Multitask deep learning for prediction of microvascular invasion and recurrence-free survival in hepatocellular carcinoma based on MRI images.

BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.

Double-modified oncolytic adenovirus armed with a recombinant interferon-like gene enhanced abscopal effects against malignant glioma.

Background: The development of new therapies for malignant gliomas has been stagnant for decades. Through the promising outcomes in clinical trials of oncolytic virotherapy, there is now a glimmer of hope in addressing this situation. To further enhance the antitumor immune response of oncolytic viruses, we have equipped a modified oncolytic adenovirus (oAds) with a recombinant interferon-like gene (YSCH-01) and conducted a comprehensive evaluation of the safety and efficacy of this modification compared to existing treatments. Methods: To assess the safety of YSCH-01, we administered the oAds intracranially to Syrian hamsters, which are susceptible to adenovirus. The efficacy of YSCH-01 in targeting glioma was evaluated through in vitro and in vivo experiments utilizing various human glioma cell lines. Furthermore, we employed a patient-derived xenograft model of recurrent glioblastoma to test the effectiveness of YSCH-01 against temozolomide. Results: By modifying the E1A and adding survivin promoter, the oAds have demonstrated remarkable safety and an impressive ability to selectively target tumor cells. In animal models, YSCH-01 exhibited potent therapeutic efficacy, particularly in terms of its distant effects. Additionally, YSCH-01 remains effective in inhibiting the recurrent GBM patient-derived xenograft model. Conclusions: Our initial findings confirm that a double-modified oncolytic adenovirus armed with a recombinant interferon-like gene is both safe and effective in the treatment of malignant glioma. Furthermore, when utilized in combination with a targeted therapy gene strategy, these oAds exhibit a more profound effect in tumor therapy and an enhanced ability to inhibit tumor growth at remote sites.

Region-Controlled Framework Interface Mediated Anion Exchange Chemical Transformation to Designed Metal Phosphosulfide Heteronanostructures.

Postsynthetic chemical transformation provides a powerful platform for creating heteronanostructures (HNs) with well-defined materials and interfaces that generate synergy or enhancement. However, it remains a synthetic bottleneck for the precise construction of HNs with increased degrees of complexity and more elaborate functions in a predictable manner. Herein, we define a general transformative protocol for metal phosphosulfide HNs based on tunable hexagonal Cu1.81S frameworks with corner-, edge- and face-controlled growth of Co2P domains. The region-controlled Cu1.81S-Co2P framework interfaces can serve as "kinetic barriers" in mediating the direction and rate between P and S anion exchange reactions, thus leading to a family of morphology and phase designed Cu3P1-xSx-Co2P HNs with hollow (branched, dotted and crown), porous and core-shell architectures. This study reveals the internal transformation mechanism between metal sulfide and phosphide nanocrystals, and opens up a new way for the rational synthesis of metastable HNs that are otherwise inaccessible.

Mn-Incorporation-Induced Phase Transition in Bottom-Up Synthesized Colloidal Sub-1-nm Ni(OH)2 Nanosheets for Enhanced Oxygen Evolution Catalysis.

Sub-1-nm structures are attractive for diverse applications owing to their unique properties compared to those of conventional nanomaterials. Transition-metal hydroxides are promising catalysts for oxygen evolution reaction (OER), yet there remains difficulty in directly fabricating these materials within the sub-1-nm regime, and the realization of their composition and phase tuning is even more challenging. Here we define a binary-soft-template-mediated colloidal synthesis of phase-selective Ni(OH)2 ultrathin nanosheets (UNSs) with 0.9 nm thickness induced by Mn incorporation. The synergistic interplay between binary components of the soft template is crucial to their formation. The unsaturated coordination environment and favorable electronic structures of these UNSs, together with in situ phase transition and active site evolution confined by the ultrathin framework, enable efficient and robust OER electrocatalysis. They exhibit a low overpotential of 309 mV at 100 mA cm-2 as well as remarkable long-term stability, representing one of the most high-performance noble-metal-free catalysts.

Phase Transformation from Amorphous RuSx to Ru-RuS2 Hybrid Nanostructure for Efficient Water Splitting in Alkaline Media.

