Search Results (3,697)

Background: Sarcopenia, systemic inflammation, and malnutrition are established poor prognostic factors in renal cell carcinoma (RCC). This study investigated the utility of a novel preoperative score combining psoas muscle density (PMD)—an imaging-based indicator of muscle quality—and the albumin–bilirubin (ALBI) grade—a blood-based biomarker of liver reserve and systemic nutritional status—for predicting disease-free survival (DFS) and overall survival (OS) in patients undergoing curative surgery for RCC. Methods: This retrospective observational study included 274 patients with non-metastatic RCC treated with radical or partial nephrectomy. Preoperative computed tomography was utilized to measure PMD, defining “low PMD” as a value below the sex-specific median (males: 47.75 Hounsfield Units [HU]; females: 46.25 HU). “Worsened ALBI” was defined as an ALBI grade ≥ 2. Patients were stratified into three risk categories: Score 0 (both normal, n = 122), Score 1 (either abnormal, n = 114), and Score 2 (both abnormal, n = 38). Results: Kaplan–Meier analysis revealed a highly significant, stepwise decline in both DFS and OS as the risk score increased (log–rank p < 0.001 and p = 0.004, respectively). Multivariate Cox regression identified the combined risk score as a robust, independent prognostic factor for DFS (Score 1: HR 1.93, 95% CI 1.11–3.37, p = 0.020; Score 2: HR 3.58, 95% CI 1.82–7.02, p < 0.001). Furthermore, after adjusting for age and comorbidities, the score remained an independent predictor of poor OS (Score 1: HR 2.35, 95% CI 1.08–5.13, p = 0.032; Score 2: HR 3.01, 95% CI 1.16–7.82, p = 0.024). The combined model synergistically enhanced risk stratification accuracy compared to evaluating either factor independently. Conclusions: The concurrent presence of preoperative low PMD and a worsened ALBI grade is a powerful, independent predictor of poor prognosis in localized RCC. Derived solely from routine preoperative imaging and laboratory tests, this straightforward scoring system effectively captures the structural and immunometabolic dimensions of cancer cachexia and host vulnerability. This tool can significantly aid in personalizing postoperative surveillance strategies and identifying high-risk patients who may warrant closer postoperative surveillance or who might be considered as high-risk candidates for adjuvant therapy discussions. Full article

Intensive yak fattening in cold alpine regions requires essential long-term high-concentration feeding, which disrupts rumen microbial homeostasis and causes inefficient digestion of nutrients. Lactobacillus may have probiotic potential for ruminants, yet its regulation of rumen function is poorly understood under high-energy diets. During a 120-day feeding experiment, 120 male Pamir yaks were allocated to four dietary treatments, with LEG and LLG serving as the primary comparison for evaluating 0.02% Lactobacillus supplementation to explore the regulatory effects of Lactobacillus supplementation on the rumen microbiota and host metabolism of yaks during a fattening process based on a concentrate feed diet via phenotypic data (body wight and nutrient digestibility) and multi-omics analyses (rumen microbial sequencing and rumen epithelial transcriptome) in a concentrate-based rearing yak model. The results showed that Lactobacillus intervention reduced OTU (Operational Taxonomic Unit) richness during the early fattening period and subsequently promoted microbial recovery through colonization resistance, which significantly enhanced microbial diversity (p < 0.05), and restructured the microbial community structure toward efficient energy utilization under high-concentrate feeding by reducing Prevotellaceae and Ruminococcaceae abundance, increasing the Bacillota/Bacteroidota ratio (p < 0.05). Concurrently, Lactobacillus enhanced the apparent digestibility of dry matter, crude protein, and fibrous components (p < 0.05). According to the transcriptomic analysis, there was an activation of signaling pathways related to IL-18 and TNF, and up-regulation of immune-and metabolism-related genes, in addition to strengthening the rumen mucosal barrier function. Multi-omics integration supported that dietary supplementation of Lactobacillus can optimize rumen fermentation, enhance nutrient digestion, and strengthen immune defense in Pamir yaks fed high-concentrate in cold seasons. These modifications demonstrate the positive effects of the Lactobacillus supplementation strategy on yak rumen health without interfering with the high-energy intensive rearing pattern. The present research presents a scientific basis for the use of targeted probiotic strategies to improve the rumen health and efficiency of alpine yak production systems. Full article

