Background: Early detection of diabetic atherosclerosis (DAS) remains challenging, and the mechanisms underlying endothelial barrier dysfunction in this condition are not fully understood. Extracellular Hsp90α (eHsp90α) and the ER stress marker GRP78 have been implicated in vascular injury; however, their roles in DAS remain unclear. Therefore, this study aimed to investigate the association of eHsp90α and GRP78 with DAS and explore the underlying mechanisms. Methods: We recruited patients with diabetes mellitus (DM) and patients with DAS. We then compared the levels and potential efficacies of serum eHsp90α and the ER stress marker GRP78 between the two groups. We subsequently conducted cytological experiments and experiments with ApoE−/− mice to further explore the underlying mechanisms involved. Results: The serological analysis revealed that the levels of serum eHsp90α and the ER stress marker GRP78 were significantly higher in the DAS group than in the DM group and that the eHsp90α level was correlated with GRP78 level. The association and preliminary discriminative performance of the combination of eHsp90α and GRP78 levels were appeared higher than that of either marker alone. In addition, GRP78 plays a mediating role in the relationship between eHsp90α and DAS. Furthermore, the expression of GRP78 was higher in both diabetic ApoE−/− mice and DAS patients than in control ApoE−/− mice and AS patients. Cytological experiments revealed that eHsp90α induced endothelial barrier dysfunction mediated by ER stress via the LRP1 receptor. Conclusions: Our findings suggest that eHsp90α and GRP78 are associated with diabetic atherosclerosis and may be associated biomarkers with potential discriminative value, although further validation is required. The eHsp90α–LRP1–ER stress pathway may contribute to endothelial barrier dysfunction. However, further large-scale and longitudinal studies are required to validate these findings.

Frailty is a global public health issue, and metabolic syndrome (MetS) is also associated with a variety of adverse health outcomes. However, the relationship between the combined effects of these two factors and the occurrence and progression of long-term diseases remains unclear. This is a population-based cohort study involving 165,555 participants from the UK Biobank. We combined frailty status scores with metabolic condition scores to assess the predictive value. Associations were assessed using multi-state model, corrected Cox models, restricted cubic spline, stratified analysis, Kaplan-Meier analysis. During the 12.7-year follow-up period, 3,585 individuals were newly diagnosed with metabolic-associated fatty liver disease (MAFLD), among whom 170 developed non-insulin-dependent diabetes mellitus (NIDDM) and 699 died from all causes. Compared with Group 1(neither frailty nor MetS), the HR and 95

AIMS:The intervention of prediabetes, with lifestyle modification as its first-line therapy, is an emerging method to prevent diabetes and cardiovascular complications. This study investigated the association of Life's Essential 8 (LE8) with cardiovascular outcomes and mortality among individuals with prediabetes, and the mediating role of inflammation in these relationships. METHODS:The main analyses included 33,745 participants with prediabetes from the UK Biobank cohort study. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Mediation analyses were conducted to examine underlying pathways. RESULTS:After multivariable adjustment, a higher LE8 score was significantly associated with lower risks of CVD incidence (HR 0.49; 95% CI 0.45, 0.53), CVD mortality (HR 0.46; 95% CI 0.35, 0.61), and all-cause mortality (HR 0.54; 95% CI 0.48, 0.60). Inflammatory biomarkers, particularly neutrophil count (mediating 9.65% of the LE8-CVD association and 17.20% of the LE8-mortality association), significantly mediated these associations. Moreover, in the genetic susceptibility analysis, LE8 adherence was associated with lower cardiovascular risk across all PRS groups (p for interaction > 0.05). CONCLUSIONS:Achieving optimal LE8 metrics is significantly associated with reduced cardiovascular risk and mortality in people with prediabetes, and systemic inflammation partially explains these associations.

BACKGROUND:The pathogenesis of early-stage skin lesions in diabetic foot (DF) remains poorly understood, and cannot be fully explained by conventional theories. Skin microbiota dysbiosis has recently emerged as a critical factor, but the underlying mechanisms remain unclear. METHODS:In this study, we integrated metabolomics and metagenomics analyses of skin samples to investigate metabolic dysregulation driven by microbial dysbiosis. RESULTS:We identified elevated serine as a key metabolic alteration strongly correlated with a dysbiotic microbiota structure. Functionally, we demonstrate that abnormal serine accumulation contributes to the dysregulation of the early skin immune microenvironment in the diabetic foot. Mechanistically, our results reveal that excess serine synergizes with lipopolysaccharide (LPS) to stimulate the release of eHsp90α from keratinocytes, which was strictly dependent on the Akt/mTOR/HIF-1α pathway. This released eHsp90α then acts as a damage-associated molecular pattern, promoting both the migration and subsequent pyroptotic cell death of macrophages. CONCLUSIONS:Collectively, our findings suggest a novel pathogenic axis where a microbiota-host derived metabolite collaborates with a bacterial endotoxin to promote inflammatory cell death, which is closely associated with early skin lesions in DF. This work not only elucidates a new mechanism for DF pathogenesis but also suggests that the serine-eHsp90α-pyroptosis axis may serve as a potential candidate for future therapeutic exploration.

