Search Results (333,967)

Research into auxetic foams—materials with a negative Poisson’s ratio— is expanding, yet their integration into orthotics for diverse neuropathic conditions remains largely unexplored. This pilot study evaluates the feasibility of fabricating custom auxetic foam insoles and characterizing vertical ground reaction force (vGRF) trends across a heterogeneous cohort. In collaboration with the NASA/Marshall Space Flight Center, six participants, including five representing varied neuropathic etiologies and one healthy control, performed randomized walking trials under three conditions: barefoot, over-the-counter (OTC) insoles, and custom auxetic prototypes. The healthy control was retained in the cohort-level analysis to preserve methodological symmetry across experimental conditions. To maintain physical rigor, vGRF data were mass-normalized (N/kg). A Friedman test (n = 6) evaluated global differences, supplemented by a dual-bootstrap analysis (1000 resamples) to quantify effect magnitudes (r) and numerical uncertainty. Although the Friedman test revealed no statistically significant global differences (Q = 0.333, df = 2, p = 0.846), a descriptively large effect size (r = 0.58) was observed for the auxetic material versus barefoot walking. However, wide 95% bootstrap confidence intervals prevent population-level inference, reinforcing the exploratory nature of these findings. Subject-specific observations showed descriptive differences in vGRF in three participants (0.17 to 1.18 N/kg), while increases in others occurred alongside confounding factors such as self-selected walking velocity. This work demonstrates the mechanical application of auxetic insole prototypes, providing a foundational rationale for future trials utilizing standardized walking velocity to isolate material performance. Full article

Objectives: Seawater-immersed burn wounds are highly susceptible to contamination, persistent inflammation, oxidative stress, and delayed healing, while current irrigation solutions remain suboptimal for such acute injuries. This study aimed to evaluate the therapeutic efficacy and underlying mechanisms of plasma-activated water (PAW) as a novel irrigation strategy for these complex wounds. Methods: The antibacterial efficacy of PAW against marine pathogens was first evaluated in vitro. Subsequently, a rat model of seawater-immersed burn injury was established in male Sprague-Dawley (SD) rats to assess the therapeutic effects of PAW irrigation on wound healing, infection control, and underlying biological mechanisms. Results: In vitro, PAW significantly eradicated two major marine pathogens, Vibrio vulnificus and Vibrio parahaemolyticus (p < 0.001). In vivo, PAW markedly accelerated wound closure, achieving complete healing in 23.60 ± 6.50 days vs. 38.67 ± 2.08 days (Normal saline group) and 58.33 ± 10.97 days (Model group) (p < 0.05). PAW significantly reduced bacterial burden, modulated inflammation by decreasing interleukin-6 and increasing interleukin-10, and alleviated oxidative stress, as evidenced by reduced malondialdehyde levels and enhanced superoxide dismutase activity. Histological evaluation demonstrated enhanced re-epithelialization, collagen deposition, and increased expression of vascular endothelial growth factor and platelet endothelial cell adhesion molecule-1. No adverse effects on serum biochemistry or major organ histopathology were observed. Conclusions: PAW may be a safe, promising, and multifunctional irrigation strategy that promotes seawater-immersed burn healing through coordinated antibacterial, anti-inflammatory, antioxidant, and pro-angiogenic effects, highlighting its strong potential for clinical translation. Full article

Background: Long noncoding RNAs (lncRNAs) have emerged as critical regulators of hepatic metabolism and disease progression. The hepatocyte nuclear factor 1 alpha antisense 1 (HNF1A-AS1) lncRNA modulates liver-specific transcription factors; however, its physiological role in diet-dependent lipid homeostasis remains poorly defined. Methods: In this study, we investigated the mouse ortholog, Hnf1a opposite strand 1 (Hnf1aos1), using AAV-mediated knockdown in C57BL/6J mice fed either a chow diet (10% kcal from fat) or a high-fat diet (HFD; 60% kcal from fat) for 12 weeks. Metabolic phenotyping included hepatic lipid quantification, histological analysis, serum biochemistry, and quantitative gene expression profiling. Results: Loss of Hnf1aos1 produced distinct, diet-dependent alterations in hepatic lipid handling. Under chow conditions, knockdown mice exhibited selective hepatic cholesterol accumulation (6.10 ± 2.9 mg/g tissue vs. 3.51 ± 1.1 mg/g in controls), accompanied by dysregulation of cholesterol clearance pathways. In contrast, under HFD conditions, knockdown precipitated severe macrovesicular degeneration, with hepatic triglyceride levels approximately doubled relative to HFD-fed controls (51.72 ± 19.8 mg/g vs. 26.34 ± 11.9 mg/g) and a numerically elevated triglyceride-to-cholesterol ratio (TG:TC ≈ 6.1:1; p = 0.0621, trend). Chow/Kd mice gained significantly less weight than chow-fed controls, whereas HFD/Kd mice exhibited weight gain comparable to HFD controls despite severe hepatic steatosis. This paradoxical phenotype suggests impaired metabolic feedback at the post-transcriptional level, in which compensatory upregulation of Hnf1a mRNA is insufficient to suppress lipid-associated genes such as Cd36, despite profound lipid overload; however, HNF1A protein levels were not directly measured in this study. Conclusion: Collectively, these findings identify Hnf1aos1 as a regulator of hepatic lipid homeostasis whose loss produces a phenotype consistent with inappropriate lipid accumulation during nutrient excess, without defining the underlying molecular mechanism. Our results support a role for Hnf1aos1 in shaping hepatic metabolic plasticity and provide insight into lncRNA-associated MASLD phenotypes. Full article

