Abstract:

Hyaluronic acid (HA)–based nanocapsules containing plant-derived bioactives are promising formulations for dermatological applications. In this study, nanocapsules containing extracts of Arnica montana, Calendula officinalis and Aesculus hippocastanum were synthesized and their structural and functional properties were characterized. Scanning electron microscopy confirmed the formation of spherical nanostructures with uniform morphology, while rheological analyses demonstrated stable viscoelastic behavior suitable for topical application. Their antimicrobial potential was assessed on microorganisms isolated from multiple regions of healthy human skin and opportunistic pathogens. A diverse panel of approx.. 100 bacterial and fungal isolates was identified using MALDI-TOF MS. Antimicrobial activity of formulations was compared with commonly used disinfectants: H₂O₂, octenidine, isopropanol and topical ophthalmic antiseptic. Arnica-based formulations showed the strongest inhibitory effect against both Gram-positive and Gram-negative bacteria, whereas chestnut extract demonstrated selective activity against Candida spp. Calendula-based formulation exhibited limited antimicrobial activity. These findings demonstrate that plant-extract-loaded HA nanocapsules exhibit selective antimicrobial properties dependent on extract type and microbial group, supporting their potential as multifunctional components of future dermatological formulations.

Abstract: This study investigated the effects of different application rates of spent mushroom substrate (SMS) from Morchella sextelata on soil properties and microbial communities in a moso bamboo (Phyllostachys edulis) plantation. Three SMS rates (2.4, 4.7, and 9.4 kg·m⁻² ) were applied, and soil samples were collected at 6 and 12 months from two depths (0–20 cm and 20–40 cm). One year after application, topsoil total phosphorus (TP) increased 12–20 fold, while available phosphorus (AP) and potassium (AK) were significantly elevated. Soil pH initially decreased but partially recovered, whereas electrical conductivity (EC) continued to rise, indicating salt accumulation. Urease (UA) and sucrase (SA) activities increased 10–17 fold and 3–5 fold, respectively, while catalase (CAT) and acid phosphatase (ACP) were temporarily suppressed. SMS application significantly altered microbial community composition, with Acidobacteriota and Basidiomycota becoming more abundant. Correlation analysis identified pH, organic matter, AP, and UA as key factors linked to microbial changes. The medium application rate (4.7 kg·m⁻² ) provided the best balance between soil improvement and environmental risk. These findings demonstrate that M. sextelata SMS can effectively enhance soil fertility while modulating microbial communities, but salt accumulation and short-term acidification warrant attention.

Abstract: Cyber Ranges (CRs) are complex socio-technical ecosystems, combining infrastructure resources, software services, learning mechanisms, and human-in-the-loop processes for cybersecurity training, education, and experimentation. However, their design and representation are conventionally described by diverse architectural representations and a lack of standardization, making them difficult to compare, integrate, and reason in an automated manner. This paper proposes a novel framework that uniquely integrates the structural, functional, informational, and decisional aspects of CR platforms, formalizing them into a common semantic framework. It models the architectural and learning characteristics of CRs, allowing the representation of design choices, operational processes, information resources, and capability development. The ontology is implemented using OWL 2 DL, which includes logical constraints and enables consistency checking and automated reasoning. Validation through instantiation and competency question assessment shows that the model allows for structured querying, traceability across abstraction levels, and capability-level reasoning. The findings indicate that ontology-based modeling can serve as a basis for more formalized CR configuration analysis and capability-focused evaluation of diverse CR platforms.

