Search Results (17,089)

Cadmium (Cd) is a major environmental pollutant due to its high mobility and persistence in soils, facilitating entry into the food chain and threatening ecosystems and human health. However, the mechanisms that enable Salix species, well adapted for Cd remediation, to both tolerate and accumulate Cd remain elusive. Here, two Salix genotypes with contrasting Cd tolerance were examined under control and Cd stress using integrated physiological, transcriptomic, and metabolomic analyses of roots and leaves. The Cd-tolerant genotype (Salix suchowensis P294) maintained biomass under Cd stress, whereas the Cd-sensitive genotype (Salix sinopurpurea × Salix integra P646) showed a ~17% reduction. P294 accumulated more Cd in its stems (132.76 mg kg⁻¹) and leaves (122.25 mg kg⁻¹) than P646 (93.54 and 56.24 mg kg⁻¹). Transcriptomics responses were stronger in roots, with 896 DEGs in P294 and 462 in P646, enriched in nitrogen metabolism, phenylpropanoid biosynthesis, and metal transport, whereas only 167 and 176 DEGs were detected in leaves for P294 and P646, respectively. Metabolomics revealed more altered metabolites in roots (125 in P294, 89 in P646), mainly organic acids, amino acids, and flavonoids, compared with leaves (46 and 66). RT-qPCR validated the root-specific upregulation of key detoxification and transport genes (ABCA7, PRX72, GSTU1, GSTU4, ZIP1). These results reveal a root-centered regulatory network underlying Cd accumulation and tolerance, integrating detoxification, redox homeostasis, and structural reinforcement, as well as providing valuable targets for genetic improvement of phytoremediation efficiency. Full article

Sclerotinia sclerotiorum (Lib.) de Bary is a globally distributed necrotrophic fungal pathogen capable of infecting a wide range of crops. While conventional chemical fungicides offer effective control, their long-term use leads to increased fungicide resistance and poses risks to the environment and human health due to pesticide residues, underscoring the urgent need to develop novel fungicides. Artemisinin, first identified in Artemisia annua, is renowned for its antimalarial activity. Here, we demonstrate that artemisinin exhibited effective antifungal activity against Sclerotinia sclerotiorum with an EC₅₀ value of 0.1 mg/mL. Treatment with artemisinin caused the mycelia surface to collapse and shrivel, accompanied by enhanced membrane permeability. Pretreating Brassica napus and Arabidopsis leaves with artemisinin increased resistance to S. sclerotiorum infection. Proteomic analysis revealed that artemisinin treatment markedly downregulated the expression of key functional proteins in S. sclerotiorum, including enzymes involved in oxalic acid biosynthesis, cell wall-associated proteins, and secreted proteins. In conclusion, artemisinin exhibits notable inhibitory effects against S. sclerotiorum and may hold potential for development as a novel fungicide. Full article

In the biodegradable metal class, Mg-based alloys are considered the most promising candidates for temporary implant manufacture. However, their high corrosion rate in physiological media is considered a main drawback for clinical translation. Conversion coatings address the limitations of Mg-based alloys and provide a strategy to control corrosion and improve surface biocompatibility. In this review paper, a detailed analysis of various conversion coating techniques, including ceramic conversion coatings based on metals, polymeric conversion coatings, bioactive conversion coatings, and hybrid conversion coatings, is performed. Attention is devoted to the corrosion process and parameters, as well as to the biological response in relation to bioactivity or biocompatibility. The main angiogenic and osteogenic signaling pathways are described based on the analyzed conversion coatings, and the evolution of the cellular response is estimated. Although significant progress has been made in the field, there are still challenges associated with synchronizing Mg alloy degradation with new bone formation and with precisely guiding cell signaling responses to achieve a desired biological response. An overall conclusion of the paper consists of the fact that conversion coatings are an important topic, as they can enhance the surface of Mg-based alloys, making them prone to clinical translation. Full article

