Search Results (88)

Background: Uncontrolled asthma remains a significant clinical challenge, often linked to impaired lung function and increased diaphragmatic workload. Recent studies have shown promising results using a triple inhaled therapy comprising beclomethasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G). This study assessed the real-world efficacy of BDP/FF/G on lung function and diaphragmatic workload in patients with uncontrolled asthma. Methods: A prospective observational study enrolled 21 adult patients diagnosed with uncontrolled asthma despite high-dose ICS/LABA therapy. Patients underwent lung function tests and right diaphragmatic ultrasound assessments at baseline and after three months of treatment with BDP/FF/G (172/5/9 mcg, administered as two inhalations every 12 h). Results: After three months, significant improvements were observed in FEV₁ (from 57.75 ± 12.30% to 75.10 ± 18.94%, p < 0.001) and FEF_25–75 (from 47.80 ± 19.23% to 75.10 ± 36.06%, p < 0.001). Additionally, during the same period, we recorded significant reductions in residual volume (from 130.10 ± 28.20% to 92.55 ± 21.18%, p < 0.001) and total airway resistance (R_tot) (from 164.60 ± 83.21% to 140.70 ± 83.25%, p < 0.05). The mean asthma control test (ACT) score increased by 5.6 points (p < 0.001), surpassing the established minimal clinically important difference (MCID) of 3 points and raising the cohort mean above the well-controlled threshold. The right diaphragmatic workload was significantly decreased, as shown by a reduction in thickening fraction (TF) (from 63.86 ± 17.67% to 40.29 ± 16.65%, p < 0.01). Correlation analysis indicated significant associations between diaphragmatic function and some lung function parameters (FEV₁, FEF_25–75, and R_tot). Conclusions: In this real-world pilot, triple BDP/FF/G was linked to improvements in airflow, hyperinflation, symptoms, and a reduction in diaphragmatic thickening fraction, indicating potential physiological benefit. Due to the small sample size, single-centre design, and 3-month follow-up, these results should be viewed as hypothesis-generating and need to be confirmed in larger, controlled, multicentre studies with longer follow-up. Full article

This work presents the synthesis, characterisation, photophysical properties, time-resolved spectroscopic behaviour, and biological evaluation of two structurally distinct heavy-atom-free BODIPY-anthracene dyads (BDP-1) and the newly designed 2,6-bis[1-(tert-butyl) 4-(prop-2-yn-1-yl) piperazine-1,4-dicarboxylate] BODIPY-anthracene (BDP-2), incorporating 2,6-alkynyl-piperazine substituents for potential application in antimicrobial photodynamic therapy. BDP-1 exhibits absorption and emission maxima at 507 nm and 516 nm, respectively, with a Stokes shift of 344 cm⁻¹ in dichloromethane (DCM), characteristic of unsubstituted BODIPYs. In contrast, BDP-2 undergoes a red-shift in the absorption maximum to 552 nm (Stokes shift of 633 cm⁻¹), which is attributed to the extended conjugation from the introduction of the alkyne groups. Time-resolved infrared spectroscopy confirmed efficient spin-orbit charge transfer intersystem crossing, and nanosecond transient absorption studies confirmed the formation of a long-lived triplet state for BDP-2 (up to 138 µs in MeCN). A binding constant (K_b) of 9.6 × 10⁴ M⁻¹ was obtained for BDP-2 when titrated with bovine serum albumin (BSA), which is higher than comparable BODIPY derivatives. BDP-2 displayed improved hemocompatibility compared to BDP-1 (<5% haemolysis of human erythrocytes up to 200 μg·mL⁻¹). Antimicrobial activity of BDP-1 and BDP-2 was most potent when irradiated at 370 nm compared to the other wavelengths employed. However, BDP-2 did not retain the potent (6 log) and rapid (within 15 min) eradication of Staphylococcus aureus achieved by BDP-1 under irradiation at 370 nm. These findings demonstrate the rational design of BDP-2 as a biocompatible, and heavy-atom-free BODIPY offering promise for targeted antimicrobial photodynamic therapeutic applications. Full article

