Subject(s)
Diet , Fathers , Spermatozoa , Male , Spermatozoa/metabolism , Humans , RNA/metabolism , RNA/genetics , Animals , Mice , Nuclear Family , FemaleABSTRACT
The C-H hydroxylation of the pyridine C3 position is a highly desirable transformation but remains a great challenge due to the inherent electronic properties of this heterocycle core which bring difficulties in chemical reactivity and regioselectivity. Herein we present an efficient method for formal C3 selective hydroxylation of pyridines via photochemical valence isomerization of pyridine N-oxides. This metal-free transformation features operational simplicity and compatibility with a diverse array of functional groups, and the resulting hydroxylated products are amenable to further elaboration to synthetically useful building blocks. The synthetic utility of this strategy is further demonstrated in the effective late-stage functionalization of pyridine-containing medicinally relevant molecules and versatile derivatizations of 3-pyridinols.
ABSTRACT
Lactate dehydrogenase A (LDHA) is known to promote the growth and invasion of various types of tumors, affects tumor resistance, and is associated with tumor immune escape. But how LDHA reshapes the tumor microenvironment and promotes the progression of renal cell carcinoma (RCC) remains unclear. In this study, we found that LDHA was highly expressed in clear cell RCC (ccRCC), and this high expression was associated with macrophage infiltration, while macrophages were highly infiltrated in ccRCC, affecting patient prognosis via M2-type polarization. Our in vivo and in vitro experiments demonstrated that LDHA and M2-type macrophages could enhance the proliferation, invasion, and migration abilities of ccRCC cells. Mechanistically, high expression of LDHA in ccRCC cells upregulated the expression of EPHA2 in exosomes derived from renal cancer. Exosomal EPHA2 promoted M2-type polarization of macrophages by promoting activation of the PI3K/AKT/mTOR pathway in macrophages, thereby promoting the progression of ccRCC. All these findings suggest that EPHA2 may prove to be a potential therapeutic target for advanced RCC.
Subject(s)
Carcinoma, Renal Cell , Disease Progression , Exosomes , Kidney Neoplasms , Macrophages , Receptor, EphA2 , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/genetics , Receptor, EphA2/metabolism , Receptor, EphA2/genetics , Humans , Kidney Neoplasms/pathology , Kidney Neoplasms/metabolism , Kidney Neoplasms/genetics , Exosomes/metabolism , Animals , Macrophages/metabolism , Macrophages/pathology , Mice , Cell Line, Tumor , Cell Proliferation , L-Lactate Dehydrogenase/metabolism , L-Lactate Dehydrogenase/genetics , Cell Movement , Gene Expression Regulation, Neoplastic , Male , Tumor Microenvironment , Prognosis , TOR Serine-Threonine Kinases/metabolism , Female , Signal Transduction , Mice, Nude , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
Traditional sound source localization (SSL) systems based on electret condenser microphone arrays are bulky because their localization accuracy depends on the size of the array. Inspired by the hearing mechanism of the parasitic fly Ormia ochracea, the localization accuracy of miniature bionic SSL devices breaks through the limitations of device size, but their ability to localize low-frequency sound sources over a wide angular range remains a challenge. In this work, a compact low-frequency SSL system with an extended directional range was prepared using two bionic micro-electro-mechanical system diaphragm based fiber-optic microphones, which form a non-coplanar array with a size of Φ44 mm × 13 mm. An algorithm for quantifying the azimuthal angle of a sound source is established for the prepared SSL system. Simulation and experimental results show that the prepared SSL system is capable of determining the propagation direction of acoustic signals with a frequency of less than 1 kHz in the azimuthal range from -90° to 90°, with a linear response in the range from -70° to 70°, and an angular measurement accuracy of the system within the range of ±7°.
