Exercise-Induced Reduction of IGF1R Sumoylation Attenuates Neuroinflammation in APP/PS1 Transgenic Mice.

INTRODUCTION: Alzheimer's Disease (AD), a progressive neurodegenerative disorder, is marked by cognitive deterioration and heightened neuroinflammation. The influence of Insulin-like Growth Factor 1 Receptor (IGF1R) and its post-translational modifications, especially sumoylation, is crucial in understanding the progression of AD and exploring novel therapeutic avenues. OBJECTIVES: This study investigates the impact of exercise on the sumoylation of IGF1R and its role in ameliorating AD symptoms in APP/PS1 mice, with a specific focus on neuroinflammation and innovative therapeutic strategies. METHODS: APP/PS1 mice were subjected to a regimen of moderate-intensity exercise. The investigation encompassed assessments of cognitive functions, alterations in hippocampal protein expressions, neuroinflammatory markers, and the effects of exercise on IGF1R and SUMO1 nuclear translocation. Additionally, the study evaluated the efficacy of KPT-330, a nuclear export inhibitor, as an alternative to exercise. RESULTS: Exercise notably enhanced cognitive functions in AD mice, possibly through modulations in hippocampal proteins, including Bcl-2 and BACE1. A decrease in neuroinflammatory markers such as IL-1ß, IL-6, and TNF-α was observed, indicative of reduced neuroinflammation. Exercise modulated the nuclear translocation of SUMO1 and IGF1R in the hippocampus, thereby facilitating neuronal regeneration. Mutant IGF1R (MT IGF1R), lacking SUMO1 modification sites, showed reduced SUMOylation, leading to diminished expression of pro-inflammatory cytokines and apoptosis. KPT-330 impeded the formation of the IGF1R/RanBP2/SUMO1 complex, thereby limiting IGF1R nuclear translocation, inflammation, and neuronal apoptosis, while enhancing cognitive functions and neuron proliferation. CONCLUSION: Moderate-intensity exercise effectively mitigates AD symptoms in mice, primarily by diminishing neuroinflammation, through the reduction of IGF1R Sumoylation. KPT-330, as a potential alternative to physical exercise, enhances the neuroprotective role of IGF1R by inhibiting SUMOylation through targeting XPO1, presenting a promising therapeutic strategy for AD.

Fabrication and characterization of chitosan/anthocyanin intelligent packaging film fortified by cellulose nanocrystal for shrimp preservation and visual freshness monitoring.

In this study, a multi-functional packaging film was fabricated, utilizing the natural polysaccharide chitosan (CS) as the base material, integrating natural blueberry anthocyanin (AN) as pH-responsive indicator, and reinforced with cellulose nanocrystals (CNCs). The implications of addition levels of CNCs on the characteristics of the films were systematically investigated, resulting in that CS-AN-CNCs 9 % film exhibited optimal performance. Specifically, the film showed a substantial enhancement in maximum tensile strength from 15 MPa to 35 MPa; On the other hand, the swelling degree properties, the oxygen permeability and water vapor permeability decreased from 159.2 % to 92.0 %, from 51.7 g/(m2d) to 12.2 g/(m2d), from 31.6 × 10-12 g/(m·s·Pa) to 1.6 × 10-12 g/(m·s·Pa), respectively. Moreover, the CS-AN-CNCs 9 % film exhibited antioxidant, antibacterial, coupled with a color metrically responsive to pH variations, displaying great potential in indicating the shrimp freshness and delaying spoilage. Another notable advantage of the-prepared packaging material lies in its completely biodegradability, therefore meeting the requirement of environmental protection. Therefore, the prepared CS-AN-CNCs film as an intelligent packaging solution with potential applications in food preservation and freshness monitoring applications.

Exercise potentially prevents colorectal cancer liver metastases by suppressing tumor epithelial cell stemness via RPS4X downregulation.