Background: Malaria remains a significant global health burden, particularly in sub-Saharan Africa, accounting for high rates of illness and death. The growing resistance to frontline antimalarial therapies underscores the urgent need for novel drug targets and therapeutics. Bromodomain-containing proteins, which regulate gene expression through chromatin remodeling, have gained attention as potential targets. Plasmodium falciparum bromodomain protein 1 (PfBDP1), a 55 kDa nuclear protein, plays a key role in recognizing acetylated lysine residues and facilitating transcription during parasite development. Methods: This study investigated ex vivo PfBDP1 gene mutations and identified potential small molecule inhibitors using computational approaches. Malaria-positive blood samples were collected. Genomic DNA was extracted, assessed for quality, and amplified using PfBDP1-specific primers. DNA sequencing and alignment were performed to determine single-nucleotide polymorphism (SNP). Structural modeling used the PfBDP1 crystal structure (PDB ID: 7M97), and active site identification was conducted using CASTp 3.0. Virtual screening and pharmacophore modeling were performed using Pharmit and AutoDock Vina, followed by ADME/toxicity evaluations with SwissADME, OSIRIS, and Discovery Studio. GROMACS was used for 100 ns molecular dynamics simulations. Results: The malaria prevalence rate stood at 12.24%, and the sample size was 165. Sequencing results revealed conserved PfBDP1 gene sequences compared to the 3D7 reference strain. Virtual screening identified nine lead compounds with binding affinities ranging from −9.8 to −10.7 kcal/mol. Of these, CHEMBL2216838 had a binding affinity of −9.9 kcal/mol, with post-screening predictions of favorable drug-likeness (8.60), a high drug score (0.78), superior pharmacokinetics, and a low toxicity profile compared to chloroquine. Molecular dynamics simulations confirmed its stable interaction within the PfBDP1 active site. Conclusions: Overall, this study makes a significant contribution to the ongoing search for novel antimalarial drug targets by providing both molecular and computational evidence for PfBDP1 as a promising therapeutic target. The prediction of CHEMBL2216838 as a lead compound with favorable binding affinity, drug-likeness, and safety profile, surpassing those of existing drugs like chloroquine, sets the stage for preclinical validation and further structure-based drug design efforts. These findings are supported by prior experimental evidence showing significant parasite inhibition and gene suppression capability of predicted hits. Full article

The mechanisms driving changes in the stability of phosphorus (P) in sediments under lake ecosystem degradation remain poorly understood. This study investigated the P-binding forms in sediments from three plateau lakes with different trophic states in Yunnan Province, China, aiming to elucidate the responses of sediment P compositions to human activities, lake trophic status, and dissolved organic matter (DOM) characteristics. The results showed that human activity directly contributed to sediment P retention. The trophic type of lake exerted a discernible effect on P mobility in the sediments, as eutrophic algae-type lakes had a higher content of sediment mobile-P. Moreover, the sediment DOM promoted the adsorption of BD-P and NH₄Cl-P. Generally, exogenous pollution caused by human activity leads to lake eutrophication and a decline in lake ecosystem stability. This variation was largely influenced by water depth. A decrease in lake ecosystem stability leads to increased P mobility in sediments, which increases the risk of endogenous pollution. The DOM plays an important role in the mobility of sediment P. These insights offer a novel perspective for understanding how lake ecosystem characteristics are related to endogenous P loads in lakes. Full article