Abstract: Social sustainability, encompassing equitable development, livable urban construction, and inclusive social governance, has become a core dimension of sustainable development goals (SDGs) and urban planning practice in the context of rapid urbanization. Taking the Yangtze River Delta (YRD) urban agglomeration—the most economically developed and urbanized region in China—as the study area, this research constructed a comprehensive evaluation index system of social sustainability from three dimensions: equitable resource allocation, livable urban environment, and inclusive social development. Based on multi-source data from 2010 to 2020 (including socioeconomic statistics, remote sensing imagery, and open geospatial data), the entropy weight-TOPSIS model was used to measure the spatiotemporal evolution characteristics of social sustainability in the YRD. Additionally, the GeoDetector model was employed to identify the key driving factors and their interactive effects on the spatial differentiation of social sustainability, and the future development trends of social sustainability under three scenarios (urban expansion, ecological priority, and coordinated development) were predicted using the PLUS model. The results showed that the overall social sustainability of the YRD presented a steady upward trend from 2010 to 2020, with a spatial pattern of "high in the core, low in the periphery" and significant inter-city disparities. Equitable resource allocation was the primary constraint on social sustainability in peripheral cities, while livable urban environment was the main advantage of core cities such as Shanghai, Nanjing, and Hangzhou. The driving factor detection indicated that per capita GDP, urban green space rate, and the number of medical and educational institutions per 10,000 people were the top three key factors affecting social sustainability, with the interactive effect of any two factors showing a dual-factor enhancement pattern. Under the coordinated development scenario, the social sustainability of the YRD will achieve the most balanced and high-quality growth by 2030, with the peripheral cities narrowing the development gap with the core cities significantly. These findings imply that future urban development in the YRD should adhere to the concept of coordinated and inclusive development, optimize the spatial allocation of public resources, and promote the integrated construction of livable cities, so as to realize the high-quality social sustainability of the urban agglomeration. This study provides a quantitative method and empirical reference for the evaluation and optimization of social sustainability in China’s urban agglomerations and even in other rapidly urbanizing regions worldwide.

Abstract: Soluble solid content (SSC) is a critical indicator of ‘Red Fuji’ apple quality, directly governing fruit grading and maturity assessment processes. Conventional SSC measurement by refractometry is destructive and time-consuming, rendering near-infrared diffuse reflectance spectroscopy (NIR-DRS) a promising nondestructive alternative. In this study, a low-cost and compact embedded spectrometer named as DLP NIR-scan Nano EVM was used to acquire NIR-DRS spectra of ‘Red Fuji’ apples for SSC prediction. To improve prediction accuracy, we combined spectral preprocessing with machine learning methods. The dataset was cleaned using Monte Carlo outlier detection, and samples were divided into calibration and validation sets via Kennard–Stone (KS) and joint X-Y distance (SPXY) algorithms. Among preprocessing methods tested, a 12-point second derivative performed best when paired with KS partitioning. For feature-wavelength selection on the preprocessed KS data, competitive adaptive reweighted sampling, Monte Carlo uninformative variable elimination, and Random Frog were applied to the second-derivative spectra. Partial least squares regression (PLSR) models were then built using both full-spectrum data and four sets of selected wavelengths. The best preprocessed PLSR model achieved R2c = 0.916, RMSEC = 0.4093%, R2p = 0.8632, and RMSEP = 0.537%. These results demonstrate that NIR-DRS, combined with appropriate preprocessing and modeling strategies, offers a reliable, rapid, and nondestructive method for apple SSC quantification, paving the way for portable, cost-effective instruments for commercial fruit quality monitoring.

Abstract: Introduction: With age and injury, the infiltration of fat in the paraspinal muscles can cause degeneration, disorganizing the structural integrity of the connective tissue, causing lower back pain (LBP). Human umbilical cord tissue allografts (UCTa) have a collagen-rich matrix with various ECM components that can replace damaged connective tissue. The objective of this study is to evaluate preliminary findings on the safety and efficacy of UCTa for the supplementation of degenerated tissue in thoracic and lumbar paraspinal muscles refractory to standard conservative methods. Materials and Methods: A total of 141 patients from an observational repository were identified with paraspinal muscle degeneration. Patients received one to three applications of UCTa, outcomes were tracked using the Numeric Pain Rating Scale, the Western Ontario and McMaster University Arthritis Index, and the Quality-of-Life Scale. Results: All groups showed positive improvement in the NPRS and WOMAC scales. Multi-application groups revealed statistically significant differences in the analyses. No adverse events or complications were reported. Discussion: Limitations included a lack of a control group and the increase of recall and response bias due to using patient-reported measures. Conclusion: This pilot investigation highlights the need for continued research through randomized controlled trials to validate efficacy, establish optimal dosage protocols, and compare UCTa to other conservative interventions.

