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Docosahexaenoic acid-phospholipids (DHA-PLs) were prepared via lipase-mediated transesterification of DHA donor and phosphatidylcholine (PC) in a purely aqueous solution. Pre-existing carriers would play the role as "artificial interfaces" to adsorb water-insoluble PC and made them disperse in water. DHA donors were concentrated by a pH-responsive method and presented as supersaturated salt solutions. 153 triacylglycerol lipase structures were analyzed and screened in silico. Transesterification was carried out to further evaluate the six lipase candidates. Lipase B from Candida antarctica (CALB) was the best biocatalyst with 34.8% of DHA incorporation and 80.0% of PLs yields (involving 38.1% PC and 41.9% sn-1 lyso-PC). Toxic organic solvents were avoided. Six possible microunits of our aqueous system consisting of three PLs donors (PC, lyso-PC, sn-glycero-3-PC) and two DHA donors (DHA and DHA salts), were simulated by molecular dynamics (MD) to illustrate the enzymatic mechanism based on diffusional channels, competitive bindings, and enzymatic structures.
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Ácidos Docosa-Hexaenoicos , Fosfolipídeos , Lecitinas , Esterificação , LipaseRESUMO
BACKGROUND: Omicron had swept the mainland China between December 2022 and January 2023, while SARS-CoV-2 still continued to evolve. To fully prepare for the next wave, it's urgent to evaluate the humoral immune response post BA.5/BF.7 breakthrough infection against predominant sublineages among existing vaccination strategies and the elders. METHOD: This study enrolled a longitudinal young-adult cohort from 2/3-dose vaccination to 1 month after breakthrough infection, and an elder cohort at 1 month after breakthrough infection. Seral samples were collected and tested for humoral immune response to SARS-CoV-2 subvariants including WT, BA.2, BA.5, BF.7, BQ.1.1, CH.1.1, XBB.1.5. RESULTS: BA.5/BF.7 breakthrough infection induced higher neutralization activity than solely vaccination in all SARS-CoV-2 strains, while the latest Omicron subvariants, BQ.1.1, CH.1.1, XBB.1.5, exhibited the strongest neutralization evasion ability. There was a negative correlation between age and humoral immune response in WT, BA.5, BQ.1.1, and XBB.1.5. Compared to non-vaccination groups, breakthrough infection in two-dose vaccination groups had significantly higher neutralizing antibody against WT, BA.2, BA.5, BF.7 but not to BQ.1.1, CH.1.1, XBB.1.5., while booster dose against the prototype prior-breakthrough would not further significantly enhance individual's humoral responses against the latest Omicron subvariants. CONCLUSIONS: Newer variants manifest increasing immune evasion from neutralization and repeated prototype-based booster vaccines may not further enhance neutralizing antibody against emerging new variants. Older adults have lower levels of neutralizing antibody. Future vaccination strategies should aim to enhance effective neutralization to contemporary variants.
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Optical differential operation based on the photonic spin Hall effect(SHE) has attracted extensive attention in image processing of edge detection, which has advantages of high speed, parallelism, and low power consumption. Here, we theoretically demonstrate tunable optical differential operation in a four-layered nanostructure of prism-graphene-air gap-substrate. It is shown that the spatial differentiation arises inherently from the photonic SHE. Furthermore, we find that the transverse spin-Hall shift induced by the photonic SHE changes dramatically near the Brewster angle with the incident angle increases at a telecommunication wavelength. Meanwhile, the Fermi energy of graphene and the thickness of the air gap can affect the transverse spin shift. Interestingly, we can easily adjust the Fermi energy of graphene in real time through external electrostatic field biasing, enabling fast edge imaging switching at a telecommunication wavelength. This may provide a potential way for future tunable spin-photonic devices, and open up more possible applications for artificial intelligence, such as target recognition, biomedical imaging, and edge detection.
