[Consumption status and growth trends of dairy products among children and adolescents in China from 1991 to 2018].

OBJECTIVE: To explore the dairy consumption among children and adolescents aged 7-17 in China. METHODS: 10 rounds of follow-up data from the "China Health and Nutrition Survey" from 1991 to 2018 were collected, and individuals aged 7-17 were selected as the study subjects. Dietary data was collected by using 3-day 24-hour dietary review method and household weighing accounting method(edible oils and seasonings). Dairy consumption was calculated by converting various dairy products into liquid milk intake using the China Food Composition. After excluding those with missing demographic information, missing data from the "3 days and 24 hours" dietary survey, and abnormal daily energy intake, 18 529 participants were included in the final analysis. Joinpoint regression model was used to analyze the trend of changes in dairy intake. RESULTS: The dairy consumption rate increased from 2.8% in 1991 to 42.3% in 2018, while it increased from 8.4% to 58.8% in urban and from 0.9% to 32.1% in rural areas. Meanwhile, the proportion of people whose dairy intake reaches the recommended intake(300 g/d) increased from 0.2% to 3.0%, and the proportion in rural area was 2.0%, which was lower than that in urban areas(4.9%). From 1991 to 2018, dairy intake increased at a rate of 12.97%(P=0.02), and the growth rate of urban and rural areas were 9.79%(P=0.03) and 15.67%(P<0.01), respectively. There was a faster growth trend from 1991-2004 compared to 2004-2018. The growth rate in urban and rural areas also showed different growth trends. CONCLUSION: The dairy intake of children and adolescents aged 7-17 in China improved significantly from 1991 to 2018, with higher consumption rate in urban areas than in rural areas, but it still need to be improved for health.

Mitochondrial quality control in cardiac ischemia/reperfusion injury: new insights into mechanisms and implications.

The current effective method for the treatment of myocardial infarction is timely restoration of the blood supply to the ischemic area of the heart. Although reperfusion is essential for reestablishing oxygen and nutrient supplies, it often leads to additional myocardial damage, creating an important clinical dilemma. Reports from long-term studies have confirmed that mitochondrial damage is the critical mechanism in cardiac ischemia/reperfusion (I/R) injury. Mitochondria are dynamic and possess a quality control system that targets mitochondrial quantity and quality by modifying mitochondrial fusion, fission, mitophagy, and biogenesis and protein homeostasis to maintain a healthy mitochondrial network. The system of mitochondrial quality control involves complex molecular machinery that is highly interconnected and associated with pathological changes such as oxidative stress, calcium overload, and endoplasmic reticulum (ER) stress. Because of the critical role of the mitochondrial quality control systems, many reports have suggested that defects in this system are among the molecular mechanisms underlying myocardial reperfusion injury. In this review, we briefly summarize the important role of the mitochondrial quality control in cardiomyocyte function and focus on the current understanding of the regulatory mechanisms and molecular pathways involved in mitochondrial quality control in cardiac I/R damage.

Melatonin and regulation of autophagy: Mechanisms and therapeutic implications.

Mitochondria are essential subcellular units that generate basic energy for the cell, as well as influence Ca2+ flux, apoptosis, and cell signaling. Mitophagy can selectively remove impaired mitochondria to preserve mitochondrial function, which is crucial for normal cellular maintenance. Mitochondrial dysfunction and mitophagy are widely reported to be linked to various pathogeneses. In addition, there is increasing evidence regarding the beneficial role of melatonin in the regulation and intervention of mitophagy progression. In this review, we focus on specific pathological conditions, including ischemia/reperfusion injury (IRI), cancer and neurodegenerative diseases, and elucidate the essential role of melatonin in the modulation of mitophagy in each of these distinct disorders.

[Spatiotemporal variations in the association of community urbanization levels with obesity incidence among Chinese adults in nine provinces].