Diabetic foot ulcers (DFUs) complicated by multidrug-resistant (MDR) bacterial infection present a significant clinical challenge that necessitates innovative therapeutic strategies. Conventional antimicrobial treatments often fail because of limited tissue penetration, antibiotic resistance, and poor efficacy against biofilm-forming pathogens. In this study, we developed a near-infrared (NIR) light-responsive aggregation-induced emission luminogen (AIEgen) with high photothermal conversion efficiency, excellent photostability, and favorable biocompatibility. Upon NIR light activation, this AIEgen can induce localized hyperthermia capable of disrupting bacterial membranes and penetrating deep into infected tissues, thereby effectively eradicating the embedded MDR pathogens and resilient biofilms. The antibacterial efficacy of the AIEgen was validated against MDR clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Pseudomonas aeruginosa (CRPA). In vitro and in vivo evaluations confirmed the potent bactericidal activity, efficient biofilm disruption ability, and minimal cytotoxicity of the AIEgen. Notably, in a DFU infection model, AIEgen administration and NIR light exposure significantly accelerated wound healing by eliminating pathogens, suppressing inflammation, promoting M2 macrophage polarization, enhancing collagen deposition, and stimulating angiogenesis. In conclusion, this AIEgen-based photothermal system offers a noninvasive, biocompatible, and deeply penetrating antibacterial strategy for the treatment of chronic MDR infections in DFUs and has great potential for clinical translation.

Microplastics, as a novel type of environmental pollutant, have garnered increasing concern for their potential threat to human health. Pulmonary fibrosis, with high mortality and limited therapy, is exacerbated by airborne contaminants like microplastics. This research assessed the pathological role of polystyrene microplastic (PS-MPs) exposure in driving airway microbial dysbiosis and subsequent fibrotic lung remodeling. Mice were intranasally instilled with PS-MPs and treated with a mixture of antibiotics. Bronchoalveolar lavage fluid was collected from the mice, and the airway microbiota, along with their associated metabolic profiles, were characterized using 16S rRNA gene sequencing, non-targeted metabolomics, and network pharmacology. Exposure to PS-MPs significantly increased the abundance of Staphylococcus, Prevotella, and Weissella in the mouse airway and altered the structure of the lung microbiota. Microbiota derived metabolites, such as 5-methoxyindole-3-carboxaldehyde (5-MC), arachidonylamide, progesterone, and oleamide, were significantly negatively correlated with Staphylococcus, Prevotella, and Weissella, with 5-MC showing the largest fold change. Experimental data demonstrated that microbiota derived 5-MC attenuated particulate induced alveolar epithelial senescence via PI3K/AKT/mTOR pathway modulation, consequently reducing fibrotic pathology. This evidence establishes that PS-MPs initiate pulmonary fibrosis through dysbiosis-mediated metabolic disruption, whereas the microbial metabolite 5-MC counteracts PS-MPs triggered fibrosis by rescuing cellular aging processes.

Diabetic patients often experience prolonged hyperglycemia, which leads to sustained harm and malfunction of various body organs. The blood urea nitrogen (BUN) to serum albumin ratio (BAR) and systemic inflammation response index (SIRI) have been proven to be reliable indicators. We aimed to investigate the association of BAR, SIRI and their combination with the risk of diabetic macrovascular diseases. A total of 2,911 participants from Nanfang Hospital diagnosed with type 2 diabetes mellitus (T2DM) were included. Restricted cubic spline (RCS) and logistic regression modelling were used to assess the relation between different values of BAR, SIRI and combined BAR-SIRI and the risk of diabetic macrovascular complications. Receiver operating curve (ROC) analysis was used to compare the predictive value of BAR, SIRI, and their combination for macrovascular outcomes. High value of BAR, SIRI and their combination were associated with increased risk of macrovascular complications (BAR: odds ratio [OR] = 1.45, 95

