Long noncoding RNA UCA1 promotes the expression and function of P-glycoprotein by sponging miR-16-5p in human placental BeWo cells.

Investigations on placental P-glycoprotein (P-gp) regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. The role of long noncoding RNA (lncRNA) on placental P-gp regulation is lacking. The present study was carried out to investigate the regulation and underlying mechanisms of lncRNA urothelial carcinoma associated 1 (UCA1) on P-gp in Bewo cells. lncRNA UCA1 inhibition or overexpression could decrease or increase ABCB1 mRNA expression, P-gp expression and its cellular efflux function, respectively. RNA-FISH revealed that lncRNA UCA1 was mainly located in the cytoplasm of Bewo cells. MicroRNA array was applied and 10 significant miRNAs was identified after lncRNA UCA1 inhibition. Databases of LncTarD, LncRNA2Target, and miRcode were further used to search potential target miRNAs of lncRNA UCA1 and miR-16-5p was screened out. Thereafter, we confirmed that miR-16-5p expression was significantly upregulated or reduced after lncRNA UCA1 knockdown or overexpression, respectively. Furthermore, we also proved that ABCB1 mRNA expression, P-gp expression and its cellular efflux function was enhanced or reduced after miR-16-5p inhibition or overexpression, respectively. The rescue experiment further indicated that miR-16-5p was involved in the positive regulation of lncRNA UCA1 on the expression and function of P-gp. Lastly, dual-luciferase reporter system, RNA-binding protein immunoprecipitation and RNA pull-down assays were performed to explore the relationships among lncRNA UCA1, miR-16-5p, and ABCB1. It was found that lncRNA UCA1(1103-1125) could directly interact with miR-16-5p and miR-16-5p could directly target ABCB1 coding DNA sequence region (882-907). In conclusion, LncRNA UCA1 could promote the expression and function of P-gp by sponging miR-16-5p in BeWo cells.

A double inducible cell ablation system for eliminating senescent astrocytes via apoptosis.

PURPOSE: Cell senescence stands as a principal risk factor for various neurodegenerative diseases, with astrocytic senescence emerging as a potentially pivotal player in the pathogenesis of aging and neurodegenerative disorders. Clearing senescent astrocytes holds promise as a potential therapeutic approach for senescence-related diseases. METHODS: In this study, we designed and constructed two plasmids aimed at inducing apoptosis in senescent astrocytes. This was achieved through the ligation of FKBP (FK506-binding protein) and FRB (FKBP and FKBP rapamycin binding domain) and the formation of caspase8 dimers, thereby achieving the purpose of eliminating senescent astrocytes. RESULTS: The developed vector system demonstrates a specifically capability to induce apoptosis in aging astrocytes, offering a targeted approach to eliminate these cells. CONCLUSION: The utilization of the double -inducible suicide gene system provides a versatile tool forstimulating cell apoptosis and inhibiting cellular senescence. This system proves valuable in exploring the intrinsic roles and molecular mechanisms of senescent cells in the occurrence and development of aging-related diseases. Ultimately, it offers a potential avenue for developing an efficient treatment system for such conditions.

Diabetes mellitus and hearing loss.

Diabetes mellitus (DM) is a major disease threatening human health and its incidence is increasing year on year. As a chronic complication of DM, hearing loss mostly occurs undetectably. However, the mechanism of this diabetes-related hearing loss (DRHL) remains unclear and there is no effective clinical treatment. Studies of animal or human pathology show that DM causes damage to the blood vessels, spiral ganglion neurons, afferent nerve fibers, the organ of Corti, and the stria vascularis of the inner ear. In recent years, more advances in pathological research have revealed the possible mechanism of DRHL. In addition, a large number of clinical studies suggest that the duration and severity of DM are closely related to the incidence and severity of DRHL. This review focuses on the relationship between DM and hearing loss. The clinical audiological characteristics of diabetic patients, risk factors for DRHL, typical pathology, and potential interventions of DRHL are summarized. This will help reveal the pathogenesis and intervention approaches for DRHL.

Effect and environmental behaviour of microplastics in soil.

