Restricted Boltzmann Machines Implemented by Spin-Orbit Torque Magnetic Tunnel Junctions.

Artificial intelligence has surged forward with the advent of generative models, which rely heavily on stochastic computing architectures enhanced by true random number generators with adjustable sampling probabilities. In this study, we develop spin-orbit torque magnetic tunnel junctions (SOT-MTJs), investigating their sigmoid-style switching probability as a function of the driving voltage. This feature proves to be ideally suited for stochastic computing algorithms such as the restricted Boltzmann machines (RBM) prevalent in pretraining processes. We exploit SOT-MTJs as both stochastic samplers and network nodes for RBMs, enabling the implementation of RBM-based neural networks to achieve recognition tasks for both handwritten and spoken digits. Moreover, we further harness the weights derived from the preceding image and speech training processes to facilitate cross-modal learning from speech to image generation. Our results clearly demonstrate that these SOT-MTJs are promising candidates for the development of hardware accelerators tailored for Boltzmann neural networks and other stochastic computing architectures.

LRFNet: A real-time medical image fusion method guided by detail information.

Multimodal medical image fusion (MMIF) technology plays a crucial role in medical diagnosis and treatment by integrating different images to obtain fusion images with comprehensive information. Deep learning-based fusion methods have demonstrated superior performance, but some of them still encounter challenges such as imbalanced retention of color and texture information and low fusion efficiency. To alleviate the above issues, this paper presents a real-time MMIF method, called a lightweight residual fusion network. First, a feature extraction framework with three branches is designed. Two independent branches are used to fully extract brightness and texture information. The fusion branch enables different modal information to be interactively fused at a shallow level, thereby better retaining brightness and texture information. Furthermore, a lightweight residual unit is designed to replace the conventional residual convolution in the model, thereby improving the fusion efficiency and reducing the overall model size by approximately 5 times. Finally, considering that the high-frequency image decomposed by the wavelet transform contains abundant edge and texture information, an adaptive strategy is proposed for assigning weights to the loss function based on the information content in the high-frequency image. This strategy effectively guides the model toward preserving intricate details. The experimental results on MRI and functional images demonstrate that the proposed method exhibits superior fusion performance and efficiency compared to alternative approaches. The code of LRFNet is available at https://github.com/HeDan-11/LRFNet.

Probability-Distribution-Configurable True Random Number Generators Based on Spin-Orbit Torque Magnetic Tunnel Junctions.

The incorporation of randomness into stochastic computing can provide ample opportunities for applications such as simulated annealing, non-polynomial hard problem solving, and Bayesian neuron networks. In these cases, a considerable number of random numbers with an accurate and configurable probability distribution function (PDF) are indispensable. Preferably, these random numbers are provided at the hardware level to improve speed, efficiency, and parallelism. In this paper, how spin-orbit torque magnetic tunnel junctions (SOT-MTJs) with high barriers are suitable candidates for the desired true random number generators is demonstrated. Not only do these SOT-MTJs perform excellently in speed and endurance, but their randomness can also be conveniently and precisely controlled by a writing voltage, which makes them a well-performed Bernoulli bit. By utilizing these SOT-MTJ-based Bernoulli bits, any PDF, including Gaussian, uniform, exponential, Chi-square, and even arbitrarily defined distributions can be realized. These PDF-configurable true random number generators can then promise to advance the development of stochastic computing and broaden the applications of the SOT-MTJs.

Highly Efficient Electrosynthesis of Glycine over an Atomically Dispersed Iron Catalyst.

