Safety evaluation of a second extension of use of the food enzyme α-amylase from the non-genetically modified Cellulosimicrobium funkei strain AE-AMT.

The food enzyme α-amylase (4-α-d-glucan glucanohydrolase i.e. EC 3.2.1.1) is produced with the non-genetically modified Cellulosimicrobium funkei strain AE-AMT by Amano Enzyme Inc. A safety evaluation of this food enzyme was made previously, in which EFSA concluded that the food enzyme did not give rise to safety concerns when used in seven food manufacturing processes. Subsequently, the applicant has requested to extend its use to include three additional processes. In this assessment, EFSA updated the safety evaluation of this food enzyme when used in a total of ten food manufacturing processes. As the food enzyme-total organic solids (TOS) are removed from the final foods in one food manufacturing process, the dietary exposure to the food enzyme-TOS was estimated only for the remaining nine processes. The dietary exposure was calculated to be up to 0.049 mg TOS/kg body weight (bw) per day in European populations. When combined with the no observed adverse effect level previously reported (230 mg TOS/kg bw per day, the highest dose tested), the Panel derived a margin of exposure of at least 4694. Based on the data provided for the previous evaluation and the revised margin of exposure in the present evaluation, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.

Safety evaluation of an extension of use of the food enzyme pullulanase from the non-genetically modified Pullulanibacillus naganoensis strain AE-PL.

The food enzyme pullulanase (pullulan 6-α-glucanohydrolase; EC 3.2.1.41) is produced with the non-genetically modified Pullulanibacillus naganoensis strain AE-PL by Amano Enzyme Inc. A safety evaluation of this food enzyme was made previously, in which EFSA concluded that this food enzyme did not give rise to safety concerns when used in one food manufacturing process. Subsequently, the applicant has requested to extend its use to include seven additional processes and to revise the previous use level. In this assessment, EFSA updated the safety evaluation of this food enzyme when used in a total of eight food manufacturing processes. As the food enzyme-total organic solids (TOS) are not carried into the final foods in two food manufacturing processes, the dietary exposure was estimated only for the remaining six processes. The dietary exposure was calculated to be up to 0.004 mg TOS/kg body weight (bw) per day in European populations. The Panel evaluated the repeated dose 90-day oral toxicity study in rats submitted in the previous application and identified a no observed adverse effect level of 643 mg TOS/kg bw per day, the highest dose tested. When compared with the calculated dietary exposure, this resulted in a margin of exposure of at least 160,750. Based on the data provided for the previous evaluation and the revised margin of exposure in the present evaluation, the Panel concluded that this food enzyme does not give rise to safety concerns under the revised intended conditions of use.

Safety evaluation of an extension of use of the food enzyme triacylglycerol lipase from the non-genetically modified Aspergillus luchuensis strain AE-L.

The food enzyme triacylglycerol lipase (triacylglycerol acylhydrolase; EC 3.1.1.3) is produced with the non-genetically modified Aspergillus luchuensis strain AE-L by Amano Enzyme Inc. A safety evaluation of this food enzyme was made previously, in which EFSA concluded that this food enzyme did not give rise to safety concerns when used in one food manufacturing process. Subsequently, the applicant has requested to extend its use to include four additional processes and to revise the previous use level. In this assessment, EFSA updated the safety evaluation of this food enzyme when used in a total of five food manufacturing processes. The dietary exposure to the food enzyme-total organic solids (TOS) was calculated to be up to 0.458 mg TOS/kg body weight (bw) per day in European populations. When combined with the no observed adverse effect level previously reported (1726 mg TOS/kg bw per day, the highest dose tested), the Panel derived a revised margin of exposure of at least 3769. Based on the data provided for the previous evaluation and the revised margin of exposure in the present evaluation, the Panel concluded that this food enzyme does not give rise to safety concerns under the revised intended conditions of use.

Impact of SiO2 doping on the structure and oil-water separation properties of a PVDF membrane: insights from molecular dynamics simulation.

