Identification of early coagulation changes associated with survival outcomes post severe burns from multiple perspectives.

Coagulation alterations manifest early after severe burns and are closely linked to mortality outcomes. Nevertheless, the precise characterization of coagulation changes associated with early mortality remains elusive. We examined alterations in indicators linked to mortality outcomes at both the transcriptomic and clinical characteristic levels. At the transcriptomic level, we pinpointed 28 differentially expressed coagulation-related genes (DECRGs) following burn injuries and endeavored to validate their causal relationships through Mendelian randomization. DECRGs tied to survival exhibit a significant association with neutrophil function, wherein the expression of CYP4F2 and P2RX1 serves as robust predictors of fatal outcomes. In terms of clinical indicators, early levels of D-dimer and alterations in serum calcium show a strong correlation with mortality outcomes. Coagulation depletion and fibrinolytic activation, stemming from the hyperactivation of coagulation pathways post-severe burns, are strongly linked to patient mortality. Monitoring these early coagulation markers with predictive value can effectively identify individuals necessitating priority critical care.

A novel approach for segmentation and quantitative analysis of breast calcification in mammograms.

Background: Breast cancer is a major threat to women's health globally. Early detection of breast cancer is crucial for saving lives. One important early sign is the appearance of breast calcification in mammograms. Accurate segmentation and analysis of calcification can improve diagnosis and prognosis. However, small size and diffuse distribution make calcification prone to oversight. Purpose: This study aims to develop an efficient approach for segmenting and quantitatively analyzing breast calcification from mammograms. The goal is to assist radiologists in discerning benign versus malignant lesions to guide patient management. Methods: This study develops a framework for breast calcification segmentation and analysis using mammograms. A Pro_UNeXt algorithm is proposed to accurately segment calcification lesions by enhancing the UNeXt architecture with a microcalcification detection block, fused-MBConv modules, multiple-loss-function training, and data augmentation. Quantitative features are then extracted from the segmented calcification, including morphology, size, density, and spatial distribution. These features are used to train machine learning classifiers to categorize lesions as malignant or benign. Results: The proposed Pro_UNeXt algorithm achieved superior segmentation performance versus UNet and UNeXt models on both public and private mammogram datasets. It attained a Dice score of 0.823 for microcalcification detection on the public dataset, demonstrating its accuracy for small lesions. For quantitative analysis, the extracted calcification features enabled high malignant/benign classification, with AdaBoost reaching an AUC of 0.97 on the private dataset. The consistent results across datasets validate the representative and discerning capabilities of the proposed features. Conclusion: This study develops an efficient framework integrating customized segmentation and quantitative analysis of breast calcification. Pro_UNeXt offers precise localization of calcification lesions. Subsequent feature quantification and machine learning classification provide comprehensive malignant/benign assessment. This end-to-end solution can assist clinicians in early diagnosis, treatment planning, and follow-up for breast cancer patients.

Microarray analysis of tRNA-derived small RNA (tsRNA) in LPS-challenged macrophages treated with metformin.

Metformin, a widely used anti-diabetic drug, has demonstrated its efficacy in addressing various inflammatory conditions. tRNA-derived small RNA (tsRNA), a novel type of small non-coding RNA, exhibits diverse regulatory functions and holds promise as both a diagnostic biomarker and a therapeutic target for various diseases. The purpose of this study is to investigate whether the abundance of tsRNAs changed in LPS versus LPS + metformin-treated cells, utilizing microarray technology. Firstly, we established an in vitro lipopolysaccharide (LPS)-induced inflammation model using RAW264.7 macrophages and assessed the protective effects of metformin against inflammatory damage. Subsequently, we extracted total RNA from both LPS-treated and metformin + LPS-treated cell samples for microarray analysis to identify differentially abundant tsRNAs (DA-tsRNAs). Furthermore, we conducted bioinformatics analysis to predict target genes for validated DA-tsRNAs and explore the biological functions and signaling pathways associated with DA-tsRNAs. Notably, metformin was found to inhibit the inflammatory response in RAW264.7 macrophages. The microarray results revealed a total of 247 DA-tsRNAs, with 58 upregulated and 189 downregulated tsRNAs in the Met + LPS group compared to the LPS group. The tsRNA-mRNA network was visualized, shedding light on potential interactions. The results of bioinformatics analysis suggested that these potential targets of specific tsRNAs were mainly related to inflammation and immunity. Our study provides compelling evidence that metformin exerts anti-inflammatory effects and modulates the abundance of tsRNAs in LPS-treated RAW264.7 macrophages. These findings establish a valuable foundation for using tsRNAs as potential biomarkers for metformin in the treatment of inflammatory conditions.

