Search Results (558)

Neurodegenerative diseases (NDDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), are becoming more prevalent and still lack effective disease-modifying therapies (DMTs). However, translational efficiency remains critically low. For example, a ClinicalTrials.gov analysis of AD programs (2002–2012) estimated ~99.6% attrition, while PD programs (1999–2019) achieved an overall success rate of ~14.9%. In vitro platforms are assessed, ranging from immortalized neuronal lines and primary cultures to human-induced pluripotent stem cell (iPSC)-derived neurons/glia, neuron–glia co-cultures (including neuroinflammation paradigms), 3D spheroids, organoids, and blood–brain barrier (BBB)-on-chip systems. Complementary in vivo toxin, pharmacological, and genetic models are discussed for systems-level validation and central nervous system (CNS) exposure realism. The therapeutic synthesis focuses on AD, covering symptomatic drugs, anti-amyloid immunotherapies, tau-directed approaches, and repurposed drug classes that target metabolism, neuroinflammation, and network dysfunction. This review links experimental models to translational decision-making, focusing primarily on AD and providing a brief comparative context from other NDDs. It also covers emerging targeted protein degradation (PROTACs). Key priorities include neuroimmune/neurovascular human models, biomarker-anchored adaptive trials, mechanism-guided combination DMTs, and CNS PK/PD-driven development for brain-directed degraders. Full article

Background/Objectives: The Achilles tendon is the largest tendon in the human body; it is frequently ruptured during sports and other dynamic physical activities. The purpose of this study was to compare recovery patterns over time between injuries to the dominant (DMT) and non-dominant (NDMT) limbs, and to examine differences in the limb symmetry index (LSI) for the uninjured side. Methods: This study includes a retrospective analysis of individuals who completed a standard rehabilitation program for 12 months and had regular checkups every three months. The study sample comprised 17 patients with DMT injuries and 17 patients with NDMT injuries, all active male recreational participants who underwent surgical repair of an Achilles tendon rupture. Outcome measures included dorsiflexion range of motion (ROM), calf circumference, plantarflexion strength, hop test performance, and the Y-Balance Test (YBT). Results: Both groups demonstrated continuous, progressive improvement in ROM, plantarflexion strength, hop test distance, and YBT scores, showing a significant main effect of time (p < 0.05). Although DMT showed greater strength than NDMT at 6 and 9 months, this difference was no longer significant at 12 months (p > 0.05). In all three YBT directions, the DMT group achieved greater reach distances than the NDMT group at 12 months (p < 0.05). At the final follow-up, both groups exceeded 90% LSI in ROM, calf circumference, plantarflexion strength, and hop performance (p < 0.05). However, in the YBT, only the DMT group surpassed 90% LSI, whereas the NDMT group showed poorer recovery. Conclusions: ROM, calf circumference, and muscle strength ultimately showed no significant differences between groups, but dynamic balance recovery was superior in the DMT group. These findings suggest that clinicians and rehabilitation specialists should consider leg dominance when designing rehabilitation programs. Full article

Novel initiation systems for the production of poly(methyl methacrylate) (PMMA) bone cements based on low-toxicity tertiary amine initiators and hydroxyapatite nanoparticles were investigated. Bicomponent systems formed by a solid component containing PMMA and benzoyl peroxide (BPO) and a liquid component containing methylmethacrylate and low-toxicity aliphatic (dimethylamino-ethoxy-ethane) (DMEE) and aromatic (dimethylamino-benzaldehyde) (DMAB) tertiary amines were tested at two amine concentrations (0.75 and 3.75 wt%) and compared with the standard tertiary amine dimethyl-p-toluidine (DMT). The components were mixed in a 2:1 ratio (solid/liquid) for 60 s. Nanocomposites were prepared using nano-hydroxyapatite inserted into the PMMA-based polymer matrix at various concentrations between 1.0 and 3.75 wt%, aiming to increase the biocompatibility of bone cements applied in cranioplasty. The concentration of tertiary amines directly affects the reaction rate, and increasing the concentration accelerates the curing reaction. Thermal analyses (DSC and TGA) revealed that the produced polymers did not show significant changes in glass transition temperature (113 °C and 115 °C), nor in onset (150–158 °C) or peak degradation temperatures (353 °C and 355 °C). The reaction with the aliphatic amine proved to be slow, as no polymerization occurred within the time period stipulated in the study. However, drastic changes did take place when the cure occurred in the presence of nano-hydroxyapatite. The cure with DMAB (3.75 wt%) that presented an exothermic peak at 37 min (53 °C) showed a peak at 16 min (70 °C), and the cure with DMEE (3.75 wt%) a peak at 11 min (62.5 °C) after the addition of nano-hydroxyapatite. In conclusion, addition of nano-hydroxyapatite significantly influenced both the time and the temperature of cure reaction in all amines studied, expanding the possibility of using new initiators in polymerization systems for cranioplasty flaps. Full article

