Engineering of cytosine base editors with DNA damage minimization and editing scope diversification.

Cytosine base editors (CBEs), which enable precise C-to-T substitutions, have been restricted by potential safety risks, including DNA off-target edits, RNA off-target edits and additional genotoxicity such as DNA damages induced by double-strand breaks (DSBs). Though DNA and RNA off-target edits have been ameliorated via various strategies, evaluation and minimization of DSB-associated DNA damage risks for most CBEs remain to be resolved. Here we demonstrate that YE1, an engineered CBE variant with minimized DNA and RNA off-target edits, could induce prominent DSB-associated DNA damage risks, manifested as γH2AX accumulation in human cells. We then perform deaminase engineering for two deaminases lamprey LjCDA1 and human APOBEC3A, and generate divergent CBE variants with eliminated DSB-associated DNA damage risks, in addition to minimized DNA/RNA off-target edits. Furthermore, the editing scopes and sequence preferences of APOBEC3A-derived CBEs could be further diversified by internal fusion strategy. Taken together, this study provides updated evaluation platform for DSB-associated DNA damage risks of CBEs and further generates a series of safer toolkits with diversified editing signatures to expand their applications.

Gray matter volume reduction with different disease duration in trigeminal neuralgia.

PURPOSE: Structural magnetic resonance imaging is widely used to explore brain gray and white matter structure in trigeminal neuralgia (TN) but has yielded conflicting findings. This study investigated the relationship between disease duration as a clinical feature of TN and changes in brain structure. METHODS: We divided 49 TN patients into three groups (TN1-TN3) based on disease duration (TN1 = 1.1 ± 0.7 (0-2) years, TN2 = 4.8 ± 1.5 (3-7) years, TN3 = 15.1 ± 5.5 (10-30) years). We used voxel-based morphometry (VBM) to compare the gray matter volume (GMV) across groups and between TN patients and 18 matched healthy control subjects. RESULTS: The TN1 group showed reduced GMV of pain-related regions in the cerebellum; the TN2 group showed reduced GMV in the thalamus and the motor/sensory cortex; and the TN3 group showed reduced GMV in the emotional and reward circuits compared with healthy controls. Similar brain regions, including bilateral hippocampi, caudate, left insular cortex, and medial superior frontal cortex, were affected in TN2 and TN3 compared with TN1. CONCLUSION: Disease duration can explain differences in structural alterations-especially in pain-related brain regions-in TN. These results highlight the advanced structural neuroimaging method that are valuable tools to assess the trigeminal system in TN and may further our current understanding of TN pathology.

Evaluation of ultralow-dose computed tomography on detection of pulmonary nodules in overweight or obese adult patients.

PURPOSE: To evaluate the accuracy of pulmonary nodule (PN) detection in overweight or obese adult patients using ultralow-dose computed tomography (ULDCT) with tin filtration at 100 kV and advanced model-based iterative reconstruction (ADMIRE). METHODS: Eighty-one patients with body mass indices of ≥25 kg/m2 were enrolled. All patients underwent low-dose chest CT (LDCT), followed by ULDCT. Two radiologists experienced in LDCT established the standard of reference (SOR) for PNs. The number, type, size, and location of PNs were identified in the SOR. Effective dose, objective image quality (IQ), and subjective IQ based on two radiologists' scores were compared between ULDCT and LDCT. The detection performances of radiologists based on ULDCT were calculated according to the nodule analyses. Logistic regression was used to test for independent predictors of PN detection sensitivity. RESULTS: Both the effective dose and objective IQ were lower for ULDCT than for LDCT (both p < 0.001). Both radiologists rated the subjective IQ of the overall IQ on ULDCT to be diagnostically sufficient. In total, 234 nodules (mean diameter, 3.4 ± 1.9 mm) were classified into 32 subsolid, 149 solid, and 53 calcified nodules according to the SOR. The overall sensitivity of ULDCT for nodule detection was 93.6%. Based on multivariate analyses, the nodule types (p = 0.015) and sizes (p = 0.013) were independent predictors of nodule detection. CONCLUSIONS: Compared with LDCT, ULDCT with tin filtration at 100 kV and ADMIRE could significantly reduce the radiation dose in overweight or obese patients while maintaining good sensitivity for nodule detection.

The role of ultrasonography in the diagnosis of talocalcaneal coalitions.

