after 100 cycles with a high Coulombic efficiency of 99.3%.

Dachengqi decoction alleviates acute lung injury by suppressing HIF-1α-mediated glycolysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) is an aggressive inflammatory disease of the lungs characterized by a high mortality rate. More and more researchers have found that herbal medicines are highly effective in preventing and treating inflammatory lung diseases. Among them, Dachengqi Decoction (DCQD) is considered to be the representative prescription of "lung-intestine combined treatment" in traditional Chinese medicine, and its potential protective mechanism against ALI is worthy of further study. AIM OF THE STUDY: Based on the theory of "lung-intestine combined treatment", the protective effect and molecular mechanism of DCQD in alleviating ALI were verified by network pharmacology and experiments. MATERIALS AND METHODS: The active ingredients of DCQD were obtained by UPLC-MS. Network pharmacology and molecular docking techniques were used to screen the active ingredient-target pathway of DCQD for ALI treatment. Additionally, the ALI model was constructed and verified in vivo according to the predicted results. RESULTS: 34 active components and 570 potential targets of DCQD were selected by network pharmacological analysis. In addition, 950 target genes of ALI and 2095 target genes related to sepsis were obtained, and 570 interlinked target genes of the two were identified. We finally screened out 199 common target genes critical to DCQD treatment of ALI and sepsis, and then enriched them with GO and KEGG. In the ALI model, studies have found that DCQD alleviates the inflammatory response of ALI, possibly by inhibiting HIF-1α-mediated glycolysis. CONCLUSION: This study confirmed the preventive effect of DCQD on ALI, and found that DCQD can improve the protective mechanism of ALI by regulating the expression of HIF-1α, down-regulating glycolysis and reducing inflammation.

p16 and p53 can Serve as Prognostic Markers for Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: The present study aimed to explore the expression and clinical significance of human papilloma virus-related pathogenic factors (p16, cyclin D1, p53) in patients with head and neck squamous cell carcinoma (HNSCC) and construct a predictive model. METHODS: The Cancer Genome Atlas was used to obtain clinical data for 112 patients with HNSCC. Expression of p16, p53, and cyclin D1 was quantified. We used the survival package of the R program to set the cut-off value. Values above the cut-off were considered positive, while values below the cut-off were negative. Kaplan-Meier analysis and univariate and multivariate Cox regression analyses were performed to investigate prognostic clinicopathological indicators and the expression of p16, p53, and cyclin D1. A predictive model was constructed based on the results of multifactor Cox regression analysis, and the accuracy of the predictive model was verified through final calibration analysis. Follow-up of patients with HNSCC at the Affiliated Hospital of Binzhou Medical University was conducted from 2015 to 2017, and reliability of the predictive model was validated based on follow-up data and molecular expression levels. RESULTS: According to the results, expression of p16 and p53 was significantly associated with prognosis (P < .05). The predictive model constructed based on the expression levels of p16 and p53 was useful for evaluating the prognosis of patients with HNSCC. The predictive model was validated using follow-up data obtained from the hospital, and the trend of the follow-up results was consistent with the predictive model. CONCLUSION: p16 and p53 can be used as key indicators to predict the prognosis of HNSCC patients and as critical immunohistochemical indicators in clinical practice. The survival model constructed based on p16 and p53 expression levels reliably predicts patient prognosis.

Herba Patriniae and its component Isovitexin show anti-colorectal cancer effects by inducing apoptosis and cell-cycle arrest via p53 activation.

