PungentDB: Bridging traditional Chinese medicine of medicine food homology and modern food flavor chemistry.

Merging traditional Chinese medicine's (TCM) principles of medicine-food homology with modern flavor chemistry, this research unveils PungentDB (http://www.pungentdb.org.cn/home), a database documenting 205 unique pungent flavor compounds from 231 TCMs. It provides detailed insights into their chemical attributes, biological targets (including IC50/EC50 values), and molecular structures (2D/3D), enriched with visualizations of target organ distribution and protein structures, exploring the pungent flavor space with the help of a feature-rich visual interface. This collection, derived from over 3249 sources and highlighting 9129 targets, delves into the compounds' unique pungent flavors-taste, aroma, and thermal sensations-and their interaction with taste and olfactory receptors. PungentDB bridges ancient wisdom and culinary innovation, offering a nuanced exploration of pungent flavors' role in enhancing food quality, safety, and sensory experiences. This initiative propels flavor chemistry forward, serving as a pivotal resource for food science advancement and the innovative application of pungent flavors.

Pulmonary Crystal-Storing Histiocytosis Misdiagnosed as Lung Cancer.

BACKGROUND: Crystalloid storage histiocytosis (CSH) is a rare clinical condition characterized by abnormally high numbers of histiocytes with a large accumulation of crystalline immunoglobulins. Due to its relative rarity, clinical diagnosis of it is frequently incomplete or incorrect. We report a case with pulmonary crystal-storing histiocytosis that was mistakenly identified as lung carcinoma. METHODS: Percutaneous lung biopsy, bronchoscopy. RESULTS: Percutaneous lung biopsy pathology shows granulomatous inflammation with massive eosinophilic infiltration, immunohistochemistry shows CD68, kappa positive, S-100, desmin, myogenin, lambda negative. The final diagnosis is pulmonary crystal-storing histiocytosis. CONCLUSIONS: To get pathology tissue for a definitive diagnosis, patients with pulmonary nodules who have changes in tumor markers or nodule size should have bronchoscopy or percutaneous lung biopsy done as soon as possible.

[Neurofilament light chain and Polyglutamine disease].

Polyglutamine (PolyQ) disease is a group of hereditary neurodegenerative diseases. It has become clear that brain damage may occur decades before the onset of symptoms. As a sensitive marker for neuro-axonal damages, neurofilament light chain (NfL) has appeared as a promising biomarker for neurological diseases. it may be used as a preclinical and clinical marker for the neurodegeneration in polyQ diseases, and is closely correlated with disease severity and progression, in particular different disease stages. This article has provided a review for the value of NfL as a biomarker in polyQ disease and its future research directions.

Microcystin-LR induces histopathological injury and cell apoptosis in the hepatopancreas of white shrimp, Litopenaeus vannamei.

Microcystin-LR (MC-LR), a common hepatotoxin produced by bloom-forming cyanobacteria, presents a serious threat to the health of aquatic animals. In this study, we studied the impact of MC-LR on hepatopancreas histopathology, enzyme activity, transcriptome, and apoptosis of Litopenaeus vannamei. Thus, shrimp postlarvae (1.63 ± 0.5 g) exposed to MC-LR at 500 µg/kg caused morphological lesions in the histology of the shrimp hepatopancreas, which exhibited swollen, lighter coloration and unclear edges. Moreover, MC-LR significantly altered the hepatopancreas enzyme activities such as the levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), acid phosphatase (ACP), alkaline phosphatase (AKP) and lysozyme (LZM), including the state of apoptosis in hepatopancreas. From the RNA-seq analysis of the hepatopancreas, a total of 728 differentially expressed genes (DEGs) were identified, and their functions in MC-LR treatment group were involved in cellular processes, metabolic processes, biological regulation, cellular components, catalytic activity and binding. The metabolic pathways primarily associated with the DEGs included reactive oxygen species, glycerophospholipid metabolism and the phospholipase D signaling pathway. Overall, q-PCR results indicated that MC-LR led to significant changes in multiple apoptosis genes of shrimp hepatopancreas. This study expand the understanding of the effect of microcystin-LR on commercially farmed crustaceans.