BACKGROUND: Patients with talocalcaneal coalitions (TCC) often undergo computed tomography (CT). However, ultrasonography diagnosis of TCC has been seldom done according to the literature. PURPOSE: To investigate the accuracy of ultrasonography in diagnosing TCC compared to CT. MATERIAL AND METHODS: Ninety-seven consecutive patients with a clinical suspicion of TCC were included. Ultrasonography was used to assess the classification and complication of TCC. The main sonographic criteria for a positive diagnosis in cases of osseous coalition were the joint space between the medial surface of talar head and the underlying sustentaculum tali of calcaneus disappearing and being replaced by a continuous hyperechoic bony structure. In cases of fibrous coalition, ultrasonography revealed a reduced space of the joint associated with an irregular, angular appearance of its outline and hypoechoic fibrous tissue inside. These data were compared with CT findings. κ statistic was applied to determine the level of agreement. The sensitivity, specificity, positive and negative predictive values, accuracy, and Youden index of ultrasonography as a diagnostic method were assessed. RESULTS: Ultrasonography findings were positive in 20 of 97 patients with a clinical suspicion of TCC. The diagnosis was confirmed by CT in 21 patients. There were one false-positive result and two false-negative results by ultrasonography. The κ value was 0.907. The sensitivity, specificity, positive and negative predictive values, accuracy, and Youden index of ultrasonography were 90.5%, 98.7%, 95.0%, 97.4%, 96.9%, and 0.892, respectively. CONCLUSION: Ultrasonography could be a reliable, accurate, and non-radioactive diagnostic imaging method in diagnosis of patients with suspected TCC.

miR-150 regulates glucose utilization through targeting GLUT4 in insulin-resistant cardiomyocytes.

MicroRNAs (miRNAs) play an important role in cardiac function and metabolism. However, whether they regulate insulin resistance (IR) of cardiomyocytes remains unclear. The aim of the present study was to shed light on this issue with a focus on miR-150. We found here that miR-150 level was elevated in myocardium of type 2 diabetes mellitus (T2DM) rat model and in insulin-resistant cardiomyocytes induced by high glucose (25 mM) and high insulin (1 µM). Deregulation of miR-150 downregulated the protein and mRNA levels of glucose transporter 4 (GLUT4) as assessed by western blot, real-time polymerase chain reaction (qPCR), and immunofluorescence assays. Overexpression of miR-150 inhibited glucose utilization in cardiomyocytes as detected by 2-deoxyglucose transport and glucose consumption assays. In contrast, knockdown of miR-150 significantly increased glucose uptake in cardiomyocytes. Moreover, GLUT4 translocation was increased after transfection of miR-150 inhibitor (AMO-150). Collectively, miR-150 reduced glucose utilization by directly decreasing the expression and translocation of GLUT4 in the cardiomyocytes with IR and therefore might be a new therapeutic target for metabolic diseases such as T2DM.

LOC101930370/MiR-1471 Axis Modulates the Hedgehog Signaling Pathway in Breast Cancer.

BACKGROUND/AIMS: Non-coding RNAs (ncRNAs) play vital regulatory roles in many tumors. However, the functional roles of these transcripts responsible for their dysregulation in breast cancer (BC) are not thoroughly understood. METHODS: We examined the expression of microRNA miR-1471 in BC specimens. Online analysis tools predicted that lncRNA LOC101930370 might act as an endogenous 'sponge' by competing for miR-1471 binding targets. Luciferase assays were used to prove the interaction of LOC101930370, miR-1471 and SHH. Edu, wound-healing and transwell assays were used to verify the contribution of miR-1471 and LOC101930370 on MCF-7 cells proliferation and metastasis. Gain and loss of function studies were performed to evaluate the relevance of Hedgehog pathway with LOC101930370/miR-1471 regulating axis in MCF-7 cells. RESULTS: The expression of miR-1471 was markedly downregulated in BC. Inhibition of miR-1471 by LOC101930370 was proved by luciferase assay. Knockdown of LOC101930370 suppressed BC cells progression. MiR-1471 inhibitor resulted in a more aggressive metastasis of MCF-7 cells. Moreover, SHH and Gli-1 expression were significantly suppressed by LOC101930370 knockdown, and upregulated by miR-1471 inhibitor transfection. CONCLUSIONS: Collectively, our study reveals the interaction between LOC101930370 and miR-1471 for the first time. LOC101930370 positively regulates the expression of SHH by sponging miR-1471, which sheds new light on lncRNA-directed diagnostics and therapeutics in BC.

Lack of CUL4B leads to increased abundance of GFAP-positive cells that is mediated by PTGDS in mouse brain.

