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Biomechanical cues play an essential role in sculpting organ formation. Comprehending how cardiac cells perceive and respond to biomechanical forces is a biological process with significant medical implications that remains poorly understood. Here, we show that biomechanical forces activate endocardial id2b (inhibitor of DNA-binding 2b) expression, thereby promoting cardiac contractility and valve formation in zebrafish. Taking advantage of the unique strengths of zebrafish, particularly the viability of embryos lacking heartbeats, we systematically compared the transcriptomes of hearts with impaired contractility to those of control hearts. This comparison identified id2b as a gene sensitive to blood flow. By generating a knock-in reporter line, our results unveiled the presence of id2b in the endocardium, and its expression is sensitive to both pharmacological and genetic perturbations of contraction. Furthermore, id2b loss-of-function resulted in progressive heart malformation and early lethality. Combining RNA-seq analysis, electrophysiology, calcium imaging, and echocardiography, we discovered profound impairment in atrioventricular (AV) valve formation and defective excitation-contraction coupling in id2b mutants. Mechanistically, deletion of id2b reduced AV endocardial cell proliferation and led to a progressive increase in retrograde blood flow. In the myocardium, id2b directly interacted with the bHLH component tcf3b (transcription factor 3b) to restrict its activity. Inactivating id2b unleashed its inhibition on tcf3b , resulting in enhanced repressor activity of tcf3b , which subsequently suppressed the expression of nrg1 (neuregulin 1), an essential mitogen for heart development. Overall, our findings identify id2b as an endocardial cell-specific, biomechanical signaling-sensitive gene, which mediates intercellular communications between endocardium and myocardium to sculpt heart morphogenesis and function.

The Tibetan Plateau (TP) serves as a vital ecological safeguard and water conservation region in China. In recent decades, substantial efforts have been made to promote vegetation greening across the TP; however, these interventions have added complexity to the local water balance and evapotranspiration (ET) processes. To investigate these dynamics, we apply the Priestley–Taylor Jet Propulsion Laboratory (PT-JPL) model to simulate ET components in the TP. Through model sensitivity experiments, we isolate the contribution of vegetation greening to ET variations. Furthermore, we analyze the role of climatic drivers on ET using a suite of statistical techniques. Based on satellite and climate data from 1982 to 2018, we found the following: (1) The PT-JPL model successfully captured ET trends over the TP, revealing increasing trends in total ET, canopy transpiration, interception loss, and soil evaporation at rates of 0.06, 0.39, 0.005, and 0.07 mm/year, respectively. The model’s performance was validated using eddy covariance observations from three flux tower sites, yielding R2 values of 0.81–0.86 and RMSEs ranging from 6.31 to 13.20 mm/month. (2) Vegetation greening exerted a significant enhancement on ET, with the mean annual ET under greening scenarios (258.6 ± 120.9 mm) being 2.9% greater than under non-greening scenarios (251.2 ± 157.2 mm) during 1982–2018. (3) Temperature and vapor pressure deficit were the dominant controls on ET, influencing 53.5% and 23% of the region, respectively, as identified consistently by both multiple linear regression and dominant factor analyses. These findings highlight the net influence of vegetation greening and offer valuable guidance for water management and sustainable ecological restoration efforts in the region.

For the management of the water cycle, it is essential to comprehend evapotranspiration (ET) and how it changes over time and space, especially in relation to vegetation. Here, using the Priestley–Taylor Jet Propulsion Laboratory (PT-JPL) model, we explored the spatiotemporal variations in ET across different time scales during 1982–2018 in the Wuding River Basin. We also quantitatively evaluated the driving mechanisms of climate and vegetation changes on ET changes. Results showed that the ET estimate by the PT-JPL model showed good agreement (R2 = 0.71–0.84) with four ET products (PML, MOD16A2, GLASS, FLDAS). Overall, the ET increased significantly at a rate of 3.11 mm/year (p < 0.01). Spatially, ET in the WRB is higher in the southeast and lower in the northwest. Attribution analysis indicated that vegetation restoration (leaf area index) was the dominant driver of ET changes (99.93% basin area, p < 0.05), exhibiting both direct effects and indirect mediation through the Vapor Pressure Deficit. Temperature influences emerged predominantly through vegetation feedbacks rather than direct climatic forcing. These findings establish vegetation restoration as a key driver of regional ET, providing empirical support for optimizing revegetation strategies in semi-arid environments.