OBJECTIVE: To explore whether the association of community urbanization levels with overweight incidence changes over time and varies by region. METHODS: The data is from the China Health and Nutrition Survey(1991-2015). The survey applied a multistage, random cluster design to draw samples. A total of 8684 adults aged 20-64 years were confined in nine provinces(autonomous regions). Based on an urbanicity score, communities were divided into two groups: low-and high-urbanization-level groups. The nine provinces(autonomous regions) were divided into four regions, including the Coast, Central, Northeast and West. Multilevel Logistic regression models was applied to examine whether the association between urbanization levels and overweight incidence changed over time and varied by region. RESULTS: 38.08% of respondents became overweight during the follow-up surveys. The interactions between the high urbanization level with the Coast(OR=0.45, 95%CI 0.34-0.60), the Central(OR=0.67, 95%CI 0.52-0.86), and the Northeast(OR=0.70, 95%CI 0.52-0.94) were statistically significant. The interaction between the high urbanization level and period was also statistically significant(OR=0.97, 95%CI 0.96-0.99). In 1991, the Coast(OR=0.99, 95%CI 0.77-1.26), the high urbanization level was positively associated with overweight incidence in the Central(OR=1.45, 95%CI 1.15-1.83), Northeast(OR=1.53, 95%CI 1.16-2.02) and West(OR=2.18, 95%CI 1.68-2.83), with statistical significance. In 2015, the high urbanization level was significantly negatively associated with overweight incidence in the Coast(OR=0.53, 95%CI 0.41-0.68) and Central(OR=0.77, 95%CI 0.62-0.97), while the association in the Northeast(OR=0.82, 95%CI 0.63-1.05) and West(OR=1.17, 95%CI 0.91-1.49) was statistically insignificant. CONCLUSION: There were spatiotemporal variations in the association between urbanization levels and overweight incidence among adults in the nine provinces(autonomous regions).

Wearable Sensors Based on Miniaturized High-Performance Hybrid Nanogenerator for Medical Health Monitoring.

Wearable sensors are important components, converting mechanical vibration energy into electrical signals or other forms of output, which are widely used in healthcare, disaster warning, and transportation. However, the reliance on batteries limits the portability of wearable sensors and hinders their application in the field of Internet of Things. To solve this problem, we designed a miniaturized high-performance hybrid nanogenerator (MHP-HNG), which combined the functions of triboelectric sensing and electromagnetic power generation as well as the advantages of miniaturization. By optimizing the design of TENG and EMG, the wearable sensor achieved a voltage output of 14.14 V and a power output of 49 mW. Based on the wireless optical communication and wireless communication technologies, the wearable sensor achieved the integration of sensing, communication, and self-powered function, which is expected to realize health monitoring, emergency warning, and rehabilitation assistance, and further extend the potential application value in the medical field.

Melatonin protects against myocardial ischemia-reperfusion injury by inhibiting excessive mitophagy through the Apelin/SIRT3 signaling axis.

Excessive or uncontrolled mitophagy may result in a drastic shortage of healthy mitochondrial for ATP supply after reperfusion, leading to irreversible myocardial damage. Melatonin, a hormone produced by the pineal gland, has been proven to ameliorate myocardial ischemia-reperfusion (I/R) injury via regulating mitophagy. However, its underlying mechanism has not been fully elucidated. The present study focused on the role of mitophagy in the cardioprotective effects of melatonin by using the myocardial I/R rat model. The rats were pretreated with or without the apelin inhibitor ML221, the sirtuin 3 (SIRT3) inhibitor 3-TYP and then subjected to I/R injury, with melatonin administrated 10 min before reperfusion. The effects of melatonin on myocardial infarct size, biomarkers of myocardial injury, oxidative stress, and mitochondrial function were detected, and the expression of apelin, SIRT3, and mitophagy-related proteins were also measured. Excessive mitophagy was activated after I/R injury and was correlated with oxidative stress and mitochondrial dysfunction. Melatonin pretreatment ameliorated myocardial injury by decreasing oxidative stress, restoring mitochondrial function, and inhibiting excessive mitophagy. However, ML221 or 3-TYP disrupted these beneficial effects of melatonin on I/R injury. Taken together, these results suggest that melatonin pretreatment ameliorates myocardial I/R injury through regulating the apelin/SIRT3 pathway to inhibit excessive mitophagy.

