Translational Research of the Acute Effects of Negative Emotions on Vascular Endothelial Health: Findings From a Randomized Controlled Study.

BACKGROUND: Provoked anger is associated with an increased risk of cardiovascular disease events. The underlying mechanism linking provoked anger as well as other core negative emotions including anxiety and sadness to cardiovascular disease remain unknown. The study objective was to examine the acute effects of provoked anger, and secondarily, anxiety and sadness on endothelial cell health. METHODS AND RESULTS: Apparently healthy adult participants (n=280) were randomized to an 8-minute anger recall task, a depressed mood recall task, an anxiety recall task, or an emotionally neutral condition. Pre-/post-assessments of endothelial health including endothelium-dependent vasodilation (reactive hyperemia index), circulating endothelial cell-derived microparticles (CD62E+, CD31+/CD42-, and CD31+/Annexin V+) and circulating bone marrow-derived endothelial progenitor cells (CD34+/CD133+/kinase insert domain receptor+ endothelial progenitor cells and CD34+/kinase insert domain receptor+ endothelial progenitor cells) were measured. There was a group×time interaction for the anger versus neutral condition on the change in reactive hyperemia index score from baseline to 40 minutes (P=0.007) with a mean±SD change in reactive hyperemia index score of 0.20±0.67 and 0.50±0.60 in the anger and neutral conditions, respectively. For the change in reactive hyperemia index score, the anxiety versus neutral condition group by time interaction approached but did not reach statistical significance (P=0.054), and the sadness versus neutral condition group by time interaction was not statistically significant (P=0.160). There were no consistent statistically significant group×time interactions for the anger, anxiety, and sadness versus neutral condition on endothelial cell-derived microparticles and endothelial progenitor cells from baseline to 40 minutes. CONCLUSIONS: In this randomized controlled experimental study, a brief provocation of anger adversely affected endothelial cell health by impairing endothelium-dependent vasodilation.

Genome-Wide Association Studies on Chinese Wheat Cultivars Reveal a Novel Fusarium Crown Rot Resistance Quantitative Trait Locus on Chromosome 3BL.

Fusarium crown rot (FCR), primarily caused by Fusarium pseudograminearum, has emerged as a new threat to wheat production and quality in North China. Genetic enhancement of wheat resistance to FCR remains the most effective approach for disease control. In this study, we phenotyped 435 Chinese wheat cultivars through FCR inoculation at the seedling stage in a greenhouse. Our findings revealed that only approximately 10.8% of the wheat germplasms displayed moderate or high resistance to FCR. A genome-wide association study (GWAS) using high-density 660K SNP led to the discovery of a novel quantitative trait locus on the long arm of chromosome 3B, designated as Qfcr.hebau-3BL. A total of 12 significantly associated SNPs were closely clustered within a 1.05 Mb physical interval. SNP-based molecular markers were developed to facilitate the practical application of Qfcr.hebau-3BL. Among the five candidate FCR resistance genes within the Qfcr.hebau-3BL, we focused on TraesCS3B02G307700, which encodes a protein kinase, due to its expression pattern. Functional validation revealed two transcripts, TaSTK1.1 and TaSTK1.2, with opposing roles in plant resistance to fungal disease. These findings provide insights into the genetic basis of FCR resistance in wheat and offer valuable resources for breeding resistant varieties.

Fine-grained urban blue-green-gray landscape dataset for 36 Chinese cities based on deep learning network.

Detailed and accurate urban landscape mapping, especially for urban blue-green-gray (UBGG) continuum, is the fundamental first step to understanding human-nature coupled urban systems. Nevertheless, the intricate spatial heterogeneity of urban landscapes within cities and across urban agglomerations presents challenges for large-scale and fine-grained mapping. In this study, we generated a 3 m high-resolution UBGG landscape dataset (UBGG-3m) for 36 Chinese metropolises using a transferable multi-scale high-resolution convolutional neural network and 336 Planet images. To train the network for generalization, we also created a large-volume UBGG landscape sample dataset (UBGGset) covering 2,272 km2 of urban landscape samples at 3 m resolution. The classification results for five cities across diverse geographic regions substantiate the superior accuracy of UBGG-3m in both visual interpretation and quantitative evaluation (with an overall accuracy of 91.2% and FWIoU of 83.9%). Comparative analyses with existing datasets underscore the UBGG-3m's great capability to depict urban landscape heterogeneity, providing a wealth of new data and valuable insights into the complex and dynamic urban environments in Chinese metropolises.

