Search Results (23,813)

In accelerated bridge construction, precast concrete girders are connected to cast-in-place concrete slab using shear transfer reinforcement across the interface plane to ensure the composite action. The steel transverse reinforcement is prone to severe corrosion due to the extensive use of de-icing salts and severe environmental conditions. As glass fiber-reinforced polymer (GFRP) reinforcement has shown to be an effective alternative to conventional steel rebars as flexural and shear reinforcement, the present research work is exploring the performance of GFRP reinforcements as shear transfer reinforcement between precast and cast-in-place concretes. Experimental testing was carried out on forty large-scale push-off specimens. Each specimen consists of two L-shaped concrete blocks cast at different times, cold joints, where GFRP reinforcement was used as shear friction reinforcement across the interface with no special treatment applied to the concrete surface at the interface. The investigated parameters included the GFRP reinforcement shape (stirrups and headed bars), reinforcement ratio, axial stiffness, and the concrete compressive strength. The relative slip, reinforcement strain, ultimate strength, and failure modes were reported. The test results showed the effectiveness and competitive shear transfer performance of GFRP compared to steel rebars. A shear friction model for predicting the shear capacity of as-cast, cold concrete joints reinforced by GFRP reinforcement is introduced. Full article

Background: Alcohol use disorder is a common condition with high morbidity and mortality and no highly effective treatments. Achieving and maintaining abstinence is necessary or desired for many persons with AUD, but is difficult due to the nature of the condition. Pharmacologic inhibition of the enzyme ALDH2, which increases levels of the substrate acetaldehyde when alcohol is imbibed, can serve as a powerful enforcer of efforts to remain abstinent. Disulfiram is an approved ALDH2 inhibitor via its active metabolite DETC-MeSO, but has many limitations, including numerous adverse effects, hepatotoxicity, oral administration, and unpredictable mechanistic activity. Methods: SOPH-110S, an analog of DETC-MeSO, was evaluated in a series of experiments to assess mechanism, pharmacokinetics in male beagle dogs, cardiovascular safety in telemeterized male beagle dogs, selectivity, off-target activity, CYP inhibition, and proof of mechanism in a rat model that included dosing and alcohol challenge followed by analysis of liver ALDH2 inhibition. Results: SOPH-110S showed high potency with a comparable IC₅₀ vs. positive controls and no physiologically relevant off-target binding in an 84-target panel. It did not inhibit or induce any major CYP enzymes or meaningfully inhibit the hERG channel. After 10 days’ dosing in rats, followed by administration of alcohol, SOPH-110S was a highly potent, dose-dependent inhibitor of ALDH2, comparable to DETC-MeSO. No cardiovascular safety concerns were found at multiples above expected clinical doses. Conclusions: The preclinical data support further clinical study of SOPH-110S as a potential ALDH2 inhibitor treatment for AUD. The FDA approved the IND to conduct a first-in-man phase 1 study in September 2025. Full article