SIRT3 and RORα are two prospective targets against mitophagy during simulated ischemia/reperfusion injury in H9c2 cells.

Autophagy during myocardial ischemia/reperfusion (MI/R) exacerbates cardiomyocyte injury. Melatonin (Mel) alleviates myocardial damage by regulating mitochondrial function and mitophagy, but the role of mitophagy in melatonin-induced cardioprotection remains unclear. This study aimed to explore the roles of sirtuin3 (SIRT3) and retinoid-related orphan nuclear receptor-α (RORα) in mitophagy during simulated ischemia reperfusion (SIR) in H9c2 cells. Our data showed that mitophagy was excessively activated after SIR injury, which was consistent with reduced cell survival, enhanced oxidative responses and mitochondrial dysfunction in H9c2 myocytes. Melatonin greatly enhanced cell viability, reduced oxidative stress and improved mitochondrial function. The effects of melatonin protection were involved in excessive mitophagy inhibition, as demonstrated by the reduced levels of mitophagy-linked proteins, including Parkin, Beclin1, NIX and BNIP3, and the LC3 II/LC3 I ratio and elevations in p62. Additionally, the decreases in SIRT3 and RORα in H9c2 myocytes after SIR were reversed by melatonin, and the above effects of melatonin were eliminated by small interfering RNA (siRNA)-mediated knockdown of SIRT3 and RORα. In brief, SIRT3 and RORα are two prospective targets in the cardioprotection of melatonin against mitophagy during SIR in H9c2 myocytes.

Survival and neurological function in patients treated with extracorporeal membrane oxygenation and therapeutic hypothermia: a protocol for updating a systematic review.

INTRODUCTION: The widespread application of extracorporeal membrane oxygenation (ECMO) has enhanced clinical outcomes for patients experiencing cardiac arrest. However, its effectiveness is still limited and falls short of the desired level. Therapeutic hypothermia, which maintains body temperatures between 32°C and 36°C in cardiac arrest patients treated with ECMO, has been proposed as a potential means of neuroprotection and increased survival rates. Nevertheless, it remains controversial, and its impact on patient complications has yet to be fully understood. Thus, this paper aims to update the protocol for a systematic review of patients treated with ECMO and therapeutic hypothermia, in order to explore its effects on survival and neurological function. METHOD AND ANALYSIS: This protocol has been developed in compliance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols 2015. The following databases will be systematically searched: PubMed, Web of Science, Cochrane Library, Embase, Ovid, CNKI, Wanfang and China Biology Medicine Disc. The database search strategy will use a combination of subject terms and free-text keywords. The search will encompass articles from the inception of each database up to 15 June 2023. Inclusion criteria encompass randomised controlled trials, cohort studies, case-control studies and quasi-experimental studies. Two researchers will independently review articles and extract relevant data based on these criteria. Any disagreements will be resolved through discussion. Data analysis will be performed using Review Manager software. ETHICS AND DISSEMINATION: Since no patient data were collected in this study, ethical approval was not required. Research findings will be released in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023435353.

Handling the Challenges of Small-Scale Labeled Data and Class Imbalances in Classifying the N and K Statuses of Rubber Leaves Using Hyperspectroscopy Techniques.