Background/Objectives: Adults at high risk of type 2 diabetes frequently show concurrent dyslipidemia, insulin resistance, and central adiposity before overt diabetes develops. We evaluated cardiometabolic responses to standardized whole-grain staple replacement and examined grain-quality patterns in free-living and country-level settings. Methods: This secondary exploratory analysis included 144 participants (48 per group) from a 12-week, three-arm randomized dietary trial. Participants were analyzed according to their randomized assignments to 100 g/day, 50 g/day, or control. Lipid, anthropometric, body composition, and composite cardiometabolic phenotypes were evaluated. Longitudinal and time-weighted cumulative effects were estimated using linear mixed-effects and regression models, with Benjamini–Hochberg false discovery rate (FDR) correction applied within the corresponding multiplicity domains. Complementary analyses included 30,769 NHANES adults without diabetes, including 12,169 with prediabetes, and descriptive country-level data on whole-grain intake, high-FPG-attributable diabetes burden, and cereal supply. Results: Within the extended phenotype panel, HWG versus control time-weighted cumulative effects included triglycerides (β = −0.220, 95% CI −0.397 to −0.043; FDR-adjusted p = 0.047), the atherogenic index of plasma (β = −0.125, −0.191 to −0.060; FDR-adjusted p = 0.002), and the triglyceride–glucose index (β = −0.301, −0.429 to −0.173; FDR-adjusted p < 0.001). Conventional lipid components showed distinct temporal responses. In NHANES, higher whole-grain exposure and more favorable grain-quality ratios were associated with lower adiposity- and insulin resistance-related phenotypes, whereas refined-grain exposure generally showed the opposite pattern. Country-level analyses showed marked heterogeneity in whole-grain intake, diabetes burden, and cereal supply context. Conclusions: Standardized whole-grain staple replacement was associated with short-term changes across several cardiometabolic dimensions in adults at high risk of type 2 diabetes, with the clearest extended-phenotype signals involving triglyceride-related and glucose–triglyceride coupling measures. NHANES identified cross-sectional grain-quality associations in free-living adults; country-level analyses described heterogeneity in whole-grain intake, diabetes burden, and cereal supply context. Full article

As urban underground spaces and infrastructure development accelerate, subsurface elements such as buried pipelines, integrated utility tunnels, subway tunnels, cavity defects, and deep-seated hidden hazards become increasingly intertwined. Consequently, urban target detection is characterized by pronounced scale discrepancies, intense environmental interference, and severely confined operational spaces. The transient electromagnetic method (TEM) is highly valuable for rapid surveys and hazard identification in urban underground spaces owing to its inherent advantages, including non-contact operation, adaptability to hardened pavements, high sensitivity to low-resistivity anomalies, and the ability to probe a broad range of depths. In recent years, research has shifted from improving isolated instrumentation to synergistically optimizing sensing platforms, transmitter–receiver systems, anti-interference methodologies, and imaging interpretation workflows. Specifically, small-loop configurations and high-frequency excitation technologies have improved shallow-sounding capabilities in confined urban spaces; anti-interference techniques have increased data reliability in complex noise environments; and apparent resistivity mapping, virtual wave-field migration, and rapid inversion methodologies have enabled profiling results to transition from qualitative identification to fine-scale interpretation. Concurrently, the evolution of ground-towed, UAV-borne, helicopter-borne, and semi-airborne platforms has progressively endowed urban TEM profiling with continuous, mobile, and scenario-specific operational capabilities. Looking to the future, further technical breakthroughs in urban TEM technology are required to improve shallow-resolution, deep-seated penetration, multi-source interference decoupling, and real-time concurrent imaging. Full article

