Metabolomics reveals early pregnancy biomarkers in sows: a non-invasive diagnostic approach.

In an effort to enhance reproductive management and reduce non-productive periods in swine breeding, this study presents a novel, non-invasive metabolomics approach for the identification of early pregnancy biomarkers in sows. Utilizing an untargeted metabolomics approach with mass spectrometry analysis, we examined saliva samples from pregnant (n = 6) and non-pregnant control sows (n = 6, artificially inseminated with non-viable sperm). Our analysis revealed 286 differentially expressed metabolites, with 152 being up-regulated and 134 down-regulated in the pregnant group. Among these, three metabolites, namely Hyodeoxycholic acid, 2'-deoxyguanosine, and Thymidine, emerged as potential early pregnancy biomarkers. These biomarkers were further evaluated using targeted LC-MS/MS quantification and qualification, accompanied by ROC curve analysis. The study confirmed Hyodeoxycholic acid and 2'-deoxyguanosine as promising biomarkers for early pregnancy detection, offering potential for future implementation in swine production environments. This research establishes a robust theoretical foundation for the development of innovative molecular diagnostic techniques and explores new avenues for molecular genetic breeding and non-invasive diagnostics, ultimately enhancing fertility and productivity in sow herds.

Weekend / holiday effect on stroke mortality in regional Australia: a ten-year retrospective study.

BACKGROUND: There is a deficiency in the evidence from rural and regional centres in Australia on the weekend effect following presentation with acute stroke. OBJECTIVE: To estimate the association between admission over a weekend/holiday and all-cause mortality 3-day, 7-day, 14-day, 1-month, 3-month, 6-month, and 12-month following acute stroke. METHODS: The records of stroke patients admitted to a main regional hospital in Australia from 2010 to 2020 were linked with the National Death Index. Time to death following ischaemic, haemorrhagic, and total stroke at different time points was modelled using Weibull, Exponential, or Gompertz regression based on best model fit determined by Akaike's information criterion. RESULTS: Of 1669 patients, 1273 (76.3%) were admitted on a weekday, and 396 (23.7%) on a weekend/ or holiday. After adjusting for age, sex, and Charlson Comorbidity Index, stroke type and country of birth, admissions over a weekend/holiday following total stroke were significantly associated with an increased risk of dying within three days from admission [hazard ratio (HR): 1.59, 95% confidence interval: 1.01-2.50]. In haemorrhagic stroke, increased risk of death was significantly higher at three days (HR: 2.19, 95% confidence interval: 1.17-4.08), 14 days (HR: 1.73, 95% confidence interval: 1.02-2.93), and 1 month (HR: 1.82, 95% confidence interval: 1.09-3.03) following admission on the weekend/ or holiday compared to those admitted during the weekdays. CONCLUSIONS: This study reports a short-term adverse weekend/holiday effect following admission for haemorrhagic stroke or total stroke. No significant weekend/holiday effect was found in ischaemic stroke.

The effects of health risk behaviors to excess mortality in the population with depression: A cohort study based on NHANES data.

BACKGROUND: The population with depression had a considerable excess mortality risk. This increased mortality may be attributed to the biological consequences of depression or the substantial prevalence of health risk behaviors (HRBs). This study aimed to quantify the combined effects of four major HRBs - smoking, excessive alcohol use, physical inactivity, and an unhealthy diet - on excess mortality among depressed individuals. METHODS: This study included 35,738 adults from the National Health and Nutrition Examination Survey 2005-06 to 2017-18, with mortality follow-up data censored through 2019. The standardized prevalence of HRBs was calculated for populations with and without depression. Poisson regression models were used to calculate the mortality rate ratio (MRR). Based on model adjusting for socio-demographic factors, the attenuation of MRR was determined after further adjustment for HRBs. RESULTS: A total of 3147 participants were identified as having depression. All HRBs showed a significantly higher prevalence among the population with depression. After adjusting for socio-demographic factors, depression was associated with 1.7 and 1.8 times higher all-cause and cardiovascular disease mortality rate, respectively. Further adjustment for all current HRBs resulted in a 21.9 % reduction in all-cause mortality rate and a 15.4 % decrease in cardiovascular disease mortality rate. LIMITATION: HRBs were reported at a single time point, and we are unable to demonstrate a causal effect. CONCLUSION: At least 1/5 of excess mortality for population with depression was attributable to HRBs. Efforts should be made to address HRBs among population with depression.