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Sewage treatment plants (STPs) are one of the crucial barriers for the environmental emission of steroid hormones. Insights into the occurrence and fate of different categories of steroid hormones in STPs could provide theoretical support for improving steroid removal by STPs. The present study investigated 22 steroid hormones in each treatment process of two STPs located in Wuxi via eight monthly sampling campaigns and compared the efficacy of Anaerobic-Anoxic-Aerobic (A2/O) and reversed A2/O treatments. The results showed that the total steroid concentrations in the influent and effluent were 27.7-256.8 ng·L-1 and 5.7-211.0 ng·L-1, respectively, and 36.3-123.6 ng·g-1 in the excess sludge. Androsterone, androstenedione, estrone, estriol, and progesterone were the main species detected in the STPs. The concentrations of most steroids increased with the rise of rainfall and temperature, whereas the removal rates were not significantly different between winter and summer. Secondary and tertiary treatment processes showed better performance in steroid removal compared with that in the primary treatment; however, reversed A2/O did not show advantages over traditional A2/O. The organic-normalized partition coefficients (lg Koc) of steroids ranged between 2 and 4.5. The values of lg Koc in STP A were slightly greater than those in STP B, indicating that the partition behavior of steroids may influence their treatment efficacies.
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Progesterona , Esgotos , Estrona , Estações do Ano , TemperaturaRESUMO
CD38 is a crucial NADase in mammalian tissues that degrades NAD+ and thus regulates cellular NAD+ levels. Abnormal CD38 expression is linked to mitochondrial dysfunction under several pathological conditions. We present a novel CD38 inhibitor, compound 1, with high potency for CD38 (IC50 of 11 nM) and minimal activity against other targets. In a Pus1 knockout (Pus1-/-) mouse model of mitochondrial myopathy, compound 1 treatment rescued the decline in running endurance in a dose-dependent manner, associated with an elevated NAD+ level in muscle tissue, increased expression of Nrf2, which is known to promote mitochondrial biogenesis, and reduced lactate production. RNA sequencing data indicated that compound 1 has a great effect on mitochondrial function, metabolic processes, muscle contraction/development, and actin filament organization via regulating the expression of relevant genes. Compound 1 is a promising candidate for its excellent in vivo efficacy, favorable pharmacokinetics, and attractive safety profile.
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Remote sensing image denoising is of great significance for the subsequent use and research of images. Gaussian noise and salt-and-pepper noise are prevalent noises in images. Contemporary denoising algorithms often exhibit limitations when addressing such mixed noise scenarios, manifesting in suboptimal denoising outcomes and the potential blurring of image edges subsequent to the denoising process. To address the above problems, a second-order removal method for mixed noise in remote sensing images was proposed. In the first stage of the method, dilated convolution was introduced into the DnCNN (denoising convolutional neural network) network framework to increase the receptive field of the network, so that more feature information could be extracted from remote sensing images. Meanwhile, a DropoutLayer was introduced after the deep convolution layer to build the noise reduction model to prevent the network from overfitting and to simplify the training difficulty, and then the model was used to perform the preliminary noise reduction on the images. To further improve the image quality of the preliminary denoising results, effectively remove the salt-and-pepper noise in the mixed noise, and preserve more image edge details and texture features, the proposed method employed a second stage on the basis of adaptive median filtering. In this second stage, the median value in the original filter window median was replaced by the nearest neighbor pixel weighted median, so that the preliminary noise reduction result was subjected to secondary processing, and the final denoising result of the mixed noise of the remote sensing image was obtained. In order to verify the feasibility and effectiveness of the algorithm, the remote sensing image denoising experiments and denoised image edge detection experiments were carried out in this paper. When the experimental results are analyzed through subjective visual assessment, images denoised using the proposed method exhibit clearer and more natural details, and they effectively retain edge and texture features. In terms of objective evaluation, the performance of different denoising algorithms is compared using metrics such as mean square error (MSE), peak signal-to-noise ratio (PSNR), and mean structural similarity index (MSSIM). The experimental outcomes indicate that the proposed method for denoising mixed noise in remote sensing images outperforms traditional denoising techniques, achieving a clearer image restoration effect.
