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We demonstrate an ultrasensitive optomechanical strain sensor based on a SiN membrane and a Fabry-Perot cavity, enabling the measurements of both static and dynamic strain by monitoring reflected light fluctuations using a single-frequency laser. The SiN membrane offers high-quality-factor mechanical resonances that are sensitive to minute strain fluctuations. The two-beam Fabry-Perot cavity is constructed to interrogate the motion state of the SiN membrane. A static strain resolution of 4.00 nÉ is achieved by measuring mechanical resonance frequency shifts of the SiN membrane. The best dynamic resolution is 4.47 pÉHz-1/2, which is close to that of the sensor using high-finesse cavity and optical frequency comb, overcoming the dependence of ultrasensitive strain sensors on narrow-linewidth laser and high-finesse cavity with frequency locking equipment. This work opens up a promising avenue for a new generation of ultrasensitive strain sensors.
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Licochalcone A (LCA) is a bioactive chalcone compound identified in licorice. This study aimed to investigate the effects of LCA on glucolipid metabolism and energy homeostasis, as well as the underlying mechanisms. Blood glucose levels, oral glucose tolerance, serum parameters, and histopathology were examined in high-fat-high-glucose diet (HFD)-induced diabetic mice, with metformin as a positive control. Additionally, changes in key markers related to glucolipid metabolism and mitochondrial function were analyzed to comprehensively assess LCA's effects on metabolism. The results showed that LCA alleviated metabolic abnormalities in HFD-induced diabetic mice, which were manifested by suppression of lipogenesis, promotion of lipolysis, reduction of hepatic steatosis, increase in hepatic glycogenesis, and decrease in gluconeogenesis. In addition, LCA restored energy homeostasis by promoting mitochondrial biogenesis, enhancing mitophagy, and reducing adenosine triphosphate production. Mechanistically, the metabolic benefits of LCA were associated with the downregulation of mammalian target of rapamycin complex 1 and activation of adenosine monophosphate-activated protein kinase, the two central regulators of metabolism. This study demonstrates that LCA can alleviate abnormal glucolipid metabolism and restore energy balance in diet-induced diabetic mice, highlighting its therapeutical potential for the treatment of diabetes.
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Chalconas , Diabetes Mellitus Experimental , Resistência à Insulina , Camundongos , Animais , Chalconas/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Dieta Hiperlipídica/efeitos adversos , Homeostase , Fígado , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por AMP/metabolismo , Metabolismo Energético , Mamíferos/metabolismoRESUMO
Pulmonary fibrosis (PF) is a lethal disease caused by inordinate repair of damaged lungs, for which limited strategies are available. Polyphyllin VI (PPVI), extracted and isolated from Paris polyphylla Smith var. chinensis (Franch.) Hara, has been regarded as an important traditional Chinese herbal medicine for the treatment of respiratory system diseases. This study evaluated effects of PPVI on PF and its underlying mechanism. Experimental procedure For evaluating the anti-PF effect of PPVI, we established an in vivo PF mouse model via intratracheal infusion of bleomycin (BLM) in mice and an in vitro PF model induced by TGF-ß1 in NIH/3T3, HPF and A549, respectively. Subsequently, the mechanism of PPVI effects was further explored using RNA sequencing (RNA-Seq). The in vivo and in vitro results demonstrated that PPVI significantly inhibited inflammation, oxidative damage, and epithelial-mesenchymal transition. Furthermore, RNA sequencing indicated that PPVI ameliorated PF by modulating inflammation and oxidative stress responses. Furthermore, dual specificity phosphatase 6 (DUSP6), was the shared and most significant differentially expressed gene associated with inflammation and oxidative stress response after PPVI treatment. Mechanistically, silencing DUSP6 can eliminate the suppressive impact on PPVI for the activation of fibroblast and the phosphorylation of ERK and AKT. Summarily, our findings revealed the potential of PPVI in mitigating PF via upregulating DUSP6 and highlighted the regulatory function of DUSP6 in the pathogenesis of PF.
