Revealing Ion Adsorption and Charging Mechanisms in Layered Metal-Organic Framework Supercapacitors with Solid-State Nuclear Magnetic Resonance.

Conductive layered metal-organic frameworks (MOFs) have demonstrated promising electrochemical performances as supercapacitor electrode materials. The well-defined chemical structures of these crystalline porous electrodes facilitate structure-performance studies; however, there is a fundamental lack in the molecular-level understanding of charge storage mechanisms in conductive layered MOFs. To address this, we employ solid-state nuclear magnetic resonance (NMR) spectroscopy to study ion adsorption in nickel 2,3,6,7,10,11-hexaiminotriphenylene, Ni3(HITP)2. In this system, we find that separate resonances can be observed for the MOF's in-pore and ex-pore ions. The chemical shift of in-pore electrolyte is found to be dominated by specific chemical interactions with the MOF functional groups, with this result supported by quantum mechanics/molecular mechanics (QM/MM) and density functional theory (DFT) calculations. Quantification of the electrolyte environments by NMR was also found to provide a proxy for electrochemical performance, which could facilitate the rapid screening of synthesized MOF samples. Finally, the charge storage mechanism was explored using a combination of ex-situ NMR and operando electrochemical quartz crystal microbalance (EQCM) experiments. These measurements revealed that cations are the dominant contributors to charge storage in Ni3(HITP)2, with anions contributing only a minor contribution to the charge storage. Overall, this work establishes the methods for studying MOF-electrolyte interactions via NMR spectroscopy. Understanding how these interactions influence the charging storage mechanism will aid the design of MOF-electrolyte combinations to optimize the performance of supercapacitors, as well as other electrochemical devices including electrocatalysts and sensors.

Hierarchically Superstructured Anisotropic Carbon Particles by Multiscale Assembly Driven by Spinodal Decomposition.

Hierarchical superstructures have novel shape-dependent properties, but well-defined anisotropic carbon superstructures with controllable size, shape, and building block dimensionality have rarely been accomplished thus far. Here, a hierarchical assembly technique is presented that uses spinodal decomposition (SD) to synthesize anisotropic oblate particles of mesoporous carbon superstructure (o-MCS) with nanorod arrays by integrating block-copolymer (BCP) self-assembly and polymer-polymer interface behaviors in binary blends. The interaction of major and minor phases in binary polymer blends leads to the formation of an anisotropic oblate particle, and the BCP-rich phase enables ordered packing and unidirectional alignment of carbon nanorods. Consequently, this approach enables precise control over particles' size, shape, and over the dimensionality of their components. Exploiting this functional superstructure, o-MCS are used as an anode material in potassium-ion batteries, and achieve a notable specific capacity of 156 mA h g-1 at a current density of 2 A g-1, and long-term stability for 3000 cycles. This work presents a significant advancement in the field of hierarchical superstructures, providing a promising strategy for the design and synthesis of anisotropic carbon materials with controlled properties, offering promising applications in energy storage and beyond.

Microscopic Origin of Electrochemical Capacitance in Metal-Organic Frameworks.

Electroconductive metal-organic frameworks (MOFs) have emerged as high-performance electrode materials for supercapacitors, but the fundamental understanding of the underlying chemical processes is limited. Here, the electrochemical interface of Cu3(HHTP)2 (HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene) with an organic electrolyte is investigated using a multiscale quantum-mechanics/molecular-mechanics (QM/MM) procedure and experimental electrochemical measurements. Our simulations reproduce the observed capacitance values and reveals the polarization phenomena of the nanoporous framework. We find that excess charges mainly form on the organic ligand, and cation-dominated charging mechanisms give rise to greater capacitance. The spatially confined electric double-layer structure is further manipulated by changing the ligand from HHTP to HITP (HITP = 2,3,6,7,10,11-hexaiminotriphenylene). This minimal change to the electrode framework not only increases the capacitance but also increases the self-diffusion coefficients of in-pore electrolytes. The performance of MOF-based supercapacitors can be systematically controlled by modifying the ligating group.

Anion-Induced Interfacial Liquid Layers on LiCoO2 in Salt-in-Water Lithium-Ion Batteries.

