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Intrauterine adhesion (IUA) is a common complication of surgical manipulation of the uterine cavity such as abortion. The pathology of IUA is characterized by fibrosis, but the pathogenesis is not fully understood. The function of Apelin-13 in IUA and related mechanisms were investigated in this study. The IUA rat model was established. The pathological changes and fibrosis degree of rat uterine tissues were detected by HE and Masson staining after intraperitoneal injection of Apelin-13. Epithelial-mesenchymal transition (EMT) of endometrial epithelial cells and endothelial-mesenchymal transition (EnMT) of vein endothelial cells were induced by TGF-ß1. Tube-forming assay using HUVEC was implemented to detect the effect of Apelin-13 upon angiogenesis. IHC staining, immunofluorescence staining, and Western blot were conducted to detect the expression levels of EMT markers, angiogenesis, and key proteins of the TGF-ß1/Smad signaling. Apelin-13 significantly alleviated IUA and fibrosis, and increased endometrial thickness and gland number in IUA rats. In addition, Apelin-13 significantly reversed EMT and EnMT induced by IUA modeling and TGF-ß1, promoted the tube-forming ability of HUVEC, and up-regulated the expression of angiogenesis-related proteins. Mechanistically, Apelin-13 significantly suppressed smad2/3 phosphorylation and inhibited the TGF-ß1/Smad signaling via its receptor APJ. Apelin-13 might alleviate IUA via repressing the TGF-ß1/Smad pathway and is expected to be a potent therapeutic option for the clinical treatment of IUA.
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Roxarsone (ROX) is the main form of arsenic pollution in the world, and developing effective methods for its elimination is beneficial to human health and the ecological environment. Herein, we report glutaraldehyde cross-linked chitosan-encapsulated CoCe-LDH (layered double hydroxides) as an outstanding catalyst for the advanced oxidation of ROX and the efficient adsorption of inorganic arsenic. 100% of ROX and more than 98.5% of As(III)/As(V) were eliminated, and over 99.3% of remaining inorganic arsenic was oxidized to low-toxicity As(V) in the peroxymonosulfate (PMS) activation system, and some specific properties of LDH are considered the main reasons. The hierarchical anion exchange has been confirmed to be beneficial for constructing a high-concentration PMS interlayer microenvironment. The unique reverse electron transfer process induced 100% selective production of singlet oxygen. This work not only develops an advanced ROX removal method but also provides a new understanding of the LDH-based advanced oxidation process.
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The bradykinin B2 receptor (B2R) is overexpressed in a wide variety of tumors and is a well-defined target for tumor imaging and therapy. The hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) scanner is considered a noninvasive and advanced instrument for precise tumor imaging. In this work, we developed a novel B2R-targeting radiotracer, 68Ga-DOTA-icatibant, for quantifying B2R expression. 68Ga-DOTA-icatibant showed high stability, fast clearance and specific binding to B2R. PET/MR imaging revealed excellent tumor accumulation, and the uptake in tumors could be blocked by DOTA-icatibant. Icatibant-mediated anti-B2R therapy downregulated B2R expression in tumor cells and inhibited the growth of HepG2 tumors, and the decrease in tumor uptake was monitored by timely PET/MR imaging. Hematoxylin and eosin (H&E) and immunohistochemical staining results further demonstrated that the efficacy of anti-B2R could be accurately monitored with the developed PET/MR imaging radiotracer. 68Ga-DOTA-icatibant can be utilized to noninvasively determine B2R expression and dynamically and sensitively monitor the efficacy of anti-B2R therapy.
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BACKGROUND: RxChange messages improve patient medication management by enhancing pharmacist-prescriber communication, but their usage patterns in the United States are not well-documented. OBJECTIVE: To determine intervention characteristics by pharmacists and prescribers using RxChange messages. METHODS: A retrospective analysis of electronic prescription and RxChange messages from 2022 and 2023, using data from Surescripts, LLC, was conducted. This included NewRx messages and RxChange Responses, categorized by seven RxChange use cases and Anatomical Therapeutic Chemical level 4 medication classes. Descriptive statistics and non-parametric tests were used for statistical analysis. RESULTS: The study analyzed 1,361,528 RxChange messages. Therapeutic interchange was the predominant use case (76.14%). Direct approvals accounted for 10.44% of requests, approvals with changes for 42.55%, and denials for 47.01%. Script clarification had the highest approval rate (64.21%), while prior authorization faced the most frequent denials (73.38%). The top denial reason was "Request addressed through alternate methods such as phone or fax" (41.50%). The most frequent drug classes observed in the data were selective beta-2 adrenoreceptor agonists, extended-spectrum penicillins, selective serotonin reuptake inhibitors, and glucagon-like peptide 1 analogues. Time from new e-prescription issuance to RxChange request submission was longer than from request to response, with a significant statistical difference (median 1.57 vs 0.27 days, p-value < 0.05). CONCLUSION: This study highlights interventions pharmacists make using RxChange with electronic prescriptions to improve patient care and medication safety. It underlined the need for improved RxChange message content and data on the effectiveness of RxChange messages in improving medication use.