Abstract: This article seeks to explore and analyze the interrelationship between environmental factors, the structure of the energy sector, and stability/resilience within the financial sector by employing data from OECD countries between 2004 and 2021. The article utilizes new data sets provided by the World Bank Group's Global Financial Development Data and Sovereign ESG Data, with specific emphasis placed on the bank capitalization indicator, which is described as the bank capital asset ratio, and is considered an important factor in sectoral stability/resilience. Using fixed effect panel data econometrics, the article suggests that methane emissions, PM2.5 air pollution, and net energy imports have statistically significant impacts on the bank capitalization process, while renewable energy and bank capitalization have positive and statistically significant associations. The positive association between fossil fuel consumption and bank capitalization suggests that there is an inherent contradiction between current sectoral stability/resilience and the challenges associated with the energy transition process. The Hausman test suggests that omitted variables may exist and that fixed effect econometrics is an appropriate model. Clustering analysis suggests that each country has an underlying regime driven by environmental factors, the structure of the energy sector, and sectoral stability/resilience. Moreover, machine learning regression analysis employing K-Nearest Neighbors (KNN) and Random Forest models indicate that significant predictive potential is possible and that energy dependence, renewable energy, and air pollution are important factors in bank capitalization processes. The article suggests that robust evidence is provided regarding environmental quality and its interrelationship with sectoral stability/resilience and has significant implications for developing macroprudential frameworks that incorporate elements of the energy transition process.

Abstract: Water-In-Salt (WIS) electrolytes are expected to replace the expensive and environmentally harmful organic electrolytes while delivering high voltages and improved system safety. In this study, we conducted a failure modes, mechanisms, and effects analysis of a highly concentrated potassium acetate (KAc) electrolyte, evaluated and degraded at 2V in a conventional EDLC carbon-based symmetric configuration. The adopted method provides a simplified yet effective approach for assessing the complexity and interconnectivity of degradation mechanisms in a WIS supercapacitor. The effects analysis included electrochemical stability studies, post-mortem characterizations (SEM-EDS and XPS), low-frequency impedance fitting, and cell reassembly using end-of-life electrodes. Among the failure modes analyzed, electrolyte decomposition and pore blocking exhibit strong physicochemical correlations and high failure rates. Therefore, they should be prioritized in the design of new WIS electrolyte compositions for next-generation energy storage systems.

Abstract: Understanding the hydration dynamics of montmorillonite clay minerals is critical for predicting their behavior in geotechnical and environmental applications. This study employs in situ environmental scanning electron microscopy (ESEM) combined with X-ray diffraction (XRD) to directly observe and quantify the wetting and drying processes of montmorillonite SWy-1 under controlled pressure and temperature conditions. To characterize the real-time wetting and drying morphologies of montmorillonite and determine the relationship between water-induced swelling and relative humidity, ESEM enabled direct visualization of water-clay interactions by precisely controlling chamber pressure (4–5.3 Torr) and temperature (~2°C) to manipulate relative humidity and induce water condensation on mineral surfaces, while quantitative analysis of particle areas before and after hydration determined swelling percentages, XRD measured basal spacing (d₀₀₁) changes across relative humidity gradients, and water-adsorption isotherms were constructed from ESEM thickness measurements. ESEM revealed distinct wetting stages with water preferentially condensing on unsaturated edge sites and external surfaces at low pressures (<4.6 Torr), followed by rapid interlayer filling at elevated pressures with characteristic structural rounding and aggregate formation, while anisotropic swelling ocurred predominantly perpendicular to clay layers, with single water-layer hydration (1W) producing ~19% swelling and two-layer hydration (2W) yielding ~32% swelling, water-adsorption isotherms exhibited exponential swelling behavior with pronounced type H3 hysteresis, logarithmic analysis revealed steeper pressure dependency during hydration (slope = 2.7249) versus dehydration (slope = 1.6702) indicating thermodynamically driven water uptake but kinetically limited desorption, and rapid dehydration kinetics occurred within 3 minutes with complete equilibration by 15 minutes. ESEM successfully bridges microscale observations and molecular-scale understanding of smectite hydration, establishing practical timescales for clay equilibration and providing critical insights for predicting clay behavior in geotechnical engineering, soil stabilization, contaminant transport, and engineered barrier design.