The incompatibility of lithium intercalation electrodes with water has impeded the development of aqueous Li-ion batteries. The key challenge is protons which are generated by water dissociation and deform the electrode structures through intercalation. Distinct from previous approaches utilizing large amounts of electrolyte salts or artificial solid-protective films, we developed liquid-phase protective layers on LiCoO2 (LCO) using a moderate concentration of 0.5∼3 mol kg-1 lithium sulfate. Sulfate ion strengthened the hydrogen-bond network and easily formed ion pairs with Li+, showing strong kosmotropic and hard base characteristics. Our quantum mechanics/molecular mechanics (QM/MM) simulations revealed that sulfate ion paired with Li+ helped stabilize the LCO surface and reduced the density of free water in the interface region below the point of zero charge (PZC) potential. In addition, in situ electrochemical surface-enhanced infrared absorption spectroscopy (SEIRAS) proved the appearance of inner-sphere sulfate complexes above the PZC potential, serving as the protective layers of LCO. The role of anions in stabilizing LCO was correlated with kosmotropic strength (sulfate > nitrate > perchlorate > bistriflimide (TFSI-)) and explained better galvanostatic cyclability in LCO cells.

Room-temperature stacking disorder in layered covalent-organic frameworks from machine-learning force fields.

The local structures of layered covalent-organic frameworks (COFs) deviate from the average crystal structures assigned from X-ray diffraction experiments. For two prototype COFs of Tp-Azo and DAAQ-TFP, density functional theory calculations have shown that the eclipsed structure is not an energy minimum and that the internal energy is lowered for an inclined stacking arrangement. Here we explore the structural disorder of these frameworks at 300 K through molecular dynamics (MD) simulations using an on-the-fly machine learning force field (MLFF). We find that an initially eclipsed stacking mode spontaneously distorts to form a zigzag configuration that lowers the free energy of the crystal. The simulated diffraction patterns show good agreement with experimental observations. The dynamic disorder from the MLFF MD trajectories is found to persist in mesoscale MD simulations of 155 thousand atoms, giving further confidence in our conclusions. Our simulations show that the stacking behaviour of layered COFs is more complicated than previously understood.

Evaluation of optimal scene time interval for out-of-hospital cardiac arrest using a deep neural network.

AIM: This study aims to develop a cardiac arrest prediction model using deep learning (CAPD) algorithm and to validate the developed algorithm by evaluating the change in out-of-hospital cardiac arrest patient prognosis according to the increase in scene time interval (STI). METHODS: We conducted a retrospective cohort study using smart advanced life support trial data collected by the National Emergency Center from January 2016 to December 2019. The smart advanced life support data were randomly partitioned into derivation and validation datasets. The performance of the CAPD model using the patient's age, sex, event witness, bystander cardiopulmonary resuscitation (CPR), administration of epinephrine, initial shockable rhythm, prehospital defibrillation, provision of advanced life support, response time interval, and STI as prediction variables for prediction of a patient's prognosis was compared with conventional machine learning methods. After fixing other values of the input data, the changes in prognosis of the patient with respect to the increase in STI was observed. RESULTS: A total of 16,992 patients were included in this study. The area under the receiver operating characteristic curve values for predicting prehospital return of spontaneous circulation (ROSC) and favorable neurological outcomes were 0.828 (95% confidence interval 0.826-0.830) and 0.907 (0.914-0.910), respectively. Our algorithm significantly outperformed other artificial intelligence algorithms and conventional methods. The neurological recovery rate was predicted to decrease to 1/3 of that at the beginning of cardiopulmonary resuscitation when the STI was 28 min, and the prehospital ROSC was predicted to decrease to 1/2 of its initial level when the STI was 30 min. CONCLUSION: The CAPD exhibits potential and effectiveness in identifying patients with ROSC and favorable neurological outcomes for prehospital resuscitation.

Protective Role of Endothelial Fibulin-4 in Valvulo-Arterial Integrity.