Wormlike Micellar Glycerol Solutions Formed from a Double-Tailed Surfactant with Two Quaternary Ammonium Head Groups.

Herein, a quaternary ammonium surfactant with dual heads and tails, N1,N1,N1,N3,N3-pentamethyl-N3-(3-(2-tetradecylhexadecanamido)propyl)propane-1,3-diaminium dibromide, abbreviated as Di-C14-N2, was synthesized. For the first time, clear observation of aggregate structures formed by surfactants in pure glycerol systems was achieved using cryogenic transmission electron microscopy (cryo-TEM). The system's rheological properties were analyzed using both steady-state shear and oscillatory rheological measurements. The lubricating efficiency of the Di-C14-N2 glycerol solution was assessed for its tribological properties using a tribological wear tester, white light interferometer, and scanning electron microscope. In glycerol, Di-C14-N2 formed long wormlike micelles, which resulted in a glycerol solution with the zero-shear viscosity of 1013 Pa·s at 90 mM, which is the most viscous glycerol system up to now. The system displayed distinct rheological properties from the aqueous system, as evidenced by two intersections in the loss and storage moduli. The formed wormlike micelles in glycerol lead to a significant alteration in the viscoelasticity of the system, thus endowing the Di-C14-N2 glycerol solution with potential as an eco-friendly lubricant. The friction coefficient of the system was found to be 23% lower and the wear rate was 83% lower than that of pure glycerol after the addition of Di-C14-N2. This demonstrates that the addition of Di-C14-N2 greatly improves the frictional properties of pure glycerol. This study offers the possibility of directly observing the aggregate structures formed by surfactants in pure glycerol systems. It contributes to the exploration of the self-assembly behavior of surfactants in nonaqueous polar media, thereby aiding in a deeper understanding of the correlation between molecular structure, mesoscale structure, and macroscopic properties.

Artificial intelligence for geoscience: Progress, challenges, and perspectives.

This paper explores the evolution of geoscientific inquiry, tracing the progression from traditional physics-based models to modern data-driven approaches facilitated by significant advancements in artificial intelligence (AI) and data collection techniques. Traditional models, which are grounded in physical and numerical frameworks, provide robust explanations by explicitly reconstructing underlying physical processes. However, their limitations in comprehensively capturing Earth's complexities and uncertainties pose challenges in optimization and real-world applicability. In contrast, contemporary data-driven models, particularly those utilizing machine learning (ML) and deep learning (DL), leverage extensive geoscience data to glean insights without requiring exhaustive theoretical knowledge. ML techniques have shown promise in addressing Earth science-related questions. Nevertheless, challenges such as data scarcity, computational demands, data privacy concerns, and the "black-box" nature of AI models hinder their seamless integration into geoscience. The integration of physics-based and data-driven methodologies into hybrid models presents an alternative paradigm. These models, which incorporate domain knowledge to guide AI methodologies, demonstrate enhanced efficiency and performance with reduced training data requirements. This review provides a comprehensive overview of geoscientific research paradigms, emphasizing untapped opportunities at the intersection of advanced AI techniques and geoscience. It examines major methodologies, showcases advances in large-scale models, and discusses the challenges and prospects that will shape the future landscape of AI in geoscience. The paper outlines a dynamic field ripe with possibilities, poised to unlock new understandings of Earth's complexities and further advance geoscience exploration.

Development and external validation of a novel modality for rapid recognition of aortic dissection based on peripheral pulse oximetry waveforms.