Advances in photodynamic therapy of pathologic scar.

Pathologic scars include keloids and hypertrophic scars due to abnormal wound healing. Both cause symptoms of itching and pain; they also affect one's appearance and may even constrain movement. Such scars place a heavy burden on the individual's physical and mental health; moreover, treatment with surgery alone is highly likely to leave more scarring. Therefore, there is an urgent need for a treatment that is both minimally invasive and convenient. Photodynamic therapy (PDT) is an emerging safe and noninvasive technology wherein photosensitizers and specific light sources are used to treat malignant tumors and skin diseases. Research on PDT from both the laboratory and clinic has been reported. These findings on the treatment of pathologic scars using photosensitizers, light sources, and other mechanisms are reviewed in the present article.

Long noncoding RNA XIST promotes cell proliferation and migration in diabetic foot ulcers through the miR-126-3p/EGFR axis.

BACKGROUND: The prevalence of diabetic foot ulcers (DFUs) has caused serious harm to human health. To date, a highly effective treatment is lacking. Long noncoding RNA X-inactive specific transcript (lncRNA XIST) has been the subject of mounting research studies, all of which have found that it serves as a protective factor against certain diseases; however, its function in DFUs is not entirely understood. This study was performed to determine the importance of the lncRNA XIST in the pathogenesis and biological function of DFUs. METHODS: Diabetic ulcer skin from rats was analysed using haematoxylin-eosin (HE), Masson's trichrome, and immunohistochemistry (IHC) staining. The differences in the expression of genes and proteins were examined with real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Next, the interaction was verified with a dual luciferase gene reporter assay. In addition, CCK-8, Transwell, and wound healing assays were used to assess the proliferation and migration of HaCaT cells. RESULTS: The lncRNA XIST and epidermal growth factor receptor (EGFR) were downregulated, while microRNA-126-3p (miR-126-3p) was increased in diabetic ulcer rat skin tissues and high glucose-induced HaCaT cells. In addition, we found that the lncRNA XIST binds to miR-126-3p and that EGFR is directly targeted by miR­126­3p. Silencing XIST contributed to upregulated miR-126-3p expression, thus lowering EGFR levels and inhibiting the proliferative and migratory abilities of high glucose-treated HaCaT cells; however, the miR-126-3p inhibitor and overexpression of EGFR reversed this effect. CONCLUSION: Decreased lncRNA XIST expression inhibits the proliferative and migratory abilities of high glucose-induced HaCaT cells by modulating the miR-126-3p/EGFR axis, causing delayed wound healing.

Interaction between long noncoding RNA and microRNA in lung inflammatory diseases.

