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Introduction: Sodium zirconium cyclosilicate (SZC) is a nonabsorbed cation-exchanger approved in China for the treatment of hyperkalemia [HK; serum potassium (sK+) levels >5.0 mmol/L]. This is the first real-world study aimed to assess the effectiveness, safety, and treatment patterns of SZC in Chinese patients with HK. Here we present the results of the first interim analysis. Methods: This multicenter, prospective, cohort study included patients aged ≥18 years with documented HK within 1-year before study enrollment day. These patients were followed up for 6 months from the enrollment day after initiating SZC treatment. The treatment was categorized into correction phase (FAS-P1) and maintenance phase (FAS-P2 new and ongoing users). Subgroup analysis was performed in patients on hemodialysis (FAS-H). The primary objective was evaluation of safety profile of SZC; secondary objectives included assessment of treatment patterns of SZC and its effectiveness. Results: Of 421 screened patients, 193, 354, and 162 patients were enrolled in the FAS-P1, FAS-P2, and FAS-H groups, respectively. sK+ levels were reduced significantly from 5.9 mmol/L to 5.0 mmol/L after the correction phase. For the maintenance phase, the mean sK+ levels were maintained at 5.2 mmol/L and 5.0 mmol/L in the FAS-P2 new and ongoing user, respectively, and 5.3 mmol/L in the FAS-H subgroup. A considerable proportion of patients showed normokalemia after 48 h of SZC treatment (FAS-P1:51.3%) which was maintained up to 6 months in the maintenance phase (FAS-P2:44%). SZC was well-tolerated. Conclusion: SZC was effective and safe for the treatment of HK in real-world clinical practice in China.
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In vivo mechanical characterization of skin finds broad applications in understanding skin aging, diagnosis of some skin diseases and assessing the effectiveness of diverse skin care strategies. Skin has a layered structure consisting of the epidermis, dermis and subcutaneous layers. Although much effort has been made towards mechanical characterization of skin, it remains a challenging issue to measure the mechanical properties of an individual layer in vivo. To address this issue, we here report a guided wave elastography method for layered human skin which incorporates the effect of muscle states. Both finite element simulations and phantom experiments have been performed to validate the method. For skin-mimicking phantoms with different fat layer thicknesses, the errors in the identified shear modulus of the skin layers are no more than 11 %. In vivo experiments have been carried out on 6 healthy subjects to demonstrate the potential use of the method in clinics. A statistical analysis indicates the muscle contraction contributes to the stiffening of the skin (p < 0.001). Finally, a phase diagram has been constructed to reveal the extent to which muscle sates (including both passive and active states) affect the measurement of elastic modulus of a skin layer, which may guide the application of the method in practice.
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Lutein possesses various physiological activities but is susceptible to light degradation, thermal degradation, and oxidative degradation. As such, protecting the activity of lutein-based products using natural extracts has become a current research. In this study, lutein was protected by complexing inulin-type fructan (ITF), soybean protein isolate (SPI), and epicatechin (EC), and the protection mechanism of epicatechin-fructan glycosylated soybean protein isolate (EC-GSPI) toward lutein was elucidated comprehensively. The results showed that the addition of EC delayed the degradation of lutein. The results of light stability experiments showed that increased EC significantly enhanced the storage time of the GSPI-Lutein system from 4 to 13 days. Additionally, the effect of EC on glycosylated soybean 7S globulin (G7S) and glycosylated soybean 11S globulin (G11S) was assessed. The light stability of G11S-Lutein and G7S-Lutein after the addition of EC was from G11S > G7S â G7S > G11S. Furthermore, the proteins purified from SPI interacted differently with EC and ITF, with soybean 7S globulin (7S) mainly interacting with EC and soybean 11S globulin (11S) mainly interacting with ITF. EC-GSPI-Lutein exhibited a good protective effect, probably due to the occurrence of hygrothermal Maillard between ITF and 11S, providing a porous structure for lutein storage. At the same time, the binding of EC to 7S significantly enhanced the antioxidant property of the solution and the stability of the protein secondary structure, thereby prolonging the storage time of lutein.