Background and Rationale: Tinospora crispa (L.) Hook.f. & Thomson (T. crispa) is a climbing medicinal plant with long-standing ethnopharmacological use, particularly in inflammatory and hepatic disorders and cancer-related conditions. There is a knowledge gap regarding how wild versus cultivated ecotypes differ in chemotype, bioactivity, and safety, and how this might support or refine traditional use. Study Objectives: This study aimed to compare wild and cultivated ecotypes of T. crispa from the Nile Delta (Egypt) in terms of quantitative and qualitative phytochemical profiles; selected in vitro biological activities (especially antioxidant and cytotoxic actions); genetic markers potentially associated with metabolic variation; and short-term oral safety in an animal model. Core Methodology: Standardized extraction of plant material from wild and cultivated ecotypes. Determination of total phenolics, total flavonoids, and major phytochemical classes (alkaloids, tannins, terpenoids). Metabolomic characterization using UHPLC-ESI-QTOF-MS, supported by NMR, to confirm key compounds such as berberine, palmatine, chlorogenic acid, rutin, and borapetoside C. In vitro bioassays including: Antioxidant activity (e.g., radical-scavenging assay with EC₅₀ determination). Cytotoxicity against human cancer cell lines, with emphasis on HepG2 hepatoma cells and calculation of IC₅₀ values. Targeted genetic analysis to detect single-nucleotide polymorphisms (SNPs) in the gen1 locus that differentiate ecotypes. A 14-day oral toxicity study in rats, assessing liver and kidney function markers and performing histopathology of liver and kidney tissues. Principal Results: The wild ecotype showed a 43–65% increase in total flavonoid and polyphenol content compared with the cultivated ecotype, as well as substantially higher levels of key alkaloids, particularly berberine (around 12.5 ± 0.8 mg/g), along with elevated chlorogenic acid and borapetoside C. UHPLC-MS and NMR analyses confirmed the identity of the main bioactive constituents and defined a distinct chemical fingerprint for the wild chemotype. Bioassays demonstrated stronger antioxidant activity of the wild extract than the cultivated one and selective cytotoxicity of the wild extract against HepG2 cells (IC₅₀ ≈ 85 µg/mL), being clearly more potent than extracts from cultivated plants. Genetic profiling detected a C → T SNP within the gen1 region that differentiates the wild ecotype and may be linked to altered biosynthetic regulation. The 14-day oral toxicity study (up to 600 mg/kg) revealed no evidence of hepatic or renal toxicity, with biochemical markers remaining within physiological limits and normal liver and kidney histology. Conclusions and Future Perspectives: The wild Nile-Delta ecotype of T. crispa appears to be a stress-adapted chemotype characterized by enriched levels of multiple bioactive metabolites, superior in vitro bioactivity, and an encouraging preliminary safety margin. These findings support further evaluation of wild T. crispa as a candidate source for standardized botanical preparations targeting oxidative stress-related and hepatic pathologies, while emphasizing the need for: More comprehensive in vivo efficacy studies. Cultivation strategies that deliberately maintain or mimic beneficial stress conditions to preserve phytochemical richness. Broader geographical and genetic sampling to assess how generalizable the present chemotypic and bioactivity patterns are across the species. Full article

In this paper, characteristic ultraviolet absorption spectra are presented for benzene and chlorobenzene in transparent hexagonal water–ice solutions at temperatures between 273 K and 78 K. In addition, the liquid solution spectra at 292 K have also been included. The two lowest symmetry-forbidden transitions from the ground state (¹A_1g) to the first excited level of symmetry (B_2u), denoted as ¹B_2u ← ¹A_1g, and the transition from the ground state to the second excited level of symmetry (¹B_1u), denoted as ¹B_1u ← ¹A_1g, of benzene are recorded. The two lowest transitions of chlorobenzene from the ground state (¹A₁) to the first excited level of symmetry (¹B₂), denoted as ¹B₂ ← ¹A₁, and the transition from the ground state to the second excited level of symmetry (¹A₁) denoted as, ¹A₁ ← ¹A₁, are also studied. The bands are obtained for slowly cooled transparent water–ice solutions. Such ice samples, that were frozen from liquid water and cooled, show gradual changes in the spectra. Our study shows the spectra at eight temperatures, separating the spectra in different regions based on the range for the bands from ground state to the first and second excited states of benzene and chlorobenzene, observing changes in the integrated absorbances as a function of the temperature. For the spectra recorded at 78 K, the peak absorbances as a function of the wavelength are presented and tentatively assigned. Peak assignments are based on the known literature of benzene and chlorobenzene. The temperature range of our study covers some of the average temperatures that have been found in the icy moons of Saturn and the polar regions of Earth. Full article

