Magneto-Mechanical Coupling Study of Magnetorheological Elastomer Thin Films for Sensitivity Enhancement.

Magnetorheological elastomer thin films (MREFs) exhibit remarkable deformability and an adjustable modulus under magnetic fields, rendering them promising in fields such as robotics, flexible sensors, and biomedical engineering. Here, we fabricated MREF by introducing magnetostrictive particles (MSPs) and evaluated the magneto-mechanical coupling effect on the enhancement of sensitivity. The saturation magnetization (Ms) in a parallel anisotropic TbDyFe-PDMS MREF was 5.8 emu/g, and the initial tensile modulus was 55% greater than that of an Iso MREF. We propose a nonlinear magnetorheological formula on the magnetostriction effect, incorporating magnetic dipole interactions and the nonlinear prestress of magnetic particles. This formula highlights the complex nonlinear relationship between the external magnetic field (H) and the key parameters that affect the enhanced MR effect of MSPs-MREF, such as saturation magnetization, remanence (Mr), magnetostriction constant (λs) and stress deviator in ferromagnetic particles (Sed) in the magnetic chain structure. Furthermore, we validate the influence of the key parameters of the rectified magnetorheological formula on a nonlinear magneto-mechanical behavior of MSPs-MREF in PDMS-based MSPs-MREF models by using finite-element simulations. Finally, we developed a biosensor based on MSPs-MREF to detect human serum albumin at low concentrations in human urine samples. There is a 4-fold increase in sensitivity, a lower detection of limit (0.442 µg/mL), and a faster response time (15 min) than traditional biosensors, which in the future might provide an effective way of detecting biomolecules of low concentrations.

Comprehensive consideration of multiple determinants from evidence to recommendations in guidelines for most traditional Chinese medicine was suboptimal: a systematic review.

BACKGROUND: The overall comprehensive consideration of the factors influencing the recommendations in the traditional Chinese medicine (TCM) guidelines remains poorly studied. This study systematically evaluate the factors influencing recommendations formation in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) clinical practice guidelines (CPGs) and TCM CPGs. METHODS: This was a methodological review in which we searched six databases and multiple related websites. The GRADE CPGs were identified as the guidelines developed by the GRADE Working Group or the two Co-Chairs. For the TCM CPGs, we randomly selected guidelines that were published by the TCM or integrative medicine academic societies from China mainland (published by the TCM or integrative medicine academic societies of China mainland). Two reviewers independently screened and extracted data. We included CPGs published in 2018-2022. We extracted information on the influencing factors of evidence to recommendation and conducted the analyses using descriptive statistics and calculated the proportion of relevant items by IBM SPSS Statistics and Microsoft Excel to compare the differences between the GRADE CPGs and the TCM CPGs. RESULTS: Forty-five GRADE CPGs (including 912 recommendations) and 88 TCM CPGs (including 2452 recommendations) were included. TCM recommendations mainly considered the four key determinants of desirable anticipated effects, undesirable anticipated effects, balance between desirable and undesirable effects, certainty of evidence, with less than 20% of other dimensions. And TCM CPGs presented more strong recommendations (for or against) and inappropriate discordant recommendations than GRADE CPGs. GRADE CPGs were more comprehensive considered about the factors affecting the recommendations, and considered more than 70% of all factors in the evidence to recommendation. CONCLUSIONS: The TCM CPGs lack a comprehensive consideration of multiple influencing determinants from evidence to recommendations. In the future, the correct application of the GRADE approaches should be emphasized.

CURATE.AI COR-Tx platform as a digital therapy and digital diagnostic for cognitive function in patients with brain tumour postradiotherapy treatment: protocol for a prospective mixed-methods feasibility clinical trial.

