A Homozygous Variant in NAA60 Is Associated with Primary Familial Brain Calcification.

BACKGROUND: Primary familial brain calcification (PFBC) is a monogenic disorder characterized by bilateral calcifications in the brain. The genetic basis remains unknown in over half of the PFBC patients, indicating the existence of additional novel causative genes. NAA60 was a recently reported novel causative gene for PFBC. OBJECTIVE: The aim was to identify the probable novel causative gene in an autosomal recessive inherited PFBC family. METHODS: We performed a comprehensive genetic study on a consanguineous Chinese family with 3 siblings diagnosed with PFBC. We evaluated the effect of the variant in a probable novel causative gene on the protein level using Western blot, immunofluorescence, and coimmunoprecipitation. Possible downstream pathogenic mechanisms were further explored in gene knockout (KO) cell lines and animal models. RESULTS: We identified a PFBC co-segregated homozygous variant of c.460_461del (p.D154Lfs*113) in NAA60. Functional assays showed that this variant disrupts NAA60 protein localization to Golgi and accelerated protein degradation. The mutant NAA60 protein alters its interaction with the PFBC-related proteins PiT2 and XPR1, affecting intracellular phosphate homeostasis. Further mass spectrometry analysis in NAA60 KO cell lines revealed decreased expression of multiple brain calcification-associated proteins, including reduced folate carrier (RFC), a folate metabolism-related protein. CONCLUSIONS: Our study replicated the identification of NAA60 as a novel causative gene for autosomal recessive PFBC, demonstrating our causative variant leads to NAA60 loss of function. The NAA60 loss of function disrupts not only PFBC-related proteins (eg, PiT2 and XPR1) but also a wide range of other brain calcification-associated membrane protein substrates (eg, RFC), and provided a novel probable pathogenic mechanism for PFBC. © 2024 International Parkinson and Movement Disorder Society.

Determinants of successful disease control through voluntary quarantine dynamics on social networks.

In the wake of epidemics, quarantine measures are typically recommended by health authorities or governments to help control the spread of the disease. Compared with mandatory quarantine, voluntary quarantine offers individuals the liberty to decide whether to isolate themselves in case of infection exposure, driven by their personal assessment of the trade-off between economic loss and health risks as well as their own sense of social responsibility and concern for public health. To better understand self-motivated health behavior choices under these factors, here we incorporate voluntary quarantine into an endemic disease model - the susceptible-infected-susceptible (SIS) model - and perform comprehensive agent-based simulations to characterize the resulting behavior-disease interactions in structured populations. We quantify the conditions under which voluntary quarantine will be an effective intervention measure to mitigate disease burden. Furthermore, we demonstrate how individual decision-making factors, including the level of temptation to refrain from quarantine and the degree of social compassion, impact compliance levels of voluntary quarantines and the consequent collective disease mitigation efforts. We find that successful disease control requires either a sufficiently low level of temptation or a sufficiently high degree of social compassion, such that even complete containment of the epidemic is attainable. In addition to well-mixed populations, we have also analyzed other more realistic social networks of contacts, including spatial lattices, small-world networks, and real social networks. Our work offers new insights into the fundamental social dilemma aspect of disease control through non-pharmaceutical interventions, such as voluntary quarantine and isolation, where the collective outcome of individual decision-making is crucial.

Macrophage-derived extracellular vesicles represent a promising endogenous iron-chelating therapy for iron overload and cardiac injury in myocardial infarction.

BACKGROUND: Cardiac iron overload and ferroptosis greatly contribute to the poor prognosis of myocardial infarction (MI). Iron chelator is one of the most promising strategies for scavenging excessive iron and alleviating cardiac dysfunction post MI. However, various side effects of existing chemical iron chelators restrict their clinical application, which calls for a more viable and safer approach to protect against iron injury in ischemic hearts. RESULTS: In this study, we isolated macrophage-derived extracellular vesicles (EVs) and identified macrophage-derived EVs as a novel endogenous biological chelator for iron. The administration of macrophage-derived EVs effectively reduced iron overload in hypoxia-treated cardiomyocytes and hearts post MI. Moreover, the oxidative stress and ferroptosis induced by excessive iron were considerably suppressed by application of macrophage-derived EVs. Mechanistically, transferrin receptor (TfR), which was inherited from macrophage to the surface of EVs, endowed EVs with the ability to bind to transferrin and remove excess protein-bound iron. EVs with TfR deficiency exhibited a loss of function in preventing MI-induced iron overload and protecting the heart from MI injury. Furthermore, the iron-chelating EVs were ultimately captured and processed by macrophages in the liver. CONCLUSIONS: These results highlight the potential of macrophage-derived EVs as a powerful endogenous candidate for iron chelation therapy, offering a novel and promising therapeutic approach to protect against iron overload-induced injury in MI and other cardiovascular diseases.