BACKGROUND: Non-coding RNAs (ncRNAs) are a group of RNAs that cannot synthesize proteins, but are critical in gene expression regulation. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), the two major family members, are intimately involved in controlling immune response, cell proliferation, apoptosis, differentiation and polarization, and cytokine secretion. Their interactions significantly influence lung inflammatory diseases and could be potential therapeutic targets. OBJECTIVES: The review aims to elucidate the role of ncRNAs, especially the interactions between lncRNA and miRNA in lung diseases, including acute and chronic lung inflammatory diseases, as well as lung cancer. And provide novel insights into disease mechanisms and potential therapeutic methods. METHODS: We conducted a comprehensive review of the latest studies on lncRNA and miRNA in lung inflammatory diseases. Our research involved searching through electronic databases like PubMed, Web of Science, and Scopus. RESULTS: We explain the fundamental characteristics and functions of miRNA and lncRNA, their potential interaction mechanisms, and summarize the newly explorations on the role of lncRNA and miRNA interactions in lung inflammatory diseases. CONCLUSIONS: Numerous lncRNAs and miRNAs have been found to partipicate in all stages of lung inflammatory diseases. While ncRNA-based therapies have been validated and developed, there remain challenges in developing more stable and effective drugs for clinical use.

A Bibliometric Analysis of the Trends and Evolution on Inhalation Injury Research.

Inhalation injury is a common complication in burn patients and is also a factor that can affect the multiple prognoses of burn patients. Attention to inhalation injury began early globally, but few articles have systematically analyzed its development. We employed bibliometric methods to analyze articles on inhalation injury published in 3 medical databases. A total of 3056 relevant articles on inhalation injury were included in our analysis and divided into 3 distinct periods based on Price's law. Notably, a slowdown in publication growth was observed in period III. The majority of these articles were authored by a small group of individuals, with a significant proportion of them being American scholars. In fact, nearly half of the articles were published by American researchers. Applying Bradford's Law, we identified 4 major output sources in the field, namely Burns, Journal of Burn Care & Research, Journal of Trauma, and Critical Care Medicine. Recent research has focused on the clinical risks and outcomes associated with inhalation injury, while basic research in this area has been relatively neglected over the last decade. In conclusion, the growth of publications on inhalation injuries has largely followed standard scientific growth patterns, with a small number of countries and established research groups contributing the majority of articles. However, the recent slowdown in scientific output is a cause for concern, and the lack of emphasis on basic research and clinical trials in this field raises questions about the foundation for widespread clinical management of inhalation injuries.

Association between Lipids, Apolipoproteins and Telomere Length: A Mendelian Randomization Study.

(1) Background: The relationship between lipids, apolipoproteins, and telomere length (TL) has been explored in previous studies; however, the causal relationship between the two remains unclear. This study aims to assess the causal relationship between lipids, apolipoproteins, and TL using the two-sample Mendelian randomization (MR) approach; (2) Methods: This study comprehensively employed both univariate MR (uvMR) and multivariate MR (mvMR) methods to genetically evaluate the associations between 21 exposures related to lipids and apolipoproteins and the outcome of TL. During the analysis process, we utilized various statistical methods, including Inverse Variance Weighting (IVW), Weighted Median, MR-Egger regression, MR-PRESSO, and outlier tests. Furthermore, to confirm the robustness of the results, we conducted several sensitivity analyses to explore potential heterogeneity; (3) Results: The uvMR analysis indicated that an increase in MUFA, MUFA/FA ratio, LDL-C, VLDL-C, total cholesterol, ApoB, and triglycerides (TG) was associated with an increase in TL. However, this relationship did not manifest in the mvMR analysis, suggesting that this association may be based on preliminary evidence; (4) Conclusions: MR analysis results suggest potential suggestive positive causal relationships between genetically predicted MUFA, MUFA/FA ratio, LDL-C, VLDL-C, total cholesterol, ApoB, and TG with TL.

Floquet Engineering the Exceptional Points in Parity-Time-Symmetric Magnonics.