A cardiac injury study in zebrafish reveals the plasticity of heart cell lineages as shown by a Notch-dependent transdifferentiation of atrial to ventricular cardiomyocytes, regenerating a cell type that is damaged in human heart failure. Heart cells with regenerative potential Obstacles to the use of stem-cell therapy in heart failure patients include the difficulty of ensuring the differentiation of cardiac progenitor cells into functional ventricular cardiomyocytes, and the delivery and integration of differentiated cells into the patient's ventricular myocardium. Neil Chi and colleagues studied the ability of specific cardiac muscle cell types to differentiate into closely related but distinct cell types in embryonic zebrafish hearts. They find that differentiated atrial cardiomyocytes can transform into ventricular cardiomyocytes when the heart is injured and that the Notch signalling pathway induces the regeneration. This work identifies an endogenous population of cardiac cells as a potential source for cardiac ventricular regeneration. Despite current treatment regimens, heart failure remains the leading cause of morbidity and mortality in the developed world due to the limited capacity of adult mammalian ventricular cardiomyocytes to divide and replace ventricular myocardium lost from ischaemia-induced infarct 1 , 2 . Hence there is great interest to identify potential cellular sources and strategies to generate new ventricular myocardium 3 . Past studies have shown that fish and amphibians and early postnatal mammalian ventricular cardiomyocytes can proliferate to help regenerate injured ventricles 4 , 5 , 6 ; however, recent studies have suggested that additional endogenous cellular sources may contribute to this overall ventricular regeneration 3 . Here we have developed, in the zebrafish ( Danio rerio ), a combination of fluorescent reporter transgenes, genetic fate-mapping strategies and a ventricle-specific genetic ablation system to discover that differentiated atrial cardiomyocytes can transdifferentiate into ventricular cardiomyocytes to contribute to zebrafish cardiac ventricular regeneration. Using in vivo time-lapse and confocal imaging, we monitored the dynamic cellular events during atrial-to-ventricular cardiomyocyte transdifferentiation to define intermediate cardiac reprogramming stages. We observed that Notch signalling becomes activated in the atrial endocardium following ventricular ablation, and discovered that inhibiting Notch signalling blocked the atrial-to-ventricular transdifferentiation and cardiac regeneration. Overall, these studies not only provide evidence for the plasticity of cardiac lineages during myocardial injury, but more importantly reveal an abundant new potential cardiac resident cellular source for cardiac ventricular regeneration.

A complex interplay involving Notch- and Erbb2-mediated signalling between cardiomyocytes guides the morphogenesis of the ventricular wall. Many organs are composed of complex tissue walls that are structurally organized to optimize organ function. In particular, the ventricular myocardial wall of the heart comprises an outer compact layer that concentrically encircles the ridge-like inner trabecular layer. Although disruption in the morphogenesis of this myocardial wall can lead to various forms of congenital heart disease 1 and non-compaction cardiomyopathies 2 , it remains unclear how embryonic cardiomyocytes assemble to form ventricular wall layers of appropriate spatial dimensions and myocardial mass. Here we use advanced genetic and imaging tools in zebrafish to reveal an interplay between myocardial Notch and Erbb2 signalling that directs the spatial allocation of myocardial cells to their proper morphological positions in the ventricular wall. Although previous studies have shown that endocardial Notch signalling non-cell-autonomously promotes myocardial trabeculation through Erbb2 and bone morphogenetic protein (BMP) signalling 3 , we discover that distinct ventricular cardiomyocyte clusters exhibit myocardial Notch activity that cell-autonomously inhibits Erbb2 signalling and prevents cardiomyocyte sprouting and trabeculation. Myocardial-specific Notch inactivation leads to ventricles of reduced size and increased wall thickness because of excessive trabeculae, whereas widespread myocardial Notch activity results in ventricles of increased size with a single-cell-thick wall but no trabeculae. Notably, this myocardial Notch signalling is activated non-cell-autonomously by neighbouring Erbb2-activated cardiomyocytes that sprout and form nascent trabeculae. Thus, these findings support an interactive cellular feedback process that guides the assembly of cardiomyocytes to morphologically create the ventricular myocardial wall and more broadly provide insight into the cellular dynamics of how diverse cell lineages organize to create form.