The Role of Microvascular Obstruction and Intra-Myocardial Hemorrhage in Reperfusion Cardiac Injury. Analysis of Clinical Data.

Microvascular obstruction (MVO) of coronary arteries promotes an increase in mortality and major adverse cardiac events in patients with acute myocardial infarction (AMI) and percutaneous coronary intervention (PCI). Intramyocardial hemorrhage (IMH) is observed in 41-50% of patients with ST-segment elevation myocardial infarction and PCI. The occurrence of IMH is accompanied by inflammation. There is evidence that microthrombi are not involved in the development of MVO. The appearance of MVO is associated with infarct size, the duration of ischemia of the heart, and myocardial edema. However, there is no conclusive evidence that myocardial edema plays an important role in the development of MVO. There is evidence that platelets, inflammation, Ca 2 + overload, neuropeptide Y, and endothelin-1 could be involved in the pathogenesis of MVO. The role of endothelial cell damage in MVO formation remains unclear in patients with AMI and PCI. It is unclear whether nitric oxide production is reduced in patients with MVO. Only indirect evidence on the involvement of inflammation in the development of MVO has been obtained. The role of reactive oxygen species (ROS) in the pathogenesis of MVO is not studied. The role of necroptosis and pyroptosis in the pathogenesis of MVO in patients with AMI and PCI is also not studied. The significance of the balance of thromboxane A2, vasopressin, angiotensin II, and prostacyclin in the formation of MVO is currently unknown. Conclusive evidence regarding the role of coronary artery spasm in the development of MVhasn't been established. Correlation analysis of the neuropeptide Y, endothelin-1 levels and the MVO size in patients with AMI and PCI has not previously been performed. It is unclear whether epinephrine aggravates reperfusion necrosis of cardiomyocytes. Dual antiplatelet therapy improves the efficacy of PCI in prevention of MVO. It is unknown whether epinephrine or L-type Ca 2 + channel blockers result in the long-term improvement of coronary blood flow in patients with MVO.

Evolutionary Game Dynamics with Environmental Feedback in a Network with Two Communities.

Recent developments of eco-evolutionary models have shown that evolving feedbacks between behavioral strategies and the environment of game interactions, leading to changes in the underlying payoff matrix, can impact the underlying population dynamics in various manners. We propose and analyze an eco-evolutionary game dynamics model on a network with two communities such that players interact with other players in the same community and those in the opposite community at different rates. In our model, we consider two-person matrix games with pairwise interactions occurring on individual edges and assume that the environmental state depends on edges rather than on nodes or being globally shared in the population. We analytically determine the equilibria and their stability under a symmetric population structure assumption, and we also numerically study the replicator dynamics of the general model. The model shows rich dynamical behavior, such as multiple transcritical bifurcations, multistability, and anti-synchronous oscillations. Our work offers insights into understanding how the presence of community structure impacts the eco-evolutionary dynamics within and between niches.

[Dielectric properties of tidal volume changes in rabbit lung tissue in the 100 MHz~1 GHz band].

This paper investigates the variation of lung tissue dielectric properties with tidal volume under in vivo conditions to provide reliable and valid a priori information for techniques such as microwave imaging. In this study, the dielectric properties of the lung tissue of 30 rabbits were measured in vivo using the open-end coaxial probe method in the frequency band of 100 MHz to 1 GHz, and 6 different sets of tidal volumes (30, 40, 50, 60, 70, 80 mL) were set up to study the trends of the dielectric properties, and the data at 2 specific frequency points (433 and 915 MHz) were analyzed statistically. It was found that the dielectric coefficient and conductivity of lung tissue tended to decrease with increasing tidal volume in the frequency range of 100 MHz to 1 GHz, and the differences in the dielectric properties of lung tissue for the 6 groups of tidal volumes at 2 specific frequency points were statistically significant. This paper showed that the dielectric properties of lung tissue tend to vary non-linearly with increasing tidal volume. Based on this, more accurate biological tissue parameters can be provided for bioelectromagnetic imaging techniques such as microwave imaging, which could provide a scientific basis and experimental data support for the improvement of diagnostic methods and equipment for lung diseases.

