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AIM: Sepsis-induced myocardial injury (SIMI) may be associated with insufficient mitophagy in cardiomyocytes, but the exact mechanism involved remains unknown. Sirtuin 3 (Sirt3) is mainly found in the mitochondrial matrix and is involved in repairing mitochondrial function through means such as the activation of autophagy. Previously, we demonstrated that the annexin-A1 small peptide (ANXA1sp) can promote Sirt3 expression in mitochondria. In this study, we hypothesized that the activation of Sirt3 by ANXA1sp induces mitophagy, thereby providing a protective effect against SIMI in mice. METHODS: A mouse model of SIMI was established via cecal ligation and puncture. Intraperitoneal injections of ANXA1sp, 3TYP, and 3MA were administered prior to modeling. After successful modeling, IL-6, TNF-α, CK-MB, and CTn-I levels were measured; cardiac function was assessed using echocardiography; myocardial mitochondrial membrane potential, ROS, and ATP production were determined; myocardial mitochondrial ultrastructure was observed using transmission electron microscopy; and the expression levels of Sirt3 and autophagy-related proteins were detected using western blotting. RESULTS: ANXA1sp significantly reduced serum IL-6, TNF-α, CK-MB, and CTn-I levels; decreased myocardial ROS production; increased mitochondrial membrane potential and ATP synthesis; and improved myocardial mitochondrial ultrastructure in septic mice. Furthermore, ANXA1sp promoted Sirt3 expression and activated the AMPK-mTOR pathway to induce myocardial mitophagy. These protective effects of ANXA1sp were reversed upon treatment with the Sirt3 blocker, 3-TYP. CONCLUSION: ANXA1sp can reverse SIMI, and the underlying mechanism may be related to the activation of the AMPK-mTOR pathway following upregulation of Sirt3 by ANXA1sp, which, in turn, induces autophagy.
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Anexina A1 , Mitofagia , Sepse , Sirtuína 3 , Animais , Sepse/complicações , Sepse/metabolismo , Mitofagia/efeitos dos fármacos , Sirtuína 3/metabolismo , Sirtuína 3/genética , Camundongos , Anexina A1/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Modelos Animais de Doenças , Autofagia , PeptídeosRESUMO
Rising wide bandgap semiconductor gallium oxide (Ga2O3) displays huge potential in performing solar-blind photodetection, with constraint in narrow detection wavebands in nature, whereas bandgap modulation through the introduction of exotic atoms into Ga2O3 has an essential effect on the tunable performance of photodetectors and the detection waveband. Here, a novel method for the preparation of (InxGa1-x)2O3 alloy films is proposed, and the continuous tuning of the bandgap in the range of 3.70-4.99 eV is achieved by varying the In-doping content. Alloy-based metal-semiconductor-metal photodetectors were fabricated, achieving a peak responsivity between 254 and 295 nm, superior performance compared to Ga2O3 photodetectors, with a photo-to-dark current ratio as high as 106, and a better optical image-sensing capability. This study offers new insight for high-performance detection of full solar-blind waveband ultraviolet light.
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BACKGROUND: Abnormal serum ferritin levels are associated with a variety of diseases. Meanwhile, abnormal serum ferritin is influenced by a variety of risk factors, but its correlation with obesity remains poorly described. OBJECTIVE: This study aimed to investigate the association of body mass index (BMI) and weight waist adjustment index (WWI) with serum ferritin in US adults. METHODS: Participants in this study took part in the National Health and Nutrition Examination Survey (NHANES) prior to the pandemic from 2017 to March 2020. Serum ferritin was used as the sole response variable and BMI and WWI were used as independent variables. Multiple linear regression was used to assess the relationship between serum ferritin and the independent variables, and smoothed curve fitting and threshold effects analysis were performed to assess the presence of non-linear relationships. To validate the sensitive individuals for the correlation between the independent and the dependent variables, a subgroup analysis was performed. RESULTS: A final total of 7552 participants were included in this study. Both independent variables had a positive relationship with serum ferritin, with effect values of (ß = 0.68, 95% CI: 0.17-1.19) when BMI was the independent variable and (ß = 8.62, 95% CI: 3.53-13.72) when WWI was the independent variable in the fully adjusted model. This positive association between the two obesity-related indexes and serum ferritin became more significant as BMI and WWI increased (P for trend < 0.001). In subgroup analyses, the positive association between the independent variables and serum ferritin was more pronounced in participants who were male, 40-59 years old, white, and had diabetes and hypertension. In addition, smoothed curve fitting and threshold effects analysis demonstrated a linear positive association of BMI and WWI with serum ferritin. CONCLUSIONS: In the US adult population, while there was a linear positive association of WWI and BMI with serum ferritin, the effect values between WWI and serum ferritin were more significant. Male, 40-59 years old, white, participants with diabetes and hypertension should be cautious that higher WWI might entail a risk of higher serum ferritin levels.