High-quality, large-weight alloy wires (>200 kg per coil) for aerospace fasteners require intermediate annealing prior to final cold drawing, as well as subsequent solution and aging heat treatments, which are critical processes during their manufacturing. However, the evolution of microstructure and mechanical properties during these procedures has not been systematically investigated. In this study, different cooling methods after intermediate annealing were comparatively investigated to clarify their influence on the microstructure evolution, precipitation behavior, and mechanical properties of Al–Zn–Mg–Cu alloy wires. The results revealed that the cold heading performance of alloy wires is determined by the strength–ductility balance, crystallographic texture, and precipitation behavior. Furnace cooling promoted η′ phase coarsening, resulting in lower strength and higher ductility, which enhanced deformation homogeneity and cold heading formability. The near-zero Δr reduced strain localization and cracking susceptibility, whereas higher Δr in water- and air-cooling samples increased anisotropy and cracking tendency. After heat treatment, strength differences became negligible, whereas elongation remained texture dependent, with the weaker texture in the furnace-cooling sample yielding superior ductility. Full article

Thaumasite sulfate attack (TSA) under elevated water pressure has important implications for the durability of deep underground concrete structures, yet the deterioration process and the coupled effect of water pressure and carbonate supply remain insufficiently understood. In this study, laboratory pressurized sulfate exposure tests were conducted to investigate the evolution of macroscopic performance and microstructure of cement mortars with different limestone powder contents (0%, 15%, and 30%) under water pressures of 0, 2.5, and 5.0 MPa. The results show that elevated water pressure promotes sulfate ingress into the mortar and accelerates later-stage strength loss; this interpretation is supported by the depth-dependent distribution of soluble SO₄²⁻ measured in mortars without limestone powder. Two-way ANOVA indicates that both water pressure and limestone powder content have significant effects on compressive strength, and their interaction becomes statistically significant at 120 d. XRD, FT-IR, and SEM/EDS results show that, under elevated water pressure and high limestone powder content, the corrosion products gradually evolve from gypsum-related products to ettringite- and thaumasite-related products, with a certain spatial differentiation. Specifically, the gray–white, mud-like surface products are consistent with thaumasite-rich assemblages, whereas the needle- and column-like crystals in the interior are consistent with ettringite-rich assemblages. Overall, elevated water pressure mainly promotes sulfate transport, while limestone powder mainly increases carbonate availability. These two factors may jointly intensify TSA deterioration in mortar through a pathway involving transport enhancement, carbonate supply, corrosion product evolution, and aggravated macroscopic damage. This study provides a reference for understanding the sulfate deterioration mechanism of limestone powder-containing cement-based materials in deep underground environments under elevated water pressure. Full article