Ruthenium (Ru)-based materials, as a class of efficient hydrogen evolution reaction (HER) catalysts, play an important role in hydrogen generation by electrolysis of water in an alkaline solution for clean hydrogen energy. Hybrid nanostructure (HN) materials, which include two or more components with distinct functionality, show better performance than their individual materials, since HN materials can potentially integrate their advantages and overcome the weaknesses. However, it remains a challenge to construct Ru-based HN materials with desired crystal phases for enhanced HER performances. Herein, a series of new Ru-based HN materials (t-Ru-RuS2, S-Ru-RuS2, and T-Ru-RuS2) through phase engineering of nanomaterials (PEN) and chemical transformation are designed to achieve highly efficient HER properties. Owing to the plentiful formation of heterojunctions and amorphous/crystalline interfaces, the t-Ru-RuS2 HN delivers the most outstanding overpotential of 16 mV and owns a small Tafel slope of 29 mV dec-1 at a current density of 10 mA cm-2, which exceeds commercial Pt/C catalysts (34 mV, 38 mV dec-1). This work shows a new insight for HN and provides alternative opportunities in designing advanced electrocatalysts with low cost for HER in the hydrogen economy.

Discovery of a Novel Bloom's Syndrome Protein (BLM) Inhibitor Suppressing Growth and Metastasis of Prostate Cancer.

Prostate cancer (PCa) is a common cancer and a major cause of cancer-related death worldwide in men, necessitating novel targets for cancer therapy. High expression of Bloom's syndrome protein (BLM) helicase is associated with the occurrence and development of PCa. Therefore, the identification and development of new BLM inhibitors may be a new direction for the treatment of PCa. Here, we identified a novel inhibitor by molecular docking and put it to systematic evaluation via various experiments, AO/854, which acted as a competitive inhibitor that blocked the BLM-DNA interaction. Cellular evaluation indicated that AO/854-suppressed tumor growth and metastasis in PC3 cells by enhancing DNA damage, phosphorylating Chk1/Chk2, and altering the p53 signaling pathway. Collectively, the study highlights the potential of BLM as a therapeutic target in PCa and reveals a distinct mechanism by which AO/854 competitively inhibits the function of BLM.

ML216-Induced BLM Helicase Inhibition Sensitizes PCa Cells to the DNA-Crosslinking Agent Cisplatin.

Using standard DNA-damaging medicines with DNA repair inhibitors is a promising anticancer tool to achieve better therapeutic responses and reduce therapy-related side effects. Cell viability assay, neutral comet assay, western blotting (WB), and cell cycle and apoptosis analysis were used to determine the synergistic effect and mechanism of ML216, a Bloom syndrome protein (BLM) helicase inhibitor, and cisplatin (CDDP), a DNA-crosslinking agent, in PCa cells. Based on the online database research, our findings revealed that BLM was substantially expressed in PCa, which is associated with a bad prognosis for PCa patients. The combination of ML216 and CDDP improved the antiproliferative properties of three PCa cell lines. As indicated by the increased production of γH2AX and caspase-3 cleavage, ML216 significantly reduced the DNA damage-induced high expression of BLM, making PC3 more susceptible to apoptosis and DNA damage caused by CDDP. Furthermore, the combination of ML216 and CDDP increased p-Chk1 and p-Chk2 expression. The DNA damage may have triggered the ATR-Chk1 and ATM-Chk2 pathways simultaneously. Our results demonstrated that ML216 and CDDP combination therapy exhibited synergistic effects, and combination chemotherapy could be a novel anticancer tactic.

Selective-Epitaxial Hybrid of Tripartite Semiconducting Sulfides for Enhanced Solar-to-Hydrogen Conversion.