Magnons serve as a testing ground for fundamental aspects of Hermitian and non-Hermitian wave mechanics and are of high relevance for information technology. This study presents setups for realizing spatiotemporally driven parity-time- (PT) symmetric magnonics based on coupled magnetic waveguides and magnonic crystals. A charge current in a metal layer with strong spin-orbit coupling sandwiched between two insulating magnetic waveguides leads to gain or loss in the magnon amplitude depending on the directions of the magnetization and the charge currents. When gain in one waveguide is balanced by loss in the other waveguide, a PT-symmetric system hosting non-Hermitian degeneracies [or exceptional points (EPs)] is realized. For ac current, multiple EPs appear for a certain gain-loss strength and mark the boundaries between the preserved PT-symmetry and the broken PT-symmetry phases. The number of islands of broken PT-symmetry phases and their extensions is tunable by the frequency and the strength of the spacer current. At EP and beyond, the induced and amplified magnetization oscillations are strong and self-sustained. In particular, these magnetization auto-oscillations in a broken PT-symmetry phase occur at low current densities and do not require further adjustments such as tilt angle between electric polarization and equilibrium magnetization direction in spin-torque oscillators, pointing to a new design of these oscillators and their utilization in computing and sensorics. It is also shown how the periodic gain-loss mechanism allows for the generation of high-frequency spin waves with low-frequency currents. For spatially periodic gain and loss acting on a magnonic crystal, magnon modes approaching each other at the Brillouin-zone boundaries are highly susceptible to PT symmetry, allowing for a wave-vector-resolved experimental realization at very low currents.

The Role and Mechanism of Metformin in Inflammatory Diseases.

Metformin is a classical drug used to treat type 2 diabetes. With the development of research on metformin, it has been found that metformin also has several advantages aside from its hypoglycemic effect, such as anti-inflammatory, anti-aging, anti-cancer, improving intestinal flora, and other effects. The prevention of inflammation is critical because chronic inflammation is associated with numerous diseases of considerable public health. Therefore, there has been growing interest in the role of metformin in treating various inflammatory conditions. However, the precise anti-inflammatory mechanisms of metformin were inconsistent in the reported studies. Thus, this review aims to summarize various currently known possible mechanisms of metformin involved in inflammatory diseases and provide references for the clinical application of metformin.

Effect of peripheral nerve block versus general anesthesia on the hemodynamics and prognosis of diabetic patients undergoing diabetic foot Surgery.

BACKGROUND: Diabetic foot ulcers (DFUs) represent a significant foot-related concern for patients with multiple co-morbidities, and surgical intervention is often employed. Notably, peripheral nerve block anesthesia (PNB) has emerged as a new approach for the surgical management of DFUs, providing sustained hemodynamic stability and superior postoperative pain control compared to general anesthesia (GEA). METHODS: The present study utilized a retrospective analysis of hospitalized patients who met the inclusion criteria for DFUs over a period of 7 years. Patients were categorized into two groups based on the type of anesthesia employed during the procedure: GEA or PNB. Extensive patient information was gathered and analyzed, such as demographics, intraoperative hemodynamic parameters, numeric rating scale (NRS) scores, and healing outcomes. The preliminary results assessed in this study were intraoperative hemodynamic stability and postoperative analgesic efficacy. RESULTS: During the study period, 117 patients received surgical therapy based on GEA, while 145 patients received PNB. Notably, the mean intraoperative blood pressure was significantly lower in the GEA group, and this difference remained statistically significant even after Bonferroni adjustment using linear mixed models. Additionally, the frequency of hypotensive episodes was higher in the GEA group (P < 0.05). Furthermore, the perioperative transfusion volume, overall intraoperative fluid input, and intraoperative bleeding volume were significantly more significant in the GEA group than in the PNB group. The postoperative pain NRS scores differed considerably between the two groups (Bonferroni corrected P < 0.01), with the GEA group exhibiting higher opioid consumption on the day of surgery and the first postoperative day when using patient-controlled intravenous analgesia (PCIA). Supplemental analgesic medication was more significant in the GEA group 24 h postoperatively. However, the two groups had no difference in hospital stay or treatment outcomes. There was no difference between the two groups regarding secondary surgery and amputation procedures. Although the 5-year mortality rate is 30.5%, no significant difference in mortality rates between the two groups was observed. CONCLUSIONS: Compared to GEA, PNB is a safe and effective alternative therapy for managing DFUs. Our findings suggest that PNB administration during surgical intervention for this condition results in more stable intraoperative hemodynamics and superior postoperative analgesic effects, despite no significant difference in overall treatment outcomes between the two groups. The two groups did not differ in re-surgery, amputation, or 5-year mortality.