The influence of different spontaneous breathing trials on regional ventilation distribution in patients with prolonged mechanical ventilation.

OBJECTIVE: This study aimed to explore the influence of different spontaneous breathing trials (SBTs) on regional ventilation distribution in patients with prolonged mechanical ventilation (PMV). METHODS: A total of 24 patients with PMV were analyzed retrospectively. They received three different SBT modes which are automatic tube compensation (ATC), continuous positive airway pressure (CPAP), and T-piece (TP), over three days, and every SBT lasted two hours. Electrical impedance tomography (EIT) was used to monitor the SBT process and five-minute EIT data from five periods (pre-SBT which is t0, at the beginning and the end of the first hour SBT are t1 and t2, at the beginning and the end of the second hour SBT are t3 and t4) were analyzed. RESULTS: In all PMV patients, the temporal skew of aeration (TSA) values at t3 were significantly different in three SBTs (ATC: 18.18±22.97; CPAP: 20.42±17.01; TP:11.26±11.79; p=0.05). In the weaning success group, TSA (t1) values were significantly different too (ATC: 11.11±13.88; CPAP: 19.09±15.77; TP: 9.09±12.74; p=0.04). In the weaning failure group, TSA (t4) values were significantly different in three SBTs (ATC: 36.67±18.46; CPAP: 15.38±11.69; TP: 17.65±17.93; p=0.04). The patient's inspiratory effort (Global flow index at t1) in patients with weaning failure under CPAP (3.51±4.31) was significantly higher than that in the ATC (1.15±1.47) and TP (0.89±1.28). The SBT mode with the best ventilation uniformity may be the one that activates the respiratory muscles the most which may be the optimal SBT. The SBT mode of most uniform ventilation distribution settings varies from patient to patient. CONCLUSION: The regional ventilation distribution was different for each individual, making the SBT with the best ventilation distribution of patients need to be personalized. EIT is a tool that can be considered for real-time assessment.

Classification of Three Anesthesia Stages Based on Near-Infrared Spectroscopy Signals.

Proper monitoring of anesthesia stages can guarantee the safe performance of clinical surgeries. In this study, different anesthesia stages were classified using near-infrared spectroscopy (NIRS) signals with machine learning. The cerebral hemodynamic variables of right proximal oxyhemoglobin (HbO2) in maintenance (MNT), emergence (EM) and the consciousness (CON) stage were collected and then the differences between the three stages were compared by phase-amplitude coupling (PAC). Then combined with time-domain including linear (mean, standard deviation, max, min and range), nonlinear (sample entropy) and power in frequency-domain signal features, feature selection was performed and finally classification was performed by support vector machine (SVM) classifier. The results show that the PAC of the NIRS signal was gradually enhanced with the deepening of anesthesia level. A good three-classification accuracy of 69.27% was obtained, which exceeded the result of classification of any single category feature. These results indicate the feasibility of NIRS signals in performing three or even more anesthesia stage classifications, providing insight into the development of new anesthesia monitoring modalities.

Full-Space Electric Field in Mo-Decorated Zn2In2S5 Polarization Photocatalyst for Oriented Charge Flow and Efficient Hydrogen Production.

Integration of photocatalytic hydrogen (H2) evolution with oxidative organic synthesis presents a highly attractive strategy for the simultaneous production of clean H2 fuel and high-value chemicals. However, the sluggish dynamics of photogenerated charge carriers across the photocatalysts result in low photoconversion efficiency, hindering the wide applications of such a technology. Herein, this work overcomes this limitation by inducing the full-space electric field via charge polarization engineering on a Mo cluster-decorated Zn2In2S5 (Mo-Zn2In2S5) photocatalyst. Specifically, this full-space electric field arises from a cascade of the bulk electric field (BEF) and local surface electric field (LSEF), triggering the oriented migration of photogenerated electrons from [Zn-S] regions to [In-S] regions and eventually to Mo cluster sites, ensuring efficient separation of bulk and surface charge carriers. Moreover, the surface Mo clusters induce a tip enhancement effect to optimize charge transfer behavior by augmenting electrons and proton concentration around the active sites on the basal plane of Zn2In2S5. Notably, the optimized Mo1.5-Zn2In2S5 catalyst achieves exceptional H2 and benzaldehyde production rates of 34.35 and 45.31 mmol gcat -1 h-1, respectively, outperforming pristine ZnIn2S4 by 3.83- and 4.15-fold. These findings mark a significant stride in steering charge flow for enhanced photocatalytic performance.