Background: Colorectal cancer (CRC) is the third most prevalent tumor globally. The liver is the most common site for CRC metastasis, and the involvement of the liver is a common cause of death in patients with late-stage CRC. Consequently, mitigating CRC liver metastasis (CRLM) is key to improving CRC prognosis and increasing survival. Exercise has been shown to be an effective method of improving the prognosis of many tumor types. However, the ability of exercise to inhibit CRLM is yet to be thoroughly investigated. Methods: The GSE157600 and GSE97084 datasets were used for analysis. A pan-cancer dataset which was uniformly normalized was downloaded and analyzed from the UCSC database: TCGA, TARGET, GTEx (PANCAN, n = 19,131, G = 60,499). Several advanced bioinformatics analyses were conducted, including single-cell sequencing analysis, correlation algorithm, and prognostic screen. CRC tumor microarray (TMA) as well as cell/animal experiments are used to further validate the results of the analysis. Results: The greatest variability was found in epithelial cells from the tumor group. RPS4X was generally upregulated in all types of CRC, while exercise downregulated RPS4X expression. A lowered expression of RPS4X may prolong tumor survival and reduce CRC metastasis. RPS4X and tumor stemness marker-CD44 were highly positively correlated and knockdown of RPS4X expression reduced tumor stemness both in vitro and in vivo. Conclusion: RPS4X upregulation may enhance CRC stemness and increase the odds of metastasis. Exercise may reduce CRC metastasis through the regulation of RPS4X.

Streptococcus taonis sp. nov., a novel bacterial species isolated from a blood culture of a patient.

One Gram stain-positive, catalase-negative, α-hemolytic, chain-forming or paired cocci, designated ST22-14T, was isolated from a blood culture of a child with suspected infection. The results of 16S rRNA gene sequences analyses showed that the most closely related species to strain ST22-14T were "Streptococcus vulneris" DM3B3T (99.2%), Streptococcus mitis NCTC 12261T (99.0%), "Streptococcus gwangjuense" ChDC B345T, (99.0%), Streptococcus oralis subsp. dentisani 7747T (99.0%), Streptococcus downii CECT 9732T (99.0%), and Streptococcus infantis ATCC 700779T (98.9%). The genome of strain ST22-14T consists of 2,053,261 bp with a G + C content of 39.4%. Average nucleotide identity values between strain ST22-14T and Streptococcus mitis NCTC 12261T or other five species were from 82.2 to 88.0%. In silico DNA-DNA hybridization of ST22-14T showed an estimated DNA reassociation value of 34.6% with the closest species. The main cellular fatty acids of strain ST22-14T were 16:0, 18:0, 14:0, 18:1ω7c and 18:1ω6c. Based on these results, strain ST22-14T should be classified as a novel species of genus Streptococcus, for which the name Streptococcus taonis sp. nov. is proposed (type strain ST22-14T = NBRC 116002T = BCRC 81402T).

Unveiling the Role of Ge in CZTSSe Solar Cells by Advanced Micro-To-Atom Scale Characterizations.

Kesterite is an earth-abundant energy material with high predicted power conversion efficiency, making it a sustainable and promising option for photovoltaics. However, a large open circuit voltage Voc deficit due to non-radiative recombination at intrinsic defects remains a major hurdle, limiting device performance. Incorporating Ge into the kesterite structure emerges as an effective approach for enhancing performance by manipulating defects and morphology. Herein, how different amounts of Ge affect the kesterite growth pathways through the combination of advanced microscopy characterization techniques are systematically investigated. The results demonstrate the significance of incorporating Ge during the selenization process of the CZTSSe thin film. At high temperature, the Ge incorporation effectively delays the selenization process due to the formation of a ZnSe layer on top of the metal alloys through decomposition of the Cu-Zn alloy and formation of Cu-Sn alloy, subsequently forming of Cu-Sn-Se phase. Such an effect is compounded by more Ge incorporation that further postpones kesterite formation. Furthermore, introducing Ge mitigates detrimental "horizontal" grain boundaries by increasing the grain size on upper layer. The Ge incorporation strategy discussed in this study holds great promise for improving device performance and grain quality in CZTSSe and other polycrystalline chalcogenide solar cells.

Manufacturing of high strength and high conductivity copper with laser powder bed fusion.

Additive manufacturing (AM), known as 3D printing, enables rapid fabrication of geometrically complex copper (Cu) components for electrical conduction and heat management applications. However, pure Cu or Cu alloys produced by 3D printing often suffer from either low strength or low conductivity at room and elevated temperatures. Here, we demonstrate a design strategy for 3D printing of high strength, high conductivity Cu by uniformly dispersing a minor portion of lanthanum hexaboride (LaB6) nanoparticles in pure Cu through laser powder bed fusion (L-PBF). We show that trace additions of LaB6 to pure Cu results in an improved L-PBF processability, an enhanced strength, an improved thermal stability, all whilst maintaining a high conductivity. The presented strategy could expand the applicability of 3D printed Cu components to more demanding conditions where high strength, high conductivity and thermal stability are required.

Engineering metal-carbide hydrogen traps in steels.

