Leveraging DNA-encoded Cell-mimics for Environment-adaptive Transmembrane Channel Release-induced Cell Death.

The advancement of cell-mimic materials, which can forge sophisticated physicochemical dialogues with living cells, has unlocked a realm of intriguing prospects within the fields of synthetic biology and biomedical engineering. Inspired by the evolutionarily acquired ability of T lymphocytes to release perforin and generate transmembrane channels on targeted cells for killing, herein we present a pioneering DNA-encoded artificial T cell mimic model (ARTC) that accurately mimics T-cell-like behavior. ARTC responds to acidic conditions similar to those found in the tumor microenvironment and then selectively releases a G-rich DNA strand (LG4) embedded with C12 lipid and cholesterol molecules. Once released, LG4 effectively integrates into the membranes of neighboring live cells, behaving as an artificial transmembrane channel that selectively transports K+ ions and disrupts cellular homeostasis, ultimately inducing apoptosis. We hope that the emergence of ARTC will usher in new perspectives for revolutionizing future disease treatment and catalyzing the development of advanced biomedical technologies.

Polyfluoroalkyl Tag Decoration Enables Significantly Enhanced Tumor Penetration Ability of a PTK7 Targeting Aptamer.

Aptamers are widely used molecular recognition tools in targeted therapy, but their ability to effectively penetrate deep into solid tumors remains a significant challenge, leading to suboptimal treatment efficacy. Here, we developed a polyfluoroalkyl (PFA) decoration strategy to enhance aptamer recognition, cell internalization, and solid tumor penetration. Our results indicate that PFA with around 11 fluorine atoms significantly improves aptamer internalization both in vitro and in vivo settings. However, we also observed that the use of PFA tags containing 19 and 23 fluorine atoms on aptamers resulted in nonspecific cell anchoring in control cell lines, affecting the specificity of aptamers. Overall, we found that using a chemical modification strategy could enhance the deep tumor penetration ability of aptamers and validate their effectiveness in vivo. This approach has significant practical applications in targeted drug delivery for cancer treatment.

Safety of repeated low-level red-light therapy for children with myopia.

BACKGROUD: To investigate the safety of repetitive low-level red-light therapy (RLRLT) in children with myopia. METHODS: Children with myopia were assigned to the RLRL and control groups. Axial length (AL) and spherical equivalent refraction (SER) were followed up at 3-, 6-, and 12-month. To evaluate the safety of RLRLT, at 6 and 12 months in the RLRL group, multifocal electroretinography (mfERG) and contrast sensitivity were recorded. Furthermore, optical coherence tomography was used to measure the relative reflectance of the ellipsoid zone (rEZR), photoreceptor outer segment (rPOSR), and retinal pigment epithelium (rRPER). RESULTS: A total of 108 children completed the trial (55 in the RLRL group and 53 in the control group). After 3, 6, and 12 months, AL was shorter and SER less myopic in the RLRL group than in the control group. Regarding the safety of the RLRLT, the response density and amplitude of the P1 wave of the first ring of the mfERG increased significantly at 6 months (P = 0.001 and P = 0.017, respectively). At 6 and 12 months, contrast sensitivity at the high spatial frequency increased. Moreover, the rEZR increased significantly at 6 months (P = 0.029), the rPOSR increased significantly at 6 and 12 months (both P < 0.001), and the increase in rPOSR was greater with greater AL regression. CONCLUSIONS: Based on retinal function and structure follow-up, RLRLT was safe within 12 months. However, rEZR and rPOSR increased, the effects of this phenomenon requires further observation.

Genetic effects and causal association analyses of 14 common conditions/diseases in multimorbidity patterns.