Vegetation net primary productivity (NPP) serves as a crucial and intuitive indicator for assessing ecosystem health. However, the nonlinear dynamics and influencing factors operating at various time scales are not yet fully understood. Here, the ensemble empirical mode decomposition (EEMD) method was used to analyze the spatiotemporal patterns of NPP and its association with hydrothermal factors and anthropogenic activities across different temporal scales for the Yellow River Basin (YRB) from 2000 to 2020. The results indicate that: (1) the annual average NPP was 236.37 g C/m2 in the YRB and increased at rates of 4.64 g C/m2/a1 (R2 = 0.86, p < 0.01) during 2000 to 2020. Spatially, nonlinear analysis indicates that 72.77% of the study area exhibits a predominantly increasing trend in NPP, while 25.17% exhibits a reversing trend. (2) On a 3-year time scale, warming has resulted in an increase in NPP in the majority of areas of the study area (69.49%). As the time scale widens, the response of vegetation to climate change becomes more prominent; especially under the long-term trend, the percentage areas of the correlation between vegetation and precipitation and temperature increased with significance, reaching 48.21% and 11.57%, respectively. (3) Through comprehensive time analysis and multivariate regression analysis, it was confirmed that both human activities and climate factors had comparable impacts on vegetation growth. Among different vegetation types, climate was still the main factor affecting grassland NPP, and only 15.74% of grassland was affected by human activities. For shrubland, forest, and farmland, human activity was a dominating factor for vegetation NPP change. There are still few studies on vegetation change using nonlinear methods in the Yellow River Basin, and most studies have not considered the effect of time scale on vegetation evolution. The findings highlight the significance of multi-time scale analysis in understanding the vegetation dynamics and providing scientific guidance for future vegetation restoration and conservation efforts.

Evapotranspiration (E), a pivotal phenomenon inherent to hydrological and thermal dynamics, assumes a position of utmost importance within the intricate framework of the water–energy nexus. However, the quantitative study of E on a large scale for the “Grain for Green” projects under the backdrop of climate change is still lacking. Consequently, this study examined the interannual variations and spatial distribution patterns of E, transpiration (Et), and soil evaporation (Eb) in the Northern Foot of Yinshan Mountain (NFYM) between 2000 and 2020 and quantified the contributions of climate change and vegetation greening to the changes in E, Et, and Eb. Results showed that E (2.47 mm/a, p < 0.01), Et (1.30 mm/a, p < 0.01), and Eb (1.06 mm/a, p < 0.01) all exhibited a significant increasing trend during 2000–2020. Notably, vegetation greening emerged as the predominant impetus underpinning the augmentation of both E and Eb, augmenting their rates by 0.49 mm/a and 0.57 mm/a, respectively. In terms of Et, meteorological factors emerged as the primary catalysts, with temperature (Temp) assuming a predominant role by augmenting Et at a rate of 0.35 mm/a. Temp, Precipitation (Pre), and leaf area index (LAI) collectively dominated the proportional distribution of E, accounting for shares of 32.75%, 28.43%, and 25.01%, respectively. Within the spectrum of predominant drivers influencing Et, Temp exerted the most substantial influence, commanding the largest proportion at 33.83%. For Eb, the preeminent determinants were recognized as LAI and Temp, collectively constituting a substantial portion of the study area, accounting for 32.10% and 29.50%, respectively. The LAI exerted a pronounced direct influence on the Et, with no significant effects on E and bare Eb. Wind speed (WS) had a substantial direct impact on both E and Et. Pre exhibited a strong direct influence on E, Et, and Eb. Relative humidity (RH) significantly affected E directly. Temp primarily influenced Eb indirectly through radiation (Rad). Rad exerted a significant direct inhibitory effect on Eb. These findings significantly advanced our mechanistic understanding of how E and its components in the NFYM respond to climate change and vegetation greening, thus providing a robust basis for formulating strategies related to regional ecological conservation and water resources management, as well as supplying theoretical underpinnings for constructing sustainable vegetation restoration strategies involving water resources in the region.

