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Diabetic cardiomyopathy is a primary myocardial injury induced by diabetes with complex pathogenesis. In this study, we identify disordered cardiac retinol metabolism in type 2 diabetic male mice and patients characterized by retinol overload, all-trans retinoic acid deficiency. By supplementing type 2 diabetic male mice with retinol or all-trans retinoic acid, we demonstrate that both cardiac retinol overload and all-trans retinoic acid deficiency promote diabetic cardiomyopathy. Mechanistically, by constructing cardiomyocyte-specific conditional retinol dehydrogenase 10-knockout male mice and overexpressing retinol dehydrogenase 10 in male type 2 diabetic mice via adeno-associated virus, we verify that the reduction in cardiac retinol dehydrogenase 10 is the initiating factor for cardiac retinol metabolism disorder and results in diabetic cardiomyopathy through lipotoxicity and ferroptosis. Therefore, we suggest that the reduction of cardiac retinol dehydrogenase 10 and its mediated disorder of cardiac retinol metabolism is a new mechanism underlying diabetic cardiomyopathy. The current challenges for diabetic cardiomyopathy (DCM) are unclear mechanisms and no effective therapy in clinics. Here, the authors found that the decrease of cardiac retinol dehydrogenase 10 in type 2 diabetes leads to retinol metabolism disorder, cardiac lipid toxicity and cardiomyopathy development, suggesting that correcting the imbalance of cardiac retinol metabolism may be an effective strategy for the treatment of DCM.

Background Triglyceride-glucose (TyG) index is considered an alternative indicator of insulin resistance and is associated with cardiovascular diseases. However, its association with subclinical myocardial injury in a general population without known cardiovascular disease has not been investigated, nor has the effect of diabetes. Methods Individuals without known cardiovascular disease were included from the Atherosclerosis Risk in Communities (ARIC) cohort. The baseline TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The association between the baseline TyG index and subclinical myocardial injury [high-sensitivity cardiac troponin T (hs-cTnT≥ 14 ng/L)] was assessed using both cross-sectional and prospective cohort designs. Results A total of 11,478 participants were involved in the cross-sectional study (mean age, 56.78 years; 42.44% male) and 8801 participants were involved in the prospective cohort study (mean age, 56.57 years; 41.36% male). Both linear (r = 0.13, p  < 0.001) and logistic regression analyses (adjusted odds ratio [aOR] = 1.33, p  < 0.001) showed a positive association between the TyG index and baseline hs-cTnT level, which was consistent in diabetic participants (aOR = 1.64, p  = 0.020) but not significant in non-diabetic participants (aOR = 0.89, p  = 0.374). After a six-year follow-up, a U-shaped association between the TyG index and incidence of hs-cTnT elevation was observed among the overall participants. Further subgroup analyses showed an L-shaped (aOR = 0.72, p  = 0.006) and a J-shaped (aOR = 2.09, p  < 0.001) association between the TyG index and incidence of hs-cTnT elevation in participants without and with diabetes, respectively. Conclusion A U-shaped association between the TyG index and the incidence of subclinical myocardial injury was observed for the first time. Diabetes may be a critical modifier of the association between the TyG index and subclinical myocardial injury. Considering the risk stratification value of the TyG index based on diabetes status may hold significant clinical value. Graphical abstract

Sonocatalytic therapy (SCT) offers a non‐invasive and deep tissue‐penetrating approach to addressing the pathological challenges of atherosclerosis. However, its therapeutic efficacy remains limited by the lack of efficient sonosensitizers. A critical challenge in SCT is simultaneously leveraging beneficial plaque microenvironment factors, such as elevated H2O2 levels, while mitigating adverse conditions, including hypoxia. Herein, a microenvironment‐regulatable single‐atom sonozyme system is presented to enable effective SCT while simultaneously refining the lesion microenvironment. The single‐atom manganese catalyst (SMC) is synthesized via MOF‐derived precursor pyrolysis followed by ion implantation, yielding atomically precise four‐coordinated active sites. Functionalized with hyaluronic acid (HA) facilitates targeted delivery of SMC‐HA to M1 macrophages. Under ultrasound (US), SMC‐HA effectively eliminates M1 macrophages, thereby reducing plaque burden and promoting lesion regression in two ApoE−/− mice models. Overall, SMC‐HA reinforces its role as an advanced sonosensitizer for SCT. This study establishes SMC‐HA‐mediated SCT as a promising therapeutic strategy for atherosclerotic plaque treatment. A tetranitrogen‐coordinated single‐atom manganese catalyst (SMC) is fabricated with outstanding sonosensitization efficiency and multi‐enzyme‐like catalytic properties. To enable better targeting of M1 macrophages, hyaluronic acid (HA) is applied to modify the surface of SMC, yielding SMC‐HA nanozymes. The SMC‐HA exhibits superior sonocatalytic activity. Finally, the as‐synthesized SMC‐HA demonstrates significantly enhanced anti‐atherosclerotic effect in ApoE–/– mouse model.

