Programmable heating and quenching for efficient thermochemical synthesis.

Conventional thermochemical syntheses by continuous heating under near-equilibrium conditions face critical challenges in improving the synthesis rate, selectivity, catalyst stability and energy efficiency, owing to the lack of temporal control over the reaction temperature and time, and thus the reaction pathways1-3. As an alternative, we present a non-equilibrium, continuous synthesis technique that uses pulsed heating and quenching (for example, 0.02 s on, 1.08 s off) using a programmable electric current to rapidly switch the reaction between high (for example, up to 2,400 K) and low temperatures. The rapid quenching ensures high selectivity and good catalyst stability, as well as lowers the average temperature to reduce the energy cost. Using CH4 pyrolysis as a model reaction, our programmable heating and quenching technique leads to high selectivity to value-added C2 products (>75% versus <35% by the conventional non-catalytic method and versus <60% by most conventional methods using optimized catalysts). Our technique can be extended to a range of thermochemical reactions, such as NH3 synthesis, for which we achieve a stable and high synthesis rate of about 6,000 µmol gFe-1 h-1 at ambient pressure for >100 h using a non-optimized catalyst. This study establishes a new model towards highly efficient non-equilibrium thermochemical synthesis.

Single hormone or synthetic agonist induces Gs/Gi coupling selectivity of EP receptors via distinct binding modes and propagating paths.

To accomplish concerted physiological reactions, nature has diversified functions of a single hormone at at least two primary levels: 1) Different receptors recognize the same hormone, and 2) different cellular effectors couple to the same hormone-receptor pair [R.P. Xiao, Sci STKE 2001, re15 (2001); L. Hein, J. D. Altman, B.K. Kobilka, Nature 402, 181-184 (1999); Y. Daaka, L. M. Luttrell, R. J. Lefkowitz, Nature 390, 88-91 (1997)]. Not only these questions lie in the heart of hormone actions and receptor signaling but also dissecting mechanisms underlying these questions could offer therapeutic routes for refractory diseases, such as kidney injury (KI) or X-linked nephrogenic diabetes insipidus (NDI). Here, we identified that Gs-biased signaling, but not Gi activation downstream of EP4, showed beneficial effects for both KI and NDI treatments. Notably, by solving Cryo-electron microscope (cryo-EM) structures of EP3-Gi, EP4-Gs, and EP4-Gi in complex with endogenous prostaglandin E2 (PGE2)or two synthetic agonists and comparing with PGE2-EP2-Gs structures, we found that unique primary sequences of prostaglandin E2 receptor (EP) receptors and distinct conformational states of the EP4 ligand pocket govern the Gs/Gi transducer coupling selectivity through different structural propagation paths, especially via TM6 and TM7, to generate selective cytoplasmic structural features. In particular, the orientation of the PGE2 ω-chain and two distinct pockets encompassing agonist L902688 of EP4 were differentiated by their Gs/Gi coupling ability. Further, we identified common and distinct features of cytoplasmic side of EP receptors for Gs/Gi coupling and provide a structural basis for selective and biased agonist design of EP4 with therapeutic potential.

Nonspecific phospholipase C4 hydrolyzes phosphosphingolipids and sustains plant root growth during phosphate deficiency.

Phosphate is a vital macronutrient for plant growth, and its availability in soil is critical for agricultural sustainability and productivity. A substantial amount of cellular phosphate is used to synthesize phospholipids for cell membranes. Here, we identify a key enzyme, nonspecific phospholipase C4 (NPC4) that is involved in phosphosphingolipid hydrolysis and remodeling in Arabidopsis during phosphate starvation. The level of glycosylinositolphosphorylceramide (GIPC), the most abundant sphingolipid in Arabidopsis thaliana, decreased upon phosphate starvation. NPC4 was highly induced by phosphate deficiency, and NPC4 knockouts in Arabidopsis decreased the loss of GIPC and impeded root growth during phosphate starvation. Enzymatic analysis showed that NPC4 hydrolyzed GIPC and displayed a higher activity toward GIPC as a substrate than toward the common glycerophospholipid phosphatidylcholine. NPC4 was associated with the plasma membrane lipid rafts in which GIPC is highly enriched. These results indicate that NPC4 uses GIPC as a substrate in planta and the NPC4-mediated sphingolipid remodeling plays a positive role in root growth in Arabidopsis response to phosphate deficiency.