Astrocytes are the most abundant cell type in the mammalian brain and are important for the functions of the central nervous system. Glial fibrillary acidic protein (GFAP) is regarded as a hallmark of mature astrocytes, though some GFPA-positive cells may act as neural stem cells. Missense heterozygous mutations in GFAP cause Alexander disease that manifests leukodystrophy and intellectual disability. Here, we show that CUL4B, a scaffold protein that assembles E3 ubiquitin ligase, represses the expression of GFAP in neural progenitor cells (NPCs) during brain development. Lack of Cul4b in NPCs in cultures led to increased generation of astrocytes, marked by GFAP and S100ß. The GFAP+ cells were also found to be more abundant in the brains of nervous system-specific Cul4b knockout mice in vivo. Moreover, we demonstrated that the increased generation of GFAP+ cells from Cul4b-null NPCs was mediated by an upregulation of prostaglandin D2 synthase PTGDS. We showed that the increased GFAP expression can be attenuated by pharmacological inhibition of the PTGDS enzymatic activity or by shRNA-mediated knockdown of Ptgds. Importantly, exogenously added PTGDS could promote the generation of GFAP+ cells from wild-type NPCs. We further observed that Ptgds is targeted and repressed by the CUL4B/PRC2 complex. Together, our results demonstrate CUL4B as a negative regulator of GFAP expression during neural development.

MR Imaging Measures of Intracranial Atherosclerosis in a Population-based Study.

Purpose To implement a magnetic resonance (MR) imaging protocol to measure intracranial atherosclerotic disease (ICAD) in a population-based multicenter study and report examination and reader reliability of these MR imaging measurements and descriptive statistics representative of the general population. Materials and Methods This prospective study was approved by the institutional review boards and compliant with HIPAA. Atherosclerosis Risk in Communities (ARIC) study participants (n = 1980) underwent brain MR imaging from 2011 to 2013 at four ARIC sites. Imaging included three-dimensional black-blood MR imaging and time-of-flight MR angiography. One hundred two participants returned for repeat MR imaging to estimate examination and reader variability. Plaque presence according to vessel segment was recorded. Quantitative measurements included lumen size and degree of stenosis, wall and/or plaque thickness, area and volume, and normalized wall index for each vessel segment. Reliability was assessed with percentage agreement, κ statistics, and intraclass correlation coefficients. Results Of the 1980 participants, 1755 (mean age, 77.6 years; 1026 women [59%]; 1234 white [70%]) completed examinations with adequate to excellent image quality. The weighted ICAD prevalence was 34.4% (637 of 1755 participants) and was higher in men than women (38.5% [302 of 729 participants] vs 31.7% [335 of 1026 participants], respectively; P = .012) and in African Americans compared with whites (41.1% [215 of 518 participants] vs 32.4% [422 of 1234 participants], respectively; P = .002). Percentage agreement of plaque identification per participant was 87.0% (interreader estimate), 89.2% (intrareader estimate), and 89.9% (examination estimate). Examination and reader reliability ranged from fair to good (κ, 0.50-0.78) for plaque presence and from good to excellent (intraclass correlation coefficient, 0.69-0.99) for quantitative vessel wall measurements. Conclusion Vessel wall MR imaging is a reliable tool for identifying and measuring ICAD and provided insight into ICAD distribution across a U.S. community-based population. (©) RSNA, 2016 Online supplemental material is available for this article.

Case report and literature review: Orally ingested toothpick perforating the lower rectum.

Introduction: Most foreign bodies (FBs) can spontaneously pass through the gastrointestinal tract. Sharp FBs are believed to be able to puncture any part of the gastrointestinal tract, causing perforation and potentially secondary damage to adjacent organs. Case description: A 44-year-old man complained of having persistent dull pain in the perianal region. He was diagnosed with a toothpick impacted into the wall of the lower rectum after accepting a digital rectal examination of the lower rectum and a pelvic computed tomography (CT). The surgeon extracted the FB using vascular forceps guided by the operator's index finger. The patient was discharged after intravenous ceftriaxone was given for 6 days. A follow-up pelvic CT performed 2 weeks after surgery revealed that the perirectal fat and muscles had already normalized. Conclusion: A systematic review of relevant literature from the past decade was performed to summarize the imaging features of an orally ingested toothpick perforating the gastrointestinal tract. The location of abdominal pain is an important clue for the diagnosis of toothpick perforation, and a CT examination is recommended as the first option for the detection of an ingested toothpick. Determining the location of the toothpick perforation and assessing the severity of local inflammation are important bases for the selection of treatment.