BACKGROUND: Multimorbidity has become an important health challenge in the aging population. Accumulated evidence has shown that multimorbidity has complex association patterns, but the further mechanisms underlying the association patterns are largely unknown. METHODS: Summary statistics of 14 conditions/diseases were available from the genome-wide association study (GWAS). Linkage disequilibrium score regression analysis (LDSC) was applied to estimate the genetic correlations. Pleiotropic SNPs between two genetically correlated traits were detected using pleiotropic analysis under the composite null hypothesis (PLACO). PLACO-identified SNPs were mapped to genes by Functional Mapping and Annotation of Genome-Wide Association Studies (FUMA), and gene set enrichment analysis and tissue differential expression were performed for the pleiotropic genes. Two-sample Mendelian randomization analyses assessed the bidirectional causality between conditions/diseases. RESULTS: LDSC analyses revealed the genetic correlations for 20 pairs based on different two-disease combinations of 14 conditions/diseases, and genetic correlations for 10 pairs were significant after Bonferroni adjustment (P<0.05/91 = 5.49E-04). Significant pleiotropic SNPs were detected for 11 pairs of correlated conditions/diseases. The corresponding pleiotropic genes were differentially expressed in the brain, nerves, heart, and blood vessels and enriched in gluconeogenesis and drug metabolism, biotransformation, and neurons. Comprehensive causal analyses showed strong causality between hypertension, stroke, and high cholesterol, which drive the development of multiple diseases. CONCLUSIONS: This study highlighted the complex mechanisms underlying the association patterns that include the shared genetic components and causal effects among the 14 conditions/diseases. These findings have important implications for guiding the early diagnosis, management, and treatment of comorbidities.

Mediating effect of the NLR on the relationship between HbA1c and left atrial stiffness in overweight patients with hypertension.

BACKGROUND: We aimed to investigate the association between hemoglobin A1c (HbA1c) and left atrial (LA) stiffness in patients with hypertension and to explore the mediating effect of the neutrophil/lymphocyte ratio (NLR) on this association. METHODS: Essential hypertensive patients (n=292) aged 18 to 83 years were enrolled and divided into two groups based on the LA stiffness index (LASI): Group I (LASI≤0.32, n=146) and Group II (LASI>0.32, n=146). The LASI was defined as the ratio of early diastolic transmitral flow velocity/lateral mitral annulus myocardial velocity (E/e') to LA reservoir strain. Multivariate linear regression analysis was performed to determine the independent predictors of the LASI. RESULTS: Age, BMI, SBP, HbA1c, CRP and the NLR were significantly greater in Group II than in Group I (P<0.05). Additionally, Group II had a greater LA volume index (LAVI), left ventricular mass index (LVMI), and E/e' and lower LA reservoir, conduit and booster pump strains than Group I (P<0.001). Univariate and multivariate linear regression models revealed that age, SBP, HbA1c, and the NLR were independently associated with the LASI. Further mediation analysis was performed to determine the mediating effect of the NLR on the association between HbA1c and the LASI and revealed that the NLR had a mediating role only in overweight hypertensive patients, and the proportion of the mediating effect was 21.9%. CONCLUSIONS: The NLR was independently correlated with the LASI and played a mediating role in the relationship between HbA1c and the LASI in overweight hypertensive patients.

Spatial-temporal patterns and influencing factors for hemorrhagic fever with renal syndrome: A 16-year national surveillance analysis in China.

Background: China is confronted with the significant menace posed by hemorrhagic fever with renal syndrome (HFRS). Nevertheless, the long-term spatial-temporal variations, regional prevalence patterns, and fundamental determinants' mechanisms for HFRS remain inadequately elucidated. Methods: Newly diagnosed cases of HFRS from January 2004 to December 2019 were acquired from the China Public Health Science Data repository. We used Age-period-cohort and Bayesian Spacetime Hierarchy models to identify high-risk populations and regions in mainland China. Additionally, the Geographical Detector model was employed to quantify the determinant powers of significant driver factors to the disease. Results: A total of 199,799 cases of HFRS were reported in mainland China during 2004-2019. The incidence of HFRS declined from 1.93 per 100,000 in 2004 to 0.69 per 100,000 in 2019. The incidence demonstrated an inverted U-shaped trend with advancing age, peaking in the 50-54 age group, with higher incidences observed among individuals aged 20-74 years. Hyperendemic areas were mainly concentrated in the northeastern regions of China, while some western provinces exhibited a potential upward trend. Geographical detector model identified that the spatial variations of HFRS were significantly associated with the relative humidity (Q = 0.36), forest cover (Q = 0.26), rainfall (Q = 0.18), temperature (Q = 0.16), and the surface water resources (Q = 0.14). Conclusions: This study offered comprehensive examinations of epidemic patterns, identified high-risk areas quantitatively, and analyzed factors influencing HFRS transmission in China. The findings may contribute to the necessary implementations for the effective prevention and control of HFRS.

Ni-Catalyzed Csp2 and Csp3 Coupling for Divergent Bisboronic Ester Synthesis.

