Search Results (598)

Background/Objectives: The role of the molecular chaperone heat shock protein 90 (Hsp90) in pain and analgesia has been recognized; however, no study to date has investigated its role in facial allodynia during headache. In the current study, we examined the role of Hsp90 and its possible connection to the endocannabinoid system utilizing a rodent model of cortical spreading depression (CSD). Methods: CSD, a physiological phenomenon associated with headache disorders, was induced by cortical injection of KCl in female Sprague Dawley rats. To selectively inhibit Hsp90, 17-AAG was applied on the dura mater 24 h before CSD induction. Periorbital allodynia was assessed by von Frey filaments, while tissue samples were subjected to LC-MS, qPCR, Western immunoblotting, and the GTPγS coupling assay. Results: Increased expression of Hsp90 was selectively observed in the periaqueductal gray (PAG) harvested 90 min after cortical KCl injection, suggesting increased cellular stress from CSD induction. Application of 17-AAG (0.5 nmol) on dura mater 24 h before CSD induction significantly prevented facial allodynia as measured by von Frey filaments. This effect was blocked by injection of the CB₁R antagonist rimonabant (1 mg/kg, ip). The pretreatment with 17-AAG significantly increased the level of anandamide (AEA) in PAG 90 min after cortical insult, as measured by LC-MS. This effect was accompanied by reduced expression of FAAH and increased expression of NAPE-PLD in the same nuclei. Conclusions: These results suggest that Hsp90 inhibition positively modulates the endocannabinoid system, causing pain relief through descending pain modulation in PAG post-CSD. Full article

Background: Purpureocillium lilacinum (P. lilacinum) is an emerging filamentous fungus known to cause opportunistic infections, particularly in immunocompromised patients. Formerly known as Paecilomyces lilacinus, this pathogen is widespread in the environment and can lead to a range of infections, from superficial skin lesions to invasive diseases. This article presents a case of deep cutaneous hyalohyphomycosis caused by P. lilacinum in a liver transplant patient, followed by a review of the literature focusing on new antifungal agents. Methods: We reported a brief case description followed by a narrative review of the literature regarding P. lilacinum cutaneous and lymphangitic infections in immunocompromised patients. Results: We conducted a review of the literature over the past 20 years, focusing on the clinical features, diagnostic challenges, and therapeutic outcomes of cutaneous and lymphangitic P. lilacinum infections in immunocompromised hosts. Conclusions: This review highlights the critical importance of early diagnosis through the analysis of biopsy samples using standard microbiological and histological techniques, complemented by innovative molecular biology methods. We also emphasise the role of appropriate antifungal treatment, despite the absence of an established standard of care, particularly in high-risk patients. Furthermore, we review and discuss the current lack of a standardised therapeutic regimen and the potential of novel antifungal agents as promising treatment options for P. lilacinum infections. Full article

Three-dimensional printing technology is fundamentally reshaping the design and fabrication of health monitoring sensors. While it holds great promise for achieving miniaturization, multi-material integration, and personalized customization, the lack of a clear selection framework hinders the optimal matching of printing technologies to specific sensor requirements. This review presents a classification framework based on existing standards and specifically designed to address sensor-related requirements, categorizing 3D printing technologies into point-based, line-based, and area-based modalities according to their fundamental fabrication unit. This framework directly bridges the capabilities of each modality, such as nanoscale resolution, multi-material versatility, and high-throughput production, with the critical demands of modern health monitoring sensors. We systematically demonstrate how this approach guides technology selection: Point-based methods (e.g., stereolithography, inkjet) enable micron-scale features for ultra-sensitive detection; line-based techniques (e.g., Direct Ink Writing, Fused Filament Fabrication) excel in multi-material integration for creating complex functional devices such as sweat-sensing patches; and area-based approaches (e.g., Digital Light Processing) facilitate rapid production of sensor arrays and intricate structures for applications like continuous glucose monitoring. The point–line–area paradigm offers a powerful heuristic for designing and manufacturing next-generation health monitoring sensors. We also discuss strategies to overcome existing challenges, including material biocompatibility and cross-scale manufacturing, through the integration of AI-driven design and stimuli-responsive materials. This framework not only clarifies the current research landscape but also accelerates the development of intelligent, personalized, and sustainable health monitoring systems. Full article