Hybrid inorganic particles combined with polymers are widely used to modify the properties of polymer membranes. However, the mechanism by which particles affect membranes remains unclear. This study investigates SiO2-hybridized PVDF membranes through molecular dynamic simulation, focusing on the interaction between SiO2 clusters and PVDF chains. It examines the impact of varying SiO2 concentrations (3.5 wt%, 6.8 wt%, 9.9 wt%, 12.8 wt%, and 15.5 wt%) on membrane stability and structure. The results indicate that adding SiO2 can inhibit PVDF chain mobility in the membrane with minimal effect on fractional free volume (FFV), except for altering interactions between PVDF-PVDF, PVDF-SiO2, and SiO2-SiO2, thereby affecting the structure of hybrid membranes. The adsorption and diffusion behavior of water and oil molecules on these membranes were also studied. It was observed that the adsorption energy and diffusion coefficient initially increase and then decrease with increasing SiO2 concentration, reaching an optimum between 6.8 wt% and 12.8 wt%. This phenomenon is attributed to the ability of optimal SiO2 concentrations to create hydrophilic channels in PVDF membranes, enhancing water affinity and reducing oil affinity. Consequently, water permeation through the hybrid membrane is promoted, improving the efficiency of oil/water separation compared to pure PVDF membranes. This research contributes to understanding the function of adding inorganic particles to polymer membranes and provides insights for designing advanced functional hybrid membranes.

Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication in Chinese population: A prospective, multicenter, randomized, two-stage study.

BACKGROUND: The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial. AIM: To evaluate the efficacy of VAT in the Chinese population. METHODS: This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778. RESULTS: In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001). CONCLUSION: VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.

Preservation of superior rectal artery in laparoscopic colectomy: The best choice for slow transit constipation?

Laparoscopic colectomy with ileorectal anastomosis may be beneficial for patients with slow transit constipation who do not respond to conservative treatment, particularly if the superior rectal artery (SRA) is preserved. Several important concerns have been addressed in this commentary. It is important to first go over the definition of surgical procedure as it is used in this text. Second, the current study lacked a control group that had SRA preservation. Thirdly, it would be best to use a prospective, randomized controlled study. Lastly, a description of the mesenteric defect's state following a laparoscopic colectomy is necessary.

Differential contribution of microbial and plant-derived organic matter to soil organic carbon sequestration over two decades of natural revegetation and cropping.

Both natural revegetation and cropping have great impact on long-term soil carbon (C) sequestration, yet the differences in their underlying mechanisms remain unclear. In this study, we investigated trends in soil organic C (SOC) accumulation during natural revegetation (VR) and cropping processes over 24 years, and explored the contributions of microbial necromass and plant-derived C to SOC formation and their primary controls. Over the course of 24 years of land use/cover change (LUCC) from 1995, SOC content exhibited a more substantial increase in VR (0.31 g kg-1 a-1) than in cropland (0.14 g kg-1 a-1) during Stage II (>10 y after LUCC), and recalcitrant organic carbon explained more of the SOC variation than easily oxidizable carbon. The higher SOC content in VR was attributed to a greater contribution of plant-derived C (14-28 %) than that in cropland (3-11 %) to SOC and a consistently lower ratio of cinnamyl (C)- to vanillyl (V)-type phenols in VR across all the assessed years. Although there were higher proportion of microbial necromass of SOC (41-84 %) in cropland than in VR, the differences were not significant. The dominant bacterial phylum of Chloroflexi and soil nitrogen content were the primary biotic and abiotic factors regulating microbial-derived and plant-derived C in both cropland and VR. However, soil phosphorus content was the main factor in cropland, while climatic factors such as mean annual precipitation were more important in VR. These results provided evidence that long-term natural revegetation enhanced SOC sequestration by greater contribution of plant-derived C to SOC formation compared to cropping. These findings underscore the synergistic contribution of vegetation and microorganisms to long-term SOC sequestration, offering insights into the different mechanisms of carbon formation during VR and cropping processes, and providing support for optimizing land management to achieve global carbon neutrality goals.

Advancements in the Transdermal Drug Delivery Systems Utilizing Microemulsion-based Gels.

Microemulsion gel, as a promising transdermal nanoparticle delivery system, addresses the limitations of microemulsions and enhances their performance in drug delivery and release. This article aims to discuss the advantages of microemulsion gel, including improved drug bioavailability, reduced drug irritation, enhanced drug penetration and skin adhesion, and increased antimicrobial properties. It explores the methods for selecting microemulsion formulations and the general processes of microemulsion preparation, as well as commonly used oil phases, surfactants, and co-surfactants. Additionally, the biomedical applications of microemulsion gel in treating conditions, such as acne and psoriasis, are also discussed. Overall, this article elucidates the significant potential of microemulsion gel in topical drug delivery, providing insights into future development and clinical applications.