INTRODUCTION: Conventional interventional modalities for preserving or improving cognitive function in patients with brain tumour undergoing radiotherapy usually involve pharmacological and/or cognitive rehabilitation therapy administered at fixed doses or intensities, often resulting in suboptimal or no response, due to the dynamically evolving patient state over the course of disease. The personalisation of interventions may result in more effective results for this population. We have developed the CURATE.AI COR-Tx platform, which combines a previously validated, artificial intelligence-derived personalised dosing technology with digital cognitive training. METHODS AND ANALYSIS: This is a prospective, single-centre, single-arm, mixed-methods feasibility clinical trial with the primary objective of testing the feasibility of the CURATE.AI COR-Tx platform intervention as both a digital intervention and digital diagnostic for cognitive function. Fifteen patient participants diagnosed with a brain tumour requiring radiotherapy will be recruited. Participants will undergo a remote, home-based 10-week personalised digital intervention using the CURATE.AI COR-Tx platform three times a week. Cognitive function will be assessed via a combined non-digital cognitive evaluation and a digital diagnostic session at five time points: preradiotherapy, preintervention and postintervention and 16-weeks and 32-weeks postintervention. Feasibility outcomes relating to acceptability, demand, implementation, practicality and limited efficacy testing as well as usability and user experience will be assessed at the end of the intervention through semistructured patient interviews and a study team focus group discussion at study completion. All outcomes will be analysed quantitatively and qualitatively. ETHICS AND DISSEMINATION: This study has been approved by the National Healthcare Group (NHG) DSRB (DSRB2020/00249). We will report our findings at scientific conferences and/or in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04848935.

Transcriptomics reveals the molecular regulation of Chinese medicine formula on improving bone quality in broiler.

Skeletal disorder is of concern to the poultry industry as it affects animal welfare and production performance. Traditional Chinese medicine could improve bone quality and reduce the incidence of bone disease, but the molecular regulation of Chinese medicine formula (CMF) on improving bone quality in broilers is still unclear. This study was performed to research the effects of CMF on skeletal performance of Cobb broilers and reveal the molecular regulation. A total of 120 one-day-old Cobb broilers were randomly allocated into 4 equal groups of 30 chickens, with 5 replicates and 6 chickens in each replicate. The control (CON) group was fed a diet without CMF, while the CMF1, CMF2, and CMF3 groups were supplemented with different CMF at 6,000 mg/kg diet, respectively. The broilers were raised to 60 d of age, then bone tissues were collected for biomechanical properties, micro-CT detection and transcriptomic sequencing analysis. The results showed that CMF3 improved the biomechanical properties of broiler tibia, via increasing the elastic modulus (P < 0.05), yield strength (P > 0.05), maximum stress (P < 0.05) and fracture stress (P < 0.05) of the tibia. Micro-CT analysis indicated that CMF3 increased the bone mineral density (BMD), bone volume/total volume (BV/TV), bone surface density (BS/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and decreased the trabecular separation (Tb.Sp) of femur cancellous bone (P < 0.05). RNA-seq analysis revealed 2,177 differentially expressed genes (DEGs) (|log2FoldChange| ≥ 1, FDR < 0.05) between the CMF3 group and CON group. Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis showed 13 pathways mostly associated with bone growth and development and bone metabolism, and we identified 39 bone-related DEGs. This study suggests that CMF3 could improve bone strength and bone microstructure of broilers, and showed a positive effect on bone performance. Our research could provide a theoretical reference for the development of pollution-free feed additives to improve the skeletal performance of broilers, which could help promote healthy farming of chickens.

[Discussion on the Authenticity Verification Method in the Verification of Medical Device Registration Quality Management System].

Authenticity verification is a very important aspect of medical device registration quality management system verification of medical device. How to verify the authenticity of samples is a problem worth discussing. This study analyzes the methods of authenticity verification from the aspects of product retention sample, registration inspection report, traceability of records, hardware facilities and equipment. In order to provide reference for relevant supervisors and inspectors in the verification of registration quality management system.

Solvent-induced proteome profiling for proteomic quantitation and target discovery of small molecular drugs.

Target identification by modification-free proteomic approaches can potentially reveal the pharmacological mechanism of small molecular compounds. By combining the recent solvent-induced protein precipitation (SIP) method with TMT-labeling quantitative proteomics, we propose solvent-induced proteome profiling (SIPP) approach to identify small molecule-protein interactions. The SIPP approach enables to depict denaturation curves of the target protein by varying concentrations of organic solvents to induce unfolding and precipitation of the cellular proteome. By using this approach, we have successfully identified the known targets of market drugs and natural products and extended the proteome information of SIP for target identification.

A novel dual-flux immunochromatographic test strip based on luminescence resonance energy transfer for simultaneous detection of ochratoxin A and deoxynivalenol.