Abstract: Background: Care for knee osteoarthritis (KOA) is frequently fragmented, and pathway-level decisions within Physical Medicine and Rehabilitation (PM&R) are influenced by local organizations. We sought expert consensus on an ideal, function-oriented KOA care itinerary deliverable in PM&R services. Methods: A two-round Real-Time Delphi study was conducted using the SmartDelphi web platform. A steering committee of five PM&R physicians developed a 37-item questionnaire covering referral/access, functional and outcome assessment, conservative management, escalation/referral thresholds, and follow-up/discharge. Round 1 was online (SERMEF osteoarthritis working group; 46 invited, 40 completed; 87.0%) with responses collected until 30 April 2025. Round 2 was an in-person, facilitated validation round on 30 May 2025 at the SERMEF Congress (A Coruña; 85 invited, 70 completed; 82.4%). Items were rated on a 6-point Likert scale; consensus strength was defined by interquartile range (IQR): strong (0–1) vs weak (≥2). No patient-level data were collected; participant characteristics were comparable across rounds, suggesting consensus refinement reflected deliberation rather than panel shifts over time. Results: Consensus supported a longitudinal, function-first pathway structured into five phases: entry/referral to PM&R; comprehensive functional assessment using a minimum outcomes dataset (pain VAS/NRS, WOMAC function, quality-of-life scale); multimodal conservative rehabilitation combining exercise/physiotherapy, education/self-management support, and indicated oral/topical therapies; reassessment-guided escalation in non-responders, reserving interventional PM&R techniques, multidisciplinary musculoskeletal pain-unit management, or orthopaedic evaluation for persistent pain and/or functional limitation; and longitudinal monitoring with defined discharge criteria. Conclusions: SERMEF PM&R experts converged on an implementation-oriented, outcomes-driven KOA itinerary centred on functioning, conservative multimodal care, structured reassessment, and explicit discharge planning.

Abstract: Drought has become a major threat among extreme weather events impacting ecosystems, the economy, food production, and livelihoods. Since the beginning of this century, it has significantly affected Nigeria's economy by reducing agricultural productivity and internally generated revenue. In Northern Nigeria, the shift from meteorological to agricultural drought has not been adequately monitored, particularly concerning future predictions using Artificial Intelligence (AI) and Remote Sensing (RS) methods. Therefore, this study employs AI and EO techniques to analyse and forecast the spatiotemporal dynamics of agricultural drought propagation in North-Central Nigeria from 2000 to 2024. The Vegetation Condition Index (VCI), the Temperature Condition Index (TCI), the Temperature Vegetation Drought Index (TVDI), and the Standardized Precipitation Evapotranspiration Index (SPEI) were used to evaluate vegetation health, temperature variation, and drought severity during the study period. For the machine learning component, Gradient Boosting Regressor was used to predict drought events over five years using cross-validation methods. This study confirms persistent drought events in 2011, 2015, and 2022, with the propagation of meteorological to agricultural drought in 2015, as indicated by VCI, TCI, and TVDI. The integration of AI and EO approaches for drought propagation assessment could enhance climate resilience efforts (SDGs 2, 13 & 15) and provide a framework for drought mitigation strategies in regions prone to drought recurrence, including the study area.