The active magnetic compensation coil.

The active magnetic compensation coil is of great significance for extensive applications, such as fundamental physics, aerospace engineering, national defense industry, and biological science. The magnetic shielding demand is increasing over past few decades, and better performances of the coil are required. To maintain normal operating conditions for some sensors, active magnetic compensation coils are often used to implement near-zero field environments. Many coil design methods have been developed to design the active compensation coil for different fields. It is opportune to review the development and challenges associated with active magnetic compensation coils. Active magnetic compensation coils are reviewed in this paper in terms of design methods, technology, and applications. Furthermore, the operational principle and typical structures of the coil are elucidated. The developments of the forward design method, inverse design method, and optimization algorithm are presented. Principles of various design methods and their respective advantages and disadvantages are described in detail. Finally, critical challenges in the active magnetic compensation coil techniques and potential research directions have been highlighted.

Correlation between tumor budding and the long-term follow-up outcomes after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

BACKGROUND: The effect of tumor budding (TB) on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after endoscopic submucosal dissection (ESD) remains unclear. We evaluated the long-term outcomes of patients with superficial ESCC after ESD and the risk factors of TB for the long-term prognosis. METHODS: We conducted a retrospective study in a Chinese hospital. All patients with ESCC treated by ESD and reported TB were included consecutively. Comparative analyses were conducted in three parts: specimen analysis, follow-up analyses of unmatched patients, and propensity score-matched (PSM) patients. Cox proportional hazard regression models were constructed to identify risk factors for overall survival and recurrence-free survival (RFS). RESULTS: A total of 437 patients were enrolled [154 TB and 283 no tumor budding (NTB)], and 258 patients (52 TB and 206 NTB) were included in the follow-up analysis. Results showed that the invasion depth, differentiation type, and positive vascular invasion (all p < 0.001) of the TB group were significantly different from the NTB group. The all-cause mortality and the median RFS time between the two groups were comparable. RFS rate at 5 years were 84.6% and 80.6%, respectively (p = 0.43). Cox analyses identified that having other cancers but not TB, as a risk factor independently associated with overall survival and RFS after ESD. CONCLUSION: TB tends to be associated with invasion depth, differentiation type, and positive vascular invasion. However, it might not affect the long-term outcomes of patients with superficial ESCC after ESD when other high-risk factors are negative.

The divergent effects of G3BP orthologs on human stress granule assembly imply a centric role for the core protein interaction network.

Liquid-liquid phase separation (LLPS) mediated by G3BP1/2 proteins and non-translating mRNAs mediates stress granule (SG) assembly. We investigated the phylogenetic evolution of G3BP orthologs from unicellular yeast to mammals and identified both conserved and divergent features. The modular domain organization of G3BP orthologs is generally conserved. However, invertebrate orthologs displayed reduced capacity for SG assembly in human cells compared to vertebrate orthologs. We demonstrated that the protein-interaction network facilitated by the NTF2L domain is a crucial determinant of this specificity. The evolution of the G3BP1 network coincided with its exploitation by certain viruses, as evident from the interaction between viral proteins and G3BP orthologs in insects and vertebrates. We revealed the importance and divergence of the G3BP interaction network in human SG formation. Leveraging this network, we established a 7-component in vitro SG reconstitution system for quantitative studies. These findings highlight the significance of G3BP network divergence in the evolution of biological processes.

Preparation of Benzo[a]fluorenes via Pd-Catalyzed Annulation of 5-(2-Bromophenyl)pent-3-en-1-ynes.

A palladium-promoted cascade cyclization of 5-(2-bromophenyl)pent-3-en-1-ynes is developed for the synthesis of benzo[a]fluorene derivatives. The reaction proceeds with oxidative addition of C-Br, insertion, C-H activation, and reductive elimination in sequential steps.

Lignocellulosic biomass-derived functional nanocellulose for food-related applications: A review.