Mycotoxins are secondary metabolites of fungi, which seriously threaten human health. Among them, ochratoxin A (OTA) and deoxynivalenol (DON) have become the main factors that pollute cereals and by-products. In order to achieve simultaneous detection of OTA and DON quantitatively, a novel dual-flux immunochromatographic assay (dICA) was established. The dual-flux assay is based on upconversion nanoparticles (UCNPs) as fluorescence tags to label antigens and gold nanoparticles (AuNPs) as fluorescence quencher to label monoclonal antibodies (mAbs). The intensity of the green fluorescence (540 nm) of UCNPs can be used as an analytical signal, indicating the formation of antigen-antibody immune complexes, thereby indicating the presence or absence of the target analyte. The intensity of the red fluorescence (660 nm) of UCNPs is not affected and can be used as a quality control signal, and the dual-flux bidirectional single-line labeling mode allows for the simultaneous detection of two different mycotoxins on two test lines. This work indicated that the developed dICA provided a sensitive, rapid, and reliable on-site simultaneous detection of multiple mycotoxins.

Quality Evaluation and Reporting Specification for Real-World Studies of Traditional Chinese Medicine.

In recent years, the real-world studies (RWS) have attracted extensive attention, and the real-world evidence (RWE) has been accepted to support the drug development in China and abroad. However, there is still a lack of standards for the evaluation of the quality of RWE. It is necessary to formulate a quality evaluation and reporting specification for RWE especially in traditional Chinese medicine (TCM). To this end, under the guidance of China Association of Chinese Medicine, the Quality Evaluation and Reporting Specification for Real-World Evidence of Traditional Chinese Medicine (QUERST) Group, including 24 experts (clinical epidemiologists, clinicians, pharmacologists, ethical reviewer and statisticians), was established to develop the specification. This specification contains the listing of classification of RWS design and RWE, the general principles and methods of RWE quality evaluation (26 tools or scales), 25 types of bias in RWS, the special considerations in evaluating the quality of RWE of TCM, and the 19 reporting standards of RWE. This specification aims to propose the quality evaluation principles and key points of RWE, and provide guidance for the proper use of RWE in the development of TCM new drugs.

Salicylic Acid Enhances Heat Stress Resistance of Pleurotus ostreatus (Jacq.) P. Kumm through Metabolic Rearrangement.

Pleurotus ostreatus (Jacq.) P. Kumm is cultivated worldwide, and its growth is seriously threatened by heat stress. Here, we performed a comprehensive analysis to investigate the influence of the phytohormone salicylic acid (SA) in P. ostreatus under HS. The results showed that the hyphal growth recovery rate and the antioxidant capacity of P. ostreatus increased with exogenous SA application (0.01 mmol/L and 0.05 mmol/L) after HS treatment. Metabolomic and transcriptomic analyses showed that SA application (0.05 mmol/L) weakened central carbon metabolism to allow cells to survive HS efficiently. In addition, SA shifted glycolysis to one-carbon metabolism to produce ROS scavengers (GSH and NADPH) and reduced ROS production by altering mitochondrial metabolism. SA also maintained nucleotide homeostasis, led to membrane lipid remodeling, activated the MAPK pathway, and promoted the synthesis of cell-wall components. This study provides a reference for further study of SA in microorganisms.

Correlation Between Retinopathy and Coronary Microcirculation Dysfunction in Patients with Type 2 Diabetes Mellitus.

PURPOSE: The aim of this study is to evaluate the correlation between retinopathy and coronary microcirculation dysfunction (CMD) in type 2 diabetes mellitus (T2DM) patients. METHODS: 198 T2DM patients with left ventricular ejection fraction (LVEF)>50%, no epicardial coronary artery stenosis diagnosis by coronary angiography (CAG) and successfully completed coronary blood flow reserve (CFR) test and laboratory examination were enrolled, and fundus examination was performed on all participants. Two groups were divided according to CFR value, including 86 patients with CMD (CFR≤2.5) in study group and 112 patients without CMD (CFR>2.5) in control group. The composition of various retinopathy in two groups was observed, and the correlation between retinopathy and CMD was analyzed using ordered logistic regression. RESULTS: There were 13 cases with arteriovenous (A/V) nicking, 4 cases with proliferative diabetic retinopathy (PDR), 14 cases with non-proliferative diabetic retinopathy (NPDR), 17 cases with diabetic retinopathy (DR) with A/V nicking, 38 cases without retinopathy in study group, and 18 cases, 7 cases, 20 cases, 4 cases and 63 cases for each in control group. After adjustment for age, gender, hypertension, diabetes duration, dyslipidemia, glycosylated hemoglobin (HbA1c), body mass index (BMI), A/V nicking, PDR and NPDR, the diference of DR with A/V nicking between study and control group remained statistically signifcant (OR 2.0, 95% CI 0.79 to 3.21, p = 0.001). CONCLUSION: DR with A/V nicking could be used as an independent predictor of T2DM patients with CMD. CFR testing should be performed on patients with this kind of eye sign, even if they do not have any symptoms of heart disease. Meanwhile, DR with A/V nicking might be served as a reference indicator of CMD in T2DM patients with chest pain who were unable to be tested for CFR.