OBJECTIVE:To investigate the associations between accelerometer-derived physical activity patterns-specifically the "weekend warrior" (WW) pattern versus regularly distributed activity-and the risk of incident microvascular complications among individuals with type 2 diabetes (T2D) and prediabetes. METHODS:This prospective cohort study utilized data from the UK Biobank, analysing 12 923 adults with T2D and prediabetes who had accelerometer-measured data. Participants were classified into three groups: active WW (≥ 150 min/week; ≥ 50% of moderate-to-vigorous physical activity [MVPA] accumulated on 1-2 days), active regular (≥ 150 min/week but not meeting WW criteria), and inactive (< 150 min/week). Hazard ratio (HR) and 95% confidence interval (CI) for incident microvascular complications and their subtypes (diabetic kidney disease [DKD], neuropathy [DN], and retinopathy [DR]) were estimated using Cox proportional hazards models. RESULTS:Over a median follow-up of 7.88 years, 1235 incident microvascular complications were documented. Compared with the inactive group, both active patterns were associated with similarly reduced risks of microvascular complications (WW: HR 0.71 [95% CI 0.61-0.82]; regularly active: HR 0.63 [95% CI 0.52-0.77]). These protective associations extended consistently to DKD, DN and DR, with no statistically significant differences between WW and regularly active groups (all p > 0.05). Findings were robust across alternative MVPA thresholds, subgroup analyses, and sensitivity analyses. CONCLUSIONS:Concentrating recommended weekly MVPA within 1-2 days offers similar microvascular protection as regularly distributed activity among individuals with T2D and prediabetes, supporting flexible approaches for this high-risk population to achieve weekly activity goals.

BACKGROUND:Type 2 diabetes mellitus (T2DM) and its complications, including diabetic lower extremity arterial disease (DLEAD) and diabetic foot (DF), impose significant health burdens worldwide. However, the differential expression of microRNAs (miRNAs) between T2DM and its complications and its causal effects remain poorly understood. METHODS:We conducted an exosome-wide association study (EWAS) comparing miRNA profiles between T2DM and its complications, including DLEAD and DF, without healthy controls. The significant miRNAs identified between DM and its complications were further validated by integrating cis-miRNA expression quantitative trait loci (cis-miR-eQTLs) and genome-wide association study (GWAS) summary data of T2DM and peripheral arterial disease (PAD) through two-sample Mendelian randomization (MR) analysis. RESULTS:We identified several differential expressions of miRNAs between T2DM, DLEAD, and DF, such as hsa-miR-409-3p between T2DM and DLEAD, hsa-miR-543 between T2DM and DF and hsa-miR-206 between DLEAD and DF. The two sample MR analysis revealed potential causal relationships between dysregulated miRNAs and T2DM and its complications, such as hsa-miR-30b-3p and hsa-miR-30b-5p showed causal associations with T2DM and PAD respectively. CONCLUSIONS:Our study elucidates the miRNA signatures associated with T2DM and its complications. These findings provide insights into the pathogenesis of T2DM and its complications and suggest potential therapeutic targets for intervention.

Frailty is a global public health issue associated with multiple adverse outcomes in later years, however, studies have shown exercise, diet, and vitamin D supplements can help reverse frailty. There is a lack of further risk stratification and evidence for secondary interventions in populations that have undergone primary prevention. This was a prospective cohort study involving 53106 physically active vulnerable individuals from the UK Biobank. We combined vitamin D with cumulative dietary risk scores to evaluate its predictive value. Correlation and predictive power were assessed using restricted cubic spline (RCS) analysis, corrected Cox models, stratified analysis, Kaplan–Meier analysis, and Harrell's c-index. During 12.7 years of follow-up, there were 870, 1317 new-onset metabolic dysfunction-associated fatty liver disease (MAFLD) and mortality. RCS analysis revealed a J-shaped negative or positive correlation in vitamin D and dietary risk score respectively. The hazard ratios (95