Concurrent high river water temperature (RWT), low dissolved oxygen (DO), and low river flow (RF) can degrade water quality and aquatic habitat, but their joint probability is rarely quantified in a fully trivariate framework. This study develops a semiparametric trivariate drawable-vine (D-vine) copula model that uses Gaussian kernel density estimation (GKDE) margins with parametric pair-copulas to estimate compound thermal–oxygen–low-flow hazards. The framework provides conditional exceedance probabilities and AND- and OR-joint return periods (RPs) for monthly synchronized RWT–RF–DO states. The analysis uses 117 synchronized monthly triplets from the Tungabhadra and 152 from the Yamuna. Kendall’s <!-- MathType@Translator@5@5@MathML2 (no namespace).tdl@MathML 2.0 (no namespace)@ --> Full article

Fresnel high-concentration photovoltaic/thermal (HCPV/T) systems operating in sandy environments are susceptible to natural lens soiling, which attenuates the effective concentrated solar input and alters electrical and thermal performance. Natural-soiling comparison tests were conducted over 0–28 d, and an SD-CNN-BiLSTM-Attention model was developed to forecast cell-center temperature and electrical power 5, 10, and 20 min ahead. At a surface soiling density of 10.760 g·m⁻², current and electrical power decreased by 38.37% and 39.28%, respectively, relative to the concurrently operated clean-reference unit; cell-center temperature and water-tank temperature rise decreased by 7.74% and 15.13%. Thermal power also showed an overall downward trend, although the magnitude was affected by relatively large measurement uncertainty. Under grouped cross-validation, temperature RMSEs were 0.473, 0.515, and 0.555 °C at 5, 10, and 20 min, corresponding to reductions of 8.34%, 21.68%, and 44.07% relative to Persistence. Electrical-power RMSEs were 0.661, 0.618, and 0.640 W, with an 18.24% reduction relative to Persistence at 20 min. Ablation analysis showed a limited contribution from surface soiling density at 5 and 10 min but a clearer contribution at 20 min. These results support electrical and thermal performance assessment and short-term operational forecasting of Fresnel HCPV/T systems in sandy environments. Full article

The core predicament of energy transition lies not in the availability of clean technologies, but in whether an economy possesses the institutional capacity and social foundation to systematically regulate its carbon-energy metabolic processes. Drawing upon co-evolutionary theory from evolutionary economics, this paper constructs a composite indicator of Low-Carbon Green Energy Eco-Co-evolution (LCEE) encompassing three functional dimensions: efficiency advancement, kinetic energy replacement, and boundary adherence. Concurrently, by integrating innovation ecosystem theory with inclusive development theory, we propose the concept of “Inclusive Potential of Regional Innovation Ecosystems” (IEP), characterizing the systemic potential for transforming innovation outcomes into social welfare across four dimensions: Knowledge Matrix Abundance (KMF), Cultural Capillary Permeation (CCP), Technological Community Succession (TCS), and Social Root Nourishment (SRN). Taking China’s 2016 intellectual property (IP) powerhouse construction pilot as the institutional prototype of Industrial Intellectual Property Upgrading Reform (IPR), we incorporate IPR, IEP, and LCEE into a unified causal analytical framework, proposing a testable transmission logic of ‘institutional supply → ecological development → co-evolutionary synergy. Using panel data from 30 Chinese provincial-level administrative regions over 2010–2022, we employ a Spatial Durbin Difference-in-Differences (SDM-DID) model to identify the direct and spatial spillover effects of IPR on LCEE, and embed a Double Machine Learning (DML) framework to test the mediating mechanism of IEP while controlling for high-dimensional nonlinear interference. The findings reveal that IPR exerts a significant and robust direct promoting effect on LCEE, generating positive spatial spillovers to neighboring regions through the public disclosure of patent information. IEP significantly promotes local LCEE, yet its spatial spillover lacks statistical support due to structural conflicts in inter-dimensional transmission attributes. IEP plays a significant partial mediating role between IPR and LCEE, with the indirect effect accounting for over one-third of the total effect, a finding robust to alternative machine learning algorithms, sample split adjustments, and exclusion of contemporaneous competing policies. Sub-path tests reveal that KMF bears the strongest mediating efficacy, serving as the primary transmission channel, while CCP exhibits full mediation—the institutional effect on LCEE in the cultural dimension depends almost entirely on the mediating transformation through the public cultural service system. Heterogeneity analysis further demonstrates full mediation in the Low-Carbon Green Energy Eco-Kinetic Replacement (KER) dimension, indicating that the institutional catalytic effect on clean energy substitution must be realized through IEP transformation. This paper provides empirical evidence for the proposed causal pathway through which institutional public goods indirectly enhance the synergistic quality of carbon-energy transition via the inclusive potential of innovation ecosystems, providing theoretical foundations and policy implications that, while grounded in China’s institutional context, may offer valuable reference points for emerging market economies facing similar dual pressures of technological constraints and green transition. Full article

