Search Results (1,532)

Human serum albumin (HSA), as a natural protein carrier, possesses excellent biocompatibility and drug binding capacity. Due to the synergistic effects of the enhanced permeability and retention (EPR) effect and Gp60/SPARC-mediated active targeting, this drug carrier demonstrates favorable tumor selectivity and can be enriched in tumor tissues to achieve long-term therapeutic effects. Particularly, HSA undergoes pH-dependent recycling through the neonatal Fc receptor (FcRn), which significantly prolongs its half-life and enhances its feasibility as a drug delivery platform. In practical clinical applications, the regulation of HSA release rates requires multiple strategies to work synergistically. Additionally, the targeting efficiency of delivery systems due to tumor heterogeneity remains a major bottleneck limiting its universality. This article systematically reviews the unique advantages, clinical applications, challenges, and future perspectives of HSA as a prodrug carrier in tumor therapy. Full article

General pustular psoriasis (GPP) is a rare, potentially life-threatening neutrophilic dermatosis. Pediatric cases are uncommon and often misdiagnosed due to overlapping clinical and histopathological features with other pustular dermatoses. We present a case of an 11-year-old boy, initially diagnosed with Sneddon–Wilkinson syndrome, who presented with disseminated pustular eruptions, with no response to antibiotics, dapsone, and glucocorticosteroids. In histopathology, we observed subcorneal neutrophilic pustules. Due to atypical features and poor treatment response, the patient underwent genetic testing, which revealed a homozygous IL36RN gene c.338C>T (p.Ser113Leu) pathogenic variant, which enabled a definitive diagnosis of GPP. Treatment with acitretin led to clinical improvement. Pediatric GPP poses diagnostic and treatment challenges. Genetic testing for IL36RN pathogenic variants may aid in the diagnosis, especially in atypical cases. The presence of the biallelic IL36RN pathogenic variant supports the diagnosis of DITRA (Deficiency of the IL-36 Receptor Antagonist, ORPHA:404546)—a monogenic autoinflammatory form of GPP. Full article

Piperine (PIP), a plant alkaloid with anti-inflammatory and antioxidant effects, has poor solubility and bioavailability, limiting its therapeutic potential in macrophage-mediated inflammatory and oxidative stress conditions. Despite various nanocarrier systems being explored for bioactive compounds, the specific combination of mannose-functionalized chitosan with dual stabilizers (TPGS and Tween 80) for enhanced macrophage targeting and piperine delivery has not been investigated. We hypothesized that this novel formulation would significantly enhance piperine solubility, macrophage uptake, and anti-inflammatory/antioxidant effects compared to conventional systems, while modulating apoptosis-related pathways. This study evaluated targeted and non-targeted nanoparticles synthesized by ionic gelation and emulsification using RAW 264.7 and THP-1 macrophages. FTIR, UV–Vis, XRD, and CHNS confirmed mannose conjugation, while SEM, TEM, and AFM revealed morphology. Physicochemical properties were assessed by DLS, encapsulation efficiency (EE%), drug loading (DL%), and stability. Biological evaluations included drug release, cytotoxicity (MTT), apoptosis analysis (Annexin V–FITC/PI staining), cellular uptake (fluorescence microscopy with coumarin-6), anti-inflammatory assays (extracellular and intracellular NO inhibition, cytokine suppression), antioxidant activity (DPPH, ABTS, FRAP, TAC), intracellular ROS/RNS, and apoptosis-related markers. Targeted nanoparticles showed larger mean size (162 nm) versus non-targeted ones (78 nm). EE% was 82% (targeted) and 92% (non-targeted). Both demonstrated sustained 72 h release. Cellular uptake was significantly greater for targeted nanoparticles. Both formulations reduced NO and pro-inflammatory cytokines, regulated apoptosis-associated markers, and induced controlled apoptosis at higher concentrations, with stronger effects observed for targeted particles. Antioxidant activity increased dose-dependently, with targeted nanoparticles showing superior intracellular ROS/RNS suppression. This novel multi-functional platform efficiently encapsulates PIP, enhances macrophage targeting, modulates apoptosis pathways, and demonstrates superior therapeutic promise for inflammation-related disorders. Full article