Preoperative risk factors and cumulative incidence of temporary ileostomy non-closure after sphincter-preserving surgery for rectal cancer: a meta-analysis.

BACKGROUND: Temporary ileostomy (TI) has proven effective in reducing the severity of anastomotic leakage after rectal cancer surgery; however, some ileostomies fail to reverse over time, leading to conversion into a permanent stoma (PS). In this study, we aimed to investigate the preoperative risk factors and cumulative incidence of TI non-closure after sphincter-preserving surgery for rectal cancer. MATERIALS AND METHODS: We conducted a meta-analysis after searching the Embase, Web of Science, PubMed, and MEDLINE databases from their inception until November 2023. We collected all published studies on the risk factors related to TI non-closure after sphincter-preserving surgery for rectal cancer. RESULTS: A total of 1610 studies were retrieved, and 13 studies were included for meta-analysis, comprising 3026 patients. The results of the meta-analysis showed that the identified risk factors included older age (p = 0.03), especially > 65 years of age (p = 0.03), male sex (p = 0.009), American Society of Anesthesiologists score ≥ 3 (p = 0.004), comorbidity (p = 0.001), and distant metastasis (p < 0.001). Body mass index, preoperative hemoglobin, preoperative albumin, preoperative carcinoma embryonic antigen, tumor location, neoadjuvant chemoradiotherapy, smoking, history of abdominal surgery, and open surgery did not significantly change the risk of TI non-closure. CONCLUSION: We identified five preoperative risk factors for TI non-closure after sphincter-preserving surgery for rectal cancer. This information enables surgeons to identify high-risk groups before surgery, inform patients about the possibility of PS in advance, and consider performing protective colostomy or Hartmann surgery.

Association of hypertension and depression with mortality: an exploratory study with interaction and mediation models.

BACKGROUND: The association of hypertension and depression with mortality has not been fully understood. We aimed to explore the possible independent or joint association of hypertension and depression with mortality. Their interaction effects on mortality and possible mediating role were also investigated. METHODS: Associations of hypertension, depression, and their interaction with all-cause and cardiovascular disease (CVD) mortality were evaluated using multivariate Cox proportional hazards regression models. The mediation analysis was conducted with a Sobel test. RESULTS: A total of 35152 participants were included in the final analysis. Hypertension and depression were independently associated with increased risk of all-cause and CVD mortality. The co-existence of hypertension and depression resulted in a 1.7-fold [95% confidence interval (CI): 1.3-2.1] increase in all-cause mortality and a 2.3-fold (95% CI: 1.4-3.7) increase in CVD mortality compared to those with neither of them. Hypertension and depression showed no significant multiplicative (P for interaction, 0.587) and additive interaction (P for relative excess risk of interaction, 0.243; P for Interaction on additive scale, 0.654) on all-cause mortality, as well as on CVD mortality. Depression did not mediate the relationship between hypertension and all-cause (Z=1.704, P=0.088) and CVD mortality (Z=1.547, P=0.122). Hypertension did not mediate the relationship between all-cause and CVD mortality as well. CONCLUSION: Hypertension and depression were related to all-cause and CVD mortality independently and the co-existence of them increased the risk of mortality. However, there is no interaction effect of them on mortality, and hypertension or depression did not mediate the association of each other with mortality.

Accelerating Oxygen Electrocatalysis Kinetics on Metal-Organic Frameworks via Bond Length Optimization.

Metal-organic frameworks (MOFs) have been developed as an ideal platform for exploration of the relationship between intrinsic structure and catalytic activity, but the limited catalytic activity and stability has hampered their practical use in water splitting. Herein, we develop a bond length adjustment strategy for optimizing naphthalene-based MOFs that synthesized by acid etching Co-naphthalenedicarboxylic acid-based MOFs (donated as AE-CoNDA) to serve as efficient catalyst for water splitting. AE-CoNDA exhibits a low overpotential of 260 mV to reach 10 mA cm-2 and a small Tafel slope of 62 mV dec-1 with excellent stability over 100 h. After integrated AE-CoNDA onto BiVO4, photocurrent density of 4.3 mA cm-2 is achieved at 1.23 V. Experimental investigations demonstrate that the stretched Co-O bond length was found to optimize the orbitals hybridization of Co 3d and O 2p, which accounts for the fast kinetics and high activity. Theoretical calculations reveal that the stretched Co-O bond length strengthens the adsorption of oxygen-contained intermediates at the Co active sites for highly efficient water splitting.

