Search Results (1,523)

Direct-acting antivirals (DAAs) have transformed hepatitis C virus (HCV) management, offering high cure rates, favorable safety, and simplified regimens. Management in immunosuppressed patients remains challenging due to drug–drug interactions (DDIs). The objective of this review is to summarize clinical outcomes, safety, and pharmacologic considerations of DAA therapy in immunosuppressed patients, including solid organ transplant recipients and those on biological agents. We reviewed clinical studies, pharmacologic databases, and guidelines to characterize DAA classes, mechanisms, and relevant DDIs in immunosuppressed HCV patients. In transplant recipients, DAAs achieved sustained virological response (SVR) > 90% with minimal graft rejection. Safety profiles were favorable, and immunosuppressant dose adjustments were rarely needed. DDIs, particularly with calcineurin inhibitors (tacrolimus, cyclosporine), require careful monitoring due to variable trough-level effects. Evidence also supports the efficacy and safety of DAAs in patients on biological agents, without compromising SVR. Pharmacokinetic data indicate DAAs maintain antiviral activity across HCV genotypes in the presence of immunosuppressants, though mTOR inhibitors may alter efficacy in certain HCV genotypes. DAAs are highly effective and safe in immunosuppressed patients, achieving high SVR rates and potential graft survival benefits. Prospective studies are needed to assess DAA therapy in patients receiving biological agents and to optimize co-administration strategies with immunosuppressive agents. Full article

The high salt content, low permeability, and fragile structure of saline–alkali land severely constrain the construction and development of irrigation channels. Compaction is an effective means of improving the soil’s engineering performance. Previous studies in this field have mostly been limited to two-dimensional numerical simulations and generally lack systematic physical experiments to support their findings, resulting in an insufficient understanding of the three-dimensional deformation mechanism and macroscopic mechanical response of soil during compaction. In view of the above limitations, this study adopts a comprehensive research framework of “physical experiment–numerical simulation”. Conducting indoor rolling model tests of control variables and simultaneously constructing the corresponding 2D and 3D discrete element models based on the MatDEM platform revealed the influence of curing agent dosage (10% and 25%), loosely laid sample thickness (10 cm and 30 cm), and number of rolling passes on the compaction effect. The test results show that the degree of compaction increases in a typical three-stage pattern of “rapid rise–slow growth–gradual stabilization” with the number of rolling passes, and the number of economic rolling passes is from 4 to 6. Increasing the dosage of the curing agent and reducing the thickness of application both significantly improve the uniformity of compaction and the final density. Numerical simulation further reveals that the 3D model can more accurately reflect the three-dimensional stress state of the soil and the spatial movement of particles, and that the simulation results are in higher agreement with the experimental data. The 2D model has greater computational efficiency and can capture the main compaction trends under specific simplified conditions, but it has deficiencies in quantitative accuracy. This study verified the effectiveness and advantages of MatDEM in simulating complex geotechnical compaction processes, providing theoretical support for an in-depth understanding of compaction mechanisms and the optimization of construction parameters using discrete element methods. Full article

Leptospirosis, caused by Leptospira spp., affects multiple domestic species and can result in significant economic and public health impacts. This scoping review, conducted following the PRISMA 2020 guidelines, searched PubMed, SciELO, and Scopus for original studies that described complete therapeutic protocols (including dose, duration, and confirmed diagnosis) in dogs, cats, cattle, pigs, horses, sheep, and goats. Thirty-five studies met the criteria: 14 (40%) in cattle, 7 (20%) in swine, 2 (5.7%) in small ruminants, 7 (20%) in dogs and cats, and 5 (14.3%) in horses. In livestock, streptomycin monotherapy has predominated, demonstrating high efficacy against renal and genital carriers, but it faces regulatory restrictions in several countries. In companion animals, treatment often addressed acute cases using doxycycline and aminopenicillins, with frequent drug combinations. Horses were mainly treated with penicillin, alone or associated with other agents. Across species, protocols showed substantial heterogeneity, lack of harmonization, and limited evaluation of bacteriological cure, with most studies published before 2000. This scarcity of recent clinical trials reinforces the neglected status of animal leptospirosis. By compiling fragmented evidence, this review identifies converging practices that may serve as a preliminary consensus, highlights discrepancies and knowledge gaps, and provides an evidence-based framework to support the development of standardized, species-specific guidelines urgently needed in a One Health context. Full article

