Search Results (35,428)

Fipronil (FPN), a widely used insecticide, poses health risks through environmental contamination. Although its toxicity is increasingly recognized, the impact of fipronil on glucose metabolism remains poorly understood. In this study, mice on a normal diet (ND) or high-fat diet (HFD) received a daily oral administration of fipronil (0, 0.25, 1, or 4 mg/kg) for 35 days. Blood glucose and insulin were measured, and glucose/insulin/pyruvate tolerance tests were performed. We found that fipronil compromised glucose tolerance in mice fed an ND. Gut microbiota composition was assessed by 16S rRNA sequencing and the expression of inflammatory factors was detected in the tissues. Serum fibroblast growth factor 15 (FGF15) and bile acid were determined. In HFD-fed mice, fipronil exacerbated glucose metabolic disorders and enhanced insulin resistance. These metabolic disturbances were associated with gut microbiota dysbiosis, particularly a marked reduction in Akkermansia muciniphila (A. muciniphila) abundance, and increased systemic inflammation. Fipronil exposure also decreased serum FGF15 and elevated serum bile acids. Our results suggest that fipronil disrupts glucose metabolism in association with gut microbiota alterations, impairment of the FGF15-bile acid axis, and induction of inflammation, highlighting its potential relevance to diabetes risk. Further studies are warranted to validate our findings. Full article

Salinity is a major limiting factor for alfalfa production. This study analyzed the differential regulatory mechanisms of ZT1 and ZT2 under salt stress (100 and 200 mM) through physiological and biochemical responses, the photosynthetic system, and transcriptome and metabolome. The results show that ZT1 is more tolerant than ZT2. Under salt stress, root vitality (30.95-66.28%), shoot dry weight (13.23–53.01%), and chlorophyll a (20.00-50.00%) decreased significantly. However, Na⁺/K⁺ (0.93-3.62 times), MDA (0.19-2.52 times), and superoxide dismutase (28.94-79.56%) increased significantly. From a physiological perspective, ZT1 and ZT2 can endow plants with salt tolerance by regulating the Na⁺/K⁺ balance, inducing osmotic agents, enhancing antioxidant activity, and regulating the photosynthetic system. In omics analysis, there were significant differences in their regulation of the biosynthetic pathways of phenylpropanin and flavonoids. ZT1’s salt tolerance is strengthened by the positive regulation of transcription factors (GRAS) and genes (CHS, POD, CAD, F3H, and PAL), together with the accumulation of (-)-epicatechin, eriodictyol, and butein. In contrast, ZT2 responded positively to salt stress via the regulation of TFs (GRAS, TRAF, and bHLH) and genes (POD, C4H, CHS, and F3′5′H), as well as the accumulation of caffeic acid. The research results will provide new insights into alfalfa cultivation and new variety breeding in saline–alkali land. Full article