Two new alkaloids from Portulaca oleracea L. and their anti-inflammatory and anticholinesterase activities.

Two new alkaloids identified as 2-(((S,Z)-1-(1H-azirin-1-yl)-5-methylhex-1-en-3-yl)oxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol and (S,Z)-1-(1H-azirin-1-yl)-5-methylhex-1-en-3-ol, named olerazirin A (1), olerazirin B (2), together with five known alkaloids, identified as cyclo (L-Val-L-Ala) (3), cyclo-(glycyl-L-leucine) (4), cyclo-(Gly-Phe) (5), cyclo (Ser-Phe) (6), (3S,6S)-3-[(1R)-1-hydroxyethyl]-6-(phenyl-methyl)-2,5-piperazinedione (7) were obtained from Portulaca oleracea L. using a range of chromatographic techniques, 1D and 2D NMR, and high-resolution electrospray ionisation time-of-flight mass spectroscopic methods, in which the compounds 3-7 were isolated from P. oleracea for the first time. In addition, the results showed that the compounds 1 and 2 have anti-inflammatory activities and compounds 1-3 and 5-7 exhibit the anticholinesterase activities.

Transcriptional patterns of human retinal pigment epithelial cells under protracted high glucose.

BACKGROUND: The retinal pigment epithelium (RPE) is essential for retinal homeostasis. Comprehensively exploring the transcriptional patterns of diabetic human RPE promotes the understanding of diabetic retinopathy (DR). METHODS AND RESULTS: A total of 4125 differentially expressed genes (DEGs) were screened out from the human primary RPE cells subjected to prolonged high glucose (HG). The subsequent bioinformatics analysis is divided into 3 steps. In Step 1, 21 genes were revealed by intersecting the enriched genes from the KEGG, WIKI, and Reactome databases. In Step 2, WGCNA was applied and intersected with the DEGs. Further intersection based on the enrichments with the GO biological processes, GO cellular components, and GO molecular functions databases screened out 12 candidate genes. In Step 3, 13 genes were found to be simultaneously up-regulated in the DEGs and a GEO dataset involving human diabetic retinal tissues. VEGFA and ERN1 were the 2 starred genes finally screened out by overlapping the 3 Steps. CONCLUSION: In this study, multiple genes were identified as crucial in the pathological process of RPE under protracted HG, providing potential candidates for future researches on DR. The current study highlights the importance of RPE in DR pathogenesis.

Design of a multi-electrode dielectric barrier discharge reactor and experimental study on the degradation of atrazine in water.

Atrazine (ATZ) is widely used in agriculture as a triazine herbicide, and its long-term use can cause serious environmental pollution. This paper independently designed a multi-electrode reactor, explored the output power and energy utilization efficiency of the dielectric barrier discharge reactor, and used the dielectric barrier discharge reactor to treat ATZ solution. The results showed that the degradation efficiency of ATZ was 96.39% at 30 min at an initial ATZ concentration of 14 mg/L, an input voltage of 34 kV, an input current of 1.38 mA, an aeration rate of 100 L/h, and a treatment water volume of 150 mL. The degradation of ATZ was significantly increased by the addition of persulfate (PS), Fe2+, and H2O2. After adding radical quenchers (EtOH, p-BQ, and FFA), the degradation efficiency of ATZ decreased, indicating that free radicals (•OH, •O2-, and 1O2) played a key role in the degradation process of ATZ.

Accumulation of γδT cells in the decidua is promoted by RANKL which upregulates ICAM-1 via NF-κB.