Bisboronic esters are critical compounds in various research fields, including drug discovery, chemical biology, and material sciences. Currently, the bisboronic esters with reactive functional groups are difficult to synthesize; this is partially due to the lack of a robust method to produce these products with diverse structures and various functional groups at specific locations. To overcome this issue, this study introduced a Ni-catalysis approach to produce bisboronic esters efficiently via cross-coupling and homocoupling using readily available halogenated boronic esters as the starting material under mild reaction conditions. This newly developed strategy enables Csp2-Csp2, Csp3-Csp3, and Csp2-Csp3 couplings, demonstrating a broad substrate scope and excellent compatibility with various functional groups.

Massively parallel screen uncovers many rare 3' UTR variants regulating mRNA abundance of cancer driver genes.

Understanding the function of rare non-coding variants represents a significant challenge. Using MapUTR, a screening method, we studied the function of rare 3' UTR variants affecting mRNA abundance post-transcriptionally. Among 17,301 rare gnomAD variants, an average of 24.5% were functional, with 70% in cancer-related genes, many in critical cancer pathways. This observation motivated an interrogation of 11,929 somatic mutations, uncovering 3928 (33%) functional mutations in 155 cancer driver genes. Functional MapUTR variants were enriched in microRNA- or protein-binding sites and may underlie outlier gene expression in tumors. Further, we introduce untranslated tumor mutational burden (uTMB), a metric reflecting the amount of somatic functional MapUTR variants of a tumor and show its potential in predicting patient survival. Through prime editing, we characterized three variants in cancer-relevant genes (MFN2, FOSL2, and IRAK1), demonstrating their cancer-driving potential. Our study elucidates the function of tens of thousands of non-coding variants, nominates non-coding cancer driver mutations, and demonstrates their potential contributions to cancer.

Self-Stimulated Photodynamic Nanoreactor in Combination with CXCR4 Antagonists for Antileukemia Therapy.

The treatment of acute myeloid leukemia (AML) remains unsatisfactory, owing to the absence of efficacious therapy regimens over decades. However, advances in molecular biology, including inhibiting the CXCR4/CXCL12 biological axis, have introduced novel therapeutic options for AML. Additionally, self-stimulated phototherapy can solve the poor light penetration from external sources, and it will overcome the limitation that traditional phototherapy cannot be applied to the treatment of AML. Herein, we designed and manufactured a self-stimulated photodynamic nanoreactor to enhance antileukemia efficacy and suppress leukemia recurrence and metastasis in AML mouse models. To fulfill our design, we utilized the CXCR4/CXCL12 biological axis and biomimetic cell membranes in conjunction with self-stimulated phototherapy. This nanoreactor possesses the capability to migrate into the bone marrow cavity, inhibit AML cells from infiltrating into the visceral organ, significantly enhance the antileukemia effect, and prolong the survival time of leukemic mice. Therefore, this nanoreactor has significant potential for achieving high success rates and low recurrence rates in leukemia treatment.

Glutamine prevents high-fat diet-induced hepatic lipid accumulation in mice by modulating lipolysis and oxidative stress.

Metabolic-associated fatty liver disease (MAFLD) is related to metabolic dysfunction and is characterized by excess fat storage in the liver. Several studies have indicated that glutamine could be closely associated with lipid metabolism disturbances because of its important role in intermediary metabolism. However, the effect of glutamine supplementation on MAFLD progression remains unclear. Here, we used a high-fat diet (HFD)-induced MAFLD C57BL/6 mouse model, and glutamine was supplied in the drinking water at different time points for MAFLD prevention and reversal studies. A MAFLD prevention study was performed by feeding mice an HFD concomitant with 4% glutamine treatment for 24 weeks, whereas the MAFLD reversal study was performed based on 4% glutamine treatment for 13 weeks after feeding mice an HFD for 10 weeks. In the prevention study, glutamine treatment ameliorated serum lipid storage, hepatic lipid injury, and oxidative stress in HFD-induced obese mice, although glutamine supplementation did not affect body weight, glucose homeostasis, energy expenditure, and mitochondrial function. In the MAFLD reversal study, there were no noticeable changes in the basic physiological phenotype and hepatic lipid metabolism. In summary, glutamine might prevent, but not reverse, HFD-induced MAFLD in mice, suggesting that a cautious attitude is required regarding its use for MAFLD treatment.

The Impact of China's Family Floating Population on the Participation of Medical Insurance in the Inflow Areas.