Abstract: Sensorineural hearing loss (SNHL) is caused by excessive noise exposure, ototoxic drugs, and aging. SNHL is frequently linked to glutamate excitotoxicity, as glutamate is the main excitatory neurotransmitter at the inner hair cell – spiral ganglion neuron synapses. However, we still do not fully understand the specific roles of different glutamate receptor subtypes both in normal signaling and in causing excitotoxic damage. The investigation of these questions demands the availability of relevant experimental models. This review aims to compare existing protocols for obtaining primary spiral ganglion neurons in vitro and to assess the utility of this model in studying glutamatergic transmission. A literature search in PubMed and Google Scholar identified 16 relevant articles in English published since 1990, when the model was first introduced. Our analysis reveals significant heterogeneity protocols in isolation and conditions of cultivation. We highlight the significant differences in glutamate concentrations when modeling excitotoxicity and the glutamate receptor agonists used to study electrophysiological properties. The most significant limitation of this model is the loss of the native microenvironment of neurons, including their dendritic and axonal contacts. Nevertheless, primary spiral ganglion neurons serve as a suitable in vitro model for investigating auditory neuron function and pathology. This in vitro model allows detailed study of the mechanisms underlying ototoxicity and otoprotection. The number of neurons and neurite length serve as reliable indicators of otoprotective effects under conditions of glutamate excitotoxicity. This work may help researchers who plan to use the primary SGNs in their laboratories, as well as those who aim to optimize their methods based on accumulated experience.

Abstract: Building details are often treated as technical externalities, subordinate to form, image and architectural narrative. Reading details as liminal spaces reverses that hierarchy. The joint concentrates transitions between inside and outside, public and private, ex-posure and protection, and those transitions are constructed as intervals, experienced through thickness, reveal, edge condition, shadow, touch and the small resistances that accompany crossing. The article develops its analysis through archival hand-drawn detail drawings from the Azrieli Architectural Archive. It defines building details as both technical assem-blies and threshold devices, points where architecture becomes accountable to percep-tion as well as to climate, labor, regulation and everyday use. A semiotic reading of large-scale sheets shows how line weight, hatching, notation and layout encode priori-ties, marking boundaries between what must be precisely resolved and what may re-main adjustable. The archive is treated as a laboratory of “detail families,” recurring junction types such as windows, stairs and envelope edges that reveal office-specific languages of joining. Two case studies, by the architects Ram Karmi and Arieh Sharon with Eldar Sharon, show how micro-variations in depth, overlap and edge control tune thresholds, pro-ducing perceptual tipping points where comfort can shift into irritation, calm into un-ease and openness into vulnerability. Although grounded in a local archive, the argu-ment addresses a broader condition of contemporary practice: standardization and digital production chains can relocate authorship and responsibility away from the joint, precisely where buildings most affect everyday conduct. The paper proposes a liminal literacy of detailing as both a historiographic method and a design ethic aimed at making threshold decisions legible, contestable and accountable in present-day workflows.