Deterministic theory of evolutionary games on temporal networks.

Recent empirical studies have revealed that social interactions among agents in realistic networks merely exist intermittently and occur in a particular sequential order. However, it remains unexplored how to theoretically describe evolutionary dynamics of multiple strategies on temporal networks. Herein, we develop a deterministic theory for studying evolutionary dynamics of any [Formula: see text] pairwise games in structured populations where individuals are connected and organized by temporally activated edges. In the limit of weak selection, we derive replicator-like equations with a transformed payoff matrix characterizing how the mean frequency of each strategy varies over time, and then obtain critical conditions for any strategy to be evolutionarily stable on temporal networks. Interestingly, the re-scaled payoff matrix is a linear combination of the original payoff matrix with an additional one describing local competitions between any pair of different strategies, whose weights are solely determined by network topology and selection intensity. As a particular example, we apply the deterministic theory to analysing the impacts of temporal networks in the mini-ultimatum game, and find that temporally networked population structures result in the emergence of fairness. Our work offers theoretical insights into the subtle effects of network temporality on evolutionary game dynamics.

Determinants of successful disease control through voluntary quarantine dynamics on social networks.

In the wake of epidemics, quarantine measures are typically recommended by health authorities or governments to help control the spread of the disease. Compared with mandatory quarantine, voluntary quarantine offers individuals the liberty to decide whether to isolate themselves in case of infection exposure, driven by their personal assessment of the trade-off between economic loss and health risks as well as their own sense of social responsibility and concern for public health. To better understand self-motivated health behavior choices under these factors, here we incorporate voluntary quarantine into an endemic disease model -- the susceptible-infected-susceptible (SIS) model -- and perform comprehensive agent-based simulations to characterize the resulting behavior-disease interactions in structured populations. We quantify the conditions under which voluntary quarantine will be an effective intervention measure to mitigate disease burden. Furthermore, we demonstrate how individual decision-making factors, including the level of temptation to refrain from quarantine and the degree of social compassion, impact compliance levels of voluntary quarantines and the consequent collective disease mitigation efforts. We find that successful disease control requires either a sufficiently low level of temptation or a sufficiently high degree of social compassion, such that even complete containment of the epidemic is attainable. In addition to well-mixed populations, our simulation results are applicable to other more realistic social networks of contacts, including spatial lattices, small-world networks, and real social networks. Our work offers new insights into the fundamental social dilemma aspect of disease control through non-pharmaceutical interventions, such as voluntary quarantine and isolation, where the collective outcome of individual decision-making is crucial.

Elevated Efficiency and Stability of Hole-Transport-Layer-Free Perovskite Solar Cells Triggered by Surface Engineering.

Surface engineering is one of the important strategies to enhance the power conversion efficiency (PCE) and stability of perovskite solar cells (PSCs). Herein, 2-chloro-1,3-dimethylimidazolidinium hexafluorophosphate (CIP) was introduced into PSCs to passivate the defects of the perovskite films. There are many F atoms in CIP molecules that have strong electronegativity and hydrophobicity. F groups can interact with Pb2+ defects, inhibit interface recombination, improve the interaction between the CIP ionic liquid and perovskite film, and reduce the defect density of perovskites, thus improving the stability of perovskite devices. Density functional theory calculation reveals that CIP can interact with uncoordinated Pb2+ in perovskites through coordination, reduce the defects of perovskite films, and inhibit nonradiation recombination. The ITO/SnO2/MAPbI3/CIP/carbon devices without hole transport layers possessed the highest PCE of 17.06%. Moreover, the unencapsulated device remains at 98.18% of the initial efficiency stored in 30-40% relative humidity for 850 h. This strategy provides an effective reference for enhancing the performance of PSCs.

Multi-Path Fusion in SFCF-Net for Enhanced Multi-Frequency Electrical Impedance Tomography.