Gut Microbiota and Respiratory Infections: Insights from Mendelian Randomization.

The role of the gut microbiota in modulating the risk of respiratory infections has garnered increasing attention. However, conventional clinical trials have faced challenges in establishing the precise relationship between the two. In this study, we conducted a Mendelian randomization analysis with single nucleotide polymorphisms employed as instrumental variables to assess the causal links between the gut microbiota and respiratory infections. Two categories of bacteria, family Lactobacillaceae and genus Family XIII AD3011, were causally associated with the occurrence of upper respiratory tract infections (URTIs). Four categories of gut microbiota existed that were causally associated with lower respiratory tract infections (LRTIs), with order Bacillales and genus Paraprevotella showing a positive association and genus Alistipes and genus Ruminococcaceae UCG009 showing a negative association. The metabolites and metabolic pathways only played a role in the development of LRTIs, with the metabolite deoxycholine acting negatively and menaquinol 8 biosynthesis acting positively. The identification of specific bacterial populations, metabolites, and pathways may provide new clues for mechanism research concerning therapeutic interventions for respiratory infections. Future research should focus on elucidating the potential mechanisms regulating the gut microbiota and developing effective strategies to reduce the incidence of respiratory infections. These findings have the potential to significantly improve global respiratory health.

Upregulation of circ_0080968 in diabetic foot ulcer inhibits wound healing via repressing the migration and promoting proliferation of keratinocytes.

BACKGROUND: Diabetic foot ulcer (DFU) is a serious chronic complication of diabetes mellitus whose pathogenesis remains unclear. Circular RNA (circRNA) refers to a group of covalently closed non-coding RNAs that are reported to be dysregulated in patients with DFU. However, the mechanism whereby dysregulation in circRNAs contributes to DFU remains unclear. In this study, we investigated the role of dysregulated circRNAs in DFU. MATERIALS AND METHODS: A gene expression dataset was downloaded from the Gene Expression Omnibus portal and analyzed by the limma package of R. The levels of 24 upregulated circRNAs were detected in two independent cohorts by RT-qPCR. Interactions between miRNAs and circRNAs were predicted through bioinformatics and confirmed using a dual luciferase assay. The circularity and subcellular localization of circRNA-080968 was examined by northern blotting after digestion with RNase-R and in situ hybridization. Cell migration and proliferation were examined using Transwell and MTT assays. The apoptotic cells were detected by flow cytometry. RESULTS: The level of circRNA-080968 was upregulated in DFU tissues compared to that of non-DFU samples and normal human wounds. CircRNA-080968 was mainly localized in the cytoplasm and its overexpression inhibited the migration and promoted the proliferation of keratinocytes. MiR-326 and miR-766-3p were identified to interact with and be negatively correlated with circRNA-080968 levels. Increased glucose upregulated circRNA-080968, and its overexpression accelerated the degradation of both miR-326 and miR-766-3p. Reduced levels of miR-326 and miR-766-3p upregulated the expression of several genes controlling cell adhesion and proliferation which are related to the pathogenesis of DFU. CONCLUSIONS: The upregulation of circRNA-080968 in DFU induced the degradation of miR-326 and miR-766-3p, which further repressed the migration and increased the proliferation of keratinocytes.

Application progress of single-cell sequencing technology in mesenchymal stem cells research.

