Aerobic exercise-induced HIF-1α upregulation in heart failure: exploring potential impacts on MCT1 and MPC1 regulation.

BACKGROUND: The terminal stage of ischemic heart disease develops into heart failure (HF), which is characterized by hypoxia and metabolic disturbances in cardiomyocytes. The hypoxic failing heart triggers hypoxia-inducible factor-1α (HIF-1α) actions in the cells sensitized to hypoxia and induces metabolic adaptation by accumulating HIF-1α. Furthermore, soluble monocarboxylic acid transporter protein 1 (MCT1) and mitochondrial pyruvate carrier 1 (MPC1), as key nodes of metabolic adaptation, affect metabolic homeostasis in the failing rat heart. Aerobic exercise training has been reported to retard the progression of HF due to enhancing HIF-1α levels as well as MCT1 expressions, whereas the effects of exercise on MCT1 and MPC1 in HF (hypoxia) remain elusive. This research aimed to investigate the action of exercise associated with MCT1 and MPC1 on HF under hypoxia. METHODS: The experimental rat models are composed of four study groups: sham stented (SHAM), HF sedentary (HF), HF short-term exercise trained (HF-E1), HF long-term exercise trained (HF-E2). HF was initiated via left anterior descending coronary artery ligation, the effects of exercise on the progression of HF were analyzed by ventricular ultrasound (ejection fraction, fractional shortening) and histological staining. The regulatory effects of HIF-1α on cell growth, MCT1 and MPC1 protein expression in hypoxic H9c2 cells were evaluated by HIF-1α activatort/inhibitor treatment and plasmid transfection. RESULTS: Our results indicate the presence of severe pathological remodelling (as evidenced by deep myocardial fibrosis, increased infarct size and abnormal hypertrophy of the myocardium, etc.) and reduced cardiac function in the failing hearts of rats in the HF group compared to the SHAM group. Treadmill exercise training ameliorated myocardial infarction (MI)-induced cardiac pathological remodelling and enhanced cardiac function in HF exercise group rats, and significantly increased the expression of HIF-1α (p < 0.05), MCT1 (p < 0.01) and MPC1 (p < 0.05) proteins compared to HF group rats. Moreover, pharmacological inhibition of HIF-1α in hypoxic H9c2 cells dramatically downregulated MCT1 and MPC1 protein expression. This phenomenon is consistent with knockdown of HIF-1α at the gene level. CONCLUSION: The findings propose that long-term aerobic exercise training, as a non- pharmacological treatment, is efficient enough to debilitate the disease process, improve the pathological phenotype, and reinstate cardiac function in HF rats. This benefit is most likely due to activation of myocardial HIF-1α and upregulation of MCT1 and MPC1.

Visual light flicker stimulation: enhancing alertness in sleep-deprived rats.

Introduction: In the evolving field of neurophysiological research, visual light flicker stimulation is recognized as a promising non-invasive intervention for cognitive enhancement, particularly in sleep-deprived conditions. Methods: This study explored the effects of specific flicker frequencies (40 Hz and 20-30 Hz random flicker) on alertness recovery in sleep-deprived rats. We employed a multidisciplinary approach that included behavioral assessments with the Y-maze, in vivo electrophysiological recordings, and molecular analyses such as c-FOS immunohistochemistry and hormone level measurements. Results: Both 40 Hz and 20-30 Hz flicker significantly enhanced behavioral performance in the Y-maze test, suggesting an improvement in alertness. Neurophysiological data indicated activation of neural circuits in key brain areas like the thalamus and hippocampus. Additionally, flicker exposure normalized cortisol and serotonin levels, essential for stress response and mood regulation. Notably, increased c-FOS expression in brain regions related to alertness and cognitive functions suggested heightened neural activity. Discussion: These findings underscore the potential of light flicker stimulation not only to mitigate the effects of sleep deprivation but also to enhance cognitive functions. The results pave the way for future translational research into light-based therapies in human subjects, with possible implications for occupational health and cognitive ergonomics.

MiR-421 mediates PM2.5-induced endothelial dysfunction via crosstalk between bronchial epithelial and endothelial cells.