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Background: With the popularity of smartphone and their increasingly rich functions, people's attachment to their phones is increasing. While people enjoy the convenience that smartphone bring (eg, accessing information and socializing), it also leads to problematic smartphone use (eg, phubbing). Previous research has shown that boredom proneness can trigger phubbing. However, the underlying psychological mechanisms are not yet clear. Methods: To address this research gap, we surveyed 556 Chinese college students (Mage = 18.89 years, SD = 1.18) during the COVID-19 pandemic and all participants completed a self-report questionnaire. Drawing the Interaction of Person-Affect-Cognition-Execution model (I-PACE) for addictive behaviors, this study developed and examined a multiple mediation model incorporating boredom proneness, loneliness, fear of missing out (FoMO), and phubbing. Results: (1) Boredom proneness could positively predict phubbing; (2) loneliness and FoMO mediated the relationship between boredom proneness and phubbing, respectively; and (3) loneliness and FoMO sequentially mediated the relationship between boredom proneness and phubbing. Conclusion: These findings are not only valuable for understanding the underlying mechanisms linking boredom proneness and phubbing, but also suggest that three types of interventions could be effectively used to decrease the risk of phubbing among college students, namely, reducing boredom proneness, relieving loneliness, and decreasing FoMO.
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As is well documented, Alzheimer's disease (AD) is the most prevalent neurodegenerative disease. Meanwhile, Schisandra polysaccharide (SCP) has been reported to exert a protective effect on the nervous system and can regulate metabolic disorders in AD-like symptoms of amyloid ß-peptide (Aß) 25-35-induced rats. Nevertheless, the underlying mechanisms and metabolic markers for the diagnosis of AD are yet to be determined. This study aimed to explore the neuroprotective effect and potential mechanism of action of SCP in AD-like symptoms of Aß25-35-induced rats by combining pharmacodynamics, metabolomics, and lipidomics. The pharmacodynamic results revealed that SCP significantly improved the spatial learning and long-term memory function and the morphology of neurons in the hippocampal CA1 region, alleviated inflammatory damage and oxidative stress, inhibited the activation of microglia and astrocytes, and increased the proportion of mature neurons of AD-like symptoms of Aß25-35-induced rats. The results of hippocampal metabolomics and serum lipidomics showed 46 and 48 potential biomarkers were identified for the SCP treatment of AD, respectively. The involved pathways principally comprised lipid metabolism, amino acid metabolism, and energy metabolism. This study elucidates the neuroprotective effect of SCP in AD and its mechanism from the perspective of metabolomics and lipidomics and provides a theoretical basis for the therapeutic effect of SCP in AD.
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Homeobox (HOX) genes encode highly conserved transcription factors that play vital roles in embryonic development. DNA methylation is a pivotal regulatory epigenetic signaling mark responsible for regulating gene expression. Abnormal DNA methylation is largely associated with the aberrant expression of HOX genes, which is implicated in a broad range of human diseases, including cancer. Numerous studies have clarified the mechanisms of DNA methylation in both physiological and pathological processes. In this review, we focus on how DNA methylation regulates HOX genes and briefly discuss drug development approaches targeting these mechanisms.
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INTRODUCTION: Ovarian aging is characterized by a gradual decline in quantity and quality of oocytes, and lower chance of fertility. Better understanding the genetic modulation during ovarian aging can further address available treatment options for aging-related ovarian diseases and fertility preservation. METHODS: A novel technique spatial transcriptomics (ST) was used to investigate the spatial transcriptome features of rat ovaries. Transcriptomes from ST spots in the young and aged ovaries were clustered using differentially expressed genes. These data were analyzed to determine the spatial organization of age-induced heterogeneity and potential mechanisms underlying ovarian aging. RESULTS: In this study, ST technology was applied to profile the comprehensive spatial imaging in young and aged rat ovary. Fifteen ovarian cell clusters with distinct gene-expression signatures were identified. The gene expression dynamics of granulosa cell clusters revealed three sub-types with sequential developmental stages. Aged ovary showed a significant decrease in the number of granulosa cells from antral follicle. Besides, a remarkable rearrangement of interstitial gland cells was detected in aging ovary. Further analysis of aging-associated transcriptional changes revealed that the disturbance of oxidative pathway was a crucial factor in ovarian aging. CONCLUSIONS: This study firstly described an aging-related spatial transcriptome changes in ovary, and identified the potential targets for prevention of ovarian aging. These data may provide the basis for further investigations of the diagnosis and treatment of aging-related ovarian disorders.