The classic design of the Practical Byzantine Fault Tolerance (PBFT) protocol relies on a centralized primary node, which not only creates a performance bottleneck but also introduces severe data censorship risks, threatening the data integrity and security of Edge Computing networks. To address this challenge, this paper proposes DC-PBFT (Decoupled PBFT), a censorship-resistant consensus protocol for Edge-Internet of Things (Edge-IoT) environments. The core innovation of DC-PBFT lies in the decoupling of the Proposer and Primary roles, supplemented by Verifiable Random Function (VRF)-based dynamic role rotation, which fundamentally eliminates the arbitrary power of a single node. Building on this, the protocol introduces a parallel group consensus mechanism: an elected Consensus Committee (CC) composed of Active Edge Nodes leads the consensus, while an independent Replica Network (RN) performs parallel validation. When a disagreement arises, the protocol triggers a global disagreement arbitration process involving all nodes to guarantee final consistency and attribute fault. To ensure long-term incentive compatibility, we also designed a hybrid election mechanism combining Proof-of-Stake and dynamic reputation, along with corresponding economic incentives and a tiered penalty system. Theoretical analysis proves that DC-PBFT satisfies Consistency and Liveness, and achieves strong censorship resistance guarantees. Simulation results demonstrate that DC-PBFT’s scalability significantly outperforms PBFT and RepChain; its reputation mechanism effectively improves long-term performance under sustained Byzantine attacks; and, compared to asynchronous censorship-resistant protocols like HoneyBadgerBFT, DC-PBFT achieves censorship resistance with over 45% lower transaction confirmation latency. Full article

Purpose: Neuroinflammation and oxidative stress are increasingly recognized as central, interconnected drivers of neurodegeneration in the visual system. This review examines the pathogenic mechanisms shared across glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and Alzheimer’s disease (AD), and evaluates the therapeutic rationale for targeting both pathways simultaneously. Methods: A narrative review of peer-reviewed literature was conducted using PubMed. Searches included the following MeSH terms: neuroinflammation, oxidative stress, retinal neurodegeneration, microglia, Müller glia, mitochondrial dysfunction, glaucoma, age-related macular degeneration, diabetic retinopathy, and Alzheimer’s disease. Priority was given to original research, systematic reviews, and high-impact publications from 2000 through 2025. However, seminal foundational works were included regardless of publication date. Studies were selected based on relevance to glial activation, mitochondrial dysfunction, reactive oxygen and nitrogen species, and disease-specific neuronal outcomes. Results: Across all four diseases, persistent microglial and Müller glial activation, mitochondrial electron transport chain dysfunction, and excess reactive oxygen species (ROS) and reactive nitrogen species (RNS) production form a self-amplifying feed-forward loop that accelerates neuronal injury. In glaucoma, these mechanisms drive intraocular pressure-independent retinal ganglion cell loss. In AMD and DR, lipid dysregulation, complement activation, and chronic hyperglycemia sustain oxidative-inflammatory injury to the retinal pigment epithelium, photoreceptors, and neurovasculature. In AD, retinal amyloid deposition and oxidative burden mirror cortical pathology, positioning the retina as a noninvasive biomarker site. Conclusions: Neuroinflammation and oxidative stress constitute unifying upstream mechanisms across major vision-threatening neurodegenerative diseases. Combination therapeutic strategies that simultaneously modulate glial activation and restore redox homeostasis may offer superior neuroprotective efficacy compared to approaches targeting isolated downstream mediators. Full article