A kinetic and thermodynamic multi-phase model has been developed to describe the adsorption of gases on ice surfaces and their subsequent diffusional loss into the bulk ice phase. This model comprises a gas phase, a solid surface, a sub-surface layer, and the ice bulk. The processes represented include gas adsorption on the surface, solvation into the sub-surface layer, and diffusion in the ice bulk. It is assumed that the gases dissolve according to Henry’s law, while the surface concentration follows the Langmuir adsorption equilibrium. The flux of molecules from the sub-surface layer into the ice bulk is treated according to Fick’s second law. Kinetic and thermodynamic quantities as applicable to the uptake of small carbonyl compounds on ice surfaces at temperatures around 200 K have been used to perform model calculations and corresponding sensitivity tests. The primary application in this study is acetic acid. The model simulations are applied by fitting the experimental data obtained from coated-wall flow-systems (CWFT) measurements, with the best curve-fit solutions providing reliable estimations of kinetic parameters. Over the temperature range from 190 to 220 K, the estimated desorption coefficient, k_des, varies from 0.02 to 1.35, while adsorption rate coefficient, k_ads, ranges from 3.92 and 4.17, and the estimated diffusion coefficient, D, changes by more than two orders of magnitude, increasing from 0.03 to 13.0. Sensitivity analyses confirm that this parameter estimation approach is robust and consistent with underlying physicochemical processes. It is shown that for shorter exposure times the loss of molecules from the gas phase is caused exclusively by adsorption onto the surface and solvation into the sub-surface layer. Diffusional loss into the bulk, on the other hand, is only important at longer exposure times. The model is a useful tool for elucidating surface and bulk process kinetic parameters, such as adsorption and desorption rate constants, solution and segregation rates, and diffusion coefficients, as well as the estimation of thermodynamic quantities, such as Langmuir and Henry constants and the ice film thickness. Full article

Structural and physicochemical deterioration in frozen foods is largely driven by ice crystal formation and growth during storage. Although biofoams offer sustainable alternatives to plastic packaging, bio-based systems designed to mitigate ice crystal-induced quality loss remain limited. In this study, a sodium alginate-based biofoam was synthesized via a facile one-pot method and evaluated for frozen fried chicken packaging. Its moisture, mechanical, and optical properties were compared with those of conventional plastic and paper packaging. The quality of frozen fried chicken was assessed in terms of moisture absorption, color, texture, pH, lipid oxidation (TBARs), and the overall appearance under different freezing conditions. The alginate biofoam exhibited exceptionally high moisture absorption (>2400%) due to its porous and hydrophilic structure, enabling effective moisture management during frozen storage. Samples packaged with the biofoam showed reduced moisture loss, lower lipid oxidation, and improved color and surface texture stability compared with conventional packaging, particularly under freeze–thaw conditions. These findings demonstrate that sodium alginate-based biofoam is a promising eco-friendly packaging material for maintaining the physicochemical quality of frozen ready-to-eat foods. Full article

Introduction: Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a major public health concern due to the limited effectiveness of current treatments, especially in the chronic stage. Objective: Here, we wanted to advance a library of 30 N,N′-disubstituted diamines as promising antichagasic agents and gain insight into the mechanism of action. Methods: The library was evaluated for activity against the T. cruzi amastigote stage and trypanocidal efficacy. In addition, selected compounds were tested as potential polyamine transport inhibitors, and a fluorescent analog was employed to investigate compound internalization. Results: Five compounds exhibited potent activity (pIC₅₀ > 6.0), particularly those with short aliphatic linkers (3–6 carbon atoms), suggesting a structure–activity relationship favouring shorter chains. Mechanistic studies showed that compound 3c strongly inhibited polyamine transport, a vital pathway in T. cruzi, though this was not a universal mechanism among active hits, indicating the potential for multiple targets. A fluorescent analog confirmed intracellular uptake in amastigotes but lacked antiparasitic activity, likely due to disrupted pharmacophoric features. Importantly, none of the compounds demonstrated trypanocidal activity in long-term assays, and some showed cytotoxicity, particularly in the benzyloxy-substituted series. Conclusions: These findings position N,N′-disubstituted diamines as a viable scaffold for Chagas disease drug discovery. However, further optimization is required to enhance selectivity, achieve trypanocidal effects, and better understand the underlying mechanisms of action. Full article

We present the results of long-term photometric and spectroscopic monitoring of the Seyfert galaxy NGC 4151 based on new observational data complemented by archival material spanning several decades. NGC 4151 is one of the most extensively studied active galactic nuclei, exhibiting pronounced variability in both optical continuum and emission-line fluxes, which makes it a key object for investigating physical processes in the central engine and the broad-line region. Our study covers the optical and near-infrared wavelength ranges, including the Ic band and the standard BVRc photometric filters. Using multi-band optical photometry and optical spectroscopy, we construct light curves of the continuum and emission lines and perform a comparative analysis of their temporal behavior during different activity states of the galaxy. The analysis focuses on variability amplitudes, long-term trends, and correlations between photometric and spectral characteristics, allowing us to examine the relationship between continuum variations and the line-emitting regions. Full article