The nutritional status of rubber trees (Hevea brasiliensis) is inseparable from the production of natural rubber. Nitrogen (N) and potassium (K) levels in rubber leaves are 2 crucial criteria that reflect the nutritional status of the rubber tree. Advanced hyperspectral technology can evaluate N and K statuses in leaves rapidly. However, high bias and uncertain results will be generated when using a small size and imbalance dataset to train a spectral estimaion model. A typical solution of laborious long-term nutrient stress and high-intensive data collection deviates from rapid and flexible advantages of hyperspectral tech. Therefore, a less intensive and streamlined method, remining information from hyperspectral image data, was assessed. From this new perspective, a semisupervised learning (SSL) method and resampling techniques were employed for generating pseudo-labeling data and class rebalancing. Subsequently, a 5-classification spectral model of the N and K statuses of rubber leaves was established. The SSL model based on random forest classifiers and mean sampling techniques yielded optimal classification results both on imbalance/balance dataset (weighted average precision 67.8/78.6%, macro averaged precision 61.2/74.4%, and weighted recall 65.7/78.5% for the N status). All data and code could be viewed on the:Github https://github.com/WeehowTang/SSL-rebalancingtest. Ultimately, we proposed an efficient way to rapidly and accurately monitor the N and K levels in rubber leaves, especially in the scenario of small annotation and imbalance categories ratios.

SMYD3 activates the TCA cycle to promote M1-M2 conversion in macrophages.

BACKGROUND: SMYD3 refers to a histone lysine methyltransferase from the SMYD family, which acts as a gene transcriptional regulator chiefly through catalysis of the histone subunit 3 at lysine 4 trimethylation (H3K4me3). Great progress has been made that epigenetic modification plays a pivotal role in regulating macrophage polarization. However, the effects of the histone lysine methyltransferase SMYD3 on macrophage polarization and phenotypic switching are unclear. RESULTS: We found that LPS/IFN-γ-stimulated macrophages gradually transformed from M1 to M2 in the late stage, and SMYD3 played a key role in this process. As demonstrated by RNA-seq assessment, SMYD3 prominently activated a metabolic pathway known as TCA cycle inside macrophages during M1-M2 conversion. Besides, by modifying H3K4me3 histone, the target genes regulated by SMYD3 were identified via the ChIP-seq assessment, including citrate synthase (CS), succinate dehydrogenase complex subunit C (SDHC) and pyruvate carboxylase (PC). SMYD3 activated the transcriptional activities of the metabolic enzymes CS, SDHC and PC through H3K4me3 by causing the aggregation of citrate, an intramacrophage metabolite, and the depletion of succinate. And additionally, it facilitated the generation of ROS, as well as the expressions of genes associated with mitochondrial respiratory chain complexes. This increased ROS production ultimately induced mitophagy, triggering the M1 to M2 phenotype switch in the macrophages. CONCLUSIONS: Our study provides a detailed intrinsic mechanism in the macrophage phenotypic transition process, in short, SMYD3 promotes the M1-M2 conversion of macrophages by activating the TCA cycle through the simultaneous regulation of the transcriptional activities of the metabolic enzymes CS, SDHC and PC.

Gender Disparities in Blood Pressure and the Role of Body Mass Index: A Birth Cohort Analysis in China.

BACKGROUND: The slow decline in cardiovascular disease (CVD) mortality and the stagnant or increasing hypertension prevalence in low- and middle-income countries necessitate investigation. Evolving gender disparities suggested that male cardiovascular health disadvantage may be preventable, offering potential for enhancing population cardiovascular health. Despite global body mass index (BMI) increases, its role in shaping the gender disparities remains underexplored. OBJECTIVE: This study investigated the birth cohort dynamics of gender disparities in systolic/diastolic blood pressure (SBP/DBP) in China, one of the world's largest low- and middle-income countries, and explored the potential role of BMI in explaining the changing gender disparities. METHODS: Data from the China Health and Nutrition Survey (1991-2015) were analyzed using multilevel growth-curve models to estimate gender- and cohort-specific SBP/DBP trajectories among individuals born between 1950 and 1975. RESULTS: Men had higher SBP and DBP than women at the sample's mean age of 41.7 years. The gender disparities in SBP and DBP increased with each successive one-year cohort from 1950 to 1975 by 0.14 mm Hg and 0.09 mm Hg, respectively. Adjusting for BMI reduced the increasing gender disparities in SBP and DBP by 31.9% and 34.4%, respectively. CONCLUSION: Chinese men experienced a greater increase in SBP/DBP across successive cohorts compared to women. The increasing gender disparities in SBP/DBP were partially attributable to a greater BMI increase across cohorts among men. Given these findings, prioritizing interventions that aim to reduce BMI, particularly among men, could potentially alleviate the burden of CVD in China through lowering SBP/DBP.