Graves’ ophthalmopathy (GO) obvious manifestation is the imbalance of Th17/Treg. N6-methyladenosine (m6A) methylation is an important regulator of Th17/Treg balance. However, few reports narrate how m6A regulators mediate the role of genes in GO progression. We explored the m6A modification of THBS1 mediated by WTAP, and the mechanism by which THBS1 regulated glycolysis and Th17/Treg balance. A total of 12 peripheral blood (4 GO samples, 4 GH samples, and 4 health samples) were collected to measure the percentage of Th17/Treg in monocytes by flow cytometry. RNA sequencing (RNA-seq) combined with MeRIP sequencing (MeRIP-seq) was used to screen differentially expressed and methylated genes. MeRIP-qPCR was performed to evaluate the m6A abundance of THBS1 after WTAP silencing. Glycolysis of CD4+ T cells was reflected by the lactate content and glucose uptake. The number of Th17 cells was increased in GO peripheral blood, whereas the Treg cells decreased. RNA-seq acquired 679 differentially expressed genes (308 up-regulated, and 371 down-regulated) in the CD4+ T cells of GO compared to healthy control. MeRIP-seq identified 3277 m6A peaks between the GO group and the healthy control group, corresponding with 2744 genes (1143 hypermethylated and 1601 hypomethylated). Combined analysis of RNA-seq and MeRIP-seq showed 81 hypermethylated and up-regulated genes. Among the six candidate genes in the PI3K-signaling pathway, THBS1 was the most significantly differentially expressed and hypermethylated. THBS1 silencing resulted in decreased lactate content and glucose uptake in CD4+ T cells. WTAP was significantly upregulated in CD4+ T cells of GO, and WTAP silencing significantly reduced m6A abundance and expression of THBS1. Upregulated and hypermethylated THBS1 mediated by WTAP promoted glycolysis of CD4+ T cells, affected Th17/Treg balance, and facilitated GO progression. We provided a novel potential target for GO treatment and revealed the molecular mechanism of WTAP and THBS1 in GO under the m6A perspective.

ObjectivesPrevious research has not yet established whether and how cardiovascular-kidney-metabolic (CKM) syndrome progression affects liver outcomes.MethodsThis prospective study utilized data from the UK Biobank (UKB) cohort, including 415,713 individuals without prevalent liver diseases or substance use disorder. The CKM syndrome stages were defined according to the Presidential Advisory from the American Heart Association. Outcomes were major adverse liver outcomes (MALOs), including hospitalization for metabolic dysfunction-associated steatotic liver disease (MASLD), severe liver disease (SLD), and liver-specific mortality. Cox proportional hazards models examined the association between CKM stages and MALOs. The CMAverse R package was used to investigate the potential mediating effects of plasma metabolomic data.ResultsAfter multivariable adjustment, a higher CKM stage was associated with elevated risks of incident MASLD hospitalization [hazard ratios (HRs) = 7.38, 95% confidence intervals (CIs): 4.34, 12.55], SLD hospitalization (HR = 3.46, 95% CI:1.94, 6.16), and liver-specific mortality (HR = 4.35; 95% CI: 1.38, 13.69). CKM components were, respectively, and cumulatively associated with MALOs (all p < 0.05). Mediation analyses indicated that tyrosine partially mediated the associations between CKM stage and MASLD-related hospitalization (7.62%), SLD-related hospitalization (9.46%), and liver-related death (11.19%), while linoleic acid-to-total fatty acids ratio partially mediated MASLD hospitalization (41.18%), SLD hospitalization (34.30%), and liver-related death (45.17%) (all q < 0.001).ConclusionCKM progression elevates MALO risk, partially mediated by amino acids and fatty acids. These findings identify high-risk patients who may benefit from targeted liver surveillance for secondary prevention of CKM syndrome.

Background: An increased risk of multiple secondary diseases has been observed in individuals with diabetes, which contributes to the growing economic burden. Few studies have established the connection of blood urea nitrogen/albumin (BAR) with diabetes, and its link to subsequent diabetic complications and mortality remains unclear. We aimed to explore the association of BAR with the onset of type 2 diabetes mellitus (T2DM) and its dynamic progression. Methods: A total of 20,039 prediabetic participants aged 40-70, without diabetes or related events at baseline, were selected from the UK Biobank. We used a multistate regression model to assess the relationships between BAR and the trajectories of T2DM progression-from pre-T2DM to T2DM, complications, and ultimately mortality. Akaike information criterion (AIC), area under the curve (AUC), and C-statistic analyses were performed to compare the diagnostic performance of BAR with that of HbA1c for assessing T2DM progressions risk. Results: Over a mean 13-year follow-up, 5621 incident T2DM cases were identified, and among them, 1295 developed diabetes macrovascular complications, 574 developed diabetes microvascular complications, and 1264 died. BAR was significantly associated with the increased risk of T2DM (HR: 1.05, 95% CI: 1.02, 1.09), subsequent macrovascular complications (HR: 1.18, 95% CI: 1.12, 1.25), microvascular complications (HR 1.18, 95% CI: 1.08, 1.28), and further death (HR 1.18, 95% CI: 1.00, 1.39). The ability of BAR (AUC: 0.938, C-statistic: 0.739, p < 0.001) to predict diabetes progression was inferior to that of hemoglobin A1c (HbA1c) (AUC: 0.949, C-statistic: 0.809, p < 0.001). Conclusions: Although BAR is significantly positively correlated with the risk of progression at different stages of diabetes, its predictive performance is inferior to that of HbA1c and comparable to that of BUN and albumin. BAR does not demonstrate sufficient clinical significance in predicting diabetes progression, highlighting the need for further investigation.