Burkitt lymphoma (BL) is a rare, aggressive B-cell lymphoma that is characterized by rapid tumor proliferation and frequent extra-nodal involvement. While prompt diagnosis and initiation of highly intensive chemotherapy results in cure rates over 90% in children and adolescents, outcomes in adults are more modest, as comorbidities and advancing age may compromise treatment tolerability. In recent years, intermediate-intensity regimens have been developed for BL. These are highly effective in patients of all ages and associated with significantly less treatment-related toxicity compared to traditional high-dose chemotherapy. This was demonstrated in a recent randomized study of dose-intensive R-CODOX-M/R-IVAC compared to the reduced-intensity DA-EPOCH-R regimen, which was associated with equivalent outcomes but with significantly fewer side effects. Regardless of the chemotherapy platform, CNS involvement at baseline predicts a significantly inferior outcome, and the development of an optimal approach for these patients is an area of unmet need in BL therapeutics. Patients with relapsed or refractory disease following frontline therapy have very short survival times, as currently available salvage options are largely ineffective. In this regard, novel agents such as anti-CD19 CAR-T cells and bi-specific antibodies are under development in BL. It is hoped that progress in novel drug development, alongside improved understanding of BL biology, to further elucidate its genetic and epigenetic vulnerabilities, will lead to improved outcomes for patients in the future. Full article

The article presents the results of a study of the possibility of using heat-treated ethylene-vinyl acetate copolymer (EVA) as a thermoplastic modifier in a photosensitive composition based on tert-butyl acrylate (tBA). The use of such a modifier in 3D printing compositions is important for improving their physical and mechanical properties at low temperatures. An attempt was also made to use EVA as a polymer chain brancher. The molecular structure of the components and their compositions, rheology, curing kinetics, and phase organization of photocured systems were studied using FTIR and NMR spectroscopy, spectrophotometry, rheometry, Photo-DSC, and scanning electron microscopy. It was found that heat treatment of EVA allows the formation of single C=C bonds in macromolecules, which are necessary for a potential crosslinking agent with tBA. It was shown that EVA effectively functions as a thickener and modifier: with an increase in the modifier concentration, the nature of the composition flow changes from Newtonian to pseudoplastic, the rate of the photochemical polymerization reaction decreases, and the degree of conversion of the system decreases. However, the formation of a heterogeneous phase structure and the absence of a continuous spatial network of chemical bonds prevent the use of EVA simultaneously as a functional additive and crosslinking agent. Full article

In the past decades, significant advancements in the biological and genetic characterization of acute leukemias and optimization of risk-adapted multi-agent treatment protocols have dramatically improved cure rates and quality of life for children with acute lymphoblastic leukemia (ALL). Despite these optimal results, patients with relapsed or chemotherapy-refractory (R/R) disease or with high-risk genetic features still face unsatisfactory outcomes. Further intensification of conventional chemotherapy has reached its limits in achieving the desired efficacy without undue side effects, necessitating innovative approaches to improve cure rates while continuing to minimize the toxicities associated with chemotherapy and hematopoietic stem cell transplantation. In the era of precision medicine, two key therapeutic strategies have emerged in hemato-oncology: molecularly targeted therapies and immunotherapies. Antibody-based and cellular immunotherapies have undoubtedly reshaped the landscape of childhood ALL treatment and have significant potential to play leading roles in current and future frontline regimens; these important therapies are well delineated in recent reviews. Molecularly targeted small molecule inhibitor therapies remain a cornerstone of precision medicine, supported by recent advancements in next-generation sequencing, which have enabled the application of transcriptomic and genomic profiling data to risk stratification and therapy optimization. Clinical trials for children with ALL have been instrumental in refining therapies and improving outcomes, a paradigm that remains critical as treatment strategies become increasingly complex. This comprehensive review focuses upon molecularly targeted therapy approaches for childhood ALL and aims to summarize findings from completed clinical trials to highlight the current landscape of ongoing and upcoming trials and to provide insights into future directions for the precision-driven optimization of pediatric B-ALL and T-ALL treatment. Full article