This study explores the relationship between borderline personality disorder (BPD) symptoms, measured using the Borderline Symptom List (BSL-23), and experiences of covert social violence, assessed via the Inventory of Covert Social Violence Against Women (IVISEM) and an open-ended survey given to 99 adults diagnosed with BPD. Quantitative data revealed significant emotional intensity, with a mean BSL-23 score of 56.81 (SD = 20.31), and a positive correlation (r = 0.29, p < 0.0034) between symptom severity and the number of self-reported disorders. The qualitative analysis highlighted themes of ‘Stigmatization and Structural Violence’ and ‘Gender Expectations’, with 62.9% of participants reporting that their emotions were pathologized as hormonal or exaggerated. The results highlight the significant emotional intensity in participants, particularly related to shame and vulnerability, suggesting these emotions are linked to structural violence perpetuated by patriarchal norms, including covert social violence. Biological explanations for emotionality, such as references to “hormonal” changes and “menstruation”, reinforce the idea that women’s intense emotions are natural, overlooking broader societal and structural factors. The results underscore the impact of the patriarchal structure, emphasizing the need for psychological approaches that address both the symptoms of BPD and the impact of societal and structural violence on women’s emotional health. The study sample underscores the main idea of the study: BPD is predominantly diagnosed in women, which underlines the need to rethink diagnostic tools and professional interventions. These results highlight the need for a feminist critique of the BSL-23 by showing how emotional symptoms are often interpreted through a gendered lens, emphasizing the importance of re-evaluating diagnostic tools to address the impact of societal and structural violence on women’s mental health. Full article

Bidirectional promoters (BDPs) regulate the transcription of two adjacent, oppositely oriented genes, offering a compact structure with significant potential for multigene expression systems. Although BDPs are evolutionarily conserved, their regulatory roles and sequence characteristics vary across species, with limited studies in fish. Here, we systematically analyzed the distribution, sequence features, and expression patterns of BDPs in the medaka (Oryzias latipes) genome. A total of 1737 divergent gene pairs, representing 13% of medaka genes, were identified as potentially regulated by BDPs. These genes are enriched in essential biological processes, including organelle function, RNA processing, and ribosome biogenesis. Transcriptomic analysis revealed that co-regulation (co-expression and co-silencing) is a prominent feature of these gene pairs, with variability influenced by tissue and sex. Sequence analysis showed that medaka BDPs are compact, with most fragments under 400 bp and an average GC content of 42.06%. Validation experiments confirmed the bidirectional transcriptional activity of three histone-related BDPs in both medaka SG3 cells and embryos, demonstrating effective and robust regulatory efficiency. This study enhances our understanding of the genomic organization and transcriptional regulation in fish and provides a valuable reference for developing species-specific multigene expression systems in fish genetic engineering. Full article

Background: Spray drying, whilst a popularly employed technique for powder formulations, has limited applications for large-scale proliposome manufacture. Objectives: Thus, the aim of this study was to investigate spray drying parameters, such as inlet temperature (80, 120, 160, and 200 °C), airflow rate (357, 473, and 601 L/h) and pump feed rate (5, 15, and 25%), for individual carbohydrate carriers (trehalose, lactose monohydrate (LMH), and mannitol) for 24 spray-dried (SD) formulations (F1–F24). Methods: Following optimization, the SD parameters were trialed on proliposome formulations based on the same carriers and named as spray-dried proliposome (SDP) formulations. Drug delivery of the formulations was assessed using a dry powder inhaler (DPI) in combination with a next-generation impactor (NGI). Results: Upon analysis, formulations F6 (SD-mannitol), F15 (SD-trehalose), and F20 (SD-LMH) demonstrated high production yields (84.01 ± 3.25, 72.55 ± 5.42, and 70.03 ± 3.39%, respectively), small particle sizes (2.96 ± 1.42, 4.55 ± 0.46, and 5.16 ± 1.32 µm, respectively) and low moisture contents (0.25 ± 0.03, 3.76 ± 0.75, and 1.99 ± 0.77%). These SD optimized parameters were then employed for SDP formulations employing dimyristoly phosphatidylcholine (DMPC) as a phospholipid and beclomethasone dipropionate (BDP) as the model drug. Upon spray drying, SDP-mannitol provided the highest production yield (82.45%) and smallest particle size (2.64 µm), as well as high entrapment efficiency (98%) and a high fine particle dose, fine particle fraction, and respirable fraction (285.81 µg, 56.84%, 86.44%, respectively). Conclusions: The study results are a promising step in the optimization of the large-scale manufacture of proliposome formulations and highlight the versatility of the instrument and variability of formulation properties with respect to the carriers employed for targeting the pulmonary system using dry powder inhalers. Full article