During the X-ray Diffraction (XRD) identification of the traditional Chinese medicine Os Draconis, the identification model often suffers from limited classification accuracy due to the difficulty in determining optimal parameters. To address this issue, this paper proposes a Hydrodynamic Improved Particle Swarm Optimization (HIIPSO) algorithm for the deep optimization of model parameters. In practical identification scenarios, the high complexity of XRD data poses severe challenges to the convergence speed and global search capability of optimization algorithms. To enhance model performance, this study introduces the interaction mechanism from fluid dynamics into the particle swarm optimization process. Specifically, HIIPSO incorporates a Voronoi neighbor topology to enhance population diversity and spatial distribution rationality. Concurrently, a hydrodynamic interaction mechanism is constructed to simulate the cooperative behavior of particles in a fluid environment, thereby effectively preventing the algorithm from falling into local optima. A theoretical analysis of the computational complexity of the HIIPSO algorithm in the parameter search task for XRD identification models was conducted, confirming that it falls within an ideal range for engineering applications. Statistical analysis of the experimental results demonstrates that, in the parameter optimization task for the Os Draconis identification model, the HIIPSO algorithm significantly outperforms traditional and other baseline algorithms across key metrics, including the optimal value, mean, standard deviation, and median of the objective function. The experimental data indicates that the HIIPSO algorithm can substantially improve the robustness and identification accuracy of the XRD-based Os Draconis identification model, making it an optimal solution for parameter optimization problems in the digital identification of complex mineral-based traditional Chinese medicines. Full article

The massive integration of variable renewable energy sources (vRES) in Central Europe is fundamentally transforming electricity price formation and straining transmission grids. However, existing academic metrics, such as the RES Capture Price, offer only a static view of investor revenues and fail to capture dynamic market rigidity and systemic risks during periods of high instantaneous vRES penetration. This study addresses this literature gap by introducing two novel and transparent methodological parameters: Market Exposure to Green Overproduction (MEGO) and the Price Divergence Coefficient (PDC). Formulated as conditional non-parametric indicators, the MEGO index quantifies the conditional probability of price collapse and the loss of market elasticity during hours when vRES penetration exceeds critical thresholds (α = 0.50 to 0.80) of systemic load. Conversely, the PDC index measures the frequency of substantial price non-convergence across neighbouring bidding zones (CZ, PL, FR) relative to the German reference market (DE). Based on an extensive dataset spanning from 2015 to mid-2026—capturing the transition to 15 min market time units— the empirical results reveal a distinct change in market behaviour. While the frequency of price collapse during high-vRES periods was lower in earlier years and temporarily reduced during the 2022 energy crisis, the post-crisis period (2024–2026) exhibits substantially higher MEGO values, with periods in which wind and solar generation exceeded 80% of instantaneous system load being associated with prices at or below 0 EUR/MWh in up to 60% of the evaluated intervals. Concurrently, the PDC analysis reveals persistent spatial price non-convergence, particularly in France and Poland. These patterns coincided with major changes in European electricity-market conditions, including the implementation of Core Flow-Based Market Coupling, variations in nuclear availability and evolving cross-border network conditions; however, the PDC indicator alone does not permit causal attribution to any individual factor. The proposed MEGO and PDC parameters provide policymakers, transmission system operators (TSOs), and investors with an intuitive diagnostic framework for dimensioning grid flexibility, energy storage, and cross-border infrastructure in the decarbonization era. Full article