Glycine is a nonessential amino acid that plays a vital role in various biological activities. However, the conventional synthesis of glycine requires sophisticated procedures or toxic feedstocks. Herein, we report an electrochemical pathway for glycine synthesis via the reductive coupling of oxalic acid and nitrate or nitrogen oxides over atomically dispersed Fe-N-C catalysts. A glycine selectivity of 70.7% is achieved over Fe-N-C-700 at -1.0 V versus RHE. Synergy between the FeN3C structure and pyrrolic nitrogen in Fe-N-C-700 facilitates the reduction of oxalic acid to glyoxylic acid, which is crucial for producing glyoxylic acid oxime and glycine, and the FeN3C structure could reduce the energy barrier of *HOOCCH2NH2 intermediate formation thus accelerating the glyoxylic acid oxime conversion to glycine. This new synthesis approach for value-added chemicals using simple carbon and nitrogen sources could provide sustainable routes for organonitrogen compound production.

Single-Atom palladium engineered cobalt nanocomposite for selective aerobic oxidation of sulfides to sulfoxides.

Developing efficient catalysts for the selective oxidation of sulfides to sulfoxides using molecular oxygen as the oxidant is a challenging task. Here, we report a novel catalyst comprising a single atom palladium engineered cobalt nanocomposite (denoted as PdCo@NC-800-0.01) for this reaction. The incorporation of single atom palladium effectively transforms an originally inactive cobalt nanocomposite into a highly efficient and selective catalyst for the oxidation of sulfides. This catalyst PdCo@NC-800-0.01 exhibited outstanding performance in the selective oxidation of sulfides to sulfoxides using O2 as the oxidant in the presence of isobutyraldehyde (IBA) under mild conditions, demonstrating high activity and excellent selectivity for a broad spectrum of sulfides with good tolerance toward various functional groups, including those susceptible to oxidation. Furthermore, the catalyst could be easily recovered and reused up to 10 times without any significant loss in activity and selectivity. Comprehensive characterizations and theoretical calculations revealed that the engineering of cobalt nanocomposite with single atom Pd greatly enhanced the ability to adsorb and activate IBA, leading to the generation of the key acyl radical. This radical then reacted with singlet oxygen 1O2 derived from molecular oxygen, producing reactive oxygen species peroxy radical, which ultimately promoted the catalytic performance.

Knowledge mapping of anaplastic thyroid cancer treatments: a bibliometric analysis (2000-2023).

Context: Anaplastic thyroid cancer (ATC) is a relatively rare and extensively malignant kind of thyroid carcinoma. The poor prognosis and high mortality rate of ATC can be attributed to its invasive features and undifferentiated phenotype. At present, there is a lack of efficacious therapeutic options. In light of the elevated fatality rate, it is vital to possess a comprehensive comprehension of the scientific terrain pertaining to ATC. To gather the perspectives of different researchers about the topic of ATC treatment, we did a bibliometric network analysis, which offers a comprehensive view of the scholarly literature. Methodology: A systematic search was conducted on the WoSCC database to identify publications pertaining to ATC treatment between the years 2000 and 2023. In this bibliometric investigation, the tools VOSviewers, CiteSpace, and the R package "bibliometrix" were employed to investigate the general attributes, developmental framework, and academic frontiers of the subject matter. Results: 1223 publications in total, written by 6937 scholars from 53 areas and 1402 institutions and published in 358 scholarly journals, were analyzed. There has been a gradual increase in the quantity of publications pertaining to ATC treatment. The United States and China emerged as the most prominent nations. The University of Texas MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Counseling Center are prominent research institutions in highly productive countries. The journal Thyroid holds a prominent position within its discipline, being widely recognized as both the most popular and highly co-cited publication. According to the available data, Maria Cabanillas has authored the highest number of published articles, while RC Smallridge has received the highest number of co-citations. It turned out that the prevailing keywords encompassed expression, therapy, apoptosis, survival, activation, proliferation, metastasis, and other related terms. Immunotherapy, targeted therapy, and prognostic factors are the emerging research hotspots and trends. Conclusions: This paper presents a complete overview of research trends and advancements in the treatment of ATC using bibliometric analysis. The acquisition of information will offer vital insights for funding and potential creative strategies in researching the treatment of ATC, which indicates the research frontiers as well as prevalent directions in recent years.