Circulating levels of asprosin in children with obesity: a systematic review and meta-analysis.

BACKGROUND: Prior studies reported that elevated asprosin level was associated with obesity in adults and animal models. However, the relationship between asprosin level and children with obeisty remains controversial. The aim of our analysis was to systematically review available literatures linking asprosin and children with obesity for a comprehensive understanding of the relationship between circulating asprosin level and obesity in children. METHODS: Eight databases were gleaned for studies published up to January 2024. Standard mean difference with 95% confidence interval (CI) and Fisher's Z transformation was calculated to evaluate the relationship between asprosin level and children with obesity using the Review Manager 5.4 Software. Other indicators were measured via mean difference with 95% CI. RESULTS: Six observational studies were included both in systematic review and meta-analysis. The current evidence indicated that no significant difference was observed in the level of circulating asprosin between the children with and without obesity (SMD = 0.37; 95% CI:-0.22-0.95, p = 0.22). However, Fisher's Z transformation suggested the positive association of circulating asprosin levels and clinical index measuring the degree of obesity: total cholesterol (Fisher's Z: 0.11, 95% CI: 0.02-0.20, p = 0.02). CONCLUSIONS: Circulating asprosin level was not independently related to childhood obesity currently. More rigorous longitudinal researches were required to disentangle the causations. However, the positive association of asprosin levels and total cholesterol indicated that asprosin might get involved in the lipid-metabolism of childhood obesity, asprosin might be a prospective bio-index and targeted treatment of total cholesterol metabolism besides the role of glucogenic and orexigenic. TRIAL REGISTRATION: Prospero ID: CRD42023426476.

De novo design of a nanoregulator for the dynamic restoration of ovarian tissue in cryopreservation and transplantation.

The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain.

Long-term decrease in Asian monsoon rainfall and abrupt climate change events over the past 6,700 years.

Asian summer monsoon (ASM) variability and its long-term ecological and societal impacts extending back to Neolithic times are poorly understood due to a lack of high-resolution climate proxy data. Here, we present a precisely dated and well-calibrated tree-ring stable isotope chronology from the Tibetan Plateau with 1- to 5-y resolution that reflects high- to low-frequency ASM variability from 4680 BCE to 2011 CE. Superimposed on a persistent drying trend since the mid-Holocene, a rapid decrease in moisture availability between ∼2000 and ∼1500 BCE caused a dry hydroclimatic regime from ∼1675 to ∼1185 BCE, with mean precipitation estimated at 42 ± 4% and 5 ± 2% lower than during the mid-Holocene and the instrumental period, respectively. This second-millennium-BCE megadrought marks the mid-to late Holocene transition, during which regional forests declined and enhanced aeolian activity affected northern Chinese ecosystems. We argue that this abrupt aridification starting ∼2000 BCE contributed to the shift of Neolithic cultures in northern China and likely triggered human migration and societal transformation.

Versatile Activated Carbon Fibers Derived from the Cotton Fibers Used as CO2 Solid-State Adsorbents and Electrode Materials.

Activated carbon has an excellent porous structure and is considered a promising adsorbent and electrode material. In this study, activated carbon fibers (ACFs) with abundant microporous structures, derived from natural cotton fibers, were successfully synthesized at a certain temperature in an Ar atmosphere and then activated with KOH. The obtained ACFs were characterized by field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), elemental analysis, nitrogen and carbon dioxide adsorption-desorption analysis, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and N2 adsorption-desorption measurement. The obtained ACFs showed high porous qualities and had a surface area from 673 to 1597 m2/g and a pore volume from 0.33 to 0.79 cm3/g. The CO2 capture capacities of prepared ACFs were measured and the maximum capture capacity for CO2 up to 6.9 mmol/g or 4.6 mmol/g could be achieved at 0 °C or 25 °C and 1 standard atmospheric pressure (1 atm). Furthermore, the electrochemical capacitive properties of as-prepared ACFs in KOH aqueous electrolyte were also studied. It is important to note that the pore volume of the pores below 0.90 nm plays key roles to determine both the CO2 capture ability and the electrochemical capacitance. This study provides guidance for designing porous carbon materials with high CO2 capture capacity or excellent capacitance performance.

