RBM15 Protects From Myocardial Infarction by Stabilizing NAE1.

RNA-binding proteins play multiple roles in several biological processes. However, the roles of RBM15-an important RNA-binding protein and a significant regulator of RNA methylation-in cardiovascular diseases remain elusive. This study aimed to investigate the biological function of RBM15 and its fundamental mechanisms in myocardial infarction (MI). Methylated RNA immunoprecipitation sequencing was used to explore the N6-methyladenosine (m6A) difference between MI and normal tissues. Our findings showed the elevated level of m6A in MI, and its transcription profile in both MI and normal tissues. RBM15 was the main regulator and its overexpression attenuated apoptosis in cardiomyocytes and improved cardiac function in mice after MI. Then, we used one target NEDD8 activating enzyme E1 subunit and its inhibitor (MLN4924) to investigate the impact of RBM15 targets on cardiomyocytes. Finally, the enhanced m6A methylation in the presence of RBM15 overexpression led to the increased expression and stability of NEDD8 activating enzyme E1 subunit. Our findings suggest that the enhanced m6A level is a protective mechanism in MI, and RBM15 is significantly upregulated in MI and promotes cardiac function. This study showed that RBM15 affected MI by stabilizing its target on the cell apoptosis function, which might provide a new insight into MI therapy.

Time-lag and accumulation responses of vegetation growth to average and extreme precipitation and temperature events in China between 2001 and 2020.

Climate change is often closely related to vegetation dynamics; time lag (Tlag) and accumulative effects (Tacc) are non-negligible phenomena when studying the interaction between climate and vegetation. But, amidst the escalating frequency of extreme climatic events, the quantification of temporal effects (Teffects) of such extremes on vegetation remains scarce. This research quantifies the Tlag and Tacc responses of China's vegetation to episodes of extreme temperature and precipitation since the early 2000s, utilizing daily meteorological data series. Overall, the precipitation in China has become wetter, and nighttime temperatures have risen significantly. The proportion of areas with Teffects ranged from 1.15 % to 15.95 %, and the correlation coefficient between the climate indices and the Normalized Difference Vegetation Index (NDVI) increased by 0.05 to 0.38 when considering the Teffects, compared to not considering it. The Tacc of vegetation had the strongest response (70.74-88.01 %) to extreme events among all the tested climate indices. Moreover, the Tacc of consecutive climate events had a greater impact on vegetation growth than individual climate event. The average Tacc for extreme temperature and extreme precipitation was 1.7-3.09 months and 2.17-3.25 months, respectively. Events like the over 95 % (R95p) and 99 % (R99p) percentile heavy precipitation and the maximum precipitation amount in one day (Rx1day) caused significant Teffects on NDVI. In addition, 90 % of grasslands exhibit Tacc, mainly contributed by the extreme precipitation indices (55.7 %), while the Teffects of forests were stronger than those of extreme temperature. Furthermore, NDVI was more affected by annual precipitation than by extreme precipitation, but the opposite was true for temperature. The results of this study highlight the importance of considering the Tlag and Tacc when predicting the effects of climate change on vegetation dynamics.

Nocturnal stomatal behaviour and its impact on water use strategies of desert herbs in the Gurbantunggut Desert, Northwest China.

Nocturnal stomatal behaviour has the potential to exert a profound influence on plant-water relations, especially water use efficiency. However, we know very less about plant functional type differences in nocturnal stomatal conductance and their roles in plant stress adaptation, especially drought adaptation. To address this critical knowledge gap, we assessed diel leaf gas exchanges in eight ephemeral and perennial herbs growing on the southern edge of the Gurbantunggut Desert, Northwest China. For both ephemeral and perennial herbs, the nocturnal stomatal conductance (gs) exceeded 30 % of daytime gs, except for an ephemeral herb (Malcolmia scorpioides). The nocturnal gs in the studied perennial herbs were significantly higher than it in the ephemeral herbs. The results suggest that circadian-driven stomatal priming plays a pivotal role in accelerating the attainment of steady-state gs during the morning for perennial herbs, thereby enhancing their capacity for carbon capture. Moreover, the nocturnal stomatal behaviour of the ephemeral herbs favored water retention in the morning, consequently enhanced intrinsic water use efficiency and long-term water use efficiency. In summary, plant functional type differences in the magnitude of nocturnal stomatal opening were related to differences in water acquisition and utilization and highlighted diverse water use strategies in the desert plants.

Real-world performance of indobufen versus aspirin after percutaneous coronary intervention: insights from the ASPIRATION registry.