Multi-frequency electrical impedance tomography (mfEIT) offers a nondestructive imaging technology that reconstructs the distribution of electrical characteristics within a subject based on the impedance spectral differences among biological tissues. However, the technology faces challenges in imaging multi-class lesion targets when the conductivity of background tissues is frequency-dependent. To address these issues, we propose a spatial-frequency cross-fusion network (SFCF-Net) imaging algorithm, built on a multi-path fusion structure. This algorithm uses multi-path structures and hyper-dense connections to capture both spatial and frequency correlations between multi-frequency conductivity images, which achieves differential imaging for lesion targets of multiple categories through cross-fusion of information. According to both simulation and physical experiment results, the proposed SFCF-Net algorithm shows an excellent performance in terms of lesion imaging and category discrimination compared to the weighted frequency-difference, U-Net, and MMV-Net algorithms. The proposed algorithm enhances the ability of mfEIT to simultaneously obtain both structural and spectral information from the tissue being examined and improves the accuracy and reliability of mfEIT, opening new avenues for its application in clinical diagnostics and treatment monitoring.

Perioperative immunotherapy for stage II-III non-small cell lung cancer: a meta-analysis base on randomized controlled trials.

Background: In recent years, we have observed the pivotal role of immunotherapy in improving survival for patients with non-small cell lung cancer (NSCLC). However, the effectiveness of immunotherapy in the perioperative (neoadjuvant + adjuvant) treatment of resectable NSCLC remains uncertain. We conducted a comprehensive analysis of its antitumor efficacy and adverse effects (AEs) by pooling data from the KEYNOTE-671, NADIM II, and AEGEAN clinical trials. Methods: For eligible studies, we searched seven databases. The randomized controlled trials (RCTs) pertaining to the comparative analysis of combination neoadjuvant platinum-based chemotherapy plus perioperative immunotherapy (PIO) versus perioperative placebo (PP) were included. Primary endpoints were overall survival (OS) and event-free survival (EFS). Secondary endpoints encompassed drug responses, AEs, and surgical outcomes. Results: Three RCTs (KEYNOTE-671, NADIM II, and AEGEAN) were included in the final analysis. PIO group (neoadjuvant platinum-based chemotherapy plus perioperative immunotherapy) exhibited superior efficacy in OS (hazard ratio [HR]: 0.63 [0.49-0.81]), EFS (HR: 0.61 [0.52, 0.72]), objective response rate (risk ratio [RR]: 2.21 [1.91, 2.54]), pathological complete response (RR: 4.36 [3.04, 6.25]), major pathological response (RR: 2.79 [2.25, 3.46]), R0 resection rate (RR: 1.13 [1.00, 1.26]) and rate of adjuvant treatment (RR: 1.08 [1.01, 1.15]) compared with PP group (neoadjuvant platinum-based chemotherapy plus perioperative placebo). In the subgroup analysis, EFS tended to favor the PIO group in almost all subgroups. BMI (>25), T stage (IV), N stage (N1-N2) and pathological response (with pathological complete response) were favorable factors in the PIO group. In the safety assessment, the PIO group exhibited higher rates of serious AEs (28.96% vs. 23.51%) and AEs leading to treatment discontinuation (12.84% vs. 5.81%). Meanwhile, although total adverse events, grade 3-5 adverse events, and fatal adverse events tended to favor the PP group, the differences were not statistically significant. Conclusion: PIO appears to be superior to PP for resectable stage II-III NSCLC, demonstrating enhanced survival and pathological responses. However, its elevated adverse event (AE) rate warrants careful consideration. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023487475.

Deoxynivalenol Detection beyond the Limit in Wheat Flour Based on the Fluorescence Hyperspectral Imaging Technique.

Deoxynivalenol (DON) is a harmful fungal toxin, and its contamination in wheat flour poses a food safety concern globally. This study proposes the combination of fluorescence hyperspectral imaging (FHSI) and qualitative discrimination methods for the detection of excessive DON content in wheat flour. Wheat flour samples were prepared with varying DON concentrations through the addition of trace amounts of DON using the wet mixing method for fluorescence hyperspectral image collection. SG smoothing and normalization algorithms were applied for original spectra preprocessing. Feature band selection was carried out by applying the successive projection algorithm (SPA), uninformative variable elimination (UVE), competitive adaptive reweighted sampling (CARS), and the random frog algorithm on the fluorescence spectrum. Random forest (RF) and support vector machine (SVM) classification models were utilized to identify wheat flour samples with DON concentrations higher than 1 mg/kg. The results indicate that the SG-CARS-RF and SG-CARS-SVM models showed better performance than other models, achieving the highest recall rate of 98.95% and the highest accuracy of 97.78%, respectively. Additionally, the ROC curves demonstrated higher robustness on the RF algorithm. Deep learning algorithms were also applied to identify the samples that exceeded safety standards, and the convolutional neural network (CNN) model achieved a recognition accuracy rate of 97.78% for the test set. In conclusion, this study demonstrates the feasibility and potential of the FHSI technique in detecting DON infection in wheat flour.