The design and synthesis of advanced semiconductors is crucial for the full utilization of solar energy. Herein, colloidal selective-epitaxial hybrid of tripartite semiconducting sulfides CuInS2 Cd(In)SMoS2 heteronanostructures (HNs) via lateral- and vertical-epitaxial growths, followed by cation exchange reactions, are reported. The lateral-epitaxial CuInS2 and Cd(In)S enable effective visible to near-infrared (NIR) solar spectrum absorption, and the vertical-epitaxial ultrathin MoS2 offer sufficient edge sulfur sites for the hydrogen evolution reaction (HER). Furthermore, the integrated structures exhibit unique epitaxial-staggered type II band alignments for continuous charge separation. They achieve the H2 evolution rate up to 8 mmol h-1 g-1 , which is ≈35 times higher than bare CdS and show no deactivation after long-term cycling, representing one of the most efficient and robust noble-metal-free photocatalysts. This design principle and transformation protocol open a new way for creating all-in-one multifunctional catalysts in a predictable manner.

Double Confinement Hydrogel Network Enables Continuously Regenerative Solar-to-Hydrogen Conversion.

Soft matter catalyst system allowing controllable manipulation of the organized nanostructure and surface property holds the potential for renewable energy. Here we demonstrate the construction of a continuously regenerative hydrogel photocatalyst that confines the metal-thiolate coordination induced nanocavity into robust micro-sized spongy network for water splitting. Thanks to low vaporization enthalpy and fast proton mobility of water molecules confining in nanocavities, the composite delivers outstanding photocatalytic H2 production (TOF of 4568 H2 h-1 ), nearly 4.5 times higher than that on the catalyst without confinements. Incorporating with conductive polymers, the TOF is substantially improved to 7819 H2 h-1 . Impressively, continuous regeneration is for the first time achieved with H2 production retention improved from 24 % to 72 % by regulating optically-active catalyst surfaces. This optical regeneration method provides new avenues for sustainable solar energy conversion.

Electroacupuncture altered expression of microRNAs in Stat5 knockout obese mice.

BACKGROUND: Increasing evidence shows that miRNAs contribute to the establishment and development of obesity by affecting many biological and pathological processes, such as adipocyte differentiation, hepatic lipid metabolism, insulin resistance, and neurological regulation of obesity. As a clinical intervention approach, acupuncture has been shown to be effective in the treatment of obesity and other metabolic diseases. Our previous whole genome study in central nervous system (CNS)-specific Stat5 knockout (NKO) obese mice found that electroacupuncture (EA) could reduce body weight and promote white browning. OBJECTIVE: To clarify the effect of EA on miRNAs and understand how it regulates gene expression. METHODS: Twelve-week-old male Stat5NKO mice with body weight 20% greater than that of Stat5fl/fl (control) mice were divided into a Stat5NKO (model) group and EA-treated Stat5NKO + EA group. A cohort of Stat5fl/fl mice of the same age were included as the control group. EA was administered under isoflurane anesthesia at unilateral ST36 and ST44 daily (left and right sides were treated every other day), 6 times per week for a total of 4 weeks. The miRNA profile was generated and miRNA regulatory networks were analyzed in the Stat5 nestin-cre mice before and after EA treatment. Autophagy-related proteins in adipocytes were detected after over-expression of miR27a. RESULTS: EA altered abnormal miRNA expression, including miRNA27a expression, and reduced the autophagy-related proteins ATG5 and ATG12. CONCLUSION: We found that EA could regulate miRNA27a-mediated autophagy-related proteins and promote white fat browning, which may contribute to weight loss. To our knowledge, this is the first report of miRNAs potentially driving the effect of EA on white fat browning through the autophagy process.

STAT3 but Not STAT5 Contributes to the Protective Effect of Electroacupuncture Against Myocardial Ischemia/Reperfusion Injury in Mice.