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The effects of cysteine (Cys), glutathione (GSH) and cystine (GCys) on sulfides and meaty aroma were studied based on concentration monitoring and metabolomics. In multi-component models, Cys and GSH demonstrated a greater capacity to decrease dimethyl trisulfide (DMTS) levels and increase the proportion of 2-methyl-3-furanthiol (MFT), compared with GCys. Moreover, no discernible difference between Cys and GSH in dynamic profiles of volatiles to further analyze the synergistic effect of both. Results of single factor experiment and optimization revealed that the optimal thermal processing was a second-order thermal procedure. Aroma profiles revealed that the addition of Cys and GSH mixture increased the meaty intensity during the optimal thermal processing. Metabolomics based on Encyclopedia of Genes and Genomes pathway annotation confirmed that Cys and GSH significantly affected the degradation of methionine and thiamine in amino acid and protein metabolic pathways, resulting in various amounts of DMTS and MFT. Research on effect and potentially metabolic mechanisms revealed that the combination of Cys and GSH at ratio of 3:7 had higher and more effective control capacity for free radical reaction of sulfides than either one alone during second-order thermal processing, which would lay theoretical foundation for the development of high-quality thermal process products.
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Cisteína , Odorantes , Cisteína/metabolismo , Glutationa/metabolismo , Cistina , SulfetosRESUMO
The present study aims to investigate the chromogenic effect and the interaction between starch-pigment complexes of corn starch (CS) and potato starch (PS) complexed with paprika red pigment. Compared to PS, CS showed 12.5 times higher adsorption capacity for paprika red pigment. Additionally, the a* value of CS-P (26.90 ± 0.23) was significantly higher than that of PS-P (22.45 ± 1.84), resulting in a corn starch-paprika red pigment complex (CS-P) with a more intense red colour. The addition of paprika red pigment significantly decreased the particle size and porosity of CS by 48.14 ± 5.29% and 17.01 ± 3.80%, respectively. Conversely, no significant impact on PS was observed. Additionally, the Fourier transform infrared (FT-IR) spectroscopy results revealed that the starch molecules and paprika red pigment were bound to each other through strong hydrogen bonds. X-diffraction (XRD) results indicated that the starch-paprika red pigment complexes have a V-shaped structure. Furthermore, the relative crystallinity of the complexes between starch and red pepper pigment showed an increasing trend, however, the relative crystallinity of CS increased significantly by 11.77 ± 0.99-49.21 ± 3.67%. Consequently, the CS-P colouring was good.
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Shear wave elastography (SWE) enables the measurement of elastic properties of soft materials in a non-invasive manner and finds broad applications in various disciplines. The state-of-the-art SWE methods rely on the measurement of local shear wave speeds to infer material parameters and suffer from wave diffraction when applied to soft materials with strong heterogeneity. In the present study, we overcome this challenge by proposing a physics-informed neural network (PINN)-based SWE (SWENet) method. The spatial variation of elastic properties of inhomogeneous materials has been introduced in the governing equations, which are encoded in SWENet as loss functions. Snapshots of wave motions have been used to train neural networks, and during this course, the elastic properties within a region of interest illuminated by shear waves are inferred simultaneously. We performed finite element simulations, tissue-mimicking phantom experiments, and ex vivo experiments to validate the method. Our results show that the shear moduli of soft composites consisting of matrix and inclusions of several millimeters in cross-section dimensions with either regular or irregular geometries can be identified with excellent accuracy. The advantages of the SWENet over conventional SWE methods consist of using more features of the wave motions and enabling seamless integration of multi-source data in the inverse analysis. Given the advantages of SWENet, it may find broad applications where full wave fields get involved to infer heterogeneous mechanical properties, such as identifying small solid tumors with ultrasound SWE, and differentiating gray and white matters of the brain with magnetic resonance elastography.
