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Diabetic cardiomyopathy (DCM) is a major cause of morbidity and mortality in diabetic patients. Reactive oxygen species (ROS) produced by oxidative stress play an important role in the development of DCM. DCM involves abnormal energy metabolism, thereby reducing energy production. Exercise has been reported to be effective in protecting the heart against ROS accumulation during the development of DCM. We hypothesize that the AMPK/PGC-1α axis may play a crucial role in exercise-induced bioenergetic metabolism and aerobic respiration on oxidative stress parameters in the development of diabetic cardiomyopathy. Using a streptozotocin/high-fat diet mouse to generate a diabetic model, our aim was to evaluate the effects of exercise on the cardiac function, mitochondrial oxidative capacity, mitochondrial function, and cardiac expression of PGC-1α. Mice fed a high-fat diet were given MO-siPGC-1α or treated with AMPK inhibitor. Mitochondrial structure and effects of switching between the Warburg effect and aerobic respiration were analysed. Exercise improved blood pressure and systolic dysfunction in diabetic mouse hearts. The beneficial effects of exercise were also observed in a mitochondrial function study, as reflected by an enhanced oxidative phosphorylation level, increased membrane potential, and decreased ROS level and oxygen consumption. On the other hand, depletion of PGC-1α attenuated the effects of exercise on the enhancement of mitochondrial function. In addition, PGC-1α may be responsible for reversing the Warburg effect to aerobic respiration, thus enhancing mitochondrial metabolism and energy homoeostasis. In this study, we demonstrate the protective effects of exercise on shifting energy metabolism from fatty acid oxidation to glucose oxidation in an established diabetic stage. These data suggest that exercise is effective at ameliorating diabetic cardiomyopathy by improving mitochondrial function and reducing metabolic disturbances.

The gas hydrates in the pore space constitutionally affect the mechanical properties of gas hydrate-bearing sediments. The hydrates contribute to the mechanical properties of hydrate-bearing sediments by densifying, bearing and bonding effects. A discrete element model of hydrate-bearing silt was established by randomly filling hydrate particles into a silt-sized granular skeleton reservoir. Three ideal types of hydrate-bearing silt, namely, distributed particulate hydrate-bearing silt (type I), cluster hydrate-bearing silt (type II) and cemented cluster hydrate-bearing silt (type III) are proposed to study the mechanical effects of hydrate. One-dimensional loading (oedometer test) was applied to the numerical sample to investigate its stress evolution, volume change, bond degradation, coordination condition and stress transmission. The main conclusions are as follows. Type III sample exhibits a convex stress path due to bonding and then the stress path gradually returns to the pseudo linear stress path of type I sample due to bond breakage. The compression curve for the type II or type III sample exhibits a structural yield stress, which corresponds to abrupt bond breakage; the compression curves for types I, II and III evolve to be approximately coincident with each other at the end of compression. The average coordination number Z in type II or type III is approximately constant before widespread bond breakage, and then it will evolve to the curve of type I; the inflexion stress of the coordination numbers corresponds to the structural yield stress. The greatest magnitude of the mean stress bearing by hydrates in type II or type III sample is near the structural yield stress; the mean stresses ps - hb and ph - hb (created by bonded silt-hydrate and hydrate-hydrate contacts, respectively) in type III sample first increase under compression and then decrease due to widespread bond breakage, and they are exceeded by ps - hu and ph - hu (created by unbonded silt-hydrate and hydrate-hydrate contacts, respectively) after reaching the structural yield stress.

Background Therapeutic tumor vaccine (TTV) that induces tumor-specific immunity has enormous potentials in tumor treatment, but high heterogeneity and poor immunogenicity of tumor seriously impair its clinical efficacy. Herein, a novel NIR responsive tumor vaccine in situ (HA-PDA@IQ/DOX HG) was prepared by integrating hyaluronic acid functionalized polydopamine nanoparticles (HA-PDA NPs) with immune adjuvants (Imiquimod, IQ) and doxorubicin (DOX) into thermal-sensitive hydrogel. Results HA-PDA@IQ NPs with high photothermal conversion efficiency (41.2%) and T 1 -relaxation efficiency were using HA as stabilizer by the one-pot oxidative polymerization. Then, HA-PDA@IQ loaded DOX via π-π stacking and mixed with thermal-sensitive hydrogel to form the HA-PDA@IQ/DOX HG. The hydrogel-confined delivery mode endowed HA-PDA@IQ/DOX NPs with multiple photothermal ablation performance once injection upon NIR irradiation due to the prolonged retention in tumor site. More importantly, this mode enabled HA-PDA@IQ/DOX NPs to promote the DC maturation, memory T cells in lymphatic node as well as cytotoxic T lymphocytes in spleen. Conclusion Taken together, the HA-PDA@IQ/DOX HG could be served as a theranostic tumor vaccine for complete photothermal ablation to trigger robust antitumor immune responses.