Bioactive compound composition and cellular antioxidant activity of fig (Ficus carica L.).

BACKGROUND: Fig (Ficus carica L.) fruit is consumed worldwide as a functional food. It contains phytochemicals that have been related to health benefits. However, the characteristic chemicals remain unclear. In this work, phytochemicals were prepared from figus by ultrasound-assisted extraction under optimized conditions. The chemical composition of fig fruit and leaves was characterized by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: One hundred and fifty-seven compounds were identified, including 58 flavonoids, 29 coumarins, 19 acids, 15 terpenoids, 11 alkaloids, and 25 other compounds. The mass spectrum (MS) fragmentation pathways of representative chemicals were elucidated. Flavonoid glycosides and prenylated flavonoids were mainly present in fig fruit, whereas coumarins were abundant in leaves. Both fig fruit and leaf extracts showed good cellular antioxidant activity. CONCLUSION: The full phytochemical profile of fig was revealed by UPLC-MS/MS. Prenylated flavonoids and prenylated coumarins were the characteristic phytochemicals. These data provided useful information for the extensive utilization of fig fruit in functional food. © 2023 Society of Chemical Industry.

Enhancing functionality and bioactivity of walnut protein through limited enzyme digestion.

BACKGROUND: Walnut protein (WP) is recognized as a valuable plant protein. However, the poor solubility and functional properties limit its application in the food industry. It is a great requirement to improve the physicochemical properties of WP. RESULTS: Following a 90 min restricted enzymatic hydrolysis period, the solubility of WP significantly increased from 3.24% to 54.54%, with the majority of WP hydrolysates (WPHs) possessing a molecular weight exceeding 50 kDa. Circular dichroism spectra showed that post-hydrolysis, the structure of the protein became more flexible, while the hydrolysis time did not significantly alter the protein's secondary structure. After hydrolysis, WP's surface hydrophobicity significantly increased from 2279 to 6100. Furthermore, WPHs exhibited a strong capacity for icariin loading and micelle formation with critical micelle concentration values of 0.71, 0.99 and 1.09 mg mL-1, respectively. Moreover, similar immuno-enhancement activities were observed in WPHs. After exposure to WPHs, the pinocytosis of RAW264.7 macrophages was significantly improved. WPH treatment also increased the production of nitric oxide, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in macrophages. Up-regulation of mRNA expressions of IL-6, inducible nitric oxide synthase (iNOS) and TNF-α was observed in a dose-dependent manner. CONCLUSION: The enhancement of functionality and bioactivity in WP can be achieved through the application of limited enzyme digestion with trypsin. This process effectively augments the nutritional value and utility of the protein, making it a valuable component in various dietary applications. © 2024 Society of Chemical Industry.

Lipidomic and metabolomic analyses reveal changes of lipids and metabolites profile in rapeseed during nitrogen deficiency.

Nitrogen is one of the most essential macronutrients for plant growth and its availability in soil is vital for agricultural sustainability and productivity. However, excessive nitrogen application could reduce the nitrogen use efficiency and produce environmental pollution. Here, we systematically determined the response in lipidome and metabolome in rapeseed during nitrogen starvation. Plant growth was severely retarded during nitrogen deficiency, while the levels of most amino acids was significantly decreased. The levels of monogalactosyl diacyglycerol (MGDG) in leaves and roots was significantly decreased, while the level of digalactosyl diacylglycerol (DGDG) was significantly decreased in roots, resulting in significant reduction of MGDG/DGDG ratio during nitrogen starvation. Meanwhile, the levels of sulfoquinovosyl diacylglycerol, phosphatidylglycerol and glucuronosyl diacylglycerol was reduced to varying extents. Moreover, the levels of metabolites in the tricarboxylic acid cycle, Calvin cycle, and energy metabolism was changed during nitrogen deficiency. These findings show that nitrogen deprivation alters the membrane lipid metabolism and carbon metabolism, and our study provides valuable information to further understand the response of rapeseed to nitrogen deficiency at metabolism level.

A critical thermal transition driving spring phenology of Northern Hemisphere conifers.