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A terahertz photonic crystal fiber with two sensing channels was designed. Graphene coated on the micro-grooves in the cladding was used as plasma material to introduce tunability. The dispersion relation, mode coupling, and sensing characteristics of the fiber were studied using the finite element method. Ultrahigh sensitivity of 2.014 THz/RIU and 0.734 GHz/°C were obtained for analytes with refractive index in the range of 1.33 to 1.4 and environment temperature in the range of 10-60 °C, respectively. Refractive index resolution can reach the order of 10-5. The dual parameter simultaneous detection, dynamic tunable characteristics, and working in the low-frequency range of terahertz enable the designed photonic crystal fiber to have application prospects in the field of biosensing.
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A terahertz surface plasmon resonance (SPR) sensor is designed based on photonic crystal fiber (PCF). Graphene is selectively coated in the cladding hole of the PCF and used as plasmonic material. The coupling mechanism, loss properties, tunability, and refractive index sensing performance of the designed SPR sensor are investigated using the finite element method. The peak of the loss spectrum corresponding to the SPR frequency can be dynamically tuned by adjusting graphene's chemical potential, and a tuning sensitivity of 767.5 GHz/eV is obtained. The SPR frequency red shifts linearly with an increase in the refractive index of analyte from 1.0 to 1.5. An average frequency sensitivity of 208.14 GHz/RIU is obtained. This research provides theoretical guidance for the design of terahertz in-fiber SPR sensors and filters.
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OBJECTIVE: To assess the long-term clinical effects of Culotte and different Crush techniques in the treatment of unprotected left main bifurcation coronary lesions to determine the best percutaneous coronary intervention strategy. METHODS: The systematic review and meta-analysis comprised search on PubMed, Embase, Cochrane Library, WanFang Data and the China National Knowledge Infrastructure literature databases to locate randomised controlled trials and cohort studies published in Chinese and/or English language till June 2021 and comprised application of Culotte and Crush stenting techniques for percutaneous coronary intervention in patients with unprotected left main bifurcation coronary lesions. The selected studies were analysed for quality, publication bias and heterogeneity. RESULTS: Of the 197 studies located, 8(4.06%) were subjected to meta-analysis. The incidence of major adverse cardiac events in the Mixed-Crush group was higher than the Culotte group (p=0.02), which, in turn, was higher than the Double Kiss Crush group (p<0.0001), The incidence of target lesion revascularisation in the Culotte group was significantly higher than Double Kiss Crush group (p<0.001). The incidence of myocardial infarction in the Culotte group was higher than the Double Kiss Crush group (p=0.04). The incidence of cardiogenic death in the Double Kiss Crush group was similar to that in the Culotte group (p=0.32). CONCLUSIONS: Patients in the Double Kiss Crush group had the most long-term benefits, while those receivingg Mixed Crush had the least long-term benefits.
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Doença da Artéria Coronariana , Humanos , Doença da Artéria Coronariana/cirurgia , Resultado do Tratamento , Fatores de Risco , Fatores de Tempo , PrognósticoRESUMO
KEY MESSAGE: ARPI, ß-AS, and UGE were cloned from G. uralensis and their regulatory effects on glycyrrhizin biosynthesis were investigated. ß-AS and UGE but not ARPI positively regulate the biosynthesis of glycyrrhizin. Glycyrrhiza uralensis Fisch. has been used to treat respiratory, gastric, and liver diseases since ancient China. The most important and widely studied active component in G. uralensis is glycyrrhizin (GC). Our pervious RNA-Seq study shows that GC biosynthesis is regulated by multiple biosynthetic pathways. In this study, three target genes, ARPI, ß-AS, and UGE from different pathways were selected and their regulatory effects on GC biosynthesis were investigated using G. uralensis hairy roots. Our data show that hairy roots knocking out ARPI or UGE died soon after induction, indicating that the genes are essential for the growth of G. uralensis hairy roots. Hairy roots with ß-AS knocked out grew healthily. However, they failed to produce GC, suggesting that ß-AS is required for triterpenoid skeleton formation. Conversely, overexpression of UGE or ß-AS significantly increased the GC content, whereas overexpression of ARPI had no obvious effects on GC accumulation in G. uralensis hairy roots. Our findings demonstrate that ß-AS and UGE positively regulate the biosynthesis of GC.