Reliable determination of radon adsorption properties in candidate adsorbents is essential for developing highly sensitive methods capable of measuring low ²²²Rn activity concentrations in air. Such measurements are increasingly important in environmental monitoring, climate research, and low-background experiments. Conventional approaches for determining the adsorption coefficient and heat of adsorption are labor- and time-intensive, limiting their suitability for comparative studies under identical conditions. Here, a recently proposed method is applied for the first time in a systematic comparative study. The approach couples solid-state nuclear track detectors (SSNTDs) with adsorbents that simultaneously act as radon collectors and alpha emitters, enabling fully parallel exposure and signal acquisition across multiple samples. Eight adsorbents—three activated carbon fabrics, two bulk activated carbons, and three synthetic zeolites—were evaluated simultaneously over a temperature range of 0–46.5 °C. Activated carbon fabrics exhibited the highest adsorption coefficients, with ACC-5092-10 reaching 11.8 ± 1.3 m³/kg at 20 °C. The heats of adsorption ranged from 24.8 ± 3.9 to 33.3 ± 5.0 kJ/mol, consistent with the literature values. For synthetic zeolites, the adsorption coefficient increased linearly with the Si:Al ratio. The influence of water content was further investigated for the five best-performing materials. The most hydrophobic material, zeolite SA-25 (Si:Al = 25), showed only a 25% reduction in adsorption coefficient under saturated humidity, whereas activated carbons exhibited strong suppression. These results demonstrate the practicality, sensitivity, and efficiency of the SSNTD–adsorbent method for comparative radon adsorption studies. Full article

Aquaculture effluent appears as an alternative for reuse, given its significant generation. However, its use must be reasonable to avoid damage to the environmental quality of the soil. In this context, the objective was to evaluate the chemical changes in Ultisol cultivated with small prickly pear cactus and irrigated with different dilutions of aquaculture effluent in the supply water. The experiment was conducted at the Water Reuse Experimental Unit, located in the Brazilian semi-arid region, Mossoró, RN, Brazil. Planting was carried out in a randomized block design with five treatments and five replications. A small prickly pear cactus was irrigated weekly for 365 days, with the gross water depth determined based on the crop’s evapotranspiration. During the experimental period, the physical-chemical characterization of the effluent dilutions was conducted every 60 days, with initial and final descriptions of the soil in the 0.0–0.20 m and 0.20–0.40 m layers. Additionally, cation exchange capacity and the exchangeable sodium percentage were determined. Multivariate statistical analysis was applied to understand chemical changes in the soil. The dilutions containing a higher proportion of aquaculture effluent in the supply water, primarily consisting of 100% effluent, exhibited the chemical changes in the soil. Using a dilution containing 25% aquaculture effluent in 75% supply water may be the most viable alternative for water supply in prickly pear cactus irrigation, with non-relevant changes in soil chemical characteristics. Full article

Background/Objectives: Down syndrome (DS) is characterised by a marked susceptibility to early-onset severe periodontitis, suggesting an intrinsic host predisposition. Interleukin-1 (IL-1) gene variants may influence inflammatory burden, yet DS-specific evidence is limited. Methods: Nineteen Caucasian adults with DS underwent a comprehensive periodontal examination and received a periodontal diagnosis according to the AAP/EFP 2018 classification. Buccal swabs were genotyped by real-time PCR for IL1A −889, IL1B +3954 and IL1RN +2018; the composite IL1A/B genotype was also evaluated. Results: All participants presented advanced, generalized periodontitis (Stage III/IV: 37%/63%; Grade B/C: 32%/68%). Variant alleles were detected in 63% for IL1A, 53% for IL1B and 37% for IL1RN, and the composite IL-1A/B genotype in 47%. Variant carriage showed associations with higher Clinical Attachment Loss (IL1A p = 0.03; IL1B p = 0.002; composite p = 0.012) and Bleeding on Probing (IL1A p = 0.02; IL1RN p = 0.05; composite p = 0.04). The composite genotype was associated with Stage IV (p = 0.027) and Grade C (p = 0.005), and tooth loss was greater among variant carriers for all polymorphisms (p = 0.01). Conclusions: In this DS cohort with advanced periodontitis, IL-1 variants (particularly the composite IL1A/B genotype) were frequently observed and were associated with greater periodontal severity and tooth loss. Full article