A growing body of evidence indicates that artificial manipulation of transcriptional regulation is a powerful approach to activate cryptic biosynthetic gene clusters (BGCs) of secondary metabolites (SMs) in fungi. In this study, one mutant strain MNP-2-OE::veA was constructed by overexpressing the global transcription regulator veA in an Arctic-derived strain Aspergillus sydowii MNP-2. Chemical investigation of the mutant OE::veA resulted in the isolation of one novel polyhydroxy anthraquinone (1) together with nine known metabolites (2–10), which were unambiguously characterized by various spectroscopic methods including 1D and 2D NMR and HR-ESI-MS as well as via comparison with literature data. Biosynthetically, compounds 1 and 10 as new arising chemicals were, respectively, formed by type II polyketide synthase (T2PK) and non-ribosomal peptide synthetase (NRPS), which were silent in the wild-type (WT) strain MNP-2. A bioassay showed that only compound 3 had weak inhibitory effect on human pathogen Candida albicans, with a MIC value of 64 ug/mL, and 4 displayed in vitro weak cytotoxic activity against HCT116 cells (IC₅₀ = 44.47 μM). These results indicate that overexpression of veA effectively awakened the cryptic BGCs in fungal strains and enhanced their structural diversity in natural products. Full article

Catastrophic mass flows originating from the high mountain cryosphere often cause cascading hazards. With increasing human activities in the alpine region and the sensitivity of the cryosphere to climate warming, cryospheric hazards are becoming more frequent in the mountain regions. Monitoring the evolution and impact of the glaciers and ice-rock avalanches and hazard consequences in the mountain regions is crucial to understand nature and drivers of mass flow process in order to prevent and mitigate potential hazard risks. In this study, the glacier and ice-rock avalanches that occurred in the Tibetan Plateau (TP) were investigated based on the Sentinel-2 satellite data and in situ observations, and the main driving forces and impacts on the regional environment, landscape, and geomorphological conditions were also analyzed. The results showed that the avalanche deposit of Arutso glacier No. 53 completely melted away in 2 years, while the deposit of Arutso glacier No. 50 melted in 7 years. Four large-scale ice-rock avalanches in the Sedongpu basin not only had significant impacts on the river flow, landscape, and geomorphologic shape in the basin, but also caused serious disasters in the region and beyond. These glacier and ice-rock avalanches were caused by temperature anomaly, heavy precipitation, climate warming, and seismic activity, etc., which act on the specific glacier properties in the high mountain regions. The study highlights scientific advances should support and benefit the remote and vulnerable mountain communities to make mountain regions safer. Full article

Streptomyces is a versatile genus widely used in drug production and biotechnological applications. This study aimed to identify and characterize bioactive compounds produced by Streptomyces UP-AC4 and UP-3.2 strains and evaluate their antibacterial and anticancer activities. The strains were identified as Streptomyces californicus and Streptomyces purpurascens via chemotaxonomy, 16S rRNA sequencing, amplified ribosomal DNA restriction analysis, and phylogenetic analysis. Bioactive compounds were extracted using heat treatments at 63 °C for 30 min or 73–110 °C for 10 min. Antibacterial activity against Staphylococcus aureus, Bacillus cereus, and Escherichia coli was assessed by agar disc assay, with MICs of 0.024–0.195 mg/mL and MBCs of 0.098–0.391 mg/mL for the most effective extracts. Anticancer activity against A549, H1299, and Lu99 lung cancer cells was evaluated using the MTT assay, showing IC₅₀ values of 0.23 ± 0.06 to 4.85 ± 0.64 mg/mL, while exhibiting no toxicity to normal fibroblast cells. HPLC analysis indicated that heat-assisted extraction of UP-AC4 at 73 °C for 10 min enriched a dinactin-associated compound as a predominant metabolite with antibiotic and anticancer activities. In conclusion, Streptomyces UP-AC4 and UP-3.2 produce promising low-cost bioactive compounds with strong potential for pharmaceutical and healthcare applications. Full article