ABSTRACT
Mitigation of nitrous oxide (N2O) emissions in full-scale wastewater treatment plant (WWTP) has become an irreversible trend to adapt the climate change. Monitoring of N2O emissions plays a fundamental role in understanding and mitigating N2O emissions. This paper provides a comprehensive review of direct and indirect N2O monitoring methods. The techniques, strengths, limitations, and applicable scenarios of various methods are discussed. We conclude that the floating chamber technique is suitable for capturing and interpreting the spatiotemporal variability of real-time N2O emissions, due to its long-term in-situ monitoring capability and high data acquisition frequency. The monitoring duration, location, and frequency should be emphasized to guarantee the accuracy and comparability of acquired data. Calculation by default emission factors (EFs) is efficient when there is a need for ambiguous historical N2O emission accounts of national-scale or regional-scale WWTPs. Using process-specific EFs is beneficial in promoting mitigation pathways that are primarily focused on low-emission process upgrades. Machine learning models exhibit exemplary performance in the prediction of N2O emissions. Integrating mechanistic models with machine learning models can improve their explanatory power and sharpen their predictive precision. The implementation of the synergy of nutrient removal and N2O mitigation strategies necessitates the calibration and validation of multi-path mechanistic models, supported by long-term continuous direct monitoring campaigns.
Subject(s)
Environmental Monitoring , Nitrous Oxide , Wastewater , Nitrous Oxide/analysis , Wastewater/analysis , Wastewater/chemistry , Environmental Monitoring/methods , Waste Disposal, Fluid/methodsABSTRACT
OBJECTIVES: The aim of the present study was to evaluate the effect of chitosan and carboxymethyl chitosan (CMCS) on dentin surface morphology and bonding strength after irradiation of Er:YAG laser. METHODS: Eighty-four laser-irradiated dentin samples were randomly distributed into three groups (n = 28/group) according to different surface conditioning process: deionized water for 60s; 1wt% chitosan for 60s; or 1wt% CMCS for 60s. Two specimens from each group were subjected to TEM analysis to confirm the presence of extrafibrillar demineralization on dentin fibrils. Two specimens from each group were subjected to morphological analysis by SEM. Seventy-two specimens (n = 24/group) were prepared, with a composite resin cone adhered to the dentin surface, and were then randomly assigned to one of two aging processes: storage in deionized water for 24 h or a thermocycling stimulation. The shear bond strength of laser-irradiated dentin to the resin composite was determined by a universal testing machine. Data acquired in the shear bond strength test was analyzed by one-way ANOVA with the Tukey honestly significant difference post hoc test and Independent Samples t-test (α = 0.05). RESULTS: CMCS group presented demineralized zone and a relatively smooth dentin surface morphology. CMCS group had significantly higher SBS value (6.08 ± 2.12) without aging (p < 0.05). After thermal cycling, both chitosan (5.26 ± 2.30) and CMCS group (5.82 ± 1.90) presented higher bonding strength compared to control group (3.19 ± 1.32) (p < 0.05). Chitosan and CMCS group preserved the bonding strength after aging process (p > 0.05). CONCLUSIONS: CMCS has the potential to be applied in conjunction with Er:YAG laser in cavity preparation and resin restoration.
Subject(s)
Chitosan , Dental Bonding , Lasers, Solid-State , Humans , Lasers, Solid-State/therapeutic use , Chitosan/pharmacology , Composite Resins/chemistry , Shear Strength , Dentin , Water/chemistry , Resin Cements/analysisABSTRACT
The successful mating of the hoverfly and the search for prey aphids are of great significance for biological control and are usually mediated by chemical cues. The odorant receptor co-receptor (Orco) genes play a crucial role in the process of insect odor perception. However, the function of Orco in the mating and prey-seeking behaviors of the hoverfly remains relatively unexplored. In this study, we characterized the Orco gene from the hoverfly, Eupeodes corollae, a natural enemy insect. We used the CRISPR/Cas9 technique to knock out the Orco gene of E. corollae, and the EcorOrco-/- homozygous mutant was verified by the genotype analysis. Fluorescence in situ hybridization showed that the antennal ORN of EcorOrco-/- mutant lack Orco staining. Electroantennogram (EAG) results showed that the adult mutant almost lost the electrophysiological response to 15 odorants from three types. The two-way choice assay and the glass Y-tube olfactometer indicated that both the larvae and adults of hoverflies lost their behavioral preference to the aphid alarm pheromone (E)-ß-farnesene (EBF). In addition, the mating assay results showed a significant decrease in the mating rate of males following the knock out of the EcorOrco gene. Although the mating of females was not affected, the amount of eggs being laid and the hatching rate of the eggs were significantly reduced. These results indicated that the EcorOrco gene was not only involved in the detection of semiochemicals in hoverflies but also plays a pivotal role in the development of eggs. In conclusion, our results expand the comprehension of the chemoreceptive mechanisms in the hoverflies and offers valuable insights for the advancement of more sophisticated pest management strategies.