BACKGROUND: Aortic dissection (AD) is a life-threatening cardiovascular emergency that is often misdiagnosed as other chest pain conditions. Physiologically, AD may cause abnormalities in peripheral blood flow, which can be detected using pulse oximetry waveforms. PURPOSE: This study aimed to assess the feasibility of identifying AD based on pulse oximetry waveforms and to highlight the key waveform features that play a crucial role in this diagnostic method. METHODS: This prospective study employed high-risk chest pain cohorts from two emergency departments. The initial cohort was enriched with AD patients (n = 258, 47% AD) for model development, while the second cohort consisted of chest pain patients awaiting angiography (n = 71, 25% AD) and was used for external validation. Pulse oximetry waveforms from the four extremities were collected for each patient. After data preprocessing, a recognition model based on the random forest algorithm was trained using patients' gender, age, and waveform difference features extracted from the pulse oximetry waveforms. The performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). The importance of features was also assessed using Shapley Value and Gini importance. RESULTS: The model demonstrated strong performance in identifying AD in both the training and external validation sets. In the training set, the model achieved an area under the ROC curve of 0.979 (95% CI: 0.961-0.990), sensitivity of 0.918 (95% CI: 0.873-0.955), specificity of 0.949 (95% CI: 0.912-0.985), and accuracy of 0.933 (95% CI: 0.904-0.959). In the external validation set, the model attained an area under the ROC curve of 0.855 (95% CI: 0.720-0.965), sensitivity of 0.889 (95% CI: 0.722-1.000), specificity of 0.698 (95% CI: 0.566-0.812), and accuracy of 0.794 (95% CI: 0.672-0.878). Decision curve analysis (DCA) further showed that the model provided a substantial net benefit for identifying AD. The median mean and median variance of the four limbs' signals were the most influential features in the recognition model. CONCLUSIONS: This study demonstrated the feasibility and strong performance of identifying AD based on peripheral pulse oximetry waveforms in high-risk chest pain populations in the emergency setting. The findings also provided valuable insights for future human fluid dynamics simulations to elucidate the impact of AD on blood flow in greater detail.

Hydrogel Microneedle Patches Loaded with Stem Cell Mitochondria-Enriched Microvesicles Boost the Chronic Wound Healing.

Rescuing or compensating mitochondrial function represents a promising therapeutic avenue for radiation-induced chronic wounds. Adult stem cell efficacies are primarily dependent on the paracrine secretion of mitochondria-containing extracellular vesicles (EVs). However, effective therapeutic strategies addressing the quantity of mitochondria and mitochondria-delivery system are lacking. Thus, in this study, we aimed to design an effective hydrogel microneedle patch (MNP) loaded with stem cell-derived mitochondria-rich EVs to gradually release and deliver mitochondria into the wound tissues and boost wound healing. We, first, used metformin to enhance mitochondrial biogenesis and thereby increasing the secretion of mitochondria-containing EVs (termed "Met-EVs") in adipose-derived stem cells. To verify the therapeutic effects of Met-EVs, we established an in vitro and an in vivo model of X-ray-induced mitochondrial dysfunction. The Met-EVs ameliorated the mitochondrial dysfunction by rescuing mitochondrial membrane potential, increasing adenosine 5'-triphosphate levels, and decreasing reactive oxygen species production by transferring active mitochondria. To sustain the release of EVs into damaged tissues, we constructed a Met-EVs@Decellularized Adipose Matrix (DAM)/Hyaluronic Acid Methacrylic Acid (HAMA)-MNP. Met-EVs@DAM/HAMA-MNP can load and gradually release Met-EVs and their contained mitochondria into wound tissues to alleviate mitochondrial dysfunction. Moreover, we found Met-EVs@DAM/HAMA-MNP can markedly promote macrophage polarization toward the M2 subtype with anti-inflammatory and regenerative functions, which can, in turn, enhance the healing process in mice with skin wounds combined radiation injuries. Collectively, we successfully fabricated a delivery system for EVs, Met-EVs@DAM/HAMA-MNP, to effectively deliver stem cell-derived mitochondria-rich EVs. The effectiveness of this system has been demonstrated, holding great potential for chronic wound treatments in clinic.