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Técnicas de Imagem por Elasticidade , Técnicas de Imagem por Elasticidade/métodos , Ultrassonografia , Física , Redes Neurais de Computação , EncéfaloRESUMO
Testing the mechanical properties of veins is important for diagnosing some cardiovascular diseases such as deep venous thrombosis. Additionally, it plays a crucial role in designing body protective products such as head protective gear, where simulations are necessary to predict the mechanical responses of bridging veins during head impacts. The data on venous mechanical properties reported in the literature have mainly been obtained from ex vivo experiments, and inferring the material parameters of veins in vivo is challenging. Here, we address this issue by proposing a guided wave elastography method in which guided waves are generated in the jugular veins with focused acoustic radiation force and tracked by an ultrafast ultrasound imaging system. Then, a mechanical model considering the effects of the perivascular soft tissues and prestresses in the veins was applied to analyze the wave motions in the jugular veins. Our model enables the development of an inverse method to infer the elastic properties of the veins from measured guided waves. Phantom experiments were performed to validate the theory, and in vivo experiments were carried out to demonstrate the usefulness of the inverse method in practice.
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The generations of dimethyl disulfide (DMDS) and dimethyl trisulfide (DMTS) in a binary or ternary model system including lipids, free amino acids and Maillard reaction products (MRPs) were studied. Various factors affecting the formation of DMDS and DMTS indicated that cysteine (Cys) and Cys MRPs could effectively decrease not only the concentrations of methionine (Met), DMDS and DMTS, but also the pH level. Rapid drops in pH limited the formation of DMDS and DMTS during Met thermal degradation. Quantitative analyses of DMDS and DMTS at acidic aqueous solutions revealed that the mixtures of MRPs derived from Cys and xylose (Xyl) had the best inhibition effect on the formation of DMDS and DMTS. The low level of DMDS and DMTS and the increasing level of furfuryl methyl sulfide and 2-thiophenecarboxaldehyde during storage indicated that MRPs derived from Cys and Xyl could effectively not only decrease the concertation of DMDS and DMTS, but also promote the development of thiophene and sulfur substituted furan. Thus, this study implied that MRPs derived from Cys/Xyl could be applied as effective substances to control the formation of DMDS and DMTS and improve the production of volatile compounds with meat-like aroma.
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Aminoácidos , Cisteína , SulfetosRESUMO
The effect of Maillard reaction products derived from cysteine on dimethyl disulfide (DMDS) and dimethyl trisulfide (DMTS) was evaluated in the ternary mixture (methionine, cysteine, and xylose) and binary mixture (methionine and 2-threityl-thiazolidine-4-carboxylic acid) during 56 days storage. Changes in concentrations revealed that the methionine/cysteine/xylose model showed lower concentrations of DMDS and DMTS than those of the binary mixture. Antioxidant ability and labeled isotopomer proportion information indicated that low levels of DMDS and DMTS in the ternary mixture were attributed to not only 2-furfurylthiol and 2-methyl-3-furanthiol (MFT) reacting with methanethiol but also the ternary mixture having stronger antioxidant activity. Correlation analysis demonstrated that MFT reacting with methanethiol and strong antioxidant ability are considered major factors controlling the formation of DMTS and DMDS, respectively. Research on the reaction mechanism of the rate-limiting step would provide the basis for preventing the development of DMDS and DMTS during storage.
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Antioxidantes , Cisteína , Xilose , Metionina , Racemetionina , Levanogestrel , Produtos Finais de Glicação AvançadaRESUMO
Background and Aims: In this study, we aimed to evaluate the diagnostic values of alpha-fetoprotein (AFP), soluble AXL (sAXL), des-γ-carboxy prothrombin (DCP), the aspartate aminotransferase-to-platelet ratio index (APRI), and the gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in hepatocellular carcinoma (HCC) and the possible underlying mechanisms of the correlations between them. Methods: We collected serum samples from 190, 128, and 75 patients with HCC, cirrhosis, and chronic viral hepatitis, and from 82 healthy subjects. Serum levels of AFP, sAXL, and DCP were determined, and APRI and GPR values were calculated. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic value of single and combined biomarkers. Results: We detected significant differences between the HCC group and other groups regarding serum AFP, sAXL, DCP, and APRI levels. GPR significantly differed between the HCC group and other groups, except for the liver cirrhosis group. AFP, sAXL, DCP, APRI, and GPR had positive correlations with each other, and AFP showed a higher area under the curve (AUC) and Youden index values, while APRI and DCP showed the highest sensitivity and specificity. Also, when AFP was combined with sAXL, DCP, APRI, and GRP, the highest AUC (0.911) and a higher net reclassification improvement value were obtained compared with those obtained for the individual biomarkers. Conclusions: AFP, sAXL, DCP, APRI, and GPR are independent risk factors for HCC, and the diagnostic performance of AFP combined with sAXL, DCP, APRI, and GPR for HCC diagnosis was superior to that of the individual biomarkers.
