Search Results (2,848)

Background: The core management of most individuals with asthma and COPD is daily treatment with inhalers such as inhaled corticosteroids (ICS) and long-acting bronchodilators. The two main types of inhalers used are pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs). Different studies have shown low adherence to inhaler treatments among subjects with asthma and COPD. In this study, we explored the differences in adherence between pMDIs and DPIs of combined ICS and long-acting β₂-agonist inhalers (ICS + LABA) in a large cohort, free from commercial biases. Methods: In this historical prospective study, we included all adult subjects with asthma and/or COPD who acquired at least one ICS + LABA inhaler between 2016 and 2019. We carried out propensity score matching and then compared the maximal number of pMDIs and DPIs purchased in any continuous 12 months during the study period. We also compared once-a-day DPIs with twice-a-day DPIs. Results: Of the 36,998 matched subjects, 5897 (15.9%) purchased pMDIs. The overall median [IQR] inhalers purchased for pMDIs and DPIs were 1 [1, 4] and 3 [1, 8], respectively; for subjects with asthma, 1 [1, 3] and 2 [1, 6]; for subjects with COPD, 1 [1, 3] and 3 [1, 10]; and for subjects with asthma–COPD overlap, 2 [1, 7] and 6 [2, 12]. For all the comparisons, p < 0.001. The once-a-day DPI group had a slight but significantly better adherence than the twice-a-day DPI group. Conclusions: For ICS + LABA therapy, the number of DPIs purchased was significantly greater than the number of pMDIs purchased, as well as the once-a-day DPI relative to the other DPIs. Overall, subjects with asthma and/or COPD had low adherence to all inhalers, with the highest adherence observed among subjects with asthma–COPD overlap. Full article

In the process of shield tunneling in clayey strata, the fine-grained clay mineral components in the soil easily adhere to the cutter plate. The clay adhering to the cutterhead and the soil compartment then solidifies and hardens, which results in the production of mud cake and clogging. At present, research on cutter plates in clayey ground is limited and has focused mostly on static tests or simplified models. There is a lack of in-depth studies on the effect of temperature on clay adhesion, which is crucial for understanding the clogging risks. In this study, we independently researched and developed a rotary adhesion tester to investigate the adhesion effect and adhesion force change in a shield cutter plate under the influence of different temperatures, water contents (ω), and clay types, revealing the change rule of the adhesion effect under the joint influence of the temperature and the consistency index (I_c). This study provides experimental evidence and an empirical model for assessing the clogging risk in shield tunneling through clay strata, offering valuable insights that support the efficient operation of earth pressure balance (EPB) shields. Full article

Selective and potent inhibitors of the NAD⁺-dependent deacetylase Sirt2 represent a valuable epigenetic strategy for the treatment of currently incurable diseases such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and multiple sclerosis. Guided by molecular docking and MM/GBSA validation studies, a lead structure-based hybridization strategy was developed, resulting in a series of very effective Sirt2 inhibitors. With RW-93, we present a highly potent and subtype selective Sirt2 inhibitor (IC₅₀ = 16 nM), which as a next generation SirReal-type inhibitor significantly surpasses established Sirt2 inhibitors and contributes to the extension of the current SAR profile. The structural modification strategy employed in this study proved to be highly promising, resulting in the identification of the most potent low-molecular-weight Sirt2 inhibitor reported to date, providing a promising target for further medicinal chemistry-driven SAR studies. Full article

Background/Objectives: The global dissemination of tet(X) variants critically threatens tigecycline efficacy as a last-resort antibiotic. The aim of this study was to characterize a tet(X6)-carrying integrative and conjugative element (ICE) in a multidrug-resistant Chryseobacterium lecithinasegens strain, SHZ29, isolated from Shanghai, China. Methods: Minimum inhibitory concentrations (MICs) were determined by broth microdilution for SHZ29. Whole genomic sequencing and bioinformatic analysis were performed to depict the structure of the novel tet(X6)-carrying ICE. Inverse PCR and conjugation experiments were conducted to investigate the transfer ability of the ICE. Results: We depicted a novel tet(X6)-carrying ICE, named ICECleSHZ29, which is 74,906 bp in size and inserted into the 3′ end of tRNA-Met-CAT gene of the C. lecithinasegens strain SHZ29, with 17 bp direct repeats (5′-tcccgtcttcgctacaa-3′). This ICE possesses a 38 kb conserved backbone and four variable regions (VR1-4), with VR3 aggregating multiple resistance genes, including tet(X6), tet(X2), erm(F), ere(D), floR, catB, sul2, ant(6)-I and bla_OXA-1327. NCBI database searching identified 13 additional ICEs sharing a similar backbone to ICECleSHZ29. These ICECleSHZ29-like ICEs could be classified into two types based on their distinct insertion sites: Type I, inserted at the tRNA-Met-CAT gene; and Type II, inserted at the tRNA-Glu-TTC gene. Phylogenetic analysis indicated that differences in integrases may result in differences in the insertion site among these ICEs. A circular intermediate form of ICECleSHZ29 was detected by inverse PCR. However, the conjugation experiments using Escherichia coli EC600 as recipients failed. Conclusions: To our knowledge, this study provides the first report of tet(X6) in C. lecithinasegens and characterizes its carrier, a novel ICE: ICECleSHZ29. Full article