The utilization of saline–alkali water resources presents a promising approach for freshwater aquaculture. Red tilapia (Oreochromis spp.) exhibits moderate salinity tolerance, but its adaptation mechanism to alkaline conditions remains poorly understood. In the current study, five alkaline carbonate concentrations in a 60-day chronic stress experiment on red tilapia were evaluated. The experimental design included a control group (CA0, 0 mmol/L) and three treatment groups (CA10, 20 mmol/L; CA30, 30 mmol/L; and CA40 40 mmol/L). The results indicated that at alkaline carbonate concentrations exceeding 20 mmol/L, the gill filaments exhibited curling and deformation, the hepatocytes displayed migration, and tissue damage increased significantly. The gill’s antioxidant capacity initially decreased and then increased, with severe gill injury in the CA40 group, leading to significantly reduced levels of SOD, CAT, and GSH-PX compared to the CA40 group (p < 0.05). Conversely, the enzymatic activities related to energy metabolism showed an opposite trend under alkaline carbonate stress. The transcriptome analyses of gill tissues across five groups identified significant alterations in key pathways, including the metabolic process (endocytosis, focal adhesion, PI3K−Akt signaling pathway, MAPK signaling pathway, and Citrate cycle (TCA cycle)), and immune responses (mTOR signaling and NOD−like receptor signaling pathways). Additionally, we screened 13 differentially expressed genes (DEGs) as potential regulators of alkaline stress and validated their expression levels using quantitative real-time PCR (qPCR). This study preliminarily elucidated the molecular mechanism of red tilapia in the physiological regulation process under chronic alkaline stress, and offers a theoretical foundation for breeding programs aimed at developing alkali-tolerant strains for aquaculture in alkaline water environments. Full article

Hierarchically porous polymers can unite macro-scale architected voids with micro-scale pores, enabling unique combinations of low density, high surface area, and controlled transport properties that are difficult to achieve with traditional methods. This review outlines the current advancements in creating such multiscale architectures using fused filament fabrication (FFF), the most widely used polymer additive manufacturing technique. Unlike earlier reviews that consider lattice architectures and foaming chemistries separately, this work integrates both within a single analysis. It begins with an overview of FFF fundamentals and how process parameters affect macropore formation. Design strategies for achieving macroporosity (≳100 µm) with a single thermoplastic are presented and categorized: 2D infill patterns, strut-based lattices, triply periodic minimal surfaces (TPMS), and Voronoi structures, along with functionally graded approaches. The discussion then shifts to functional filaments incorporating chemical or physical blowing agents, thermally expandable or hollow microspheres, and sacrificial porogens, which create microporosity (≲100 µm) either in situ or through post-processing. Each material approach is connected to case studies that demonstrate its application. A comparative analysis highlights the advantages of each method. Key challenges such as viscosity control, thermal gradient management, dimensional instability during foaming, environmental concerns, and the absence of standardized porosity measurement techniques are addressed. Finally, emerging solutions and future directions are explored. Overall, this review provides a comprehensive perspective on strategies that enhance FFF’s capability to fabricate hierarchically porous polymer structures. Full article

Aspergillus fumigatus is an opportunistic filamentous fungus that primarily affects the respiratory tract of the human body. Depending on its host’s immune response, the pathogen can cause invasive pulmonary aspergillosis (IPA). Biofilm formation by A. fumigatus increases virulence and resistance against antifungals and immune response and is one important factor in IPA development. Here, two human-like models, precision cut lung slices (PCLS) and a biofilm co-culture model, have been developed to test the anti-biofilm activity of voriconazole, amphotericin B, as well as luliconazole against A. fumigatus. In both assays, metabolically active A. fumigatus biofilms were examined at different biofilm developmental stages using an XTT assay. A decrease in the metabolic activity of the fungal biofilms was detected for each of the tested agents in both assays. Significant anti-biofilm effects exist against early-stage biofilm in the co-culture model. In the PCLS assay, amphotericin B showed the strongest inhibition after 24 h. In conclusion, the applied PCLS ex vivo model can be used to study the property and activity of certain antifungal compounds against Aspergillus biofilm. With its close resemblance to human conditions, the PCLS model has the potential for improving the current understanding of biofilm treatments in laboratory settings. Full article