Bisphenol A (BPA) is a widely used endocrine-disrupting chemical that has been linked to oxidative stress and inflammation. This study investigated whether carvacrol (CAR), a natural monoterpene with antioxidant potential, mitigates BPA-induced hepatorenal toxicity in rats. Forty-two male Wistar albino rats were allocated into six groups (n = 7/group): control, vehicle (corn oil), BPA (25 mg/kg/day), and BPA co-administered with CAR (12.5, 25, or 50 mg/kg/day) by oral gavage for 30 days. Oxidative status was assessed in liver and kidney homogenates by measuring malondialdehyde (MDA), reduced glutathione (GSH), and the activities of superoxide dismutase (SOD) and catalase (CAT). In addition, histopathological evaluations were performed, and pro-inflammatory gene expression (NF-κB, TNF-α, and IFN-γ) was quantified by RT-qPCR. BPA induced a consistent pro-oxidant pattern, including increased hepatic MDA with depleted antioxidant defenses, and upregulated inflammatory transcripts. Carvacrol attenuated these alterations in a dose-dependent manner, and the CAR50 group was associated with statistically supported improvements across the oxidative stress panel, pro-inflammatory transcript expression, and histopathology scores. Overall, these findings identify carvacrol as a candidate for further preclinical evaluation against BPA-triggered oxidative and inflammatory disturbances in vivo; however, human-relevant extrapolation will require careful attention to dose scaling, bioavailability, and metabolism. Full article

Background: Magnesium sulfate (MgSO₄) has been investigated as an adjuvant in perioperative analgesia because of its antagonistic effects on the N-methyl-D-aspartate receptor (NMDA receptor) and its potential to attenuate central sensitization. However, clinical findings regarding its analgesic efficacy remain inconsistent across surgical procedures. Lumbar microdiscectomy is a common spinal procedure in which effective early postoperative pain control is important for patient comfort and early mobilization. This study aimed to evaluate the effect of intraoperative MgSO₄ administration on early postoperative analgesia and perioperative outcomes in patients undergoing lumbar microdiscectomy. Methods: This retrospective single-center cohort study included thirty-eight patients with American Society of Anesthesiologists (ASA) physical status I–II who underwent elective single-level lumbar microdiscectomy under general anesthesia. Patients were divided into two groups according to intraoperative magnesium administration: a control group receiving standard anesthesia without MgSO₄ (n = 19) and an MgSO₄ group receiving an intravenous MgSO₄ bolus of 30 mg/kg followed by a continuous infusion of 10 mg/kg/h until skin closure (n = 19). Postoperative pain intensity was assessed using the Numeric Rating Scale (NRS) at 0, 5, 10, 15, and 30 min after admission to the post-anesthesia care unit. Secondary outcomes included intraoperative remifentanil consumption, extubation time, and time to first mobilization. Complementary in silico analyses included molecular docking and protein–protein interaction (PPI) network analysis. Results: Postoperative NRS scores were numerically lower in the MgSO₄ group; however, between-group differences were not statistically significant. Mean intraoperative remifentanil consumption was numerically lower in the MgSO₄ group (236 ± 166 µg) compared with the control group (319 ± 298 µg), without statistical significance (p = 0.27). Repeated-measures analysis demonstrated the significant effect of time on postoperative NRS scores, whereas the overall group effect was not significant. Molecular analyses indicated stable morphine binding to opioid receptors and highlighted glutamatergic signaling components as central nodes within the interaction network. Conclusions: Intraoperative MgSO₄ administration was not associated with significant improvements in early postoperative pain scores or perioperative recovery parameters following lumbar microdiscectomy. Molecular analyses provide exploratory in silico insights and should be interpreted cautiously given the retrospective design and the in silico nature of these findings. Full article

The growing demand for healthier meat products has led to efforts to reduce synthetic additives, such as nitrites, in processed meats. This study evaluated the effect of enriched safflower oil with oleoresin from Capsicum annuum var. Anaheim (ESO) as a functional ingredient in the reformulation of Frankfurt-style pork sausages with reduced nitrite content. Five formulations were evaluated: a negative control without additives (F1 (0% ESO, 0% nitrite), a positive control containing only sodium nitrite F2 (0% ESO, 0.15% nitrite = 93.8 mg/kg), and three experimental treatments contained ESO and nitrite: F3 (0.5% ESO, 0.075% nitrite = 46.9 mg/kg), F4 (1% ESO, 0.05% nitrite = 31.3 mg/kg), and F5 (1.5% ESO, 0% nitrite), stored under refrigeration (4 °C) for five weeks. Physicochemical (pH, color, texture profile, proximate composition, residual chlorides and nitrites), oxidative (TBARS), and microbiological (total viable count) analyses were conducted over 5 weeks of storage. Results showed that formulation F4 provided the best balance between oxidative stability microbial control and nitrite residual content, maintaining TBARS levels below the 1.0 mg MDA/kg rancidity threshold (0.33 ± 0.01 mg MDA/kg), TVC within the 6.0 log CFU/g limit for processed meats (3.89 log CFU/g) and 1.15 mg/kg of nitrite residual at the end of the storage period. These findings suggest a synergistic effect between ESO and nitrites. Since addition of ESO was consistent with improved cured color development, likely due to the combined effect of reduced nitrite levels and the natural pigments from Anaheim chili. These findings demonstrate that ESO is a promising natural additive to partially replace nitrites, contributing to the development of healthier and safer processed meat alternatives. Full article