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Remodeling the endogenous regenerative microenvironment in wounds is crucial for achieving scarless, functional tissue regeneration, especially the functional recovery of skin appendages such as sweat glands in burn patients. However, current approaches mostly rely on the use of exogenous materials or chemicals to stimulate cell proliferation and migration, while the remodeling of a pro-regenerative microenvironment remains challenging. Herein, we developed a flexible sono-piezo patch (fSPP) that aims to create an endogenous regenerative microenvironment to promote the repair of sweat glands in burn wounds. This patch, composed of multifunctional fibers with embedded piezoelectric nanoparticles, utilized low-intensity pulsed ultrasound (LIPUS) to activate electrical stimulation of the target tissue, resulting in enhanced pro-regenerative behaviors of niche tissues and cells, including peripheral nerves, fibroblasts, and vasculatures. We further demonstrated the effective wound healing and regeneration of functional sweat glands in burn injuries solely through such physical stimulation. This noninvasive and drug-free therapeutic approach holds significant potential for the clinical treatment of burn injuries.
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AIMS: There is limited real-world data on cyclosporin A (CsA)-induced liver injury (CILI). This study aims to investigate the incidence, clinical classification and risk factors of CILI, thereby providing evidence to inform the treatment of CILI. METHODS: Inpatients receiving haematopoietic stem cell transplantation (HSCT) and treated with CsA were included. Patient information was collected to assess suspicious CILI by the Roussel Uclaf causality assessment method (RUCAM) scale. We evaluated the pattern and severity of CILI. The independent risk factors of CILI were identified by multivariable logistic regression. RESULTS: A total of 216 allogeneic HSCT (allo-HSCT) recipients were included in this study. The incidence of CILI was 15.3% (95% confidence interval [CI]: 10.4%-20.1%). Among these cases, 84.8% displayed a hepatocellular pattern, and 90.9% of CILI was of mild severity. Baseline alanine aminotransferase (ALT) level (OR = 1.030, 95% CI: 1.008-1.053, P = .008) and trough concentration level of CsA (OR = 1.007, 95% CI: 1.002-1.012, P = .009) were identified as independent risk factors for CILI. CONCLUSIONS: The incidence of CILI in allo-HSCT recipients is notably high. Recipients with elevated baseline ALT levels and higher exposure to CsA are more susceptible to developing CILI.
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The association between post-traumatic growth (PTG) and cognitive empathy is well documented; however, few studies have tested the causal pathways explaining this association in school bullying victims' later recovery and growth in the long term. This study used a longitudinal design to examine the reciprocal relations between cognitive empathy and post-traumatic growth (PTG) in school bullying victims. We screened 725 adolescents who had experienced school bullying as our final subjects out of the 2173 adolescents we surveyed over three periods (November 2019, 2020, and 2021). Controlling for gender, cross-lagged analysis revealed that both cognitive empathy at T1 and T2 predicted adolescents' later PTG at T2 (γ = 0.096, p < 0.05) and T3 (γ = 0.085, p < 0.05), respectively, but the predictive effect across time points from PTG to cognitive empathy was not significant. The results delineated a specific directionality in the relation between cognitive empathy and PTG and suggested an important role of cognitive empathy in fostering school bullying victims' later recovery and growth. These findings contribute to ongoing research into ways researchers and educators may help and support school bullying victims.