Inhibition of SGLT1 Alleviates the Glycemic Variability-Induced Cardiac Fibrosis via Inhibition of Activation of Macrophage and Cardiac Fibroblasts.

Glycemic variability has been considered one of the predictors of diabetes complications in patients with diabetes mellitus (DM). In this work, we evaluated whether glycemic variability induces cardiac fibrosis through regulating cardiac fibroblast activation and macrophage polarization. Moreover, we determined whether glucose transporter sodium-glucose cotransporter 1 (SGLT1) plays an important role in this process. Glycemic variability-induced mice were established using DM mice (GVDM mice), and intermittent high-glucose (IHG) treatment was used to simulate glycemic variability in RAW264.7 macrophages and cardiac fibroblasts. The short hairpin RNA for SGLT1 was used to knock down SGLT1. The results showed that glycemic variability aggravated the cardiac fibrosis in GVDM mice. Additionally, glycemic variability promoted the expression of fibrogenic cytokine and the extracellular matrix proteins in left ventricular tissues and cardiac fibroblasts. GVDM mice showed a higher incidence of macrophage infiltration and M1 polarization in left ventricular tissues. Moreover, IHG-promoted RAW264.7 macrophages tended to differentiate to M1 phenotype. SGLT1 knockdown alleviated cardiac fibrosis in GVDM mice and inhibited activations of cardiac fibroblast and macrophage M1 polarization. Our results indicated that glycemic variability aggravates cardiac fibrosis through activating cardiac fibroblast and macrophage M1 polarization, which could be partially inhibited by SGLT1 knockdown.

N, S-Doped Carbon Dots Prepared by Peanut Protein Isolates and Cysteamine as Highly Sensitive Fluorescent Sensors for Fe2+, Fe3+ and Lactoferrin.

Lactoferrin (LF) is an iron-binding glycoprotein with various biological activities that has been extensively used in food and medical applications. Several methods for detecting LF have been reported, but they still face challenges in terms of sensitivity and simplicity of detection. To achieve an accurate and efficient detection of LF, we developed a method for the determination of LF in lactoferrin supplements using carbon dots (CDs) fluorescent probes. The N, S-doped PPI carbon dots (N, S-PPI-CDs) were prepared using a protein (peanut protein isolate) and cysteamine as precursors. The prepared N, S-PPI-CDs exhibited intense blue fluorescence and good biocompatibility, while the fluorescence intensity of the N, S-PPI-CDs showed a good linear relationship with Fe2+/Fe3+ concentration (0-2 µM). The N, S-PPI-CDs exhibited a high potential ability to rapidly detect Fe2+/Fe3+ within 30 s, with a limit of detection (LoD) of 0.21 µM/0.17 µM. Due to the reversible binding of LF to Fe, the N, S-PPI-CDs showed a high sensitivity and selectivity for LF, with a limit of detection (LoD) of 1.92 µg/mL. In addition, LF was quantified in real sample LF supplements and showed a fluctuation in recovery of less than 2.48%, further demonstrating the effectiveness of the fluorescent N, S-PPI-CDs sensor.

Thymic Egress Is Regulated by T Cell-Derived LTßR Signal and via Distinct Thymic Portal Endothelial Cells.