Background: With the transformation of China's economy and society, the floating population has also shown a new development trend, from individual migration to co-migration with family members. In 2020, among the 376 million floating population, the population flowing to cities and towns was 330 million, accounting for nearly 88.1%. The family mobility of the floating population is not just a simple personal gathering or geographical migration, but a profound adjustment of the living environment, social interaction and the interests of family members. Migrants no longer simply play the role of " urban passers-by", but gradually move with spouses, children, parents, and even settle in the city, which will inevitably produce different public service and social security needs. Objective: To explore the impact of floating population's familyization on the participation of medical insurance in the inflow areas. Methods: This study adopted the form of non-systematic literature review. The key words were floating population and medical insurance. The related analysis of PubMed, Embase, CNKI, Wanfang, and VIP databases were reviewed and summarized. Results: Due to the flow between domestic immigrants and regions, their medical insurance is difficult to be guaranteed. The domestic floating population's demand for health services is increasing, but the coverage of medical services provided by medical insurance is not comprehensive enough. Conclusion: It is necessary to integrate the medical insurance system and improve the adaptability of medical insurance to family mobility; protect the welfare needs of migrant families and increase their willingness to participate in medical insurance at the destination; pay attention to the interaction and integration of floating population families, understand and guide them to participate in the status quo of medical insurance, and improve the status quo.

Thermophoretic glycan profiling of extracellular vesicles for triple-negative breast cancer management.

Triple-negative breast cancer (TNBC) is a highly metastatic and heterogeneous type of breast cancer with poor outcomes. Precise, non-invasive methods for diagnosis, monitoring and prognosis of TNBC are particularly challenging due to a paucity of TNBC biomarkers. Glycans on extracellular vesicles (EVs) hold the promise as valuable biomarkers, but conventional methods for glycan analysis are not feasible in clinical practice. Here, we report that a lectin-based thermophoretic assay (EVLET) streamlines vibrating membrane filtration (VMF) and thermophoretic amplification, allowing for rapid, sensitive, selective and cost-effective EV glycan profiling in TNBC plasma. A pilot cohort study shows that the EV glycan signature reaches 91% accuracy for TNBC detection and 96% accuracy for longitudinal monitoring of TNBC therapeutic response. Moreover, we demonstrate the potential of EV glycan signature for predicting TNBC progression. Our EVLET system lays the foundation for non-invasive cancer management by EV glycans.

Rapid identification of SARS-CoV-2 variants using stable high-frequency mutation sites.

Respiratory infectious viruses, including SARS-CoV-2, undergo rapid genetic evolution, resulting in diverse subtypes with complex mutations. Detecting and differentiating these subtypes pose significant challenges in respiratory virus surveillance. To address these challenges, we integrated ARMS-PCR with molecular beacon probes, allowing selective amplification and discrimination of subtypes based on adjacent mutation sites. The method exhibited high specificity and sensitivity, detecting as low as 104 copies/mL via direct fluorescence analysis and ~106 copies/mL using real-time PCR. Our robust detection approach offers a reliable and efficient solution for monitoring evolving respiratory infections, aiding early diagnosis and control measures. Further research could extend its application to other respiratory viruses and optimize its implementation in clinical settings.

Enhancing Specific Fluorescence In Situ Hybridization with Quantum Dots for Single-Molecule RNA Imaging in Formalin-Fixed Paraffin-Embedded Tumor Tissues.

Single-molecule fluorescence in situ hybridization (smFISH) represents a promising approach for the quantitative analysis of nucleic acid biomarkers in clinical tissue samples. However, low signal intensity and high background noise are complications that arise from diagnostic pathology when performed with smFISH-based RNA imaging in formalin-fixed paraffin-embedded (FFPE) tissue specimens. Moreover, the associated complex procedures can produce uncertain results and poor image quality. Herein, by combining the high specificity of split DNA probes with the high signal readout of ZnCdSe/ZnS quantum dot (QD) labeling, we introduce QD split-FISH, a high-brightness smFISH technology, to quantify the expression of mRNA in both cell lines and clinical FFPE tissue samples of breast cancer and lung squamous carcinoma. Owing to its high signal-to-noise ratio, QD split-FISH is a fast, inexpensive, and sensitive method for quantifying mRNA expression in FFPE tumor tissues, making it suitable for biomarker imaging and diagnostic pathology.

Changes in the global epidemiological characteristics of cystic echinococcosis over the past 30 years and projections for the next decade: Findings from the Global Burden of Disease Study 2019.