In recent years, nanocellulose (NC) has gained significant attention due to its remarkable properties, such as adjustable surface chemistry, extraordinary biological properties, low toxicity and low density. This review summarizes the preparation of NC derived from lignocellulosic biomass (LCB), including cellulose nanofibrils (CNF), cellulose nanocrystals (CNC), and lignin-containing cellulose nanofibrils (LCNF). It focuses on examining the impact of non-cellulosic components such as lignin and hemicellulose on the functionality of NC. Additionally, various surface modification strategies of NC were discussed, including esterification, etherification and silylation. The review also emphasizes the progress of NC application in areas such as Pickering emulsions, food packaging materials, food additives, and hydrogels. Finally, the prospects for producing NC from LCB and its application in food-related fields are examined. This work aims to demonstrate the effective benefits of preparing NC from lignocellulosic biomass and its potential application in the food industry.

Early administration of ketorolac after cardiac surgery and postoperative complications: Analysis of the MIMIC-IV database.

Inflammation may contribute to postoperative cardiac complications and ketorolac, an anti-inflammatory agent inhibiting cyclooxygenase (COX), shows promise in enhancing cardiac graft patency by suppressing endothelial cell proliferation in animal studies. However, the safety of postoperative ketorolac use remains controversial. This study investigates the association between early ketorolac application and complications following cardiac surgery. Data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database fueled this retrospective cohort study. The primary outcome is a composite of mortality, pulmonary insufficiency, severe acute kidney injury (AKI), hemorrhage or hematoma, infection, cardiogenic shock, and cerebrovascular infarction postcardiac surgery. Propensity score matching (PSM; 1:1 match, caliper 0.2), multivariate logistic regression, interaction stratification analysis, pairwise algorithmic, and overlap weight model analyses were employed. Following inclusion and exclusion criteria, 7143 patients who underwent valvular surgery or coronary artery bypass grafting (CABG) were included. PSM created a balanced cohort of 3270 individuals (1635 in the ketorolac group). The matched cohort exhibited an 8.1% overall rate of postoperative complications, with a lower composite outcome rate in patients receiving ketorolac within 48 h of surgery compared with those without (PSM, OR 0.70 [95% CI, 0.54-0.90]). Consistent associations were observed in total cohort analyses, sensitivity, and subgroup analyses. Early ketorolac use within 48 h post-CABG or valvular procedures in adults is independently associated with a lower incidence of composite postoperative adverse events. Prospective trials are warranted to assess causality.

Gasdermin-E-mediated pyroptosis drives immune checkpoint inhibitor-associated myocarditis via cGAS-STING activation.

Immune checkpoint inhibitor (ICI)-induced myocarditis involves intensive immune/inflammation activation; however, its molecular basis is unclear. Here, we show that gasdermin-E (GSDME), a gasdermin family member, drives ICI-induced myocarditis. Pyroptosis mediated by GSDME, but not the canonical GSDMD, is activated in myocardial tissue of mice and cancer patients with ICI-induced myocarditis. Deficiency of GSDME in male mice alleviates ICI-induced cardiac infiltration of T cells, macrophages, and monocytes, as well as mitochondrial damage and inflammation. Restoration of GSDME expression specifically in cardiomyocytes, rather than myeloid cells, in GSDME-deficient mice reproduces ICI-induced myocarditis. Mechanistically, quantitative proteomics reveal that GSDME-dependent pyroptosis promotes cell death and mitochondrial DNA release, which in turn activates cGAS-STING signaling, triggering a robust interferon response and myocardial immune/inflammation activation. Pharmacological blockade of GSDME attenuates ICI-induced myocarditis and improves long-term survival in mice. Our findings may advance the understanding of ICI-induced myocarditis and suggest that targeting the GSDME-cGAS-STING-interferon axis may help prevent and manage ICI-associated myocarditis.

Unlocking the potential of HHLA2: identifying functional immune infiltrating cells in the tumor microenvironment and predicting clinical outcomes in laryngeal squamous cell carcinoma.