Background/Objectives: Psoriasis is a chronic, recurrent inflammatory skin disorder with a steadily rising prevalence worldwide. Current therapeutic strategies include topical and systemic treatments selected based on disease severity and associated comorbidities; however, no therapy provided a definitive cure. Topical therapy is associated with a lower risk of systemic adverse effects, although the altered skin barrier observed in psoriasis may significantly reduce the bioavailability of active pharmaceutical ingredients. The aim of this study was to develop and evaluate the efficacy of a topical formulation containing triterpenoid acids derived from lavender extract (Lavandula angustifolia Mill.) as a potential adjunctive approach for symptom management in patients with psoriasis and chronic kidney disease (CKD). Methods: Following removal of the volatile oil, oleanolic, ursolic, pomolic, and rosmarinic acids were identified and quantified. The preparation was analyzed in terms of organoleptic properties, colloidal stability, pH determination, and rheological characteristics. The clinical study included 18 patients (both sexes) aged 28 to 71 years, with psoriasis and CKD of varying etiologies. Urinary albumin/creatinine ratio (uACR) and estimated glomerular filtration rate (eGFR) were used as renal biomarkers, while high-sensitive C-reactive protein (hs-CRP), hs-CRP/albumin, and neutrophil–lymphocyte ratio (NLR) were selected as inflammatory biomarkers. Laboratory assessments were performed at baseline and after 60 days of topical treatment with the lavender extract-based formulation. Clinical outcomes were evaluated using validated measures of psoriasis severity and patient impact, including the Psoriasis Area and Severity Index (PASI), the Investigator Global Assessment (IGA), and the Dermatology Life Quality Index (DLQI). Results: The formulation contained 1.4% rosmarinic acid and up to 8% ursolic acid (extract mass) and demonstrated good stability, a pH of 5.5, favorable local tolerability, antiproliferative activity, reduction in pruritus, and no treatment-related adverse effects. Efficacy and tolerability scores showed statistically significant improvements at 60 days (T2) after topical terpenoid administration compared with baseline (T0): PASI (0.722 ± 0.714 vs. 2.044 ± 0.690 at T0, p < 0.001), DLQI (3.889 ± 1.997 vs. 13.333 ± 3.361 at T0, p < 0.001), and IGA (0.556 ± 0.616 at T2 vs. 2.167 ± 0.618, p < 0.001). uACR decreased significantly over the study period (308.714 ± 240.782 after 60 days vs. 379.78 ± 308.81 at T0, p < 0.001), while eGFR values remained similar at baseline and follow-up. All evaluated inflammatory biomarkers showed significant reductions: hs-CRP (4.33 ± 2.127 at T2 vs. 9.7 ± 10.045 at T0, p < 0.009), hs-CRP/albumin ratio (0.105 ± 0.052 at T2 vs. 0.241 ± 0.225, p < 0.011), and NLR (2.154 ± 2.171 vs. 2.253 ± 0.256 at baseline, p = 0.027). Linear regression analysis identified no predictors of responsiveness to topical triterpenoid therapy in patients with psoriasis and CKD. Conclusions: This topical lavender extract-based formulation showed promising clinical and anti-inflammatory effects and favorable local tolerability in this pilot cohort of psoriasis patients with CKD. However, these findings should be considered preliminary and require confirmation in larger randomized controlled studies. Full article

Rotor machining errors strongly influence the air-film pressure distribution of aerostatic spindles and fundamentally limit performance enhancement. However, existing studies rarely provide a comprehensive statistical characterization based on measured manufacturing errors. To address this gap, a multi-scale modeling framework based on harmonic analysis of form errors is developed. Measured surface topography data from a batch of rotors are decomposed to establish a harmonic statistical model, which is then incorporated into a modified Reynolds equation together with macro-scale and micro-scale error components. The static performance of the aerostatic spindle is subsequently analyzed. Results show that low-order harmonics (1st–5th) dominate cylindricity errors, with amplitudes following a log-normal distribution. The statistical bounds are described by 3σ envelopes. When the eccentricity ε exceeds 0.3, barrel-shaped errors reduce the load capacity by more than 15%, whereas waist-drum-shaped errors exhibit a self-stabilizing tendency under small deviations. Performance degradation can be partially mitigated by adjusting the supply pressure and orifice diameter. This study addresses the research gap in understanding the impact of measured manufacturing errors on aerostatic spindle performance and provides a quantitative basis for tolerance allocation and performance optimization. Full article