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With the rapid development of intelligent electronic devices, conductive fibers have become very critical to signal transmission devices. However, metal-based rigid conductive wires, such as high-modulus copper and silver wires, are prone to signal failure owing to tensile breakage under large strain conditions. Therefore, strain-insensitive stretchable conductive fibers for signal transmission are critical for next-generation wearable devices. Herein, a stretchable conductive fiber with a built-in helical structure is constructed by a "speed discrepancy" fiber-coating strategy with mass scalable production (60 cm/min). Such a "speed discrepancy" strategy is the key mechanism to template-free fabricate a built-in helical structure of the stretchable conductive fiber. The resultant fiber exhibits high conductivity (873 S/cm), stable insensitive signal transmission with a high quality factor (47.4), and a low relative resistance change (â¼6%) under large strain. The built-in helical structure inspired by loofah whiskers endows the fiber with excellent strain insensitivity, and it can withstand large strains. On the proof of concept, our fiber can be seamlessly knitted, woven, and braided into smart textiles as an ideal signal transmission device under large strains, which will undoubtedly promote the development of intelligent electronic textiles and next-generation wearable devices.
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Objective: To investigate the effects of Moringa Oleifera Leaf Extract (MOLE) plus rosiglitazone (RSG) on glucose and lipid metabolism, serum leptin, and the Akt/GSK3ß/ß-Catenin signaling pathway in type 2 diabetic (T2D) rats. Methods: Sixty male Sprague-Dawley (SD) rats were randomly divided into six groups: the normal group, the model group, the RSG group, the low- and high-dose MOLE group, and the MOLE+RSG group. The normal group was fed a standard rat diet, while the other groups were given a single intraperitoneal injection of low-dose streptozomycin (STZ) (35 mg/kg) and fed a high-sugar and high-fat diet. After 8 weeks, the treatment outcomes were evaluated by measuring key parameters of blood glucose and lipid metabolism and the protein kinase B (AKT) / Glycogen synthase kinase 3beta (GSK3ß) /ß-Catenin signaling pathway in the T2D rats. Results: Compared with the normal group, the model group showed significantly increased levels of blood glucose, blood lipids, serum leptin, free fatty acid (FFA), and tumor necrosis factor-α (TNF-α). Compared with the model group, the RSG, low-dose MOLE, and high-dose MOLE groups displayed effective control of blood glucose, blood lipids, serum leptin, FFA, and TNF-α. The MOLE+RSG group surpassed the RSG group in regulating glucose, lipid metabolism, and serum leptin levels in T2D rats. In addition, the MOLE+RSG group also had superiority over the RSG group in activating the AKT/GSK3ß/ß-Catenin pathway. Conclusion: MOLE plus RSG can effectively reduce blood glucose and blood lipids in T2DM rats.
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The adult brain is made up of anatomically and functionally distinct regions with specific neuronal compositions. At the root of this neuronal diversity are neural stem and progenitor cells (NPCs) that produce many neurons throughout embryonic development. During development, NPCs switch from initial expanding divisions to neurogenic divisions, which marks the onset of neurogenesis. Here, we aimed to understand when NPCs switch division modes to generate the first neurons in the anterior-most part of the zebrafish brain, the telencephalon. To this end, we used the deep learning-based segmentation method Cellpose and clonal analysis of individual NPCs to assess the production of neurons by NPCs in the first 24 h of zebrafish telencephalon development. Our results provide a quantitative atlas detailing the production of telencephalic neurons and NPC division modes between 14 and 24 h postfertilization. We find that within this timeframe, the switch to neurogenesis is gradual, with considerable heterogeneity in individual NPC neurogenic potential and division rates. This quantitative characterization of initial neurogenesis in the zebrafish telencephalon establishes a basis for future studies aimed at illuminating the molecular mechanisms and regulators of early neurogenesis.