Self-labeling enzymes, like SNAP-, CLIP- and Halo-tag have found wide application in biology, biochemistry, materials science and bioengineering. For example, they have been applied with high versatility to rewrite genetic information inside the living cell by providing rationally programmable RNA-targeting strategies of protein-based effectors. Such approaches benefit from the engineering capability of the small molecule-based self-labeling moieties. Here, we further engineered that approach to control RNA-targeting by light. Specifically, we combined two orthogonal self-labeling enzymes for the recruitment of two distinct fusion proteins to a target RNA inside the living cell and achieved concurrent assembly and disassembly of distinct guide RNA–protein conjugates. We applied this to control RNA base editing and achieved a photo-induced swap of two distinct editing events. Overall, this work describes new ways for tool development, RNA imaging, and transcript engineering. Full article

Access to in-laboratory polysomnography (PSG) is restricted by prolonged waiting lists, and first-night effects can distort typical sleep architecture. This study evaluates the PneumoWave biosensor as a scalable, unobtrusive alternative for longitudinal single-channel home sleep apnea monitoring. Over three nights in an uncontrolled home environment, the biosensor’s respiratory rate agreement was evaluated against smartwatch-derived respiratory rate estimates, whilst apnea/hypopnea detection was compared with concurrent pulse oximetry. PneumoWave and smartwatch devices demonstrated good correlation (r = 0.870; p < 0.001). The PneumoWave device showed strong measurement agreement and provided a highly predictive screening pathway for patients with intermediate-to-high obstructive sleep apnea (OSA) risk. Longitudinal analysis confirmed consistent multi-night performance without first-night effect biases (ICC = 0.956, p < 0.001). Furthermore, its intuitive design yielded zero patient-induced setup errors, highlighting its operational robustness for self-administered use. Combining this continuous chest wall monitor with the STOP-Bang clinical questionnaire has the potential to provide an effective predictive screening pathway, improving community OSA screening and assisting clinical triage. Further validation against full polysomnography is warranted before clinical adoption. Full article

Background: Edible insects constitute a highly nutritious, environmentally sustainable and culturally significant food resource with considerable potential to contribute to food system transformation within academic and broader societal contexts. Although global interest in entomophagy continues to increase, there remains limited research exploring the knowledge, perceptions, attitudes and consumption practices of university populations within rural South African settings. Methods: Three concurrent cross-sectional quantitative studies were conducted at the University of Venda (UNIVEN), located in Thohoyandou, Vhembe District, Limpopo Province, South Africa. Study 1 evaluated the knowledge, attitudes and consumption patterns of edible insects among 200 students. Study 2 examined knowledge and utilisation of edible insects among 390 students. Study 3 investigated knowledge and perceptions regarding edible insects among 200 university staff members. Structured questionnaires covering socio-demographic characteristics, knowledge, perceptions, attitudes and food frequency practices were administered across all studies. Data analysis was performed using SPSS version 28 through descriptive statistics, frequencies and percentages. Analyses were descriptive only; no inferential testing, factor analysis or regression was undertaken, and the three studies are compared as a descriptive synthesis rather than pooled into a single dataset. Results: Findings across all study groups demonstrated high levels of awareness regarding edible insects, with awareness reported by 85% of participants in Study 1 and 100% in Study 2, and 98% of staff members acknowleded the ecological importance of insects. Mopane worms (Gonimbrasia belina), termites and grasshoppers emerged as the most recognised and frequently consumed edible insect species. Consumption prevalence was notably high, reported at 91% in Study 1 and 69.2% in Study 2 and 66.3% among staff in Study 3. General attitudes towards entomophagy were largely favourable, with 41% of students expressing excitement about edible insect consumption and 91.1% of staff supporting the commercialisation of edible insects. Key barriers influencing consumption included religious restrictions (25.1%, reported in Study 2 only; participants with religious dietary prohibitions were excluded at sampling in Studies 1 and 3, limiting cross-study comparability of this barrier), cultural taboos (3%), inadequate market availability and limited awareness regarding nutritional benefits. Staff members further demonstrated positive environmental and sustainability perceptions, with 84.1% recognising edible insects as environmentally beneficial and viable future food sources. Conclusions: Across three independent cross-sectional studies conducted at the University of Venda, broadly similar patterns of awareness, attitudes, perceptions and edible insect consumption were observed. Although the studies differed in sampling and measurement, they consistently suggest that edible insects remain culturally accepted among many students and staff. Nevertheless, challenges relating to nutritional literacy, market accessibility and policy integration continue to limit broader adoption. Strengthening nutrition education initiatives and incorporating edible insects into institutional food systems may enhance the contribution of edible insects towards food security, sustainable protein provision and nutrition sustainability within Limpopo Province and beyond. Full article