OBJECTIVE: PM2.5 is closely linked to vascular endothelial injury and has emerged as a major threat to human health. Our previous research indicated that exposure to PM2.5 induced an increased release of miR-421 from the bronchial epithelium. However, the role of miR-421 in PM2.5-induced endothelial injury remains elusive. MATERIALS AND METHODS: We utilized a subacute PM2.5-exposure model in mice in vivo and an acute injury cell model in vitro to simulate PM2.5-associated endothelial injury. We also used quantitative real-time polymerase chain reaction, western blot, enzyme-linked immunosorbent assay, and immunohistochemistry to investigate the role of miR-421 in PM2.5-induced endothelial injury. RESULTS: Our findings reveal that inhibition of miR-421 attenuated PM2.5-induced endothelial injury and hypertension. Mechanistically, miR-421 inhibited the expression of angiotensin-converting enzyme 2 (ACE2) in human umbilical vein endothelial cells and upregulated the expression of the downstream molecule inducible nitric oxide synthase (iNOS), thereby exacerbating PM2.5-induced endothelial injury. CONCLUSIONS: Our results indicate that PM2.5 exposure facilitates crosstalk between bronchial epithelial and endothelial cells via miR-421/ACE2/iNOS signaling pathway, mediating endothelial damage and hypertension. MiR-421 inhibition may offer a new strategy for the prevention and treatment of PM2.5-induced vascular endothelial injury.

SGLT2i Alleviates Atherosclerosis by Inhibiting NHE1 Activation to Protect against Macrophage Senescence Induced by Angiotensin II.

BACKGROUND: Sodium-dependent glucose transporter (SGLT2) inhibitors (SGLT2i) have been found to have anti-atherosclerotic effects in clinical treatment. OBJECTIVES: The aim of this study was to explore whether angiotensin II (Ang II) induces changes in the expression of Na+/H+ exchanger of cytoplasmic membrane channel proteins (NHE1) and SGLT2 in macrophages and whether dapagliflozin (DAPA), an SGLT2i, protects against Ang II induced macrophage senescence by inhibiting NHE1 activation to alleviate Atherosclerosis (AS). METHODS: After intervention with DAPA plus gavage or feeding them a high-fat diet, the mice's aortas were dissected, and oil red O staining was performed. Cell proliferation and toxicity detection, western blot, immunofluorescence, and ß-galactosidase staining methods were adopted to detect cell activity, expressions of senescence-related genes, and number of senescent cells after different concentrations of Ang II or DAPA or plasmid NHE1 were treated with RAW264.7 cells. RESULTS: (1) The formation of AS plaques in ApoE -/- mice showed a downward trend under DAPA. (2) After the intervention of Ang II, the cell activity of RAW264.7 decreased, and the expression of senescent cells and related genes increased. (3) Under the Ang II condition, the expression of SGLT2 and NHE1 increased, and SGLT2, NHE1, and senescence-related genes decreased with the addition of DAPA. (4) The expression of NHE1, senescent cells and related genes decreased in RAW264.7 cells after DAPA treatment with plasmid NHE1 intervention. CONCLUSION: SGLT2i alleviates atherosclerosis by inhibiting NHE1 activation to protect against macrophage senescence induced by Ang II.

Exercise training decreases lactylation and prevents myocardial ischemia-reperfusion injury by inhibiting YTHDF2.

Exercise improves cardiac function and metabolism. Although long-term exercise leads to circulating and micro-environmental metabolic changes, the effect of exercise on protein post-translational lactylation modifications as well as its functional relevance is unclear. Here, we report that lactate can regulate cardiomyocyte changes by improving protein lactylation levels and elevating intracellular N6-methyladenosine RNA-binding protein YTHDF2. The intrinsic disorder region of YTHDF2 but not the RNA m6A-binding activity is indispensable for its regulatory function in influencing cardiomyocyte cell size changes and oxygen glucose deprivation/re-oxygenation (OGD/R)-stimulated apoptosis via upregulating Ras GTPase-activating protein-binding protein 1 (G3BP1). Downregulation of YTHDF2 is required for exercise-induced physiological cardiac hypertrophy. Moreover, myocardial YTHDF2 inhibition alleviated ischemia/reperfusion-induced acute injury and pathological remodeling. Our results here link lactate and lactylation modifications with RNA m6A reader YTHDF2 and highlight the physiological importance of this innovative post-transcriptional intrinsic regulation mechanism of cardiomyocyte responses to exercise. Decreasing lactylation or inhibiting YTHDF2/G3BP1 might represent a promising therapeutic strategy for cardiac diseases.