Single-Cell Sequencing (SCS) technology plays an important role in the field of Mesenchymal Stem Cells (MSCs) research. This paper comprehensively describes the application of SCS technology in the field of MSCs research, including (1) SCS enables more precise MSCs characterization and biomarker definition. (2) SCS reveals the prevalent gene expression heterogeneity among different subclusters within MSCs, which contributes to a more comprehensive understanding of MSCs function and diversity in developmental, regenerative, and pathological contexts. (3) SCS provides insights into the dynamic transcriptional changes experienced by MSCs during differentiation and the complex web of important signaling pathways and regulatory factors controlling key processes within MSCs, including proliferation, differentiation and regulation, and interactions mechanisms. (4) The analytical methods underpinning SCS data are rapidly evolving and converging with the field of histological research to systematically deconstruct the functions and mechanisms of MSCs. This review provides new perspectives for unraveling the biological properties, heterogeneity, differentiation potential, biological functions, and clinical potential of MSCs at the single-cell level.

Metformin Improves Burn Wound Healing by Modulating Microenvironmental Fibroblasts and Macrophages.

Metformin, a biguanide, exerts different functions through various signaling pathways. In order to investigate the function and mechanism of metformin in burn wounds, we established burn rat models, subcutaneously injected metformin to treat the wounds, and observed the morphologies and the expression of collagen I, collagen III, fibronectin, and pro-inflammatory markers. In vitro experiments were performed to investigate the effects of metformin on the proliferation, migration, and collagen I synthesis of the mouse embryonic fibroblast (NIH 3T3) cell line and on the proliferation, apoptosis, and immune response of the mouse mononuclear macrophage (RAW 264.7) cell line. Finally, we studied the regulatory effects of metformin on a co-culture of RAW 264.7/NIH 3T3 cells. We found that 100 mM of metformin reduced dermal thickness, collagen I deposition, and mRNA expression of IL1ß and CCL2 in rat burn wounds. In vitro experiments revealed that metformin inhibited the proliferation of NIH 3T3 and RAW 264.7 cells. Metformin attenuated NIH 3T3 cell migration via the AMPK/mTOR pathway and attenuated collagen I synthesis through the TGFß1/Smad3 pathway. Metformin inhibited the apoptosis of RAW 264.7 cells induced by 10 µg/mL LPS. Metformin downregulated the mRNA expression of IL1ß and CCL2 in RAW 264.7 cells under 1 µg/mL LPS induction by inhibiting NF-κB p65 phosphorylation. In a RAW 264.7/NIH 3T3 co-culture, metformin attenuated collagen I synthesis in NIH 3T3 cells by inhibiting RAW 264.7 paracrine secretion of TGF-ß1. This provides new evidence related to the development of metformin for potentially improving burn wound healing.

Skyrmion Echo in a System of Interacting Skyrmions.

We consider helical rotation of skyrmions confined in the potentials formed by nanodisks. Based on numerical and analytical calculations we propose the skyrmion echo phenomenon. The physical mechanism of the skyrmion echo formation is also proposed. Because of the distortion of the lattice, impurities, or pinning effect, confined skyrmions experience slightly different local fields, which leads to dephasing of the initial signal. The interaction between skyrmions also can contribute to the dephasing process. However, switching the magnetization direction in the nanodiscs (e.g., by spin transfer torque) also switches the helical rotation of the skyrmions from clockwise to anticlockwise (or vice versa), and this restores the initial signal (which is the essence of skyrmion echo).

The expression profile of lung long non-coding RNAs and mRNAs in a mouse model of smoke inhalation injury.

To study the potential expression of lung long non-coding RNAs (lncRNAs) and mRNAs during smoke inhalation injury (SII), using a SII mouse model that we created in our previous work. Microarray was used to investigate the lncRNAs and mRNAs profiles. A bioinformatics analysis was performed. Changes in the top 10 down-regulated and 10 up-regulated lncRNAs were validated using Quantitative Reverse Transcription-PCR (RT-qPCR). The acute lung injury (ALI) mouse model was successfully induced by smoke inhalation, as confirmed by the aberrantly modified cell numbers of red blood cells and neutrophils counts, increased levels of TNF-α, IL-1ß, Bax, caspase-7, caspase-3, and decreased Bcl-2 content in lung tissues. When compared to the control mice, 577 lncRNAs and 517 mRNAs were found to be aberrantly expressed in the SII mice. According to the Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, the altered mRNAs were enriched in acute-phase response, oxidoreductase activity, oxidation-reduction process, glutathione metabolism, the wnt signaling pathway, and ferroptosis. A lncRNA-related competitive endogenous RNA (ceRNA) network, including 383 lncRNAs, 318 MicroRNAs (miRNAs), and 421 mRNAs specific to SII, was established. The changes in NONMMUT026843.2, NONMMUT065071.2, ENSMUST00000235858.1, NONMMUT131395.1, NONMMUT122516.1, NONMMUT057916.2, and NONMMUT013388.2 in the lung matched the microarray results. Our findings help to provide a more comprehensive understanding of the pathogenesis of SII as well as new insights into potential therapeutic targets.