Background: Wugeng San (WGS) is a traditional Tibetan medicinal preparation that has long been used to treat inflammatory and arthritic conditions. However, its contemporary pharmacological validation and the mechanisms underlying its action in rheumatoid arthritis (RA) have not been fully investigated. Objective: For the first time, this study aimed to systematically investigate the therapeutic effects of WGS on RA, identify its potential targets, and elucidate its action mechanisms. Methods: This study, as the first comprehensive investigation of WGS in RA, employed integrated multiple approaches including chemical component identification via UPLC-Q-TOF/MS, network pharmacology, bioinformatics, machine learning, and in vivo efficacy assessment and mechanism verification in a collagen-induced arthritis (CIA) rat model, a widely accepted experimental model that mimics the key pathological features of RA. Results: The results demonstrated that WGS reduced the severity of arthritis in a dose-dependent manner, as evidenced by decreased paw swelling, normalized body weight, and restored levels of pro- and anti-inflammatory cytokines. The high dose of WGS (252 mg/kg) showed an effect comparable to that of methotrexate (0.2 mg/kg). Histological analysis revealed that WGS reduced synovial hyperplasia, cartilage erosion and bone destruction, decreased osteoclast numbers, and promoted osteoblast activity. Eighty-four compounds were identified using UPLC-Q-TOF/MS. Network pharmacology and machine learning analyses indicated SYK as a key target enriched in the NF-κB signaling and osteoclast differentiation pathways. Experimental validation confirmed that WGS suppressed the phosphorylation of SYK and NF-κB pathway components (p65, IκBα, and IKKα/β), decreased MMP1/MMP3 levels, and modulated the Bax/Bcl-2 ratio to promote apoptosis. Conclusions: In conclusion, WGS exhibits strong anti-arthritic effects through “multi-component, multi-target, and multi-pathway” mechanisms, likely attributable to the inhibition of the SYK/NF-κB signaling axis, suppression of matrix degradation, and regulation of cellular apoptosis. This research offers a pharmacological basis for repurposing WGS as a promising natural candidate for RA therapy. Full article

This study proposes a three-stage chronological production simulation method to enhance inter-provincial resource coordination. The core innovation lies in combining the “multi-time-scale decomposition” strategy with the “intra-provincial balancing and inter-provincial mutual assistance” mechanism. A three-stage optimization model for annual chronological production simulation is constructed. Specifically, the inter-provincial monthly medium-term mutual assistance stage takes into account the constraints of inter-provincial monthly transaction electricity volume, so as to adapt to the current situation in China where inter-provincial medium-term power transactions are mostly carried out on a monthly cycle. Simulation analysis was conducted based on a case study built with actual data from the Chongqing and Sichuan power grids in the southwestern region of China, which verifies the effectiveness of the proposed method. Full article

Agricultural byproducts cellulose-rich (~40%) sugarcane bagasse (SCB) and rice husk (RH) wastes may be used as fiber sources in biomaterials manufacturing. The hybrid biomass fibers are two kinds of fibers that should generate a biocomposite according to the functions and physical, chemical, and mechanical properties of materials. The biocomposite was synthesized using the solvothermal method. The FeCl₃.6H₂O was dissolved in C₂H₃NaO₂ and C₆H₆O₂ and later heated at 60 °C. The SCB and RH fiber (1:1) are added with HDMA into the mixture, then placed in a Teflon stainless steel autoclave at 200 °C for 6 h. The biocomposite was employed as a green adsorbent to treat wastewater through simultaneous adsorption. The biocomposite had 2.637 mmol g⁻¹ of amine groups, which makes smaller magnetic particles and a high surface area of up to 79%. The pseudo-second-order kinetic model followed the Cu(II) and Pb(II) ions adsorption for 4 h (240 min), and the maximum adsorption capacities were 35.042 mg g⁻¹ and 67.127 mg g⁻¹, respectively, at the pH of 5. The biocomposite not only got rid of metal ions, but it also worked well to get rid of dye, total suspended solids (TSSs), and chemical oxygen demand (COD) as pollutants in wastewater. The biocomposite still worked well after being used four times. Full article

Recently, Quzhou Aurantii Fructus Extract (QAFE) was reported to exert anti-inflammatory effects on different types of respiratory diseases; however, it is yet to be determined whether it is effective in patients with idiopathic pulmonary fibrosis (IPF). The purpose of this study is to explore the capacity of QAFE to fight fibrotic disease, in particular how it works in relation to the regulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway. QAFE was made with Quzhou Fructus Aurantii (QAF), and the content of four flavonoids in the samples prepared was analyzed by high-performance liquid chromatography (HPLC). The therapeutic effect of QAFE was experimented by establishing IPF models in mice and in cells. Identification of the mechanism of QAFE in IPF through knockout or knockdown of the Nrf2 gene. The experiments suggest that QAFE has the potential to prevent IPF-induced inflammation, collagen deposition, oxidative stress, and apoptosis of cells. Silencing Nrf2 by knockdown or knockout is enough to prevent the capacity of QAFE to inhibit the process of inflammation, oxidative stress, and collagen deposition to cause more serious lung injury and HO-1 expression downregulation. QAFE is a potential new antifibrotic drug in IPF with an effect on the Nrf2/HO-1 pathway that reduces inflammation and oxidative stress. Full article