Shallow groundwater in saline soils creates a self-reinforcing cycle where waterlogging-induced root hypoxia impairs the ATP-dependent sodium exclusion mechanisms that plants rely on for salt tolerance. We conducted a two-year field experiment to test whether subsurface drainage must precede root-zone aeration for oxygen delivery to be effective. The experimental site was located in Heyang County, Weinan City, on the Guanzhong Plain of Shaanxi Province, north-central China—a major alluvial agricultural region representative of shallow-groundwater-induced salinization. The site had saturated paste electrical conductivity of 6.0 dS m⁻¹ and groundwater depth fluctuating between 0.5 and 1.4 m. A randomized complete block design with 2 × 2 factorial arrangement compared four treatments: control (CK), subsurface drainage only (SD), root-zone aeration only (RA), and both interventions combined (SD + RA). Drainage increased air-filled porosity from 5.8% to 13.5%, crossing the 10.2% threshold (95% CI: 9.1–11.3%) where gas-phase continuity emerges according to segmented regression analysis. Without drainage, aeration achieved only 4.2 mg L⁻¹ dissolved oxygen with high spatial variability (CV 12.5%), while the combined treatment reached 6.8 mg L⁻¹ (CV 6.8%). Root ATP content increased by 89% in SD + RA compared to control, accompanied by 56% lower root Na⁺ and 185% higher K⁺/Na⁺ ratio. These physiological changes correlated with 31% higher grain yield (7580 vs. 5798 kg ha⁻¹). The synergy index of 1.40 (95% CI: 1.28–1.52) indicated that combined effects exceeded the sum of individual treatments by 40%. Methane emissions declined by 62%, and the system achieved a 2.9-year payback period with a benefit–cost ratio of 4.08. These results establish drainage as a physical prerequisite for effective oxygenation, providing a mechanistic explanation for the variable performance of aeration systems reported in previous studies. Full article

Neem (Azadirachta indica A. Juss) extracts are widely used in agriculture as organic pesticides, but their effects on soil microbiota are uncertain. This study evaluated the impact of aqueous extracts of neem leaves and seeds on soil microbial activity, maize (Zea mays L.) development, and arbuscular mycorrhizal fungus (AMF) dynamics. The experiment used a 2 × 3 + 1 factorial design, with two extract sources (leaf and seed), three concentrations (5%, 10%, and 20%), and a control. The soil treated with 20% seed extract showed the highest microbial respiration (16,512 mg C-CO₂·kg⁻¹·day⁻¹) and total organic carbon (15.10 g·kg⁻¹) but the lowest microbial biomass (1330 mg·kg⁻¹) and microbial quotient (0.10%), indicating a stressed microbial environment. Paradoxically, maize plants under this same treatment exhibited a superior height, stem diameter, and biomass. Furthermore, the AMF spore density significantly increased in the seed extract treatments, suggesting a stress-induced reproductive response. These findings reveal that, although neem seed extract can negatively affect soil microbiota, it promotes maize growth, likely due to its organic and bioactive compounds. Thus, neem extract demonstrates potential as an organic input, but its application must be carefully managed due to potential ecological trade-offs. Full article

Ceftobiprole is a fifth-generation beta-cephalosporin with high inter-individual pharmacokinetic variability in critically ill patients. However, data on its pharmacokinetics and central nervous system (CNS) penetration are limited. This study developed and validated a rapid LC-MS/MS method for quantifying ceftobiprole in human plasma and CSF. Sample preparation involved protein precipitation of 50 µL aliquots. Analysis used gradient elution on an ACQUITY UPLC^® HSS T3 column (2.1 × 100 mm, 1.8 µm) with 0.2% formic acid and acetonitrile and was detected by positive ion electrospray, achieving a 3.5 min run time. The method was linear from 0.100 to 25.0 mg/L in plasma and 0.0500 to 15.0 mg/L in CSF. Intra- and inter-run precision and accuracy were within ±15% at all quality control levels. All validation parameters, including selectivity, matrix effects, recovery, and stability under various conditions, met acceptance criteria. Potential interference from the prodrug ceftobiprole medocaril was evaluated and found to be negligible. The method was successfully applied to samples from three patients, revealing a CSF penetration range of 11.9% to 36.5%. This validated LC-MS/MS method enables simple and rapid quantification of ceftobiprole in plasma and cerebrospinal fluid, filling the gap in data on its CNS penetration and supporting routine drug concentration monitoring in critically ill patients. Full article