Soil microplastic pollution is currently a worldwide concern. Microplastics are organic pollutants that are abundant in the natural environment, are persistent and difficult to degrade and may endanger human health while harming the environment. This article offers a bibliometric analysis of the environmental behaviour of microplastics in soils, as well as a thorough statistical analysis of research goals and trends in this field. We conducted a thorough search of all relevant literature from 2012 to 2022 in the Web of Science core database. The data analysis shows that, starting in 2012, there has been an upward trend in the number of articles about soil microplastic pollution. It can also be seen that China is relatively ahead of the curve in this area of research, followed by the United Kingdom and the United States. This article also systematically describes the research hotspots in this field. The results show that the current research on soil microplastics is mainly focused on their identification, enrichment and toxicity, whereas studies on the migration and transformation of soil microplastics and the mechanism of interaction with other pollutants are still lacking. Our results provide ideas and prospects for future research in this field.

Calibration experiments based on a CO2 absorption cell for the 1.57-µm spaceborne IPDA LIDAR.

The spaceborne IPDA LIDAR has the potential to measure the global atmosphere CO2 column concentrations with high accuracy. For this kind of LIDAR, system calibration experiments in the laboratory are of high importance. In this study, a specially-customized CO2 absorption cell is employed to simulate the CO2 column absorption of the spaceborne platform. Then calibration experiments are constructed for the receiving system and the entire LIDAR system. The absorption of several different XCO2 concentrations from 400 to 415 ppm in the atmosphere is equivalent to that of the absorption cell charged with different pressures of pure CO2. Under the zero pressure of the absorption cell, the calculated equivalent column average concentration (XCO2) is 12.53 ppm, which acts as system bias. In the calibration experiments, the absolute errors are all less than 1 ppm. And the standard deviations (STDs) are less than 1.1 ppm (148-shot averaging) and 0.8 ppm (296-shot averaging) for receiving system and less than 1.2 ppm and 0.9 ppm for the IPDA LIDAR system. All the results of different average times are close to each other and less than 1 ppm, which proves the high accuracy of the IPDA LIDAR system. In addition, the XCO2 concentrations Allan deviation of 0.25 ppm and 0.35 ppm at 100 s shows that the receiving system and IPDA LIDAR system function with long-term stability. Using a CO2 absorption cell as a standard calibration device in the laboratory validates the measurement accuracy and stability of the spaceborne IPDA LIDAR prototype. Furthermore, the proposed absorption cell may serve as a standard calibration device for related atmosphere trace gases sounding research.

Lanthanide-Organic Frameworks with Uncoordinated Lewis Base Sites: Tunable Luminescence, Antibiotic Detection, and Anticounterfeiting.

Several new isostructural lanthanide metal-organic frameworks (Ln-MOFs), {[Ln2(L)3DMA4]·2DMA}n (1-Ln, where Ln = Eu, Tb, or EuxTb1-x), were first constructed via the solvothermal reactions of 4,6-di(4-carboxyphenyl)pyrimidine and Ln3+ ions. 1-Ln exhibits a 4-connected two-dimensional framework endowed with uncoordinated Lewis base sites. An exploration of luminescence sensing demonstrated 1-Eu can be used for the selectivity detection of dimetridazole and metronidazole antibiotics in other antibiotics, blood plasma, and urine, acting as an exceptional recyclable luminescent probe. More importantly, the luminescent inks of 1-Ln are invisible, color adjustable, and stabilized, which may greatly improve their anticounterfeiting applications.

MEF2C ameliorates learning, memory, and molecular pathological changes in Alzheimer's disease in vivo and in vitro

Myocyte enhancer factor 2C (MEF2C) is highly expressed in the nervous system, and regulates neuro-development, synaptic plasticity, and inflammation. However, its mechanism in Alzheimer's disease (AD) is underestimated. In this study, the role and mechanism of MEF2C were investigated in the brain tissue specimens from patients with AD, APPswe/PSEN1dE9 double transgenic (APP/PS1_DT) mice, and SH-SY5Y cells treated with ß-amyloid peptide (Aß). The results indicated that the expression of MEF2C is significantly reduced, and the expression of MEF2C/Aß in different parts of brain is negatively correlated in patients with AD. Knockdown of MEF2C promotes cell apoptosis and the level of ß-amyloid precursor protein cleaving enzyme 1 (BACE) but reduces BACE2 expression. In addition, knockdown of enhances the generation and aggregation of Aß in the cortex of APP/PS1_DT mice, reduces the expression of synaptic proteins, exacerbates the ability of learning and memory of APP/PS1_DT mice, damages the structure of mitochondria, increases the oxidative stress (OS) level, and inhibits the expression levels of members of the Nrf2-ARE signal pathway. In summary, inhibition of MEF2C exacerbates the toxic effect of Aß and , damages synaptic plasticity, reduces the ability of learning and memory of APP/PS1 mice, and increases the level of OS via the Nrf2-ARE signal pathway.