Abstract: Background: The diagnosis of autonomic dysfunction underlying Hereditary Coproporphyria (HCP) represents a major clinical challenge. Given the nonspecific and episodic nature of its crises, neurological and gastrointestinal symptoms are frequently misinterpreted and misdiagnosed as anxiety disorders or psychosomatic syndromes, severely delaying proper therapeutic management. Although HCP is characterized by the accumulation of porphyrin precursors, the high variability in tissue damage—ranging from refractory Small Intestinal Bacterial Overgrowth (SIBO) to inflammatory oncological processes (such as cholangiocarcinoma and cutaneous lymphomas)—suggests the necessity of an external catalyst. I postulate that abnormal iron metabolism is the primary driver of this pathological progression. Hypothesis: Iron overload mediated by the HFE mutation, combined with low ferroxidase activity (ceruloplasmin), generates an excess of non-transferrin-bound iron (NTBI) in the ferrous state (Fe2+). Furthermore, the high demand for heme synthesis driven by elevated hemoglobin forces the defective CPOX enzymatic pathway, massively increasing the accumulation of isomer III precursors. Free Fe2+ then acts as an oxidizing agent, transforming the inert coproporphyrinogen III into highly reactive and toxic coproporphyrin III. Mechanism: The oxidation of these isomers triggers systemic oxidative stress. Locally, oxidized porphyrins induce autonomic neuropathy in the myenteric plexus, paralyzing gastrointestinal motility and promoting intractable SIBO. Systemically, the massive biliary excretion of these reactive compounds causes chronic chemical inflammation in the bile ducts, increasing the risk of cholangiocarcinoma. Concurrently, cutaneous deposition of oxidized porphyrins generates chronic antigenic stimulation in the dermis, potentially acting as a trigger for lymphoproliferative neoplasms, such as marginal zone B-cell lymphoma. Clinical Relevance: This model suggests that patients with overlapping HFE and CPOX mutations face both autonomic dysfunction (SIBO) and elevated oncological risk due to chronic inflammation. Early management through therapeutic phlebotomies to reduce hemoglobin-driven heme demand and halt Fe2+-mediated oxidation, alongside intestinal binders, could prevent both neurogastrointestinal damage and long-term malignant transformation.

Abstract: Unlike geometry, spheres in topology have been seen as topological invariants, where their structures are defined as topological spaces. Forgetting the exact notion of geometry, and the impossibility of embedding one into another, homotopy theory relates how a sphere of one dimension can wrap around, or map into, a sphere of another dimension. This paper revisits the classical theory of homotopy groups of spheres, providing a detailed exploration of their computation and structure. We place special emphasis on the pivotal role of Hopf fibrations in revealing the higher homotopy groups of spheres, particularly the exotic and fascinating case of π₃(S²). Furthermore, we explore the elegant geometric connection to Villarceau circles, demonstrating how these circles on a torus are intimately linked to the Hopf fibration of S³. This work serves as a comprehensive guide, bridging abstract algebraic topology with tangible geometric phenomena. This version expands significantly on the foundational ideas, providing deeper insights and connections to contemporary research, including stable homotopy theory, the Adams conjecture, and generalizations to Calabi-Yau manifolds.

Abstract: Under resource constraints, technology-based SMEs are highly sensitive to the return on training investment. This study analyzes the impact of different training strategies on employee performance, focusing on the relationship between skills gap and training effectiveness. Based on skills assessment, training records, and performance appraisal data of 2,784 technical personnel in a technology-based SME, a skills gap index was constructed, and two types of investment methods were distinguished: general training and job-oriented training. A multiple regression model was used to analyze the relationship between training duration and performance changes. The results show that implementing job-oriented training for employees with skills gaps in the upper quartile resulted in an average performance score improvement of 0.21 standard deviations, while the improvement from general training was less than 0.06. The research results provide a quantitative basis for SMEs to optimize the allocation of training resources.

Abstract: 1,4-Dimethoxy-2,3-dinitrobenzene (1) reduction using sodium hydrosulfite gave 3,6-dimethoxybenzene-1,2-diamine (2) and 3,6-dimethoxy-2-nitroaniline (3) in 24% and 59% yield respectively. The nitroaniline 3 was acetylated with acetyl chloride to give N-(3,6-dimethoxy-2-nitrophenyl)acetamide (4) in 65% yield and with acetic anhydride to give N,N’-(3,6-dimethoxy-2-nitrophenyl)diacetamide (5) in 78% yield. Novel compounds 4 and 5 were characterized by FT-IR, 1H and 13C-NMR, and HRMS. The X-ray crystal structure of acetamide 4 is presented.