Multiple sclerosis (MS) is a chronic neuroinflammatory and autoimmune disorder of the central nervous system (CNS) whose cause remains unknown. Disease-modifying therapies (DMTs) are the current standard of care, yet growing evidence highlights the importance of complementary lifestyle-based interventions, including nutrition, in modulating disease activity. Given the influence of diet on immune function, several studies have examined its effects in MS, with particular attention to specific dietary patterns and macronutrients. However, fewer studies have focused on micronutrients, bioactive compounds, and minerals and their influence in MS. In this narrative review, we report the latest evidence on micronutrients such as vitamins and essential metals, along with polyphenols and minerals like salt, in both experimental autoimmune encephalomyelitis (EAE) and MS. We also discuss how these dietary components may influence the gut microbiota, which is considered a contributor to disease onset due to its interaction with the immune system in the gut–brain axis. While findings for vitamins B, C, E, and K remain heterogeneous, vitamins A and D show the most consistent immunological and clinical effects, with immunomodulatory, antioxidative, and neuroprotective effects in both EAE and MS. Polyphenols also display anti-inflammatory and neuroprotective properties in EAE and, to a lesser extent, in clinical studies. Lastly, evidence suggests the importance of balanced salt intake and adequate levels of essential metals, as dysregulation may contribute to comorbidities or enhance inflammatory pathways relevant to MS. Although only a limited number of studies have explored these aspects, the gut microbiota appears to be differentially affected by these dietary factors. Overall, advancing our understanding of how these components interact with immune and microbial pathways may support the development of personalized nutritional strategies to complement current therapies and improve patient outcomes. Full article

This narrative review explores the impact of diet and physical exercise both as a risk factor of central nervous system inflammatory diseases, but more importantly as potential adjunctive disease modifiers in Multiple Sclerosis (MS), Neuromyelitis Optica Spectrum Disorders (NMOSD), and Myelin Oligodendrocyte Glycoprotein (MOG) antibody-associated disease (MOGAD). The majority of evidence relies on MS preclinical and clinical studies, but preclinical studies also support the benefit of lifestyle intervention in NMOSD and MOGAD. In MS, adherence to healthy diets (particularly Mediterranean and MIND diets) could lead to a milder disease course with reduced relapse rates, while structured exercise from early disease stages promotes neuroprotection by upregulating neurotrophic factors and preserving brain volume, possibly impacting disease progression. The ketogenic diet and intermittent caloric restriction also showed promising results. Physical activity, including both aerobic training and resistance training, emerges as a potential disease-modifying strategy by promoting neuroprotection, reducing inflammation, and supporting functional and cognitive outcomes, particularly when implemented early in the disease course. A synergistic approach alongside disease-modifying treatments (DMTs) would further positively modulate core pathological processes. Evidence for NMOSD and MOGAD warrants further investigation. We highlight that integrating personalized lifestyle strategies would be beneficial from the early stages. However, future large-scale, standardized trials are required to fully confirm the neuroprotective potential of diet and exercise across the entire spectrum of CNS disorders. Full article