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Changes in flavor quality of thermal process flavorings with beef-like odor (TPFB) affected sensory properties upon storage. The changes in sensory quality and odorants of TPFB stored at 50 â for 168 days were evaluated using sensomics approach. The aroma profiles of TPFB gradually changed from stronger meaty notes to stronger burnt and soybean paste-like notes during storage. Forty-two quantified odor-active compounds with flavor dilution ≥ 27 were assessed using the odor activity value concept. Correlation analysis indicated that a decreasing trend of meaty note was closely associated with 5-methyl furfural, dimethyl disulfide, dimethyl trisulfide, furfuryl methyl sulfide and furfuryl thioacetate, which all enriched with time. Omission and addition tests showed that dimethyl disulfide, dimethyl trisulfide and furfuryl thioacetate with the concentration increasing considerably reduced the intensity of meaty note, particularly for dimethyl trisulfide. Therefore, the formation of dimethyl trisulfide should be limited to produce high-quality TPFB during storage.
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Odorantes , Compostos Orgânicos Voláteis , Animais , Bovinos , Odorantes/análise , Compostos Orgânicos Voláteis/análise , Técnicas de Diluição do Indicador , Aromatizantes/análiseRESUMO
Shear wave elastography (SWE) of human skeletal muscles allows for measurement of muscle elastic properties in vivo and has important applications in sports medicine and for the diagnosis and treatment of muscle-related diseases. Existing methods of SWE for skeletal muscles rely on the passive constitutive theory and have so far been unable to provide constitutive parameters describing muscle active behavior. In the present paper, we overcome this limitation by proposing a SWE method for quantitative inference of active constitutive parameters of skeletal muscles in vivo. To this end, we investigate the wave motion in a skeletal muscle described by a constitutive model in which muscle active behavior has been defined by an active parameter. An analytical solution relating shear wave velocities to both passive and active material parameters of muscles is derived, based upon which an inverse approach has been developed to evaluate these parameters. To demonstrate the usefulness of the reported method, in vivo experiments were carried out on 10 volunteers to obtain constitutive parameters, particularly those describing active deformation behaviors of living muscles. The results reveal that the active material parameter of skeletal muscles varies with warm-up, fatigue and rest. STATEMENT OF SIGNIFICANCE: Existing shear wave elastography methods are limited to imaging the passive parameters of muscles. This limitation is addressed in the present paper by developing a method to image the active constitutive parameter of living muscles using shear waves. We derived an analytical solution demonstrating the relationship between constitutive parameters of living muscles and shear waves. Relying on the analytical solution, we proposed an inverse method to infer active parameter of skeletal muscles. We performed in vivo experiments to demonstrate the usefulness of the theory and method; the quantitative variation of the active parameter with muscle states such as warm-up, fatigue and rest has been reported for the first time.