Modulating charge oriented accumulation via interfacial chemical-bond on In2O3/Bi2MoO6 heterostructures for photocatalytic nitrogen fixation.

Photocatalytic nitrogen fixation presents an eco-friendly approach to converting atmospheric nitrogen into ammonia (NH3), but the process faces challenges due to rapid interface charge recombination. Here, we report an innovative charge transfer and oriented accumulation strategy using an In-O-Mo bond-modulated S-scheme heterostructure composed of In2O3/Bi2MoO6 (In/BMO) synthesized using a simple electrostatic assembly. The unique interfacial arrangement with optimal photocatalyst configuration (3 % In/BMO) enabled enhanced photogenerated electron separation and transfer, leading to a remarkable nitrogen fixation rate of approximately 150.9 µmol·gcat-1·h-1 under visible light irradiation. The performance of the photocatalyst was 9-fold and 27-fold higher than that of its pristine components, Bi2MoO6 and In2O3, respectively. The experimental and theoretical evaluation deemed interfacial In-O-Mo bonds crucial for rapid transfer and charge-oriented accumulation. Whereas the generated internal electric field drove the spatial separation and transfer of photo-generated electrons and holes, significantly enhancing the photocatalytic N2-to-NH3 conversion efficiency. The proposed work lays the foundation for designing S-scheme heterostructures with highly efficient interfacial bonds, offering a promising avenue for substantial improvements in photocatalytic nitrogen fixation.

Containing misinformation: Modeling spatial games of fake news.

The spread of fake news on social media is a pressing issue. Here, we develop a mathematical model on social networks in which news sharing is modeled as a coordination game. We use this model to study the effect of adding designated individuals who sanction fake news sharers (representing, for example, correction of false claims or public shaming of those who share such claims). By simulating our model on synthetic square lattices and small-world networks, we demonstrate that social network structure allows fake news spreaders to form echo chambers and more than doubles fake news' resistance to distributed sanctioning efforts. We confirm our results are robust to a wide range of coordination and sanctioning payoff parameters as well as initial conditions. Using a Twitter network dataset, we show that sanctioners can help contain fake news when placed strategically. Furthermore, we analytically determine the conditions required for peer sanctioning to be effective, including prevalence and enforcement levels. Our findings have implications for developing mitigation strategies to control misinformation and preserve the integrity of public discourse.

[Role of mitochondrial dynamics in diabetic cardiomyopathy and regulatory mechanisms].

Cardiovascular complications are the leading cause of death in diabetic patients. Among them, diabetic cardiomyopathy (DCM) is a type of specific cardiomyopathy excluding myocardial damage caused by hypertension and coronary heart disease. It is characterized by abnormal metabolism of cardiomyocytes and gradual decline of cardiac function. The clinical manifestations of DCM are impaired diastolic function in early stage and impaired systolic function in late stage. Eventually it developed into heart failure. Mitochondria are the main organelles that provide energy in cardiomyocytes. Mitochondrial dynamics refers to the dynamic process of mitochondrial fusion and fission, which is an important approach for mitochondrial quality control. Mitochondrial dynamics plays a crucial role in maintaining mitochondrial homeostasis and cardiac function. The proteins that regulate mitochondrial fission are mainly Drp1 and its receptors, Fis1, MFF, MiD49 and MiD51. The protein that performs mitochondrial outer membrane fusion is Mfn1/2, and the inner membrane fusion protein is Opa1. This paper reviews recent progress on mitochondrial dynamics in DCM. The main contents are as follows: mitochondrial dynamics imbalance in both type 1 and 2 DCM is manifested as increased fission and inhibited fusion. The molecular mechanism of the former is mainly associated with up-regulated Drp1 and down-regulated Opa1, while the molecular mechanism of the latter is mainly associated with up-regulated Drp1 and down-regulated Mfn1/2. Increased mitochondrial fission and inhibited fusion can lead to mitochondrial dysfunction and promote the development of DCM. The active ingredients of the traditional Chinese medicine such as punicalagin, paeonol and endogenous substance melatonin can improve mitochondrial function and alleviate the symptoms of DCM by inhibiting mitochondrial fission or promoting mitochondrial fusion. This article is helpful to further understand the role and mechanism of mitochondrial dynamics in DCM, and provide new treatment methods and intervention strategies for clinical DCM patients based on mitochondrial dynamics.