Background: Childhood asthma is clinically heterogeneous, yet simple clinical approaches for describing concurrent disease burden are limited. We tested whether a two-axis phenotype matrix—built from early-onset and/or high-burden wheeze and atopic load—is associated cross-sectionally with treatment-defined severity and control in school-aged children with asthma. This exploratory, unvalidated classification requires prospective external validation before clinical use. Methods: In a two-center retrospective cross-sectional study, 337 children aged 6–12 years with physician-confirmed asthma were classified into four clinical strata (low-burden, familial/atopic-dominant, wheeze-dominant, atopic-wheezing). The primary outcome was moderate-to-severe asthma, defined by controller treatment step and deliberately independent of acute events. Variables independently associated with the outcomes were identified using multivariable logistic regression with prespecified sensitivity analyses; trends across ordered wheezing-onset categories were assessed using the Cochran–Armitage trend test, adjusted associations were confirmed by likelihood-ratio tests, and secondary outcomes were false-discovery-rate corrected. Results: The atopic-wheezing stratum was the largest group (140/337, 41.5%) and carried the highest burden: moderate-to-severe asthma 49.3% vs. 17.4% in low-burden and uncontrolled asthma 42.1% vs. 13.0% (both q < 0.01). Adverse outcomes were generally more frequent with earlier wheezing onset (moderate-to-severe asthma 26.9% to 57.9% from no early wheeze to onset ≤ 12 months; p for trend <0.001). After adjustment, the atopic-wheezing stratum had the largest adjusted odds ratios for both moderate-to-severe asthma (aOR 4.49, 95% CI 1.91–10.54) and uncontrolled asthma (aOR 4.78, 95% CI 1.85–12.35), and remained significant across all sensitivity analyses. Passive smoke exposure was independently associated with uncontrolled asthma (aOR 1.86, 95% CI 1.13–3.05) but not severity. The FEV1/FVC z-score differed significantly across strata and was lowest in the atopic-wheezing group (median z-score −1.28 vs. +0.10 in low-burden; p < 0.001). Conclusions: The co-occurrence of high atopic load with early-onset or high-burden wheezing defined the clinical stratum with the highest observed treatment requirement and poorest control, using only routine history and standard allergy work-up. Passive smoke exposure was independently associated with uncontrolled asthma. Full article