BACKGROUND: Indobufen is widely used in patients with aspirin intolerance in East Asia. The OPTION trial launched by our cardiac center examined the performance of indobufen based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, the vast majority of patients with acute coronary syndrome (ACS) and aspirin intolerance were excluded. We aimed to explore this question in a real-world population. METHODS: Patients enrolled in the ASPIRATION registry were grouped according to the DAPT strategy that they received after PCI. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. Propensity score matching (PSM) was adopted for confounder adjustment. RESULTS: A total of 7135 patients were reviewed. After one-year follow-up, the indobufen group was associated with the same risk of MACCE versus the aspirin group after PSM (6.5% vs. 6.5%, hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.65 to 1.52, P = 0.978). However, BARC type 2, 3, or 5 bleeding was significantly reduced (3.0% vs. 11.9%, HR = 0.24, 95% CI = 0.15 to 0.40, P < 0.001). These results were generally consistent across different subgroups including aspirin intolerance, except that indobufen appeared to increase the risk of MACCE in patients with ACS. CONCLUSIONS: Indobufen shared the same risk of MACCE but a lower risk of bleeding after PCI versus aspirin from a real-world perspective. Due to the observational nature of the current analysis, future studies are still warranted to further evaluate the efficacy of indobufen based DAPT, especially in patients with ACS. TRIAL REGISTRATION: Chinese Clinical Trial Register ( https://www.chictr.org.cn ); Number: ChiCTR2300067274.

A case of repeated in-stent restenosis of coronary artery as a primary manifestation of seronegative antiphospholipid antibody syndrome.

BACKGROUND: Antiphospholipid antibody syndrome (APS) is a multisystemic autoimmune disorder which affects many organs or systems; however, coronary artery is relatively less frequently involved. CASE PRESENTATION: A 65-year-old female with effort chest pain was hospitalized for unstable angina in Janurary, 2015. Coronary angiography revealed sub-total occlusion of proximal left anterior descending (LAD) coronary artery, where a drug-eluting stent was successfully deployed. The patient experienced multiple in-stent stenosis at LAD coronary artery and coronary artery bypass graft (CABG) surgery was advised. Subsequently, severe stenosis of left circumflex (LCX) coronary artery emerged, and the patient suffered persistent in-stent restenosis. Eventually, the patient was diagnosed with seronegative antiphospholipid antibody syndrome and salvaged by immunosuppressants. CONCLUSIONS: Repeated in-stent restenosis could be a primary manifestation of seronegative antiphospholipid antibody syndrome, and suppression of autoimmune activity and inflammation other than purely coronary revascularization might be a better option.

Differential eco-physiological performance to declining groundwater depth in Central Asian C3 and C4 shrubs in the Gurbantunggut Desert.

Resources in water-limited ecosystems are highly variable and unpredictable, and the maintenance of functional diversity among coexisting species is a crucial ecological strategy through which plants mitigate environmental stress. The comparison of differential eco-physiological responses among co-occurring plants in harsh environments could help provide deep insights into the coexistence mechanisms of competing species. Two coexisting desert shrubs with different photosynthetic pathways (Haloxylon ammodendron and Tamarix ramosissima) were selected in the Gurbantunggut Desert located in northwest China. This study detected variations in the water sources, photosynthetic parameters, stem water status, and non-structural carbohydrates of the two shrubs at three sites with different groundwater table depths during the growing seasons of 2015 and 2016 to identify distinct eco-physiological performances in coexisting plants with different functional types under fluctuating water conditions. The water sources of H. ammodendron shifted from soil water to groundwater, while T. ramosissima extracted water mainly from deep soil layers at both sites. Significant reductions in carbon assimilation and stomatal conductance in H. ammodendron with deeper groundwater table depth were detected during most drought periods, but no significant decreases in transpiration rate were detected with declining groundwater table depth. For T. ramosissima, all of these gas exchange parameters decreased with the progression of summer drought, and their relative reduction rates were larger compared with those of H. ammodendron. The stem water status of H. ammodendron deteriorated, and the relative reduction rates of water potential increased with deeper groundwater, whereas those of T. ramosissima did not differ with greater groundwater depth. These findings indicated that prolonged drought would intensify the impact of declining groundwater depth on the eco-physiology of both shrubs, but the extent to which the shrubs would respond differed. The two shrubs were segregated along the water-carbon balance continuum: the C3 shrub T. ramosissima maximized its carbon fixation at an enormous cost of water, while greater carbon fixation was achieved with far greater water economy for H. ammodendron. These results demonstrated that the two shrubs prioritized carbon gain and water loss differently when faced with limited water sources. These mechanisms might mitigate competitive stress and enable their coexistence.