Background/Objectives: Essential oils (EOs) have multi-target antifungal activity, but their translation is limited by volatility and poor aqueous dispersibility. Randomly methylated β-cyclodextrin (RAMEB) inclusion may enhance effective exposure and thereby alter susceptibility, stress responses, and biofilm outcomes in a species-dependent manner. This study quantified species-specific planktonic and biofilm susceptibility to four EOs and their RAMEB complexes across clinically relevant Candida species. Methods: Lavender (L), lemon balm (B), peppermint (P), and thyme (T) oils and their RAMEB complexes (RL, RB, RP, and RT) were tested against C. albicans and non-albicans Candida. Susceptibility thresholds were used to derive phase plasticity metrics. Functional inhibition was assessed via planktonic metabolism/viability and established biofilm metabolism/viability/biomass. Mechanistic signatures were captured by ROS/RNS measurements and a qPCR analysis of antioxidant genes (CAT1, GPX1, and SOD1) was performed. Mixed-effects models and multivariate/unsupervised and interpretable classification approaches (k-means, PCA, and CRT) were used to integrate endpoints and stratify response phenotypes. Results: Susceptibility thresholds were strongly species-structured (lowest MIC₉₀/EC₁₀ for C. albicans; higher thresholds and broader sublethal windows in non-albicans species). RAMEB complexation produced formulation-dependent shifts in efficacy, with RT emerging as the most consistent broad-spectrum inhibitory condition across compartments. Biofilm biomass was comparatively insensitive even when viability was suppressed, indicating a decoupling of structural biomass from biocidal activity. Mechanistic signatures were broadly conserved across species and linked to antioxidant-program engagement, with CAT1-related rules contributing to responder/tolerant classification. Conclusions: Integrating MIC/EC plasticity with functional and mechanistic markers supports the rational selection of EO formulations; RAMEB complexation, particularly RT, prioritizes candidates for further pharmaceutical optimization while highlighting species-specific vulnerabilities. Full article

The ripe fruits of blackcurrant (Ribes nigrum L.) are rich in vitamin C, anthocyanins, and flavonoids. Besides being consumed fresh, the fruits can be processed into fruit juices, jams, wines, and other products, exhibiting considerable economic and nutritional value. Flavonoids are a class of important plant secondary metabolites with antioxidant, anti-inflammatory, and anti-cancer properties. Although previous studies have confirmed the involvement of multiple structural genes and transcription factors in flavonoid biosynthesis, the specific role of the dihydroflavonol 4-reductase (DFR) gene in regulating flavonoid accumulation during fruit development of blackcurrant remains to be clearly elucidated. In this study, we identified an RnDFR gene located in the nucleus and cytoplasm, which has the same expression trend as flavonoid content in fruit development stages. Overexpression of RnDFR improved the flavonoid accumulation and upregulated the expression levels of related structural genes (4CL, CHS, LDOX, ANR, and UFGT) in tomato. Transiently overexpressing RnDFR in blackcurrant fruit also increased the content of flavonoids and DFR enzyme activity, whereas silencing RnDFR resulted in the opposite effect. In addition, overexpression of RnDFR in tomato seedlings improved cold and drought tolerance by increasing flavonoid accumulation, reducing membrane lipid peroxidation damage and enhancing the activities of antioxidant enzymes. This study systematically reveals the key role of RnDFR in flavonoid biosynthesis and the enhancement of cold and drought tolerance, and offers an important theoretical basis for future efforts to optimize flavonoid content in blackcurrant and improve fruit nutritional quality. Full article