Quantification of neuron production and neural progenitor division modes in zebrafish embryonic telencephalon up to 24 h postfertilization using deep learning-based segmentation and clonal analysis methods.
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Risk control in complex transport construction is complicated due to the dangerous nature of high variation and unpredictability. Most of the current research analysis focuses on the health, safety, and environment (HSE) risk assessment and employee performance evaluation, which neglects the impact of HSE risks on employee performance. Consequently, this research develops a framework to evaluate employee performance and identify key factors affecting performance. The employee performance indicators and HSE indicators are established by reviewing related literature. Using data from questionnaires, an artificial neural network- (ANN-) based model of employee activity effectiveness is then developed to evaluate employee performance. Sensitivity analysis is implemented to determine the key factors affecting employee performance. The Hong Kong-Zhuhai-Macau Bridge, a large-scale cross-sea channel project, is taken as a case study for validation. The model results show that the employees are satisfied with the effect of HSE management in general, but the psychological stress they perceive becomes large. The indicators of risk control and employee participation positively impact employee performance, while job satisfaction has a negative impact on performance. These findings indicate that operators should pay more attention to employees' psychological perception of work and form a standardized process management and control plan to prevent cumbersome processes from increasing employees' workload. This study helps construction systems and managers to identify the areas of strengths and weaknesses in their HSE management. The research only focuses on the impact of HSE risks on managers' performance in the complex transport construction project. In the future, further engineering projects and employee performance in composite scenarios can be investigated to improve the overall productivity.
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Engenharia , Redes Neurais de Computação , Humanos , Hong Kong , Macau , Medição de RiscoRESUMO
The grain-refining mechanism with minor Sr - Sc - La and ultrasonic vibration treatment (UVT) in the hypereutectic Al-20Si alloy were studied. The results demonstrated that the microstructure of the hypereutectic Al-20Si alloy could be refined significantly, further improve its mechanical properties. The desirable refinement of the microstructure was achieved using 0.2% Sr, 0.15% Sc, and 0.3% La under UVT, achieving the highest grain circularity coefficient, hardness, elongation, and area reduction. The tensile strength was the largest with the addition of 0.2% La. The findings of this study provide theoretical and experimental guidelines for the fabrication of structural materials for application in automotive, aerospace, and deep-sea equipment.
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Approximately 15% of US adults have circulating levels of uric acid above its solubility limit, which is causally linked to the disease gout. In most mammals, uric acid elimination is facilitated by the enzyme uricase. However, human uricase is a pseudogene, having been inactivated early in hominid evolution. Though it has long been known that uric acid is eliminated in the gut, the role of the gut microbiota in hyperuricemia has not been studied. Here, we identify a widely distributed bacterial gene cluster that encodes a pathway for uric acid degradation. Stable isotope tracing demonstrates that gut bacteria metabolize uric acid to xanthine or short chain fatty acids. Ablation of the microbiota in uricase-deficient mice causes severe hyperuricemia, and anaerobe-targeted antibiotics increase the risk of gout in humans. These data reveal a role for the gut microbiota in uric acid excretion and highlight the potential for microbiome-targeted therapeutics in hyperuricemia.
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Gota , Hominidae , Hiperuricemia , Adulto , Animais , Humanos , Camundongos , Gota/genética , Gota/metabolismo , Hominidae/genética , Hiperuricemia/genética , Mamíferos/metabolismo , Urato Oxidase/genética , Ácido Úrico/metabolismo , Evolução MolecularRESUMO
Both biomedical applications and safety assessments of manufactured nanomaterials require a thorough understanding of the interaction between nanomaterials and cells, including how nanomaterials enter cells, transport within cells, and leave cells. However, compared to the extensively studied uptake and trafficking of nanoparticles (NPs) in cells, less attention has been paid to the exocytosis of NPs. Yet exocytosis is an indispensable process of regulating the content of NPs in cells, which in turn influences, even decides, the toxicity of NPs to cells. A comprehensive understanding of the mechanisms and influencing factors of the exocytosis of NPs is not only essential for the safety assessment of NPs but also helpful for guiding the design of safe and highly effective NP-based materials for various purposes. Herein, we review the current status and progress of studies on the exocytosis of NPs. Firstly, we introduce experimental procedures and considerations. Then, exocytosis mechanisms/pathways are summarized with a detailed introduction of the main pathways (lysosomal and endoplasmic reticulum/Golgi pathway) and the role of microtubules; the patterns of exocytosis kinetics are presented and discussed. Subsequently, the influencing factors (initial content and location of intracellular NPs, physiochemical properties of NPs, cell type, and extracellular conditions) are fully discussed. Although there are inconsistent results, some rules are obtained, like smaller and charged NPs are more easily excreted. Finally, the challenges and future directions in the field have been discussed.