Thymic blood vessels at the perivascular space (PVS) are the critical site for both homing of hematopoietic progenitor cells (HPCs) and egress of mature thymocytes. It has been intriguing how different opposite migrations can happen in the same place. A subset of specialized thymic portal endothelial cells (TPECs) associated with PVS has been identified to function as the entry site for HPCs. However, the cellular basis and mechanism underlying egress of mature thymocytes has not been well defined. In this study, using various conventional and conditional gene-deficient mouse models, we first confirmed the role of endothelial lymphotoxin beta receptor (LTßR) for thymic egress and ruled out the role of LTßR from epithelial cells or dendritic cells. In addition, we found that T cell-derived ligands lymphotoxin (LT) and LIGHT are required for thymic egress, suggesting a crosstalk between T cells and endothelial cells (ECs) for thymic egress control. Furthermore, immunofluorescence staining analysis interestingly showed that TPECs are also the exit site for mature thymocytes. Single-cell transcriptomic analysis of thymic endothelial cells suggested that TPECs are heterogeneous and can be further divided into two subsets depending on BST-1 expression level. Importantly, BST-1hi population is associated with thymic egressing thymocytes while BST-1lo/- population is associated with HPC settling. Thus, we have defined a LT/LIGHT-LTßR signaling-mediated cellular crosstalk regulating thymic egress and uncovered distinct subsets of TPECs controlling thymic homing and egress, respectively.

Neutrophil-to-lymphocyte ratio is associated with coronary microvascular dysfunction in type 2 diabetes mellitus patients.

AIMS: Our study is aimed to investigate the relationship between neutrophil-to-lymphocyte ratio (NLR) and coronary microvascular dysfunction (CMD) in type 2 diabetes mellitus (T2DM) patients. METHODS: We retrospect the consecutive medical files of 160 T2DM patients and recorded their clinical information and laboratory findings. Patients were divided into CMD group (n = 87) and non-CMD group (n = 73). We compared the NLR values of the two groups. Meanwhile we also observed the prevalence of CMD at different NLR levels. Then, logistic regression and ROC analysis were performed. RESULTS: NLR value of CMD group was significantly lower than non-CMD group (2.01 ± 0.74 vs 2.53 ± 0.69, P＜0.001). Prevalence of CMD in low (NLR ≤ 1.53, n = 30), medium (1.53 < NLR ≤ 2.20, n = 53) and high (NLR > 2.20, n = 77) group were 90%, 61.1%, and 39.2% respectively. The prevalence of CMD significantly increased as NLR level decreased. After adjusting potential related factors, NLR was still significantly correlated with CMD (OR = 0.295, 95 %CI:0.162-0.539, P < 0.001). The area under ROC curve (AUC) was 0.707 (95 %CI:0.627-0.786, P < 0.001). CONCLUSIONS: Our results showed that NLR is associated with CMD in T2DM patients, and the prevalence of CMD may increase as NLR level decrease.

Glucose fluctuation accelerates cardiac injury of diabetic mice via sodium-dependent glucose cotransporter 1 (SGLT1).

Recent studies have shown that blood glucose fluctuation is associated with complications of diabetes mellitus (DM). SGLT1 (sodium-dependent glucose cotransporter 1), is highly expressed in pathological conditions of heart, and is expressed in cardiomyocytes induced by high glucose. Herein, we constructed a diabetic mouse model with glucose fluctuation to investigate whether SGLT1 is involved in glucose fluctuation-induced cardiac injury. Echocardiography, histology examination, and TUNEL staining were performed to evaluate cardiac dysfunction and damage. To assess glucose fluctuation-induced oxidative stress, reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were measured. To assess mitochondrial dysfunction, mitochondrial membrane potential (MMP), ATP content, mitochondrial respiratory chain complex activity, and expression of mitochondrial fusion and fission proteins were determined. The results indicated that diabetic mice with glucose fluctuation showed elevation of cardiac SGLT1 expression, left ventricular dysfunction, oxidative stress and mitochondrial dysfunction. Knockdown of SGLT1 could abrogate the effects of glucose fluctuation on cardiac injury. Thus, our study highlighted that SGLT1 plays an important role in glucose fluctuation induced cardiac injury through oxidative stress and mitochondrial dysfunction.

Intermittent high glucose induces pyroptosis of rat H9C2 cardiomyocytes via sodium-glucose cotransporter 1.