Natural tyrosinase inhibitors are an important group of compounds with cosmetical and medicinal applications. With the aim of finding new types of natural tyrosinase inhibitors from ornamental and medicinal plants, Lycopodium japonicum was selected and studied. As a result, fifteen structurally diverse secondary metabolites 1–15 were isolated and identified. Their chemical structures were identified by analysis of their spectral data and compared with those reported in the literature. In the tyrosinase inhibitory bioassay, five phytochemicals, 4, 12, 13, 14, and 15, exhibited significant inhibitory effects, with half-maximal inhibitory concentration (IC₅₀) values ranging from 1.46 to 6.82 mM. Additionally, molecular docking studies disclosed that Lys376, Lys379, Gln307, and other amino acid residues played key roles in the potential binding interactions between the active compounds and the tyrosinase. These findings suggest that the species L. japonicum is a warehouse of natural tyrosinase inhibitors. Full article

The automotive industry utilizes high-strength low-alloy (HSLA) steels and advanced high-strength steels (AHSS) to manufacture various components, including front and rear rails, chassis, and roll bars, among others. In countries where de-icing salts are used, these steels are exposed to a localized corrosive environment. This research aims to characterize the corrosion behavior of AHSS [dual-phase (DP), ferrite–bainite (FB), and complex-phase (CP)] using electrochemical techniques such as cyclic potentiodynamic polarization (CPP) curves and electrochemical noise (EN), by immersing the steels in NaCl, CaCl₂, and MgCl₂ solutions. Optical microscopy (OM) is used to observe the microstructure of the tested samples. The CPP corrosion behavior of AHSS exposed to chloride solutions exhibits corrosion densities in the range of 10⁻² and 10⁻³ mA/cm². The results generally indicated that AHSS are susceptible to localized corrosion due to the presence of positive hysteresis in the CPP. Zn results show that DP780 presented higher corrosion resistance, with 845 Ω·cm², whereas FB780 presented 253 Ω·cm² when exposed to NaCl. Additionally, the type of corrosion is localized. Full article

The direct deposition of highly concentrated polyelectrolyte complexes based on poly(ethyleneimine) (PEI) and poly(sodium methacrylate) (PMANa) onto inorganic sand microparticles (F100 and F200) resulted in the formation of versatile core-shell composites with fast removal properties in dynamic conditions toward anionic charged pollutants. Herein, in situ-generated nonstoichiometric PEI/PMANa polyelectrolyte complexes were directly precipitated as a soft organic shell onto solid sand microparticles at a 5% mass ratio (organic/inorganic part = 5%, w/w%). The sorption of an anionic model pollutant (Indigo Carmine (IC)) onto the composite particles in dynamic conditions depended on the inorganic core size, the flow rate, the bed type (fixed or fluidized) and the initial dye concentration. The maximum sorption capacity, after 10 cycles of sorption/desorption of IC onto F100@P5% and F200@P5%, was between 16 and 18 mg IC/mL composite. The newly synthesized core-shell composites could immobilize IC at a high flow rate (8 mL/min), either from concentrated (C_IC = 60 mg/L) or very diluted (C_IC = 0.2 mg/L) IC aqueous solution, demonstrating that this type of material could be promising in water treatment or efficient in solid-phase extraction (concentration factor of 2000). Full article