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BACKGROUND: Early angiogenesis provides nutrient supply for bone tissue repair, and insufficient angiogenesis will lead tissue engineering failure. Lanthanide metal nanoparticles (LM NPs) are the preferred materials for tissue engineering and can effectively promote angiogenesis. Holmium oxide nanoparticles (HNPs) are LM NPs with the function of bone tissue "tracking" labelling. Preliminary studies have shown that HNPs has potential of promote angiogenesis, but the specific role and mechanism remain unclear. This limits the biological application of HNPs. RESULTS: In this study, we confirmed that HNPs promoted early vessel formation, especially that of H-type vessels in vivo, thereby accelerating bone tissue repair. Moreover, HNPs promoted angiogenesis by increasing cell migration, which was mediated by filopodia extension in vitro. At the molecular level, HNPs interact with the membrane protein EphrinB2 in human umbilical vein endothelial cells (HUVECs), and phosphorylated EphrinB2 can bind and activate VAV2, which is an activator of the filopodia regulatory protein CDC42. When these three molecules were inhibited separately, angiogenesis was reduced. CONCLUSION: Overall, our study confirmed that HNPs increased cell migration to promote angiogenesis for the first time, which is beneficial for bone repair. The EphrinB2/VAV2/CDC42 signalling pathway regulates cell migration, which is an important target of angiogenesis. Thus, HNPs are a new candidate biomaterial for tissue engineering, providing new insights into their biological application.
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Materiales Biocompatibles , Movimiento Celular , Holmio , Células Endoteliales de la Vena Umbilical Humana , Neovascularización Fisiológica , Ingeniería de Tejidos , Ingeniería de Tejidos/métodos , Humanos , Animales , Holmio/química , Movimiento Celular/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Ratones , Nanopartículas del Metal/química , Óxidos/química , Óxidos/farmacología , Efrina-B2/metabolismo , Transducción de Señal/efectos de los fármacos , Masculino , Nanopartículas/químicaRESUMEN
OBJECTIVES: Mycophenolic acid (MPA) is recommended for lupus nephritis (LN) treatment, but with large inter-individual variability in pharmacokinetics (PK). The aim of this study is to reveal the relationship between MPA exposure and disease response and adverse drug reactions in pediatric LN patients. METHOD: This was a population-based observational cohort study. A total of 86 pediatric LN patients treated with mycophenolate mofetil (MMF) for induction therapy were enrolled. The area-under the concentration-time curve (AUC) was calculated using MPA concentrations according to a limited sampling strategy. Receiver operating characteristic analysis was performed to assess the MPA-AUC threshold values. The cumulative incidence of renal remission and inactive SLE over time was evaluated by Kaplan-Meier's analysis. RESULTS: MPA-AUC was identified as an independent factor associated with renal remission and lupus activity at 6 and 12 months after MMF treatment, and the improved renal remission rates was correlated with higher MPA-AUC, with thresholds of 29.81 and 30.63 µg·h·mL - 1 at 6 and 12 months, respectively. Furthermore, the thresholds for maintaining the hypoactive state of LN were 30.96 and 31.19 µg·h·mL - 1at 6 months and 12 months, respectively. Patients reaching target thresholds for MPA-AUC achieved renal response or stable disease earlier. In addition, the MPA-AUC threshold for decreasing MMF-related adverse reactions was 50.80 µg·h·mL - 1. CONCLUSION: The initial and long-term treatments of pediatric LN patients with MMF should be individualized according to the MPA-AUC, and the recommended MPA exposure is 31.19-50.80 µg·h·mL - 1.
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Background: Ticagrelor is a commonly used antiplatelet agent, but due to the stringent criteria for trial population inclusion and the limited sample size, its safety profile has not been fully elucidated. Method: We utilized OpenVigil 2.1 to query the FDA Adverse Event Reporting System database and retrieved reports by the generic name "ticagrelor" published between 1 October 2010 and 31 March 2023. Adverse drug events (ADEs) were classified and described according to the preferred terms and system organ classes in the Medical Dictionary of Regulatory Activity. Proportional reporting ratio (PRR), reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) were used to detect signals. Results: The number of ADE reports with ticagrelor as the primary suspect drug was 12,909. The top three ADEs were dyspnea [1824 reports, ROR 7.34, PRR 6.45, information component (IC) 2.68], chest pain (458 reports, ROR 5.43, PRR 5.27, IC 2.39), and vascular stent thrombosis (406 reports, ROR 409.53, PRR 396.68, IC 8.02). The highest ROR, 630.24, was found for "vascular stent occlusion". Cardiac arrest (137 reports, ROR 3.41, PRR 3.39, IC 1.75), atrial fibrillation (99 reports, ROR 2.05, PRR 2.04, IC 1.03), asphyxia (101 reports, ROR 23.60, PRR 23.43, IC 4.51), and rhabdomyolysis (57 reports, ROR 2.75, PRR 2.75, IC 1.45) were suspected new adverse events of ticagrelor. Conclusion: The FAERS database produced potential signals associated with ticagrelor that have not been recorded in the package inserts, such as cardiac arrest, atrial fibrillation, asphyxia, and rhabdomyolysis. Further clinical surveillance is needed to quantify and validate potential hazards associated with ticagrelor-related adverse events.