Abstract: Modern insurance organizations have adopted artificial intelligence in narrow, task-specific roles, resulting in fragmented systems that optimize isolated functions without fundamentally reshaping the underwriting and claims lifecycle. This “incrementalism” yields a human-default, sequential process plagued by structural bottlenecks, inconsistent risk evaluation, and limited transparency. This paper introduces NEXUS (Next-Generation Executive Underwriting and Settlement Intelligence), a framework to re-architect insurance as an AI-native system. NEXUS transitions AI from a peripheral tool to the primary orchestrator of end-to-end processes, conceptualizing the insurance lifecycle as a conversational, agent-orchestrated workflow. It is realized through a unified conversational interface that coordinates a decentralized ecosystem of specialized, collaborative AI agents each responsible for domain-specific reasoning such as geospatial risk assessment, financial verification, or medical outcome analysis. The central innovation is the Truth Score Engine (TSE), a governance-first aggregation mechanism that non-linearly synthesizes agent outputs by weighting evidentiary provenance, confidence estimates, and cross-agent consistency. The TSE governs decisions via a Three-Tiered Confidence Protocol: • High Confidence (>90%) validates outcomes for immediate human sign-off without re-verification; • Medium Confidence (60-90%) routes decision summaries for targeted human review of specific flags; • Low Confidence (<60%) escalates cases as ‘’Risky,’’ reverting to traditional manual investigation. This protocol yields a single, auditable decision artifact while preserving full traceability of the reasoning pathway. By embedding multi-agent coordination, contextual awareness, and tiered governance at the architectural level, NEXUS demonstrates a scalable pathway toward adaptive, transparent insurance systems. It ensures precision, combats fraud, and dramatically reduces settlement time, positioning AI-native governance as a foundational requirement for deploying trusted, autonomous decision-making in high-stakes financial domains.

Abstract: Many medicines do not dissolve well in water, which can limit how quickly and effectively they work. One proven way to improve this is to attach a natural sugar molecule to the drug. In this study, we investigate paracetamol β-D-glucoside (C₁₄H₁₉NO₇), a modified form of paracetamol in which glucose is chemically linked to the drug through a β-glycosidic bond. This simple molecular change increases water solubility by 6–8 times compared to regular paracetamol, allowing faster dissolution and more flexible liquid formulations. The sugar–drug link is stable under normal body conditions but breaks apart under specific environments. At neutral pH (similar to blood), the compound remains highly stable, with a half-life exceeding 1000 hours at 25 ℃. Under acidic conditions similar to the stomach (pH 2, 37 ℃), it breaks down within minutes, releasing active paracetamol. Natural enzymes in the intestine and liver can also rapidly cleave the bond, enabling controlled and site-specific drug activation. Computer simulations confirm the proposed breakdown mechanism and support the experimental findings. Stability testing was performed under internationally recognised pharmaceutical guidelines (ICH, USP, FDA, EMA), showing predictable behaviour and acceptable impurity control. Formulation strategies such as protective coatings and temperature management suggest a projected shelf life of 2–3 years. Importantly, when the compound breaks down, it releases both paracetamol and a small amount of glucose. This creates a dual-action system that provides pain relief while also contributing mild energy support during illness. Paracetamol β-D-glucoside, therefore, represents a practical and scientifically validated approach to improving a widely used medicine.

Abstract: The quantitative PCR standard curve is the central analytical tool for validating qPCR assays and can also be used to estimate target concentrations in test samples. This review explains how qPCR standard curves are constructed, validated, and analysed for different purposes. We first examine an idealised standard curve generated using an exceptionally high number of replicates, far exceeding typical routine use. This approach clearly illustrates fundamental qPCR characteristics and provides an educational framework for defining and estimating PCR efficiency, limit of detection, and limit of quantification. Furthermore, we demonstrate that, in theory, variation in threshold crossing points across replicates can be used to estimate the number of target molecules in a sample. This method, which we term variance PCR, could complement digital PCR and potentially extend the dynamic range of absolute quantification. We also analyse a representative standard curve as typically processed in routine qPCR workflows. This includes validating its dynamic range, assessing the impact of outliers, estimating PCR efficiency and precision, and finally applying the curve to determine the concentration of test samples.