Electroacupuncture (EA) can help reduce infarct size and injury resulting from myocardial ischemia/reperfusion (I/R); however, the underlying molecular mechanism remains unknown. We previously reported that STAT5 plays a critical role in the cardioprotective effect of remote ischemic preconditioning (RIPC). Here, we assessed the effects of electroacupuncture pretreatment (EAP) on myocardial I/R injury in the presence and/or absence of Stat5 in mice and investigated whether EAP exerts its cardioprotective effects in a STAT5-dependent manner. Adult Stat5 fl/fl and Stat5-cKO mice were exposed to EAP at Neiguan (PC6) for 7 days before the induction of I/R injury by left anterior descending (LAD) coronary artery ligation. The myocardial infarct size (IS), area at risk, and apoptotic rate of cardiomyocytes were detected. RT-qPCR and western blotting were used to measure gene and protein expression, respectively, in homogenized heart tissues. RNA-seq was used to identify candidate genes and pathways. Our results showed that EAP decreased IS and the rate of cardiomyocyte apoptosis. We further found that STAT5 was activated by EAP in Stat5 fl/fl mice but not in Stat5-cKO mice, whereas the opposite was observed for STAT3. Following EAP, the levels of the antiapoptotic proteins Bcl-xL, Bcl-2, and p-AKT were increased in the presence of Stat5, while that of interleukin 10 (IL-10) was increased in both Stat5 fl/fl and Stat5-cKO. The gene expression profile in heart tissues was different between Stat5 fl/fl and the Stat5-cKO mice with EAP. Importantly, the top 30 DEGs under EAP in the Stat5-cKO mice were enriched in the IL-6/STAT3 signaling pathway. Our results revealed for the first time that the protective effect of EAP following myocardial I/R injury was attributable to, but not dependent on, STAT5. Additionally, we found that EAP could activate STAT3 signaling in the absence of the Stat5 gene, and could also activate antiapoptotic, survival, and anti-inflammatory signaling pathways.

Soft chemistry of metastable metal chalcogenide nanomaterials.

The metastable nature of metal chalcogenide nanomaterials (MCNs) provides us with fresh perspectives and plentiful grounds in the search of new strategies for physicochemical tuning. In the past decade, numerous efforts have been devoted to synthesizing and modifying diverse emerging MCNs based on their "soft chemistry", that is, gently regulating the composition, structure, phase, and interface while not entirely disrupting the original features. This tutorial review focuses on design principles based on the metastability of MCNs, such as ion mobility and vacancy, thermal and structural instability, chemical reactivity, and phase transition, together with corresponding soft chemical approaches, including ion-exchange, catalytic growth, segregation or coupling, template grafting or transformation, and crystal-phase engineering, and summarizes recent advances in their preparation and modification. Finally, prospects for the future development of soft chemistry-directed synthetic guidelines and metastable metal chalcogenide-derived nanomaterials are proposed and highlighted.

Bloom helicase explicitly unwinds 3'-tailed G4DNA structure in prostate cancer cells.

G-quadruplex DNA (G4DNA) structure, which widely exists in the chromosomal telomeric regions and oncogenic promoter regions, plays a pivotal role in extending telomeric DNA with the help of telomerase in human cells. Bloom (BLM) helicase, a crucial member of the family of genome surveillance proteins, plays an essential role in DNA metabolic and repair pathways, including DNA replication, repair, transcription, recombination during chromosome segregation, and assuring telomere stability. The unwinding of G4DNA requires the participation of DNA helicase, which is crucial for maintaining chromosomal stability in cancer cells. Using fluorescence polarization and the electrophoretic mobility shift assay (EMSA), this study aimed to investigate the DNA-binding and unwinding properties of BLM helicase, cloned and purified from prostate cancer cells, toward G4DNA. The results revealed that BLM helicase derived from prostate cancer cells could bind and unwind G4DNA. The molecular affinity of bond between G4DNA and the helicase was dependent on the single-stranded DNA (ssDNA) terminals in G4DNA; the helicase was effectively bound to the G4DNA when the helicase monomer sufficiently covered approximately 10 nucleotides at the 3' or 5' ssDNA tail of G4DNA. For the unwinding of G4DNA, there was an apparent requirement of a 3' ssDNA tail and ATP; a G4DNA with only a 3' ssDNA tail was identified to be the most suitable substrate to be unwound by BLM helicase and required 3' ssDNA tails of at least 10 nt in length for efficient unwinding. Besides, BLM helicase was loosely bound and partly unwound the blunt-ended G4DNA. Although further mechanistic studies are warranted, the experimental results presented in this study are beneficial to further our understanding of the functional implication of BLM helicase in prostate cancer cells.

Macromolecular aging: ATP hydrolysis-driven functional and structural changes in Escherichia coli RecQ helicase.