Despite growing interest in predicting plant phenological shifts, advanced spring phenology by global climate change remains debated. Evidence documenting either small or large advancement of spring phenology to rising temperature over the spatio-temporal scales implies a potential existence of a thermal threshold in the responses of forests to global warming. We collected a unique data set of xylem cell-wall-thickening onset dates in 20 coniferous species covering a broad mean annual temperature (MAT) gradient (-3.05 to 22.9°C) across the Northern Hemisphere (latitudes 23°-66° N). Along the MAT gradient, we identified a threshold temperature (using segmented regression) of 4.9 ± 1.1°C, above which the response of xylem phenology to rising temperatures significantly decline. This threshold separates the Northern Hemisphere conifers into cold and warm thermal niches, with MAT and spring forcing being the primary drivers for the onset dates (estimated by linear and Bayesian mixed-effect models), respectively. The identified thermal threshold should be integrated into the Earth-System-Models for a better understanding of spring phenology in response to global warming and an improved prediction of global climate-carbon feedbacks.

Naturally occurring prenylated stilbenoids: food sources, biosynthesis, applications and health benefits.

Prenylated stilbenoids are a unique class of natural phenolic compounds consisting of C6-C2-C6 skeleton with prenyl substitution. They are potential nutraceuticals and dietary supplements presented in some edible plants. Prenylated stilbenoids demonstrate promising health benefits, including antioxidant, anti-cancer, anti-inflammatory, anti-microbial activities. This review reports the structure, bioactivity and potential application of prenylated stilbeniods in food industry. Edible sources of these compounds are compiled and summarized. Structure-activity relationship of prenylated stilbenoids are also highlighted. The biosynthesis strategies of prenylated stilbenoids are reviewed. The findings of these compounds as food preservative, nutraceuticals and food additive are discussed. This paper combines the up-to-date information and gives a full image of prenylated stilbenoids.

New insights of flavonoid glycosidases and their application in food industry.

Flavonoids are significant natural nutraceuticals and a key component of dietary supplements. Given that flavonoid glycosides are more plentiful in nature and less beneficial to human health than their aglycone counterparts, they serve as potential precursors for flavonoid production. Glycosidases have shown substantial potential within the food industry, particularly in enhancing the organoleptic properties of juice, wine, and tea. When applied to food resources, glycosidases can amplify their biological activities, thereby improving the performance of functional foods. This review provides up-to-date information on flavonoid glycosidases, including their catalytic mechanisms, biochemical properties, and natural sources, as well as their applications within the food industry. The use of flavonoid glycosidases in improving food quality is also reviewed.

An update of aurones: food resource, health benefit, biosynthesis and application.

Aurones are a subclass of active flavonoids characterized with a scaffold of 2-benzylidene-3(2H)-benzofuranone. This type of chemicals are widely distributed in fruit, vegetable and flower, and contribute to human health. In this review, we summarize the natural aurones isolated from dietary plants. Their positive effects on immunomodulation, antioxidation, cancer prevention as well as maintaining the health status of cardiovascular, nervous system and liver organs are highlighted. The biosynthesis strategies of plant-derived aurones are elaborated to provide solutions for their limited natural abundance. The potential application of natural aurones in food coloration are also discussed. This paper combines the up-to-date information and gives a full image of dietary aurones.

Ion recognition properties of 2,2'-bibenzimidazole regulated by ammonium-modified pillar[5]arenes.

With the increasing issues of environmental degradation and health problem, the selective detection of toxic ions has attracted considerable attention from researchers. Chemical fluorescent sensors with the advantages of facile operation, high sensitivity, rapid response, and easy visualization are emerging as powerful detection tools towards ions. However, the selective recognition of ions is always hindered by the presence of other interfering substances. Herein, we show that supramolecular host-guest interaction based on a pillar[5]arene provides a new opportunity to regulate the ionic recognition properties of guest molecules. A pillar[5]arene-based host-guest complex HG was constructed through the host-guest interaction between ammonium functionalized pillar[5]arene (HAP5) and 2,2'-bibenzimidazole (G). The host-gust complex HG can realize the successive, highly selective, and sensitive detection of specific ions. It was found that only in the presence of HAP5, the sensitivity towards cations was evidently enhanced, and selective successive recognition for I- and HSO4- was achieved. Those results indicate that the introduction of HAP5 can effectively improve the ion recognition performance of 2,2'-bibenzimidazole, so it is a feasible strategy using supramolecular host-guest interaction to regulate the ionic recognition properties of guest molecules.