Background Homeostasis of the vessel wall is cooperatively maintained by endothelial cells (ECs), smooth muscle cells, and adventitial fibroblasts. The genetic deletion of fibulin-4 (Fbln4) in smooth muscle cells (SMKO) leads to the formation of thoracic aortic aneurysms with the disruption of elastic fibers. Although Fbln4 is expressed in the entire vessel wall, its function in ECs and relevance to the maintenance of valvulo-arterial integrity are not fully understood. Methods and Results Gene silencing of FBLN4 was conducted on human aortic ECs to evaluate morphological changes and gene expression profile. Fbln4 double knockout (DKO) mice in ECs and smooth muscle cells were generated and subjected to histological analysis, echocardiography, Western blotting, RNA sequencing, and immunostaining. An evaluation of the thoracic aortic aneurysm phenotype and screening of altered signaling pathways were performed. Knockdown of FBLN4 in human aortic ECs induced mesenchymal cell-like changes with the upregulation of mesenchymal genes, including TAGLN and MYL9. DKO mice showed the exacerbation of thoracic aortic aneurysms when compared with those of SMKO and upregulated Thbs1, a mechanical stress-responsive molecule, throughout the aorta. DKO mice also showed progressive aortic valve thickening with collagen deposition from postnatal day 14, as well as turbulent flow in the ascending aorta. Furthermore, RNA sequencing and immunostaining of the aortic valve revealed the upregulation of genes involved in endothelial-to-mesenchymal transition, inflammatory response, and tissue fibrosis in DKO valves and the presence of activated valve interstitial cells. Conclusions The current study uncovers the pivotal role of endothelial fibulin-4 in the maintenance of valvulo-arterial integrity, which influences thoracic aortic aneurysm progression.

Cationic Additive with a Rigid Solvation Shell for High-Performance Zinc Ion Batteries.

Despite substantial progresses, in aqueous zinc ion batteries (AZIBs), developing zinc metal anodes with long-term reliable cycling capabilities is nontrivial because of dendritic growth and related parasitic reactions on the zinc surface. Here, we exploit the tip-blocking effect of a scandium (Sc3+ ) additive in the electrolyte to induce uniform zinc deposition. Additional to the tri-valency of Sc3+ , the rigidity of its hydration shell effectively prevents zinc ions from concentrating at the surface tips, enabling highly stable cycling under challenging conditions. The shell rigidity, quantified by the rate constant of the exchange reaction (kex ), is established as a key descriptor for evaluating the tip-blocking effect of redox-inactive cations, explaining inconsistent results when only the valence state is considered. Moreover, the tip-blocking effect of Sc3+ is maintained in blends with organic solvents, allowing the zinc anode to cycle reliably even at -40 °C without corrosion.

A unifying mechanism for cation effect modulating C1 and C2 productions from CO2 electroreduction.

Electrocatalysis, whose reaction venue locates at the catalyst-electrolyte interface, is controlled by the electron transfer across the electric double layer, envisaging a mechanistic link between the electron transfer rate and the electric double layer structure. A fine example is in the CO2 reduction reaction, of which rate shows a strong dependence on the alkali metal cation (M+) identity, but there is yet to be a unified molecular picture for that. Using quantum-mechanics-based atom-scale simulation, we herein scrutinize the M+-coupling capability to possible intermediates, and establish H+- and M+-associated ET mechanisms for CH4 and CO/C2H4 formations, respectively. These theoretical scenarios are successfully underpinned by Nernstian shifts of polarization curves with the H+ or M+ concentrations and the first-order kinetics of CO/C2H4 formation on the electrode surface charge density. Our finding further rationalizes the merit of using Nafion-coated electrode for enhanced C2 production in terms of enhanced surface charge density.

On the importance of the electric double layer structure in aqueous electrocatalysis.

To design electrochemical interfaces for efficient electric-chemical energy interconversion, it is critical to reveal the electric double layer (EDL) structure and relate it with electrochemical activity; nonetheless, this has been a long-standing challenge. Of particular, no molecular-level theories have fully explained the characteristic two peaks arising in the potential-dependence of the EDL capacitance, which is sensitively dependent on the EDL structure. We herein demonstrate that our first-principles-based molecular simulation reproduces the experimental capacitance peaks. The origin of two peaks emerging at anodic and cathodic potentials is unveiled to be an electrosorption of ions and a structural phase transition, respectively. We further find a cation complexation gradually modifies the EDL structure and the field strength, which linearly scales the carbon dioxide reduction activity. This study deciphers the complex structural response of the EDL and highlights its catalytic importance, which bridges the mechanistic gap between the EDL structure and electrocatalysis.

Tailoring a Dynamic Metal-Polymer Interaction to Improve Catalyst Selectivity and Longevity in Hydrogenation.