Effect of biochar on biochemical properties of saline soil and growth of rice.

To amend physical properties of coastal saline soil for rice production, six biochar treatments (0, 0.5, 1, 2, 4 and 6 kg biochar per m2 soil) were set up as CK, T1, T2, T3, T4 and T5, respectively and their effect on the biochemical properties of coastal saline soil and rice growth characteristics were evaluated in a barrel planting experiment. The results showed that compared with CK (with no biochar added), the soil EC of T1 and T2-T5 was reduced by 11.5 %, but increased by 8.8-62.9 %, respectively. The available potassium and organic matter contents of T1-T5 increased ranging from 3.7-10.2 % to 8.0-46.8 %, respectively. With the increase of the biochar amount, the urease activity of soil in the 0-10 cm deep soil showed an increasing trend by 194.8-744.6 % with T1-T5, compared with that of the CK treatment. The activity of alkaline phosphatase in soil increased first and then decreased, and its increment with T1-T5 was between 28.2 and 64.8 % in comparison with that of CK. With more biochar added to soil, the leaf dry weight, root dry weight, total dry matter mass, total root length, single panicle quality and weight per 100 grains showed a trend of increase first and then decrease. The highest incremental values of all measurements were obtained with T1 by 21.8 %, 23.9 %, 13.8 %, 33.9 %, 30.8 % and 11.6 % respectively, compared with those with CK. However, adding biochar in soil demonstrated insignificant effect on the weight of single panicle, panicle length, stem thickness, tillers, setting rate, soil hydrolyzable nitrogen, available phosphorus content, rice protein, amylose, and taste quality among all treatments. In summary, the application of 0.5 kg m-2 biochar can improve the biochemical properties of saline soil and therefore increase rice yield.

Review Article Imaging Evaluation for the Size of Saccular Intracranial Aneurysm.

BACKGROUND: In addition to evaluate the morphologic characteristics of intracranial aneurysms, the dimension of the aneurysm is an important parameter for selecting treatment strategies, determining follow-up period, and predicting the risk of rupture. High-resolution vessel wall imaging has an increasingly dominant role in measuring aneurysm size and assessing the risk of rupture accurately. The size of saccular intracranial aneurysm may play an important role as a predictor of the rupture risk. With the rapid improvement in radiological techniques, different noninvasive imaging methods have respective characteristics in saccular intracranial aneurysms (sIA) measurement and morphologic description. Although most studies believe that the larger the aneurysm, the higher the risk of rupture, there is still a synergistic effect of multiple factors (such as location, morphology, history of aneurysmal subarachnoid hemorrhage, and even patient factors) to explain the rupture of small aneurysms. METHODS: A literature search was performed of intracranial aneurysm size and risk of rupture. RESULTS: The specificity and sensitivity of different imaging methods for evaluating intracranial aneurysms varied based on sizes. Rupture risk of aneurysms was associated with multiple factors. A comprehensive assessment that considered aneurysm size in conjunction with other relevant factors would be helpful in guiding options of management. CONCLUSIONS: Accurate measurement of the dimension of sIA is an important basis in the selection of appropriate treatment including intravascular intervention or surgical clipping, as well as for determining the follow-up cycles for conservative or postoperative treatment. A uniform definition of sIA size is recommended to facilitate the integration of similar studies and to accomplish rapid and effective screening of cases in sIA treatment.

Case Report: Dislocation of lateral menisci secondary to congenital lateral tibiofemoral cartilage thickening in both knees.

A 24-year-old male patient complained of mild knee pain after jogging. The subsequent knee MRI demonstrated bilateral lateral thickened tibiofemoral cartilages, evidenced by deformities of the bilateral subchondral bone beneath the lateral femoral condyle cartilage. The corresponding dislocations of almost all the left lateral meniscus and part of the right lateral meniscus to the center of the joint were detected. After excluding diagnoses of congenital ring-shaped meniscus, bucket handle tear of the C-shaped lateral meniscus, and central tear of the discoid meniscus, the displacement of all or part of the lateral meniscus into the intercondylar notch was considered a consequence of congenital thickening of the lateral superior and inferior cartilage. This case may report a new variant of knee joint pathology.

NEXMIF variants are associated with epilepsy with or without intellectual disability.