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Glycyrrhiza uralensis/metabolismo , Ácido Glicirrízico/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/metabolismo , Edição de Genes , Regulação da Expressão Gênica de Plantas , Técnicas de Inativação de Genes , Vetores Genéticos , Glycyrrhiza uralensis/genética , Ácido Glicirrízico/análise , Transferases Intramoleculares/genética , Transferases Intramoleculares/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/genética , Plantas Geneticamente Modificadas , Plantas Medicinais , UDPglucose 4-Epimerase/genética , UDPglucose 4-Epimerase/metabolismoRESUMO
Salt stress is the main abiotic stress that limits crop yield and agricultural development. Therefore, it is imperative to study the effects of salt stress on plants and the mechanisms through which plants respond to salt stress. In this study, we used transcriptomics and metabolomics to explore the effects of salt stress on Sophora alopecuroides. We found that salt stress incurred significant gene expression and metabolite changes at 0, 4, 24, 48, and 72 h. The integrated transcriptomic and metabolomic analysis revealed that the differentially expressed genes (DEGs) and differential metabolites (DMs) obtained in the phenylpropanoid biosynthesis pathway were significantly correlated under salt stress. Of these, 28 DEGs and seven DMs were involved in lignin synthesis and 23 DEGs and seven DMs were involved in flavonoid synthesis. Under salt stress, the expression of genes and metabolites related to lignin and flavonoid synthesis changed significantly. Lignin and flavonoids may participate in the removal of reactive oxygen species (ROS) in the root tissue of S. alopecuroides and reduced the damage caused under salt stress. Our research provides new ideas and genetic resources to study the mechanism of plant responses to salt stress and further improve the salt tolerance of plants.
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Regulação da Expressão Gênica de Plantas , Metaboloma , Fenilpropionatos/metabolismo , Proteínas de Plantas/metabolismo , Tolerância ao Sal , Sophora/metabolismo , Transcriptoma , Perfilação da Expressão Gênica , Lignina/biossíntese , Proteínas de Plantas/genética , Sophora/genética , Sophora/crescimento & desenvolvimento , Estresse FisiológicoRESUMO
A novel tetrabutylammonium iodide (TBAI)-promoted three-component reaction of carboxylic acid with alkene and alcohol has been developed, which represents facile and straightforward access to polysubstituted γ-lactone skeletons in moderate-to-good yields. This methodology is distinguished by the use of a commercial catalyst and readily available starting materials, wide substrate scope, and operational simplicity. Mechanistic studies suggested that this transformation went through a radical process.
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We propose to suppress acoustic wave coupling between a Si3N4 membrane resonator and its support structure through cascaded low-frequency resonators fabricated on the silicon substrate of the membrane. The on-chip silicon resonators are designed to ensure that the frequencies of their oscillatory motion are well separated from the mechanical modes of the membrane resonator. Using optical interferometry, we characterize the displacement response of the membrane frame with the vibration isolation; mechanical isolation >30 dB from the mounting surface is achieved. Thus, we reliably fabricate Si3N4 membrane resonators with mechanical quality factors of around 2×106 at room temperature.