Controlling metal-support interactions is important for tuning the catalytic properties of supported metal catalysts. Here, premade Pd particles are supported on stable polymers containing different ligating functionalities to control the metal-polymer interactions and their catalytic properties in industrially relevant acetylene partial hydrogenation. The polymers containing strongly ligating groups (e.g., Ar-SH and Ar-S-Ar) can form a polymer overlayer on the Pd surface, which enables selective acetylene adsorption and partial hydrogenation to ethylene without deactivation. In contrast, polymers with weakly ligating groups (e.g., Ar-O-Ar) do not form an overlayer, resulting in non-selective hydrogenation and fast deactivation, similar to Pd catalysts on conventional inorganic supports. The results imply that tuning the metal-polymer interactions via rational polymer design can provide an efficient way of synthesizing selective and stable catalysts for hydrogenation.

Dynamic metal-polymer interaction for the design of chemoselective and long-lived hydrogenation catalysts.

Metal catalysts are generally supported on hard inorganic materials because of their high thermochemical stabilities. Here, we support Pd catalysts on a thermochemically stable but "soft" engineering plastic, polyphenylene sulfide (PPS), for acetylene partial hydrogenation. Near the glass transition temperature (~353 K), the mobile PPS chains cover the entire surface of Pd particles via strong metal-polymer interactions. The Pd-PPS interface enables H2 activation only in the presence of acetylene that has a strong binding affinity to Pd and thus can disturb the Pd-PPS interface. Once acetylene is hydrogenated to weakly binding ethylene, re-adsorption of PPS on the Pd surface repels ethylene before it is further hydrogenated to ethane. The Pd-PPS interaction enables selective partial hydrogenation of acetylene to ethylene even in an ethylene-rich stream and suppresses catalyst deactivation due to coke formation. The results manifest the unique possibility of harnessing dynamic metal-polymer interaction for designing chemoselective and long-lived catalysts.

Role of PAR1-Egr1 in the Initiation of Thoracic Aortic Aneurysm in Fbln4-Deficient Mice.

OBJECTIVE: Remodeling of the extracellular matrix plays a vital role in cardiovascular diseases. Using a mouse model of postnatal ascending aortic aneurysms (termed Fbln4SMKO), we have reported that abnormal mechanosensing led to aneurysm formation in Fbln4SMKO with an upregulation of the mechanosensitive transcription factor, Egr1 (Early growth response 1). However, the role of Egr1 and its upstream regulator(s) in the initiation of aneurysm development and their relationship to an aneurysmal microenvironment are unknown. Approach and Results: To investigate the contribution of Egr1 in the aneurysm development, we deleted Egr1 in Fbln4SMKO mice and generated double knockout mice (DKO, Fbln4SMKO; Egr1-/-). Aneurysms were prevented in DKO mice (42.8%) and Fbln4SMKO; Egr1+/- mice (26%). Ingenuity Pathway Analysis identified PAR1 (protease-activated receptor 1) as a potential Egr1 upstream gene. Protein and transcript levels of PAR1 were highly increased in Fbln4SMKO aortas at postnatal day 1 before aneurysm formed, together with active thrombin and MMP (matrix metalloproteinase)-9, both of which serve as a PAR1 activator. Concordantly, protein levels of PAR1, Egr1, and thrombin were significantly increased in human thoracic aortic aneurysms. In vitro cyclic stretch assays (1.0 Hz, 20% strain, 8 hours) using mouse primary vascular smooth muscle cells induced marked expression of PAR1 and secretion of prothrombin in response to mechanical stretch. Thrombin was sufficient to induce Egr1 expression in a PAR1-dependent manner. CONCLUSIONS: We propose that thrombin, MMP-9, and mechanical stimuli in the Fbln4SMKO aorta activate PAR1, leading to the upregulation of Egr1 and initiation of ascending aortic aneurysms.

Matrix mechanotransduction mediated by thrombospondin-1/integrin/YAP in the vascular remodeling.

The extracellular matrix (ECM) initiates mechanical cues that activate intracellular signaling through matrix-cell interactions. In blood vessels, additional mechanical cues derived from the pulsatile blood flow and pressure play a pivotal role in homeostasis and disease development. Currently, the nature of the cues from the ECM and their interaction with the mechanical microenvironment in large blood vessels to maintain the integrity of the vessel wall are not fully understood. Here, we identified the matricellular protein thrombospondin-1 (Thbs1) as an extracellular mediator of matrix mechanotransduction that acts via integrin αvß1 to establish focal adhesions and promotes nuclear shuttling of Yes-associated protein (YAP) in response to high strain of cyclic stretch. Thbs1-mediated YAP activation depends on the small GTPase Rap2 and Hippo pathway and is not influenced by alteration of actin fibers. Deletion of Thbs1 in mice inhibited Thbs1/integrin ß1/YAP signaling, leading to maladaptive remodeling of the aorta in response to pressure overload and inhibition of neointima formation upon carotid artery ligation, exerting context-dependent effects on the vessel wall. We thus propose a mechanism of matrix mechanotransduction centered on Thbs1, connecting mechanical stimuli to YAP signaling during vascular remodeling in vivo.