Background Cancer‐associated cardiac cachexia (CACC) refers to cardiac injury in cancer patients in a malignant state, but preclinical animal models remain inadequately developed. Methods This study established CACC models in C57BL/6J and BALB/c mice using orthotopic, intra‐abdominal, and hematogenous metastatic tumor induction. Multimodal cardiac assessments, including echocardiography, transmission electron microscopy for myocardial ultrastructural and mitochondrial analysis, and ex vivo cardiomyocyte contractility assays, were systematically applied. Results Metastatic burden triggered CACC characterized by cardiac mass reduction, epicardial fat depletion, interstitial fibrosis, and electrocardiographic abnormalities. Histopathological analysis revealed cardiomyocyte atrophy, myofibrillar disarray, mitochondrial dysfunction, and ubiquitin‐mediated Myh6 degradation via MuRF‐1, accompanied by compensatory Myh7 upregulation. These findings mechanistically link tumor‐induced cachexia to cardiac dysfunction through contractile protein remodeling. Conclusion This work establishes a preclinical framework for targeting ubiquitin pathways to mitigate the morbidity of cancer‐related cardiopathy. Our integrated approach delineates a hierarchical progression from subcellular dysfunction to macroscopic cardiac deterioration. This work establishes a preclinical framework for targeting ubiquitin pathways to mitigate the morbidity of cancer‐related cardiopathy. Our integrated approach delineates a hierarchical progression from subcellular dysfunction to macroscopic cardiac deterioration. These findings mechanistically link tumor‐induced cachexia to cardiac dysfunction through contractile protein remodeling.

The association between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD) is controversial. HDL-C is one content type of high-density lipoprotein (HDL). HDL consists of diverse proteins and lipids and can be classified into different subclasses based on size, shape, charge, and density, and can change dynamically in disease states. Therefore, HDL-C levels alone cannot represent HDLs’ cardioprotective role. In this review, we summarized the methods for separating HDL subclasses, the studies on the association between HDL subclasses and cardiovascular risk (CVR), and the impact of lipid-modifying medications and nonpharmacological approaches (exercise training, dietary omega fatty acids, and low-density lipoprotein apheresis) on HDL subclasses. As HDL is a natural nanoplatform, recombinant HDLs (rHDLs) have been used as a delivery system in vivo by loading small interfering RNA, drugs, contrast agents, etc. Therefore, we further reviewed the HDL subclasses used in rHDLs and their advantages and disadvantages. This review would provide recommendations and guidance for future studies on HDL subclasses’ cardioprotective roles.

Mouse metabolic and behavioral phenotypes are tightly linked to strain, age and disease state, with distinct dysregulation in each disease model, underscoring the need for standardized preclinical experimental conditions.

An evaporation duct is a kind of atmospheric event with a refractive index exceeding the curvature of the Earth, which mostly exists on the ocean surface. Evaporation ducts have a great influence on radar, such as causing blind zones or achieving over-the-horizon detection. However, there is a lack of effective technology for evaporation duct detection, especially for passive methods. Global Navigation Satellite System Reflectometry (GNSS-R) has demonstrated potential in various remote sensing applications. However, its utilization for evaporation duct retrieval has not yet been successfully achieved. This study investigates the impact of evaporation ducts on GNSS-R delay maps (DMs), demonstrating that they elevate the non-specular point region, with the extent of this rising zone correlating with the evaporation duct height (EDH). Through semi-physical simulation, the rise signal is modeled. During a four-day experiment, GPS-R DMs with obvious features of evaporation ducts were repeatedly observed. Additionally, this study attempts to find the maximum code delay in the experimental data. The EDH is retrieved using the maximum code delay and GPS elevation angle, exhibiting a 4 m error relative to the reference model under the condition that all effective waveforms are successfully received. The results demonstrate that the GNSS-R offers a promising passive method for evaporation duct detection.