Aging has been considered a phenomenon that can be only applied to cells or organisms. Here, we show that RecQ helicase from E. coli displays an aging phenomenon: this macromolecular motor loses its structure and function after hydrolyzing a certain number of ATP molecules. The aging process was only triggered by repeated catalytic cycles. These observations lead to a new concept: macromolecule aging.

Comparative study of gene expression profiles rooted in acute myocardial infarction and ischemic/reperfusion rat models.

Mining data in depth of genome-wide sequencing data generated from pathological target tissues under disease conditions is necessary for seeking novel functional genes, and developing more biological study directions for the field. Based on our previous published RNA-seq data generated from acute myocardial ischemia and ischemia-reperfusion in rat heart, we re-analysed these two data sets using bioinformatics tools. All these raw fastq files were extracted from Illumina BCL using the Illumina CASAVA program. Four groups were obtained: UD (genes up-regulated in MI but down-regulated in I/R injury), DU (genes down-regulated in MI but up-regulated in I/R injury), UU (genes both up-regulated in MI and I/R injury), and DD (genes both down-regulated in MI and I/R injury) groups. The results showed that 304 common genes in the UD group, 236 common genes in the DU group, 318 common genes in the UU group, and 159 common genes in the DD group detected by comparing data sets of the MI and the I/R injury. We then listed the top 30 DEGs for each group, and carried out GO and KEGG analyses for enrichment and pathway studies for those top expressed genes. Further analysis of INTERPRO Protein Domains and Features enriched by DEGs showed that 20% of the Domains enriched were related to c-type lectin, and 17% of these domains are related to neurotransmitter-gated ion-channel. 15% of PFAM Protein Domains were about Neurotransmitter-gated ion-channel. There were only 8 SMART Protein Domains DEGs enriched and 37.5% of which were concerned about leucine-rich. Collagen involvement in Reactome Pathways accounted for 22.7%. We found that only a few DEGs in these two disease conditions have been reported in the literatures, suggesting that there are many new genes would be considered in the future studies. These analyses would provide some information for seeking more novel targets of these two clinic diseases, acute myocardial ischemia and myocardial ischemia/reperfusion.

The Antithrombotic Effects of Low Molecular Weight Fragment from Enzymatically Modified of Laminaria Japonica Polysaccharide.

BACKGROUND Laminaria japonica polysaccharide (LJP), a fucose enriched sulfated polysaccharide has been demonstrated to have excellent anticoagulant and antithrombotic activities. However, the antithrombotic effect of low molecular weight polysaccharide from enzymatically modified of LJP (LMWEP) remains unknown. MATERIAL AND METHODS LMWEP was prepared by fucoidanase enzymatic hydrolysis, and the antithrombotic and anticoagulant activities, and the underlying mechanism were investigated thoroughly. Rats were randomly divided into 6 groups (8 rats in each group): the blank control group, the blank control group treated with LMWEP (20 mg/kg), the model group, the model group treated with heparin (2 mg/kg), the model group treated with LJP (20 mg/kg), and the model group treated with LMWEP (20 mg/kg). After 7 days of intravenous administration, blood was collected for biochemical parameters examinations. RESULTS LMWEP increased the activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), 6-keto prostaglandin F1alpha (6-Keto-PGF1alpha), and endothelial nitric oxide synthase (eNOS). In addition, LMWEP decreased fibrinogen (FIB), endothelin-1 (ET-1), thromboxane B2 (TXB2), erythrocyte sedimentation rate (ESR), and hematocrit (HCT). CONCLUSIONS LMWEP, an enzymatically modified fragment with a molecular weight of 25.8 kDa, is a potential antithrombotic candidate for treatment of thrombosis related diseases.

Electroacupuncture Reduces Body Weight by Regulating Fat Browning-Related Proteins of Adipose Tissue in HFD-Induced Obese Mice.