Bi-layered nanofibrous membrane with osteogenic and antibacterial functions for periodontal tissue regeneration.

Guided tissue regeneration (GTR) membranes have great potential to promote periodontal tissue regeneration and reestablishment. However, the regeneration potential and microbial infection resistance of current GTR membranes still need to be improved. Here, a bi-layered nanofibrous membrane on the basis of poly (lactic-co-glycolic acid) (PLGA)/gelatin with osteogenic and antibacterial functions was fabricated for periodontal tissue regeneration. The antimicrobial layer (AL) of the bi-layered nanofibrous membrane was composed of nanofibrous PLGA/gelatin nanofibers loaded with nano-silver (nAg), while the osteoconductive layer (OL) of the nanofibrous membrane consisted of PLGA/gelatin nanofibers loaded with nano-hydroxyapatite (nHA). The bi-layered nanofibrous membrane was examined by scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectrometry (XPS) and X-ray diffractometry (XRD). The results showed that nHA and nAg particles were well evenly loaded or embedded in PLGA/gelatin nanofibers. The cell culture experiments suggested that the bi-layered nanofibrous membrane possessed good cytocompatibility and the OL of the bi-layered nanofibrous membrane possessed an enhanced osteogenic capacity for human osteoblast-like cells (MG63), which was verified by the good cell viability and the increased alkaline phosphatase (ALP) activity, respectively. The results of in vitro antimicrobial study displayed that the AL of the bi-layered nanofibrous membrane possessed an effective antibacterial capability. In conclusion, the prepared bi-layered nanofibrous membrane with osteogenic and antibacterial functions may have great potential for periodontal tissue regeneration and reestablishment.[Formula: see text].

Tandem mass tag-based serum proteomic profiling revealed diabetic foot ulcer pathogenesis and potential therapeutic targets.

Diabetic foot ulcer (DFU), one of the most serious complications of diabetes mellitus, is associated with a high amputation rate and decreased life quality. The impact of blood serum proteins on the occurrence and development of DFU has attracted a lot of interest. In this study, we aimed to define and compare the serum proteome of patients with DFU and healthy control (HC) to provide new insights into DFU pathogenesis. DFU patients and age- and sex-matched HCs were enrolled in this study (n = 54). We screened alterations in blood serum proteins from DFU patients and HC using a tandem mass tag (TMT) method based on liquid chromatography-mass spectrometry (LC-MS/MS) quantitative proteomics, and the differentially expressed proteins (DEPs) were further validated by parallel reaction monitoring (PRM) and enzyme-linked immunosorbent assay (ELISA). A total of 173 DEPs (100 up-regulated and 73 down-regulated) were identified between the DFU and HC groups (P < 0.05). Proteomic and bioinformatics analyses indicated that the proteins in the DFU group were mainly related to extracellular matrix (ECM)-receptor interaction and complement and coagulation cascades. The up-regulated DEPs were further verified by PRM and ELISA. LRG1, CD5L, CRP, IGHA1, and LBP were proved upregulated in DFU and these proteins are mainly related to immune response and complement activation. Our findings help to provide a more comprehensive understanding of the pathogenesis of DFU and new insight into potential therapeutic targets.