Background/Objectives: Radon exposure has recently been associated with asthma morbidity, including increased airway inflammation and school absenteeism in children, though limited data on underlying biological mechanisms exist. Interleukin-6 (IL-6), a pleiotropic cytokine implicated in both Type 2-low airway inflammation and radon-related lung carcinogenesis, may represent a key mechanistic link between radon exposure and asthma morbidity. We aimed to evaluate the association between indoor radon exposure and plasma IL-6 levels in children with asthma and whether this relationship differs by allergic sensitization status. Methods: We analyzed baseline data from the School Inner-City Asthma Study, a prospective cohort of children aged 4–13 years with persistent asthma. Monthly indoor radon concentrations at each participant’s residential ZIP Code Tabulation Area were estimated using a validated spatiotemporal prediction model. Plasma IL-6 was measured from baseline blood samples. Multivariable linear mixed-effects models with random intercepts for school were used to assess the association between radon exposure and IL-6, adjusting for demographic, clinical, and socioeconomic covariates. Effect modification by allergic sensitization was evaluated using an interaction term. Results: Among 144 participants, 62.5% were allergen-sensitized. The median home radon concentration was 46.6 Bq/m³ (range 30.7–99.9), and the mean plasma IL-6 was 0.22 pg/mL (SD 0.41). A significant interaction was observed between radon exposure and allergic sensitization status (β-interaction = –0.012; p = 0.014), indicating differential effects by phenotype. Among non-sensitized children, higher radon exposure was associated with increased IL-6 levels (β = 0.0088; p = 0.044), corresponding to a 0.32 pg/mL rise in IL-6 per 37 Bq/m³ increase in radon. No significant association was observed among sensitized children. Conclusions: Indoor radon exposure is associated with higher plasma IL-6 levels in non-sensitized children with asthma, suggesting a potential IL-6–mediated pathway linking radon exposure to asthma morbidity in the Type 2-low phenotype. These findings highlight heterogeneity in environmental asthma responses and support further investigation into radon mitigation as a modifiable factor to improve asthma outcomes. IL-6 may serve as a biomarker to identify children most susceptible to radon-related airway inflammation, guiding personalized mitigation strategies and targeted interventions to improve asthma outcomes. Future studies should incorporate direct home radon measurements, comprehensive endotyping panels, and longitudinal biomarker sampling to validate these findings and elucidate whether IL-6 trans-signaling pathways mediate radon-induced airway injury in non-allergic asthma. Full article

Advanced gastric (GAC) or gastroesophageal junction (GEJAC) adenocarcinoma continues to carry a poor prognosis. Understanding GAC/GEJAC at the molecular level has provided a new understanding and the basis for individualized approaches to treatment. The current biomarker-driven therapy focuses on four areas: microsatellite instability (MSI), human epidermal growth factor receptor-2 (HER2), programmed death ligand-1 (PD-L1) combined positive score, and claudin 18.2 (CLDN18.2). However, because of improving technology, the focus has shifted to cancer cell-surface proteins and peptides. Each of these GAC/GEJAC subgroups provides a different treatment pathway. The agents utilized to treat advanced GAC/GEJAC include immune checkpoint inhibitors (ICIs), chemotherapy, monoclonal antibodies (mAbs), and antibody–drug conjugate (ADC) therapy, as well as bispecific antibodies (BsAbs), but they are certainly not limited to the above. Drug development has shifted in recent years to establish different mechanisms that are attempting more sophisticated and targeted approaches, such as BsAbs and ADCs. Meanwhile, the development of cytotoxics has tapered off. Along with these developments in drug therapy, more therapies directed at CLDN18.2, HER2, MSI, EGFR, HER3 and trophoblast cell-surface antigen 2 (TROP2) are underway. Here we review future areas in advanced GAC, including zanidatamab’s potential role in HER2-positive advanced GAC and deciphering the abundance of anti-CLDN18.2, extending beyond investigative therapies. Full article