Exercise Inhibits Doxorubicin-Induced Cardiotoxicity via Regulating B Cells.

BACKGROUND: Doxorubicin is an effective chemotherapeutic agent, but its use is limited by acute and chronic cardiotoxicity. Exercise training has been shown to protect against doxorubicin-induced cardiotoxicity, but the involvement of immune cells remains unclear. This study aimed to investigate the role of exercise-derived B cells in protecting against doxorubicin-induced cardiotoxicity and to further determine whether B cell activation and antibody secretion play a role in this protection. METHODS: Mice that were administered with doxorubicin (5 mg/kg per week, 20 mg/kg cumulative dose) received treadmill running exercise. The adoptive transfer of exercise-derived splenic B cells to µMT-/- (B cell-deficient) mice was performed to elucidate the mechanism of B cell regulation that mediated the effect of exercise. RESULTS: Doxorubicin-administered mice that had undergone exercise training showed improved cardiac function, and low levels of cardiac apoptosis, atrophy, and fibrosis, and had reduced cardiac antibody deposition and proinflammatory responses. Similarly, B cell pharmacological and genetic depletion alleviated doxorubicin-induced cardiotoxicity, which phenocopied the protection of exercise. In vitro performed coculture experiments confirmed that exercise-derived B cells reduced cardiomyocyte apoptosis and fibroblast activation compared with control B cells. Importantly, the protective effect of exercise on B cells was confirmed by the adoptive transfer of splenic B cells from exercised donor mice to µMT-/- recipient mice. However, blockage of Fc gamma receptor IIB function using B cell transplants from exercised Fc gamma receptor IIB-/- mice abolished the protection of exercise-derived B cells against doxorubicin-induced cardiotoxicity. Mechanistically, we found that Fc gamma receptor IIB, an important B cell inhibitory receptor, responded to exercise and increased B cell activation threshold, which participated in exercise-induced protection against doxorubicin-induced cardiotoxicity. CONCLUSIONS: Our results demonstrate that exercise training protects against doxorubicin-induced cardiotoxicity by upregulating Fc gamma receptor IIB expression in B cells, which plays an important anti-inflammatory role and participates in the protective effect of exercise against doxorubicin-induced cardiotoxicity.

A novel universal small-molecule detection platform based on antibody-controlled Cas12a switching.

Molecular diagnostics play an important role in illness detection, prevention, and treatment, and are vital in point-of-care test. In this investigation, a novel CRISPR/Cas12a based small-molecule detection platform was developed using Antibody-Controlled Cas12a Biosensor (ACCBOR), in which antibody would control the trans-cleavage activity of CRISPR/Cas12a. In this system, small-molecule was labeled around the PAM sites of no target sequence(NTS), and antibody would bind on the labeled molecule to prevent the combination of CRISPR/Cas12a, resulting the decrease of trans-cleavage activity. Biotin-, digoxin-, 25-hydroxyvitamin D3 (25-OH-VD3)-labeled NTS and corresponding binding protein were separately used to verify its preformance, showing great universality. Finally, one-pot detection of 25-OH-VD3 was developed, exhibiting high sensitivity and excellent specificity. The limit of detection could be 259.86 pg/mL in serum within 30 min. This assay platform also has the advantages of low cost, easy operation (one-pot method), and fast detection (∼30 min), would be a new possibilities for the highly sensitive detection of other small-molecule targets.

Development of antibody-aptamer sandwich-like immunosensor based on RCA and Nicked-PAM CRISPR/Cas12a system for the ultra-sensitive detection of a biomarker.