Racetrack NbTi superconducting coil is a key component in Maglev train systems due to its excellent mechanical processing performance and lower construction cost. However, dynamic pressures during high-speed operations can influence contact pressures and cause internal filament damage, leading to critical current degradation and quench, which threaten the stable operation of the superconducting magnet. Considering that the NbTi coil has a typical hierarchical structure and comprises thousands of filaments, this study constructs an efficient multiscale framework combining the finite element method (FEM) and self-consistent clustering analysis (SCA) to study the multiscale responses of the NbTi coil. The mechanical responses of the two-scale racetrack coil under monotonic and periodic pressures are investigated, and the effects of the friction contacts between strands are also discussed. The study reveals that internal contacts significantly influence local contact pressures and microscopic stresses, and periodic loading leads to stress accumulation with cycle times. The proposed framework efficiently captures critical microscale responses and can be applied to other multiscale materials and structures. Full article

Cylindrospermopsis raciborskii is a toxin-producing cyanobacterium that is easy to overlook. It has strong environmental adaptability and is currently spreading around the world and gradually dominating to form a persistent bloom, causing ecological and environmental risks and drinking water safety issues. In this study, we systematically investigated the inhibitory effects of oleic acid on C. raciborskii and elucidated the underlying mechanisms through morphological observation, physiological assays, and bioinformatics analysis. Our results demonstrated that oleic acid strongly inhibits the growth of C. raciborskii, with a 72 h half-maximal effective concentration (EC₅₀) of 0.903 mg·L⁻¹. At 1.6 mg·L⁻¹, oleic acid achieved an inhibition rate of 99.5% within 48 h, indicating rapid suppression of cyanobacterial growth. Physiological analyses revealed that oleic acid severely impaired photosynthetic activity, as evidenced by significant reductions in key parameters (rETRmax, α, Fv/Fm, and Fv/Fo) and altered photosynthetic pigment composition, suggesting structural and functional damage to the photosynthetic apparatus. Morphological observations further showed that oleic acid disrupted filament integrity, inducing cell shrinkage, cytoplasmic vacuolation, cell wall detachment, membrane rupture, and eventual cellular disintegration. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that oleic acid interferes with multiple metabolic processes, including nutrient and cofactor synthesis, membrane transport, and signal transduction, ultimately triggering algal cell death. This study highlights oleic acid as a promising eco-friendly agent for mitigating C. raciborskii blooms, offering potential applications in ecological prevention and emergency bloom control. Full article

The cytosolic pH (pH_i) of mammalian cells is tightly maintained at values ~7.2. Cytoplasmic acidosis (pH_i < 6.8) occurs when the intracellular proton concentration ([H⁺]_i) exceeds the buffering capacity of the cytosol and transport processes to extrude protons are exhausted. During intracellular acidosis, the contractility of cardiac and skeletal muscle cells is strongly reduced, often at sufficient Ca²⁺ levels. A contraction of striated muscle is achieved when the intracellular calcium (Ca²⁺) concentration rises above resting levels. The amplitude and kinetics of Ca²⁺ signals are controlled by Ca²⁺ handling proteins and force is generated if Ca²⁺ ions interact with contractile filaments of the sarcomere. Some aspects of this phenomenon, such as the biochemical origin of excessive protons in working muscle cells and molecular interactions of protons with Ca²⁺ handling proteins or contractile filaments, are not yet fully understood. This review summarizes our current understanding of how striated muscle cells handle Ca²⁺ and H⁺ and how a rise in [H⁺]_i may interfere with Ca²⁺ signaling in the working skeletal muscle (fatigue) or during ischemic events in cardiac muscle. Finally, we briefly address experimental strategies to measure Ca²⁺ signaling at different pH values with fluorescent probes and highlight their limitations. Full article