Objective: This study investigated the influence of electroacupuncture (EA) and its potential underlying mechanisms on adipose tissue in obese mice. Methods: Three-week-old male C56BL/6 mice were randomly divided to feed or not to feed high-fat diet (HFD), named HFD group and chow diet (CD) group, respectively. After 12 weeks, CD and HFD mice were randomly divided into two groups, respectively, to receive or not receive EA for 4 weeks. Body weight (BW) was monitored. Intraperitoneal glucose tolerance test and metabolic chamber recordings were performed. Blood samples and adipose tissue were collected for the analysis of leptin, triglyceride levels, and fat browning-related proteins. Results: EA significantly reduced food intake, BW, and white adipose tissue (WAT)/BW ratio; decreased the adipocyte size and serum concentrations of triglyceride (TG) and cholesterol; and increased oxygen consumption in HFD mice. Compared with the CD mice, the HFD mice had elevated fasting serum glucose level and impaired glucose tolerance; however, these parameters were decreased by EA treatment. Meanwhile, EA promoted the protein and mRNA expressions of UCP1, PRDM16, and PGC-1α in adipose tissue, and activated sympathetic nerves via p-TH, A2AR, and ß3AR in white adipose tissue. Conclusions: EA reduced food intake, BW, TG, and cholesterol, and improved glucose tolerance in HFD mice. This ameliorative effect of EA on obesity-related symptoms associated with its promoted adipose tissue plasticity via activating sympathetic nerves.

Four 14(13 → 12)-Abeolanostane Triterpenoids with 6/6/5/6-Fused Ring System from the Roots of Kadsura coccinea.

Four new rearranged 6/6/5/6-fused lanostane-type triterpenoids, kadcoccitanes A-D (1-4), were isolated from the roots of Kadsura coccinea, and their structures were mainly elucidated by comprehensive analysis of their spectroscopic data. Additionally, the structure of 1 was ambiguously verified by single-crystal X-ray diffraction, while the structure of 2, which features a novel 8,16-epoxy motif, was validated by quantum chemical calculation of NMR parameters and ECD spectrum. Moreover, 1 and 4 were found to exhibited anticoagulant activity, while 3 and 4 were found to possess anti-platelet aggregation activity.

(+)- and (-)-Alternarilactone A: Enantiomers with a Diepoxy-Cage-like Scaffold from an Endophytic Alternaria sp.

The enantiomers (+)- and (-)-alternarilactone A (1), the first examples of dibenzo-α-pyrones bearing a diepoxy-cage-like moiety, were isolated from the endophytic fungus Alternaria sp. hh930. The deficiency in 1H-1H COSY and HMBC correlations caused by the highly oxidized caged system of 1 and the deceptive and ambiguous signals such as "W" couplings in NMR data increased the risk of structure misassignment of 1. By performing a quantum chemical calculation of the NMR chemical shifts together with a DP4+ probability analysis and single-crystal X-ray crystallographic experiment, their structures were unambiguously determined, and their absolute configurations were determined by ECD calculations.

miR-494-3p reduces insulin sensitivity in diabetic cardiomyocytes by down-regulation of insulin receptor substrate 1 / 生理学报

More and more evidence suggests that microRNA is widely involved in the regulation of cardiovascular function. Our preliminary experiment showed that miR-494-3p was increased in heart of diabetic rats, and miR-494-3p was reported to be related to metabolism such as obesity and exercise. Therefore, this study was aimed to explore the role of miR-494-3p in diabetic myocardial insulin sensitivity and the related mechanism. The diabetic rat model was induced by high fat diet (45 kcal% fat, 12 weeks) combined with streptozotocin (STZ, 30 mg/kg), and cardiac tissue RNA was extracted for qPCR. The results showed that the level of miR-494-3p was significantly up-regulated in the myocardium of diabetic rats compared with the control (P < 0.05). The level of miR-494-3p in H9c2 cells cultured in high glucose and high fat medium (HGHF) was significantly increased (P < 0.01) with the increase of sodium palmitate concentration, whereas down-regulation of miR-494-3p in HGHF treated cells led to an increase in insulin-stimulated glucose uptake (P < 0.01) and the ratio of p-Akt/Akt (P < 0.05). Over-expression of miR-494-3p in H9c2 cell line significantly inhibited insulin-stimulated glucose uptake and phosphorylation of Akt (P < 0.01). Bioinformatics combined with Western blotting experiments confirmed insulin receptor substrate 1 (IRS1) as a target molecule of miR-494-3p. These results suggest that miR-494-3p reduces insulin sensitivity in diabetic cardiomyocytes by down-regulating IRS1.