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SUMMARY: Taurine (Tau) has been found to inhibit triple-negative breast cancer (TNBC) invasion and metastasis. However, its effect on tumor-promoting macrophages and tumor suppressor macrophages in breast cancer progression remains unknown. In this study, we investigated the effects of Tau on macrophage polarization and its role in TNBC cell growth, invasion, and metastasis. We induced human THP-1 monocytes to differentiate into M2 macrophages through exogenous addition of interleukin-4. We used the TNBC cell lines MDA-MB-231 and BT-549 cultured in a conditioned medium from M2 macrophages to investigate the effect of Tau on tumor growth and invasion. We analyzed macrophage subset distribution, M1 and M2 macrophage-associated markers, and mRNA expression by quantitative polymerase chain reaction. We also detected the PTEN-PI3K/Akt/mTOR signaling pathway that mediates M1 macrophage to suppress tumor invasion using western blotting. Our results showed that Tau inhibits breast cancer metastasis to the lungs in vivo and cell invasion by altering the polarization of tumor-associated macrophage in vitro. In addition, Tau can up-regulate PTEN expression, suppress the PI3K-Akt signaling pathway, and promote the M1 polarization of macrophages, which ultimately inhibits the metastasis of TNBC cells. Our findings suggest that Tau inhibits the activation of the PI3K-Akt-mTOR signaling pathway by up-regulating PTEN, promotes the proportion of M1 macrophages in tumor-associated macrophage, and suppresses the invasion and metastasis of TNBC. This provides a potential therapeutic approach to influence cancer progression and metastasis.
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Photocatalytic hydrogen production is a prevalent method for hydrogen synthesis. However, high recombination rate of photogenerated carriers and high activation energy barrier of H remain persistent challenge. Here, the two-step hydrothermal method is utilized to prepare dual S-defect mediated catalyst molybdenum sulfide/zinc indium sulfide (MSv/ZISv), which has high hydrogen production rate of 8.83 mmol g-1h-1 under simulated sunlight. The achieved rate is 21.91 times higher than pure ZnIn2S4 substrate. Defects in ZIS within MSv/ZISv modify the primitive electronic structure by creating defect state that retaining good reducing power, leading to the rapid separation of electron-hole pairs and the generation of additional photogenerated carriers. The internal electric field further enhances the migration toward to cocatalyst. Simultaneously, the defects introduced on the MoS2 cause electron rearrangement, leading to electron clustering on both S vacancies and edge S. Thereby MSv/ZISv exhibits the lowest activation energy barrier and |ΔGH*|. This work explores the division of synergies between different types of S defects, providing new insights into the coupling of defect engineering.
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Osteoarthritis (OA) is a degenerative disease characterised by articular cartilage destruction, and its complex aetiology contributes to suboptimal clinical treatment outcomes. A close association exists between glucose metabolism dysregulation and OA pathogenesis. Owing to the unique environment of low oxygen and glucose concentrations, chondrocytes rely heavily on their glycolytic capacity, exhibiting distinct spatiotemporal differences. However, under pathological stimulation, chondrocytes undergo excessive glycolytic activity while mitochondrial respiration and other branches of glucose metabolism are compromised. This metabolic change induces cartilage degeneration by reprogramming the inflammatory responses. Sirtuins, a highly conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, regulate glucose metabolism in response to energy fluctuations in different cellular compartmentsï¼alleviating metabolic stress. SIRT1, the most extensively studied sirtuin, participates in maintaining glucose homeostasis in almost all key metabolic tissues. While actively contributing to the OA progression and displaying diverse biological effects in cartilage protection, SIRT1's role in regulating glucose metabolism in chondrocytes has not received sufficient attention. This review focuses on discussing the beneficial role of SIRT1 in OA progression from a metabolic regulation perspective based on elucidating the primary characteristics of chondrocyte glucose metabolism. We also summarise the potential mechanisms and therapeutic strategies targeting SIRT1 in chondrocytes to guide clinical practice and explore novel therapeutic directions.