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In ultrasonic array imaging, 3D ultrasonic wavefields are normally recorded by an ultrasonic piezo array transducer. Its performance is limited by the configuration and size of the array transducer. In this paper, a method based on digital holographic interferometry is proposed to record the 3D ultrasonic wavefields instead of the array transducer, and the measurement system consisting of a pulsed laser, ultrasonic excitation, and synchronization and control circuit is designed. A consecutive sequence of holograms of ultrasonic wavefields are recorded by the system. The interferograms are calculated from the recorded holograms at different time sequence. The amplitudes and phases of the transient ultrasonic wavefields are recovered from the interferograms by phase unwrapping. The consecutive sequence of transient ultrasonic wavefields are stacked together to generate 3D ultrasonic wavefields. Simulation and experiments are carried out to verify the proposed technique, and preliminary results are presented.
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In this study, a strain named WXCDD105, which has strong antagonistic effects on Botrytis cinerea and Cladosporium fulvum Cooke, was screened out from the rhizosphere of healthy tomato plants. The tomato plants had inhibition diameter zones of 5.00 mm during the dual culture for four days. Based on the morphological and physiological characteristics, the 16S rDNA sequence, and the gyrB gene sequence analysis, the strain WXCDD105 was identified as Bacillus subtilis suBap. subtilis. The results of the mycelial growth test showed that the sterile filtrate of the strain WXCDD105 could significantly inhibit mycelial growth of Botrytis cinerea and Cladosporium fulvum Cooke. The inhibition rates were 95.28 and 94.44%, respectively. The potting experiment showed that the strain WXCDD105 made effective the control of tomato gray mold and tomato leaf mold. The control efficiencies were 74.70 and 72.07%. The antagonistic test results showed that the strain WXCDD105 had different degrees of inhibition on 10 kinds of plant pathogenic fungi and the average inhibition rates were more than 80%. We also found that the strain WXCDD105 stimulated both the seed germination and seedling growth of tomatoes. Using the fermentation liquid of WXCDD105 (108 cfu·mL−1) to treat the seeds, the germination rate and radicle length were increased. Under the treatment of the fermentation liquid of the strain WXCDD105 (106 cfu·mL−1), nearly all physiological indexes of tomato seedlings were significantly higher than that of the control groups. This could not only keep the nutritional quality of tomato fruits but also prevent them from rotting. This study provided us with an excellent strain for biological control of tomato gray mold, tomato leaf mold, and tomato growth promotion. This also laid the technical foundation for its application.
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Bacillus subtilis/crescimento & desenvolvimento , Controle Biológico de Vetores , Doenças das Plantas/prevenção & controle , Plântula/microbiologia , Bacillus subtilis/genética , Botrytis/patogenicidade , Cladosporium/patogenicidade , Frutas/microbiologia , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/microbiologia , Doenças das Plantas/microbiologia , Folhas de Planta/microbiologiaRESUMO
Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible lung disease, and developing an effective treatment remains a challenge. The limited therapeutic options are primarily delivered by the oral route, among which pirfenidone (PFD) improves pulmonary dysfunction and patient quality of life. However, its high dose and severe side effects (dyspepsia and systemic photosensitivity) limit its clinical value. Intratracheal aerosolization is an excellent alternative method for treating lung diseases because it increases the concentration of the drug needed to reach the focal site. Tetrahedral framework nucleic acid (tFNA) is a drug delivery system with exceptional delivery capabilities. Therefore, we synthesized a PFD-tFNA (Pt) complex using tFNA as the delivery vehicle and achieved quantitative nebulized drug delivery to the lungs via micronebulizer for lung fibrosis treatment. In vivo, Pt exhibited excellent immunomodulatory capacity and antioxidant effects. Furthermore, Pt reduced mortality, gradually restored body weight and improved lung tissue structure. Similarly, Pt also exhibited superior fibrosis inhibition in an in vitro fibrosis model, as shown by the suppression of excessive fibroblast activation and epithelial-mesenchymal transition (EMT) in epithelial cells exposed to TGF-ß1. Conclusively, Pt, a complex with tFNA as a transport system, could enrich the therapeutic regimen for IPF via intratracheal aerosolization inhalation.