Fungal laccases are promising oxidative enzymes for bioremediation applications, particularly in the degradation of synthetic dyes present in industrial effluents. Here, we evaluated the inhibitory effects of sodium chloride (NaCl) and sodium sulfate (Na₂SO₄) on the activity of Trametes versicolor laccase and its ability to decolorize Congo Red (CR), Malachite Green (MG), and Remazol Brilliant Blue R (RBBR). Enzyme assays revealed concentration-dependent inhibition, with IC₅₀ values of 0.22 ± 0.04 M for NaCl and 1.00 ± 0.09 M for Na₂SO₄, indicating stronger inhibition by chloride. Kinetic modeling showed mixed-type inhibition for both salts. Despite this effect, the enzyme maintained significant activity: after 12 h, decolorization efficiencies reached 95 ± 4.0% for MG, 88 ± 3.0% for RBBR, and 75 ± 3.0% for CR, even in the presence of 0.5 M salts. When applied to a mixture of the three dyes, decolorization decreased only slightly in saline medium (94.04 ± 4.0% to 83.43 ± 5.1%). FTIR spectra revealed minor structural changes, but toxicity assays confirmed marked detoxification, with radicle length in lettuce seeds increasing from 20–38 mm (untreated dyes) to 41–48 mm after enzymatic treatment. Fungal growth assays corroborated reduced toxicity of treated dyes. These findings demonstrate that T. versicolor laccase retains functional robustness under ionic stress, supporting its potential application in saline textile wastewater remediation. Full article

This study investigates the anti-obesity and antidiabetic potential of P. palmata extracts produced through sequential enzymatic and alkaline treatments. Among the treatment groups, the extract treated solely with Alcalase^® (Alc) demonstrated the highest protein content (10.11 ± 0.15%) and degree of hydrolysis (30.36 ± 0.77%), significantly outperforming other treatments (p < 0.05). The Alc extract also exhibited superior inhibitory activity against porcine pancreatic lipase and α-amylase, achieving the lowest IC₅₀ for lipase (2.29 ± 0.87 mg.mL⁻¹) and showing significant enzyme inhibition across all tested concentrations (p < 0.05). Ultrafiltration of the Alc extract revealed that peptide fractions < 1 kDa and 1–3 kDa were most effective in enzyme inhibition, with IC₅₀ values of 3.25–3.55 mg.mL⁻¹ for both lipase and α-amylase. Peptides were identified via LC-MS/MS analysis and database searching using SequestHT, resulting in 536 sequences, of which bioinformatic screening yielded 51 non-toxic, non-allergenic candidates (PeptideRanker score > 0.6); four of these contained known inhibitory motifs for lipase and α-amylase. Molecular docking confirmed strong binding affinities between these peptides and their respective enzymes, supporting their potential as natural enzyme inhibitors. These findings indicate the functional food potential of Alcalase^®-derived P. palmata peptides for managing obesity and type 2 diabetes. Full article

Background: Dupilumab, a monoclonal antibody targeting the IL-4/IL-13 receptor, has shown significant efficacy in improving asthma control and reducing exacerbations in patients with severe eosinophilic asthma. However, there is a lack of knowledge about real-world data on clinical remission rates and their predictors. Objective: This study aimed to evaluate clinical outcomes, remission rates, and predictive factors of remission in a real-life cohort of patients with severe eosinophilic asthma treated with dupilumab. Methods: We conducted a retrospective, bicentric, observational study including 52 patients with severe eosinophilic asthma treated with dupilumab. Clinical, functional, and biomarkers were assessed at baseline, 6 months, and 12 months. Statistical analyses included logistic regression to identify independent predictors of clinical remission. Results: After 12 months of treatment, 48.2% of patients achieved clinical remission. Dupilumab significantly improved asthma control and lung function (including FVC and FEF_25–75), reduced exacerbation rates, and maintenance therapy. High blood eosinophil levels (>490 cells/µL), high FeNO levels (>25 ppb), a history of CRSwNP, and better baseline FEV1 were associated with asthma remission. Conversely, obesity (BMI > 30) and related comorbidities (such as GERD, OSAS, and hypertension) and bronchiectasis were associated with a lower likelihood of remission. Multivariate analysis confirmed higher baseline FEV1 (OR 2.94; IC 1.13–7.6), positive history of CRSwNP (OR 8.03; IC 1.41–45.5), and higher baseline blood eosinophils (OR 1.003 IC 1.001–1.006) as independent predictors of clinical remission. Conclusions: These results are in line with the known effectiveness of dupilumab in severe eosinophilic asthma and identified a history of CRSwNP, higher baseline FEV1, and elevated blood eosinophils as key predictors of clinical remission. These findings may contribute to a more personalized approach to treatment selection, emphasizing the importance of comorbidity assessment together with type 2 inflammation biomarkers. Further prospective studies are needed to validate these results. Full article