Synergistic Control of Structural Disorder and Surface Bonding Nature to Optimize the Functionality of Manganese Oxide as an Electrocatalyst and a Cathode for Li-O2 Batteries.

An efficient way to improve the electrocatalyst and Li-O2 battery performances of metal oxide is developed by an exquisite synergistic control over structural disorder and surface bonding nature. The effects of amorphous nature and surface chemical environment on the functionalities of metal oxide are systematically investigated with well-crystalline and amorphous MnO2 nanocrystals with/without surface anchoring of highly oxidized iodate clusters. The amorphous MnO2 nanocrystal containing anchored iodate clusters shows much better performance as an oxygen evolution electrocatalyst and cathode catalyst for Li-O2 batteries than both iodate-free amorphous and well-crystalline homologues, underscoring the remarkable advantage of simultaneous enhancement of structural disorder and surface electron density. In situ X-ray absorption spectroscopic analysis demonstrates the promoted formation of double (MnO) bond, a critical step of oxygen evolution reaction, upon amorphization caused by the poor orbital overlap inside highly disordered crystallites. The beneficial effects of iodate anchoring and amorphization on electrocatalyst functionality are attributable to the alteration of surface bonding character, stabilization of Jahn-Teller active Mn3+ species, and enhanced charge transfer of interfaces. The present study underscores that fine-tuning of structural disorder and surface bonding nature provides an effective methodology to explore efficient metal oxide-based electrocatalysts.

Recent updates on the molecular network of elastic fiber formation.

Elastic fibers confer elasticity and recoiling to tissues and organs and play an essential role in induction of biochemical responses in a cell against mechanical forces derived from the microenvironment. The core component of elastic fibers is elastin (ELN), which is secreted as the monomer tropoelastin from elastogenic cells, and undergoes self-aggregation, cross-linking and deposition on to microfibrils, and assemble into insoluble ELN polymers. For elastic fibers to form, a microfibril scaffold (primarily formed by fibrillin-1 (FBN1)) is required. Numerous elastic fiber-associated proteins are involved in each step of elastogenesis and they instruct and/or facilitate the elastogenesis processes. In this review, we designated five proteins as key molecules in elastic fiber formation, including ELN, FBN1, fibulin-4 (FBLN4), fibulin-5 (FBLN5), and latent TGFß-binding protein-4 (LTBP4). ELN and FBN1 serve as building blocks for elastic fibers. FBLN5, FBLN4 and LTBP4 have been demonstrated to play crucial roles in elastogenesis through knockout studies in mice. Using these molecules as a platform and expanding the elastic fiber network through the generation of an interactome map, we provide a concise review of elastogenesis with a recent update as well as discuss various biological functions of elastic fiber-associated proteins beyond elastogenesis in vivo.

Radix Sophorae Flavescentis inhibits proliferation and induces apoptosis of AGS human gastric cancer cells.

Traditional herbal medicines are being increasingly used worldwide to treat cancer. Radix Sophorae Flavescentis (RSF) is a Chinese herb, which has numerous pharmacological properties, including anti­tumour effects. In this study, we investigated the mechanisms underlying RSF­induced apoptosis in human gastric cancer cells (AGS cells). We found that RSF treatment (20­200 µg/ml) inhibited the proliferation of AGS cells and increased the sub­G1 phase ratio. RSF­induced cell death was associated with the downregulation of BCl­2 and upregulation of Bax. In addition to increasing the expression levels of apoptosis­mediating surface antigen FAS and Fas ligand, RSF also activated caspase­3; however, mitogen­activated protein kinase appeared to inhibit RSF­induced cell death. RSF also led to an increased production of reactive oxygen species. Based on these results, we propose that RSF could be a potential therapeutic agent for gastric cancer.

Role of Thrombospondin-1 in Mechanotransduction and Development of Thoracic Aortic Aneurysm in Mouse and Humans.