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Antioxidantes , Fibrose Pulmonar Idiopática , Piridonas , Piridonas/química , Piridonas/farmacologia , Piridonas/administração & dosagem , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/patologia , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Humanos , Camundongos , Ácidos Nucleicos/química , Ácidos Nucleicos/farmacologia , Sistemas de Liberação de Medicamentos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/administração & dosagem , Camundongos Endogâmicos C57BL , MasculinoRESUMO
Obesity and type 2 diabetes mellitus (T2DM), as common metabolic diseases, are pathologically characterized by overnutrition and insulin resistance (IR), which subsequently lead to glucose and lipid metabolism disorders. The liver, a major metabolic organ of the body, integrates hormone and metabolic signals to regulate the synthesis of lipids and glucose as well as their transport to peripheral tissues, hence playing an essential role in the development of obesity and T2DM. Adenosine 5'-monophosphate-activated protein kinase (AMPK) is a central regulator involved in cellular and organismal metabolism in eukaryotes, which activates processes that produce ATP and diminishes its consumption. In addition, AMPK also regulates mitochondrial homeostasis and promotes autophagy, both of which are associated with the pathogenesis of IR. Therefore, increasing AMPK activity is considered a promising therapeutic strategy to prevent obesity and T2DM. In this review, we summarize the role of hepatic AMPK in obesity and T2DM and the potential of using AMPK activators as therapeutics for metabolic disorders.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Doenças Metabólicas , Proteínas Quinases Ativadas por AMP , Glucose , Humanos , Fígado , ObesidadeRESUMO
PURPOSE: To determine the effects of isoliquiritigenin (ISL), a chalcone compound isolated from licorice, on type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: 8-week-old C7BL/6 mice were used to establish the T2DM animal model by feeding with high-fat-high-glucose diet (HFD) combined with intraperitoneal injection of streptozotocin. The animals were treated with ISL for 3 weeks. Blood glucose levels, oral glucose tolerance, and insulin tolerance were examined, serum parameters were determined, histologic sections were prepared, activities of enzymes related to glucolipid metabolism were analyzed, and the mitochondrial function was investigated to evaluate effects of ISL on metabolism. The underlying mechanisms of ISL alleviating insulin resistance and restoring metabolic homeostasis were analyzed in HepG2 and INS-1 cells. RESULTS: ISL exhibits a potent activity in relieving hyperglycemia of type 2 diabetic mice. It alleviates insulin resistance and restores metabolic homeostasis without obvious adversary effects in HFD-induced diabetic mice. The metabolic benefits of ISL treatment include promoting hepatic glycogenesis, inhibiting hepatic lipogenesis, reducing hepatic steatosis, and sensitizing insulin signaling. Mechanistically, ISL activates adenosine monophosphate-activated protein kinase (AMPK) and inhibits mammalian target of rapamycin complex 1 (mTORC1). It also suppresses mitochondrial function and reduces ATP production. CONCLUSION: Our findings demonstrate that ISL is able to significantly reduce blood glucose level and alleviate insulin resistance without obvious side effects in diabetic mice, hence uncovering a great potential of ISL as a novel drug candidate in prevention and treatment of T2DM.
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The mechanistic target of rapamycin (mTOR) is a pivotal regulator of cell metabolism and growth. In the form of two different multi-protein complexes, mTORC1 and mTORC2, mTOR integrates cellular energy, nutrient and hormonal signals to regulate cellular metabolic homeostasis. In type 2 diabetes mellitus (T2DM), pathological conditions and end-organ complications can be attributed to aberrant mTOR. Substantial evidence suggests that two mTOR-mediated signaling schemes, mTORC1-p70S6 kinase 1 (S6K1) and mTORC2-protein kinase B (AKT), play a critical role in insulin sensitivity and that their dysfunction contributes to the development of T2DM. This review summarizes our current understanding of the role of mTOR signaling in T2DM and its associated complications, as well as the potential use of mTOR inhibitors in the treatment of T2DM.