Characteristics of blood immune cell profile and their correlation with disease progression in patients infected with HIV-1.

BACKGROUND: Antiretroviral therapy (ART) can reduce viral load in individuals infected with human immunodeficiency virus (HIV); however, some HIV-infected individuals still cannot achieve optimal immune recovery even after ART. Hence, we described the profile of peripheral immune cells and explored the association with disease progression in patients infected with HIV-1. METHODS: Mass cytometry analysis was used to characterize the circulating immune cells of 20 treatment-naïve (TNs), 20 immunological non-responders (INRs), 20 immunological responders (IRs), and 10 healthy controls (HCs). Correlation analysis was conducted between cell subpopulation percentages and indicators including HIV-1 cell-associated (CA)-RNA, DNA, CD4+ T cell count, and CD4/CD8 ratio. RESULTS: Global activation, immunosenescence, and exhaustion phenotypes were observed in myeloid cells and T cells from individuals with HIV-1 infection. We also found that specific subsets or clusters of myeloid, CD4+ T, and CD8+ T cells were significantly lost or increased in TN individuals, which could be partially restored after receiving ART. The percentages of several subpopulations correlated with HIV-1 CA-RNA, DNA, CD4+ T cell count, and CD4/CD8 ratio, suggesting that changes in immune cell composition were associated with therapeutic efficacy. CONCLUSION: These data provide a complete profile of immune cell subpopulations or clusters that are associated with disease progression during chronic HIV-1 infection, which will improve understanding regarding the mechanism of incomplete immune recovery in INRs.

Uric acid and evaluate the coronary vascular stenosis gensini score correlation research and in gender differences.

BACKGROUND AND AIMS: Recent studies have shown that the negative effect of uric acid (UA) on coronary arteries determines the severity of atherosclerotic disease. This study aims to explore the relationship between serum UA level and Gensini score, which reflects the severity of coronary artery disease. METHODS: A total of 860 patients with suspected coronary heart disease who were admitted to hospital due to angina pectoris or myocardial ischemia related symptoms and received coronary angiography were selected. Based on the findings of the angiography, they were categorized into two groups: the coronary heart disease (CHD) group (n = 625) and the control group (n = 235). The uric acid levels and other clinical data were compared between these groups. Additionally, the prevalence of coronary heart disease and Gensini score were compared between the groups, considering gender-specific quartiles of uric acid levels. The clinical baseline data were analyzed using appropriate statistical methods, and multivariate logistic regression analysis was conducted to identify independent risk factors for coronary heart disease. RESULTS: Of 860 patients (mean age, 63.97 ± 11.87 years), 528 were men (mean age, 62.06 ± 11.5 years) and 332 were women (mean age, 66.99 ± 10.11 years). The proportion of smoking, diabetes, hypertension, and hyperlipidemia in the coronary heart disease group was higher than that in the control group (P < 0.05). HbA1C, Gensini score, BMI, TG and hsCRP in the coronary heart disease group were higher than those in the control group (P < 0.05), and HDL-C was lower than that in the control group (P < 0.05). There were no significant differences in age, heart rate, Cr, TC and LDL-C between the two groups (P > 0.05).Multivariate logistic regression analysis showed that age, hypertension, hsCRP and SUA levels increased the risk of coronary heart disease, and the difference was statistically significant(OR = 1.034,95%CI 1.016-1.052, P = 0.001; OR = 1.469,95%CI 1.007-2.142, P = 0.046;OR = 1.064,95%CI 1.026-1.105, P = 0.001; OR = 1.011,95%CI 1.008-1.014, P < 0.001). CONCLUSION: Serum uric acid is positively correlated with Gensini score in patients with coronary heart disease, which is an independent factor for evaluating the degree of coronary artery stenosis and has a predictive effect.

Sevoflurane preconditioning protects against acute MI/R injury via enhancing AdipoR1-Cav3 interaction and alleviating endoplasmic reticulum stress.