In brief: The mechanism underlying the accumulation of γδT cells in the decidua, which helps maintain maternal-fetal immunotolerance in early pregnancy, is unknown. This study reveals that DSC-derived RANKL upregulates ICAM-1 expression via the NF-κB pathway to enable γδT cell accumulation in the early decidua. Abstract: Decidual γδT (dγδT) cells help maintain maternal-fetal immunotolerance in early pregnancy. However, the mechanism underlying the accumulation of γδT cells in the decidua is unknown. Previous work showed that RANKL upregulated intercellular adhesion molecule 1 (ICAM-1) in decidual stromal cells (DSCs), and Rankl knockout mice had limited dγδT cell populations. In this study, we measured the expression levels of RANKL/RANK and ICAM-1 in DSCs, in addition to the integrins of ICAM-1 on dγδT cells, and the number of dγδT cells from patients with recurrent spontaneous abortion (RSA) and normal pregnant women in the first trimester. RSA patients showed significantly decreased RANKL/RANK and ICAM-1/CD11a signaling in decidua, and a decreased percentage of dγδT cells, which was positively correlated with DSC-derived RANKL and ICAM-1. Next, an in vitro adhesion experiment showed that the enhanced attraction of human DSCs to dγδT cells after RANKL overexpression was almost completely aborted by anti-ICAM-1. Furthermore, Rankl knockout mice showed a significant reduction in NF-κB activity compared with wild-type controls. Finally, we applied a selective NF-κB inhibitor named PDTC to validate the role of NF-κB in RANKL-mediated ICAM-1 upregulation. Taken together, our data show that DSC-derived RANKL upregulates ICAM-1 expression via the NF-κB pathway to enable γδT cell accumulation in the early decidua. A reduction in RANKL/ICAM-1 signaling in DSCs may result in insufficient accumulation of γδT cells in decidua and, in turn, RSA.

Numerical simulation of shoegear-rail coupling vibration under different initial contact forces.

As cities have grown, conductor rail power supplies have been widely used in the field of urban rail transit. In order to improve the running performance of trains and reduce the occurrence of accidents, it is necessary to understand the vibration of shoegear-rail system under different initial contact forces and explore the dynamic performance of shoegear-rail system. Therefore, according to the structure of shoegear-rail system, a coupling model of shoegear-rail system is established in this paper. On the basis of the model, the numerical simulation of the shoegear-rail system under different initial contact forces is carried out, and finally the vibration data of the shoegear-rail system under different initial contact forces are obtained. The results show that with the increase of initial contact force in the range of 70-160 N, the vibration amplitude of the electric shoegear and the fluctuation amplitude of the contact force increase, but the maximum absolute shear force value of the conductor rail decreases. It indicates that the lower initial contact force, the better the performance of shoegear-rail system.

Clinical Outcomes of Ileostomy Closure during versus after Adjuvant Chemotherapy in Patients with Rectal Cancer.

Background: Protective ileostomy can effectively prevent severe anastomotic leakage after rectal cancer surgery; however, the optimal timing for ileostomy closure during adjuvant chemotherapy remains unclear. This study aimed to explore the safety and long-term outcomes of early ileostomy closure during adjuvant chemotherapy. Method: Patients who underwent laparoscopic rectal cancer surgery combined with protective ileostomy and adjuvant chemotherapy between April 2017 and April 2021 were retrospectively evaluated. Patients were divided into an early closure group during chemotherapy (group A) and a late closure group after chemotherapy (group B). Results: A total of 215 patients were included in this study, with 115 in group A and 100 in group B. There were no significant differences in demographic and clinical characteristics between the two groups. In group A, durations of stoma status (p < 0.001) and low anterior resection syndrome (LARS) (p < 0.001) were shorter, and rectal stenosis (p=0.036) and stoma-related complications (p=0.007), especially stoma stenosis (p=0.041), were less common. However, compliance with chemotherapy was worse (p=0.009). There were no significant differences in operative time, postoperative hospital stay, postoperative complications, incidence and severity of LARS, disease-free survival, or overall survival between groups. Conclusion: Early ileostomy closure can effectively reduce the duration of stoma status, duration of LARS, rectal stenosis, and stoma-related complications while not affecting surgical complications and oncological outcomes. Ileostomy closure should not be delayed because of adjuvant chemotherapy. However, follow-up should be strengthened to increase compliance and integrity with chemotherapy.

A hemodynamic model of artery bypass graft considering microcirculation function.

BACKGROUND: The incidence of arterial stenosis is increasing year by year. In order to better diagnose and treat arterial stenosis, numerical simulation technology has become a popular method. OBJECTIVE: A novel model is constructed to investigate the influence of microcirculation on the hemodynamics of artery bypass graft. METHODS: In this paper, a severely narrow artery bypass graft model is considered. The geometric shape includes a narrow artery tube and a bypass graft of the same diameter with a 45° suture angle. The fluid-structure interaction model is considered by finite element numerical calculation, and the flow is simulated with microcirculation as the outlet boundary condition. The changes of blood flow velocity, pressure and wall shear stress are analyzed. RESULTS: The results show that blood almost entirely flows into the graft tube and there is no recirculation area at the anastomosis. CONCLUSION: The artery bypass graft model considering microcirculation function could simulate the physiological characteristics of blood flow more reasonably, and it provide helps for clinicians to diagnose and treat arterial stenosis.