All-in-one, all-optical logic gates using liquid metal plasmon nonlinearity.

Electronic processors are reaching the physical speed ceiling that heralds the era of optical processors. Multifunctional all-optical logic gates (AOLGs) of massively parallel processing are of great importance for large-scale integrated optical processors with speed far in excess of electronics, while are rather challenging due to limited operation bandwidth and multifunctional integration complexity. Here we for the first time experimentally demonstrate a reconfigurable all-in-one broadband AOLG that achieves nine fundamental Boolean logics in a single configuration, enabled by ultrabroadband (400-4000 nm) plasmon-enhanced thermo-optical nonlinearity (TONL) of liquid-metal Galinstan nanodroplet assemblies (GNAs). Due to the unique heterogeneity (broad-range geometry sizes, morphology, assembly profiles), the prepared GNAs exhibit broadband plasmonic opto-thermal effects (hybridization, local heating, energy transfer, etc.), resulting in a huge nonlinear refractive index under the order of 10-4-10-5 within visual-infrared range. Furthermore, a generalized control-signal light route is proposed for the dynamic TONL modulation of reversible spatial-phase shift, based on which nine logic functions are reconfigurable in one single AOLG configuration. Our work will provide a powerful strategy on large-bandwidth all-optical circuits for high-density data processing in the future.

USP28 Serves as a Key Suppressor of Mitochondrial Morphofunctional Defects and Cardiac Dysfunction in the Diabetic Heart.

BACKGROUND: The majority of people with diabetes are susceptible to cardiac dysfunction and heart failure, and conventional drug therapy cannot correct diabetic cardiomyopathy progression. Herein, we assessed the potential role and therapeutic value of USP28 (ubiquitin-specific protease 28) on the metabolic vulnerability of diabetic cardiomyopathy. METHODS: The type 2 diabetes mouse model was established using db/db leptin receptor-deficient mice and high-fat diet/streptozotocin-induced mice. Cardiac-specific knockout of USP28 in the db/db background mice was generated by crossbreeding db/m and Myh6-Cre+/USP28fl/fl mice. Recombinant adeno-associated virus serotype 9 carrying USP28 under cardiac troponin T promoter was injected into db/db mice. High glucose plus palmitic acid-incubated neonatal rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes were used to imitate diabetic cardiomyopathy in vitro. The molecular mechanism was explored through RNA sequencing, immunoprecipitation and mass spectrometry analysis, protein pull-down, chromatin immunoprecipitation sequencing, and chromatin immunoprecipitation assay. RESULTS: Microarray profiling of the UPS (ubiquitin-proteasome system) on the basis of db/db mouse hearts and diabetic patients' hearts demonstrated that the diabetic ventricle presented a significant reduction in USP28 expression. Diabetic Myh6-Cre+/USP28fl/fl mice exhibited more severe progressive cardiac dysfunction, lipid accumulation, and mitochondrial disarrangement, compared with their controls. On the other hand, USP28 overexpression improved systolic and diastolic dysfunction and ameliorated cardiac hypertrophy and fibrosis in the diabetic heart. Adeno-associated virus serotype 9-USP28 diabetic mice also exhibited less lipid storage, reduced reactive oxygen species formation, and mitochondrial impairment in heart tissues than adeno-associated virus serotype 9-null diabetic mice. As a result, USP28 overexpression attenuated cardiac remodeling and dysfunction, lipid accumulation, and mitochondrial impairment in high-fat diet/streptozotocin-induced type 2 diabetes mice. These results were also confirmed in neonatal rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes. RNA sequencing, immunoprecipitation and mass spectrometry analysis, chromatin immunoprecipitation assays, chromatin immunoprecipitation sequencing, and protein pull-down assay mechanistically revealed that USP28 directly interacted with PPARα (peroxisome proliferator-activated receptor α), deubiquitinating and stabilizing PPARα (Lys152) to promote Mfn2 (mitofusin 2) transcription, thereby impeding mitochondrial morphofunctional defects. However, such cardioprotective benefits of USP28 were largely abrogated in db/db mice with PPARα deletion and conditional loss-of-function of Mfn2. CONCLUSIONS: Our findings provide a USP28-modulated mitochondria homeostasis mechanism that involves the PPARα-Mfn2 axis in diabetic hearts, suggesting that USP28 activation or adeno-associated virus therapy targeting USP28 represents a potential therapeutic strategy for diabetic cardiomyopathy.