Circadian rhythm disruption has been increasingly implicated in asthma and glucocorticoid (GC) resistance. In this study, we discovered that disruption of the brain and muscle ARNT-like 1 (BMAL1), a significant activator of the circadian clock transcription, not only exacerbated allergic inflammation but also induced GC resistance. The absence of BMAL1 intensified airway inflammation by activating the NF-κB and AP-1 pathways and also impaired the anti-inflammatory effect of GC. Our findings indicated that the deletion of BMAL1 reduced the phosphorylation level of the GC receptor (GR-Ser211), which has a direct effect on the efficacy of GC and serves as a key indicator of GR activation. Additionally, BMAL1 has a negative regulatory effect on the phosphatase dual specificity protein phosphatase 4 (DUSP4) of p38 mitogen-activated protein kinase (p38MAPK), which plays a crucial role in the phosphorylation of GR. Consequently, our findings suggest that the absence of BMAL1 results in the resistance of airway epithelial cells to GC due to the inhibition of GR phosphorylation via the DUSP4-p38MAPK axis in HDM-induced asthma. We demonstrated that the inhibition of DUSP4 restored GR activation and improved GC responsiveness, highlighting a potential therapeutic strategy for GC resistance driven by circadian disruption. Regulating the sleep disorder and circadian rhythm of patients with asthma could become a potential treatment to increase GC sensitivity.

The key genes and the remodeling of immune cell composition in Graves’ ophthalmopathy (GO) orbital adipose tissue remain unclear. We aimed to explore key genes and understand their association with immune components in GO pathogenesis. The study analyzed the mRNA, lncRNA, and single-cell RNA sequencing (scRNA-seq) expression profiles of orbital adipose tissue from GO patients using GSE58331, GSE143789, and GSE194323 respectively to screen the differential expressed genes (DEGs), which were further subjected to pathway and network analyses, along with investigation of their association with immunocyte proportions. A total of 70 DEGs of GO orbital adipose were screened out and were closely associated with immune-related pathways. The intersection between WGCNA and PPI defined 17 hub genes. GO group presented significantly higher abundances of CD8+ T cells, CD8 naïve, and effector memory cells than the normal group. In processing scRNA-seq data, we found that the proportion of B cells, CD4+ T cells, CD8+ T cells, monocytes, and NK cells was significantly higher in the GO group than in the control. Among them, CSF1R, MRC1, VSIG4, and C1QA were downregulated considerably in monocytes in the GO group compared to the normal group, which were confirmed by RT-qPCR and immunofluorescence of monocytes from GO patients. Overexpression of C1QA markedly decreased the expression of the M1 macrophage marker CD86, while enhanced the M2 marker CD206. Most DElncRNAs at bulk and single-cell levels shared 9 interacting proteins encoded by the hub genes. RT-qPCR verified that lncRNA PCED1B-AS1 expression was up-regulated in monocytes from GO patients compared to control. GO involves gene expression alterations and immune cell remodeling in orbital adipose tissue. The downregulation of C1QA in monocytes and its role in promoting M2 macrophage polarization suggest its involvement in shaping the GO immune microenvironment.