Subject(s)
Diptera , Receptors, Odorant , Animals , Female , Male , Odorants , Receptors, Odorant/genetics , In Situ Hybridization, Fluorescence , Diptera/genetics , Insecta/genetics , Pheromones , Mutagenesis , Insect Proteins/geneticsABSTRACT
An innovative two-step process with p-toluenesulfonic acid (p-TsOH) and oxidation treatment was proposed for the efficient preparation of carboxylated nanocellulose from hybrid Pennisetum. Approximately 90 % of lignin was dissolved by p-TsOH acid under the optimal condition (80 °C, 20 min). Near-complete delignification (down to 0.5 %) and introduction of carboxylate groups (up to 1.48 mmol/g) could be achieved simultaneously during cellulose oxidation treatments without the requirement for bleaching. However, different oxidation methods expressed different efficiency and sustainability. 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) oxidation has higher selectivity for the carboxylation reaction but with detriment to the aquatic environment. Fenton oxidation is more energy-consuming due to the lower carboxylate contents of products (maximum 188 µmol/g), with the carboxylic groups present as carboxylic acids, but competitive in terms of environmental sustainability, especially when renewable energy sources are available. The nanocelluloses obtained by the two oxidation methods differ in morphology and have different application prospects.
Subject(s)
Benzenesulfonates , Pennisetum , Cyclic N-Oxides , Cellulose , Carboxylic AcidsABSTRACT
A new species of the extant staphylinid genus Vicelva Moore & Legner, V. rasilis sp. nov., is reported from mid-Cretaceous Kachin amber of northern Myanmar. Vicelva rasilis is distinguishable from extant members of Vicelva by the smoother dorsal surface of head, pronotum and elytra, less prominent median projection of clypeus, unnotched mesal edge of mandibles, semiglabrous antennomere 6, and longer tarsomere 1. The pollen-containing coprolite attached to the beetle and the crystals within the beetle body provide valuable information about the biology and taphonomy of the fossil.
ABSTRACT
This study explored the application of swelling pretreatment as a solution to the high cost and contamination associated with the process of 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated oxidation for nanocellulose preparation. The results demonstrated that swelling significantly expanded the fibers while preserving the degree of polymerization (DP) of cellulose (approximately 95 %). The native crystal structure and hydrogen bonding of cellulose were disrupted after swelling, leading to a reduction in crystallinity and crystallite size, and the decrease of bonding energy and content of intermolecular O6-Hâ¯O3'. The TEMPO-mediated oxidation processes of cellulose fibers with or without swelling were successfully fitted using a consecutive first-order reaction kinetic model. The fitting results indicated that swelling significantly reduced the activation energy of TEMPO-mediated oxidation and enhanced the reaction rate. Among three swelling systems, the NaOH/thiourea/water system exhibited the optimal promotion effect. Consequently, the swelling treatment enables a significant reduction of 30 % in the catalyst dose for the TEMPO-mediated oxidation while preserving a competitive reaction rate, yield, and product performance. Lower catalyst dosage helps to reduce cost and environmental impact, facilitating the industrial application of the TEMPO-mediated oxidation process.
Subject(s)
Cellulose , Cyclic N-Oxides , Oxidation-Reduction , Cellulose/chemistry , Cyclic N-Oxides/chemistry , Kinetics , Catalysis , Water/chemistry , Polymerization , Hydrogen Bonding , Nanostructures/chemistry , Thiourea/chemistryABSTRACT
The morphology of beetles of the recently defined superfamilies Erotyloidea, Nitiduloidea and Cucujoidea is varied. Determining the systematic positions of Mesozoic fossils within these groups can often be challenging. Here we describe and illustrate a puzzling cucujiform beetle, Isocryptophilus exilipunctus Li & Cai gen. & sp. nov., based on an individual from mid-Cretaceous Burmese amber. While we cannot definitively pinpoint the exact phylogenetic position of Isocryptophilus, its possible affinity to Erotylidae is discussed in light of our phylogenetic analyses. A broader-sampled morphological matrix, coupled with a robust molecular phylogeny of these groups, will be promising for clarifying the systematic placement of the fossil.