Environmental pollutants, lifestyle factors, and intrinsic metabolism can amplify reactive oxygen and nitrogen species (ROS/RNS) generation beyond antioxidant capacity. The resulting oxidative stress damages macromolecules, perturbs redox signaling, and may accelerate biological aging. This review synthesizes evidence published mainly in 2020–2025 on how major pollutant classes (air pollutants, metals, pesticides, nanoparticles, and micro-/nanoplastics) induce ROS through shared nodes mitochondrial electron transport disruption, NADPH oxidase activation, and redox cycling/Fenton chemistry and how these signals propagate to epigenetic remodeling (DNA methylation, histone modifications, and non-coding RNAs). To move beyond descriptive cataloging, we grade the strength of evidence by study context (cell culture, animal models, human observational studies, and clinically oriented biomarker research), highlight convergent findings and unresolved controversies, and specify key methodological limits. We then compare oxidative-stress biomarker platforms by analytical specificity, pre-analytical susceptibility, and translational readiness, distinguishing validated markers from exploratory redox-epigenetic and multi-omics signatures. Finally, we discuss how exposomics and AI-assisted multi-omics integration may support biomarker discovery while emphasizing current constraints (confounding, batch effects, and limited prospective validation) that must be addressed for clinical translation. Full article

Renal surgery for localized renal cell carcinoma carries substantial risk of acute kidney injury (AKI) regardless of surgical approach. This prospective study evaluated early biohumoral markers for AKI detection after robotic renal surgery and assessed their prognostic value for 12-month functional outcomes. Adults undergoing robotic renal tumor surgery with a healthy contralateral kidney were enrolled; AKI followed KDIGO 2012 criteria. Biomarkers measured at baseline and 2/24/72 h were serum β2-microglobulin (sβ2) serum IL-6, as well as urinary β2-microglobulin (uβ2), cystatin C (uC), and α2-macroglobulin (uα2M). Kidney function at 12 months was staged according to KDOQI criteria. Among 170 patients (35 radical nephrectomy, RN; 135 partial nephrectomy, PN), 33 developed AKI, more frequently after RN (p < 0.001); baseline biomarkers levels were similar. sβ2 was significantly higher at 2/24/72 h, and at 2 h, it achieved an AUC of 0.78 (cut-off 0.17: sensitivity 82%, specificity 60%), remaining the earliest independent predictor of AKI (p = 0.015). IL-6 differed at 24 h (AUC 0.80), uC at 72 h (AUC 0.73) and uβ2 at 72 h (AUC 0.66). Clinical AKI predicted KDOQI stage progression at 12 months (p < 0.001). Bulldog clamps (mean ischemia time 17.2 ± 6.9 min) were not associated with AKI (p = 0.99) or with KDOQI stage progression (p = 0.54). RN confers a higher AKI risk than PN. sβ2 at 2 h is the earliest actionable marker, complemented by IL-6 (24 h) and uC (72 h); short warm ischemia during robotic PN appears safe. Sequential multimarker assessment may improve recognition of AKI and support timely nephroprotective strategies. Full article

Chronic liver diseases, including fibrosis and hepatocellular carcinoma (HCC), are primarily driven by oxidative stress, yet traditional antioxidant therapies often lack the specificity and efficacy required for clinical success. This review evaluates the emerging therapeutic potential of two atypical globins, cytoglobin (CYGB) and neuroglobin (NGB), exploring their unique hexacoordinated heme structures that enable potent reactive oxygen and nitrogen species (ROS/RNS) scavenging and redox-regulated signaling. We summarize a broad range of in vitro and in vivo evidence demonstrating that these globins deactivate hepatic stellate cells, reduce extracellular matrix accumulation, and function as tumor suppressors by modulating pathways such as Raf/MEK/ERK and NRF2. In human cohorts, CYGB expression levels inversely correlate with the progression of Metabolic Dysfunction-Associated Steatohepatitis (MASH) and HCC, highlighting its potential as a clinical biomarker. Furthermore, recombinant protein therapies involving CYGB and NGB show promise in promoting collagen degradation and inhibiting malignant transformation. We conclude that CYGB and NGB represent sophisticated catalytic redox regulators that offer a novel therapeutic paradigm for restoring redox homeostasis. While delivery and pharmacokinetic barriers remain, these globins are highly promising candidates for first-in-class biologics in hepatology. Full article