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Técnicas de Imagem por Elasticidade , Músculo Esquelético , Humanos , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologiaRESUMO
BACKGROUND: In most regions around the globe, average dietary calcium intake is relatively low. Consumers increasingly supplement calcium with milk. However, commercial high-calcium milk has the problem of low calcium bioaccessibility. This study was to explore calcium fortified milk containing calcium carbonate (CaCO3 ) loaded solid-in-oil-in-water emulsion as a potential novel calcium fortified milk with higher calcium bioaccessibility. RESULTS: The CaCO3 loaded solid-in-oil-in-water (S/O/W) emulsion with good physical stability (zeta potential -33.34 ± 0.96 mV, mean particle size 4.49 ± 0.02 µm) and high calcium bioaccessibility (32.34%) was prepared when the concentration of xanthan gum was 4 g L-1 . Furthermore, the physicochemical properties and gastrointestinal fate of calcium fortified milk (calcium contents, 1.25 mg mL-1 , 1.35 mg mL-1 , and 1.45 mg mL-1 ) with different proportions of CaCO3 loaded S/O/W emulsion and pure milk were investigated. The calcium fortified milk (calcium content, 1.25 mg mL-1 ) with a small amount of CaCO3 loaded S/O/W emulsion did not significantly affect the physicochemical properties of pure milk and had similar rheological properties and higher calcium bioaccessibility to commercial high-calcium milk. Excessive calcium ion (Ca2+ ) weakens the electrostatic interaction of milk sample system and causes aggregation of colloidal particles, which was attributed to more insoluble calcium soap formation. CONCLUSION: This study showed that the S/O/W emulsion delivery system improved the dispersion stability and bioaccessibility of CaCO3 . These findings contribute to the development of calcium fortified milk with improved physicochemical properties and higher calcium bioaccessibility. © 2023 Society of Chemical Industry.
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Cálcio , Leite , Animais , Emulsões/química , Cálcio da Dieta , Digestão , Carbonato de Cálcio , Água/químicaRESUMO
Mechanical stresses across different length scales play a fundamental role in understanding biological systems' functions and engineering soft machines and devices. However, it is challenging to noninvasively probe local mechanical stresses in situ, particularly when the mechanical properties are unknown. We propose an acoustoelastic imaging-based method to infer the local stresses in soft materials by measuring the speeds of shear waves induced by custom-programmed acoustic radiation force. Using an ultrasound transducer to excite and track the shear waves remotely, we demonstrate the application of the method by imaging uniaxial and bending stresses in an isotropic hydrogel and the passive uniaxial stress in a skeletal muscle. These measurements were all done without the knowledge of the constitutive parameters of the materials. The experiments indicate that our method will find broad applications, ranging from health monitoring of soft structures and machines to diagnosing diseases that alter stresses in soft tissues.
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Engenharia , Músculo Esquelético , Imagens de Fantasmas , Estresse Mecânico , Músculo Esquelético/diagnóstico por imagemRESUMO
INTRODUCTION: Hyperkalaemia (HK) is a potentially life-threatening electrolyte imbalance associated with several adverse clinical outcomes. The efficacy and negative effects of currently existing treatment options have made HK management questionable. Sodium zirconium cyclosilicate (SZC), a novel highly selective potassium binder, is approved for the treatment of HK. The present study will be aimed to assess the safety, effectiveness and treatment patterns of SZC in Chinese patients with HK in a real-world clinical setting as it is required by China's drug review and approval process. METHODS AND ANALYSIS: This is a multicentre, prospective cohort study which plans to enrol 1000 patients taking SZC or willing to take SZC from approximately 40 sites in China. Patients ≥18 years of age at the time of signing the written informed consent and with documented serum potassium levels ≥5.0 mmol/L within 1 year before study enrolment day will be included. Eligible patients will receive SZC treatment and will be followed up for 6 months from enrolment day. The primary objective will be to evaluate the safety of SZC for the management of HK in Chinese patients in terms of adverse events (AEs), serious AEs as well as discontinuation of SZC. The secondary objectives will include understanding the SZC dosage information in terms of its effectiveness and treatment patterns under real-world clinical practice and assessing effectiveness of SZC during the observational period. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University (approval number: YJ-JG-YW-2020). All the participating sites have received the ethics approval. Results will be disseminated through national and international presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05271266.