RATIONALE: Abnormal mechanosensing of smooth muscle cells (SMCs) resulting from the defective elastin-contractile units has been suggested to drive the formation of thoracic aortic aneurysms; however, the precise molecular mechanism has not been elucidated. OBJECTIVE: The aim of this study was to identify the crucial mediator(s) involved in abnormal mechanosensing and propagation of biochemical signals during the aneurysm formation and to establish a basis for a novel therapeutic strategy. METHODS AND RESULTS: We used a mouse model of postnatal ascending aortic aneurysms ( Fbln4SMKO; termed SMKO [SMC-specific knockout]), in which deletion of Fbln4 (fibulin-4) leads to disruption of the elastin-contractile units caused by a loss of elastic lamina-SMC connections. In this mouse, upregulation of Egr1 (early growth response 1) and angiotensin-converting enzyme leads to activation of Ang II (angiotensin II) signaling. Here, we showed that the matricellular protein, Thbs1 (thrombospondin-1), was highly upregulated in SMKO ascending aortas and in human thoracic aortic aneurysms. Thbs1 was induced by mechanical stretch and Ang II in SMCs, for which Egr1 was required, and reduction of Fbln4 sensitized the cells to these stimuli and led to higher expression of Egr1 and Thbs1. Deletion of Thbs1 in SMKO mice prevented the aneurysm formation in ≈80% of DKO (SMKO;Thbs1 knockout) animals and suppressed Ssh1 (slingshot-1) and cofilin dephosphorylation, leading to the formation of normal actin filaments. Furthermore, elastic lamina-SMC connections were restored in DKO aortas, and mechanical testing showed that structural and material properties of DKO aortas were markedly improved. CONCLUSIONS: Thbs1 is a critical component of mechanotransduction, as well as a modulator of elastic fiber organization. Maladaptive upregulation of Thbs1 results in disruption of elastin-contractile units and dysregulation of actin cytoskeletal remodeling, contributing to the development of ascending aortic aneurysms in vivo. Thbs1 may serve as a potential therapeutic target for treating thoracic aortic aneurysms.

α-MnO2 Nanowire-Anchored Highly Oxidized Cluster as a Catalyst for Li-O2 Batteries: Superior Electrocatalytic Activity and High Functionality.

An effective chemical way to optimize the oxygen electrocatalyst and Li-O2 electrode functionalities of metal oxide can be developed by the control of chemical bond nature with the surface anchoring of highly oxidized selenate (SeO4 2- ) clusters. The bond competition between (Se6+ -O) and (Mn-O) bonds is quite effective in stabilizing Jahn-Teller-active Mn3+ state and in increasing oxygen electron density of α-MnO2 nanowire (NW). The selenate-anchored α-MnO2 NW shows excellent oxygen electrocatalytic activity and electrode performance for Li-O2 batteries, which is due to the improved charge transfer kinetics and reversible formation/decomposition of Li2 O2 . The present study underscores that the surface anchoring of highly oxidized cluster can provide a facile, effective way of improving the oxygen electrocatalyst and electrochemical performances of nanostructured metal oxide in Li-O2 cells.

Effects of Gamisoyo-San Decoction, a Traditional Chinese Medicine, on Gastrointestinal Motility.

BACKGROUND: Gamisoyo-San decoction (GSS), a traditional Chinese medicine, has been used to treat various gastrointestinal (GI) symptoms and diseases such as functional dyspepsia. The purpose of this study was to investigate the effect of GSS on GI motility functions in mice. METHODS: Percent intestinal transit rate (ITR%) and gastric emptying (GE) values were measured using Evans Blue and phenol red, respectively, in normal mice and in mice with experimentally induced GI motility dysfunction (GMD). RESULTS: In normal mice, GSS (0.01-1 g/kg) induced higher GE values than non-treated controls. Also, GSS could increase GE in loperamide-induced and cisplatin-induced GE delay models. In addition, GSS increased ITR% in a dose-dependent manner. Loperamide decreased ITR% and GSS recovered this loperamide-induced decrease in ITR%. To examine the effect of GSS on GMD, we used acetic acid (AA)-induced and streptozotocin (STZ)-induced mouse GMD models. The AA mouse model showed a significant decrease in ITR%. However, intragastric treatment with GSS significantly recovered this inhibition. Furthermore, STZ-induced diabetic mice showed a significant reduction in ITR%, which was also significantly inhibited by GSS. CONCLUSION: These results demonstrate that GSS can modulate bowel activity and that it could be used as a gastroprokinetic agent in the treatment of GI motility diseases.