ABSTRACT
Based on the efficiency of the catalytic ozonation techniques (HDWS+O3 and MnFe2O4 @SBC+O3) in enhancing the sludge dewaterability, the effectiveness in synchronized abatement antibiotics and antibiotic resistance genes (ARGs) was conducted to determine. The results revealed that catalytic ozonation conditioning altered the distribution of target antibiotics (tetracycline (TC), oxytetracycline (OTC), norfloxacin (NOR), ofloxacin (OFL)) in the dewatered filtrate, the dewatered sludge cake and the extra-microcolony/cellular polymers (EMPS/ECPS) layers, achieving the redistribution from solid-phase adsorption to liquid-phase dissolution. The total degradation rate was over 90% for TC and OTC, 72-78% for NOR and OFL; the abatement efficiency of eleven ARGs reached 1.47-3.01 log and 1.64-3.59 log, respectively, and more than four eARGs were eliminated. The effective abatement of the absolute abundance of Mobile genetic elements (MGEs) (0.91-1.89 log) demonstrated that catalytic ozonation conditioning could also significantly inhibit horizontal gene transfer (HGT). The abundance of resistant bacteria was greatly reduced and the signal transduction of the typical ARGs host bacteria was inhibited. The highly reactive oxidation species (ROS) generated were responsible for the abatement of antibiotics and ARGs. These findings provided new insights into the sludge conditioning for ideal and synchronized reduction in volume and hazardousness by catalytic ozonation processes in sludge treatment.
Subject(s)
Oxytetracycline , Ozone , Sewage/microbiology , Anti-Bacterial Agents/pharmacology , Tetracycline , Bacteria/genetics , Genes, Bacterial , Norfloxacin , OfloxacinABSTRACT
Constructed wetlands use vegetation and microorganisms to remove contaminants like nitrogen and phosphorus from water. For mariculture, the impact of salinity on the efficiency of wastewater treatment of wetlands is unneglectable. However, little is known about their impact on the microbiome in constructed wetlands. Here, we set four salinity levels (15, 22, 29, and 36) in Salicornia constructed wetlands, and the experiment was conducted for a period of 72 days. The 15 group exhibited the highest removal rates of nitrogen compounds and phosphate, compared to the other salinity groups, the nosZ gene exhibited significantly higher expression in the 22 group (p < 0.05), indicated that microorganisms in 22 salinity have higher denitrification abilities. The three dominant phyla identified within the microbiomes were Proteobacteria, known for their diverse metabolic capabilities; Cyanobacteria, important for photosynthesis and nitrogen fixation; and Firmicutes, which include many fermenters. The ecological network analysis revealed a 'small world' model, characterized by high interconnectivity and short path lengths between microbial species, and had higher co-occurrence (45.13%) observed in this study comparing to the Erdös-Réyni random one (32.35%). The genus Microbulbifer emerged as the sole connector taxon, pivotal for integrating different microbial communities involved in nitrogen removal. A negative correlation was observed between salinity levels and network complexity, as assessed by the number of connections and diversity of interactions within the microbial community. Collectively, these findings underscore the critical role of microbial community interactions in optimizing nitrogen removal in constructed wetlands, with potential applications in the design and management of such systems for improved wastewater treatment in mariculture.
Subject(s)
Chenopodiaceae , Microbiota , Nitrogen , Salinity , Wastewater , Wetlands , Chenopodiaceae/metabolism , Nitrogen/metabolism , Wastewater/chemistry , Wastewater/microbiology , Bacteria/metabolism , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Phosphorus/metabolism , Waste Disposal, Fluid/methods , Biodegradation, Environmental , Denitrification , Proteobacteria/genetics , Proteobacteria/isolation & purificationABSTRACT
Thoroughly exploring carbon emissions within Urban Rail Transit (URT) systems is crucial for effectively reducing emissions while satisfying increasing energy demands. This study evaluated the spatiotemporal characteristics of carbon emissions in China's URT sector. Tapio decoupling and the Logarithmic Mean Divisia Index, used to scrutinize decoupling states and identify principal contributing factors, respectively, revealed the following: (1) Total emissions increased by 217 %, with significant spatiotemporal heterogeneity from 2015 to 2022. Type I and Type II cities accounted for >85 % of emissions but exhibited lower carbon intensity. (2) Most URT cities showed expansion-negative decoupling between economic growth and carbon emissions. Developed regions show strong decoupling, and the overall decoupling status improved in 2021-2022. (3) Emissions growth was influenced by energy intensity and economic activity, and transportation intensity was the main inhibitor for Type I cities and a driving force for other cities. Finally, recommendations for carbon emission reduction in the URT industry are proposed.