Targeting heat shock protein 47 alleviated doxorubicin-induced cardiotoxicity and remodeling in mice through suppression of the NLRP3 inflammasome.

AIM: Doxorubicin-induced cardiotoxicity (DIC) is an increasing problem, occurring in many cancer patients receiving anthracycline chemotherapy, ultimately leading to heart failure (HF). Unfortunately, DIC remains difficult to manage due to an ignorance regarding pathophysiological mechanisms. Our work aimed to evaluate the role of HSP47 in doxorubicin-induced HF, and to explore the molecular mechanisms. METHODS AND RESULTS: Mice were exposed to multi-intraperitoneal injection of doxorubicin (DOX, 4mg/kg/week, for 6 weeks continuously) to produce DIC. HSP47 expression was significantly upregulated in serum and in heart tissue in DOX-treated mice and in isolated cardiomyocytes. Mice with cardiac-specific HSP47 overexpression and knockdown were generated using recombinant adeno-associated virus (rAVV9) injection. Importantly, cardiac-specific HSP47 overexpression exacerbated cardiac dysfunction in DIC, while HSP47 knockdown prevented DOX-induced cardiac dysfunction, cardiac atrophy and fibrosis in vivo and in vitro. Mechanistically, we identified that HSP47 directly interacted with IRE1α in cardiomyocytes. Furthermore, we provided powerful evidence that HSP47-IRE1α complex promoted TXNIP/NLRP3 inflammasome and reinforced USP1-mediated NLRP3 ubiquitination. Moreover, NLRP3 deficiency in vivo conspicuously abolished HSP47-mediated cardiac atrophy and fibrogenesis under DOX condition. CONCLUSION: HSP47 was highly expressed in serum and cardiac tissue after doxorubicin administration. HSP47 contributed to long-term anthracycline chemotherapy-associated cardiac dysfunction in an NLRP3-dependent manner. HSP47 therefore represents a plausible target for future therapy of doxorubicin-induced HF.

Generation of spatiotemporal vortices in nonlinear photonic crystals.

Spatiotemporal vortices (STOVs) are a new, to the best of our knowledge, type of structured light in which the optical phase circulates in space-time. In this work, we propose to generate STOVs via second harmonic generation in lithium niobate nonlinear photonic crystals (NPCs) with a linearly chirped Gaussian pulse as the fundamental wave. The structural function of the NPC is derived by the inverse design method. Numerical simulations of the intensity and phase profiles of the generated second harmonic waves are performed with both the amplitude-phase-modulated and the simplified binary-phase-modulated NPCs. We anticipate our study will be valuable for the experimental generation and manipulation of STOVs in NPCs.

Selective Electrochemical Oxidation of Benzylic C-H to Benzylic Alcohols with the Aid of Imidazolium Radical Mediators.

Selective oxidation of benzylic C-H to benzylic alcohols is a well-known challenge in the chemical community since benzylic C-H is more prone to be overoxidized to benzylic ketones. In this work, we report the highly selective electro-oxidation of benzylic C-H to benzylic alcohols in an undivided cell in ionic liquid-based solution. As an example, the selectivity toward xanthydrol could be as high as 95.7% at complete conversion of xanthene, a typical benzylic C-H compound, on gram-scale in imidazolium bromide/H2O/DMF. Mechanism investigation reveals that the imidazolium radical generated in situ participants in a proton-coupled electron transfer process and low-barrier hydrogen bonds stabilize the reaction intermediates, together steering the redox equilibrium, favoring benzylic alcohols over benzylic ketones.