Whether and how sevoflurane preconditioning (SevoPre) exerts protection against acute myocardial ischemia/reperfusion (MI/R) injury remains elusive. We observed significant myocardial injury, as evidenced by infarct size, cardiomyocyte apoptosis, and circulating troponin-I, at 3 h of MI/R in both wildtype and adiponectin knockout mice. The injury was significantly ameliorated by SevoPre in wildtype mice, but not in adiponectin knockout mice. In wildtype mice, we found that MI/R could increase endoplasmic reticulum stress of cardiomyocytes, and impair association of adiponectin receptor 1 and ceveolin-3, both of which processes were largely restored by SevoPre. In summary, we demonstrated that significant injury had already took place at 3 h of MI/R, which could be ameliorated by SevoPre via promoting affinity of adiponectin receptor 1 and ceveolin-3, and then attenuating endoplasmic reticulum stress of cardiomyocytes.

1-Indanone retards cyst development in ADPKD mouse model by stabilizing tubulin and down-regulating anterograde transport of cilia.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. Cyst development in ADPKD involves abnormal epithelial cell proliferation, which is affected by the primary cilia-mediated signal transduction in the epithelial cells. Thus, primary cilium has been considered as a therapeutic target for ADPKD. Since ADPKD exhibits many pathological features similar to solid tumors, we investigated whether targeting primary cilia using anti-tumor agents could alleviate the development of ADPKD. Twenty-four natural compounds with anti-tumor activity were screened in MDCK cyst model, and 1-Indanone displayed notable inhibition on renal cyst growth without cytotoxicity. This compound also inhibited cyst development in embryonic kidney cyst model. In neonatal kidney-specific Pkd1 knockout mice, 1-Indanone remarkably slowed down kidney enlargement and cyst expansion. Furthermore, we demonstrated that 1-Indanone inhibited the abnormal elongation of cystic epithelial cilia by promoting tubulin polymerization and significantly down-regulating expression of anterograde transport motor protein KIF3A and IFT88. Moreover, we found that 1-Indanone significantly down-regulated ciliary coordinated Wnt/ß-catenin, Hedgehog signaling pathways. These results demonstrate that 1-Indanone inhibits cystic cell proliferation by reducing abnormally prolonged cilia length in cystic epithelial cells, suggesting that 1-Indanone may hold therapeutic potential to retard cyst development in ADPKD.

GDF11 promotes wound healing in diabetic mice via stimulating HIF-1ɑ-VEGF/SDF-1ɑ-mediated endothelial progenitor cell mobilization and neovascularization.

Non-healing diabetic wounds (DW) are a serious clinical problem that remained poorly understood. We recently found that topical application of growth differentiation factor 11 (GDF11) accelerated skin wound healing in both Type 1 DM (T1DM) and genetically engineered Type 2 diabetic db/db (T2DM) mice. In the present study, we elucidated the cellular and molecular mechanisms underlying the action of GDF11 on healing of small skin wound. Single round-shape full-thickness wound of 5-mm diameter with muscle and bone exposed was made on mouse dorsum using a sterile punch biopsy 7 days following the onset of DM. Recombinant human GDF11 (rGDF11, 50 ng/mL, 10 µL) was topically applied onto the wound area twice a day until epidermal closure (maximum 14 days). Digital images of wound were obtained once a day from D0 to D14 post-wounding. We showed that topical application of GDF11 accelerated the healing of full-thickness skin wounds in both type 1 and type 2 diabetic mice, even after GDF8 (a muscle growth factor) had been silenced. At the cellular level, GDF11 significantly facilitated neovascularization to enhance regeneration of skin tissues by stimulating mobilization, migration and homing of endothelial progenitor cells (EPCs) to the wounded area. At the molecular level, GDF11 greatly increased HIF-1ɑ expression to enhance the activities of VEGF and SDF-1ɑ, thereby neovascularization. We found that endogenous GDF11 level was robustly decreased in skin tissue of diabetic wounds. The specific antibody against GDF11 or silence of GDF11 by siRNA in healthy mice mimicked the non-healing property of diabetic wound. Thus, we demonstrate that GDF11 promotes diabetic wound healing via stimulating endothelial progenitor cells mobilization and neovascularization mediated by HIF-1ɑ-VEGF/SDF-1ɑ pathway. Our results support the potential of GDF11 as a therapeutic agent for non-healing DW.