The present study offers a systematic review of the current state of research on lattice structures manufactured by additive technologies for biomedical applications, with the aim of identifying common patterns, such as the use of triply periodic minimal surfaces (TPMS) for bone scaffolds, as well as technological gaps and future research opportunities. Employing the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology, the review process ensures methodological rigor and replicability across the identification, screening, eligibility, and inclusion phases. Additionally, PRISMA was tailored by prioritizing technical databases and engineering-specific inclusion criteria, thereby aligning the methodology with the scope of this field. In recent years, a substantial surge in interdisciplinary research has underscored the promise of architected porous structures in enhancing mechanical compatibility, fostering osseointegration, and facilitating personalized medicine. A growing body of literature has emerged that explores the optimization of geometric features to replicate the behavior of biological tissues, particularly bone. Additive manufacturing (AM) has played a pivotal role in enabling the fabrication of complex geometries that are otherwise unachievable by conventional methods. The applications of lattice structures range from permanent load-bearing implants, commonly manufactured through selective laser melting (SLM), to temporary scaffolds for tissue regeneration, often produced with extrusion-based processes such as fused filament fabrication (FFF) or direct ink writing (DIW). Notwithstanding these advances, challenges persist in areas such as long-term in vivo validation, standardization of mechanical and biological testing, such as ISO standards for fatigue testing, and integration into clinical workflows. Full article

This paper presents the development and validation of a cost-effective 3D-printed conductive phantom for EEG sensing system validation that achieves 85% cost reduction (£48.10 vs. £300–£500) and 48-hour fabrication time while providing consistent electrical properties suitable for standardized electrode testing. The phantom was fabricated using conductive PLA filament in a two-component design with a conductive upper section and a non-conductive base for structural support. Comprehensive validation employed three complementary approaches: DC resistance measurements (821–1502 $\mathsf{\Omega }$), complex impedance spectroscopy at 100 Hz across anatomical regions (3.01–6.4 k$\mathsf{\Omega }$ with capacitive behavior), and 8-channel EEG system testing (5–11 k$\mathsf{\Omega }$ impedance range). The electrical characterization revealed spatial heterogeneity and consistent electrical properties suitable for comparative electrode evaluation and EEG sensing system validation applications. To establish context, we analyzed six existing phantom technologies including commercial injection-molded phantoms, saline solutions, hydrogels, silicone models, textile-based alternatives, and multi-material implementations. This analysis identifies critical accessibility barriers in current technologies, particularly cost constraints (£5000–20,000 tooling) and extended production timelines that limit widespread adoption. The validated 3D-printed phantom addresses these limitations while providing appropriate electrical properties for standardized EEG electrode testing. The demonstrated compatibility with clinical EEG acquisition systems establishes the phantom’s suitability for electrode performance evaluation and multi-channel system validation as a standardized testing platform, ultimately contributing to democratized access to EEG sensing system validation capabilities for broader research communities. Full article

Bone-related defects present a key challenge in orthopaedics. The current gold standard, autografts, poses significant limitations, such as donor site morbidity, limited supply, and poor morphological adaptability. This study investigates the potential of scaffold geometry to induce osteogenic differentiation of human adipose-derived stem cells (hADSCs) through mechanotransduction, without the use of chemical inducers. Four distinct poly-(L)-lactic acid (PLA) scaffold architectures—Traditional Cross (Tc), Triangle (T), Diamond (D), and Gyroid (G)—were fabricated using fused filament fabrication (FFF) 3D printing. hADSCs were cultured on these scaffolds, and their response was evaluated utilising an alkaline phosphatase (ALP) assay, immunofluorescence, and extensive proteomic analyses. The results showed the D scaffold to have the highest ALP activity, followed by Tc. Proteomics results showed that more than 1200 proteins were identified in each scaffold with unique proteins expressed in each scaffold, respectively Tc—204, T—194, D—244, and G—216. Bioinformatics analysis revealed structures with complex curvature to have an increased expression of proteins involved in mid- to late-stage osteogenesis signalling and differentiation pathways, while the Tc scaffold induced an increased expression of signalling and differentiation pathways pertaining to angiogenesis and early osteogenesis. Full article

