LncRNA CCRR maintains Ca2+ homeostasis against myocardial infarction through the FTO-SERCA2a pathway.

Cardiac conduction regulatory RNA (CCRR) has been documented as an antiarrhythmic lncRNA in our earlier investigation. This study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca2+ homeostasis in myocardial infarction (MI). Overexpression of CCRR via AAV9-mediated delivery not only partially reversed ischemia-induced contractile dysfunction but also alleviated abnormal Ca2+ homeostasis and reduced the heightened methylation level of SERCA2a following MI. These effects were also observed in CCRR over-expressing transgenic mice. A conserved sequence domain of CCRR mimicked the protective function observed with the full length. Furthermore, silencing CCRR in healthy mice led to intracellular Ca2+ overloading of cardiomyocytes. CCRR increased SERCA2a protein stability by upregulating FTO expression. The direct interaction between CCRR and FTO protein was characterized by RNA-binding protein immunoprecipitation (RIP) analysis and RNA pulldown experiments. Activation of NFATc3 was identified as an upstream mechanism responsible for CCRR downregulation in MI. This study demonstrates that CCRR is a protective lncRNA that acts by maintaining the function of FTO, thereby reducing the m6A RNA methylation level of SERCA2a, ultimately preserving calcium homeostasis for myocardial contractile function in MI. Therefore, CCRR may be considered a promising therapeutic strategy with a beneficial role in cardiac pathology.

LncRNA CCRR Attenuates Postmyocardial Infarction Inflammatory Response by Inhibiting the TLR Signalling Pathway.

BACKGROUND: Timely and proper suppression of inflammation can effectively reduce myocardial injury and promote the postmyocardial infarction (post-MI) wound-healing process. We have previously found that cardiac conduction regulatory RNA (CCRR), a long noncoding RNA (lncRNA) transcribed by the gene located on chromosome 9, with abundant expression in the heart, elicits antiarrhythmic effects in heart failure, and this is a continuing study on the role of CCRR in MI. METHODS: CCRR was overexpressed in CCRR transgenic mice or after injection of adeno-associated virus-9 (AAV-9). MI surgery was performed, and cardiac function was assessed in vivo by echocardiography, followed by histologic analyses. Western blot analysis and qRT-PCR were performed to investigate the effects of CCRR on macrophages, cardiomyocytes, and cardiomyocytes cocultured with macrophages. Through microarray analysis and RNA-binding protein immunoprecipitation (RIP) and other related techniques were also employed to study the effects of CCRR on Toll-like receptor (TLR)2 and TLR4. RESULTS: We found that CCRR level was significantly decreased with increases in proinflammatory cytokines and activation of the TLR signalling pathway in the heart of the 3-day MI mice. CCRR overexpression downregulated TLR2 and TLR4 in MI and effectively inhibited the inflammatory responses in primary cardiomyocytes and macrophages cultured under hypoxic conditions. Downregulation of CCRR induced excessive inflammatory responses by activating the TLR signalling pathway. CCRR acted by suppressing TLR2 and TLR4 to inhibit the secretion of proinflammatory factors to reduce infarct size, thereby improving cardiac function. CONCLUSIONS: CCRR protected cardiomyocytes against MI injury by suppressing inflammatory response through targeting the TLR signalling pathway.

Model of Urban Marketing Strategy Based on Ecological Environment Quality.

Ecological environment quality is increasingly becoming a critical priority in measuring the sustainable development of modern cities. Reflecting on the reality of contemporary urban development, we create a structural equation model with city image and ecological quality as the antecedents of sustainable urban development, reflect on and expand the existing models of sustainable urban development, and further explore the mechanisms of various urban marketing factors on the shaping of city image. The study found that the continuous improvement of city marketing assets contributes to the process of shaping sustainable city branding. City image has a direct and significant positive impact on city recognition, city reputation, and perceived quality. Ecological environment quality also has a direct effect on city recognition and no direct effect on perceived quality or city reputation. However, ecological environment quality can affect city's reputation by acting on perceived quality through city recognition and then enhance the competitiveness of city sustainable development. The case practice of shaping a city's image by ecological environment quality illustrates the pragmatic return of humanism in contemporary urban development. While the halo effect of city image still exists, a good city reputation becomes another important influence on perceived quality and sustainability. This study facilitates the development of urban sustainable development theory and the extension of urban branding innovation theory, which will promote international dialogue in the field of urban eco-environment in China.

Modeling of the Ecological Carrying Index of reclaimed land in coastal city: A sustainable marine ecology perspective.

In recent years, Wenzhou City located on the southeast coast of China has experienced the largest scale of land reclamation projects in China. However, the extent to which such projects still bring about the destruction of marine resources and the environment. So, in this study, a marine ecological development carrying capacity index model was established and analyzed the ecological carrying capacity index of the reclaimed sea area in Wenzhou with the detection and warning conditions to propose a marine ecological protection supervision mechanism. By the proposed mechanism, five primary-level indicators and 10 corresponding secondary-level indicators were established. The obtained results showed that the ecological carrying index of the reclaimed area in Wenzhou falls within the range, 2.35-5.45, which is indicative of small geographic differences. These results suggest that in future, a detection and early warning mechanism for the determination of the ecological carrying capacity of reclaimed sea areas should be established. Furthermore, the strict implementation of the reclamation project development evaluation management control system is recommended, and it is also necessary to reasonably adjust the planning and construction of the sea area.