Hydrogen embrittlement reduces the durability of the structural steels required for the hydrogen economy. Understanding how hydrogen interacts with the materials plays a crucial role in managing the embrittlement problems. Theoretical models have indicated that carbon vacancies in metal carbide precipitates are effective hydrogen traps in steels. Increasing the number of carbon vacancies in individual metal carbides is important since the overall hydrogen trapping capacity can be leveraged by introducing abundant metal carbides in steels. To verify this concept, we compare a reference steel containing titanium carbides (TiCs), which lack carbon vacancies, with an experimental steel added with molybdenum (Mo), which form Ti-Mo carbides comprising more carbon vacancies than TiCs. We employ theoretical and experimental techniques to examine the hydrogen trapping behavior of the carbides, demonstrating adding Mo alters the hydrogen trapping mechanism, enabling hydrogen to access carbon vacancy traps within the carbides, leading to an increase in trapping capacity.

Exciplex-forming cohost systems with 2,7-dicyanofluorene acceptors for high efficiency red and deep-red OLEDs.

Two 2,7-dicyaonfluorene-based molecules 27-DCN and 27-tDCN are utilized as acceptors (A) to combine with hexaphenylbenzene-centered donors (D) TATT and DDT-HPB for probing the exciplex formation. The photophysical characteristics reveal that the steric hindered 27-tDCN not only can increase the distance of D and A, resulting in a hypsochromic emission, but also dilute the concentration of triplet excitons to suppress non-radiative process. The 27-tDCN-based exciplex-forming blends exhibit better photoluminescence quantum yield (PLQY) as compared to those of 27-DCN-based pairs. In consequence, among these D:A blends, the device employing DDT-HPB:27-tDCN blend as the emissiom layer (EML) exhibits the best EQE of 3.0% with electroluminescence (EL) λmax of 542 nm. To further utilize the exciton electrically generated in exciplex-forming system, two D-A-D-configurated fluorescence emitter DTPNT and DTPNBT are doped into the DDT-HPB:27-tDCN blend. The nice spectral overlap ensures fast and efficient Förster energy transfer (FRET) process between the exciplex-forming host and the fluorescent quests. The red device adopting DDT-HPB:27-tDCN:10 wt% DTPNT as the EML gives EL λmax of 660 nm and maximum external quantum efficiency (EQEmax) of 5.8%, while EL λmax of 685 nm and EQE of 5.0% for the EML of DDT-HPB:27-tDCN:10 wt% DTPNBT. This work manifests a potential strategy to achieve high efficiency red and deep red OLED devices by incorporating the highly fluorescent emitters to extract the excitons generated by the exciplex-forming blend with bulky acceptor for suppressing non-radiative process.

A stable delivery system for curcumin: Fabrication and characterization of self-assembling acylated kidney bean protein isolate nanogels.

The construction of protein-based nano-gels as curcumin delivery system effectively enhances the stability and bioavailability of curcumin. In this study, acylation modification and self-assembly techniques were jointly employed to construct acylated kidney bean protein isolate (AKBPI)-nanogels. Optimal conditions for AKBPI-nanogels were determined to be pH 7, concentration of 2 mg/mL, and temperature at 90℃ for 30 min. The optimized AKBPI-nanogels exhibited excellent uniformity as evidenced by decreasing average particle size (137.35 nm) and polydispersity index (0.38). Acylation enhanced the intermolecular interactions within the nanogel by reducing the polarity of tyrosine microenvironment and free sulfhydryl groups. AKBPI-nanogels demonstrated remarkable characteristics in terms of pH sensitivity, salt concentration, and storage tolerance. The curcumin-loaded AKBPI-nanogels exhibited an encapsulation efficiency of 92.30 % and maintained high antioxidant activity. In simulated gastrointestinal digestion, AKBPI-nanogels facilitated the controlled release and higher bioavailability of curcumin. Therefore, AKBPI-nanogels can be a stable tool for delivering curcumin.

Association of health information technology-driven multidisciplinary approaches with low-density lipoprotein cholesterol target achievement in patients with an acute coronary syndrome.