The main objective of this study was to evaluate the long-term mechanical performance and shrinkage behavior of ultrahigh-performance concrete (UHPC) in which the granulated ground blast-furnace slag (GGBFS), used as part of the binder, is replaced partially or fully with ferronickel slag (FNS). The aim was to identify potential strength reduction and expansion problems associated with the use of FNS powder. For steam-cured UHPC, the compressive strength of the FNS100 (124.8 MPa) was comparable to that of the control case (FNS0, 125.1 MPa), and the tensile strength showed only a 0.3 MPa difference. Under constant-temperature and constant-humidity conditions, all mixtures satisfied the design strength standard of 120 MPa by the end of the curing period. Considering constant-temperature and constant-humidity conditions, shrinkage evaluation revealed that the FNS100_NON_AD (no shrinkage-reducing and expansive agents) exhibited 3.8 times greater shrinkage compared to FNS0, while other mixtures remained within a narrow range. These results indicate that shrinkage was governed more by the presence and type of admixtures than by the FNS replacement rate itself. This study demonstrated that FNS has sufficient potential for use as a binder in UHPC and encourages further research to optimize admixture use for long-term durability and shrinkage control. Full article

Background: Amlodipine besylate (AML) is recognized as a calcium channel blocker curative for hypertension. However, the drug emerged recently as an antibacterial cure that competently prevails over resistant strains. Methods: Incorporating amlodipine into zein nanoparticles was employed to innovate a suitable carrier for loading and targeting deep corneal infection. The Box–Behnken design was adopted to produce various formulations of amlodipine-loaded zein nanoparticles (AML-ZNs) with diversity in composition concentration (% w/v), comprising zein, Labrafac, and poloxamer 407. Results: Relying on the optimization criterion, the chosen preference formulation concentration (% w/v) consists of 2.068 for zein, 0.75 for Labrafac, and 1.0 for Poloxamer. Morphological micrography of AML-ZNs showed regular spherical particles in the nanometric scale, and physicochemical characterization procedures confirmed system suitability. While tracking eyedrop optimum features, sodium alginate was selected for coating nanoparticles to improve stability and system viscosity. Both pH and sterility were also considered and maintained. Comparative studies were conducted pre- and post-coating, and the assessed features for the final selected formulation were 349.9 ± 5.8 nm, 0.2186 ± 0.0271, −55.45 ± 1.84 mV, 81.293 ± 0.9%, and 19.3 ± 0.19 cp for size, PDI, surface charge, entrapment, and viscosity, respectively. The AML-ZNs-Alg formulation demonstrates a more controlled pattern of release of roughly 40% of the drug released after 48 h, while the permeation profile shows 37 ± 3.52% permeated after 24 h, confirmed visually. In vitro microbial assay alongside the corneal in vivo microbial and histological pathology evaluation proved the efficacy of amlodipine as an antibacterial agent. Conclusions: These findings highlighted that the prepared AML-ZNs-Alg eyedrop can be a promising system as an antibacterial therapy. Full article

Consumer demand for organic and nitrite-free meat products has stimulated the search for sustainable alternatives to synthetic curing agents. Conventional nitrites are effective in stabilizing color, inhibiting lipid oxidation, and suppressing pathogens, but their use raises health concerns due to potential nitrosamine formation. This study investigated the application of Portulaca oleracea powder as a multifunctional ingredient to fully replace sodium nitrite in organic cooked frankfurters. Two formulations were produced: control frankfurters with sodium nitrite and experimental frankfurters with purslane powder 1.2%. Physicochemical, oxidative, proteomic, and antioxidant parameters were monitored during refrigerated storage. Purslane incorporation improved the lipid profile by increasing α-linolenic acid and lowering the ω-6/ω-3 ratio, while peroxide, thiobarbituric acid reactive substances (TBARS), and acid values remained significantly lower than in nitrite-containing controls after 10 days. Protein oxidation was also reduced, and SDS-PAGE profiles confirmed that the major structural muscle proteins remained stable, indicating that purslane addition did not disrupt the core proteome. Antioxidant assays showed strong ferric-reducing antioxidant power (FRAP) activity 13.7 mg GAE/g and enhanced 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging capacity 22.3%, highlighting purslane’s contribution to oxidative stability. Although redness (a*) was lower than in nitrite controls, overall color stability (L*, b*) remained high. Taken together, purslane enhanced oxidative stability and quality attributes of nitrite-free organic frankfurters; microbiological validation is ongoing and will be reported separately. Full article