Biomarkers are the most sensitive reactants and early indicators of many kinds of diseases. The development of highly sensitive and simple techniques to quantify them is challenging. In this study, based on rolling cycle amplification (RCA) and the Nicked PAM/CRISPR-Cas12a system (RNPC) as a signal reporter, a sandwich-type method was developed using antibody@magnetic beads and aptamer for the high-sensitive detection of the C-reactive protein (CRP). The antibody-antigen (target)-aptamer sandwich-like reaction was coupled to RCA, which can produce hundreds of similar binding sites and are discriminated by CRISPR/Cas12a for signal amplification. The ultrasensitivity is achieved based on the dual-signal enhancing strategy, which involves the special recognition of aptamers, RCA, and trans-cleavage of CRISPR/Cas12a. By incorporating the CRISPR/Cas12a system with cleaved PAM, the nonspecific amplification of the RCA reaction alone was greatly reduced, and the dual signal output of RCA and Cas12a improved the detection sensitivity. Our assay can be performed only in two steps. The first step takes only 20 min of target capture, followed by a one-pot reaction, where the target concentration can be obtained by fluorescence values as long as there are 37 °C reaction conditions. Under optimal conditions, this system detected CRP with high sensitivity. The fabricated biosensor showed detection limits of 0.40 pg/mL in phosphate-buffered saline and 0.73 pg/mL in diluted human serum and a broad linear dynamic range of 1.28 pg/mL to 100 ng/mL within a total readout time of 90 min. The method could be used to perform multi-step signal amplification, which can help in the ultrasensitive detection of other proteins. Overall, the proposed biosensor might be used as an immunosensor biosensor platform.

Exercise-induced circular RNA circUtrn is required for cardiac physiological hypertrophy and prevents myocardial ischaemia-reperfusion injury.

AIMS: Regular exercise training benefits cardiovascular health and effectively reduces the risk for cardiovascular disease. Circular RNAs (circRNAs) play important roles in cardiac pathophysiology. However, the role of circRNAs in response to exercise training and biological mechanisms responsible for exercise-induced cardiac protection remain largely unknown. METHODS AND RESULTS: RNA sequencing was used to profile circRNA expression in adult mouse cardiomyocytes that were isolated from mice with or without exercise training. Exercise-induced circRNA circUtrn was significantly increased in swimming-trained adult mouse cardiomyocytes. In vivo, circUtrn was found to be required for exercise-induced physiological cardiac hypertrophy. circUtrn inhibition abolished the protective effects of exercise on myocardial ischaemia-reperfusion remodelling. circUtrn overexpression prevented myocardial ischaemia-reperfusion-induced acute injury and pathological cardiac remodelling. In vitro, overexpression of circUtrn promoted H9 human embryonic stem cell-induced cardiomyocyte growth and survival via protein phosphatase 5 (PP5). Mechanistically, circUtrn directly bound to PP5 and regulated the stability of PP5 in a ubiquitin-proteasome-dependent manner. Hypoxia-inducible factor 1α-dependent splicing factor SF3B1 acted as an upstream regulator of circUtrn in cardiomyocytes. CONCLUSION: The circRNA circUtrn is upregulated upon exercise training in the heart. Overexpression of circUtrn can prevent myocardial I/R-induced injury and pathological cardiac remodelling.

Risk factors and predictive model for acute kidney Injury Transition to acute kidney disease in patients following partial nephrectomy.