Diagnostic Performance of [18F]-Labeled PET/CT Tracers for Lymph Node/Bone Metastasis and Biochemical Recurrence Detection in Advanced Prostate Cancer: A Meta-Analysis.

PURPOSE: The aim of this study was to explore the diagnostic value of different fluorine-18 (18F)-labeled tracers for lymph node/bone metastasis and biochemical recurrence detection in advanced prostate cancer (PCa). METHODS: PubMed, Embase, Web of Science, Cochrane databases, and the WHO International Clinical Trial Center were searched. The inclusion criteria were determined based on the Preferred Report Items of the Systematic Review and Meta-Analysis Guidelines. The Quality Assessment of Diagnostic Accuracy Studies-2 was used to assess the quality assessment of the included studies. The quantitative analysis of the included literature was performed on the patient and lesion basis, and the equivocal findings were considered negative or positive results, respectively. RESULTS: Thirty-seven articles were included. On the patient basis, the pooled sensitivity and specificity of [18F]-labeled tracers were 0.80 (95% confidence interval [CI]: 0.78-0.83) and 0.89 (95% CI: 0.87-0.90) when equivocal results were considered to be positive and 0.80 (95% CI: 0.77-0.82) and 0.87 (95% CI: 0.85-0.89) when equivocal results were considered to be negative. On the lesion basis, the pooled sensitivity and specificity of [18F]-labeled tracers were 0.82 (95% CI: 0.80-0.83) and 0.91 (95% CI: 0.90-0.92) when equivocal lesions were regarded as positive and 0.81 (95% CI: 0.80-0.82) and 0.91 (95% CI: 0.90-0.92) when equivocal lesions were considered to be negative. CONCLUSION: [18F]-labeled tracers have high diagnostic efficacy for lymph node/bone metastasis and biochemical recurrence in advanced PCa.

Selective Bonding Effect of Heterologous Oxygen Vacancies in Z-Scheme Cu2O/SrFe0.5Ta0.5O3 Heterojunctions for Constructing Efficient Interfacial Charge-Transfer Channels and Enhancing Photocatalytic NO Removal Performances.

An interfacial structure is crucial to the photoinduced electron transport for a heterostructure photocatalyst. Constructing an interfacial electron channel with an optimized interfacial structure can efficiently improve the electron-transfer efficiency. Herein, the rapid electron-transfer channels were built up in a Cu2O/SrFe0.5Ta0.5O3 heterojunction (Cu2O/SFTO) based on the selective bonding effect of heterologous surface oxygen vacancies in the SFTO component. The heterologous surface oxygen vacancies, namely, VO-Fe and VO-Ta, respectively, adjacent to Fe and Ta atoms, were introduced into fabricating the Z-scheme Cu2O/SFTO heterojunction. Compared with sample Cu2O/SFTO with VO-Fe, the photocatalytic NO removal efficiency of sample Cu2O/SFTO with VO-Fe and VO-Ta was increased by 22.5%. The enhanced photocatalytic performance originated from the selective bonding effect of heterologous VO-Fe and VO-Ta on the interfacial electron-separating and -transfer efficiency. VO-Fe is the main body to construct the interfacial electron-transfer channels by forming interfacial Fe-O-Cu(I) bonds, which causes lattice distortion at the interface, and VO-Ta can optimize the structure of interfacial channels by balancing the electron density of SFTO to control the average space of the interface transition zone. This research provides a new cognitive perspective for constructing double perovskite oxide-based heterostructure photocatalysts.

Predictive value of coagulation profiles for both initial and repeated immunoglobulin resistance in Kawasaki disease: A prospective cohort study.