Fallopian tube wrapping as a cause of catheter malfunction in peritoneal dialysis: a report of two cases and management strategies.

Background: Catheter malfunction is a common problem following the placement of a peritoneal dialysis (PD) catheter, and it is characterized by inadequate dialysate drainage, which can also limit infusion. Common causes include constipation, catheter migration, catheter kinking, omental wrapping, and fibrin obstruction. However, catheter obstruction by other intra-abdominal organs has been observed infrequently. Case Description: We present two cases of female PD patients experiencing catheter dysfunction after catheter implantation. The first case involves a 28-year-old female who suffered from problematic drainage and infusion of dialysate 1 month after catheter insertion, evidenced by catheter displacement from the pelvis on abdominal X-ray. The second case concerns a 49-year-old female PD patient who also encountered a bidirectional catheter malfunction 40 days post-implantation. Conservative methods failed to restore the catheter function in both patients. Laparoscopic examination revealed fallopian tube, not the omentum, was tightly wrapped around the PD catheter in both cases. Finally, laparoscopic surgery with catheter fixation restored the catheter function, enabling continued continuous ambulatory peritoneal dialysis (CAPD) with favorable outcomes. Conclusions: Our findings indicate that healthcare providers should consider fallopian tube wrapping as a potential cause of catheter dysfunction. Prompt consideration and utilization of laparoscopy with catheter fixation can play an important role in restoring catheter function and improving patient outcomes.

Impact on Image Quality and Diagnostic Performance of Dual-Layer Detector Spectral CT for Pulmonary Subsolid Nodules: Comparison With Hybrid and Model-Based Iterative Reconstruction.

OBJECTIVE: To evaluate the image quality and diagnostic performance of pulmonary subsolid nodules on conventional iterative algorithms, virtual monoenergetic images (VMIs), and electron density mapping (EDM) using a dual-layer detector spectral CT (DLSCT). METHODS: This retrospective study recruited 270 patients who underwent DLSCT scan for lung nodule screening or follow-up. All CT examinations with subsolid nodules (pure ground-glass nodules [GGNs] or part-solid nodules) were reconstructed with hybrid and model-based iterative reconstruction, VMI at 40, 70, 100, and 130 keV levels, and EDM. The CT number, objective image noise, signal-to-noise ratio, contrast-to-noise ratio, diameter, and volume of subsolid nodules were measured for quantitative analysis. The overall image quality, image noise, visualization of nodules, artifact, and sharpness were subjectively rated by 2 thoracic radiologists on a 5-point scale (1 = unacceptable, 5 = excellent) in consensus. The objective image quality measurements, diameter, and volume were compared among the 7 groups with a repeated 1-way analysis of variance. The subjective scores were compared with Kruskal-Wallis test. RESULTS: A total of 198 subsolid nodules, including 179 pure GGNs, and 19 part-solid nodules were identified. Based on the objective analysis, EDM had the highest signal-to-noise ratio (164.71 ± 133.60; P < 0.001) and contrast-to-noise ratio (227.97 ± 161.96; P < 0.001) among all image sets. Furthermore, EDM had a superior mean subjective rating score (4.80 ± 0.42) for visualization of GGNs compared to other reconstructed images (all P < 0.001), although the model-based iterative reconstruction had superior subjective scores of overall image quality. For pure GGNs, the measured diameter and volume did not significantly differ among different reconstructions (both P > 0.05). CONCLUSIONS: EDM derived from DLSCT enabled improved image quality and lesion conspicuity for the evaluation of lung subsolid nodules compared to conventional iterative reconstruction algorithms and VMIs.

Integrated Comparative Transcriptome and Weighted Gene Co-Expression Network Analysis Provide Valuable Insights into the Mechanisms of Pinhead Initiation in Chinese Caterpillar Mushroom Ophiocordyceps sinensis (Ascomycota).