Survival rates for those with metastatic osteosarcoma (OS) have not improved over the last four decades. It is imperative that novel approaches to treating and curing OS be sought. We, therefore, turned our attention to Brusatol (Bru), a naturally occurring Nrf2 inhibitor reported to elicit anti-cancer effects in a multitude of tumour models. Importantly there is emerging evidence that Nrf2 is implicated in chemoradiotherapy resistance in OS and that inhibiting Nrf2 may represent a desirable route to treating OS. Surprisingly, using the human OS cell line, MG63, we actually found that Bru promoted cell growth. Compared to control, normoxic cultures, the application of Bru (50 nM) over 3 days led to an increase in cell number by approximately 1.7-fold. A similar outcome occurred for cells under hypoxic conditions, although the extent of cell growth was significantly less at around 1.3-fold. Furthermore, Bru prevented MG63 differentiation in response to co-treatment with the calcitriol analogue, EB1089, and the lipid growth factor, lysophosphatidic acid. The extent of inhibition was profound at approximately 2.8-fold. The application of the Nrf2 activator, dimethyl fumarate, did not rescue these phenotypes. Whilst Bru has shown promise in other cancer models, it would appear, from our findings, that this agent may not be suitable for the treatment of OS. Full article

Leishmaniasis is a parasitic disease caused by Leishmania spp., transmitted by sandflies, and endemic in 98 countries. Leishmania infantum, the main agent of visceral leishmaniasis in Europe, commonly infects both humans and animals, with dogs as the principal domestic reservoir. Clinical manifestations in dogs depend on the host immune response. A robust Th1 response facilitates macrophage activation and parasite control, while persistently elevated TNF-α and IL-6 can lead to chronic inflammation and tissue damage. Current treatments reduce parasite load but rarely achieve complete cure and are often associated with relapses and resistance. Artemisia annua, source of artemisinin, could be a promising alternative to canine leishmaniasis. Despite its potential, no published studies have investigated its effect specifically against Leishmania infantum as well as its possible dual action: antiparasitic and immunomodulation. We conducted in vitro evaluations of a standardized Artemisia annua extract. Leishmanicidal activity was assessed against both promastigote and amastigote stages, and cytokine modulation was evaluated in RAW 264.7 macrophages. The extract showed strong leishmanicidal activity without cytotoxicity and significantly reduced TNF-α and IL-6 levels under inflammatory conditions, and in both cases, efficiency was correlated with artemisinin content. These results support Artemisia annua as a promising safer therapeutic adjuvant candidate for canine leishmaniasis, targeting both the parasite and the host inflammatory response. Full article

The impregnation and curing process of dry bushing requires the epoxy material for bushing to have a good process performance. In addition, the actual operating conditions of dry bushing put forward high requirements on the dielectric properties of the epoxy material. Amine accelerators can not only improve the technological properties of epoxy materials such as gel time and curing exothermic temperature rise by regulating the reaction rate of epoxy resin and anhydride curing agent, but also optimize the dielectric properties of epoxy materials by regulating the crosslinking density of epoxy materials. However, there are many types of amine accelerators, and the effects of amine accelerators with different nucleophilicity on epoxy materials vary greatly. In this paper, four kinds of amine accelerators with different nucleophilic ability were selected to study the influence of the nucleophilic ability of amine accelerators on the process and dielectric properties of epoxy materials. The results show that the stronger the nucleophilicity of the amine accelerator, the shorter the gel time of the epoxy mixture and the higher the exothermic temperature rise during curing, indicating a poorer processing performance. However, stronger nucleophilicity also endows the epoxy material with superior dielectric properties. Among them, the strong nucleophilic ability of TEA shortens the gel time of the material by 50% and increases the curing exothermic temperature rise by 55.3% compared with the weak nucleophilic ability of the DET epoxy system; the dielectric constant and dielectric loss of the material are reduced by 8.3% and 39.5%, respectively, and the breakdown strength is improved by 11.4%. This paper reveals the contradictory relationship between the process and dielectric performance of epoxy materials triggered by the difference in the nucleophilic ability of amine accelerators, and it also provides a new research idea for the improvement of the process and in the dielectric performance of epoxy materials for dry bushing. Full article