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Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Serina-Treonina Quinases TOR , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
An in-fiber Michelson interferometric sensor was presented by fabricating a concavity on the end face of a single mode fiber using a single CO2 laser pulse. Reflected beams from the bottom and air-cladding boundary of the concavity are coupled into the fiber core and superimpose to generate a two-beam in-fiber Michelson interferometer. Compared with other laser-machining methods where multiple scanning cycles with precise manipulation are needed, the proposed method is more straightforward because only a single laser pulse is used to construct the sensor. The concavity constructed by the CO2 laser is very smooth, and its shape could be controlled flexibly by changing the position of the single mode fiber and the parameters of the CO2 laser pulse, so the fringe visibilities of the proposed sensors could be more than 15 dB, which is higher than that of the most reported laser-machining in-fiber Michelson interferometers. The proposed sensor was demonstrated by measuring the temperature with a sensitivity of 11.13 pm/°C. Furthermore, the proposed device is compact (<100 µm), economical, and robust. These advantages make it a promising candidate in practical applications.
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A multicomponent composite membrane (P-S-T/C) with three-phase interface heterostructure is ingeniously designed. A polydopamine (PDA)-modified conductive carbon fiber cloth (CFC) is used as the substrate. Activated poly(vinylidene fluoride) (PVDF) with titanium dioxide (TiO2) and a silicon dioxide (SiO2) aerogel are electrospun as the top layer. The three-phase interface heterostructure was formed by TiO2, conductive CFC, and the SiO2 aerogel. Its photocatalytic performance is validated by photodegradation of organic dyes in a low-oxygen (O2) water environment. On combining with the capillary condensation of a bilayer structure, P-S-T/C exhibits excellent removal capability for anionic and cationic dyes. Moreover, P-S-T/C exhibits excellent stability and recyclability under simulated sunlight. The mechanism study indicates that the separated photogenerated carriers diffuse to the composite membrane surface rapidly on the three-phase interface of P-S-T/C. The abundant O2 adsorbed on the porous SiO2 aerogel surface acts as an electron (e-)-trapping agent, which can also decrease the work function of the composite materials. Superoxide radicals (â¢O2 -) play a dominant role in the reaction of photodegradation supported by a free radical-trapping experiment. This work paves a way to design a membrane with photocatalytic performance by constructing the interface heterostructure.
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Calcium acts as a universal secondary messenger that transfers developmental cues and stress signals for gene expression and adaptive growth. A prior study showed that abiotic stresses induce mutually independent cytosolic Ca2+ ([Ca2+]cyt) and nucleosolic Ca2+ ([Ca2+]nuc) increases in Arabidopsis thaliana root cells. However, gene expression networks deciphering [Ca2+]cyt and [Ca2+]nuc signalling pathways remain elusive. Here, using transgenic A. thaliana to selectively impair abscisic acid (ABA)- or methyl jasmonate (MeJA)-induced [Ca2+]cyt and [Ca2+]nuc increases, we identified [Ca2+]cyt- and [Ca2+]nuc-regulated ABA- or MeJA-responsive genes with a genome oligo-array. Gene co-expression network analysis revealed four Ca2+ signal-decoding genes, CAM1, CIPK8, GAD1, and CPN20, as hub genes co-expressed with Ca2+-regulated hormone-responsive genes and hormone signalling genes. Luciferase complementation imaging assays showed interactions among CAM1, CIPK8, and GAD1; they also showed interactions with several proteins encoded by Ca2+-regulated hormone-responsive genes. Furthermore, CAM1 and CIPK8 were required for MeJA-induced stomatal closure; they were associated with ABA-inhibited seed germination. Quantitative reverse transcription polymerase chain reaction analysis showed the unique expression pattern of [Ca2+]-regulated hormone-responsive genes in cam1, cipk8, and gad1. This comprehensive understanding of distinct Ca2+ and hormonal signalling will allow the application of approaches to uncover novel molecular foundations for responses to developmental and stress signals in plants.