Enhancement of broad-spectrum disease resistance in wheat through key genes involved in systemic acquired resistance.

Systemic acquired resistance (SAR) is an inducible disease resistance phenomenon in plant species, providing plants with broad-spectrum resistance to secondary pathogen infections beyond the initial infection site. In Arabidopsis, SAR can be triggered by direct pathogen infection or treatment with the phytohormone salicylic acid (SA), as well as its analogues 2,6-dichloroisonicotinic acid (INA) and benzothiadiazole (BTH). The SA receptor non-expressor of pathogenesis-related protein gene 1 (NPR1) protein serves as a key regulator in controlling SAR signaling transduction. Similarly, in common wheat (Triticum aestivum), pathogen infection or treatment with the SA analogue BTH can induce broad-spectrum resistance to powdery mildew, leaf rust, Fusarium head blight, and other diseases. However, unlike SAR in the model plant Arabidopsis or rice, SAR-like responses in wheat exhibit unique features and regulatory pathways. The acquired resistance (AR) induced by the model pathogen Pseudomonas syringae pv. tomato strain DC3000 is regulated by NPR1, but its effects are limited to the adjacent region of the same leaf and not systemic. On the other hand, the systemic immunity (SI) triggered by Xanthomonas translucens pv. cerealis (Xtc) or Pseudomonas syringae pv. japonica (Psj) is not controlled by NPR1 or SA, but rather closely associated with jasmonate (JA), abscisic acid (ABA), and several transcription factors. Furthermore, the BTH-induced resistance (BIR) partially depends on NPR1 activation, leading to a broader and stronger plant defense response. This paper provides a systematic review of the research progress on SAR in wheat, emphasizes the key regulatory role of NPR1 in wheat SAR, and summarizes the potential of pathogenesis-related protein (PR) genes in genetically modifying wheat to enhance broad-spectrum disease resistance. This review lays an important foundation for further analyzing the molecular mechanism of SAR and genetically improving broad-spectrum disease resistance in wheat.

Intensifying urban imprint on land surface warming: Insights from local to global scale.

Increasing urbanization exacerbates surface energy balance perturbations and the health risks of climate warming; however, it has not been determined whether urban-induced warming and attributions vary from local, regional, to global scale. Here, the local surface urban heat island (SUHI) is evidenced to manifest with an annual daily mean intensity of 0.99°C-1.10°C during 2003-2018 using satellite observations over 536 cities worldwide. Spatiotemporal patterns and mechanisms of SUHI tightly link with climate-vegetation conditions, with regional warming effect reaching up to 0.015°C-0.138°C (annual average) due to surface energy alterations. Globally, the SUHI footprint of 1,860 cities approximates to 1% of the terrestrial lands, about 1.8-2.9 times far beyond the urban impervious areas, suggesting the enlargements of the imprint of urban warming from local to global scales. With continuous development of urbanization, the implications for SUHI-added warming and scaling effects are considerably important on accelerating global warming.

A Novel Polymer Nanoparticle Polydimethyl Diallyl Ammonium Chloride as An Adjuvant Enhances the Immune Response of SARS-CoV-2 Subunit Vaccine.

The Coronavirus Disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has a significant impact on global health and the economy. It has underscored the urgent need for a stable, easily produced and effective vaccine. This study presents a novel approach using SARS-CoV-2 spike (S) protein-conjugated nanoparticles (NPs) in combination with cyclic GMP-AMP (cGAMP) (S-NPs-cGAMP) as a subunit vaccine. When mice are immunized, the antiserum of S-NPs-cGAMP group exhibits a 16-fold increase in neutralizing activity against a pseudovirus, compared to S protein group. Additionally, S-NPs-cGAMP induces even higher levels of neutralizing antibodies. Remarkably, the vaccine also triggers a robust humoral immune response, as evidenced by a notable elevation in virus-specific IgG and IgM antibodies. Furthermore, after 42 days of immunization, there is an observed increase in specific immune cell populations in the spleen. CD3+ CD4+ and CD3+ CD8+ T lymphocytes, as well as B220+ CD19+ and CD3- CD49b+ NK lymphocytes, show an upward trend, indicating a positive cellular immune response. Moreover, the S-NPs-cGAMP demonstrates promising results against the Delta strain and exhibits good cross-neutralization potential against other variants. These findings suggest that pDMDAAC NPs is potential adjuvant and could serve as a versatile platform for future vaccine development.