Pressure overload–induced cardiac hypertrophy is a common cause of heart failure (HF), and emerging evidence suggests that excessive oxidized lipids have a detrimental effect on cardiomyocytes. However, the key regulator of lipid toxicity in cardiomyocytes during this pathological process remains unknown. Here, we used lipidomics profiling and RNA-seq analysis and found that phosphatidylethanolamines (PEs) and Acsl4 expression are significantly increased in mice with transverse aortic constriction (TAC)–induced HF compared to sham-operated mice. In addition, we found that overexpressing Acsl4 in cardiomyocytes exacerbates pressure overload‒induced cardiac dysfunction via ferroptosis. Notably, both pharmacological inhibition and genetic deletion of Acsl4 significantly reduced left ventricular chamber size and improved cardiac function in mice with TAC-induced HF. Moreover, silencing Acsl4 expression in cultured neonatal rat ventricular myocytes was sufficient to inhibit hypertrophic stimulus‒induced cell growth. Mechanistically, we found that Acsl4-dependent ferroptosis activates the pyroptotic signaling pathway, which leads to increased production of the proinflammatory cytokine IL-1β, and neutralizing IL-1β improved cardiac function in Acsl4 transgenic mice following TAC. These results indicate that ACSL4 plays an essential role in the heart during pressure overload‒induced cardiac remodeling via ferroptosis-induced pyroptotic signaling. Together, these findings provide compelling evidence that targeting the ACSL4-ferroptosis-pyroptotic signaling cascade may provide a promising therapeutic strategy for preventing heart failure.

Uncovering the trade-offs and synergy relationship of multiple ecosystem services (ESs) is important for scientific ecosystem management and the improvement of ecological service functions. In this study, we investigated the spatiotemporal changes of four typical ES types (i.e., water yield (WY), carbon storage (CS), soil conservation (SC), and habitat quality (HQ)) from 2001 to 2020 in the Han River Basin (HRB). Meanwhile, the trade-offs and synergies between paired ESs and the socioecological drivers of these ESs were further explored. The results showed that grassland, cropland, and bare land decreased by 12,141.3 km2, 624.09 km2, and 22.1 km2 during the study period, respectively, which can be attributed to their conversion to forests in the HRB. Temporally, the WY, CS, and SC all showed a continuously increasing trend. Spatially, WY and HQ exhibited bipolar clustering characteristics, with WY exhibiting low-value clustering in the upstream and high-value clustering in the downstream, while CS showed the clustering characteristics of a scattered distribution of cold and hot spots from 2001 to 2020. The spatial patterns of aggregation locations in CS and HQ were relatively similar, with clusters of higher ES values mainly distributed in the western and central regions and clusters of lower ES values mainly located in the eastern and southeastern regions, while the aggregation of WY was spatially concentrated. Overall, the CS showed a significant positive correlation with HQ, but a significant negative correlation with WY. Spatially, WY and HQ, CS, and SC showed a substantial trade-off relationship in the northwest and southeast parts of the study area, while HQ, CS, and SC mainly exhibited a synergistic relationship in most parts of the study area. Slope and temperature had high influencing factor coefficients on multiple ESs; the mixed effect of terrain and natural factors was significantly greater than the impact of a single factor on ESs, and terrain factors played an essential role in the changes in ESs. The findings can provide technical and theoretical support for integrated scientific ecosystem management and sustainable development at the local scale.

While the adult human heart has very limited regenerative potential, the adult zebrafish heart can fully regenerate after 20% ventricular resection. Although previous reports suggest that developmental signaling pathways such as FGF and PDGF are reused in adult heart regeneration, the underlying intracellular mechanisms remain largely unknown. Here we show that H2O2 acts as a novel epicardial and myocardial signal to prime the heart for regeneration in adult zebrafish. Live imaging of intact hearts revealed highly localized H2O2 （-30 μM） production in the epicardium and adjacent compact myocardium at the resection site. Decreasing H2O2 formation with the Duox inhibitors diphenyleneiodonium （DPI） or apocynin, or scavenging H2O2 by catalase overexpression markedly impaired cardiac regeneration while exogenous H2O2 rescued the inhibitory effects of DPI on cardiac regeneration, indicating that H2O2 is an essential and sufficient signal in this process. Mechanistically, elevated H2O2 destabilized the redox-sensitive phosphatase Dusp6 and hence increased the phosphorylation of Erk1/2. The Dusp6 inhibitor BCI achieved similar pro-regenerative effects while transgenic overexpression of dusp6 impaired cardiac regeneration. H2O2 plays a dual role in recruiting immune cells and promoting heart regeneration through two relatively independent pathways. We conclude that H2O2 potentially generated from Duox/Nox2 promotes heart regeneration in zebrafish by unleashing MAP kinase signaling through a derepression mechanism involving Dusp6.