OBJECTIVES: Variants in NEXMIF had been reported associated with intellectual disability (ID) without epilepsy or developmental epileptic encephalopathy (DEE). It is unkown whether NEXMIF variants are associated with epilepsy without ID. This study aims to explore the phenotypic spectrum of NEXMIF and the genotype-phenotype correlations. MATERIALS AND METHODS: Trio-based whole-exome sequencing was performed in patients with epilepsy. Previously reported NEXMIF variants were systematically reviewed to analyze the genotype-phenotype correlations. RESULTS: Six variants were identified in seven unrelated cases with epilepsy, including two de novo null variants and four hemizygous missense variants. The two de novo variants were absent in all populations of gnomAD and four hemizygous missense variants were absent in male controls of gnomAD. The two patients with de novo null variants exhibited severe developmental epileptic encephalopathy. While, the patients with hemizygous missense variants had mild focal epilepsy with favorable outcome. Analysis of previously reported cases revealed that males with missense variants presented significantly higher percentage of normal intellectual development and later onset age of seizure than those with null variants, indicating a genotype-phenotype correlation. CONCLUSION: This study suggested that NEXMIF variants were potentially associated with pure epilepsy with or without intellectual disability. The spectrum of epileptic phenotypes ranged from the mild epilepsy to severe developmental epileptic encephalopathy, where the epileptic phenotypes variability are potentially associated with patients' gender and variant type.

Whole-brain in vivo base editing reverses behavioral changes in Mef2c-mutant mice.

Whole-brain genome editing to correct single-base mutations and reduce or reverse behavioral changes in animal models of autism spectrum disorder (ASD) has not yet been achieved. We developed an apolipoprotein B messenger RNA-editing enzyme, catalytic polypeptide-embedded cytosine base editor (AeCBE) system for converting C·G to T·A base pairs. We demonstrate its effectiveness by targeting AeCBE to an ASD-associated mutation of the MEF2C gene (c.104T>C, p.L35P) in vivo in mice. We first constructed Mef2cL35P heterozygous mice. Male heterozygous mice exhibited hyperactivity, repetitive behavior and social abnormalities. We then programmed AeCBE to edit the mutated C·G base pairs of Mef2c in the mouse brain through the intravenous injection of blood-brain barrier-crossing adeno-associated virus. This treatment successfully restored Mef2c protein levels in several brain regions and reversed the behavioral abnormalities in Mef2c-mutant mice. Our work presents an in vivo base-editing paradigm that could potentially correct single-base genetic mutations in the brain.

Morphological and molecular evidence reveals a new species of Anteaeolidiella (Mollusca, Nudibranchia, Aeolidiidae) from the Yellow Sea, China.

During an investigation of nudibranch gastropods in the Yellow Sea, several specimens were collected from the intertidal zone of Qingdao, Shandong Province, China. Morphological observation of their external and internal anatomy revealed that they represent an undescribed species belonging to the genus Anteaeolidiella M. C. Miller, 2001. This new species, Anteaeolidiella decorus sp. nov., can be differentiated from other congeners by both external morphology and internal anatomy. Phylogenetic analyses of two mitochondrial (COI, 16S rRNA) and a nuclear (H3) gene using Bayesian inference, maximum likelihood analysis, and species delimitation analyses also support the separation of Anteaeolidiella decorus sp. nov. from its congeners.

Dual-energy computed tomography in reducing the effective radiation dose of computed tomography urography in patients with urinary calculi.

Background: To evaluate the diagnostic performance of split-bolus single-phase dual-energy computed tomography (DECT) with virtual non-contrast computed tomography (VNCT) compared to three-phase computed tomography (CT) urography in patients with urinary calculi, and to examine the performance of split-bolus single-phase DECT when reducing the effective dose. Methods: A total of 48 patients with abdominal pain or hematuria suggestive of unilateral urinary calculi were enrolled and randomly divided into the experimental and control groups, with 24 cases in each group. Patients in the experimental group underwent split-bolus single-phase DECT to obtain a mixed nephrographic excretory phase. Patients in the control group accepted a single-bolus three-phase CT urography scan (non-contrast, nephrographic phase, and excretory phase). The CT values and the contrast-to-noise ratio (CNR) of 7 segments of the urinary tract were measured and compared between the two groups by using the Mann-Whitney U test. The dose-length product (DLP) and effective dose of each patient were compared between the two groups using an independent t-test. Results: Among all 48 patients, 35 calculi were detected in the experimental group (n=24), and 47 calculi were detected in the control group (n=24). There was no significant difference between the two groups in both CT value measurements and the CNR. The mean DLP and mean effective dose of the experimental group were significantly lower than those of the control group, and the effective dose in the experimental group was decreased by 40% compared with the control group. Conclusions: The application of DECT combined with split-bolus nephrographic excretory phase CT urography can reveal the urinary calculi covered by a contrast medium and also reduce the effective dose exposure to patients.