Advances in the study of the effects of gut microflora on microglia in Alzheimer's disease.

Alzheimer's disease (AD) is a central nervous system (CNS) degenerative disorder, is caused by various factors including ß-amyloid toxicity, hyperphosphorylation of tau protein, oxidative stress, and others. The dysfunction of microglia has been associated with the onset and advancement of different neurodevelopmental and neurodegenerative disorders, such as AD. The gut of mammals harbors a vast and complex population of microorganisms, commonly referred to as the microbiota. There's a growing recognition that these gut microbes are intrinsically intertwined with mammalian physiology. Through the circulation of metabolites, they establish metabolic symbiosis, enhance immune function, and establish communication with different remote cells, including those in the brain. The gut microbiome plays a crucial part in influencing the development and performance of microglia, as indicated by recent preclinical studies. Dysbiosis of the intestinal flora leads to alterations in the microglia transcriptome that regulate the interconversion of microglia subtypes. This conversation explores recent research that clarifies how gut bacteria, their byproducts, and harmful elements affect the activation and characteristics of microglia. This understanding opens doors to innovative microbial-based therapeutic strategies for early identification and treatment goals in AD.

The risk factors of postoperative hypoxemia in patients with Stanford type A acute aortic dissection.

Hypoxemia is one of the most common complications in patients after Stanford type A acute aortic dissection surgery. The aim of this study was to investigate the association of circulating ANG II level with postoperative hypoxemia and to identify the risk factors for postoperative hypoxemia in Stanford type A acute aortic dissection patients. In this study, 88 patients who underwent Stanford type A acute aortic dissection surgery were enrolled. Postoperative hypoxemia is defined by the oxygenation index (OI). Perioperative clinical data were collected and the serum ANG II and sACE2 levels were measured. The differences in the basic characteristics, intraoperative details, biochemical parameters, laboratory test data and clinical outcomes were compared between the hypoxemia group and the non-hypoxemia group by univariate analysis. Multivariate logistic regression analysis was performed on the variables with P < .1 in univariate analysis or that were considered clinically important to identify risk factors for postoperative hypoxemia. Twenty-five patients (28.4%) were considered to have postoperative hypoxemia (OI ≤ 200 mm Hg). The ANG II concentration remained a risk factor associated with postoperative hypoxemia [OR = 1.018, 95% CI (1.003-1.034), P = .022]. The other risk factors remaining in the logistic regression model were BMI [OR = 1.417, 95% CI (1.159-1.733), P = .001] and cTnI [OR = 1.003, 95% CI (1.000-1.005), P = .032]. Elevated levels of ANG II, BMI and cTnI are risk factors for postoperative hypoxemia in patients with Stanford type A acute aortic dissection.

The Gender Gap in Life Expectancy in Urban and Rural China, 2013-2018.