Hypertension is the leading global risk factor for cardiovascular diseases, and its pathogenesis is closely linked to excessive sympathetic activation, which markedly elevates the risk of stroke, heart failure and other adverse cardiovascular events. Traditional therapies mainly target peripheral mechanisms, whereas the clinical efficacy of renal denervation highlights the critical role of central regulation in sympathetic hyperactivity. This review focuses on the core sympathetic nuclei including the rostral ventrolateral medulla (RVLM) and paraventricular nucleus (PVN), with epigenetic regulation as a key innovative perspective. We systematically summarize the upstream driving effects of reactive oxygen species (ROS) and neuroinflammation, and emphasize lncRNA/miRNA-mediated post-transcriptional regulation and the modulatory actions of gasotransmitters. Under stress conditions, aberrant activation of ROS and neuroimmune pathways, epigenetic reprogramming, and hyperexcitability of central sympathetic neurons act as key events in sympathetic overactivation, which interact synergistically to promote hypertension. Integrating evidence from multiple hypertensive animal models and clinical studies, we discuss multimodal interventions including pharmacotherapy, nanozyme biotechnology and neuromodulation, analyze current translational challenges, and provide a theoretical framework for developing central-targeted antihypertensive therapies. Full article

Patients with left ventricular dysfunction undergoing cardiac surgery face a heightened risk of perioperative complications, including postcardiotomy shock (PCS). Conventional management with inotropes and vasopressors can exacerbate end-organ dysfunction, underscoring the need for alternative strategies. The planned use of mechanical circulatory support (MCS) devices, such as the Impella, offers a proactive approach to mitigating PCS in high-risk patients. This study presents our early experience at Johns Hopkins with planned Impella utilization in high-risk cardiac surgery. We detail our risk stratification methodology, patient selection criteria, and perioperative management strategies. Our proposed risk stratification scoring system incorporates surgical intent, preoperative myocardial function, anticipated postoperative course, and exit strategy to identify optimal candidates for perioperative MCS. We describe the intraoperative central placement technique for the Impella 5.5, perioperative management protocols—including anticoagulation strategies and weaning protocols—and postoperative device extraction. A retrospective review of our first 11 consecutive patients with severely reduced left ventricular ejection fraction (<30%) who underwent Impella-assisted cardiac surgery demonstrated favorable outcomes, with no postoperative mortality and a two-year follow-up. Our findings suggest that planned Impella use in high-risk cardiac surgery is both feasible and beneficial. However, further studies are necessary to validate these results, assess long-term outcomes, and evaluate cost-effectiveness. Full article

Background/Objectives: Longer oligoarginines are very effective cell-penetrating peptides. It has been shown that a minimal number of positively charged side chains is necessary for efficient cellular uptake. But a highly positively charged peptide may interact with its cargo molecule, thereby reducing its efficiency. Several chemical modifications were tested to improve the internalization of short tetraarginine derivatives. Aromatic groups, such as Dabcyl at the N-terminus, Trp in the sequence, and AMBA or PABA in the backbone, were used to improve internalization. The other useful modification was the aza-glycine substitution in the case of penetratin. Methods: In this study, the effect of aza-glycine insertion into the peptide Dabcyl-RRRRK(Cf) on internalization was studied and compared with that of the Trp-modified peptide Dabcyl-RRWRRK(Cf). To explain the noticed difference in the biological activity of peptides, DFT calculations and the prediction of membrane-binding free energy (ΔΔF) from a peptide sequence were performed. Results: It turned out that the position of the aza-glycine moiety does not have an influence on the cellular uptake. The aza-glycine-containing peptide showed higher internalization than the Dabcyl-RRRRK(Cf) peptide. Besides this, these peptides have similar or higher cellular uptake than that of octaarginine at lower concentrations (c < 2 µM). The aza-glycine affected not only cellular uptake but also the entry mechanism. The structure of peptides depended on the amino acids (Trp, Gly, or azaGly) in their sequences and their positions. Conclusions: These may result in the different amphiphilicity of peptides, and thus changes in the hydrophobic moment and in the binding affinity of peptides to the negatively charged membrane surface. Full article

In this study, five solvent fractions from Litsea cubeba (Lour.) Pers. fruit were extracted and investigated for their antioxidant profiles. Results showed that the petroleum ether fraction (PEF) and n-butanol fraction (NBF) exhibited prominent free radical scavenging capacities in DPPH, ABTS, and hydroxyl radical assays. Gas chromatography–mass spectrometry (GC-MS) identified citral as the dominant bioactive component in both active fractions. Further mechanism analysis demonstrated that citral exerted potent antioxidant effects via dual pathways: direct free radical scavenging and transition metal ion chelation. These findings not only elucidate the material basis and molecular mechanism underlying the antioxidant activity of L. cubeba but also provide a scientific rationale for the high-value utilization of citral-rich fractions in functional foods, cosmetics, and healthcare products. Full article