Soil heavy metal contamination has emerged as a global environmental and public health challenge. Among them, cadmium (Cd) is of particular concern due to its high mobility and ecotoxicity. To identify the key limiting factors and their nonlinear threshold effects for Cd accumulation in maize grains (Grain-Cd) in heterogeneous soil environments, a coordinated sampling campaign of soil and maize was conducted at the municipal scale in Chongqing, China. A total of 499 paired soil–maize samples were obtained, and the correlations between Grain-Cd concentrations and soil physicochemical properties, as well as soil Cd pollution characteristics, were quantitatively evaluated using the integrated Random Forest (RF) model and SHAP (SHapley Additive exPlanations) algorithm instead of traditional linear statistical methods. The results showed that the average Cd content in the soil of maize-growing areas in Chongqing City was 0.30 mg·kg⁻¹, with a variation coefficient (CV) of 53%, and the spatial heterogeneity was significant. The average Cd content in maize grains was 0.03 mg·kg⁻¹, with an exceedance rate of 9.6% over the Chinese National Standard (0.10 mg·kg⁻¹), indicating a certain food safety risk. The RF model achieved a high predictive accuracy for Grain-Cd (R² = 0.815, RMSE = 0.028 mg·kg⁻¹, MAE = 0.013 mg·kg⁻¹), which was significantly superior to the traditional linear regression model (R² = 0.526, RMSE = 0.0459 mg·kg⁻¹). The available Cd (avlCd) in the soil was identified as the core controlling factor for the Grain-Cd content, while total soil Cd (SCd) only showed its positive contribution at contents higher than 0.5 mg·kg⁻¹. Soil pH, CEC (cation exchange capacity), and total phosphorus (TP) exerted significant influences on the Grain-Cd by regulating soil avlCd. The dependence of Grain-Cd on these soil factors was typically nonlinear, and an obvious turning point (threshold) existed for each factor with its occurring level in soil, determined by SHAP analyses as avlCd: 0.29 mg·kg⁻¹, pH: 6.58, CEC: 18.9 cmol (+)/kg, and TP: 0.5 g·kg⁻¹, respectively. This study clarifies the nonlinear regulatory mechanisms of key soil factors on Cd accumulation in maize grains in Chongqing, and the established RF-SHAP framework and identified soil factor thresholds lay a scientific foundation for the interpretable quantification of the soil–maize Cd system, while providing a scientific basis for the precise, targeted remediation of Cd-contaminated dryland farmland and the assurance of regional maize production safety. Full article

Nitrogen (N) and phosphorus (P) are essential nutrients that play critical roles in plant physiological processes and the accumulation of N and P in broccoli head was significantly correlated with yield. Therefore, there is a need for a rapid, non-destructive diagnosis of crop status by detecting deficiencies in essential nutrients. This study evaluated the effects of N and P deficiency on field grown broccoli (Brassica oleracea L. var. italica Plenk) using a plant-induced electrical signal (PIES) sensor, in which needle electrodes are inserted into the stem to measure electrical conductivity reflecting plant water and ion status. Four treatments were established, including the control (N100P100) with sufficient N and P supply, N deficiency (N0P100), P deficiency (N100P0), and combined N–P deficiency (N0P0). For sufficient supply, urea and fused phosphate (FP) were applied at rates of 122 kg N ha⁻¹ and 71 kg P ha⁻¹, respectively. Soil, stem, and leaf nutrient contents, growth parameters, and stress related indicators were analyzed and their relationship with PIES values were evaluated. PIES was highest in control (N100P100) and lowest under N–P deficiency (N0P0). Higher PIES values were observed during the vegetative stage, whereas values declined during the reproductive stage, reflecting changes in physiological activity. Growth parameters such as shoot and root weight and stem diameter were generally superior in the control (N100P100) treatment, while leaf calcium (Ca), magnesium (Mg), and potassium (K) concentrations showed no significant differences among treatments. Total N content in leaves was higher in N fertilized treatments (control and P deficiency). Photosynthesis-related parameters, including soil plant analysis development (SPAD), Fv/Fm, and chlorophyll content, were lowest under N–P deficiency, which was reflected in the PIES. Principal component analysis (PCA) showed that the PIES was closely associated with growth and photosynthetic parameters and clearly distinguished N sufficient treatments (control and P deficiency) from N deficient treatments (N0P100, N0P0). Overall, these findings suggest that PIES monitoring can serve as a sensitive physiological indicator of nutrient stress and may be applied as an early diagnostic tool before visible growth inhibition occurs in broccoli cultivation. Full article