BACKGROUND: Intravenous immunoglobulin (IVIG) resistance prediction remains substantial in Kawasaki disease (KD), with limited data on the predictive value of coagulation profile for IVIG resistance, particularly for repeated IVIG resistance. Therefore, the aim of our study was to testify the predictive validity of coagulation profile for both initial IVIG resistance and repeated IVIG resistance in KD. METHODS: A total of 385 KD patients were prospectively recruited between April 2015 and May 2019. Coagulation and other profiles were evaluated between the IVIG-responsive and IVIG-resistant groups. Multivariate logistic regression analysis was applied to determine the association between coagulation profiles and IVIG resistance. ROC curves analysis was further performed to assess the validity of coagulation profiles in predicting both initial IVIG resistance and repeated IVIG resistance. RESULTS: Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen degradation products (FDPs), and D-dimer were significantly increased in the initial IVIG-resistant group with antithrombin III (ATIII) and thrombin time (TT) significantly reduced. Meanwhile, ATIII was declined markedly in repeated IVIG-resistant patients. Multivariate logistic regression analysis showed that PT, APTT, D-dimer, and ATIII were independent risk factors for predicting initial IVIG resistance and ATIII for predicting repeated IVIG-resistant patients with KD. PT, APTT, D-dimer, and ATIII cutoff values of 13.95 s, 41.15 s, 1.48 mg/L, and 89.5% yielded sensitivities of 73%, 32%, 71%, and 81%, and specificities of 55%, 88%, 62%, and 51% for predicting initial IVIG resistance, respectively. The cutoff value of ATIII for predicting repeated IVIG resistance was 68.5%, with sensitivity of 71% and specificity of 55%. CONCLUSIONS: KD patients who have hypercoagulation during the acute phase might be at higher risk of developing IVIG resistance.

The effect of maternal exposure to di-(2-ethylhexyl)-phthalate on fetal cardiac development in mice.

Accumulating evidence has suggested a link between maternal di-(2-ethylhexyl)-phthalate (DEHP) exposure and various developmental abnormalities. However, the evidence regarding the effect of maternal DEHP exposure on fetal cardiac development is scarce. The present study aimed to determine the effect of maternal DEHP exposure on fetal cardiac development in mice and explore the possible involved mechanism preliminarily. The C57BL mice were randomly divided into four groups: the vehicle group (corn oil, n = 10), 250 mg kg-1 DEHP group (n = 15), 500 mg kg-1 DEHP group (n = 20) and 1 g kg-1 DEHP group (n = 20). Pregnant dams in different group received respective intervention by gavage once daily from embryonic day (E)6.5 to E14.5. Maternal weights were monitored every day and samples were collected at E15.5. Hematoxylin and eosin staining was used to examine fetal cardiac malformations. Real-time quantitative polymerase chain reaction and western blot were applied to detect peroxisome proliferator-activated receptor (PPAR)α/PPARγ/Nkx2.5/Gata4/Tbx5/Mef2c/Chf1 mRNA and protein expression, respectively. Maternal DEHP exposure significantly decreased maternal body weight, fetal weight and placental weight, and remarkably elevated fetal cardiac malformations rate. The phenotypes of cardiac anomalies mainly include septal defects, ventricular myocardium noncompaction and cardiac hypoplasia. Higher doses DEHP (500 mg kg-1 and 1 g kg-1 ) could significantly decreased fetal cardiac Gata4/Mef2c/Chf1 expression, while PPARγ expression was upregulated. Maternal exposure to higher doses of DEHP could result in fetal cardiac development malformations in mice and it might have resulted from the inhibition of cardiac GATA4/Mef2c/Chf1 expression via PPARγ activation.

Facile Synthesis of Size-Tunable Functional Polyimidazolium Macrocycles through a Photochemical Closing Strategy.

A synthetic strategy for the preparation of a series of polyimidazolium macrocycles from the corresponding dicarbene-derived metallacycles is described. Photodimerization of terminal cinnamic esters (UV-irradiation, λ=365 nm) produces the closed metallacycles with perfect stereoselectivity and high yields. Subsequent removal of the template from the photodimerization product results in polyimidazolium macrocycles. The size and shape of the receptor can be tuned easily by changing the length and breadth of the internal bridging groups of the ligands. Preliminary investigation shows the potential of the macrocycle as iodide sensor.

Pure separation of acetylene based on a sulfonic acid and amino group functionalized Zn-MOF.

The dual-ligand strategy was employed to synthesize a new microporous material, [Zn3(SNDC)(AmTAZ)3(H2O)]·H2O·CH3CN (1), incorporating sulfonic acid and amino groups for enhancing gas adsorption and separation. The activated 1 (named 1a) exhibited selective adsorption of acetylene over carbon dioxide and methane. Hence, the dual-ligand strategy optimized the pore environment and provided an effective approach for pure separation of gases.