This study presents a multifunctional theranostic platform based on anisotropic gold nanostars (AuNSs) functionalized with 2-thiouracil (2-TU) for cancer diagnostics and photothermal therapy (PTT). The unique plasmonic properties of AuNSs, combined with the anticancer and photothermal potential of 2-TU, were harnessed to create a system capable of simultaneous colorimetric biosensing and therapeutic action. Under dual-wavelength irradiation (660 nm and 525 nm), the AuNSs–2-TU conjugate demonstrated enhanced photothermal conversion efficiency, selective cancer cell targeting, and signal amplification, resulting in a significant reduction in the IC₅₀ for MCF-7 breast cancer cells. The system exhibited minimal cytotoxicity to normal fibroblasts (WS1), ensuring therapeutic precision. Compared to conventional spherical gold nanoparticles, this platform provides superior multifunctionality, including real-time biosensing with simple, naked-eye colorimetric readouts. These results highlight the potential of the AuNSs–2-TU conjugate as an innovative, minimally invasive nanotheranostic platform suitable for integrated cancer detection and treatment, particularly in resource-constrained settings. Full article

Intermittent claudication (IC) is the most frequent symptomatic manifestation of lower-extremity peripheral artery disease (PAD). Supervised exercise therapy (SET) and endovascular revascularization (ER) are established treatments, but their relative and combined effects on health-related quality of life (HRQoL) remain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing SET, ER, and ER+SET, with HRQoL as the primary outcome. Methods: Following PRISMA 2020, PubMed, Embase, and CENTRAL were used in December 2024. Eligible RCTs enrolled with IC (excluding critical limb-threatening ischemia) and reported validated HRQoL outcomes at ≥3 months. Two reviewers independently extracted data and assessed risk of bias using the Cochrane RoB 2.0 tool. Random-effects meta-analyses pooled standardized mean differences (SMDs) for HRQoL and mean differences (MDs) for walking distance. Results: Five RCTs (n = 728) were included. Compared with optimal medical therapy, both SET and ER improved HRQoL and walking distance. At 12 months, no significant effect was observed between SET and ER (SMD 0.02; 95% CI: −0.18 to 0.22). ER+SET was superior to SET alone (SMD 0.35; 95% CI: 0.12–0.57). Beyond 24 months, improvements were sustained with SET but attenuated with ER, accompanied by higher reintervention rates in ER-containing arms (approximately 20–30% by 2 years). Adverse events were rare (<1%). Conclusions: Given moderate-certainty evidence (GRADE), SET should remain the first-line therapy for intermittent claudication because it provides durable improvements in patient-centered outcomes with minimal harm. Endovascular revascularization (ER) can provide faster symptom relief, but its long-term benefits are constrained by restenosis and repeat procedures, particularly in femoropopliteal disease. Full article

Sewage sludge is increasingly recognized as a major reservoir for pharmaceuticals and emerging contaminants that are only partially removed by conventional wastewater treatment. This study provides the first comprehensive assessment of these contaminants in biosolids generated from ten major wastewater treatment plants (WWTPs) across Jordan. Different pharmaceuticals were quantified in the sludge samples generated. The results revealed concentrations ranging from 10 to over 2000 µg kg⁻¹, with antibiotics typically showing the highest enrichment (e.g., ciprofloxacin up to 2165 µg kg⁻¹, ofloxacin up to 303 µg kg⁻¹). Anti-inflammatory compounds such as diclofenac reached 196 µg kg⁻¹, while the antimicrobial triclosan exceeded 4700 µg kg⁻¹ in some sludge samples. Carbamazepine, a recalcitrant antiepileptic drug, ranged between 50 and 223 µg kg⁻¹, reflecting both widespread use and strong persistence. Elevated levels of quaternary ammonium compounds (QACs) were also detected. The highest levels were generally associated with large urban WWTPs and plants receiving industrial discharges. Environmental risk assessment (ERA) indicated that the risk for soil biota was acceptable for most cases for low application doses (5–10 t/ha) except for WWTP6-MD, WWTP8-S, and WWTP9-IC, where the risk was non-acceptable. Severe limitations in the risk assessment were noted: reliable toxicity endpoints in terrestrial soil organisms such as microbiota, collembola, and earthworms are few, while deriving endpoints via aquatic available data is not always reliable. Overall, the findings demonstrate that Jordanian sewage sludge contains environmentally relevant levels of pharmaceuticals and QACs and that risk assessment is, therefore, pertinent before any stabilization and realistic land application scenarios are chosen. Full article