Infrared-selective stealth films, which concurrently offer high visible transmittance, suppressed infrared emission, and selective thermal dissipation, have emerged as compelling candidates for infrared protection and thermal-target stealth. However, traditional multilayer architectures are predominantly designed through empirical trial-and-error protocols, which inherently hinder the synergistic optimisation of multiband spectral performance and yield suboptimal parameter-tuning efficiency. To circumvent this bottleneck, we introduce a reinforcement learning (RL)-driven multi-objective optimisation framework that automates the design of composite thin-film configurations. The optimised multilayer film structure consists of TiO₂/ITO/Ag/ZnO/SiO₂, with layer thicknesses of 180, 656, 10, 33.75 and 50 nm, respectively. Spectral characterisation reveals a weighted average visible transmittance of 79.77% over the 0.38–0.78 μm range, alongside blackbody-weighted average emissivities of 33.93%, 72.93%, and 19.94% in the 3–5, 5–8, and 8–14 μm bands, respectively. Consequently, the spectral profile exhibits high visible transparency, deep suppression of emissivity within the atmospheric windows (3–5 and 8–14 μm), and markedly elevated emissivity in the non-atmospheric band (5–8 μm). Analysis of the electromagnetic field distribution and power-loss density along the thickness direction reveals that the energy transmission and dissipation behaviours across distinct bands are synergistically governed by multilayer interference, interfacial multiple reflections, and lossy interlayer coupling mechanisms. Furthermore, angle-resolved infrared-emissivity analysis calibrated against the normal-incidence FDTD spectrum confirms that the structure retains robust polarisation adaptability and pronounced spectral selectivity at incidence angles up to 80°. The above results demonstrate the effectiveness of the reinforcement learning-driven optimisation framework for the automated co-design of multiband spectral responses. Moreover, the uncovered multilayer interference and loss-coupling mechanisms furnish a solid physical foundation for further performance refinement and rational design of transparent stealth coatings. Full article

Background: Berberine, an isoquinoline alkaloid present in Berberis spp., Coptis chinensis and Hydrastis canadensis, is among the most widely consumed metabolic-health supplements, popularized as “nature’s Ozempic”. Concurrent, often undisclosed use with prescription drugs is common in older adults, yet berberine is far from inert. Objective: To synthesize the evidence on berberine as a perpetrator of supplement–drug interactions, propose a four-axis mechanistic taxonomy, with product quality treated separately as a modifier of exposure rather than as a mechanism, and derive a clinically actionable risk-stratification framework. Methods: Structured narrative review, prepared per the SANRA quality criteria; PubMed/MEDLINE, Scopus, Web of Science and Embase were searched up to May 2026. Results: Despite very low systemic exposure (oral bioavailability 0.68% in rats; low ng/mL plasma concentrations in humans), high luminal, enterocytic and hepatic concentrations generate interaction liability, documented in humans for a few pairs and mechanistic for most, along four mechanistic axes: inhibition, and transcriptional induction, of CYP3A4, with CYP2D6/CYP2C9 inhibition that is quasi-irreversible through a metabolite-intermediate complex; transporter modulation (P-glycoprotein, OCT1/OCT2, and MATE1); pharmacodynamic additivity (hypoglycemia, hypotension, and QT prolongation); and microbiome- and gut-barrier-mediated effects, the last of these being a candidate axis rather than a demonstrated one. Product-quality variability is treated separately, as a modifier of exposure. The clinical anchor is increased cyclosporine exposure in renal-transplant recipients (AUC +34.5%; trough 29.3% above control). These elements are integrated into a three-tier risk-stratification framework that combines perpetrator potency, victim-drug vulnerability, and patient vulnerability, with each tier being linked to a defined pharmacy action. Conclusions: In patients on multiple medications, and particularly when berberine is co-administered with drugs of narrow therapeutic index, it should be managed as an active pharmacological perpetrator rather than as an inert supplement. Unstandardized product quality and an unsettled European regulatory framework, under which national limits differ by more than an order of magnitude, further widen the uncertainty around the dose actually delivered. Berberine use should therefore be elicited routinely at medication reconciliation and stratified by mechanism, by victim-drug vulnerability, and by patient risk, with particular attention to metabolic self-medication in the GLP-1 era. Full article