Background: Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS), characterised by inflammation, demyelination, and progressive neurodegeneration. Although current disease-modifying therapies (DMTs) can reduce relapse rates and inflammatory activity, they rarely stop long-term progression or repair neurological damage. In recent years, cell-based therapies have emerged as promising approaches to promote immune regulation and neuroregeneration in MS. Methods: This review summarises the current clinical evidence from studies in humans investigating cell-based treatments for MS, including autologous haematopoietic stem cell transplantation (AHSCT), mesenchymal stem cells (MSCs), and neural stem or progenitor cells (NSCs). A systematic literature search was performed using PubMed, Scopus, and ClinicalTrials.gov, focusing on human clinical trials that met specific inclusion criteria. Results: Prevailing findings show that AHSCT provides the most consistent benefit, achieving long-term immune reconstitution and remission in patients with highly active relapsing–remitting MS (RRMS), although it carries procedural risks. MSC therapies have demonstrated good safety and biological activity, especially when delivered intrathecally (IT) in progressive MS, though clinical results remain variable. Conclusions: NSC-based treatments are still at an early stage of clinical research but show potential for CNS repair. The main limitations across studies include differences in protocols, small sample sizes, and short follow-up periods. Further large-scale, randomised controlled trials are needed to confirm long-term efficacy, define optimal delivery methods, and establish standardised clinical protocols. Full article

Iron is essential for numerous physiological processes, including oxygen transport, energy metabolism, and immune function. This study evaluated the efficacy and safety of three iron formulations combining heme and non-heme iron, comparing them with existing market products and the original form of iron. The formulations tested were GlobiFer^® Forte, a combination of heme and non-heme iron containing 18 mg of elemental iron (hereinafter referred to as nutraceutical product 1); GlobiFer^®, a combination of heme and non-heme iron containing 14 mg of elemental iron (hereinafter referred to as nutraceutical product 2); and a double dose of nutraceutical product 2. Using an in vitro 3D intestinal barrier model, all three formulations significantly increased tight junction protein expression and TEER values, indicating preserved barrier integrity. Iron absorption analysis revealed that all three iron formulations had higher absorption rates than controls. Nutraceutical product 1 showed the highest absorption, associated with increased expression of the iron transporters such as the primary non-heme iron transporter, DMT1, and the leading apical heme transporter, HCP-1. All three new formulations increased ferritin and ferroportin levels, markers of systemic iron storage and regulation. Nutraceutical product 1 was found to be the most effective, based on percentage. Overall, combining heme and non-heme iron improved intestinal absorption and supported iron metabolism, with Nutraceutical Product 1 proving the most promising in terms of efficacy and safety. These results support the development of optimised dual-source iron supplements to improve bioavailability and maintain intestinal barrier integrity, prerequisites for better efficacy and tolerability in clinical use. Full article

Background/Objectives: We conducted an untargeted metabolomic study in serum, urine, and fecal water in colorectal cancer (CRC) patients compared to healthy controls. The aim was to define the interactions between metabolites and microbiota. Methods: Effluents were collected before colonoscopy. Metabolites were analyzed using LC-HRMS. Bioinformatics analyses included Limma test, along with spectral house and public databases for annotations. Whole-genome shotgun sequencing was performed on fecal samples. Species–metabolite interactions were calculated using Spearman correlation. Interleukins and inflammatory proteins were measured. Results: Fifty-three patients (11 stage I, 10 stage II, 10 stage III, and 22 stage IV) and twenty controls were included. Derivatives of deoxycholic acid, cholic acid, and fatty acids were lower in serum, while urinary bile acids were higher in stage IV CRC patients (versus controls). Metabolites related to tryptophan and glutamate were found significantly altered in stage IV: upregulation of kynurenine and downregulation of indole pathways. This was linked to increased inflammatory protein and microbial metabolites and to the imbalance between virulent pro-inflammatory bacteria (Escherichia and Desulfovibrio) and symbiotic (Ruminococcus and Bifidobacterium) bacteria. Conclusions: E. coli-related tryptophan catabolism shift is shown through stage IV CRC as compared to controls. As a consequence, tryptophan/kynurenine metabolite may become a promising marker for detecting the failure to immune response during therapy. Full article

