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Background: Cardiomyocyte death induced by autophagy inhibition is an important cause of cardiac dysfunction. In-depth exploration of its mechanism may help to improve cardiac dysfunction. In our previous study, we found that β1-adrenergic receptor autoantibodies (β1-AAs) induced a decrease in myocardial autophagy and caused cardiomyocyte death, thus resulting in cardiac dysfunction. Through tandem mass tag (TMT)-based quantitative proteomics, autophagy-related S100a9 protein was found to be significantly upregulated in the myocardial tissue of actively immunized mice. However, whether S100a9 affects the cardiac function in the presence of β1-AAs through autophagy and the specific mechanism are currently unclear. Methods: In this study, the active immunity method was used to establish a β1-AA-induced mouse cardiac dysfunction model, and RT-PCR and western blot were used to detect changes in gene and protein expression in cardiomyocytes. We used siRNA to knockdown S100a9 in cardiomyocytes. An autophagy PCR array was performed to screen differentially expressed autophagy-related genes in cells transfected with S100a9 siRNA and negative control siRNA. Cytoplasmic nuclear separation, co-immunoprecipitation (Co-IP), and immunofluorescence were used to detect the binding of S100a9 and hypoxia inducible factor-1α (HIF-1α). Finally, AAV9-S100a9-RNAi was injected into mice via the tail vein to knockdown S100a9 in cardiomyocytes. Cardiac function was detected via ultrasonography. Results: The results showed that β1-AAs induced S100a9 expression. The PCR array indicated that Atg9a changed significantly in S100a9siRNA cells and that β1-AAs increased the binding of S100a9 and HIF-1α in cytoplasm. Knockdown of S100a9 significantly improved autophagy levels and cardiac dysfunction. Conclusion: Our research showed that β1-AAs increased S100a9 expression in cardiomyocytes and that S100a9 interacted with HIF-1α, which prevented HIF-1α from entering the nucleus normally, thus inhibiting the transcription of Atg9a. This resulted in autophagy inhibition and cardiac dysfunction. [ABSTRACT FROM AUTHOR]

The metabolism of cells and blood circulation allow for the constant production and destruction of red blood cells. Erythrocyte formation allows red blood cells to regenerate, which is crucial for maintaining the equilibrium of the organism. Erythrocyte formation is a multi‐step, intricate process with distinct structural and functional characteristics at each stage. Erythropoiesis is regulated by a number of signaling pathways; malfunctional regulatory mechanisms may result in disease and aberrant erythropoiesis. Therefore, this article focuses on a review of the erythroid formation process, related signaling pathways, and red blood cell lineage diseases. [ABSTRACT FROM AUTHOR]

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Global ocean governance is the concretization of global governance. Various interest groups interact with and coordinate ocean issues. Global ocean governance is inevitably linked to the new global governance landscape. In recent years, a series of new scenarios in global governance have emerged. These situations have further shaped the plurality of participants and the diversity of mechanisms in global ocean governance. Science and technology innovation and application are prerequisites and prime movers for the evolution of global ocean governance. Major worldwide crises, represented by global climate change and the coronavirus disease 2019 pandemic, have added great uncertainty to the future development of global ocean governance. The divergence of interests and positions between emerging countries and developed countries, as well as the reshaping of the global geopolitical landscape in recent years, has led to the stagnation or deadlock of a series of international negotiations and international cooperation platforms related to global ocean governance. With the deepening of global governance, non-state actors are not only objects of ocean governance but also bearers of legal obligations and enjoy varying degrees of legal rights, participating in agenda setting, rule construction, and monitoring implementation at different levels of ocean governance. From a critical jurisprudence perspective, in the practice of global ocean governance, the relationship between non-governmental organizations, states, and international organizations is more likely to be one of reconciliation than the "state–civil society" dichotomy of moral imagination. This new set of circumstances exposes the divisive and fragmented nature of global ocean governance. This study concludes that the new situation of global ocean governance constitutes a historic opportunity for countries to reexamine the role of the rule of law during the Anthropocene to bridge the fragmentation and gaps in mechanisms and achieve a truly integrated, holistic, and closely nested global ocean governance. The question of how to implement the rule of law requires the introduction of theoretical perspectives such as the Anthropocene, complex systems theory, and the community of a shared future for humanity to undertake a fundamental critical reflection and rethinking of global ocean governance. [ABSTRACT FROM AUTHOR]

Angiotensin II type 1 receptor (AT1R) is a promising therapeutic target for cardiovascular diseases. Compared with orthosteric ligands, allosteric modulators attract considerable attention for drug development due to their unique advantages of high selectivity and safety. However, no allosteric modulators of AT1R have been applied in clinical trials up to now. Except for the classical allosteric modulators of AT1R such as antibody, peptides and amino acids, cholesterol and biased allosteric modulators, there are non-classical allosteric modes including the ligand-independent allosteric mode, and allosteric mode of biased agonists and dimers. In addition, finding the allosteric pockets based on AT1R conformational change and interaction interface of dimers are the future of drug design. In this review, we summarize the different allosteric mode of AT1R, with a view to contribute to the development and utilization of drugs targeting AT1R allostery. [ABSTRACT FROM AUTHOR]