The initiation and formation of the "pinhead" is the key node in growth process of Ophiocordyceps sinensis (Chinese Cordyceps). The research on the mechanism of changes in this growth stage is the basis for realizing the industrialization of its artificial cultivation. Clarifying the mechanisms of pinhead initiation is essential for its further application. Here, we performed a comprehensive transcriptome analysis of pinhead initiation process in O. sinensis. Comparative transcriptome analysis revealed remarkable variation in gene expression and enriched pathways at different pinhead initiation stages. Gene co-expression network analysis by WGCNA identified 4 modules highly relevant to different pinhead initiation stages, and 23 hub genes. The biological function analysis and hub gene annotation of these identified modules demonstrated that transmembrane transport and nucleotide excision repair were the topmost enriched in pre-pinhead initiation stage, carbohydrate metabolism and protein glycosylation were specially enriched in pinhead initiation stage, nucleotide binding and DNA metabolic process were over-represented after pinhead stage. These key regulators are mainly involved in carbohydrate metabolism, synthesis of proteins and nucleic acids. This work excavated the candidate pathways and hub genes related to the pinhead initiation stage, which will serve as a reference for realizing the industrialization of artificial cultivation in O. sinensis.

Asymptomatic infection and disappearance of clinical symptoms of COVID-19 infectors in China 2022-2023: a cross-sectional study.

To explore the clinical characteristics of patients infected with SARS-CoV-2 nationwide, especially the effect factors of asymptomatic infection and disappearance of clinical symptoms. A total of 66,448 COVID-19 patients in China who have been diagnosed by nucleic acid test or rapid antigen test were surveyed online (December 24, 2022 to January 16, 2023). Our cross-sectional study used descriptive analyses and binary Logistics regression model to assess the correlation between the clinical characteristics and relative factors, including age, gender, pre-existing conditions, reinfection, vaccination and treatment. A total of 64,515 valid questionnaires were collected. Among included participants, 5969 of which were asymptomatic. The symptoms were mainly upper respiratory symptoms, including dry and itchy throat (64.16%), sore throat (59.95%), hoarseness (57.90%), nasal congestion (53.39%). In binary Logistics regression model, we found that male, no pre-existing conditions, reinfection and vaccination have positive correlations with the appearance of asymptomatic COVID-19 patients. In Cox proportional-hazards regression model, considering all clinical symptoms disappeared in 14 days as outcome, we found that ≤ 60 years old, male, no pre-existing conditions, vaccination and adopted treatment have positive correlations with rapid amelioration of clinical symptoms in COVID-19 patients. The clinical symptoms of the participants were mainly upper respiratory symptoms which were according with the infection of Omicron variant. Factors including age, gender, pre-existing conditions and reinfection could influence the clinical characteristics and prognosis of COVID-19 patients. Importantly, vaccination has positive significance for the prevention and treatment of COVID-19. Lastly, the use of Chinese medicine maybe beneficial to COVID-19 patients, however, reasonable guidance is necessary.

Analysis of intra-fractional positioning correction performed by cone beam computed tomography in SBRT treatments.

PURPOSE: This study aims to evaluate the positioning correction extracted from Intra-fraction Cone Beam (IF-CBCT) images obtained during Stereotactic Body Radiotherapy (SBRT) treatments, and to assess whether its magnitude justifies its acquisition. In addition, the results obtained in lung, liver, and pancreas SBRTs with two deep inspiration breath-hold systems (DIBH), and for prostate with/without ultrasound (US) monitoring were compared. METHODS: 1449 treatments, performed with two linear accelerators (LINACs) were retrospectively analyzed. DIBH were performed either with a spirometry-based device or a surface-guidance system and one LINAC was equipped with US monitoring system for prostate. Significance tests were used to account for differences between units. RESULTS: Group systematic error (M) was approximately -0.7 mm for DIBH treatments in superior-inferior (SI) direction with no difference (p > 0.7) between LINACs. Moreover, there was a SI difference of 0.5 mm for prostate treatments (p = 0.008), in favor of the US monitored one. In anterior-posterior (AP) direction, only liver treatments exhibited differences between LINACs, with the spirometer-based system being 0.8 mm inferior (p = 0.003). M<0.4 mm in left-right (LR) direction was found for all locations and LINACs. The spirometer-based system resulted in lower standard deviation of systematic and random errors in most components and locations, with a greater effect observed in liver SBRTs. CONCLUSIONS: The corrections made with IF-CBCT during SBRT treatments were not negligible. Both DIBH systems were effective in managing respiratory movements. However, the spirometry-based system was slightly more accurate. In addition, US monitoring of the prostate appeared to be useful in reducing target shift.