Proper waste sorting is crucial for biodegradable plastics (BDPs) recycling, whose global production is increasing dynamically. BDPs can be sorted using near-infrared (NIR) sorting, but little research is available about the effect of surface contamination on their NIR spectrum, which affects their sortability. As BDPs are often heavily contaminated with food waste, understanding the effect of surface contamination is necessary. This paper reports on a study on the influence of artificially induced surface contamination using food waste and contamination from packaging waste, biowaste, and residual waste on the BDP spectra. In artificially contaminated samples, the absorption bands (ADs) changed due to the presence of moisture (1352–1424 nm) and fatty acids (1223 nm). In real-world contaminated samples, biowaste samples were most affected by contamination followed by residual waste, both having altered ADs at 1352–1424 nm (moisture). The packaging waste-contaminated sample spectra closely followed those of clean and washed samples, with a change in the intensity of ADs. Accordingly, two approaches could be followed in sorting: (i) affected wavelength ranges could be omitted, or (ii) contaminated samples could be used for optimizing the NIR database. Thus, surface contamination affected the spectra, and knowing the wavelength ranges containing this effect could be used to optimize the NIR database and improve BDP sorting. Full article

The combined treatment with calcipotriol (Cal) and betamethasone dipropionate (BDP) has emerged as the leading anti-psoriatic topical treatment. Fixed-dose Cal/BDP is available in different formulations, including ointment, gel, foam, and cream. This review examines the mechanism of action of Cal/BDP underlying its therapeutic effect and compiles the evidence regarding its efficacy and safety compared to monotherapy with topical corticosteroids. The dual-action of Cal/BDP targets the inflammatory pathways and abnormal keratinocyte proliferation, both of them fundamental mechanisms of psoriasis pathogenesis. A large number of randomized, double-blind studies support Cal/BDP superiority over topical corticosteroids, demonstrating its broad efficacy across several degrees of psoriasis severity and its capability to provide early significant clinical improvements. This increased efficacy is achieved without negative effects on the safety profile, since the incidence of adverse effects reported with Cal/BDP is usually similar to that of BDP and even lower than that of Cal alone. The combination therapy rapid onset of action, coupled with a simplified dosing regimen, has been identified as crucial for improving long-term adherence and patient outcomes. In conclusion, Cal/BDP is confirmed as a versatile, effective, and convenient option for the patient in psoriasis management. Full article

An overproducing date fruit with limited industrial utilization leads to significant waste and losses, especially in the early stage of date maturity known as bisr. This study aimed to investigate the potential use of bisr date powder (BDP) at different concentrations (25%, 50%, and 100%) as a natural sweetener instead of sugar and barley flour as a source of dietary fiber, vitamins, and minerals instead of wheat flour (50%) in biscuit production over storage periods of 7, 14, and 21 days. The analysis revealed that the bisr Al-Khalas powder sample had a moisture content of 11.84%, ash content of 2.30%, and crude fiber content of 10.20%. Additionally, it had a low protein (2.50%) and fat (0.77%) content, with total carbohydrates at 82.59%. The gradual substitution of bisr Al-Khalas in biscuit production resulted in an increased moisture, ash, fat, protein, crude fiber, and iron content, as well as a decrease in total carbohydrate percentage. A chemical analysis of bisr Al-Khalas powder demonstrated high levels of antioxidants, with 248.49 mg gallic acid/g of phenolic compounds, 31.03 mg quercetin/g of flavonoids, and an antioxidant activity ranging from 42.30%, as shown by the DPPH test. The peroxide content was 0.009 mg equivalent/kg. Biscuit samples with different proportions of bisr Al-Khalas showed an improved resistance to oxidation compared to samples without bisr Al-Khalas, with increased resistance as the percentage of replacement increased during storage. Physical properties such as the diameter, height, and spread percentage, as well as organoleptic properties like color, flavor, aroma, and taste, were significantly enhanced with higher levels of bisr Al-Khalas in the mixture. Biscuit samples fortified with 100% pure bisr Al-Khalas powder were found to be less acceptable, while samples with a 25% substitution did not negatively impact sensory properties. In addition, acrylamide and hydroxymethylfurfural (HMF) were not detected in bisr powder and biscuit samples prepared at different concentrations (25%, 50%, and 100%). In conclusion, the study suggests that bisr Al-Khalas powder, an underutilized waste product, has the potential to add value to commercial biscuit production due to its high nutritional value and extended storage period resulting from its potent antioxidant activity. Full article