ABSTRACT
RATIONALE: The emerging evidence suggested that senescence regulator genes were involved in multi cancers, which may be utilized as new targets for cancers. However, the dysregulation and clinical impact of senescence regulator genes in clear cell renal cell cancer (ccRCC) were still in foggy. METHODS: Using multiomics data from TCGA-KIRC and other datasets, we comprehensively investigated the function of senescence regulator genes in ccRCC. ccRCC patients could be remodeled into 2 significant different groups basing on senescence regulators expression: senescence-pattern cancer subtype1 (SPCS1) and subtype2 (SPCS2). We further explored clinical characteristics, functional analysis, tumor immune microenvironment, immunotherapy response, genomic mutation and drug sensitivity between the 2 subtypes. Besides, senescence-pattern related risk model was established to determine the patient's prognosis of ccRCC. Finally, the overview of MECP2 function was investigated in multi cancers. RESULTS: ccRCC patients could be divided into SPCS1 (normal aging group) and SPCS2 (Aging disorder group). The 2 subtypes showed significant different clinical characteristics and biological process in ccRCC. SPCS2, an aggressive subtype, comprised higher clinical stage and worse prognosis of ccRCC patients. SPCS2 subtype indicated activated oncogenic signaling pathway and metabolic signatures to prompt cancer expansion. SPCS2 subgroup owned immunocompromised status, which induced immune dysfunction and low ICI therapy response. The genome-copy numbers of SPCS2, including arm-gain and arm-loss was significantly more frequent than SPCS1. In addition, the 2 subtypes argue contrasting drug sensitivity profiles in clinical specimens and matched cell lines. Finally, we constructed a prognostic risk model consisted of each subtype's leading biomarkers, which exerted a satisfied performance for ccRCC patients. CONCLUSION: Senescence regulator-related signature could modify functional pathways and tumor immune microenvironment by genome mutation and pathway interaction. Senescence regulator-related molecular subtype strengthen the understanding of ccRCC' characterization and guide clinical treatment. Targeting senescence regulators may be regard as a proper way in ccRCC.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/genetics , Tumor Microenvironment/genetics , Immunotherapy , Aging , Kidney Neoplasms/drug therapy , Kidney Neoplasms/genetics , PrognosisABSTRACT
In the context of global climate change, sudden rainstorms and typhoons induce fluctuations in hydraulic shocks to wastewater treatment plants (WWTPs) in coastal areas, causing two challenges of stable effluent quality and low-carbon operation. We established a quantitative evaluation method for resistance of wastewater treatment processes to hydraulic shocks based on the water-energy-carbon nexus using operational data from a WWTP in southeast coastal China from July 2018 to December 2022. The effects of hydraulic shocks on the operational stability of the anaerobic-anoxic-oxic-membrane bioreactor (A2/O-MBR) process were analyzed following five steps. The results showed that the gray water footprint (GWF) of the process was 9.3% lower than that of the A2/O process. The energy footprint (ENF) and carbon footprint (CF) were approximately 2.1 times and 1.7 times higher than those of the A2/O process, respectively. The resistance to hydraulic shocks of the A2/O-MBR process is approximately 5.5 times higher than that of the A2/O process. In conclusion, the A2/O-MBR process exhibits higher process operational stability when subjected to hydraulic shocks, which is more conducive to the efficient and stable operation of WWTPs in rainstorm and typhoon-prone areas. The evaluation methodology provides qualitative technical support for selecting upgrading processes for WWTPs in different regions.
ABSTRACT
Beetles have a remote evolutionary history dating back to the Carboniferous, with Mesozoic fossils playing a pivotal role in elucidating the early evolution of extant families. Despite their exceptional preservation in amber, deciphering the systematic positions of Mesozoic trogossitid-like beetles remains challenging. Here, we describe and illustrate a new trogossitid-like lineage from mid-Cretaceous Kachin amber, Foveapeltis rutai Li, Kolibác, Liu & Cai, gen. et sp. nov. Foveapeltis stands out within the Cleroidea due to the presence of a significant large cavity on each hypomeron. While the exact phylogenetic placement of Foveapeltis remains uncertain, we offer a discussion on its potential affinity based on our constrained phylogenetic analyses.