Immunogenicity and protective efficacy of a trimeric full-length S protein subunit vaccine for porcine epidemic diarrhea virus.

Porcine epidemic diarrhea virus (PEDV) has caused serious economic losses to the pig husbandry worldwide, and the effects of existing commercialized vaccines are suboptimal. Therefore, research to develop an efficacious vaccine for prevention and control of PEDV is essential. In this study, we designed and produced trimerized proteins of full-length PEDV spike (S) protein, S1 subunit, and a tandem of multiple epitopes of S protein using an efficient mammalian expression vector system in HEK 293F cells. The immunogenicity of two commercial adjuvants, M401 and M103, was also evaluated in mice. Enzyme-linked immunosorbent assays demonstrated that all immunized mice generated highly systemic PEDV S-specific IgG and IgA antibodies. Mice in S/M103-immunized group generated the highest neutralizing antibody titer with 1:96. Compared with control group, the subunit vaccines elicited multifunctional CD3+CD4+ and CD3+CD8+ T cells, B220+CD19+ B cells, and CD3-CD49b+ natural killer cells in the spleen. PEDV S/M103 vaccine, which had the best immune effect, was selected for further evaluation in piglets. Immunization with S/M103 vaccine induced high levels of S-specific IgG, IgA, and neutralizing antibodies, and increased the proliferation of peripheral blood mononuclear cells and the expression levels of interferon-γ and interleukin-4 in peripheral blood of piglets. Virus challenge test results showed significantly lower diarrheal index scores and fecal viral loads, and less pathological damage to the intestines in S/M103-immunized piglets than in controls, indicating that S/M103 provides good protection against the virulent virus challenge. Our findings suggest that trimeric PEDV S/M103 has potential as a clinical vaccine candidate.

Enhancement of Chondrogenic Markers by Exosomes Derived from Cultured Human Synovial Fluid-Derived Cells: A Comparative Analysis of 2D and 3D Conditions.

OBJECTIVE: The goal of this pilot study was to investigate the effects of exosomes derived from synovial fluid-derived cells (SFDCs) cultured under normoxic conditions in a two-dimensional (2D) monolayer or encapsulated within a three-dimensional (3D) matrix for chondrogenic differentiation in vitro and cartilage defect repair in vivo. DESIGN: Synovial fluid samples were obtained from three patients, and SFDCs were isolated and expanded either in a 2D monolayer culture or seeded within a transglutaminase cross-linked gelatin (Col-Tgel) to create a 3D gel culture. Exosomes derived from each environment were isolated and characterized. Then, their effects on cartilage-cell proliferation and chondrogenic differentiation were assessed using an in vitro organoid model, and their potential for enhancing cartilage repair was evaluated using a rat cartilage defect model. RESULTS: SFDCs obtained from different donors reached a state of senescence after four passages in 2D culture. However, transferring these cells to a 3D culture environment mitigated the senescence and improved cell viability. The 3D-cultured exosomes exhibited enhanced potency in promoting chondrogenic differentiation, as evidenced by the increased expression of chondrogenic genes and greater deposition of cartilage-specific extracellular matrix. Furthermore, the 3D-cultured exosomes demonstrated superior effectiveness in enhancing cartilage repair and exhibited better healing properties compared to exosomes derived from a 2D culture. CONCLUSIONS: The optimized 3D culture provided a more favorable environment for the proliferation of human synovial cells and the secretion of exosomes compared to the 2D culture. The 3D-cultured exosomes exhibited greater potential for promoting chondrogenic gene expression in vitro and demonstrated improved healing properties in repairing cartilage defects compared to exosomes derived from the 2D culture.

A novel recombinant S-based subunit vaccine induces protective immunity against porcine deltacoronavirus challenge in piglets.

IMPORTANCE: As an emerging porcine enteropathogenic coronavirus that has the potential to infect humans, porcine deltacoronavirus (PDCoV) is receiving increasing attention. However, no effective commercially available vaccines against this virus are available. In this work, we designed a spike (S) protein and receptor-binding domain (RBD) trimer as a candidate PDCoV subunit vaccine. We demonstrated that S protein induced more robust humoral and cellular immune responses than the RBD trimer in mice. Furthermore, the protective efficacy of the S protein was compared with that of inactivated PDCoV vaccines in piglets and sows. Of note, the immunized piglets and suckling pig showed a high level of NAbs and were associated with reduced virus shedding and mild diarrhea, and the high level of NAbs was maintained for at least 4 months. Importantly, we demonstrated that S protein-based subunit vaccines conferred significant protection against PDCoV infection.