Viral diseases pose a major threat to tomato cultivation, mainly due to the lack of effective antiviral control methods. Plant growth-promoting microorganisms (PGPMs) represent a promising and sustainable strategy for virus disease management, as, in addition to plant growth, they can promote resistance to pathogens. In this study, we examined the antiviral potential of selected PGPMs against three economically important and genetically distinct tomato viruses, tomato spotted wilt virus (TSWV, Orthotospovirus tomatomaculae), cucumber mosaic virus (CMV, Cucumovirus CMV), and tomato brown rugose fruit virus (ToBRFV, Tobamovirus fructirugosum) under controlled greenhouse conditions. The efficacy of each PGPM was assessed by monitoring disease development via visual scoring and DAS-ELISA. Our results indicate a significant TSWV symptom attenuation upon the application of Paraburkholderia eburnea EP3 and the yeast isolate SRL248, though, without a respective reduction in virus accumulation. However, no antiviral effect was observed by any PGPM tested against CMV or ToBRFV. A targeted gene expression analysis revealed a PGPM-specific induction of salicylic acid-dependent defense and RNA silencing markers, indicating priming of host immune responses. Overall, this work increases our knowledge on the antiviral potential of PGPMs showing a strain- and virus-specific effect primarily associated with enhanced symptom tolerance. Full article

Background: Effective pain control is fundamental in pediatric dentistry. Supraperiosteal infiltration (SPA) and inferior alveolar nerve block (IANB) are the most used local anesthesia (LA) techniques. This review evaluated the available evidence on intraligamentary anesthesia (ILA) to assess its efficacy, safety, and viability as an alternative to conventional techniques. Methods: The review protocol was registered in PROSPERO (CRD420261284494) and conducted in accordance with PRISMA guidelines. Three databases were searched for RCTs published in English after 2000 involving children. Studies that compared ILA, delivered via either traditional or computer-controlled systems (CC-ILA), with other LA techniques were included. Risk of bias was assessed using the Cochrane’s RoB 2.0 tool. Meta-analysis was performed using a random-effects model with Stata/SE 18.0. Results: The database search yielded 347 records; after duplicate removal, 153 articles were screened. Thirty-four papers were assessed, of which thirteen studies were included, and three were retained for the meta-analysis. Significantly lower pain perception and improved physiological parameters were reported with ILA compared with IANB. CC-ILA demonstrated greater efficacy and reduced procedural discomfort than conventional ILA. Patients favored CC-ILA over IANB (68.0% vs. 32.0%). Postoperative lip biting occurred more frequently following IANB and CC-SPA than after ILA. Overall risk of bias was low. Meta-analysis revealed no significant difference in pain perception between ILA and IANB (z = −0.26; p = 0.79). Conclusions: ILA, particularly CC-ILA, appears to be an effective, safe, and well-tolerated technique and may be considered a valid anesthetic option in pediatric dentistry. The review did not receive any funding. Full article

Nuclear Factor Y (NF-Y) transcription factors play pivotal roles in plant adaptation to abiotic stress, yet their genomic landscape and functional mechanisms in cabbage (Brassica oleracea var. capitata L.) remain underexplored. Here, we performed a genome-wide identification of the NF-Ys in cabbage, identifying 53 BoNF-Ys classified into three subfamilies: 20 BoNF-YAs, 22 BoNF-YBs, and 11 BoNF-YCs. Phylogenetic clustering revealed evolutionary conservation with their Arabidopsis orthologs. Domain analysis revealed that all BoNF-YA members contain the CBF_NF-YA domain, while all BoNF-YB and BoNF-YC members possess the CBFD_NFYB_HMF conserved domain. The BoNF-Y genes were named according to their chromosomal locations. Bioinformatic analysis showed that BoNF-Y proteins range in size from 131 to 642 amino acids, with molecular weights of 14.82–73.18 kDa, theoretical pI values of 4.57–9.96, instability indices between 33.02 and 73.48, aliphatic indices of 45.3–86.26, and grand average of hydropathicity (GRAVY) values ranging from −1.139 to −0.367. Promoter cis-element profiling uncovered stress- and hormone-responsive motifs, including abscisic acid-responsive elements (ABREs), TC-rich repeats, and ethylene-responsive elements (EREs). RNA sequencing (RNA-seq) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) conducted under salt stress (256 mM) identified three salt-responsive candidate genes (BoNF-YA14, BoNF-YB9, and BoNF-YC8). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighted significantly expressed genes’ roles in MAPK signaling, proline metabolism, and phytohormone transduction pathways. This study conducted a comprehensive survey of the BoNF-Y gene family in cabbage. It could serve as a theoretical foundation for further functional identification and utilization of BoNF-Y family members and their role in the interaction between cabbage and salt stress. Full article