Integrative genome-centric metagenomics for surface water surveillance: Elucidating microbiomes, antimicrobial resistance, and their associations.

Surface water ecosystems are intimately intertwined with anthropogenic activities and have significant public health implications as primary sources of irrigation water in agricultural production. Our extensive metagenomic analysis examined 404 surface water samples from four different geological regions in Chile and Brazil, spanning irrigation canals (n = 135), rivers (n = 121), creeks (n = 74), reservoirs (n = 66), and ponds (n = 8). Overall, 50.25 % of the surface water samples contained at least one of the pathogenic or contaminant bacterial genera (Salmonella: 29.21 %; Listeria: 6.19 %; Escherichia: 35.64 %). Furthermore, a total of 1,582 antimicrobial resistance (AMR) gene clusters encoding resistance to 25 antimicrobial classes were identified, with samples from Brazil exhibiting an elevated AMR burden. Samples from stagnant water sources were characterized by dominant Cyanobacteriota populations, resulting in significantly reduced biodiversity and more uniform community compositions. A significant association between taxonomic composition and the resistome was supported by a Procrustes analysis (p < 0.001). Notably, regional signatures were observed regarding the taxonomic and resistome profiles, as samples from the same region clustered together on both ordinates. Additionally, network analysis illuminated the intricate links between taxonomy and AMR at the contig level. Our deep sequencing efforts not only mapped the microbial landscape but also expanded the genomic catalog with newly characterized metagenome-assembled genomes (MAGs), boosting the classification of reads by 12.85 %. In conclusion, this study underscores the value of metagenomic approaches in surveillance of surface waters, enhancing our understanding of microbial and AMR dynamics with far-reaching public health and ecological ramifications.

Nano-Fe3O4: Enhancing the tolerance of Elymus nutans to Cd stress through regulating programmed cell death.

Cadmium (Cd) poses a significant threat to plant growth and the environment. Nano-Fe3O4 is effective in alleviating Cd stress in plants. Elymus nutans Griseb. is an important fodder crop on the Qinghai-Tibetan Plateau (QTP). However, the potential mechanism by which nano-Fe3O4 alleviates Cd stress in E. nutans is not well understood. E. nutans were subjected to single Cd, single nano-Fe3O4, and co-treatment with nano-Fe3O4 and Cd, and the effects on morphology, Cd uptake, antioxidant enzyme activity, reactive oxygen species (ROS) levels and programmed cell death (PCD) were studied to clarify the regulatory mechanism of nano-Fe3O4. The results showed that Cd stress significantly decreased the germination percentage and biomass of E. nutans. The photosynthetic pigment content decreased significantly under Cd stress. Cd stress also caused oxidative stress and lipid peroxidation, accumulation of excessive ROS, resulting in PCD, but the effect of nano-Fe3O4 was different. Seed germination, seedling growth, and physiological processes were analyzed to elucidate the regulatory role of nano-Fe3O4 nanoparticles in promoting photosynthesis, reducing Cd accumulation, scavenging ROS, and regulating PCD, to promote seed germination and seedling growth in E. nutans. This report provides a scientific basis for improving the tolerance of Elymus to Cd stress by using nano-Fe3O4.