Background Phototherapy-triggered immunogenic cell death (ICD) rarely elicits a robust antitumour immune response, partially due to low antigen exposure and inefficient antigen presentation. To address these issues, we developed novel methylene blue-loaded ovalbumin/polypyrrole nanoparticles (MB@OVA/PPY NPs) via oxidative polymerization and π–π stacking interactions. Results The as-prepared MB@OVA/PPY NPs with outstanding photothermal conversion efficiency (38%) and photodynamic properties were readily internalized into the cytoplasm and accumulated in the lysosomes and mitochondria. Upon 808 nm and 660 nm laser irradiation, the MB@OVA/PPY NPs not only ablated tumour cells by inducing local hyperthermia but also damaged residual tumour cells by generating a large amount of reactive oxygen species (ROS), finally triggering the release of many damage-associated molecular patterns (DAMPs). Moreover, the MB@OVA/PPY NPs synergized with DAMPs to promote the maturation and improve the antigen presentation ability of DCs in vitro and in vivo. Conclusions This work reported a PPY NPs-based nanoplatform to encapsulate the therepeutic proteins and absorb the functional molecules for combination therapy of tumours. The results demonstrated that the prepared MB@OVA/PPY NPs could be used as effective nanotherapeutic agents to eliminate solid tumours and trigger a powerful antitumour immune response.

In a previous study from our group, argon has shown to significantly attenuate brain injury, reduce brain inflammation and enhance M 2 microglia/macrophage polarization until 7 days after ischemic stroke. However, the long-term effects of argon have not been reported thus far. In the present study, we analyzed the underlying neuroprotective effects and potential mechanisms of argon, up to 30 days after ischemic stroke. Argon administration with a 3 h delay after stroke onset and 1 h after reperfusion demonstrated long-term neuroprotective effect by preserving the neurons at the ischemic boundary zone 30 days after stroke. Furthermore, the excessive microglia/macrophage activation in rat brain was reduced by argon treatment 30 days after ischemic insult. However, long-lasting neurological improvement was not detectable. More sensorimotor functional measures, age- and disease-related models, as well as further histological and molecular biological analyses will be needed to extend the understanding of argon’s neuroprotective effects and mechanism of action after ischemic stroke.

Primary liver cancer is the third leading cause of cancer death in the world, and the lack of effective treatments is the main reason for the high mortality. Corosolic acid (CA) has been proved to have antitumor activity. In this study, we found that CA can sensitize liver cancer cells to ferroptosis, which is a regulated form of cell death characterized by iron-dependent lipid peroxides reaching lethal levels. Here, we revealed that CA can inhibit glutathione (GSH) synthesis via HERPUD1, decreasing the cellular GSH level and causing liver cancer cells to become more sensitive to ferroptosis. Mechanistically, further studies found that HERPUD1 reduced the ubiquitination of the GSS-associated E3 ubiquitin ligase MDM2, which promoted ubiquitination of GSS, thereby inhibiting GSH synthesis to increase ferroptosis susceptibility. Importantly, a mouse xenograft model also demonstrated that CA inhibits tumor growth via HERPUD1. Collectively, our findings suggesting that CA is a candidate component for the development of treatments against liver cancer.

Background In recent years, argon has been shown to exert neuroprotective effects in an array of models. However, the mechanisms by which argon exerts its neuroprotective characteristics remain unclear. Accumulating evidence imply that argon may exert neuroprotective effects via modulating the activation and polarization of microglia/macrophages after ischemic stroke. In the present study, we analyzed the underlying neuroprotective effects of delayed argon application until 7 days after reperfusion and explored the potential mechanisms. Methods Twenty-one male Wistar rats underwent transient middle cerebral artery occlusion or sham surgery randomly for 2 h using the endoluminal thread model. Three hours after transient middle cerebral artery occlusion induction and 1 h after reperfusion, animals received either 50% vol Argon/50% vol O 2 or 50% vol N 2 /50% vol O 2 for 1 h. The primary outcome was the 6-point neuroscore from 24 h to d7 after reperfusion. Histological analyses including infarct volume, survival of neurons (NeuN) at the ischemic boundary zone, white matter integrity (Luxol Fast Blue), microglia/macrophage activation (Iba1), and polarization (Iba1/Arginase1 double staining) on d7 were conducted as well. Sample size calculation was performed using nQuery Advisor + nTerim 4.0. Independent t test, one-way ANOVA and repeated measures ANOVA were performed, respectively, for statistical analysis (SPSS 23.0). Results The 6-point neuroscore from 24 h to d7 after reperfusion showed that tMCAO Ar group displayed significantly improved neurological performance compared to tMCAO N 2 group ( p  = 0.026). The relative numbers of NeuN-positive cells in the ROIs of tMCAO Ar group significantly increased compared to tMCAO N 2 group ( p  = 0.010 for cortex and p  = 0.011 for subcortex). Argon significantly suppressed the microglia/macrophage activation as revealed by Iba1 staining ( p  = 0.0076) and promoted the M2 microglia/macrophage polarization as revealed by Iba1/Arginase 1 double staining ( p  = 0.000095). Conclusions Argon administration with a 3 h delay after stroke onset and 1 h after reperfusion significantly alleviated neurological deficit within the first week and preserved the neurons at the ischemic boundary zone 7 days after stroke. Moreover, argon reduced the excessive microglia/macrophage activation and promoted the switch of microglia/macrophage polarization towards the anti-inflammatory M2 phenotype. Studies making efforts to further elucidate the protective mechanisms and to benefit the translational application are of great value.