Objective: Controlling of low-density lipoprotein cholesterol (LDL-C) in patients with acute coronary syndrome (ACS) remains a challenge. Health information technology (HIT) is increasingly being applied to close quality gaps in chronic illness care. The aim of this study was to perform a qualitative review of the association of implementing HIT on lipid management processes of care and LDL-C goal attainment in patients with ACS. Method: Eligible patients with a discharge diagnosis of ACS from January 2018 to December 2021 at a tertiary medical center were retrospectively reviewed. An HIT system with a multidisciplinary approach including initiating high-intensity statin therapy, periodic laboratory follow-up, titration of lipid-lowering agents, patient education, patient-level and system-level interventions involving database monitoring and outreach by centralized care teams was introduced in October 2018. Electronical medical records including data on medications and laboratory findings at discharge and within 1 year were compared before and after implementing the HIT system. Results: A total of 2001 ACS patients (average age 63 ± 12.7 years, 79.66 % men) were analyzed. The LDL-C < 70 mg/dL goal attainment rates (36.52 %, 53.57 %, 59.22 %, 62.18 % in 2018-2021) and medium serum LDL-C levels (80.5 mg/dL, 68 mg/dL, 65 mg/dL, 64 mg/dL in 2018-2021) significantly improved within 6 months (2018 as the reference, all p<0.001). The LDL-C attainment rate at 12 months also steadily increased (53.80 %, 61.82 %, 64.21 % in 2019-2021, p = 0.019). Most of the patients switched to a high-intensity statins regimen at discharge (0.57 %, 63.67 %, 72.41 %, 84.44 %, in 2018-2021, p<0.001 with 2018 as the reference), with low adverse event rates. The maintenance rates of high-intensity statin regimens at 12 months continued to improve (41.36 %, 49.04 %, 61.39 % in 2019-2021, p<0.001). Conclusions: Efforts to control LDL-C should be increased in ACS patients by initiating and intensifying statin treatment earlier. Our results confirmed that a team-based strategy with HIT improved LDL-C target achievement for most patients with ACS.

N6-methyladenosine demethylase FTO regulates synaptic and cognitive impairment by destabilizing PTEN mRNA in hypoxic-ischemic neonatal rats.

Hypoxic-ischemic brain damage (HIBD) can result in significant global rates of neonatal death or permanent neurological disability. N6-methyladenosine (m6A) modification of RNA influences fundamental aspects of RNA metabolism, and m6A dysregulation is implicated in various neurological diseases. However, the biological roles and clinical significance of m6A in HIBD remain unclear. We currently evaluated the effect of HIBD on cerebral m6A methylation in RNAs in neonatal rats. The m6A dot blot assay showed a global augmentation in RNA m6A methylation post-HI. Herein, we also report on demethylase FTO, which is markedly downregulated in the hippocampus and is the main factor involved with aberrant m6A modification following HI. By conducting a comprehensive analysis of RNA-seq data and m6A microarray results, we found that transcripts with m6A modifications were more highly expressed overall than transcripts without m6A modifications. The overexpression of FTO resulted in the promotion of Akt/mTOR pathway hyperactivation, while simultaneously inhibiting autophagic function. This is carried out by the demethylation activity of FTO, which selectively demethylates transcripts of phosphatase and tensin homolog (PTEN), thus promoting its degradation and reduced protein expression after HI. Moreover, the synaptic and neurocognitive disorders induced by HI were effectively reversed through the overexpression of FTO in the hippocampus. Cumulatively, these findings demonstrate the functional importance of FTO-dependent hippocampal m6A methylome in cognitive function and provides novel mechanistic insights into the therapeutic potentials of FTO in neonatal HIBD.

Enabling AI in synthetic biology through Construction File specification.

The Construction File (CF) specification establishes a standardized interface for molecular biology operations, laying a foundation for automation and enhanced efficiency in experiment design. It is implemented across three distinct software projects: PyDNA_CF_Simulator, a Python project featuring a ChatGPT plugin for interactive parsing and simulating experiments; ConstructionFileSimulator, a field-tested Java project that showcases 'Experiment' objects expressed as flat files; and C6-Tools, a JavaScript project integrated with Google Sheets via Apps Script, providing a user-friendly interface for authoring and simulation of CF. The CF specification not only standardizes and modularizes molecular biology operations but also promotes collaboration, automation, and reuse, significantly reducing potential errors. The potential integration of CF with artificial intelligence, particularly GPT-4, suggests innovative automation strategies for synthetic biology. While challenges such as token limits, data storage, and biosecurity remain, proposed solutions promise a way forward in harnessing AI for experiment design. This shift from human-driven design to AI-assisted workflows, steered by high-level objectives, charts a potential future path in synthetic biology, envisioning an environment where complexities are managed more effectively.

Ligand effect of cyclometallated iridium(iii) complexes on N-alkylation of amines in hydrogen borrowing reactions.