Oxford Nanopore long read-based shotgun metagenomic data sets of simulated bacterial communities originating from fresh spinach and surface water.

Oxford Nanopore long reads of simulated bacterial communities from fresh spinach and surface water were generated (R9.4.1+SQK-LSK109 and R10.4+SQK-LSK112; 0.5, one, and two million reads). Salmonella enterica serotype Heidelberg, Montevideo, or Typhimurium was included alone or in combination in the spinach community, while the water community harbored Pseudomonas aeruginosa.

Development of a Novel Peptide-Based PET Tracer [68Ga]Ga-DOTA-BP1 for BCMA Detection in Multiple Myeloma.

B-cell maturation antigen (BCMA) has emerged as a promising tumor marker for the diagnosis and treatment of multiple myeloma. The noninvasive and rapid detection of BCMA expression in vivo provides significant value in screening and evaluating multiple myeloma patients receiving BCMA-targeted therapy. We identified the BCMA-targeting peptide BP1 from a one-bead-one-compound (OBOC) peptide library using a high-throughput microarray strategy. The BCMA-targeting specificity and affinity of BP1 were assessed by surface plasmon resonance imaging (SPRi), flow cytometry, and confocal imaging. BCMA-positive (H929) and BCMA-negative (K562) subcutaneous tumor models were established and labeled with 68Ga for BP1, followed by PET imaging and biodistribution studies. PET imaging demonstrated that 68Ga-labeled BP1 has significant specific uptake in multiple myeloma, enabling rapid identification of BCMA expression and precise delineation of the disease. Thus, BP1 represents an ideal candidate for multiple myeloma imaging.

Ablation of Akt2 rescues chronic caloric restriction-provoked myocardial remodeling and dysfunction through a CDK1-mediated regulation of mitophagy.

Chronic caloric restriction triggers unfavorable alterations in cardiac function albeit responsible scenarios remain unclear. This work evaluated the possible involvement of Akt2 in caloric restriction-evoked cardiac geometric and functional changes and responsible processes focusing on autophagy and mitophagy. Akt2 knockout and WT mice were subjected to caloric restriction for 30 weeks prior to assessment of myocardial homeostasis. Caloric restriction compromised echocardiographic parameters (decreased LV wall thickness, LVEDD, stroke volume, cardiac output, ejection fraction, fractional shortening, and LV mass), cardiomyocyte contractile and intracellular Ca2+ capacity, myocardial atrophy, interstitial fibrosis and mitochondrial injury associated with elevated blood glucocorticoids, autophagy (LC3B, p62, Atg7, Beclin-1), and mitophagy (Pink1, Parkin, TOM20), dampened cardiac ATP levels, mitochondrial protein PGC1α and UCP2, anti-apoptotic protein Bcl2, intracellular Ca2+ governing components Na+-Ca2+ exchanger, phosphorylation of SERCA2a, mTOR (Ser2481) and ULK1 (Ser757), and upregulated Bax, phospholamban, phosphorylation of Akt2, AMPK, and ULK1 (Ser555), the responses except autophagy markers (Beclin-1, Atg7), phosphorylation of AMPK, mTOR and ULK1 were negated by Akt2 ablation. Levels of CDK1 and DRP1 phosphorylation were overtly upregulated with caloric restriction, the response was reversed by Akt2 knockout. Caloric restriction-evoked changes in cardiac remodeling and cardiomyocyte function were alleviated by glucocorticoid receptor antagonism, Parkin ablation and Mdivi-1. In vitro experiment indicated that serum deprivation or glucocorticoids evoked GFP-LC3B accumulation and cardiomyocyte dysfunction, which was negated by inhibition of Akt2, CDK1 or DRP1, whereas mitophagy induction reversed Akt2 ablation-evoked cardioprotection. These observations favor a protective role of Akt2 ablation in sustained caloric restriction-evoked cardiac pathological changes via correction of glucocorticoid-induced mitophagy defect in a CDK1-DRP1-dependent manner.