Two novel ketone alkaloids from Portulaca oleraceaL. and their anti-inflammatory activities.

Eleven compounds were obtained from Portulaca oleracea L., including two novel ketone alkaloids, (1, 2), 4-hydroxy-3-methoxybenzamide (3) (isolated for the first time), ß-adenosine (4), oleracrylimide A and B (5, 6), oleracein H, C, D, Q and A (7-11). The two novel ketone alkaloids were identified as 5-acetyl-5-methylcyclopent-2-ene-1-carboxamide (1), named oleraciamide H, and (2 R,3S,4R,5R)-5-((R)-1,2-dihydroxyethyl)-3,4-dihydroxytetrahydrofuran-2-yl glycinate (2), named oleracone Q by spectroscopic methods, including 1D, 2D NMR and compound fingerprints. Additionally, their anti-inflammatory activities were tested via RAW 264.7 cells induced by LPS and found that they could significantly inhibit the release of IL-1ß and TNF-α.

Numerical investigation of quantitative pulmonary pressure ratio in different degrees of stenosis.

BACKGROUND: Pulmonary artery stenosis endangers people's health. Quantitative pulmonary pressure ratio (QPPR) is very important for clinicians to quickly diagnose diseases and develop treatment plans. OBJECTIVE: Our purpose of this paper is to investigate the effects of different degrees (50% and 80%) of pulmonary artery stenosis on QPPR. METHODS: An idealized model is established based on the normal size of human pulmonary artery. The hemodynamic governing equations are solved using fluid-structure interaction. RESULTS: The results show that the QPPR decreases with the increase of stenosis degree, and it is closely related to the pressure drop at both ends of stenosis. Blood flow velocity and wall shear stress are sensitive to the stenosis degree. When the degree of stenosis is 80%, the amplitude of changes of blood flow velocity and wall shear stress at both ends of stenosis is lower. CONCLUSIONS: The results suggest that the degree of pulmonary artery stenosis has a significant impact on QPPR and hemodynamic changes. This study lays a theoretical foundation for further study of QPPR.

Interference with SPARC inhibits Benzophenone-3 induced ferroptosis in osteoarthritis: Evidence from bioinformatics analyses and biological experimentation.

The aim of this study is to conduct a thorough evaluation of the association between Benzophenone-3 (BP-3) exposure and OA, offering critical insights into the underlying mechanisms involved. The National Health and Nutrition Examination Survey (NHANES) database was utilized to investigate the correlation between BP-3 and osteoarthritis. Proteomic sequencing from clinical sample and the PharmMapper online tool were employed to predict the biological target of BP-3. Cellular molecular assays and transfection studies were performed to verify the prediction from bioinformatics analyses. Through cross-sectional analysis of the NHANES database, we identified BP-3 as a risk factor for OA development. The results of proteomic sequencing showed that Secreted Protein Acidic and Rich in Cysteine (SPARC) was significantly elevated in the area of damage compared to the undamaged area. SPARC was also among the potential biological targets of BP-3 predicted by the online program. Through in vitro cell experiments, we further determined that the toxicological effects of BP-3 may be due to SPARC, which elevates intracellular GPX4 levels, activates the glutathione system, and promotes lipid peroxidation to mitigate ferroptosis. Inhibiting SPARC expression has been shown to reduce inflammation and ferroptosis in OA contexts. This research provides an expansive understanding of BP-3's influence on osteoarthritis development. We have identified SPARC as a potent target for combating chondrocyte ferroptosis in BP-3-associated osteoarthritis.

The role of deubiquitinases in cardiac disease.

Deubiquitinases are a group of proteins that identify and digest monoubiquitin chains or polyubiquitin chains attached to substrate proteins, preventing the substrate protein from being degraded by the ubiquitin-proteasome system. Deubiquitinases regulate cellular autophagy, metabolism and oxidative stress by acting on different substrate proteins. Recent studies have revealed that deubiquitinases act as a critical regulator in various cardiac diseases, and control the onset and progression of cardiac disease through a board range of mechanism. This review summarizes the function of different deubiquitinases in cardiac disease, including cardiac hypertrophy, myocardial infarction and diabetes mellitus-related cardiac disease. Besides, this review briefly recapitulates the role of deubiquitinases modulators in cardiac disease, providing the potential therapeutic targets in the future.