Colorectal cancer (CRC) is the most prevalent cancer of the digestive tract. Herba Patriniae (also known as Bai Jiang Cao, HP) have been widely used to manage diarrhea, ulcerative colitis, and several cancers, including CRC. Nonetheless, the molecular mechanisms underlying the pharmacological action of HP on CRC remain unclear. This study investigated the underlying mechanisms of HP against CRC using network pharmacology analysis and in vitro and in vivo experiments. The results revealed nine bioactive compounds of HP. Furthermore, 3460 CRC-related targets of the identified active compounds were predicted from the Gene Expression Omnibus (GEO) database. Furthermore, 65 common targets were identified through the intersection of two related targets. Moreover, ten hub genes, including CDK4, CDK2, CDK1, CCND1, CCNB1, CCNA2, MYC, E2F1, CHEK1, and CDKN1A were identified through the topological analysis. Meanwhile, the GO and KEGG pathway analysis revealed that the core target genes were majorly enriched in the p53 and HIF-1 signaling pathways. Moreover, HP promoted apoptosis and suppressed cell proliferation by activating the p53 signaling pathway in a dose-dependent manner, while a similar effect was observed for Isovitexin (the primary component of HP). Overall, this study provides valuable insights into the underlying mechanisms of HP and its component Isovitexin against CRC, providing a theoretical foundation for additional experimental verification of its clinical application.

Bidirectional Invisible Photoresponse Implemented in a Traps Matrix-Combination toward Fully Optical Artificial Synapses.

Fully optical artificial synapses are crucial hardware for neuromorphic computing, which is very promising to address the future large-scale computing capacity problem. The key characteristic required in a semiconductor device to emulate synaptic potentiation and depression in a fully optical artificial synapse is the bidirectional photoresponse. This work integrates wide-band-gap TiO2 polycrystals and narrow-band-gap PbS quantum dots into a graphene transistor simultaneously, providing the device with both near-ultraviolet and near-infrared photoresponses through the photogating effect. Moreover, the TiO2 serves as a hole-trapping matrix and the PbS as an electron-trapping matrix, which impose opposite effects to the device after photoexcitation, resulting in a photoresponse in the opposite polarity. As a result, the device demonstrates a wavelength-dependent bidirectional photoresponse, which enables it to be utilized as a fully optical artificial synapse. By using near-ultraviolet or near-infrared lights as stimuli, the device successfully mimics synaptic plasticity, including synaptic potentiation/depression, paired-pulse facilitation, and spike-rating-dependent plasticity, as well as the human brain-like transition of short-term memory and long-term memory and learning-experience behavior. This work validates the methodology of combining different trap matrices to achieve the bidirectional photoresponse, which can significantly inspire future research in fully optical artificial synapses.

Supramolecular Responsive Chitosan Microcarriers for Cell Detachment Triggered by Adamantane.

Supramolecular responsive microcarriers based on chitosan microspheres were prepared and applied for nonenzymatic cell detachment. Briefly, chitosan microspheres (CSMs) were first prepared by an emulsion crosslinking approach, the surface of which was then modified with ß-cyclodextrin (ß-CD) by chemical grafting. Subsequently, gelatin was attached onto the surface of the CSMs via the host-guest interaction between ß-CD groups and aromatic residues in gelatin. The resultant microspheres were denoted CSM-g-CD-Gel. Due to their superior biocompatibility and gelatin niches, CSM-g-CD-Gel microspheres can be used as effective microcarriers for cell attachment and expansion. L-02, a human fetal hepatocyte line, was used to evaluate cell attachment and expansion with these microcarriers. After incubation for 48 h, the cells attached and expanded to cover the entire surface of microcarriers. Moreover, with the addition of adamantane (AD), cells can be detached from the microcarriers together with gelatin because of the competitive binding between ß-CD and AD. Overall, these supramolecular responsive microcarriers could effectively support cell expansion and achieve nonenzymatic cell detachment and may be potentially reusable with a new cycle of gelatin attachment and detachment.

Recent preparation, modification and application progress of starch nanocrystals: A review.