Background: Despite ongoing changes in the global epidemiology of cystic echinococcosis (CE), there is a lack of research conducted to date. Methods: We extracted data on incidence and disability-adjusted life years for 204 countries and territories from 1990 to 2019 to evaluate the epidemiological characteristics and burden of CE through the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. We used locally weighted linear regression to analyse the primary driving factors of the prevalence of CE at the national and regional levels and utilised a Bayesian Age-Period-Cohort model to forecast the global incidence of CE in the next decade. Results: Globally, the incidence of CE remained constantly high from 1990 (2.65 per 100 000 population) to 2019 (2.60 per 100 000 population), resulting in an estimated 207 368 new cases in 2019. We observed substantial variations in the disease burden regarding its spatiotemporal distribution, population demographics, and Socio-Demographic Index levels. According to established models, factors such as health care capacity, livestock husbandry, agricultural activities, rural populations, and education levels are likely to play significant roles in determining the prevalence of CE across different countries. By 2030, the worldwide number of CE cases could reach as high as 235 628, representing an increase of 13.63% compared to 2019. Conclusions: Over the past three decades, the global burden of CE has persistently remained high, especially in Central Asia, as well as North Africa and the Middle East. Efforts should focus on more effective prevention and control measures in these key regions and should specifically target vulnerable populations to prevent the escalation of epidemics.

Stress systems exacerbate the inflammatory response after corneal abrasion in sleep-deprived mice via the IL-17 signaling pathway.

Sleep deprivation (SD) has a wide range of adverse health effects. However, the mechanisms by which SD influences corneal pathophysiology and its post-wound healing remain unclear. This study aimed to examine the basic physiological characteristics of the cornea in mice subjected to SD and determine the pathophysiological response to injury after corneal abrasion. Using a multi-platform water environment method as an SD model, we found that SD leads to disturbances of corneal proliferative, sensory, and immune homeostasis as well as excessive inflammatory response and delayed repair after corneal abrasion by inducing hyperactivation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis. Pathophysiological changes in the cornea mainly occurred through the activation of the IL-17 signaling pathway. Blocking both adrenergic and glucocorticoid synthesis and locally neutralizing IL-17A significantly improved corneal homeostasis and the excessive inflammatory response and delay in wound repair following corneal injury in SD-treated mice. These results indicate that optimal sleep quality is essential for the physiological homeostasis of the cornea and its well-established repair process after injury. Additionally, these observations provide potential therapeutic targets to ameliorate SD-induced delays in corneal wound repair by inhibiting or blocking the activation of the stress system and its associated IL-17 signaling pathway.

THE EFFECTS OF DRAINAGE TUBE ON PAIN AND FUNCTIONAL RECOVERY AFTER UNICOMPARTMENTAL KNEE ARTHROPLASTY.

Objective: The objective of this study was to evaluate the impact of drainage tube placement on postoperative pain, recovery, and opioid consumption within a 72-hour period following unicompartmental knee arthroplasty (UKA). Methods: Patients with medial knee osteoarthritis who underwent UKA from January 2019 to August 2020 were enrolled in the study and divided into two groups based on whether they received a drain postoperatively. Results: The drainage group had significantly lower VAS scores on day 1, day 2, and day 3, in addition to significantly smaller changes in the circumference of the knee joint within 3 days postoperatively (P <0.05). The ROM in the drainage group significantly increased at 3 days and 1 month post-surgery, with a statistically significant difference in morphine consumption between the two groups at 3 days (P<0.05). The incidence of postoperative nausea and vomiting (5 cases) and wound bleeding (1 case) was lower in the drainage group compared to the non-drainage group (P<0.05). Conclusions: The placement of a drainage tube in UKA may reduce the swelling of knee joint and pain, which not only reduces the use of Opioid but also facilitates early functional activities of the knee joint. Level of Evidence III; Retrospective Comparative Study.

Objetivo: O objetivo deste estudo foi avaliar o impacto da implantação do tubo de drenagem na dor pós-operatória, na recuperação e no consumo de opioides em um período de 72 horas após a artroplastia unicompartimental do joelho (UKA). Métodos: Pacientes com osteoartrite medial do joelho submetidos à UKA de janeiro de 2019 a agosto de 2020 foram incluídos no estudo e divididos em dois grupos com base no fato de terem ou não recebido um dreno no pós-operatório. Resultados: O grupo de drenagem apresentou escores EVA significativamente menores no dia 1, no dia 2 e no dia 3, além de alterações significativamente menores na circunferência da articulação do joelho em 3 dias de pós-operatório (P <0,05). A ADM no grupo de drenagem aumentou significativamente em 3 dias e 1 mês após a cirurgia, com uma diferença estatisticamente significativa no consumo de morfina entre os dois grupos em 3 dias (P<0,05). A incidência de náuseas e vômitos no pós-operatório(5 casos) e sangramento da ferida (1 caso) foi menor no grupo de drenagem em comparação com o grupo sem drenagem (P<0,05). Conclusão: A utilização de tubo de drenagem na UKA pode reduzir o edema articular do joelho e a dor, reduzindo o uso de opioides e facilitando as atividades funcionais iniciais da articulação do joelho. Nível de Evidência III; Estudo Comparativo Retrospectivo.