BACKGROUND: HHLA2 (human endogenous retrovirus-H long terminal repeat-associating protein 2) represents a recently identified member of the B7 immune checkpoint family, characterized by limited expression in normal tissues but notable overexpression in various cancer types. Nevertheless, the precise function and interaction with immune cells remain poorly understood, particularly in laryngeal squamous cell carcinoma (LSCC). This investigation endeavored to elucidate the biological significance of HHLA2 within the tumor microenvironment of human LSCC tissues and delineate the clinical relevance and functional roles of HHLA2 in LSCC pathogenesis. METHODS: Through multiplexed immunohistochemistry analyses conducted on tissue microarrays sourced from LSCC patients (n = 72), the analysis was executed to assess the expression levels of HHLA2, density and spatial patterns of CD68+HLA-DR+CD163- (M1 macrophages), CTLA-4+CD4+FoxP3+ (CTLA-4+Treg cells), CTLA-4+CD4+FoxP3- (CTLA-4+Tcon cells), exhausted CD8+T cells, and terminally exhausted CD8+T cells in LSCC tissues. Survival analysis was conducted to evaluate the prognostic significance of HHLA2 and these immune checkpoints or immune cell populations, employing COX regression analysis to identify independent prognostic factors. RESULTS: Kaplan-Meier (K-M) survival curves revealed a significant association between HHLA2 expression and overall survival (OS) in LSCC. Elevated levels of HHLA2 were linked to reduced patient survival, indicating its potential as a prognostic marker (HR: 3.230, 95%CI 0.9205-11.34, P = 0.0067). Notably, increased infiltration of CD68+ cells (total macrophages), STING+CD68+HLA-DR+CD163- (STING+M1 macrophages), CTLA-4+CD4+FoxP3+, CTLA-4+CD4+FoxP3-, PD-1+LAG-3+CD8+T cells, and PD-1+LAG-3+TIM-3+CD8+T cells strongly linked to poorer survival outcomes (P < 0.05). A discernible trend was observed between the levels of these immune cell populations, STING+CD68+ (STING+ total macrophages), CD68+HLA-DR+CD163-, STING+CD68+CD163+HLA-DR- (STING+M2 macrophages), PD-1+LAG-3-CD8+T cells, PD-1+TIM-3+CD8+T cells, and PD-1+LAG-3+TIM-3-CD8+T cells and prognosis. Importantly, multivariate COX analysis identified HHLA2 as an independent predictive factor for OS in LSCC patients (HR = 3.86, 95% CI 1.08-13.80, P = 0.038). This underscored the potential of HHLA2 as a critical marker for predicting patient outcomes in LSCC. CONCLUSIONS: HHLA2 emerged as a detrimental prognostic biomarker for assessing OS in LSCC patients. Relative to other immune checkpoints, HHLA2 exhibited heightened predictive efficacy for the prognosis of LSCC patients.

Continuous therapy in HHV-8 negative Multicentric Castleman Disease and prolonged progression-free survival.

The optimal treatment endpoints and duration of continuous therapy for multicentric Castleman disease (MCD) remain controversial. We retrospectively analyzed data from 123 patients with Human Herpesvirus (HHV)-8 negative MCD. We demonstrated that continuous therapy significantly enhanced progression-free survival (PFS) in patients who achieved an optimal response after initial treatment. These findings underscore the critical role of continuous therapy in HHV-8 negative MCD. Further studies with larger cohorts are required to validate these findings.

Plastome Evolution, Phylogenomics, and DNA Barcoding Investigation of Gastrochilus (Aeridinae, Orchidaceae), with a Focus on the Systematic Position of Haraella retrocalla.

Gastrochilus is an orchid genus containing about 70 species in tropical and subtropical Asia with high morphological diversity. The phylogenetic relationships among this genus have not been fully resolved, and the plastome evolution has not been investigated either. In this study, five plastomes of Gastrochilus were newly reported, and sixteen plastomes of Gastrochilus were used to conduct comparative and phylogenetic analyses. Our results showed that the Gastrochilus plastomes ranged from 146,183 to 148,666 bp, with a GC content of 36.7-36.9%. There were 120 genes annotated, consisting of 74 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. No contraction and expansion of IR borders, gene rearrangements, or inversions were detected. Additionally, the repeat sequences and codon usage bias of Gastrochilus plastomes were highly conserved. Twenty hypervariable regions were selected as potential DNA barcodes. The phylogenetic relationships within Gastrochilus were well resolved based on the whole plastome, especially among main clades. Furthermore, both molecular and morphological data strongly supported Haraella retrocalla as a member of Gastrochilus (G. retrocallus).