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Glucosa , Osteoartritis , Sirtuina 1 , Animales , Humanos , Cartílago Articular/patología , Glucosa/metabolismo , Osteoartritis/metabolismo , Sirtuina 1/metabolismo , Sirtuinas/metabolismoRESUMEN
Shape memory polymers (SMPs), which initiate shape transformation in response to environmental stimuli, have attracted significant attention in both academic research and technological innovation. The combination of functional nanomaterials and SMPs has led to the emergence of a variety of shape memory polymeric nanocomposites (SMPNs) with multifunctional properties. This has injected new vitality and vigor into fields such as tissue engineering, biomedicine, optical sensing, aerospace and mechanical engineering. In this review article, we present a brief introduction to the fundamentals of SMPs and SMPNs, followed by a discussion of the recent advances in their multifunctional applications in biomedical manufacturing, drug delivery devices, mechanical sensing, micro-engines, etc. The opportunities and challenges in the future development of SMPs are also discussed.
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Nanocompuestos , Polímeros , Ingeniería de Tejidos , Sistemas de Liberación de MedicamentosRESUMEN
Sodium-ion batteries (SIBs) are considered as an alternative to and even replacement of lithium-ion batteries in the near future in order to address the energy crisis and scarcity of lithium resources due to the wide distribution and abundance of sodium resources on the earth. The exploration and development of high-performance anode materials are critical to the practical applications of advanced SIBs. Among various anode materials, bimetallic oxides (BMOs) have attracted special research attention because of their abundance, easy access, rich redox reactions, enhanced capacity and satisfactory cycling stability. Although many BMO anode materials have been reported as anode materials in SIBs, very limited studies summarized the progress and prospect of BMOs in practical applications of SIBs. In this review, recent progress and challenges of BMO anode materials for SIBs have been comprehensively summarized and discussed. First, the preparation methods and sodium storage mechanisms of BMOs are discussed. Then, the challenges, optimization strategies, and sodium storage performance of BMO anode materials have been reviewed and summarized. Finally, the prospects and future research directions of BMOs in SIBs have been proposed. This review aims to provide insight into the efficient design and optimization of BMO anode materials for high-performance SIBs.
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BACKGROUND: Oral inflammatory diseases are localized infectious diseases primarily caused by oral pathogens with the potential for serious systemic complications. However, publicly available datasets for these diseases are underutilized. To address this issue, a web tool called OralExplorer was developed. This tool integrates the available data and provides comprehensive online bioinformatic analysis. METHODS: Human oral inflammatory disease-related datasets were obtained from the GEO database and normalized using a standardized process. Transcriptome data were then subjected to differential gene expression analysis, immune infiltration analysis, correlation analysis, pathway enrichment analysis, and visualization. The single-cell sequencing data was visualized as cluster plot, feature plot, and heatmaps. The web platform was primarily built using Shiny. The biomarkers identified in OralExplorer were validated using local clinical samples through qPCR and IHC. RESULTS: A total of 35 human oral inflammatory disease-related datasets, covering 6 main disease types and 901 samples, were included in the study to identify potential molecular signatures of the mechanisms of oral diseases. OralExplorer consists of 5 main analysis modules (differential gene expression analysis, immune infiltration analysis, correlation analysis, pathway enrichment analysis and single-cell analysis), with multiple visualization options. The platform offers a simple and intuitive interface, high-quality images for visualization, and detailed analysis results tables for easy access by users. Six markers (IL1ß, SRGN, CXCR1, FGR, ARHGEF2, and PTAFR) were identified by OralExplorer. qPCR- and IHC-based experimental validation showed significantly higher levels of these genes in the periodontitis group. CONCLUSIONS: OralExplorer is a comprehensive analytical platform for oral inflammatory diseases. It allows users to interactively explore the molecular mechanisms underlying the action and regression of these diseases. It also aids dental researchers in unlocking the potential value of transcriptomics data related to oral diseases. OralExplorer can be accessed at https://smuonco.shinyapps.io/OralExplorer/ (Alternate URL: http://robinl-lab.com/OralExplorer ).