Curling Leaf 1, Encoding a MYB-Domain Protein, Regulates Leaf Morphology and Affects Plant Yield in Rice.

The leaf is the main site of photosynthesis and is an important component in shaping the ideal rice plant architecture. Research on leaf morphology and development will lay the foundation for high-yield rice breeding. In this study, we isolated and identified a novel curling leaf mutant, designated curling leaf 1 (cl1). The cl1 mutant exhibited an inward curling phenotype because of the defective development of sclerenchymatous cells on the abaxial side. Meanwhile, the cl1 mutant showed significant reductions in grain yield and thousand-grain weight due to abnormal leaf development. Through map-based cloning, we identified the CL1 gene, which encodes a MYB transcription factor that is highly expressed in leaves. Subcellular localization studies confirmed its typical nuclear localization. Transcriptome analysis revealed a significant differential expression of the genes involved in photosynthesis, leaf morphology, yield formation, and hormone metabolism in the cl1 mutant. Yeast two-hybrid assays demonstrated that CL1 interacts with alpha-tubulin protein SRS5 and AP2/ERF protein MFS. These findings provide theoretical foundations for further elucidating the mechanisms of CL1 in regulating leaf morphology and offer genetic resources for practical applications in high-yield rice breeding.

Unusual spin-orbit torque switching in perpendicular synthetic antiferromagnets with strong interlayer exchange coupling.

Synthetic antiferromagnet (SAF) is an outstanding system for controlling magnetic coupling via tuning the layer thickness and material composition. Here, we control the interlayer exchange coupling (IEC) in a perpendicularly magnetized SAF Pt/Co/Ir/CoFeB/MgO multilayer, which is tuned by varying the nonmagnetic layer Ir thickness and the magnetic layer Co thickness. And we study the spin-orbit torque (SOT) driven magnetization switching of the SAF. In the SAF with a weak IEC, the SOT-driven switching behavior is similar to that of a single ferromagnet system, which is dominated by the external magnetic field. In contrast, in the SAF with an ultra-strong IEC, the saturation magnetic field is large than 50 kOe, and the SOT-driven switching behavior is decided by the effective magnetic field. The effective field is correlated to the external magnetic field, the IEC field, magnetic moments of CoFeB and Co, and magnetic anisotropy. These results may advance the understanding of SOT switching of perpendicular SAFs and promote the applications of SAFs with low stray fields and lower power in spintronic devices.

Temperate Lianas Have More Acquisitive Strategies than Host Trees in Leaf and Stem Traits, but Not Root Traits.

Increasingly, tropical studies based on aboveground traits have suggested that lianas have a more acquisitive strategy than trees, thereby possibly explaining the increase in lianas relative to trees in many tropical forests under global change. However, few studies have tested whether this pattern can be extended to root traits and temperate forests. In this study, we sampled 61 temperate liana-host tree pairs and quantified 11 commonly studied functional traits representative of plant economics in roots, stems, and leaves; we aimed to determine whether root, stem and leaf traits are coordinated across lifeforms, and whether temperate lianas are also characterized by more fast and acquisitive traits than trees. Our results showed that leaf and stem traits were coordinated across lifeforms but not with root traits, suggesting that aboveground plant economics is not always correlated with belowground economics, and leaf and stem economic spectra cannot be expanded to the root directly. Compared with host trees, lianas had more acquisitive leaf and stem traits, such as higher specific leaf area and lower leaf dry matter content, leaf carbon content, leaf mass per area, and wood density, suggesting that lianas have a more acquisitive strategy than host trees in the temperate forest. The differences between lianas and trees in plant strategy may drive their contrasting responses to the changing temperate forest environment under global change.

Cardiac fibroblast heat shock protein 47 aggravates cardiac fibrosis post myocardial ischemia-reperfusion injury by encouraging ubiquitin specific peptidase 10 dependent Smad4 deubiquitination.