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Few studies have focused on the exploration of the relationship between dietary fiber intake (DFI) and health-related quality of life (HRQoL) and its mediators in hypertensive patients. This study is a cross-sectional survey and the data were obtained from hypertensive patients from Suzhou, China. The DFI, office systolic blood pressure and diastolic blood pressure, anxiety and depression, and HRQoL were investigated. We hypothesized that blood pressure, anxiety, and depression mediated the association between DFI and HRQoL, and used Pearson correlations, linear regression, and bootstrap tests to validate this relationship. A total of 211 hypertensive patients aged 20 to 64 years were included in this study. The average DFI was 12.4 ± 5.2 g/d, and the scores of physical component summary and mental component summary (MCS) were 46.5 ± 6.1 and 46.4 ± 6.4, respectively. DFI was positively correlated with physical component summary (r = 0.17, p = 0.014) and MCS (r = 0.27, P < .001). After controlling for sociodemographic and clinical characteristics, neither systolic blood pressure nor diastolic blood pressure showed mediating effects in the mediated model of DFI on MCS, whereas anxiety (b = -0.30; 95% confidence interval, -0.41 to -0.18) fully mediated the improvement in MCS by DFI (F = 11.14, P < .001). Because the MCS of HRQoL encompassed the assessment of depression, we did not analyze the mediating effect of depression in this model in order to avoid variable duplication. The decreased DFI is a risk factor for lower HRQoL, and anxiety mediated the relationship between DFI and MCS. Further research should focus on increasing DFI and reducing anxiety levels in hypertensive patients to improve their quality of life.
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An optical spectrometer is a basic spectral instrument that probes microscopic physical and chemical properties of macroscopic objects but generally suffers from difficulty in broadband time-resolved measurement. In this work, we report the creation of ultrabroadband white-light laser with a 3-dB bandwidth covering 385 to 1,080 nm, pulse energy of 1.07 mJ, and pulse duration of several hundred femtoseconds by passing 3-mJ pulse energy, 50-fs pulse duration Ti:Sapphire pulse laser through a cascaded fused silica plate and chirped periodically poled lithium niobate crystal. We utilize this unprecedented superflat, ultrabroadband, and intense femtosecond laser light source to build a single-shot (i.e., single-pulse) subpicosecond pulse laser ultraviolet-visible-near-infrared spectrometer and successfully measure various atomic and molecular absorption spectra. The single-shot ultrafast spectrometer may open up a frontier to monitor simultaneously the ultrafast dynamics of multiple physical and chemical processes in various microscopic systems.
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Alkbh5 is one of the primary demethylases responsible for reversing N6-methyladenosine (m6A) modifications on mRNAs, and it plays a crucial role in many physiological and pathological processes. Previous studies have shown that Alkbh5 is required for maintaining the function of leukemia stem cells but is dispensable for normal hematopoiesis. In this study, we found that Alkbh5 deletion led to a moderate increase in the number of multiple progenitor cell populations while compromising the long-term self-renewal capacity of hematopoietic stem cells (HSCs). Here, we used RNA-seq and m6A-seq strategies to explore the underlying molecular mechanism. At the molecular level, Alkbh5 may regulate hematopoiesis by reducing m6A modification of Cebpa and maintaining gene expression levels. Overall, our study unveiled an essential role for Alkbh5 in regulating HSC homeostasis and provides a reference for future research in this area.