SETD2 Deficiency Confers Sensitivity to Dual Inhibition of DNA Methylation and PARP in Kidney Cancer.

SETD2 deficiency alters the epigenetic landscape by causing depletion of H3K36me3 and plays an important role in diverse forms of cancer, most notably in aggressive and metastatic clear-cell renal cell carcinomas (ccRCC). Development of an effective treatment scheme targeting SETD2-compromised cancer is urgently needed. Considering that SETD2 is involved in DNA methylation and DNA repair, a combination treatment approach using DNA hypomethylating agents (HMA) and PARP inhibitors (PARPi) could have strong antitumor activity in SETD2-deficient kidney cancer. We tested the effects of the DNA HMA 5-aza-2'-dexoxydytidine (DAC), the PARPi talazoparib (BMN-673), and both in combination in human ccRCC models with or without SETD2 deficiency. The combination treatment of DAC and BMN-673 synergistically increased cytotoxicity in vitro in SETD2-deficient ccRCC cell lines but not in SETD2-proficient cell lines. DAC and BMN-673 led to apoptotic induction, increased DNA damage, insufficient DNA damage repair, and increased genomic instability. Furthermore, the combination treatment elevated immune responses, upregulated STING, and enhanced viral mimicry by activating transposable elements. Finally, the combination effectively suppressed the growth of SETD2-deficient ccRCC in in vivo mouse models. Together, these findings indicate that combining HMA and PARPi is a promising potential therapeutic strategy for treating SETD2-compromised ccRCC. SIGNIFICANCE: SETD2 deficiency creates a vulnerable epigenetic status that is targetable using a DNA hypomethylating agent and PARP inhibitor combination to suppress renal cell carcinoma, identifying a precision medicine-based approach for SETD2-compromised cancers.

Piezo1：the potential new therapeutic target for fibrotic diseases.

Fibrosis is a pathological process that occurs in various organs, characterized by excessive deposition of extracellular matrix (ECM), leading to structural damage and, in severe cases, organ failure. Within the fibrotic microenvironment, mechanical forces play a crucial role in shaping cell behavior and function, yet the precise molecular mechanisms underlying how cells sense and transmit these mechanical cues, as well as the physical aspects of fibrosis progression, remain less understood. Piezo1, a mechanosensitive ion channel protein, serves as a pivotal mediator, converting mechanical stimuli into electrical or chemical signals. Accumulating evidence suggests that Piezo1 plays a central role in ECM formation and hemodynamics in the mechanical transduction of fibrosis expansion. This review provides an overview of the current understanding of the role of Piezo1 in fibrosis progression, encompassing conditions such as myocardial fibrosis, pulmonary fibrosis, renal fibrosis, and other fibrotic diseases. The main goal is to pave the way for potential clinical applications in the field of fibrotic diseases.

Cloning of the wheat leaf rust resistance gene Lr47 introgressed from Aegilops speltoides.

Leaf rust, caused by Puccinia triticina Eriksson (Pt), is one of the most severe foliar diseases of wheat. Breeding for leaf rust resistance is a practical and sustainable method to control this devastating disease. Here, we report the identification of Lr47, a broadly effective leaf rust resistance gene introgressed into wheat from Aegilops speltoides. Lr47 encodes a coiled-coil nucleotide-binding leucine-rich repeat protein that is both necessary and sufficient to confer Pt resistance, as demonstrated by loss-of-function mutations and transgenic complementation. Lr47 introgression lines with no or reduced linkage drag are generated using the Pairing homoeologous1 mutation, and a diagnostic molecular marker for Lr47 is developed. The coiled-coil domain of the Lr47 protein is unable to induce cell death, nor does it have self-protein interaction. The cloning of Lr47 expands the number of leaf rust resistance genes that can be incorporated into multigene transgenic cassettes to control this devastating disease.

Scale dependence of urban green space cooling efficiency: A case study in Beijing metropolitan area.