PURPOSE: Acute kidney disease (AKD) is believed to be involved in the transition from acute kidney injury (AKI) to chronic kidney disease in general populations, but little is understood about this possibility among kidney surgical populations. This study aimed to elucidate the incidence of AKD after partial nephrectomy and risk factors that promote the AKI to AKD transition. METHODS: From January 2010 to January 2020, this study retrospectively collected a dataset of consecutive patients with renal masses undergoing partial nephrectomy in 4 urological centers. Cox proportional regression analyses were adopted to identify risk factors that promoted the AKI to AKD transition. To avoid overfitting, the results were then verified by logistic least absolute shrinkage and selection operator (LASSO) regression. A nomogram was then constructed and validated for AKI to AKD transition prediction. RESULTS: AKI and AKD occurred in 228 (21.4%) and 42 (3.9%) patients among a total of 1062 patients, respectively. In patients with AKI, multivariable Cox regression analysis and LASSO regression identified that age (HR 1.078, 1.029-1.112, p < 0.001), baseline eGFR (HR 1.015, 1.001-1.030, p < 0.001), RENAL score (HR1.612, 1.067-2.437, p = 0.023), ischemia time > 30 min (HR 7.284, 2.210-23.999, p = 0.001), and intraoperative blood loss > 300ml (HR 8.641, 2.751-27.171, p < 0.001) were risk factors for AKD transition. These five risk factors were then integrated into a nomogram. The nomogram showed excellent discrimination, calibration, and clinical net benefit ability. CONCLUSION: Around 3.9% patients following partial nephrectomy would transit from AKI to AKD. Intraoperative blood loss and ischemia time need to be diminished to avoid on-going functional decline. Our nomogram can accurately predict the transition from AKI to AKD.

Tailoring the optical and mechanical properties of cellulose nanocrystal film by sugar alcohols and its pH/humidity-responsive behavior.

Cellulose nanocrystals (CNC) have gained widespread attention in intelligent food packaging because of their iridescent optical properties. Here, we report a CNC composite film employing CNC, sugar alcohols (e.g., maltol, erythritol, mannitol, sorbitol, and xylitol) and natural pigment anthocyanins, which has a special iridescent color that can be used as a pH and humidity sensor. The effects of five sugar alcohols with different addition ratios on the structural, optical, and mechanical properties of the CNC films were investigated. The results demonstrated that the addition of sugar alcohol made composite films exhibiting a red-shift of λmax, a more uniform color in visual observation, and a larger pitch. Among them, the CNC-mannitol composite film with a ratio of 10:1 exhibited the best mechanical properties, possessing a tensile stress strength of 57 MPa and toughness of 137 J/m3. Subsequently, anthocyanins were incorporated to this composite film, which showed a marked color change along with the pH from 2 to 12 and exhibited a reversible color change from red to transparent upon a relative humidity change from 35 % to 85 %. Overall, such multi-environment-responsive iridescent films with excellent mechanical properties have a great potential for use in intelligent food packaging applications.

Serum ANGPTL4 and SIRT1 factor levels and the Carotid Atherosclerotic plaque stability relationship analysis.

This study was to investigate the relationship between the levels of Angiopoietin-Like Protein 4 (ANGPTL4) and Silent Mating-type Information Regulation 2 Homolog 1 (SIRT1) and the stability of carotid atherosclerotic plaque. For this purpose, 108 patients with coronary heart disease in our hospital from Jan 2021 to May 2022 were selected as the coronary heart disease (CHD) group and 80 patients with the healthy examination as the control group. Patients' serum levels of ANGPTL4 and SIRT1 were collected, and their stability of carotid atherosclerotic plaque was determined by carotid ultrasound. According to their stability results, patients were divided into three subgroups: No plaque, Stable plaque, and Unstable plaque. The serum ANGPTL4 and SIRT1 levels were analyzed in different groups, and the correlation between their serum levels and the stability of carotid atherosclerotic plaque was analyzed by rank correlation. Results showed that the CHD group's serum ANGPTL4 and SIRT1 levels were lower, with statistical significance (P<0.05); A statistically significant difference in serum ANGPTL4 and SIRT1 levels were observed among patients with No plaques, Stable plaques, and Unstable plaques (P<0.05); A negative correlation was observed between serum levels of ANGPTL4 and SIRT1 and the stability of carotid atherosclerotic plaque (r=-0.438, -0.717, P<0.001); Serum ANGPTL4 and SIRT1 can be used as the evaluation method of carotid atherosclerotic plaque stability. When ANGPTL4 ≤ 30.17mg/L and SIRT1 ≤ 6.91µg/L, patients were more likely to develop unstable plaques; When ANGPTL4 ≤ 30.40mg/L and SIRT1 ≤ 6.87µg/L, patients were more likely to develop plaques (instability and/or stability). In conclusion, the serum levels of ANGPTL4 and SIRT1 in patients with CHD decreased. ANGPTL4 and SIRT1 will participate in the formation and development of carotid plaque, which can be used as a serological evaluation index to evaluate the occurrence and carotid atherosclerotic plaque's stability.