Due to the advantages of wide sources, high biocompatibility and favorable biodegradability, starch nanocrystals (SNCs) have gradually attracted attention and have bright development prospects in food, agriculture, materials, medicine and other fields. However, the traditional preparation method of SNCs is time-consuming and inefficient, and the physicochemical properties cannot fully meet the needs of multiple applications. Fortunately, the unique onion-like structure of starch granules and the large number of hydroxyl groups present on the surface entitle SNCs to efficient preparation and modification. This paper comprehensively reviewed the improvement methods of SNCs preparation process in recent years, and the advantages and disadvantages of the two improvement strategies were compared. Besides, the importance of introducing different pretreatment methods into the SNCs preparation process was emphasized. It also focused on the different modification treatment and application progress of SNCs, especially in the starch-based surface coating of fruits and vegetables. The information will contribute to further improve the preparation efficiency and physicochemical properties of SNCs, and ultimately expand the application field.

Ultrasound-Activated NIR Chemiluminescence for Deep Tissue and Tumor Foci Imaging.

Fluorescence imaging requires real-time external light excitation; however, it has the drawbacks of autofluorescence and shallower penetration depth, limiting its application in deep tissue imaging. At the same time, ultrasound (US) has high spatiotemporal resolution, deep penetrability, noninvasiveness, and precise localization of lesions; thus, it can be a promising alternative to light. However, US-activated luminescence has been rarely reported. Herein, an US-activated near-infrared (NIR) chemiluminescence (CL) molecule, namely, PNCL, is designed by protoporphyrin IX as a sonosensitizer moiety and a phenoxy-dioxetane precursor containing a dicyanomethyl chromone acceptor scaffold (NCL) as the US-responsive moiety. After therapeutic US radiation (1 MHz), the singlet oxygen (1O2), as an "intermediary", oxidizes the enol-ether bond of the NCL moiety and then emits NIR light via spontaneous decomposition. Combining the deep penetrability of US with a high signal-to-background ratio of NIR CL, the designed probe PNCL successfully realizes US-activated deep tissue imaging (∼20 mm) and selectively turns on signals in specific tumor foci. Bridging US chemistry with luminescence using an "intermediary" will provide new imaging methods for accurate cancer diagnosis.

The Modulation of Sucrose Nonfermenting 1-Related Protein Kinase 2.6 State by Persulfidation and Phosphorylation: Insights from Molecular Dynamics Simulations.

SnRK2.6 (SUCROSE NONFERMENTING 1-RELATED PROTEIN KINASE2.6) has been characterized as a molecular switch for the intracellular abscisic acid (ABA) signal-transduction pathway. Normally, SnRK2.6 is kept in an "off" state, forming a binary complex with protein phosphatase type 2Cs (PP2Cs). Upon stressful conditions, SnRK2.6 turns into an "on" state by its release from PP2Cs and then phosphorylation at Ser175. However, how the "on" and "off" states for SnRK2.6 are fine-tuned, thereby controlling the initiation and braking processes of ABA signaling, is still largely unclear. SnRK2.6 activity was tightly regulated through protein post-translational modifications (PTM), such as persulfidation and phosphorylation. Taking advantage of molecular dynamics simulations, our results showed that Cys131/137 persulfidation on SnRK2.6 induces destabilized binding and weakened interactions between SnRK2.6 and HAB1 (HYPERSENSITIVE TO ABA1), an important PP2C family protein. This unfavorable effect on the association of the SnRK2.6-HAB1 complex suggests that persulfidation functions are a positive regulator of ABA signaling initiation. In addition, Ser267 phosphorylation in persulfidated SnRK2.6 renders a stable physical association between SnRK2.6 and HAB1, a key characterization for SnRK2.6 inhibition. Rather than Ser175, HAB1 cannot dephosphorylate Ser267 in SnRK2.6, which implies that the retained phosphorylation status of Ser267 could ensure that the activated SnRK2.6 reforms the binary complex to cease ABA signaling. Taken together, our findings expand current knowledge concerning the regulation of persulfidation and phosphorylation on the state transition of SnRK2.6 and provide insights into the fine-tuned mechanism of ABA signaling.