Dinuclear iridium complexes with the general formula (C^N)2Ir(µ-Cl)2Ir(C^N)2 (C^N = bidentate ligand with carbon and nitrogen donor atoms) were prepared and used in catalytic systems for N-alkylation of amines through the hydrogen borrowing pathway. Triphenylphosphine derivatives were used as auxiliary in catalytic systems to provide excellent conversion of amines to N-alkylation products in yields ranging from 57% to 100%. The catalytic ability of the catalyst depends on the structure of its coordination ligands, including bidentate ligands (C^N) and triphenylphosphine derivatives. These catalytic systems adopt an environmentally friendly and sustainable reaction process through a hydrogen self-transfer strategy, using readily available alcohols as alkylating agents without the need for bases, solvents, and other additives, showing potential in the synthetic and pharmaceutical industries.

Corrigendum: The prevalence, incidence, and persistence of self-reported visual impairment among Chinese population with diabetes mellitus: evaluation from a nationally representative survey, 2015-2018.

[This corrects the article DOI: 10.3389/fpubh.2023.978457.].

Retrospective study: risk assessment model for osteoporosis-a detailed exploration involving 4,552 Shanghai dwellers.

Background: Osteoporosis, a prevalent orthopedic issue, significantly influences patients' quality of life and results in considerable financial burden. The objective of this study was to develop and validate a clinical prediction model for osteoporosis risk, utilizing computer algorithms and demographic data. Method: In this research, a total of 4,552 residents from Shanghai were retrospectively included. LASSO regression analysis was executed on the sample's basic characteristics, and logistic regression was employed for analyzing clinical characteristics and building a predictive model. The model's diagnostic capacity for predicting osteoporosis risk was assessed using R software and computer algorithms. Results: The predictive nomogram model for bone loss risk, derived from the LASSO analysis, comprised factors including BMI, TC, TG, HDL, Gender, Age, Education, Income, Sleep, Alcohol Consumption, and Diabetes. The nomogram prediction model demonstrated impressive discriminative capability, with a C-index of 0.908 (training set), 0.908 (validation set), and 0.910 (entire cohort). The area under the ROC curve (AUC) of the model was 0.909 (training set), 0.903 (validation set), and applicable to the entire cohort. The decision curve analysis further corroborated that the model could efficiently predict the risk of bone loss in patients. Conclusion: The nomogram, based on essential demographic and health factors (Body Mass Index, Total Cholesterol, Triglycerides, High-Density Lipoprotein, Gender, Age, Education, Income, Sleep, Alcohol Consumption, and Diabetes), offered accurate predictions for the risk of bone loss within the studied population.

The prevalence, incidence, and persistence of self-reported visual impairment among Chinese population with diabetes mellitus: evaluation from a nationally representative survey, 2015-2018.

Aims: Our aim was to investigate the prevalence, incidence, and persistence of visual impairment (VI) and their correlates among the Chinese population with diabetes mellitus (DM) over 3 years. Materials and methods: The China Health and Retirement Longitudinal Survey is the first nationally representative longitudinal survey of the Chinese population. A cross-sectional analysis of prevalent VI in 2015 consisted of 2,173 participants with DM. A longitudinal observation of incident and persistent VI consisted of 1,633 participants from 2015 to 2018. Risk factors of VI were identified via univariate and multivariate logistic regression analyses. Results: Among our study population with DM, 11.8% reported VI in 2015, 4.5% had persistent VI from 2015 to 2018, and 8.9% developed VI in 2018. Factors identified to be correlated to VI (p < 0.05) were older age, being a woman, lower educational attainment, living in a rural area, application of DM medication and non-pharmacological treatment, receiving DM-related tests, use of spectacles, and poorer health status. Conclusion: This most recent national data provides a baseline for future public health initiatives on VI among the Chinese population with DM. With multiple risk factors identified, these could provide concurrent targets for various public health strategies and interventions with the aim of reducing the burden of VI among the population with DM in China.

Non-Destructive Screening of Sodium Metabisulfite Residue on Shrimp by SERS with Copy Paper Loaded with AgNP.