Capturing cerium ions via hydrogel microspheres promotes vascularization for bone regeneration.

The rational design of multifunctional biomaterials with hierarchical porous structure and on-demand biological activity is of great consequence for bone tissue engineering (BTE) in the contemporary world. The advanced combination of trace element cerium ions (Ce3+) with bone repair materials makes the composite material capable of promoting angiogenesis and enhancing osteoblast activity. Herein, a living and phosphorylated injectable porous hydrogel microsphere (P-GelMA-Ce@BMSCs) is constructed by microfluidic technology and coordination reaction with metal ion ligands while loaded with exogenous BMSCs. Exogenous stem cells can adhere to and proliferate on hydrogel microspheres, thus promoting cell-extracellular matrix (ECM) and cell-cell interactions. The active ingredient Ce3+ promotes the proliferation, osteogenic differentiation of rat BMSCs, and angiogenesis of endotheliocytes by promoting mineral deposition, osteogenic gene expression, and VEGF secretion. The enhancement of osteogenesis and improvement of angiogenesis of the P-GelMA-Ce scaffold is mainly associated with the activation of the Wnt/ß-catenin pathway. This study could provide novel and meaningful insights for treating bone defects with biofunctional materials on the basis of metal ions.

Oncological features and prognosis of colorectal cancer in human immunodeficiency virus-positive patients: A retrospective study.

BACKGROUND: Due to the prolonged life expectancy and increased risk of colorectal cancer (CRC) among patients with human immunodeficiency virus (HIV) infection, the prognosis and pathological features of CRC in HIV-positive patients require examination. AIM: To compare the differences in oncological features, surgical safety, and prognosis between patients with and without HIV infection who have CRC at the same tumor stage and site. METHODS: In this retrospective study, we collected data from HIV-positive and -negative patients who underwent radical resection for CRC. Using random stratified sampling, 24 HIV-positive and 363 HIV-negative patients with colorectal adenocarcinoma after radical resection were selected. Using propensity score matching, we selected 72 patients, matched 1:2 (HIV-positive:negative = 24:48). Differences in basic characteristics, HIV acquisition, perioperative serological indicators, surgical safety, oncological features, and long-term prognosis were compared between the two groups. RESULTS: Fewer patients with HIV infection underwent chemotherapy compared to patients without. HIV-positive patients had fewer preoperative and postoperative leukocytes, fewer preoperative lymphocytes, lower carcinoembryonic antigen levels, more intraoperative blood loss, more metastatic lymph nodes, higher node stage, higher tumor node metastasis stage, shorter overall survival, and shorter progression-free survival compared to patients who were HIV-negative. CONCLUSION: Compared with CRC patients who are HIV-negative, patients with HIV infection have more metastatic lymph nodes and worse long-term survival after surgery. Standard treatment options for HIV-positive patients with CRC should be explored.

Melatonin-encapsuled silk fibroin electrospun nanofibers promote vascularized bone regeneration through regulation of osteogenesis-angiogenesis coupling.

The repair of critical-sized bone defects poses a significant challenge due to the absence of periosteum, which plays a crucial role in coordinating the processes of osteogenesis and vascularization during bone healing. Herein, we hypothesized that melatonin-encapsuled silk Fibronin electrospun nanofibers (SF@MT) could provide intrinsic induction of both osteogenesis and angiogenesis, thereby promoting vascularized bone regeneration. The sustained release of melatonin from the SF@MT nanofibers resulted in favorable biocompatibility and superior osteogenic induction of bone marrow mesenchymal stem cells (BMMSCs). Interestingly, melatonin promoted the migration and tube formation of human umbilical vein endothelial cells (HUVECs) in a BMMSC-dependent manner, potentially through the upregulation of vascular endothelial growth factor (VEGFA) expression in SF@MT-cultured BMMSCs. SF@MT nanofibers enhanced the BMMSC-mediated angiogenesis by activating the PI3K/Akt signaling pathway. In vivo experiments indicated that the implantation of SF@MT nanofibers into rat critical-sized calvarial defects significantly enhances the production of bone matrix and the development of new blood vessels, leading to an accelerated process of vascularized bone regeneration. Consequently, the utilization of melatonin-encapsulated silk Fibronin electrospun nanofibers shows great promise as a potential solution for artificial periosteum, with the potential to regulate the coupling of osteogenesis and angiogenesis in critical-sized bone defect repair.