A major quality challenge in the application of titanium alloys is the persistence of substances known as “hard-alpha inclusions”. Although hard-alpha inclusions are extremely rare and typically small in size in high-quality titanium alloys for aero-engine disks, their hard and brittle nature poses a non-negligible threat to the structural integrity of the disks. Due to the extreme scarcity of natural hard-alpha inclusions, most previous studies have focused on “synthetic dense hard-alpha particles” rather than “real porous hard-alpha inclusions”, inevitably over-looking the differences between them. In this work, a method of introducing titanium nitride sponge preforms into the electrode preparation step of the smelting process is proposed and implemented, successfully fabricating real porous hard-alpha inclusions in TC4 titanium alloy disks. On this basis, the detection characteristics of ultrasonic non-destructive testing for such porous hard-alpha inclusions are investigated, and a probability of detection (POD) model for these defects is established for the first time. A defect distribution model of porous hard-alpha inclusions for the probabilistic damage tolerance assessment of disks is also derived. This work reveals that, unlike the “linear” behavior of traditional models, the new defect distribution model adheres to a “cubic polynomial” relationship. Full article

Background/Objectives: The 3-ketoacyl-CoA synthase (KCS) enzyme is a key and rate-limiting component in the biosynthesis of very long-chain fatty acids (VLCFAs). Through controlling VLCFA production, KCS plays an essential role in plant cuticle formation. The necrotrophic fungus Botrytis cinerea can infect all aboveground parts of rose plants (flowers, leaves, and stems), causing severe economic losses. KCS restricts pathogen invasion by influencing cuticle formation and enhances tolerance to environmental stresses. While the KCS gene family has been well-studied in some plants, it remains unexplored in rose (Rosa × hybrida Hort.), a species of significant ornamental and economic value. Methods: In this study, we conducted a genome-wide analysis of the RcKCS gene family in rose, identifying 18 non-redundant genes. Phylogenetic, structural, and synteny analyses were performed to investigate the evolutionary relationships, gene architecture, and duplication events. The expression patterns of RcKCS genes in rose petals during Botrytis cinerea infection were examined, and transient overexpression and silencing of RcKCS6 were used to study its function. Results: RcKCS6 was found to be upregulated during gray mold infection, and transient overexpression reduced lesion size on infected petals. Conclusions: Our study provides the first comprehensive analysis of the RcKCS gene family in rose and highlights RcKCS6 as a potential candidate for improving resistance to gray mold in rose through molecular breeding. Full article

As freshwater resources become increasingly limited, exploiting brackish and marine waters for aquaculture is viewed as a promising alternative. Nile tilapia (Oreochromis niloticus), although considered euryhaline, shows relatively restricted tolerance to salinity compared with other tilapia species, making it an ideal model to study adaptive responses to osmotic stress. Serotonin (5-HT) and dopamine (DA) are key modulators of stress responses through their activation of metabotropic G protein-coupled receptors (GPCRs). In this study, we investigated the transcriptional profiles of metabotropic serotonin and dopamine receptors across the brain, intestine, and liver of Nile tilapia reared in different salinity conditions (0 ppt, 16 ppt, 30 ppt). The results showed both dopamine and serotonin metabotropic receptors were duplicated with potential neofunctionalization, contributing to osmoregulatory capacity. Nile tilapia showed altered brain drd1, htr1 and htr7 subtypes in response to salt change. Meanwhile, the drd3 subtype showed pronounced alterations in the intestine and liver under elevated salinity. Notable transcriptional alterations in htr4 subtypes were observed in both brain and liver, suggesting their potential involvement in modulating energy balance and stress adaptation. Correlation network analyses further demonstrated coordinated regulation among receptor paralogues in the brain. These findings provide potential targets, such as ligand analog additives or genetic enhancement, for future functional validation and for improving salinity tolerance in Nile tilapia culture. Full article