Despite complications were significantly reduced due to the popularity of percutaneous coronary intervention (PCI) in clinical trials, reperfusion injury and chronic cardiac remodeling significantly contribute to poor prognosis and rehabilitation in AMI patients. We revealed the effects of HSP47 on myocardial ischemia-reperfusion injury (IRI) and shed light on the underlying molecular mechanism. We generated adult mice with lentivirus-mediated or miRNA (mi1/133TS)-aided cardiac fibroblast-selective HSP47 overexpression. Myocardial IRI was induced by 45-min occlusion of the left anterior descending (LAD) artery followed by 24 h reperfusion in mice, while ischemia-mediated cardiac remodeling was induced by four weeks of reperfusion. Also, the role of HSP47 in fibrogenesis was evaluated in cardiac fibroblasts following hypoxia-reoxygenation (HR). Extensive HSP47 was observed in murine infarcted hearts, human ischemic hearts, and cardiac fibroblasts and accelerated oxidative stress and apoptosis after myocardial IRI. Cardiac fibroblast-selective HSP47 overexpression exacerbated cardiac dysfunction caused by chronic myocardial IRI and presented deteriorative fibrosis and cell proliferation. HSP47 upregulation in cardiac fibroblasts promoted TGFß1-Smad4 pathway activation and Smad4 deubiquitination by recruiting ubiquitin-specific peptidase 10 (USP10) in fibroblasts. However, cardiac fibroblast specific USP10 deficiency abolished HSP47-mediated fibrogenesis in hearts. Moreover, blockage of HSP47 with Col003 disturbed fibrogenesis in fibroblasts following HR. Altogether, cardiac fibroblast HSP47 aggravates fibrosis post-myocardial IRI by enhancing USP10-dependent Smad4 deubiquitination, which provided a potential strategy for myocardial IRI and cardiac remodeling.

Diminished arachidonate 5-lipoxygenase perturbs phase separation and transcriptional response of Runx2 to reverse pathological ventricular remodeling.

BACKGROUND: Arachidonate 5-lipoxygenase (Alox5) belongs to a class of nonheme iron-containing dioxygenases involved in the catalysis of leukotriene biosynthesis. However, the effects of Alox5 itself on pathological cardiac remodeling and heart failure remain elusive. METHODS: The role of Alox5 in pathological cardiac remodeling was investigated by Alox5 genetic depletion, AAV9-mediated overexpression in cardiomyocytes, and a bone marrow (BM) transplantation approach. Neonatal rat cardiomyocytes were used to explore the effects of Alox5 in vitro. Molecular and signaling pathways were revealed by CUT &Tag, IP-MS, RNA sequencing and bioinformatic analyses. FINDINGS: Untargeted metabolomics showed that serum 5-HETE (a primary product of Alox5) levels were little changed in patients with cardiac hypertrophy, while Alox5 expression was significantly upregulated in murine hypertensive cardiac samples and human cardiac samples of hypertrophy, which prompted us to test whether high Alox5 levels under hypertensive stimuli were directly associated with pathologic myocardium in an enzymatic activity-independent manner. Herein, we revealed that Alox5 deficiency significantly ameliorated transverse aortic constriction (TAC)-induced hypertrophy. Cardiomyocyte-specific Alox5 depletion attenuated hypertensive ventricular remodeling. Conversely, cardiac-specifical Alox5 overexpression showed a pro-hypertrophic cardiac phenotype. Ablation of Alox5 in bone marrow-derived cells did not affect pathological cardiac remodeling and heart failure. Mechanically, Runx2 was identified as a target of Alox5. In this regard, Alox5 PEST domain could directly bind to Runx2 PTS domain, promoting nuclear localization of Runx2 in an enzymatic activity-independent manner, simultaneously contributed to liquid-liquid phase separation (LLPS) of Runx2 at specific domain in the nucleus and increased transcription of EGFR in cardiomyocytes. Runx2 depletion alleviated hypertrophy in Ang II-pretreated Alox5-overexpressing cardiomyocytes. INTERPRETATION: Overall, our study demonstrated that targeting Alox5 exerted a protective effect against cardiac remodeling and heart failure under hypertensive stimuli by disturbing LLPS of Runx2 and substantial reduction of EGFR transcription activation in cardiomyocytes. Our findings suggest that negative modulation of Alox5-Runx2 may provide a therapeutic approach against pathological cardiac remodeling and heart failure. FUNDING: National Natural Science Foundation of China.