This study investigates the acoustic performance of Ecoflex™ 00-35, a highly flexible silicone rubber, for use in soft and adaptable vibration and noise control systems. Under normal conditions, Ecoflex™ 00-35 consists of two components—Part A and Part B—which are mixed and cured at room temperature to form an elastomer. In this study, curing parameters such as the A/B mixing ratio, thinning agent addition, and curing pressure were varied to examine their effects on acoustic behavior. The microstructure of the prepared samples was analyzed using scanning electron microscopy (SEM), while sound absorption properties were measured using impedance tubes. Test results demonstrated that modifying curing parameters, applying vacuum, and incorporating a thinning agent increased the average cell diameter, leading to the fabrication of a moderate sound absorber with a sound absorption coefficient ranging from 0.35 to 0.60 in the low- to mid-frequency ranges. Further enhancement in low-frequency absorption was achieved by applying low pressure for a short duration, allowing cell expansion. In contrast, the addition of a thinning agent significantly improved absorption at higher frequencies. These findings highlight the influence of processing conditions on the acoustic behavior of soft silicone elastomers and provide valuable insights into their structure–property relationships. Ultimately, this study contributes to the development of advanced materials for acoustic damping and noise control applications. Full article

In this study, cement, short-cut carbon fibers, and polymer water-absorbing resin were used as the main materials, with high-performance water-reducing polycarboxylic acid agent as the modified material. A new conductive cement-based grouting material was developed by incorporating functional additives. Its mix design was optimized based on initial setting time, fluidity, bleeding rate, and compressive strength. The optimal ratio of the grouting material was determined as follows: 0.4 wt% of high water-absorbent resin, 0.25 wt% of high-efficiency water reducer, 0.8 wt% of short-cut carbon fibers, and a water–cement ratio of 0.8:1. The electrical conductivity of the grouting material was studied in depth under different dosages of short-cut carbon fibers, considering factors such as curing age, temperature, and pressure conditions. The results show that with the increase in curing age, the volume resistivity of the specimen gradually increases; the resistivity of the conductive cementitious grouting material decreases with the rise in temperature, showing a negative temperature coefficient effect; additionally, the doping of an appropriate amount of short-cut carbon fibers enables the conductive cementitious grouting specimen to exhibit good pressure-sensitive properties. Field test verification indicates that the new cementitious conductive grouting material has excellent conductive properties, and the grouting quality can be effectively evaluated via high-density electrical testing. Full article

Parkinson’s disease (PD) is a progressive, irreversible neurodegenerative disorder characterized by motor impairments and a wide spectrum of non-motor symptoms, including gastrointestinal dysfunction, sleep disturbances, depression, and cognitive decline. These manifestations arise from disturbances across multiple systems—gastrointestinal, neuroendocrine, immune, enteric, and central nervous systems. Alterations in the gut microbiota may play a causal role in PD onset and frequently accompany disease progression. The gut–brain axis, particularly the vagus nerve, is increasingly recognized as a key communication pathway whose dysregulation contributes to systemic dysfunction and the breakdown of homeostasis, ultimately driving PD pathology. Currently, there is no cure for PD, and existing treatments primarily target symptom relief. Effective management of PD requires a comprehensive approach that integrates multiple pharmacologically active agents aimed at restoring impaired organ functions and, when possible, neutralizing toxic factors that accelerate disease progression. One promising therapeutic avenue lies in functional gut bacteria, which form the basis for developing live biotherapeutic products, postbiotics, and bacterial vesicles. In this review, we summarize current data on the effects of probiotics in PD, drawing on both animal models and clinical studies. We highlight the role of probiotics in modulating PD pathophysiology and discuss their potential as adjunctive therapeutic agents. To provide a broader perspective, we also include sections describing the clinical manifestations of PD, gut microbiota alterations associated with the disease, and the role of artificial intelligence, particularly machine learning, in constructing functional models of PD. Full article