Urban Green Space (UGS), providing environmental, social and economic benefits simultaneously, has been regarded as a cost-effective Nature-based Solution (NbS) to combat the effects of urban heat island (UHI). Under the dual pressure of increasing demand for limited land resources and mitigating UHI, how to scientifically and effectively use the limited space to obtain the maximum cooling efficiency (scaling of cooling intensity and UGS size) is an important component of strategic urban green planning. However, the scale dependence of UGS cooling effect has not yet been sufficiently quantified, particularly with respect to involving small and medium size UGS. Here, we explored the size-dependent UGS cooling efficiency in Beijing using 10,003 UGS patches extracted from high-resolution remote sensing images. We found that 5922 UGS (59.20 %) exhibited a "cooling island effect", the cooling service of UGS could reduce land surface temperature by 0.06 ± 0.05 °C to 3.81 ± 1.01 °C, and the cooling intensity enhanced nonlinearly with increasing size and closely related to the complexity of UGS shape and vegetation quality. We further showed that the cooling efficiency of small, medium and large UGS was -0.004 ± 0.03 (n = 2201), 0.79 ± 0.01 (n = 3570), 0.19 ± 0.03 (n = 151), respectively, suggesting that strategic urban greening to combat urban heat should target on increasing medium-sized UGS and managing the layout of green space. These findings emphasize the significance of considering and further exploring the scale dependence of UGS cooling effect in mitigating urban heat.

Temporal dynamics of ecosystem, inherent, and underlying water use efficiencies of forests, grasslands, and croplands and their responses to climate change.

BACKGROUND: Understanding temporal trends and varying responses of water use efficiency (WUE) to environmental changes of diverse ecosystems is key to predicting vegetation growth. WUE dynamics of major ecosystem types (e.g., forest, grassland and cropland) have been studied using various WUE definitions/metrics, but a comparative study on WUE dynamics and their driving forces among different ecosystem types using multiple WUE metrics is lacking. We used eddy covariance measurements for 42 FLUXNET2015 sites (396 site years) from 1997 to 2014, as well as three commonly used WUE metrics (i.e., ecosystem, inherent, and underlying WUE) to investigate the commonalities and differences in WUE trends and driving factors among deciduous broadleaf forests (DBFs), evergreen needleleaf forests (ENFs), grasslands, and croplands. RESULTS: Our results showed that the temporal trends of WUE were not statistically significant at 73.8% of the forest, grassland and cropland sites, and none of the three WUE metrics exhibited better performance than the others in quantifying WUE. Meanwhile, the trends observed for the three WUE metrics were not significantly different among forest, grassland and cropland ecosystems. In addition, WUE was mainly driven by atmospheric carbon dioxide concentration at sites with significant WUE trends, and by vapor pressure deficit (VPD) at sites without significant trends (except cropland). CONCLUSIONS: Our findings revealed the commonalities and differences in the application of three WUE metrics in disparate ecosystems, and further highlighted the important effect of VPD on WUE change.

Urban environments provide new perspectives for forecasting vegetation phenology responses under climate warming.

Given that already-observed temperature increase within cities far exceeds the projected global temperature rise by the end of the century, urban environments often offer a unique opportunity for studying ecosystem response to future warming. However, the validity of thermal gradients in space serving as a substitute for those in time is rarely tested. Here, we investigated vegetation phenology dynamics in China's 343 cities and empirically test whether phenological responses to spatial temperature rise in urban settings can substitute for those to temporal temperature rise in their natural counterparts based on satellite-derived vegetation phenology and land surface temperature from 2003 to 2018. We found prevalent advancing spring phenology with "high confidence" and delaying autumn phenology with "medium confidence" under the context of widespread urban warming. Furthermore, we showed that space cannot substitute for time in predicting phenological shifts under climate warming at the national scale and for most cities. The thresholds of ~11°C mean annual temperature and ~600 mm annual precipitation differentiated the magnitude of phenological sensitivity to temperature across space and through time. Below those thresholds, there existed stronger advanced spring phenology and delayed autumn phenology across the spatial urbanization gradients than through time, and vice versa. Despite the complex and diverse relationships between phenological sensitivities across space and through time, we found that the directions of the temperature changes across spatial gradients were converged (i.e., mostly increased), but divergent through temporal gradients (i.e., increased or decreased without a predominant direction). Similarly, vegetation phenology changes more uniformly over space than through time. These results suggested that the urban environments provide a real-world condition to understand vegetation phenology response under future warming.

Transcriptome analysis reveals key genes involved in the resistance to Cryphonectria parasitica during early disease development in Chinese chestnut.