Angiotensin 1-7 increases cardiac tolerance to ischemia/reperfusion and mitigates adverse remodeling of the heart-The signaling mechanism.

BACKGROUND: The high mortality rate of patients with acute myocardial infarction (AMI) remains the most pressing issue of modern cardiology. Over the past 10 years, there has been no significant reduction in mortality among patients with AMI. It is quite obvious that there is an urgent need to develop fundamentally new drugs for the treatment of AMI. Angiotensin 1-7 has some promise in this regard. OBJECTIVE: The objective of this article is analysis of published data on the cardioprotective properties of angiotensin 1-7. METHODS: PubMed, Scopus, Science Direct, and Google Scholar were used to search articles for this study. RESULTS: Angiotensin 1-7 increases cardiac tolerance to ischemia/reperfusion and mitigates adverse remodeling of the heart. Angiotensin 1-7 can prevent not only ischemic but also reperfusion cardiac injury. The activation of the Mas receptor plays a key role in these effects of angiotensin 1-7. Angiotensin 1-7 alleviates Ca2+ overload of cardiomyocytes and reactive oxygen species production in ischemia/reperfusion (I/R) of the myocardium. It is possible that both effects are involved in angiotensin 1-7-triggered cardiac tolerance to I/R. Furthermore, angiotensin 1-7 inhibits apoptosis of cardiomyocytes and stimulates autophagy of cells. There is also indirect evidence suggesting that angiotensin 1-7 inhibits ferroptosis in cardiomyocytes. Moreover, angiotensin 1-7 possesses anti-inflammatory properties, possibly achieved through NF-kB activity inhibition. Phosphoinositide 3-kinase, Akt, and NO synthase are involved in the infarct-reducing effect of angiotensin 1-7. However, the specific end-effector of the cardioprotective impact of angiotensin 1-7 remains unknown. CONCLUSION: The molecular nature of the end-effector of the infarct-limiting effect of angiotensin 1-7 has not been elucidated. Perhaps, this end-effector is the sarcolemmal KATP channel or the mitochondrial KATP channel.

The role of ß-adrenergic receptors in the regulation of cardiac tolerance to ischemia/reperfusion. Why do ß-adrenergic receptor agonists and antagonists protect the heart?

BACKGROUND: Catecholamines and ß-adrenergic receptors (ß-ARs) play an important role in the regulation of cardiac tolerance to the impact of ischemia and reperfusion. This systematic review analyzed the molecular mechanisms of the cardioprotective activity of ß-AR ligands. METHODS: We performed an electronic search of topical articles using PubMed databases from 1966 to 2023. We cited original in vitro and in vivo studies and review articles that documented the cardioprotective properties of ß-AR agonists and antagonists. RESULTS: The infarct-reducing effect of ß-AR antagonists did not depend on a decrease in the heart rate. The target for ß-blockers is not only cardiomyocytes but also neutrophils. ß1-blockers (metoprolol, propranolol, timolol) and the selective ß2-AR agonist arformoterol have an infarct-reducing effect in coronary artery occlusion (CAO) in animals. Antagonists of ß1- and ß2-АR (metoprolol, propranolol, nadolol, carvedilol, bisoprolol, esmolol) are able to prevent reperfusion cardiac injury. All ß-AR ligands that reduced infarct size are the selective or nonselective ß1-blockers. It was hypothesized that ß1-AR blocking promotes an increase in cardiac tolerance to I/R. The activation of ß1-AR, ß2-AR, and ß3-AR can increase cardiac tolerance to I/R. The cardioprotective effect of ß-AR agonists is mediated via the activation of kinases and reactive oxygen species production. CONCLUSIONS: It is unclear why ß-blockers with the similar receptor selectivity have the infarct-sparing effect while other ß-blockers with the same selectivity do not affect infarct size. What is the molecular mechanism of the infarct-reducing effect of ß-blockers in reperfusion? Why did in early studies ß-blockers decrease the mortality rate in patients with acute myocardial infarction (AMI) and without reperfusion and in more recent studies ß-blockers had no effect on the mortality rate in patients with AMI and reperfusion? The creation of more effective ß-AR ligands depends on the answers to these questions.