Multivalent Aptamer-Based Lysosome-Targeting Chimeras (LYTACs) Platform for Mono- or Dual-Targeted Proteins Degradation on Cell Surface.

Selective protein degradation platforms have opened novel avenues in therapeutic development and biological inquiry. Antibody-based lysosome-targeting chimeras (LYTACs) have emerged as a promising technology that extends the scope of targeted protein degradation to extracellular targets. Aptamers offer an advantageous alternative owing to their potential for modification and manipulation toward a multivalent state. In this study, a chemically engineered platform of multivalent aptamer-based LYTACs (AptLYTACs) is established for the targeted degradation of either single or dual protein targets. Leveraging the biotin-streptavidin system as a molecular scaffold, this investigation reveals that trivalently mono-targeted AptLYTACs demonstrate optimum efficiency in degrading membrane proteins. The development of this multivalent AptLYTACs platform provides a principle of concept for mono-/dual-targets degradation, expanding the possibilities of targeted protein degradation.

Serpin peptidase inhibitor, clade E, member 2 is associated with malignant progression and clinical prognosis in oral squamous cell carcinoma.

Background/purpose: The serpin peptidase inhibitor, clade E, member 2 (SERPINE2), is upregulated in breast cancer, prostate cancer, and urothelial carcinoma; however, limited information exists regarding its expression in oral cancer. Therefore, this study aimed to analyze the association between SERPINE2 expression and oral squamous cell carcinoma (OSCC) outcomes. Materials and methods: SERPINE2 mRNA and protein expression in patients with head and neck squamous cell carcinoma and OSCC were investigated using online databases and tissue-array analysis. Its relationship with clinicopathological characteristics, OSCC prognosis and its biological function in OSCC cells were explored. Results: Analysis using online databases revealed higher SERPINE2 expression in tumor tissues and its role as a prognostic factor. High SERPINE2 protein levels were significantly correlated with adverse pathological parameters, including advanced clinical stage and tumor status (P < 0.001), lymph nodes (P = 0.014), and distant metastases (P = 0.013). High SERPINE2 expression was associated with worse overall survival (P < 0.001) and was identified as an independent prognostic factor for OSCC. In vitro studies revealed that SERPINE2 knockdown significantly reduced cell proliferation, migration, and invasion in OSCC cell lines. Conclusion: This study suggests that SERPINE2 may serve as a prognostic biomarker and potential therapeutic target for oral cancer.

Empagliflozin ameliorates the impaired osteogenic differentiation ability of adipose-derived stem cells in diabetic osteoporosis by activating autophagy.

Adipose-derived stem cells (ASCs) from diabetic osteoporosis (DOP) mice showed impaired osteogenic differentiation capacity. Recent studies have shown that in addition to antidiabetic drugs, sodium-glucose co-transporter inhibitor-2 (SGLT-2), empagliflozin, can play multipotent roles through various mechanisms of action. In this study, we aimed to investigate the effects and underlying mechanisms of empagliflozin on osteogenic differentiation of ASCs in DOP mice. Our results showed that osteogenic differentiation potential and autophagy activity weakened in DOP-ASCs when compared to controls. However, empagliflozin enhanced autophagy flux by promoting the formation of autophagosomes and acidification of autophagic lysosomes, resulting in an increase in LC3-II expression and a decrease in SQSTM1 expression. Furthermore, empagliflozin contributed to the reversal of osteogenesis inhibition in DOP-ASCs induced by a diabetic microenvironment. When 3-methyladenine was used to block autophagy activity, empagliflozin could not exert its protective effect on DOP-ASCs. Nonetheless, this study demonstrated that the advent of cellular autophagy attributed to the administration of empagliflozin could ameliorate the impaired osteogenic differentiation potential of ASCs in DOP mice. This finding might be conducive to the application of ASCs transplantation for promoting bone fracture healing and bone regeneration in DOP patients.