A systematic elucidation of soil ammonia (NH₃) volatilization (SAV) and the underlying drivers is imperative for evaluating NH₃ pollution mitigation strategies and advancing sustainable agricultural practices. Currently, no scientific consensus has been established on the effects of maize–soybean intercropping on SAV across varying nitrogen (N) application rates. A consecutive field experiment was conducted over a 2-year period from 2024 to 2025 with a split-plot design. The experiment comprised three cropping systems (maize monocropping (MM), soybean monocropping (MS), and maize–soybean intercropping (IMS)) and three N application rates (no N application (NN), 20% reduced N application (20%RN), and conventional N application (ConN)). The results demonstrated that N application markedly increased SAV. Accumulative SAV was 4.94–6.01 kg ha⁻¹ under NN treatment, whereas it was 8.21–27.89 kg ha⁻¹ under ConN treatment, 7.25–21.52 kg ha⁻¹ under 20%RN treatment. Under ConN treatment, the accumulative SAV in IMS was 21.34 kg·ha⁻¹ and 27.89 kg·ha⁻¹ in 2024 and 2025, respectively, which were significantly higher than those in MM by 16.80% and 13.33%. Under 20% RN treatment, the accumulative SAV in IMS was 15.46 kg·ha⁻¹ and 19.24 kg·ha⁻¹ in 2024 and 2025, respectively, which were lower than those in MM by 3.07% and 10.59%. SAV was positively correlated with soil ammonium N concentration. Moreover, within an appropriate range, SAV increased in response to rising soil water content and temperature. Collectively, maize–soybean intercropping integrated with a 20% nitrogen reduction mitigated environmental risks associated with reactive nitrogen losses. This system constitutes a stable yield, resource-efficient, and ecologically sustainable cropping practice. Full article

Human serum albumin (HSA) is the most abundant protein in plasma, and the redox state of circulating HSA has been used as a biomarker of systemic oxidative stress (OS) for decades. While informative, many traditional biomarkers of OS measure short-lived or downstream products of oxidative damage that offer limited perspectives on the dynamic and integrated processes that govern systemic redox biology within human populations. By moving beyond single-analyte damage markers and towards coordinated patterns of protein modifications, HSA-Cys³⁴ adductomics offers a systems-level approach that simultaneously captures change in multiple layers of OS. Because of its high abundance in plasma and HSA’s unique and highly reactive single free thiol (Cys³⁴), HSA-Cys³⁴ serves as an ideal sentinel target for monitoring reactions with reactive oxygen species (ROS), reactive nitrogen species (RNS), and electrophilic species produced by endogenous metabolism and responses to exogenous chemical exposures. The reaction of HSA with ROS, RNS, and reactive electrophiles yields a diverse array of protein modifications, including direct oxidation products (sulfenic, sulfinic, and sulfonic acid), low molecular weight thiol-disulfide exchange, and lipid peroxidation (LPO)-derived reactive aldehydes. With a mean residence time of about a month, these accumulated adducts serve as an integrated picture of oxidative and electrophilic stress that together function as a molecular record of systemic redox physiology. Previous studies using high-resolution mass spectrometry-based adductomics have enabled global untargeted analysis of HSA-Cys³⁴ modifications, yielding an expansive inventory of novel redox signatures of environmental stressors and disease states. In this paper we review the chemistry and biology underlying OS-related modifications of HSA-Cys³⁴ and highlight the important role of HSA-Cys³⁴ adducts as integrative biomarkers of OS at the interface of molecular biology, exposure assessment, and public health research. Full article