ABSTRACT
In this paper, a novel, simple and mild soft template assisted strategy and further carbonization approach has been constructed to the size-tunable preparation of porous Cu-N-C/Surfactant catalysts successfully. Note that the pluronic F127 has a significant influence on the synthesis of porous Cu-N-C/F127 with the atomically dispersed Cu-N4 and adjacent Cu atomic clusters (ACs) than other surfactants owing to their particular non-ionic structure. By combining a series of experimental analysis and density functional theory (DFT) calculations, the synergistic effects between the adjacent Cu ACs and atomically dispersed Cu-N4 are favorable for manipulating the binding energy of O2 adsorption and intermediates desorption at the atomic interface of catalysts, resulting in an excellent electrocatalytic ORR performance with a faster kinetics for Cu-N-C/F127 than those of the Cu-N-C, Cu-N-C/CTAB, Cu-N-C/SDS, and comparable with the commercial Pt/C catalyst. This method not only provides a novel approach for synthesizing highly effective copper based single atom catalysts toward ORR, but also offers an in-depth understanding of the synergisms of adjacent ACs on the Cu single atoms (SAs) for highly effective electrocatalytic ORR and Zn-air Battery.
ABSTRACT
Anaerobic methanotrophic archaea (ANME) belonging to the family Methanoperedenaceae are crucial for the global carbon cycle and different biogeochemical processes, owing to their metabolic versatility to couple anaerobic oxidation of methane (AOM) with different electron acceptors. A universal feature of Methanoperedenaceae is the abundant genes encoded in their genomes associated with extracellular electron transfer (EET) pathways. Candidatus. 'Methanoperedens manganicus', an archaeon belonging to the family Methanoperedenaceae, was recently enriched in a bioreactor performing AOM coupled with Mn (IV) reduction. Using this EET-capable ANME, we tested the hypothesis in this study that ANME can catalyse the humic-dependent AOM for growth. A two-year incubation showed that AOM activity can be sustained by Ca. 'M. manganicus' consortium in a bioreactor fed only with humic acids and methane. An isotopic mass balance batch test confirmed that the observed AOM was coupled to the reduction of humic acids. The increase of relative abundance of Ca. 'M. manganicus', and the total archaea population in the microbial community suggested that Ca. 'M. manganicus' can grow on methane and humic acids. The observation of humic-dependent AOM led to a subsequent hypothesis that humic acids could be used as the electron shuttle to mediate the EET in dissimilatory Mn (IV) reduction by Ca. 'M. manganicus'. We tested this hypothesis by adding humic acids to a Ca. 'M. manganicus' dominated-culture, which showed that the AOM rate was doubled by the addition of humic acids. X-ray photoelectron spectroscopy (XPS) showed that quinone moieties were consumed when humic acids worked as electron acceptors while remaining stable when functioning as a shuttle for electron transfer. The results of our study suggest that humic acids may serve as electron shuttles to allow ANME to access more electron acceptors through long-range EET.
Subject(s)
Humic Substances , Methane , Anaerobiosis , Methane/metabolism , Electrons , Archaea/metabolism , Oxidation-Reduction , OxidantsABSTRACT
Failure of proper ventricular trabeculation is often associated with congenital heart disease. Support from endocardial cells, including the secretion of extracellular matrix and growth factors is critical for trabeculation. However, it is poorly understood how the secretion of extracellular matrix and growth factors is initiated and regulated by endocardial cells. We find that genetic knockout of histone deacetylase 3 in the endocardium in mice results in early embryo lethality and ventricular hypotrabeculation. Single cell RNA sequencing identifies significant downregulation of extracellular matrix components in histone deacetylase 3 knockout endocardial cells. Secretome from cultured histone deacetylase 3 knockout mouse cardiac endothelial cells lacks transforming growth factor ß3 and shows significantly reduced capacity in stimulating cultured cardiomyocyte proliferation, which is remarkably rescued by transforming growth factor ß3 supplementation. Mechanistically, we identify that histone deacetylase 3 knockout induces transforming growth factor ß3 expression through repressing microRNA-129-5p. Our findings provide insights into the pathogenesis of congenital heart disease and conceptual strategies to promote myocardial regeneration.