In order to prompt the appearance of the shrimp color, sodium metabisulfite is frequently added in shrimp processing, which is, however, prohibited in China and many other countries. This study aimed to establish a surface-enhanced Raman spectroscopy (SERS) method for screening sodium metabisulfite residues on shrimp surfaces, in a non-destructive manner. The analysis was carried out using a portable Raman spectrometer jointly with copy paper loaded with silver nanoparticles as the substrate material. The SERS response of sodium metabisulfite gives two fingerprint peaks at 620 (strong) and 927 (medium) cm-1, respectively. This enabled unambiguous confirmation of the targeted chemical. The sensitivity of the SERS detection method was determined to be 0.1 mg/mL, which was equal to residual sodium metabisulfite on the shrimp surface at 0.31 mg/kg. The quantitative relationship between the 620 cm-1 peak intensities and the concentrations of sodium metabisulfite was established. The linear fitting equation was y = 2375x + 8714 with R2 = 0.985. Reaching an ideal balance in simplicity, sensitivity, and selectivity, this study demonstrates that the proposed method is ideally suitable for in-site and non-destructive screening of sodium metabisulfite residues in seafood.

In Situ Redox Synthesis of Highly Stable Au/Electroactive Polyimide Composite and Its Application on 4-Nitrophenol Reduction.

In this study, we developed a series of Au/electroactive polyimide (Au/EPI-5) composite for the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) using NaBH4 as a reducing agent at room temperature. The electroactive polyimide (EPI-5) synthesis was performed by chemical imidization of its 4,4'-(4.4'-isopropylidene-diphenoxy) bis (phthalic anhydride) (BSAA) and amino-capped aniline pentamer (ACAP). In addition, prepare different concentrations of Au ions through the in-situ redox reaction of EPI-5 to obtain Au nanoparticles (AuNPs) and anchored on the surface of EPI-5 to form series of Au/EPI-5 composite. Using SEM and HR-TEM confirm the particle size (23-113 nm) of the reduced AuNPs increases with the increase of the concentration. Based on CV studies, the redox capability of as-prepared electroactive materials was found to show an increase trend: 1Au/EPI-5 < 3Au/EPI-5 < 5Au/EPI-5. The series of Au/EPI-5 composites showed good stability and catalytic activity for the reaction of 4-NP to 4-AP. Especially, the 5Au/EPI-5 composite shows the highest catalytic activity when applied for the reduction of 4-NP to 4-AP within 17 min. The rate constant and kinetic activity energy were calculated to be 1.1 × 10-3 s-1 and 38.9 kJ/mol, respectively. Following a reusability test repeated 10 times, the 5Au/EPI-5 composite maintained a conversion rate higher than 95%. Finally, this study elaborates the mechanism of the catalytic reduction of 4-NP to 4-AP.

Bone marrow mesenchymal stem cell-derived exosomal microRNAs target PI3K/Akt signaling pathway to promote the activation of fibroblasts.

BACKGROUND: Fibroblast plays a major role in tendon-bone healing. Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) can activate fibroblasts and promote tendon-bone healing via the contained microRNAs (miRNAs). However, the underlying mechanism is not comprehensively understood. Herein, this study aimed to identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets, and to verify their effects as well as mechanisms on fibroblasts. AIM: To identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets and verify their effects as well as mechanisms on fibroblasts. METHODS: BMSC-derived exosomal miRNAs data (GSE71241, GSE153752, and GSE85341) were downloaded from the Gene Expression Omnibus (GEO) database. The candidate miRNAs were obtained by the intersection of three data sets. TargetScan was used to predict potential target genes for the candidate miRNAs. Functional and pathway analyses were conducted using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, respectively, by processing data with the Metascape. Highly interconnected genes in the protein-protein interaction (PPI) network were analyzed using Cytoscape software. Bromodeoxyuridine, wound healing assay, collagen contraction assay and the expression of COL I and α-smooth muscle actin positive were applied to investigate the cell proliferation, migration and collagen synthesis. Quantitative real-time reverse transcription polymerase chain reaction was applied to determine the cell fibroblastic, tenogenic, and chondrogenic potential. RESULTS: Bioinformatics analyses found two BMSC-derived exosomal miRNAs, has-miR-144-3p and has-miR-23b-3p, were overlapped in three GSE datasets. PPI network analysis and functional enrichment analyses in the GO and KEGG databases indicated that both miRNAs regulated the PI3K/Akt signaling pathway by targeting phosphatase and tensin homolog (PTEN). In vitro experiments confirmed that miR-144-3p and miR-23b-3p stimulated proliferation, migration and collagen synthesis of NIH3T3 fibroblasts. Interfering with PTEN affected the phosphorylation of Akt and thus activated fibroblasts. Inhibition of PTEN also promoted the fibroblastic, tenogenic, and chondrogenic potential of NIH3T3 fibroblasts. CONCLUSION: BMSC-derived exosomes promote fibroblast activation possibly through the PTEN and PI3K/Akt signaling pathways, which may serve as potential targets to further promote tendon-bone healing.