Background: Bariatric surgery (BS) is the most effective long-term treatment for severe obesity, but many patients develop food intolerances that either reduce protein and micronutrient intake or shift consumption toward easily tolerated, calorie-dense “safe” foods (e.g., sweets, ice cream, sugar-sweetened beverages, refined-flour snacks), compromising nutrient adequacy and weight-loss maintenance. This narrative review summarizes evidence on the prevalence, mechanisms, and clinical impact of food intolerances after BS, focusing on red meat, dairy, water, cereal, and vegetables, and offers practical nutritional management strategies. Methods: A targeted literature search of PubMed and Cochrane Library from the past 10 years was conducted. Studies were selected based on relevance and quality. Results: Intolerance patterns vary by food type and surgical method. Red meat is the most frequently problematic food, with some patients symptomatic for years despite gradual improvement. Dairy products cause gastrointestinal discomfort in some cases, partly due to lactose intolerance. Cereal products may initially cause swallowing difficulties but are generally well tolerated two years postoperatively. Water intolerance mainly occurs shortly after sleeve gastrectomy (SG), linked to sleeve aperistalsis and edema, resolving within weeks. Cooked vegetables are overall well tolerated across procedures. Mechanisms behind intolerance include mechanical restriction, altered gastric emptying, exaggerated entero-hormonal responses, and new taste aversions. Conclusions: Food intolerances are a common, procedure-specific consequence of BS, requiring systematic assessment and personalized dietary management. Early management—modification of consistency, portion control, and supplementation—can improve product tolerance, prevent nutritional deficiencies, and support sustainable weight loss. However, further prospective studies on the mechanisms of food intolerances are needed. Full article

Background: Inhibiting α-glucosidase and α-amylase is a well-established strategy for managing postprandial hyperglycemia in type 2 diabetes mellitus. However, the adverse effects of current α-glucosidase inhibitors (α-GIs) underscore the need for safer alternatives. Methods: This study introduces an efficient, metal-free, and environmentally friendly protocol for the selective, high-yield synthesis of 1,2-disubstituted benzimidazoles. The reaction between o-phenylenediamine and various aromatic aldehydes proceeds smoothly in water at room temperature, using cost-effective and eco-friendly catalysts such as acetylsalicylic acid (ASA) or salicylic acid (SA). The methodology exhibits broad versatility, enabled by the use of different o-phenylenediamines and a wide range of aromatic and heteroaromatic aldehydes. Results: Selected compounds were assessed for their inhibitory activity against α-glucosidase and α-amylase. While all exhibited low α-amylase inhibition, several showed significant α-glucosidase inhibition, with compounds 8s (IC₅₀ = 0.39 ± 0.04 μM), 8k (IC₅₀ = 7.4 ± 1.6 μM) and 8r (IC₅₀ = 13.8 ± 2.7 μM) emerging as the most promising candidates. Notably, none of these compounds affected Caco-2 cell viability at concentrations up to 30 μM. Additionally, compounds 8r and 8s exhibited antioxidant properties, which may be relevant in counteracting the excessive production of free radicals associated with diabetes. Preliminary molecular docking and 500 ns molecular dynamics (MD) simulations were carried out on compounds 3k, 8i, 8k, and 8p–8s to support and interpret the experimental biological findings qualitatively. Full article

Background/Objectives: While pentadecanoic acid (C15:0), present in whole dairy fat, has broad anticancer activities at high concentrations, the presence of C15:0 anticancer activities at naturally occurring circulating concentrations is less clear. Methods: Using an independent service to run the Eurofins OncoPanel^TM Cell Proliferation Assay, C15:0 was screened for dose-dependent antiproliferation activities against 94 human cancer cell lines at 10 concentrations ranging between 1.5 nM and 50 µM. Oncogenic alterations were compared between cell lines in which C15:0 did or did not have antiproliferation activities. Results: C15:0 had dose-dependent antiproliferation activities (EC50 ≤ 50 µM) among 13 (13.8%) cancer cell lines, most of which were non-Hodgkin B-cell lymphomas (n = 8, 61.5% of C15:0-responsive cell lines), but also included liver (n = 2, 15.4%), breast (n = 2, 15.4%), and lung (n = 1, 7.7%) cancers. C15:0 had robust antiproliferation activities (EC₅₀, IC₅₀ and GI₅₀ ≤ 50 µM) in four cell lines, all of which were non-Hodgkin B-cell lymphomas. When comparing oncogenic alterations among C15:0-responsive versus non-responsive cancer cell lines (n = 79 with available data on DepMap), 4 of 18 (22%) C15:0-responsive cell lines had a CCND3 mutation compared to 1 of 61 (1.6%) non-responsive cell lines (p = 0.007, OR = 17.1, 95% CI 1.8–165). Three of four (75%) of the most C15:0-responsive B-cell lymphomas had the CCND3 alteration (p = 0.0004, OR = 180, 95% CI 8.9–3632). Conclusions: C15:0 has selective dose-dependent anticancer activities at naturally occurring concentrations. The potential use of C15:0 against cancers with CCND3 genetic alterations warrants further exploration. Further, there is a need to better understand the potential role of nutritional C15:0 deficiencies and CCND3 alterations on the observed rise in certain types of cancers, especially among young adults. Full article