TadA orthologs enable both cytosine and adenine editing of base editors.

Cytidine and adenosine deaminases are required for cytosine and adenine editing of base editors respectively, and no single deaminase could enable concurrent and comparable cytosine and adenine editing. Additionally, distinct properties of cytidine and adenosine deaminases lead to various types of off-target effects, including Cas9-indendepent DNA off-target effects for cytosine base editors (CBEs) and RNA off-target effects particularly severe for adenine base editors (ABEs). Here we demonstrate that 25 TadA orthologs could be engineered to generate functional ABEs, CBEs or ACBEs via single or double mutations, which display minimized Cas9-independent DNA off-target effects and genotoxicity, with orthologs B5ZCW4, Q57LE3, E8WVH3, Q13XZ4 and B3PCY2 as promising candidates for further engineering. Furthermore, RNA off-target effects of TadA ortholog-derived base editors could be further reduced or even eliminated by additional single mutation. Taken together, our work expands the base editing toolkits, and also provides important clues for the potential evolutionary process of deaminases.

TadA reprogramming to generate potent miniature base editors with high precision.

Although miniature CRISPR-Cas12f systems were recently developed, the editing efficacy and targeting range of derived miniature cytosine and adenine base editors (miniCBEs and miniABEs) have not been comprehensively addressed. Moreover, functional miniCBEs have not yet be established. Here we generate various Cas12f-derived miniCBEs and miniABEs with improved editing activities and diversified targeting scopes. We reveal that miniCBEs generated with traditional cytidine deaminases exhibit wide editing windows and high off-targeting effects. To improve the editing signatures of classical CBEs and derived miniCBEs, we engineer TadA deaminase with mutagenesis screening to generate potent miniCBEs with high precision and minimized off-target effects. We show that newly designed miniCBEs and miniABEs are able to correct pathogenic mutations in cell lines and introduce genetic mutations efficiently via adeno-associated virus delivery in the brain in vivo. Together, this study provides alternative strategies for CBE development, expands the toolkits of miniCBEs and miniABEs and offers promising therapeutic tools for clinical applications.

Aloe-Emodin Derivative, an Anthraquinone Compound, Attenuates Pyroptosis by Targeting NLRP3 Inflammasome in Diabetic Cardiomyopathy.

Diabetic cardiomyopathy (DCM) is widely recognized as a major contributing factor to the development of heart failure in patients with diabetes. Previous studies have demonstrated the potential benefits of traditional herbal medicine for alleviating the symptoms of cardiomyopathy. We have chemically designed and synthesized a novel compound called aloe-emodin derivative (AED), which belongs to the aloe-emodin (AE) family of compounds. AED was formed by covalent binding of monomethyl succinate to the anthraquinone mother nucleus of AE using chemical synthesis techniques. The purpose of this study was to investigate the effects and mechanisms of AED in treating DCM. We induced type 2 diabetes in Sprague-Dawley (SD) rats by administering a high-fat diet and streptozotocin (STZ) injections. The rats were randomly divided into six groups: control, DCM, AED low concentration (50 mg/kg/day), AED high concentration (100 mg/kg/day), AE (100 mg/kg/day), and positive control (glyburide, 2 mg/kg/day) groups. There were eight rats in each group. The rats that attained fasting blood glucose of ˃16.7 mmol/L were considered successful models. We observed significant improvements in cardiac function in the DCM rats with both AED and AE following four weeks of intragastric treatment. However, AED had a more pronounced therapeutic effect on DCM compared to AE. AED exhibited an inhibitory effect on the inflammatory response in the hearts of DCM rats and high-glucose-treated H9C2 cells by suppressing the pyroptosis pathway mediated by the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain 3 (NLRP3) inflammasome. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of differentially expressed genes showed a significant enrichment in the NOD-like receptor signaling pathway compared to the high-glucose group. Furthermore, overexpression of NLRP3 effectively reversed the anti-pyroptosis effects of AED in high-glucose-treated H9C2 cells. This study is the first to demonstrate that AED possesses the ability to inhibit myocardial pyroptosis in DCM. Targeting the pyroptosis pathway mediated by the NLRP3 inflammasome could provide a promising therapeutic strategy to enhance our understanding and treatment of DCM.