Background/Objectives: Immediate-type hypersensitivity reactions (HSRs) to proton pump inhibitors (PPIs) represent a clinically relevant adverse drug reaction and pose diagnostic and management challenges, including variable cross-reactivity (CR). Drug provocation testing (DPT) is the diagnostic gold standard, but real-life use after testing remains uncertain. This study aimed to describe clinical features, diagnostic outcomes, CR profiles, and real-life PPI use in patients with immediate-type PPI hypersensitivity. Methods: Single-center ambispective study of 40 patients evaluated for immediate-type PPI HSRs (2014–2023). Index reactions, culprit PPI, and skin test/DPT results were recorded retrospectively. Patients tolerating an alternative PPI on DPT were followed prospectively; real-life tolerance and use were assessed by structured telephone interview. Results: Among 40 patients (87.5% female; mean age 48 years), lansoprazole was the most frequent culprit (50%); anaphylaxis occurred in 65%. Skin tests were positive in 25% (n = 9), and a shorter interval from reaction to testing was associated with positivity (p = 0.025). CR was detected in 25% (n = 10), most often between lansoprazole and pantoprazole. All 29 patients undergoing DPT tolerated at least one alternative PPI. In real-life follow-up (n = 27), 11 (40.7%) restarted PPIs without recurrence; 1 (3.7%) developed a mild cutaneous reaction despite negative testing. Fifteen (55.6%) did not restart therapy; 4 (14.8%) cited drug-related anxiety or physician-advised avoidance. Conclusions: In immediate-type PPI hypersensitivity, skin test sensitivity appears time-dependent, supporting early evaluation. DPT identifies safe alternatives, yet behavioral and clinician-related barriers limit real-life implementation; addressing these barriers is essential to optimize PPI allergy management. Full article

The Taylor approximation theorem is a fundamental tool in numerical analysis, providing a local polynomial representation of smooth functions. In practical computations, a function f is approximated by a finite Taylor polynomial $P_n$, and controlling the resulting truncation error is of central importance. In this paper, we introduce two novel a posteriori error estimation techniques for Taylor polynomial approximations. The proposed estimators are fully computable and do not require prior bounds on the $(n+1)$st derivatives of f. We prove that the estimators converge to the exact error both pointwise and in the $L^2$-norm as $n\to \infty$, and we establish their asymptotic sharpness through effectivity analysis. Based on these results, we develop two adaptive algorithms that automatically determine the minimal degree n required to achieve a prescribed tolerance, either at a specific point or over a domain. We further extend the analysis to multivariate functions and show that analogous estimators and effectivity properties hold in higher dimensions. Numerical experiments are presented to validate the theoretical results and demonstrate the practical performance of the proposed methods. Full article

Accurate, non-contact vital-sign monitoring promises a scalable alternative to conventional sensors, yet low signal quality and long recording times have limited real-life adoption. We present a dual-modality system that combines Eulerian video magnified remote photoplethysmography (rPPG) from facial videos with optical flow-based shoulder tracking to estimate heart rate (HR) and respiratory rate (RR) from ultra-short 15 s recordings. With 200 participants, each providing 2 videos, 387 videos passed strict usability criteria, excluding flicker, blur, occlusion, and low illumination. For 15 s recordings, the HR estimates reached 98.5% accuracy within a ±10 beats per minute tolerance (MAE = 3.25, RMSE = 4.88, r = 0.93; p < 0.05) and the RR estimates achieved 98.4% accuracy within a ±5 respirations per minute tolerance (MAE = 0.69, RMSE = 0.87, r = 0.90; p < 0.05), exceeding prior studies that required 30 to 60 s recording lengths. Computational analysis on a standard home computer confirmed feasibility, with near real-time performance achievable on optimized hardware. By integrating complementary modalities and rigorous video quality control, the system overcomes low-SNR challenges, delivering high-fidelity, clinically validated vital signs monitoring. These results establish a robust, scalable, and precise framework for clinical and home care, demonstrating that accurate, contact-free HR and RR monitoring can now be achieved in seconds, making rapid, real-life vital signs assessment practical and accessible. Full article