The Beneficial Effect of the SGLT2 Inhibitor Dapagliflozin in Alleviating Acute Myocardial Infarction-Induced Cardiomyocyte Injury by Increasing the Sirtuin Family SIRT1/SIRT3 and Cascade Signaling.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have a variety of cardiovascular and renoprotective effects and have been developed as novel agents for the treatment of heart failure. However, the beneficial mechanisms of SGLT2i on cardiac tissue need to be investigated further. In this study, we established a mouse model of acute myocardial infarction (AMI) using coronary artery constriction surgery and investigated the role of dapagliflozin (DAPA) in protecting cardiomyocytes from hypoxic injury induced by AMI. In vitro experiments were done using hypoxic cultured H9c2 ventricular cells to verify this potential mechanism. Expression of the SIRT family and related genes and proteins was verified by qPCR, Western blotting and immunofluorescence staining, and the intrinsic potential mechanism of cardiomyocyte death due to AMI and hypoxia was comprehensively investigated by RNA sequencing. The RNA sequencing results of cardiomyocytes from AMI mice showed that the SIRT family may be mainly involved in the mechanisms of hypoxia-induced cardiomyocyte death. In vitro hypoxia-induced ventricular cells showed the role of dapagliflozin in conferring resistance to hypoxic injury in cardiomyocytes. It showed that SIRT1/3/6 were downregulated in H9c2 cells in a hypoxic environment, and the addition of dapagliflozin significantly increased the gene and protein expression of SIRT1, 3 and 6. We then verified the underlying mechanisms induced by dapagliflozin in hypoxic cardiomyocytes using RNA-seq, and found that dapagliflozin upregulated the hypoxia-induced gene downregulation, which includes ESRRA, EPAS1, AGTRAP, etc., that associated with SIRTs-related and apoptosis-related signaling to prevent H9c2 cell death. This study provides laboratory data for SGLT2i dapagliflozin treatment of AMI and confirms that dapagliflozin can be used to treat hypoxia-induced cellular necrosis in cardiomyocytes, in which SIRT1 and SIRT3 may play an important role. This opens up further opportunities for SGLT2i in the treatment of heart disease.

Hypoxic microenvironment promotes diabetic wound healing by polarizing macrophages to the M2 phenotype in vivo.

BACKGROUND: In diabetic wounds, M2 polarization of macrophages regulates the transition from an inflammatory phase to a proliferative phase. Prior investigations have demonstrated the potential of deferoxamine (DFO) in creating a localized hypoxic microenvironment, which could stimulate angiogenesis by promoting vascular endothelial growth factor (VEGF) secretion in diabetic wound healing. Nevertheless, there is still no clear information on whether this chemically induced hypoxic microenvironment modulates macrophage polarization to promote diabetic wound healing. METHODS: The 18 diabetic mice were randomly divided into three groups: a control group (n = 6), a 100µM DFO group (n = 6), and a 200µM DFO group (n = 6). Subsequently, a full-thickness wound with a diameter of 1.00 cm was created on the dorsal region of the diabetic mice. Observe wound closure regularly during treatment. At the end of the observation, tissue specimens were collected for a series of experiments and analyses, including hematoxylin and eosin (H&E), Masson, immunofluorescent, and immunohistochemical staining. The role and mechanism of DFO in regulating macrophage polarization were studied using RAW264.7 cells. RESULTS: In comparison to the control group, the administration of DFO notably facilitates wound healing in diabetic mice. In diabetic wounds, DFO increases blood supply by upregulating VEGF, which promotes angiogenesis. Additionally, The expression of HSP70 and CD206 were also upregulated by DFO in both vivo and in vitro, while iNOS expression was downregulated. Additionally, knk437 inhibited the expression of HSP70 in RAW264.7 cells, resulting in a reduction of M2 polarization and an increase in M1 polarization. CONCLUSION: The induction of a hypoxic microenvironment by DFO has been found to exert a substantial influence on the process of diabetic wound healing. DFO treatment enhances the capacity of diabetic wounds to stimulate angiogenesis and modulate macrophage polarization that may be associated with HSP70 expression, thereby expediting the transition of these wounds from an inflammatory to a proliferative state.