Non-hormone-treated beef steers (n = 1625; 371 ± 8.4 kg) were used to determine the impact of a direct-fed microbial (DFM) on growth performance, carcass characteristics, health parameters, and economic outcomes in finishing beef cattle. Steers were blocked based on initial BW, sorted into three optimal marketing groups for each day of enrollment, randomly assigned to one of two treatments (12 replicates per treatment), and fed for an average of 133 days before harvest. Treatments included the following: (1) control (CON) and (2) 50 mg/head per day of a DFM (BDP) containing Lactobacillus animalis 506, Propionibacterium freudenreichii 507, Bacillus licheniformis 809, and Bacillus subtilis 597 (BOVAMINE DEFEND^® Plus). Steers were weighed in drafts by pen on a certified scale at closeout, and both pens within a block were harvested on the same day. Carcass characteristics and liver scores were collected upon slaughter. Data were analyzed as part of a completely randomized block design with the pen as the experimental unit. There was no difference in dry matter intake and final body weight between treatments. The BDP steers exhibited a lower number of total outs (deads and removed) throughout the experiment (p < 0.01). Average daily gain (ADG) tended to be greater (p < 0.06), and feed efficiency (p < 0.01) was greater, for steers receiving BDP. Although there were no statistical differences in hot carcass weight and quality grade between treatments, there was a lower incidence of liver abscess scores (p < 0.01) in the BDP steers. These data suggest that BOVAMINE DEFEND^® Plus supplementation improves growth performance during the finishing phase, reduces overall mortality, and improves feed to gain efficiency. Full article

The introduction of inhaled corticosteroids (ICSs) changed over a few decades the treatment focus of mild-to-moderate asthma from bronchodilation to reduction in inflammation. This was achieved by inhaling a suitable corticosteroid (CS), giving a high, protracted airway concentration at a low total dose, thereby better combining efficacy and tolerance than oral therapy. Successful trials with the potent, lipophilic “skin” CS beclomethasone dipropionate (BDP) paved the way, suggesting that ICSs require a very low water solubility, prolonging their intraluminal dissolution within airways. The subsequent ICS development, with resulting clinical landmarks, is exemplified here with budesonide (BUD), showing that a similar efficacy/safety relationship is achievable by partly alternative mechanisms. BUD is much less lipophilic, giving it a 100-fold higher water solubility than BDP and later developed ICSs, leading to its more rapid intraluminal dissolution and faster airway and systemic uptake rates. In airway tissue, a BUD fraction is reversibly esterified to intracellular fatty acids, a lipophilic conjugate, which prolongs airway efficacy. Another mechanism is that the rapidly absorbed bulk fraction, via short plasma peaks, adds anti-inflammatory activity at the blood and bone marrow levels. Importantly, these plasma peaks are too short to provoke systemic adverse actions. Controlled clinical trials with BUD changed the use of ICS from a last resort to first-line treatment. Starting ICS treatment immediately after diagnosis (“early intervention”) became a landmark for BUD. An established dose response made BUD suitable for the treatment of patients with all degrees of asthma severity. With the development of the budesonide/formoterol combination inhaler (BUD/FORM), BUD contributed to the widely used BUD/FORM maintenance and reliever therapy (MART). Recent studies demonstrated the value of BUD/FORM as a generally recommended as-needed therapy for asthma (“anti-inflammatory reliever”, AIR). These abovementioned qualities have all influenced international asthma management and treatment guidelines. Full article