Erbium-165 (¹⁶⁵Er) is an Auger electron emitter with 7.2 electrons per decay and very few other emissions, making it an interesting candidate for Auger electron therapy. We present here a procedure for producing ¹⁶⁵Er by the ^natHo(p,n)¹⁶⁵Er nuclear reaction on a 16.5 MeV medical cyclotron. The target was prepared by pressing a Ho₂O₃:Al 1:1 (w/w) powder mixture on a Ag disc with a cylindrical depression in the center. With a 0.1 mm Nb foil in front, degrading the energy to 15 MeV, and water cooling at the back of the Ag disc, the target could withstand irradiation at currents up to 45 µA without showing any signs of damage. The beam tolerance of the target was also estimated by calculating the temperature and heat dissipation in the target via the numerical solution of the heat transport equations. For a 180 mg target, the production yield was 12.3 ± 1.9 MBq/µAh. The separation of two neighboring lanthanides is challenging, which led us to study the distribution coefficients for Er and Ho on commercially available LN2 resin for both HNO₃ and HCl eluents. Based on these values, we propose a purification procedure involving two successive LN2 columns for separating the ¹⁶⁵Er from Ho and Al, followed by a small TK221 column to concentrate the final eluate. No radionuclidic impurities were detected, and the chemical impurities found in the final formulation were traces of Ho, Er, Ca, Pb, and Fe. For three different chelators (DOTA, DTPA, and CHX-A″-DTPA), the effective molar activity of the final formulation was measured. The stability of the three complexes formed was also assessed upon incubation in mouse serum for 28 h. Full article

Background/Objectives: Retinoids are the gold standard for topical anti-aging treatments; however, their application is frequently limited by skin irritation and poor tolerability, particularly in sensitive or aged populations. Consequently, there is a growing demand for plant-based alternatives that offer comparable efficacy with an improved safety profile. The present study aims to explore the effects of rosemary aqueous extract (RE) on skin aging and its potential as a safe and effective alternative to retinol. Methods: Comparative RNA sequencing was employed to analyze the transcriptomic profiles of RE and retinol in human dermal fibroblasts (HDFs). Efficacy of collagen synthesis was evaluated using in vitro 2D and 3D skin models. As aging is associated with chronic inflammation, the responses of HDFs from young versus elderly donors under chronic IL-1β stimulation were compared, and a novel inflammaging model combining repetitive UVA irradiation with chronic cytokine (IL-1β and TNF-α) stimulation was utilized. Potential for neurogenic irritation was assessed by measuring transient receptor potential vanilloid subtype 1 (TRPV1) expression in SH-SY5Y neuronal cells. Results: RE was revealed to regulate gene expression in a pattern analogous to retinol, while also modulating distinct pathways related to wound healing and oxidative stress. RE not only enhanced collagen I synthesis but also protected against UVA-induced damage by preserving epidermal thickness, restoring the dermal-epidermal junction (DEJ), and reducing inflammation. Furthermore, RE demonstrated protective effects in the inflammaging model, effectively countering the synergistic damage caused by combined intrinsic and extrinsic stressors. Notably, RE downregulated TRPV1 expression in SH-SY5Y cells, suggesting a potential of reducing skin itching sensation. Conclusions: These findings position RE as a multifaceted anti-aging ingredient that not only represents a promising candidate for a retinol alternative, but also in the context of inflammaging and sensitive skin conditions, highlighting its potential impact on the future of anti-aging skincare. Full article