The use of antioxidants in the dermatocosmetic industry has become increasingly popular to help protect and stabilize other sensitive active ingredients, prolonging the effectiveness and durability of the cosmetic product. Grape pomace, as the main by-product generated through winemaking, and Polygonum cuspidatum, concentrate bioactive metabolites with high antioxidant activity. Hydroalcoholic extracts obtained from grape pomace (Merlot and Feteasca Neagra varieties) and the root and flower of Japanese knotweed, respectively, alone and in mixtures, were characterized, and preliminary assays were conducted for their incorporation in two gel-based cosmetic formulations. The characterization of the extracts revealed the presence of catechin, vanillic acid, caffeic acid, myricetin, resveratrol, and kaempferol. The hydroalcoholic extract of P. cuspidatum flower and root was found to have the highest content of total phenolic compounds (10.920 ± 0.268 mg GAE/mL, respectively, 4.751 ± 0.072 mg GAE/mL), and the highest antioxidant activity (expressed as DPPH Radical Scavenging Capacity, IC₅₀) by 28.04 ± 1.12 µg GAE/mL and 83.91 ± 1.13 µg GAE/mL, respectively. Catechin was the most abundant polyphenol found in pomace extract (687.87 mg/kg). The type and the concentration of the plant extract used in dermatocosmetic gel formulations influenced their antioxidant activity. Encapsulation of P. cuspidatum flower extract in liposomes prior to their incorporation into the gel formulation demonstrated the role of liposomes in enhancing the stability and modulation of phenolic compound delivery. It is worth noting that this dermatocosmetic formulation, which contains the flower extract of P. cuspidatum, was the subject of a pending patent application. Full article

Bone density is considered one of the many factors influencing bone structure and DNA preservation. For this reason, it is of interest in fields such as anthropology, palaeontology, and genetics. This study describes a method for bone density assessment by gradient centrifugation in Sodium Poly-Tungstate (SPT) solutions (from 2.1 to 2.6 g/cm³). Fifty milligrams of bone powder (size range of 20–50 µm) were used, with an average recovery of 89.9 (IC = 3.3% at 95% of probability). In the first phase of the experiment, the protocol was applied to ten femurs: three exhumed from the WWII mass grave of Ossero, three aged (43–50 years old) femurs from a museum collection and four fresh controls. In the subsequent phase, the analysis was extended to three petrous bones, three metacarpals, and three metatarsals exhumed from the WWII mass grave. The SPT density gradient profiles revealed marked differences among the three femur sample sets: more than 80% of the powder from control femurs was recovered in fractions with a density ≤ 2.2 g/cm³, whereas approximately 45% of the femurs from the mass grave showed a density > 2.6 g/cm³. The remaining three aged femurs displayed peculiar density patterns. Among the other bone types, metatarsals showed the lowest density values, followed by petrous bones and metacarpals. To detect degradation signatures, all nineteen bone powders were also analysed by ATR-FTIR. The femurs from the mass grave exhibited spectral features consistent with mineral recrystallisation and degradation of the organic phase, whereas the other three aged femurs showed peculiar spectral profiles; metacarpals, petrous bones and metatarsals showed intermediate spectra. PCA was applied to SPT and ATR-FTIR data, revealing correlations that support the SPT method as a novel tool for bone quality assessment. Although based on a limited sample size, this preliminary work demonstrates that SPT gradient analysis is an effective, low-cost, rapid and reliable method for assessing bone density, with potential applications in different disciplines studying aged bone samples. Lastly, principal component analysis (PCA) revealed a correlation between bone density and the yield of DNA recovered from the ten femoral specimens. Full article