This research aimed to examine the effects of different dietary levels of nano-selenium (NSE) on the reproductive performance, gonad hormones, histopathology, growth performance, feed utilization, and body indices in adult Nile tilapia, Oreochromis niloticus, broodstock for 90 days. The initial weights of the fish were 278.6 ± 5.5 (males) and 178.4 ± 1.6 (females). They were distributed randomly to 15 tanks with 20 fish in each tank (15 females and 5 males, sex ratio 3:1), with each treatment conducted with three replicates. The contents of NSE in five isocaloric and isonitrogenous practical feeds were 0 mg/kg (control), 1 mg/kg (T1), 2 mg/kg (T2), 3 mg/kg (T3), and 4 mg/kg (T4). Results show that the final weight (FW), weight gain (WG), specific growth rate (SGR), protein efficiency ratio (PER), and feed conversion ratio (FCR) were significantly better in T2 and T1, followed by the control, in comparison with others. On the other hand, growth efficiency was decreased in T3 and T4 of both males and females. Referring to body indices and reproductive performance, females were higher than males in the hepatosomatic index (HSI), where the lowest treatment was the control and T4 for both males and females. Female Nile tilapia brood fish given NSE improved reproductive performance indicators (egg number, total egg, and fry number) when compared with the control. With increasing levels of NSE in the feed, the levels of testosterone and progesterone hormones were increased. The highest values for testosterone were in T4, followed by T3, then T2, T1, and the control. The same trend was observed across the progesterone treatments. Additionally, the results of histopathological examination indicate differences in tissues between different treatments as a result of the addition of NSE. These results indicate that NSE supplementation at low levels could lead to improved growth and reproductive efficiency of Nile tilapia. Full article

The safe and precise regulation of therapeutic gene expression remains a major challenge for mammalian synthetic biology and cell-based therapies. Many existing inducible systems rely on non-mammalian regulatory components or ligands with limited clinical compatibility. Designer receptors exclusively activated by designer drugs (DREADDs) offer a human G protein-coupled receptor (GPCR)-based framework for pharmacological control of intracellular signaling, yet their application as clinically relevant gene-regulation platforms remains underexplored. Here, we report a clozapine-responsive gene switch that couples a designer GPCR to signaling-dependent transcriptional control. By linking clozapine-activated receptors to cyclic adenosine monophosphate (cAMP)- or calcium-responsive synthetic promoters, receptor activation is converted into robust transgene expression across a broad dynamic range, with sensitivity to sub-nanomolar to low-nanomolar clozapine concentrations. In vivo, alginate-encapsulated reporter cells implanted in C57BL/6J mice responded to systemic or local clozapine administration with efficient secretion of a reporter protein, achieving robust induction at low daily doses (0.3 mg/kg) following either oral administration or local delivery. Together, these results establish a human GPCR-based clozapine-responsive gene switch that integrates regulation by a clinically used small molecule with modular transcriptional outputs, providing an additional approach for pharmacologically controllable gene expression in mammalian cells and in vivo. Full article