BACKGROUND: Gender differences in mortality are embedded within mortality transitions. Rural residents generally lag behind their urban counterparts in the transitions. The study objective is to identify major causes of death that drive gender differences in mortality in urban and rural China. METHODS: We use age-, gender-, urban-rural- and cause-specific mortality data (2013-2018) derived from the national mortality surveillance system that covered about 24% of the Chinese population. We apply Arriaga's method to decompose age- and cause-specific contributions to the gender gap in life expectancy at birth. Analyses are stratified by urban-rural residence. RESULTS: Women had a higher life expectancy at birth than men in both urban and rural areas. Cancers, cardiovascular disease, external causes, and respiratory disease accounted for more than 90% of the gender gap in both areas during 2013-2018. In urban areas, the gender gap decreased from 5.17 years in 2013-2015 to 4.98 years in 2016-2018. In rural areas, the gender gap stayed rather constant (2013-2015: 5.68 years; 2016-2018: 5.65 years). Traffic accidents, among external causes, contributed the most to decreasing the gender gap (urban: -0.07 years; rural: -0.10 years), especially in the 0-44 age group. However, the decrease in the gender gap was counteracted by an increase in the gender gap attributable to ischemic heart disease (urban: +0.05 years; rural: +0.08 years) and lung cancer (urban: +0.02 years; rural: +0.05 years) in older age groups. The gender gap attributable either to cerebrovascular disease or to chronic lower respiratory disease decreased in urban areas but increased in rural areas. CONCLUSIONS: The urban-rural variations in the cause-specific contributions to the gender gap in China suggest the necessity of implementing urban-rural-specific interventions to improve population health and health equity.

Urbanization and systolic/diastolic blood pressure from a gender perspective: Separating longitudinal from cross-sectional association.

There has been a generally negative view of the impact of urbanization on a rising burden of non-communicable diseases including cardiovascular disease. However, the evidence on the relationship between urbanization and cardiovascular health has remained inconclusive. A comprehensive picture of the relationship is lacking, given an implicit assumption that the longitudinal association between changes in cardiovascular health and an increasingly urbanized environment is similar between less and more urbanized communities, men and women. We used the longitudinal data on adults (18-64 years) from the China Health and Nutrition Survey (1991-2015) and employed within-between random-effects models to disaggregates the longitudinal and cross-sectional associations between urbanization and systolic/diastolic blood pressure (SBP/DBP) and examined heterogeneities in the longitudinal association by average urbanization level and gender. We found that the positive longitudinal association of urbanization with SBP/DBP was stronger in less urbanized than more urbanized communities. The cross-sectional association between urbanization and SBP was negative and significant, although the cross-sectional association between urbanization and DBP was of no statistical significance. Moreover, the positive longitudinal association between urbanization and DBP was stronger among men than women, although the gender heterogeneity in the longitudinal association of urbanization with SBP was not significant.

Human expansion into Asian highlands in the 21st Century and its effects.

Most intensive human activities occur in lowlands. However, sporadic reports indicate that human activities are expanding in some Asian highlands. Here we investigate the expansions of human activities in highlands and their effects over Asia from 2000 to 2020 by combining earth observation data and socioeconomic data. We find that ∼23% of human activity expansions occur in Asian highlands and ∼76% of these expansions in highlands comes from ecological lands, reaching 95% in Southeast Asia. The expansions of human activities in highlands intensify habitat fragmentation and result in large ecological costs in low and lower-middle income countries, and they also support Asian developments. We estimate that cultivated land net growth in the Asian highlands contributed approximately 54% in preventing the net loss of the total cultivated land. Moreover, the growth of highland artificial surfaces may provide living and working spaces for ∼40 million people. Our findings suggest that highland developments hold dual effects and provide new insight for regional sustainable developments.

Probing DNA's interstrand orientation with gold nanoparticles.

The interstrand orientation of a DNA duplex plays a pivotal role in its biological and chemical functions. Therefore, developing an efficient way to determine (control and monitor) the parallel or antiparallel conformation of a DNA duplex is of great significance, which, however, remains a big challenge under some circumstances. In this work, we demonstrate that gold nanoparticles tagged on DNA are especially useful in trapping and detecting a special interstrand orientation of a DNA double helix, based on inherent electrostatic and steric repulsions between nanoparticles which will affect their self-assembly into a large structure. More importantly, some of the conformations revealed by the gold nanoparticle assay may even not be thermodynamically preferred and thus will be hard to detect using currently available methods. This simple, straightforward, and efficient methodology capable of dictating and probing a special DNA duplex structure provides a useful tool for conformational analyses and functional explorations of biomolecules as well as biophysical and nanobiomedical research.