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Hiperpotassemia , Humanos , China , Hiperpotassemia/tratamento farmacológico , Potássio , Estudos Prospectivos , Estudos Multicêntricos como AssuntoRESUMO
Calcium carbonate (CaCO3) has poor suspension stability, which severely limits its application in food processing and products. In this study, sodium caseinate (NaCas) and sodium caseinate (NaCas)-xanthan gum (XG) mixtures were compared for the stable preparation of solid/oil/water (S/O/W) emulsions for the delivery of calcium carbonate (CaCO3) to solve the problem of poor suspension stability. The physical stability, particle size distribution, and microstructure of S/O/W emulsions were investigated to prove the successful construction of the system. The dynamic surface pressure and surface swelling properties of 2.0 wt% NaCas with different concentrations of XG were investigated to clarify the effect of interfacial properties of NaCas-XG mixtures on the emulsion stability of S/O/W emulsions. The results showed that the addition of XG resulted in enhanced physical stability, reduced particle size distribution, and enhanced encapsulation effect of the emulsion, forming a more three-dimensional core-shell structure via dendritic links. XG had a significant effect on the dynamic properties of the NaCas adsorption membrane: NaCas interacted with XG and the diffusion (kdiff) of NaCas to the interface decreased in short adsorption time, thus limiting the protein adsorption effectiveness; the presence of XG reduced the penetration (kP) and rearrangement (kR) rates at the interface during long adsorption times. Meanwhile, the NaCas-XG mixture has a high swelling elasticity. The results of this study can be used to improve the quality of related emulsion products or to prepare delivery systems for bioactive compounds.
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Caseínas , Polissacarídeos Bacterianos , Emulsões/química , Caseínas/química , Polissacarídeos Bacterianos/química , Manipulação de AlimentosRESUMO
Roasting influences the color, flavor, and antioxidant activities of peanuts. However, the biochemical mechanisms that occur during roasting are not well known. In this study, the dynamic changes in non-volatile and volatile metabolites in raw, light, and dark roasted peanuts were investigated using ultra-performance liquid chromatography with a widely targeted metabolomic approach based on tandem mass spectrometry and gas chromatography-mass spectrometry. A total of 738 non-volatile metabolites (comprising 12 subclasses) and 71 volatile metabolites (comprising 14 subclasses) were identified in raw and roasted peanuts. Significantly different non-volatile and volatile metabolites were detected. Among them, amino acids, sugars, and lipids (lysophosphatidylethanolamines and oxidized fatty acids) were found to be highly linked to flavor formation. In addition, the enhanced color and antioxidant activities of peanuts were attributed to the Maillard reaction and sugar degradation. These results provide comprehensive insights into the quality improvements of peanuts during roasting.
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Antioxidantes , Arachis , Arachis/química , Cromatografia Gasosa-Espectrometria de Massas , Reação de Maillard , Espectrometria de Massas em Tandem , Temperatura AltaRESUMO
Ultrasound effectively inhibited strawberry softening but the mechanism was not clear. In this study, physical data including firmness, soluble pectin (SP) contents, pectin esterase (PE), polygalacturonase (PG) activity and transcriptome sequencing data were analyzed to explore the mechanism of strawberry response to ultrasonic treatment. After 24 days storage, the firmness reduction rate and soluble contents (SP) increased rate of the strawberry treated with ultrasound (25 kHz, 0.15 W/cm2) for 3 min decreased 41.70 and 63.12% compared with the control, respectively. While the PG and PE enzyme activities of ultrasound-treated strawberries were significantly lower than control after storage for 18 days. A total of 1,905 diferentially expressed genes (DEGs) were identified between ultrasound-treated and control, with 714 genes upregulated and 1,254 genes downregulated, including 56 genes in reactive oxygen species (ROS), auxin (AUX), ethylene (ETH) and jasmonic acid (JA) signaling pathways. At 0 h, 15 genes including LOX, JMT, ARP, SKP, SAUR, IAA, ARF, and LAX were significantly upregulated compared with the control group, which means reactive oxygen specie, auxin, ethylene and jasmonic acid-mediated signaling pathway respond to ultrasound immediately. ERF109, ERF110, and ACS1_2_6 downregulated before 2 days storage indicated ethylene signaling pathway was inhibited, while after 2 days, 9 genes including ERF027, ERF109, and ERF110 were significantly upregulated indicating that the response of the ethylene signaling pathway was lagging. Therefore, in strawberry ultrasound enhanced ROS scavenging and activated JA biosynthesis, which acts as a signal for delaying the activation of ET signaling pathway, thus suppressing the activity of pectin-degrading enzymes PE and PG, and ultimately inhibiting postharvest softening.