Background/Objectives: Stress echocardiography (SE) had been recommended by professional societies for assessing patients with suspected angina. SE protocols are variable across hospitals and countries in the recommendation of the cessation of rate-controlling medication (RCMx) prior to SE. Some expert opinion papers recommend the cessation of beta receptor blockers (BBs) and rate-controlling calcium channel blockers 48 h prior to SE to improve the diagnostic accuracy of the test. There is no evidence that the continuation of RCMx can affect the outcome of SE and short-term major adverse cardiovascular events (MACEs). To investigate the efficacy of Dobutamine SE in a cohort of patients where the cessation of rate-controlling medication has not been mandated, we reviewed our data over a one-year period in patients investigated for suspected coronary artery disease (CAD). Methods: A retrospective data analysis was performed on 227 consecutive patients who underwent Dobutamine SE between January 2022 and January 2023 in a single centre. In addition to dobutamine, the protocol allowed the administration of intravenous atropine (maximum dose of 1.2 mg) and a “top up” handgrip exercise at the discretion of the performing cardiologist. We assessed the Dobutamine SE outcome (positive vs. negative), target heart rate (THR, 85% of maximum age predicted), and the achieved peak HR in the two groups with RCMx and without RCMx. We analysed the patients’ characteristics and 12-month outcomes of a combined MACE of death, non-fatal MI, stroke, admission with angina, and unplanned revascularisation. Results: Of the 227 patients, 61% were on No-RCMx (male 40%). Ninety-three percent of the patients on RCMx were on BB and 7% on other rate-controlling medications. The THR was achieved in 74% of the patients with-RCMx and 90% in the without-RCMx groups p = 0.0018. Positive Dobutamine SE was observed in 48% (43/89) of patients on RCMx vs. 28% (39/138) on No-RCMx (p = 0.0022). Patients who did not reach THR 43% (16/37) had positive Dobutamine SE compared to 35% (66/190) who reached THR (p = 0.626). There was no difference between groups in the peak WMSI. Logistic regression analysis showed that being on RCMx was independently associated with positive Dobutamine SE (OR 2.03, 95% CI 1.06–3.91, and p = 0.034). The MACE rate was higher in patients where the THR was not achieved (9/37, 24.0%) vs. where THR was achieved (9/190, 4.7%), p < 0.001, in both the with-RCMx (7/30, 23% vs. 6/66, 9.1%, p = 0.013) and without-RCMx (2/14, 14% vs. 3/124, 2.4%; p = 0.025) groups, respectively. RCMx was independently associated with MACE (OR 3.68, 95% CI 1.227–11.046, and p = 0.020). Conclusions: The use of RCMx proved to be a predictor of both SE and MACE outcomes irrespective of the achieved THR. Our data supports the practice that patients referred for Dobutamine SE on RCMx can continue taking them without impact on the test accuracy. Full article

Background/Objectives: Severe asthma in routine practice often involves long-standing disease, multimorbidity, and prior biologic failure—settings underrepresented in pivotal tezepelumab trials. This study evaluated 52-week real-world effectiveness and safety of tezepelumab in a highly comorbid, predominantly T2-high, biologic-experienced severe asthma cohort from the Canary Islands. Methods: TEZNERIFE is a multicenter, retrospective study including consecutive adolescents and adults with GINA Step 5 severe uncontrolled asthma treated with tezepelumab 210 mg every 4 weeks for 12 months. Clinical outcomes, lung function, type 2 biomarkers, upper airway symptoms, and Biologics Asthma Response Score (BARS) were assessed at baseline, 26 weeks, and 52 weeks. Results: Fifty-six patients (mean age 53.5 years, 71% female, mean asthma duration 30 years, 84% T2-high; 71% with ≥1 prior biologic) were analyzed. ACT improved from 11.5 ± 3.7 to 15.9 ± 4.7 at 26 weeks and 17.5 ± 4.7 at 52 weeks (both p < 0.0001), while annualized exacerbations declined from 2.79 ± 2.0 to 0.50 ± 0.72 and 0.51 ± 0.89 (both p < 0.0001). Maintenance oral corticosteroid dose fell from 10.2 ± 8.3 to 6.9 ± 2.4 mg/day at 52 weeks (p = 0.014). FEV1% predicted increased from 69.3 ± 19.2% to 75.3 ± 17.7% and 76.2 ± 20.6% (p = 0.004 and p = 0.001), and blood eosinophils decreased from 234 ± 231 to 146 ± 120 and 147 ± 110 cells/µL (p = 0.001 and p = 0.013). At one year, 18.9% and 67.9% were classified as good and intermediate responders by BARS; 13.2% were insufficient responders. Two patients discontinued due to non-serious adverse events, while no treatment-related serious events occurred. Conclusions: In this difficult-to-treat, multimorbid, biologic-experienced population, tezepelumab achieved sustained improvements in asthma control, exacerbations, lung function, eosinophilic inflammation, and corticosteroid exposure over 52 weeks, supporting upstream alarmin inhibition as a versatile strategy in complex severe asthma. Full article