Spatiotemporal Variation of the Association between Urbanicity and Incident Hypertension among Chinese Adults.

Urbanization is believed to result in a transition towards energy-dense diets, sedentary lifestyles, and a subsequent increase in the burden of hypertension (HTN) and other cardiovascular diseases (CVDs) in developing countries. However, the extent to which this occurs is likely dependent on social contexts. We performed multilevel logistic regression models to examine whether the association between incident HTN and the degree to which a community exhibits urban features varied by region (the Northeast, East Coast, Central, and West) within China and period. We used longitudinal data from the China Health and Nutrition Survey (1991-2015) and stratified analyses by sex. Among women, the positive association between medium-to-high urbanicity and HTN onset generally shifted to negative between 1991 and 2015. The high urbanicity was associated with lower odds of developing HTN in the East Coast from the early 1990s. The negative association between high urbanicity and HTN occurrence became statistically significant during 1991-2015 in the Northeastern and Central Regions, while the association remained positive and non-significant in the West. Among men, the relationship between urbanicity and incident HTN was generally non-significant, except for the East Coast in which the negative association between high urbanicity and HTN occurrence became statistically-significant in more recent years. Our findings suggest that, when a subnational region or the society as a whole has become more economically developed, higher urbanicity might turn out to be a protective factor of cardiovascular health. Moreover, improvements made to communities' urban features might be more effective in preventing HTN for women than for men.

Melatonin Attenuates Anoxia/Reoxygenation Injury by Inhibiting Excessive Mitophagy Through the MT2/SIRT3/FoxO3a Signaling Pathway in H9c2 Cells.

PURPOSE: Autophagy caused by ischemia/reperfusion (I/R) increases the extent of cardiomyocyte damage. Melatonin (Mel) diminishes cardiac injury through regulating autophagy and mitochondrial dynamics. However, illustrating the specific role of mitophagy in the cardioprotective effects of melatonin remains a challenge. The aim of our research was to investigate the impact and underlying mechanisms of melatonin in connection with mitophagy during anoxia/reoxygenation (A/R) injury in H9c2 cells. METHODS: H9c2 cells were pretreated with melatonin with or without the melatonin membrane receptor 2 (MT2) antagonist 4-P-PDOT, the MT2 agonist IIK7 and the sirtuin 3 (SIRT3) inhibitor 3-TYP for 4 hours and then subjected to A/R injury. Cell viability, cellular apoptosis, necrosis levels and oxidative markers were assessed. The expression of SIRT3 and forkhead box O3a (FoxO3a), mitochondrial function and the levels of mitophagy-related proteins were also evaluated. RESULTS: A/R injury provoked enhanced mitophagy in H9c2 myocytes. In addition, increased mitophagy was correlated with decreased cellular viability, increased oxidative stress and mitochondrial dysfunction in H9c2 cells. However, melatonin pretreatment notably increased cell survival and decreased cell apoptosis and oxidative response after A/R injury, accompanied by restored mitochondrial function. The inhibition of excessive mitophagy is involved in the cardioprotective effects of melatonin, as shown by the decreased expression of the mitophagy-related molecules Parkin, Beclin1, and BCL2-interacting protein 3-like (BNIP3L, best known as NIX) and decreased light chain 3 II/light chain 3 I (LC3 II/LC3 I) ratio and upregulation of p62 expression. Moreover, the decreased expression of SIRT3 and FoxO3a in A/R-injured H9c2 cells was abrogated by melatonin, but these beneficial effects were attenuated by the MT2 antagonist 4-P-PDOT or the SIRT3 inhibitor 3-TYP and enhanced by the MT2 agonist IIK7. CONCLUSION: These results indicate that melatonin protects H9c2 cells during A/R injury through suppressing excessive mitophagy by activating the MT2/SIRT3/FoxO3a pathway. Melatonin may be a useful candidate for alleviating myocardial ischemia/reperfusion (MI/R) injury in the future, and the MT2 receptor might become a therapeutic target.