Mitochondrial transcription factor A (TFAM) plays a crucial role in mitochondrial fission beyond its canonical function in mtDNA maintenance. However, how TFAM regulates mitochondrial fission remains only partially understood. Fluorescence microscopy and TEM analyses showed that TFAM knockdown inhibited mitochondrial fission, whereas TFAM overexpression promoted mitochondrial fragmentation, and this mitochondrial morphology phenotype was supported by TEM-based ultrastructural observations in zebrafish embryos with tfam disruption. Depletion of Drp1 and MFF in TFAM-overexpressing cells led to elongated mitochondria, indicating that TFAM promotes Drp1- and MFF-dependent mitochondrial fission, which was further supported by the inhibitory effects of Mdivi-1 (Drp1 inhibitor) and Compound C (AMPK inhibitor) on TFAM-induced mitochondrial fission. Western blot and immunofluorescence analyses revealed that TFAM overexpression enhanced the mitochondrial localization and Sirt3-dependent mitochondrial protein deacetylation of Sirtuin 3 (Sirt3), increased phosphorylation of AMPK and MFF, and promoted mitochondrial recruitment of phosphorylated Drp1. Proteinase K protection and cycloheximide chase assays further supported intramitochondrial localization of Sirt3 and increased stability of mitochondrial Sirt3 upon TFAM overexpression. FRET imaging and co-immunoprecipitation demonstrated a direct TFAM-Sirt3 interaction mediated by TFAM’s HMG-box A domain. Targeted mutagenesis or deletion of the HMG-box A domain disrupted the TFAM-Sirt3 interaction, impaired Sirt3 mitochondrial localization and Sirt3-dependent mitochondrial protein deacetylation, and abolished TFAM-mediated mitochondrial fission. Analysis of TCGA data showed that high TFAM-SIRT3 co-expression is associated with overall survival across cancers, particularly in Kidney Renal Clear Cell Carcinoma (KIRC), where TFAM is downregulated (whereas SIRT3 is not). Together, these findings demonstrate that TFAM promotes mitochondrial fission via direct interaction with Sirt3, thereby activating the AMPK/MFF/Drp1 pathway.

Deep learning has been increasingly recognized as a promising tool in solving kinds of physical problems beyond powerful approximations. A multi-domain physics-informed neural network (mPINN) is proposed to solve the non-uniform heat conduction and conjugate natural convection with the discontinuity of temperature gradient on the interface. Local radial basis function method (LRBF) is applied to compute the case without the analytical solution and is regarded as the benchmark solver. Each physical domain matches a private neural network and all neural networks are connected by the shared information of temperature and heat flux on the interface. Joint training and separate training are utilized to minimize the loss function, which usually consists of the residual of boundary conditions, interface conditions and governing equations. Joint training minimizes the sum of all losses from neural networks with one shared optimizer, while separate training owns its private optimizer. Local adaptive activation function (LAAF) is used to accelerate the convergence and acquire a lower loss value when compared with its fixed counterpart. The numerical experiments on three types of residual points, uniform, Gauss-Lobatto and random, are conducted and it can be concluded that the uniform residual points can obtain the most accurate solution than the random and Gauss-Lobatto. Joint training is more accurate than the separate training when the number of residual points is relatively small, while the separate training performs better than the joint training for the large number of residual points. Numerous test cases on multi-domain heat transfer and fluid flow show the accuracy of the proposed mPINN. Local and global heat transfer rates show good agreements with the results from LRBF. Excepting the forward problems, the thermal conductivity ratio, the constant source and the characteristic parameters of natural convection are accurately learned from sparsely distributed data points.

The Global Navigation Satellite System Occultation Sounder II (GNOS-II) payload onboard the Chinese Fengyun-3E (FY-3E) satellite is the world’s first operational spaceborne mission that can utilize reflected signals from multiple navigation systems for Earth remote sensing. The satellite was launched into an 836-km early-morning polar orbit on 5 July 2021. Different GNSS signals show different characteristics in the observations and thus require different calibration methods. With an average data latency of less than 3 h, many near real-time applications are possible. This article first introduces the FY-3E/GNOS-II mission and instrument design, then describes the extensive calibration methods for the multi-GNSS measurements, and finally presents application results in the remote sensing of ocean surface winds, land soil moisture and sea ice extent. Especially, the ocean surface wind product has been used in operational applications such as assimilation in the numerical weather prediction model and monitoring of tropical cyclones. Currently, GNOS-II has been carried by FY-3E, FY-3F (launched in August 2023) and FY-3G (launched in April 2023). It will be also carried by future follow-on FY series and a more complete multi-GNSS reflectometry constellation will be established.