The excellent moisture transport properties of yarns play a crucial role in improving the liquid moisture transfer behavior within textiles and maintaining their thermal-wet comfort. However, the current research on the moisture management performance of fabrics made from yarns with excellent liquid transport properties primarily compares the wicking results, without considering the varying requirements of testing conditions due to differences in human sweating rates during daily activities. Moreover, the understanding of moisture transport mechanisms in yarns within fabrics under different testing conditions remains insufficient. In this study, two types of twisted combination yarns, composed of hydrophobic profiled polyester filaments and hydrophilic spun yarns to form a hydrophobic-hydrophilic gradient along the axial direction of the yarn, were developed and compared with profiled polyester filaments to understand the liquid migration behaviors in the knitted fabrics formed by these yarns. Results showed that hydrophobic profiled polyester filament yarn demonstrated superior liquid transport performance with infinite saturated liquid supply (vertical wicking test). In contrast, the twisted combination yarns exhibited better moisture diffusion properties under limited liquid droplet supply conditions (droplet diffusion test and moisture management test). These contradictory findings indicated that the amount of liquid moisture supply in testing conditions significantly affected the moisture transport performance of yarns within fabrics. It was revealed that the liquid moisture in the twisted combination yarns migrated through capillary wicking for moisture transfer. Under an infinite saturated liquid supply condition, the higher the content of hydrophilic fibers in the spun yarns, the greater the amount of moisture transferred, demonstrating an excellent liquid transport performance. Under the limited liquid droplet supply conditions, both the volume of liquid water and the moisture absorption capacity of the yarn jointly influence internal moisture migration within the yarn. It provided a theoretical reference for testing the internal moisture wicking performance of fabrics under different states of human sweating. Full article

Beach Sand Mycobiome is currently among the most important health challenges for viticulture in the world. Remarkably, the study of fungal communities in coastal beach sand and recreational waters remains underexplored despite their potential implications for human health. This research aimed to assess the prevalence of fungal species and the antifungal susceptibility profiles of fungi recovered from the beaches of the Persian Gulf and the Sea of Oman. Sand and seawater samples from 39 stations distributed within 13 beaches along the coastline were collected between May and July 2023. The grown isolates were identified at the species level based on morphological characteristics and DNA sequencing. Antifungal susceptibility testing was performed according to the Clinical Laboratory Standards Institute guidelines. Of 222 recovered isolates, 206 (92.8%) filamentous fungi and 16 (7.2%) yeast strains were identified. Sand-recovered fungi comprised 82.9%, while water-originated fungi accounted for 17.1%. The DNA sequencing technique categorized 191 isolates into 13 genera and 26 species. The most recovered genus was Aspergillus (68.9%), and Aspergillus terreus sensu stricto was the commonly identified species (26.14%). Voriconazole was the most effective antifungal drug against Aspergillus species. Research on fungal contamination levels at these locations could provide a foundation for establishing regulatory frameworks to diminish fungal risks, thereby enhancing public health protection. The ecological significance of fungal communities in sandy beaches to human infections remains to be explored, and earlier reports in the literature may motivate researchers to focus on detecting this mycobiome in natural environments where further investigation is warranted. Ultimately, our discovery serves as a reminder that much remains to be learned about pathogenic fungi and underscores the need for vigilance in areas where emerging pathogens have not yet been identified. Full article

The filamentous fungal genus Aspergillus represents an industrially significant group of eukaryotic microorganisms. For nearly a century, it has been widely utilized in the production of diverse high-value products, including organic acids, industrial enzymes, recombinant proteins, and various bioactive natural compounds. With the rapid advancement of synthetic biology, Aspergillus has been extensively exploited as a heterologous chassis for the production of heterologous proteins (e.g., sweet proteins and antibodies) and the synthesis of natural products (e.g., terpenoids and polyketides) due to its distinct advantages, such as superior protein secretion capacity, robust precursor supply, and efficient eukaryotic post-translational modifications. In this review, we provide a comprehensive summary of the advancements in the successful expression of heterologous proteins and the biosynthesis of natural products using Aspergillus platforms (including Aspergillus niger, Aspergillus nidulans, and Aspergillus oryzae) in recent years. Emphasis is placed on the applications of A. oryzae in the heterologous biosynthesis of terpenoids. More importantly, we thoroughly examine the current state of the art in utilizing CRISPR-Cas9 for genetic modifications in A. oryzae and A. niger. In addition, future perspectives on developing Aspergillus expression systems are discussed in this article, along with an exploration of their potential applications in natural product biosynthesis. Full article