RNA m6A-Regulated circ-ZNF609 Suppression Ameliorates Doxorubicin-Induced Cardiotoxicity by Upregulating FTO.

Cardiac death is a major burden for cancer survivors, yet there is currently no effective treatment for doxorubicin (DOX)-induced cardiotoxicity. Here, we report that circ-ZNF609 knockdown knockdown had cardioprotective effects against DOX-induced cardiomyocyte toxicity. Mechanistically, circ-ZNF609 knockdown alleviated DOX-induced cardiotoxicity through attenuating cardiomyocyte apoptosis, reducing reactive oxygen species production, ameliorating mitochondrial nonheme iron overload. circ-ZNF609 inhibition blocked the elevation of RNA N6-methyladenosine (RNA m6A) methylation level in DOX-treated mice hearts, whereas m6A demethylase fat mass and obesity associated (FTO) acted as the downstream factor of circ-ZNF609. Moreover, the stability of circ-ZNF609 was regulated by RNA m6A methylation alteration, and suppression of RNA m6A methylation by methyltransferase like 14 (METTL14) modulated the function of circ-ZNF609. These data suggest that circ-ZNF609 inhibition represents a potential therapy for DOX-induced cardiotoxicity.

Does controlling shareholders' share pledge exacerbate excessive financialization of enterprises?-Evidence from performance pressure perspective.

Based on the perspective of performance pressure, we explore the influence of controlling shareholders' share pledge on excessive financialization behavior of enterprises and its internal mechanism. The results show that the share pledge of controlling shareholders is positively correlated with the excessive financialization behavior of enterprises. After the controlling shareholder's share pledge, the actual performance of the enterprise is lower than expected, causing the short-sighted behavior of the management, which makes the management willing to conspire with the controlling shareholder to cause the excessive financialization of the enterprise. The results are especially evident among the uncertainty of economic policy is low, the industry competition is not fierce and the executives have overseas experience.

Brain metabolism in Alzheimer's disease: biological mechanisms of exercise.

Alzheimer's disease (AD) is a major subtype of neurodegenerative dementia caused by long-term interactions and accumulation of multiple adverse factors, accompanied by dysregulation of numerous intracellular signaling and molecular pathways in the brain. At the cellular and molecular levels, the neuronal cellular milieu of the AD brain exhibits metabolic abnormalities, compromised bioenergetics, impaired lipid metabolism, and reduced overall metabolic capacity, which lead to abnormal neural network activity and impaired neuroplasticity, thus accelerating the formation of extracellular senile plaques and intracellular neurofibrillary tangles. The current absence of effective pharmacological therapies for AD points to the urgent need to investigate the benefits of non-pharmacological approaches such as physical exercise. Despite the evidence that regular physical activity can improve metabolic dysfunction in the AD state, inhibit different pathophysiological molecular pathways associated with AD, influence the pathological process of AD, and exert a protective effect, there is no clear consensus on the specific biological and molecular mechanisms underlying the advantages of physical exercise. Here, we review how physical exercise improves crucial molecular pathways and biological processes associated with metabolic disorders in AD, including glucose metabolism, lipid metabolism, Aß metabolism and transport, iron metabolism and tau pathology. How metabolic states influence brain health is also presented. A better knowledge on the neurophysiological mechanisms by which exercise improves AD metabolism can contribute to the development of novel drugs and improvement of non-pharmacological interventions.

MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation.

Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c) is a mitochondrial-derived peptide composed of 16 amino acids encoded by the 12S rRNA region of the mitochondrial genome. The MOTS-c protein is transferred to the nucleus during metabolic stress and directs the expression of nuclear genes to promote cell balance. Different tissues co-expressed the protein with mitochondria, and plasma also contained the protein, but its level decreased with age. In addition, MOTS-c has been shown to improve glucose metabolism in skeletal muscle, which indicates its benefits for diseases such as diabetes, obesity, and aging. Nevertheless, MOTS-c has been used less frequently in disease treatment, and no effective method of applying MOTS-c in the clinic has been developed. Throughout this paper, we discussed the discovery and physiological function of mitochondrial-derived polypeptide MOTS-c, and the application of MOTS-c in the treatment of various diseases, such as aging, cardiovascular disease, insulin resistance, and inflammation. To provide additional ideas for future research and development, we tapped into the molecular mechanisms and therapeutic potentials of MOTS-c to improve diseases and combined the technology with synthetic biology in order to offer a new approach to its development and application.

Synthesis and characterization of cellulose nanocrystal-Fe composite nanoparticles and their digestion behavior in simulated gastric fluid.

Cellulose nanocrystals (CNC) exhibit great potential as a food emulsifier or functional material template. Herein, CNC-Fe nanoparticles were successfully prepared via an in situ chemical reduction approach. Zeta potential measurements, low-field nuclear magnetic resonance spectroscopy, and atomic force microscopy showed that Fe(III) ions were adsorbed onto CNC when FeCl3 was added to a CNC dispersion. Micromorphological analysis revealed small (diameter = 10.0 ± 2.4 nm) spherical nanoparticles synthesized on the surface of aggregated CNC after the reduction of the Fe(III) ions. Fourier transform infrared spectroscopy revealed an intense peak at 779 cm-1 in the CNC-Fe nanoparticles, which was attributed to FeO stretching vibrations. X-ray photoelectron spectroscopy indicated that the valence state of Fe in CNC-Fe nanoparticles was predominantly ferrous. The synthesized CNC-Fe nanoparticles demonstrated excellent colloidal stability in a dispersion for 21 d and complete, rapid, and spontaneous dissolution in vitro simulated gastric fluid. Our results highlight the potential use of CNC as a template for loading Fe into nanoparticles for Fe fortification in food.

METTL14 is required for exercise-induced cardiac hypertrophy and protects against myocardial ischemia-reperfusion injury.

RNA m6A modification is the most widely distributed RNA methylation and is closely related to various pathophysiological processes. Although the benefit of regular exercise on the heart has been well recognized, the role of RNA m6A in exercise training and exercise-induced physiological cardiac hypertrophy remains largely unknown. Here, we show that endurance exercise training leads to reduced cardiac mRNA m6A levels. METTL14 is downregulated by exercise, both at the level of RNA m6A and at the protein level. In vivo, wild-type METTL14 overexpression, but not MTase inactive mutant METTL14, blocks exercise-induced physiological cardiac hypertrophy. Cardiac-specific METTL14 knockdown attenuates acute ischemia-reperfusion injury as well as cardiac dysfunction in ischemia-reperfusion remodeling. Mechanistically, silencing METTL14 suppresses Phlpp2 mRNA m6A modifications and activates Akt-S473, in turn regulating cardiomyocyte growth and apoptosis. Our data indicates that METTL14 plays an important role in maintaining cardiac homeostasis. METTL14 downregulation represents a promising therapeutic strategy to attenuate cardiac remodeling.

Protective effect of irisin against Alzheimer's disease.

Despite being one of the greatest global challenges for health and social care in the 21st century, Alzheimer's disease (AD) lacks specific medicine. Irisin, an exercise-generated muscle factor, emerges as a potential hormone for AD prevention and treatment because of its role in promoting the browning of white adipose tissue, accelerating energy expenditure, regulating energy metabolism, and improving insulin resistance. The study reviews classic hallmarks of AD and irisin's physiology before discussing the possible mechanism by which irisin protects against AD in terms of its effects related to molecular biology and cellular biology. Results reveal that irisin sharpens learning memory by inducing the production of brain-derived neurotrophic factor (BDNF), lowers the production of inflammatory factors, protects neurology through astrocytes, and ameliorates AD symptoms by improving insulin resistance. The review aims to facilitate future experimental studies and clinical applications of irisin in preventing and treating AD.