Some of the millions of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have developed new sequelae after recovering from the initial disease, termed post-acute sequelae of coronavirus disease 2019 (PASC). One symptom is anxiety, which is likely due to three etiologies: brain structural changes, neuroendocrine disruption, and neurotransmitter alterations. This review provides an overview of the current literature on the pathophysiological pathways linking coronavirus disease 2019 to anxiety, as well as the possible mechanisms of action in which an increasingly scrutinized treatment method, enhanced external counter-pulsation (EECP), is able to alleviate anxiety. SARS-CoV-2 triggers increased inflammatory cytokine production, as well as oxidative stress; these processes contribute to the aforementioned three etiologies. The potential treatment approach of EECP, involving sequenced inflation and deflation of specifically-placed airbags, has become of increasing interest, as it has been found to alleviate PASC-associated anxiety by improving patient cardiovascular function. These functional improvements were achieved by EECP stimulating anti-inflammatory and pro-angiogenic processes, as well as improving endothelial cell function and coronary blood flow, partially via counteracting against the negative effects of SARS-CoV-2 infection on the renin–angiotensin–aldosterone system. Therefore, EECP could promote both psychosomatic and cardiac rehabilitation. Further research, though, is still needed to fully determine its benefits and mechanism of action.

Transcatheter aortic valve replacement (TAVR) is a relatively new treatment method for aortic stenosis (AS) and has been demonstrated to be suitable for patients with varying risk levels. Indeed, among high-risk patients, TAVR outcomes are comparable to, or even better, than that of the traditional surgical aortic valve replacement (SAVR) method. TAVR outcomes, with respect to post-surgical functional capacity and quality of life, have also been found to be improved, especially when combined with cardiac rehabilitation (CR). CR is a multidisciplinary system, which integrates cardiology with other medical disciplines, such as sports, nutritional, mind-body, and behavioral medicine. It entails the development of appropriate medication, exercise, and diet prescriptions, along with providing psychological support, ensuring the cessation of smoking, and developing risk factor management strategies for cardiovascular disease patients. However, even with CR being able to improve TAVR outcomes and reduce post-surgical mortality rates, it still has largely been underutilized in clinical settings. This article reviews the usage of CR during both pre-and postoperative periods for valvular diseases, and the factors involved in influencing subsequent patient prognoses, thereby providing a direction for subsequent research and clinical applications.

To address the building settlement issues induced by an urban geological hazard in a northern city, this study utilizes settlement monitoring data from 16 high-rise buildings. The non-uniform temporal data were processed using the Akima interpolation method to construct a settlement prediction model based on a backpropagation (BP) neural network. The model’s predictive performance was validated against traditional approaches, including the hyperbolic and exponential curve methods, and was further employed to estimate the stabilization time of building settlements. Additionally, spatiotemporal characteristics of settlement behavior under the influence of geological hazards were investigated through a comparative analysis of deformation data across the building group. The results demonstrate that the BP neural network model achieves a 58.3% improvement in predictive accuracy compared to traditional empirical methods, effectively capturing the settlement evolution of buildings. The model also provides reliable predictions for the time required for buildings to reach a stable state. The temporal evolution of building settlement exhibits a distinct three-stage pattern: (1) an initial abrupt phase dominated by rapid water and soil loss; (2) a rapid settlement phase primarily driven by the consolidation of sandy and clayey soils; and (3) a slow consolidation phase governed by the prolonged consolidation of cohesive soils. Spatially, building deformations show significant regional heterogeneity, and the existence of potential finger-like preferential pathways for water and soil loss appears to exert a substantial influence on differential settlements.