BACKGROUND: Chestnut blight, one of the most serious branch diseases in Castanea caused by Cryphonectria parasitica, which has ravaged across American chestnut and most of European chestnut since the early twentieth century. Interestingly, the Chinese chestnut is strongly resistant to chestnut blight, shedding light on restoring the ecological status of Castanea plants severely affected by chestnut blight. To better explore the early defense of Chinese chestnut elicited in response to C. parasitica, the early stage of infection process of C. parasitica was observed and RNA sequencing-based transcriptomic profiling of responses of the chestnut blight-resistant wild resource 'HBY-1' at 0, 3 and 9 h after C. parasitica inoculation was performed. RESULTS: First, we found that 9 h was a critical period for Chinese chestnut infected by C. parasitica, which was the basis of further study on transcriptional activation of Chinese chestnut in response to chestnut blight in the early stage. In the transcriptome analysis, a total of 283 differentially expressed genes were identified between T9 h and Mock9 h, and these DEGs were mainly divided into two clusters, one of which was metabolism-related pathways including biosynthesis of secondary metabolites, phenylpropanoid biosynthesis, amino sugar and nucleotide sugar metabolism, and photosynthesis; the other was related to plant-pathogen interaction and MAPK signal transduction. Meanwhile, the two clusters of pathways could be connected through junction among phosphatidylinositol signaling system, phytohormone signaling pathway and α-Linolenic acid metabolism pathway. It is worth noting that genes associated with JA biosynthesis and metabolic pathway were significantly up-regulated, revealing that the entire JA metabolic pathway was activated in Chinese chestnut at the early stage of chestnut blight infection. CONCLUSION: We identified the important infection nodes of C. parasitica and observed the morphological changes of Chinese chestnut wounds at the early stage of infection. In response to chestnut blight, the plant hormone and MAPK signal transduction pathways, plant-pathogen interaction pathways and metabolism-related pathways were activated at the early stage. JA biosynthesis and metabolic pathway may be particularly involved in the Chinese chestnut resistance to chestnut blight. These results contributes to verifying the key genes involved in the resistance of Chinese chestnut to C. parasitica.

RNA mis-splicing drives viral mimicry response after DNMTi therapy in SETD2-mutant kidney cancer.

Tumors with mutations in chromatin regulators present attractive targets for DNA hypomethylating agent 5-aza-2'-deoxycytidine (DAC) therapy, which further disrupts cancer cells' epigenomic fidelity and reactivates transposable element (TE) expression to drive viral mimicry responses. SETD2 encodes a histone methyltransferase (H3K36me3) and is prevalently mutated in advanced kidney cancers. Here, we show that SETD2-mutant kidney cancer cells are especially sensitive in vitro and in vivo to DAC treatment. We find that the viral mimicry response are direct consequences of mis-splicing events, such as exon inclusions or extensions, triggered by DAC treatment in an SETD2-loss context. Comprehensive epigenomic analysis reveals H3K9me3 deposition, rather than DNA methylation dynamics, across intronic TEs might contribute to elevated mis-splicing rates. Through epigenomic and transcriptomic analyses, we show that SETD2-deficient kidney cancers are prone to mis-splicing, which can be therapeutically exacerbated with DAC treatment to increase viral mimicry activation and provide synergy with combinatorial immunotherapy approaches.

A stronger advance of urban spring vegetation phenology narrows vegetation productivity difference between urban settings and natural environments.

Climate change is posing dramatic effects on terrestrial vegetation dynamics. The links between vegetation phenology or vegetation activity (growth) and climate change have been widely reported, yet, less is known about the impacts of phenological shifts on vegetation growth. Urban settings characterized by urban heat island and CO2 dome are often used as ideal natural laboratories to understand how vegetation responds to global climate change. Here we assessed the impacts of phenology changes on vegetation growth in China using satellite phenology metrics and gross primary production (GPP) data from 2003 to 2018 and urban-natural contrast analysis. Compared with natural environments, phenological metrics (e.g., start/end of growing season (SOS/EOS), and the length of growing season (GSL), etc.) were observed to change more dramatically in urban environments. Furthermore, we found that GPP in both settings increased over time but with a higher increment in the urban environments, and the urban-natural vegetation productivity gap had been diminishing at a rate of 16.9 ± 6.76 g C m-2 y-1. The narrowing of the urban-natural GPP difference over time can be attributed to a more advanced SOS and extended GSL in urban settings than their natural counterparts, particularly SOS shift. These findings suggested that the distinct urban phenological shifts would become increasingly important in offsetting the loss of vegetation productivity induced by urbanization.