Role of irisin in physiology and pathology.

Irisin, out-membrane part of fibronectin type III domain-containing 5 protein (FNDC5), was activated by Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) during physical exercise in skeletal muscle tissues. Most studies have reported that the concentration of irisin is highly associated with health status. For instance, the level of irisin is significantly lower in patients with obesity, osteoporosis/fractures, muscle atrophy, Alzheimer's disease, and cardiovascular diseases (CVDs) but higher in patients with cancer. Irisin can bind to its receptor integrin αV/ß5 to induce browning of white fat, maintain glucose stability, keep bone homeostasis, and alleviate cardiac injury. However, it is unclear whether it works by directly binding to its receptors to regulate muscle regeneration, promote neurogenesis, keep liver glucose homeostasis, and inhibit cancer development. Supplementation of recombinant irisin or exercise-activated irisin might be a successful strategy to fight obesity, osteoporosis, muscle atrophy, liver injury, and CVDs in one go. Here, we summarize the publications of FNDC5/irisin from PubMed/Medline, Scopus, and Web of Science until March 2022, and we review the role of FNDC5/irisin in physiology and pathology.

Long-Term Activation of Glucagon-like peptide-1 receptor by Dulaglutide Prevents Diabetic Heart Failure and Metabolic Remodeling in Type 2 Diabetes.

Background Mechanistic insights of glucagon-like peptide-1 receptor agonists remain incompletely identified, despite the efficacy in heart failure observed in clinical trials. Here, we evaluated the effects of dulaglutide on heart complications and illuminated its underlying mechanism. Methods and Results We used mice with high-fat diet (HFD)/streptozotocin-induced type 2 diabetes to investigate the effects of dulaglutide upon diabetic cardiac dysfunction. After the onset of diabetes, control and diabetic mice were injected subcutaneously with either dulaglutide (type 2 diabetes-dulaglutide and control-dulaglutide groups) or vehicle (type 2 diabetes-vehicle and control-vehicle groups) for 8 weeks. Subsequently, heart characteristics, cardiometabolic profile and mitochondrial morphology and function were evaluated. Also, we analyzed the effects of dulaglutide on neonatal rat ventricular myocytes treated with high glucose plus palmitic acid. In addition, wild type and AMP-activated protein kinase α2 mutant mice were used to evaluate the underlying mechanism. In type 2 diabetes mouse model, dulaglutide ameliorated insulin resistance, improved glucose tolerance, reduced hyperlipidemia, and promoted fatty acid use in the myocardium. Dulaglutide treatment functionally attenuated cardiac remodeling and dysfunction and promoted metabolic reprogramming in diabetic mice. Furthermore, dulaglutide improved mitochondria fragmentation in myocytes, and simultaneously reinstated mitochondrial morphology and function in diabetic hearts. We also found that dulaglutide preserved AMP-activated protein kinase α2-dependent mitochondrial homeostasis, and the protective effects of dulaglutide on diabetic heart was almost abated by AMP-activated protein kinase α2 knockout. Conclusions Dulaglutide prevents diabetic heart failure and favorably affects myocardial metabolic remodeling by impeding mitochondria fragmentation, and we suggest a potential strategy to develop a long-term activation of glucagon-like peptide-1 receptor-based therapy to treat diabetes associated cardiovascular complications.