Cardiomyocyte death is an important pathogenic process in cardiac complications of diabetes. Diabetic patients often suffer glycemic variability. Pyroptosis is a form of programmed cell death triggered by inflammasomes and related with caspase-1 and gasdermin D activation. The present study was designed to examine the effects of intermittent high glucose simulating glycemic variability on the pyroptosis of cardiomyocytes in vitro. Rat H9C2 cardiomyocytes were incubated with normal glucose (NG), constant high glucose (CHG) and intermittent high glucose (IHG). Results showed that compared to CHG treatment, IHG further inhibited cell proliferation and promoted cell death of H9C2 cardiomyocytes. In addition, IHG upregulated higher levels of the expressions of inflammasome NLR family pyrin domain containing 3 (NLRP3) and adaptor protein apoptosis-associated speck-like protein containing CARD domain (ASC) and increased higher levels of activated caspase-1 and gasdermin D than CHG treatment. Moreover, the production of reactive oxygen species (ROS) and activation of NF-κB that is induced by IHG were significantly higher than that induced by CHG. Knockdown of sodium-glucose cotransporters 1 (SGLT1) in H9C2 cardiomyocytes was performed and the effects of SGLT1 on IHG-induced pyroptosis was evaluated. The results demonstrated that knockdown of SGLT1 partially reduced IHG-induced pyroptosis, ROS generation and NF-κB activation. Our results indicated that IHG is harmful to cardiomyocytes and it might be partially because of the SGLT1-depedent pyroptosis in cardiomyocytes.

Inhibition of SGLT1 protects against glycemic variability-induced cardiac damage and pyroptosis of cardiomyocytes in diabetic mice.

AIMS: Glycemic variability has been shown to be more harmful in the development of diabetic complication than sustained chronic hyperglycemia. In this present study, we tried to reveal the effects of glycemic variability on cardiac damage in diabetic mice and investigate whether sodium-glucose cotransporter 1 (SGLT1), an important cardiac glucose transporter, functions as an important mediator in the process. MATERIALS AND METHODS: Type 2 diabetes mellitus (DM) mice were induced by a high-fat diet and intraperitoneal injection of streptozotocin (STZ), and then glycemic variability in type 2 diabetes mellitus (GVDM) was induced by alternately injecting insulin and glucose to DM mice. In order to determine the roles of SGLT1 in GVDM mice, SGLT1 inhibition was performed using shRNA against SGLT1. The blood glucose level, the cardiac function and myocardial injury were assessed. And the expressions of SGLT1 and the activations of NLRP3/caspase-1 pathway and NF-κB in left ventricular tissues were measured. KEY FINDINGS: The results showed that SGLT1 was highly expressed in heart of GVDM mice compared to control and DM groups, and knockdown of SGLT1 reduced glycemic variability in GVDM mice. Moreover, glycemic variability impaired cardiac function, aggravated cardiac injury and induced NLRP3/caspase-1-mediated inflammatory response and pyroptosis. And knockdown of SGLT1 significantly attenuated the cardiac damages that induced by glycemic variability. SIGNIFICANCE: The results indicated that glycemic variability could cause cardiac damage and induce inflammatory response and pyroptosis of cardiomyocytes in diabetic mice, which could be partially blocked by SGLT1 silence.

Knockdown of SGLT1 prevents the apoptosis of cardiomyocytes induced by glucose fluctuation via relieving oxidative stress and mitochondrial dysfunction.

Fluctuations in the concentration of glucose in the blood is more detrimental than a constantly high level of glucose with respect to the development of cardiovascular complications associated with diabetes mellitus (DM). Sodium glucose cotransporter 2 (SGLT2) inhibitors have been developed as antidiabetic drugs with cardiovascular benefits; however, whether inhibition of SGLT1 protects the diabetic heart remains to be determined. This study investigated the role of SGLT1 in rat H9c2 cardiomyocytes subjected to fluctuating levels of glucose and the underlying mechanisms. The results indicated that knockdown of SGLT1 restored cell proliferation and suppressed the cytotoxicity associated with fluctuating glucose levels. Oxidative stress was induced in H9c2 cells subjected to fluctuating glucose levels, but these changes were effectively reversed by knockdown of SGLT1, as manifested by reductions in the level of intracellular reactive oxygen species and increased antioxidant activity. Further study demonstrated that knockdown of SGLT1 attenuated the mitochondrial dysfunction in H9c2 cells exposed to fluctuating glucose levels, by restoring mitochondrial membrane potential and promoting mitochondrial fusion. In addition, knockdown of SGLT1 downregulated the expression of Bax, upregulated the expression of Bcl-2, and reduced the activation of caspase-3 in H9c2 cells subjected to fluctuating levels of glucose. Collectively, our results show that knockdown of SGLT1 ameliorates the apoptosis of cardiomyocyte caused by fluctuating glucose levels via regulating oxidative stress and combatting mitochondrial dysfunction.