Mg alloy AZ31B was directly bonded to SK7 with a low alloy content, DP980 with a high Mn content, 316L with a high Cr and high Ni content by laser-gas tungsten arc welding (GTAW) and hybrid direct lap welding. The results showed that the tensile loads of AZ31B/SK7 and AZ31B/DP980 joints were 283 N/mm and 285 N/mm respectively, while the tensile load of AZ31B/316L joint was only 115 N/mm. The fracture and interface microstructures were observed using scanning electron microscopy (SEM), electron probe microanalysis (EPMA), and identified through X-ray diffractometry (XRD). For AZ31B/SK7 and AZ31B/DP980, the interface of the front reaction area and the keyhole reaction area was mainly composed of an Fe-Al phase and an Al-Mn phase. However, for AZ31B/316L, the interface of the keyhole reaction area was mainly composed of an Fe-Al phase and an Al-Mn phase, but a multi-layer composite structure consisting of the Mg₁₇Al₁₂ compound layer and eutectic layer was formed in the front reaction area, which led to a deterioration in the joint property. The influencing mechanism of Mn, Cr and Ni elements in steel on the properties and interface structure of the laser-GTAW lap joint between the Mg alloy and the steel was systematically analyzed. Full article

The Sangu River basin significantly contributes to national economy significantly; however, exposures to water-related hazards are frequent. As it is expected that water-related disasters will increase manifold in the future due to global warming, the Government of Bangladesh has formulated the Bangladesh Delta Plan 2100 (BDP-2100) to enhanced climate resilience. Accordingly, this study assessed the hydro-meteorological characteristics of the Sangu River basin under the changing climate. This study scientifically selected five General Circulation Models (GCMs) to include the model climate sensitivity and statistically bias-corrected their outputs. The Water and Energy Budget-based Rainfall-Runoff-Inundation (WEB-RRI) model was used to simulate the hydrological responses of the basin. The analysis of five GCMs under the Representative Concentration Pathway (RCP8.5) revealed that all selected GCMs estimate a 2–13% increase in annual rainfall and a 3–12% increase in annual discharge in the near-future (2025–2050), whereas four GCMs project an 11–52% increase in annual rainfall and a 7–59% increase in annual discharge in the far-future (2075–2100). The projected more frequent and intense increased extreme rainfall and flood occurrences in the future indicate an increase in flood disaster risk, whereas increased meteorological and hydrological drought in the future reflects a scarcity of water during dry periods. The number of projected affected people shows an increasing trend due to the increased inundation in the future. However, an increasing trend of transpiration indicates agricultural productivity will increase in the future. Policymakers can utilize this evidence-based information to implement BDP-2100 and to reduce the disaster risks in the basin. Full article

In situ capping and biochemical oxidation are two of the most commonly used methods for internal phosphorus (P) control, but there are few studies on the combined use of these two methods. In this study, two lanthanum (La)-based materials, La-modified bentonite (LMB) and the La-modified attapulgite and chitosan composite (LMA&C), were combined with calcium nitrate (CN) to investigate the effect on sediment P control. Results showed that SRP removal rates by LMB+CN and LMA&C+CN were much higher than that by LMB, LMA&C and CN alone. LMB+CN and LMA&C+CN decreased DGT-labile P flux both in overlying water and surface 65 mm sediment, while LMB and LMA&C had an effect only on overlying water and surface 10~40 mm sediment, and CN was effective only on sediments. LMB and LMA&C transformed NH₄Cl-P, BD-P, NaOH-SRP and NaOH-NRP in surface 20 mm sediment to HCl-P and Residual-P on day 60. CN transformed NaOH-SRP and NaOH-NRP to BD-P, resulting in the increase in NH₄Cl-P. LMB+CN and LMA&C+CN sequestered P in the surface 20 mm mainly as HCl-P and Residual-P, and mainly as BD-P in −20~−60 mm. Results indicate that the combination of capping by La-based material and oxidation by CN is a promising method for sediment P control. Full article