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Hipertensão , Humanos , Adulto , Masculino , Pessoa de Meia-Idade , Feminino , Índice de Massa Corporal , Inquéritos Nutricionais , Obesidade/epidemiologia , FerritinasRESUMO
The importance of serum ferritin has been demonstrated in many liver diseases, but its relationship with liver stiffness remains unclear. The objective of this study was to investigate the association between serum ferritin levels and participants' liver stiffness measurement (LSM) in the United States population. We conducted a screening of participants from National Health and Nutrition Examination Survey (NHANES) 2017.1 to 2020.3 to ensure that participants included in this study had complete serum ferritin and LSM information. Association between the independent variable (serum ferritin) and the dependent variable (LSM) was investigated by multiple linear regression and subgroup analysis was performed to identify sensitive individuals, and we subsequently assessed whether there was a non-linear relationship between the 2 using smoothed curve fitting and threshold effect models. The final 7143 participants were included in this study. There was a positive association between participants' serum ferritin concentration and LSM, with an effect value of (ß = 0.0007, 95% confidence interval (CI): 0.0002-0.0011) in the all-adjusted model. The smoothing curve and threshold effect models indicated a non-linear positive correlation between serum ferritin and LSM, which was more pronounced when serum ferritin concentration exceeded 440 ng/mL. Subsequent subgroup analysis showed that this positive correlation was more pronounced in males (ß = 0.0007, 95% CI: 0.0001-0.0012), age >60 years (ß = 0.00015, 95% CI: 0.0007-0.0023), black participants (ß = 0.00018, 95% CI: 0.0009-0.0026), and participants with body mass index (BMI) <25 kg/m2 (ß = 0.00012, 95% CI: 0.0005-0.0020). In U.S. adults, there was a positive correlation between serum ferritin levels and liver stiffness, which was more pronounced when serum ferritin exceeded 440 ng/mL. Our study suggested that regular serum ferritin testing would be beneficial in monitoring changes in liver stiffness. Male, age >60 years, black participants, and those with a BMI < 25 kg/m2 should be of greater consideration.
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Ferritinas , Fígado , Adulto , Humanos , Masculino , Estudos Transversais , Ferritinas/sangue , Fígado/diagnóstico por imagem , Inquéritos Nutricionais , Feminino , Pessoa de Meia-Idade , Negro ou Afro-AmericanoRESUMO
The novel coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, the World Health Organization has confirmed that COVID-19 is a global infectious disease pandemic. This is the third acute infectious disease caused by coronavirus infection in this century, after sudden acute respirator syndrome and Middle East respiratory syndrome. The damage mechanism of SARS-CoV-2 is still unclear. It is possible that protein S binds to angiotensin-converting enzyme 2 receptors and invades alveolar epithelial cells, causing direct toxic effects and an excessive immune response. This stimulates a systemic inflammatory response, thus forming a cytokine storm, which leads to lung tissue injury. In severe cases, the disease can lead to acute respiratory distress syndrome, septic shock, metabolic acidosis, coagulation dysfunction, and multiple organ dysfunction syndromes. Patients with severe COVID-19 have a relatively high mortality rate. Currently, there are no specific antiviral drugs for the treatment of COVID-19. Most patients need to be admitted to the intensive care unit for intensive monitoring and supportive organ function treatments. This article reviews the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment methods of severe COVID-19 and puts forward some tentative ideas, aiming to provide some guidance for the diagnosis and treatment of severe COVID-19.