MpoxNet: dual-branch deep residual squeeze and excitation monkeypox classification network with attention mechanism.

While the world struggles to recover from the devastation wrought by the widespread spread of COVID-19, monkeypox virus has emerged as a new global pandemic threat. In this paper, a high precision and lightweight classification network MpoxNet based on ConvNext is proposed to meet the need of fast and safe detection of monkeypox classification. In this method, a two-branch depth-separable convolution residual Squeeze and Excitation module is designed. This design aims to extract more feature information with two branches, and greatly reduces the number of parameters in the model by using depth-separable convolution. In addition, our method introduces a convolutional attention module to enhance the extraction of key features within the receptive field. The experimental results show that MpoxNet has achieved remarkable results in monkeypox disease classification, the accuracy rate is 95.28%, the precision rate is 96.40%, the recall rate is 93.00%, and the F1-Score is 95.80%. This is significantly better than the current mainstream classification model. It is worth noting that the FLOPS and the number of parameters of MpoxNet are only 30.68% and 31.87% of those of ConvNext-Tiny, indicating that the model has a small computational burden and model complexity while efficient performance.

Underlying mechanisms governing on distribution and stratification of DOM during seasonal freeze-thaw cycles.

During the freeze-thaw cycles of ice-covered lakes, DOM undergoes a series of transformations including enrichment, dispersion, and filtration. However, the mechanisms and influence factors on lake pollution processes remain unclear. Therefore, this study investigates the distribution of DOM components and elucidate the role of ice-layer sieving its mechanisms within ice-water-sediments. Study identifies significant variations in the characteristics of DOM, protein-like substances tend to migrate towards the ice layer, while humic-like substances predominantly remain in water. This selective distribution is primarily influenced by the physical and chemical properties of DOM during the freezing process. The ice layer acts as a sieve, allowing smaller molecules such as protein-like substances to pass through more easily, while larger molecules like humic-like substances are retained in the water. Additionally, Temperature plays a pivotal role in affecting the contents of DOM. As the temperature decreases, the solubility of DOM decreases, leading to its precipitation and enrichment in sediments. Conversely, an increase in temperature can facilitate the release of DOM from sediments into the water. Furthermore, high content of total dissolved solids can affect the solubility and stability of DOM, potentially leading to changes in its composition and distribution. These insights provide a deeper understanding of the complex interplay between thermal processes and chemical dynamics within ice-covered aquatic environments. They offered valuable insights into the behavior of organic pollutants in frozen lake systems. The findings have potential implications for environmental management strategies aimed at mitigating the effects of climate.

20-Deoxyingenol Activates Mitophagy Through TFEB and Promotes Functional Recovery After Spinal Cord Injury.

Spinal cord injury (SCI) can lead to permanent paralysis and various motor, sensory and autonomic nervous system dysfunction. The complex pathophysiological processes limit the effectiveness of many clinical treatments. Mitochondria has been reported to play a key role in the pathogenesis of SCI; while mitophagy is a protective mechanism against mitochondrial dysfunction. However, there is recently little drugs that may targeted activate mitophagy to treat SCI. In this study, we evaluated the role of 20-Deoxyingenol (20-DOI) in SCI and explored its potential mechanisms. We used a SCI rat model and evaluated the functional outcomes after the injury. Western blotting and immunofluorescence techniques were used to analyze the levels of mitophagy, apoptosis, and TFEB-related signaling pathways. Our research results show that 20-DOI significantly improves the apoptosis of neural cells after TBHP stimulation and functional recovery after spinal cord injury. In addition, mitophagy, TFEB levels, and apoptosis are related to the mechanism of 20-DOI treatment for spinal cord injury. Specifically, our research results indicate that 20-DOI restored the autophagic flux after injury, thereby inducing mitophagy, eliminating the accumulation of Cyto C, and inhibiting apoptosis. Further mechanism research suggests that 20-DOI may regulate mitophagy by promoting TFEB nuclear translocation. These results indicate that 20-DOI can significantly promote recovery after spinal cord injury, which may be a promising treatment method for spinal cord injury.

Fisetin suppresses ferroptosis through Nrf2 and attenuates intervertebral disc degeneration in rats.