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Biología Computacional , Programas Informáticos , Humanos , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos , Transcriptoma/genética , Bases de Datos Factuales , Factores de Intercambio de Guanina Nucleótido RhoRESUMEN
In recent years, Artocarpus heterophyllus Lam. (jackfruit) polysaccharides (namely JFP-Ps) have attracted much attention due to their multiple biological activities. This study aimed to explore the protective effects and the underlying mechanisms of JFP-Ps on cyclophosphamide (Cp)-induced liver damage. The protective effect of JFP-Ps was evaluated using HE staining, antioxidant testing, enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (RT-qPCR), Western blot and ultra-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) metabolomics analysis. The results showed that Cp caused pathological liver damage, activated oxidative stress and downregulated cytokine expression, while JFP-Ps treatment was found to exert antioxidant effects and play immune regulatory roles through mitogen-activated protein kinase/nuclear factor-κB (MAPK/NF-κB) related inflammation and cell apoptosis pathways to protect the Cp-induced liver injury. Metabolomic results showed that the liver-protective effects of JFP-Ps were mainly related to aminoacyl transfer ribonucleic acid (tRNA) biosynthesis, sphingolipid metabolism, purine metabolism and the citrate cycle. These results indicate that JFP-Ps have great potential application in alleviating liver injury.
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Artocarpus , Animales , Ratones , Espectrometría de Masas en Tándem , Hígado , Polisacáridos/farmacología , Antioxidantes/farmacología , Ciclofosfamida/toxicidadRESUMEN
Developing high-performance microwave absorption (MA) materials becomes an urgent concern in the field of electromagnetic protection. Constructing porous framework is an efficient approach to MA owing to the abilities of adjusting impedance matching and providing more reflection and scattering paths for electromagnetic waves. Herein, a cellulose nanofibril (CNF)/honeycomb-like carbon-shell encapsulated FeCoNi@C/carbon nanotube (CNT) composite aerogel was fabricated via a facile freeze-drying method. The super-lightweight composites showed a distinctive gradient structure for reflection and scattering inside aerogel pores, micrometer small pores, and nano-fillers on the pore walls. The composite aerogel showed an ideal minimum reflection loss (RLmin) of -43.6 dB and remarkable adjustable effective absorption bandwidth (EAB) of 12.18 GHz due to good impedance matching, unique gradient porous structure, and synergies of multiple loss mechanisms. Therefore, this work will provide a viable strategy to improve the MA capability of absorbers by taking full advantage of constructing gradient reflection and scattering porous structure.
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Elliptical Gaussian beams generated by laser diodes (LDs) often exhibit asymmetrical divergence angle distribution, which limits their practical applications. In this study, we propose what we believe is a novel approach to shape and collimate the elliptical output beam from a LD. The design process involves the construction of two freeform reflective surfaces on a reference circle using a three-dimensional point-by-point iterative method, based on the law of conservation of energy, the vector reflection theory, and Fermat's principle. The output beam's maximum divergence angle is effectively compressed to 3.1579 mrad. The design is compact with a folded optical path and antenna size of 368.8c m 3. This paper presents a comprehensive design and optimization process, along with an in-depth analysis of the system's performance, thereby offering novel insights for emerging optical design practitioners.
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Periodontitis, an inflammatory disease, can cause significant damage to the oral tissues which support the teeth. During the early development of periodontitis, periodontal ligament fibroblasts (PDLFs) undergo metabolic reprogramming regulated by hypoxia-inducible factor 1α (HIF-1α), which is strongly linked to the progression of inflammation. However, the precise mechanisms by which PDLFs regulate HIF-1α and its associated metabolic reprogramming during early inflammation remain unclear. This study illustrated that brief and low-dose exposure to Escherichia coli (E. coli) lipopolysaccharide (LPS) can serve as a non-hypoxic stimulus, effectively replicating early periodontal inflammatory reactions. This is evidenced by the upregulation of HIF-1α expression and the activation of HIF-1α-mediated crucial glycolytic enzymes, namely lactate dehydrogenase a, pyruvate kinase, and hexokinase 2, concomitant with an augmentation in the inflammatory response within PDLFs. We observed that the effects mentioned and their impact on macrophage polarization were notably attenuated when intracellular and extracellular stores of Ca2+ were depleted using BAPTA-AM and Ca2+-free medium, respectively. Mechanistically, our findings demonstrated that the transcriptional process of HIF-1α is regulated by Ca2+ during E. coli LPS stimulation, mediated through the signal transducer and activator of transcription 3 (STAT3) pathway. Additionally, we observed that the stabilization of intracellular HIF-1α proteins occurs via the endothelin (ET)-1-endothelin A receptor pathway, independent of hypoxia. Taken together, our research outcomes underscore the pivotal involvement of Ca2+ in the onset of early periodontitis by modulating HIF-1α and glycolysis, thereby presenting novel avenues for early therapeutic interventions.