BackgroundExcess weight is a progressive metabolic epidemic, and inflammation plays an important role in the progression of disease. Insulin resistance (IR) is an important feature of obesity, but it does not reflect systemic inflammation. Currently, there is a lack of effective clinical tools for early risk stratification and intervention in physically active people.MethodsThis was a prospective cohort of 72,262 overweight but physically active persons in the UK Biobank. The TyG was combined with hsCRP, waist circumference (WC), or body mass index (BMI) as indices of IR. Adjusted Cox regression, interaction tests, restricted cubic splines (RCS) analysis, Kaplan-Meier analysis, and Harrell's C-index were used to examine the relations and time-dependent predictive power.ResultsDuring 12.7 years of follow-up, 1,477 participants developed metabolic dysfunction-associated fatty liver disease (MAFLD). RCS analysis suggested TyG-hsCRP had a nonlinear positive correlations with all-cause mortality. Compared to the lowest quartile group, the corrected hazard ratio (HR) (95% confidence interval [CI]) of new-onset MAFLD in maximum quartile groups for TyG-hsCRP was 1.94(1.62-2.32), for TyG-WC was 1.78(1.44-2.18), for TyG-BMI was 1.36(1.12-1.65), and for TyG was 1.41(1.15-1.72). The relation between C-index of TyG-hsCRP and MAFLD was higher than that of other TyG indices. Similar results were observed in all-cause mortality.ConclusionTyG-hsCRP is superior to other indices for identifying risk of MAFLD and all-cause mortality in overweight but physically active people. Our findings suggest the importance of inflammatory metabolism and provide evidence for effectively early anti-inflammatory treatments.

Type 2 diabetes mellitus (T2DM), atherosclerotic cardiovascular disease (CVD) and chronic kidney disease (CKD) are closely linked at epidemiological, pathophysiological, and molecular levels, forming cardio-renal-metabolic (CRM) disease. Their multimorbidity leads to multi-organ dysfunction and increased cardiovascular risk, making prevention and management crucial in clinical and public health practice. We included 398,689 participants from UK Biobank free of CRM diseases at baseline. We used both traditional and multi-state regression model to assess the relationships between AIP-BRI —defined as the product of the atherogenic index of plasma (AIP) and the body roundness index (BRI) —and CRM diseases. Besides, we employed the restricted cubic spline (RCS) approach to visualize the dose-response relationship between AIP-BRI values and three main transition stages (baseline→first CRM diseases (FCRM), FCRM disease→ double CRM (DCRM) diseases, and DCRM diseases→triple CRM (TCRM) disease). Over a a median follow-up period of 12.7 years, 61,539 individuals developed FCRM disease. Among these, 10,714 further developed DCRM diseases, while 1,332 advanced to TCRM diseases. According to our study, AIP-BRI was significantly associated with the progression of CRM diseases in fully adjusted model (HR [95

Regulation of excessive inflammation and impaired cell proliferation is crucial for healing diabetic wounds. Although plant-to-mammalian regulation offers effective approaches for chronic wound management, the development of a potent plant-based therapeutic presents challenges. This study aims to validate the efficacy of turmeric-derived nanoparticles (TDNPs) loaded with natural bioactive compounds. TDNPs can alleviate oxidative stress, promote fibroblast proliferation and migration, and reprogram macrophage polarization. Restoration of the fibroblast-macrophage communication network by TDNPs stimulates cellular regeneration, in turn enhancing diabetic wound healing. To address diabetic wound management, TDNPs are loaded in an ultralight-weight, high swelling ratio, breathable aerogel (AG) constructed with cellulose nanofibers and sodium alginate backbones to obtain TDNPs@AG (TAG). TAG features wound shape-customized accessibility, water-adaptable tissue adhesiveness, and capacity for sustained release of TDNPs, exhibiting outstanding performance in facilitating in vivo diabetic wound healing. This study highlights the potential of TDNPs in regenerative medicine and their applicability as a promising solution for wound healing in clinical settings.

Background:The epidemiology and severity of asthma vary by sex and age. The diagnosis, treatment, and management of asthma in female patients are quite challenging. However, there is hitherto no comprehensive and standardized guidance for female patients with asthma.Methods:Corresponding search strategies were determined based on clinical concerns regarding female asthma. Search terms included "sex hormones and lung development", "sex hormone changes and asthma", "hormones and asthma immune response", "women, asthma", "children, asthma", "puberty, asthma", "menstruation, asthma", "pregnancy, asthma", "lactation, asthma", "menopause, asthma", "obesity, asthma", and "women, refractory, severe asthma". Literature was retrieved from PubMed/Medline, Embase, Cochrane Library, China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Data with the search date of July 30, 2022 as the last day. This consensus used the Grading of Recommendations Assessment, Development, and Evaluation to evaluate the strength of recommendation and quality of evidence.Results:We collected basic research results and clinical evidence-based medical data and reviewed the effects of sex hormones, classical genetics, and epigenetics on the clinical presentation and treatment response of female patients with asthma under different environmental effects. Based on that, we formulated this expert consensus on the management of female asthma throughout the life cycle.Conclusions:This expert consensus on the management of asthma in women throughout the life cycle provides diagnosis, treatment, and research reference for clinical and basic medical practitioners.