Low back pain, primarily caused by intervertebral disc degeneration (IVDD), lacks effective pharmacological treatments. Oxidative stress has been identified as a significant contributor to IVDD. This study aims to establish an in vitro model of IVDD induced by oxidative stress and identify potential therapeutic agents and their underlying mechanisms. By screening the natural product library, fisetin emerged as the most promising compound in suppressing cell death induced by oxidative stress in nucleus pulposus cells (NPCs). Furthermore, our investigation revealed that the cell death induced by oxidative stress was predominantly associated with ferroptosis, and fisetin demonstrated the ability to inhibit ferroptosis in NPCs. Mechanistic exploration suggested that the impact of fisetin on ferroptosis may be mediated through the Nrf2/HO-1 (Nuclear factor erythroid 2-related factor 2/heme oxygenase-1) axis. Notably, the in vivo study demonstrated that fisetin could alleviate IVDD in rats. These findings highlight fisetin as a potential therapeutic option for IVDD and implicate the involvement of the Nrf2/HO-1 pathway in its mechanism of action.

Hepatic epithelioid angiomyolipoma is scattered and unsuitable for surgery: a case report.

Hepatic epithelioid angiomyolipoma (HEAML) is a rare tumour of mesenchymal tissue with a malignant tendency. Occurring most frequently in women, the relative incidence in men and women, according to incomplete statistics, is approximately 1:5. In rare cases, disease occurrence and development is hidden. Lesions are generally discovered as chance findings by patients; abdominal pain is the first symptom, and imaging has no specificity in diagnosing the disease. Therefore, great difficulties exist in the diagnosis and treatment of HEAML. Here, the case of a 51-year-old female patient with a history of hepatitis B, and abdominal pain over 8 months as the initial symptom, is described. The patient was found to have multiple intrahepatic angiomyolipoma. Due to the small and scattered foci, complete resection was impossible, and because of her history of hepatitis B, conservative treatment was undertaken, with the patient undergoing regular follow-up. When hepatic cell carcinoma could not be excluded, the patient was treated with transcatheter arterial chemoembolization. No tumour neogenesis or metastasis was detected at the 1-year follow-up.

Modification mechanism of protein in rice adjuncts upon extrusion and its effects on nitrogen conversion during mashing.

The traditional production of wort with adjunct-introduced was achieved by double mashing procedure, which hindered the utilization of proteins in adjunct and led to a deficiency of nitrogen in wort. In this study, the modification mechanism of the extrusion pretreatment on the structure characterization of rice flour protein was investigated. The decoction mashing procedure was performed to enhance the nitrogen conversion of the extruded rice adjunct. Decreased solubility along with disrupted secondary and tertiary structures of rice protein were observed after extrusion. As a result, the total nitrogen, free amino nitrogen, and free amino acids content of wort with extruded rice adjunct-introduced were improved by 23.28 %, 34.67 %, and 7.33 %, respectively, which could be verified by the electrophoretic patterns of the wort protein. The application of extrusion as a pretreatment of adjuncts can promote the protein availability of adjuncts in the decoction mashing stage.

A novel adhesive dual-sensitive hydrogel for sustained release of exosomes derived from M2 macrophages promotes repair of bone defects.

The repair of bone defects remains a huge clinical challenge. M2 macrophage-derived exosomes (M2-Exos) can act as immunomodulators to promote fracture healing; however, how to retain the sustained release of exosomes to the target area remains a challenge. Here, we report a composite hydrogel loaded with M2-Exos aiming to accelerate bone defect healing. It was verified that the F127/HA-NB hydrogel had a dense network structure, tissue adhesiveness, and dual sensitivity to temperature and light. F127/HA-NB loaded with M2-Exos (M2-Exos@F127/HA-NB) exhibited good biocompatibility and achieved sustained release of exosomes for up to two weeks. The study showed that both M0-Exos and M2-Exos@F127/HA-NB significantly promoted osteogenic differentiation of rat bone marrow mesenchymal stem cells. The mechanism study implied that M2-Exos activates the Wnt/ß-catenin signaling pathway to promote osteogenic differentiation of BMSCs. Finally, we evaluated the osteogenetic effects of M2-Exos@F127/HA-NB in a rat cranial defect model, and the results showed that M2-Exos@F127/HA-NB had superior bone regeneration-promoting effects. This study provides a new strategy for cell-free treatment of bone defects.