The white-rot fungus Coriolopsis trogii MUT3379 produces Lac3379-1 laccase at high yields due to the previous development of a robust fermentation process. Throughout the extended use of this strain, we observed the occurrence of substrate-specific guaiacol and ABTS (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)) oxidizing enzymes other than Lac3379-1 Since we did not succeed in producing these enzymes in significant amounts by conventional strain selection and fermentation tools, we developed an approach based on protoplast preparation and regeneration to isolate stable producers of these alternative oxidative enzymes from the complex multinucleate mycelium of C. trogii MUT3379. A cost-effective and efficient protocol for protoplast preparation was developed by using the enzymatic cocktail VinoTaste Pro by Novozymes. A total of 100 protoplast-derived clones were selected and screened to produce laccases and other oxidative enzymes. A variable spectrum of oxidative activity levels, including both high and low producers, was revealed. Notably, a subset of clones exhibited diverse guaiacol/ABTS positive enzymatic patterns. These findings suggest that it is possible to isolate different lineages from the mycelium of C. trogii MUT337, each producing a distinct pattern of oxidative enzymes. This highlights the potential of protoplast-mediated genome separation to uncover novel metabolic traits that would otherwise remain cryptic. These data hold outstanding significance for accessing and producing novel oxidative enzymes from native fungal populations. Full article

Advances in distributed electric propulsion and urban air mobility technologies have spurred a surge of research on electric Vertical Take-Off and Landing (eVTOL) aircraft. Distributed Multi-Propeller Tilting-Wing (DMT) eVTOL configurations offer higher forward flight speed and efficiency. However, aerodynamic challenges during the transition phase have limited their practical application. This study develops a high-fidelity body-fitted mesh CFD numerical simulation method for flow field calculations of DMT aircraft. Using the reverse overset assembly method and CPU-GPU collaborative acceleration technology, the accuracy and efficiency of flow field simulations are enhanced. Using the established method, the influence of dynamic tilting speeds on the flow field of this configuration is investigated. This paper presents the variations in the aerodynamic characteristics of the tandem propellers and tilt-wings throughout the full tilt process under different tilting speeds, analyzes the mechanisms behind reductions in the propeller’s aerodynamic performance and tilt-wing lift overshoot, and conducts a detailed comparison of flow field distribution characteristics under fixed-angle tilting, slow tilting, and fast tilting conditions. The study explores the influence mechanism of tilting speed on blade tip vortex-lifting surface interactions and interference between tandem propellers and tilt-wings, providing valuable conclusions for the aerodynamic design and safe transition implementation of DMT aircraft. Full article

This paper focuses on the creation of map documentation for the revitalization of the Horní Bečva reservoir. A detailed spatial model of the reservoir and its bed was created using a combination of surveying methods. The results include map documentation, and a digital terrain model was generated, supporting efforts to restore the ecological functions of the area. Processed data were integrated and processed in Geus and Atlas DMT software environments, resulting in a detailed digital terrain model (TIN-based) enhanced with hypsometric shading. The model was further used to calculate the volume of the water body. Full article

Purpose: As cancer treatments and survival rates continue to improve, integrating supportive complementary therapies into oncology practice is increasingly important. Identifying patient- and clinic-level considerations can guide the selection and integration of evidence-based and effective therapies. Using the Behavioural Design Space (BDS), this study illustrates how a design framework can facilitate the identification of patient needs, clinic requirements, and system-level constraints prior to implementing a digital meditation tool (DMT). Methods: A cross-sectional survey of cancer patients in active treatment to assess distress, attitudes, barriers, and knowledge of meditation. Descriptive statistics and binary multivariate logistic regressions examined associations between patient characteristics and interest in meditation or using a DMT. Findings were mapped onto the six elements of the BDS framework in consultation with clinic staff. Results: Among 148 patients surveyed, 65% had never meditated, yet 42% expressed interest in using a DMT. Greater engagement in stress-coping activities was the strongest predictor of interest in both learning meditation and using a DMT. Female sex increased, while age decreased, the odds of interest in using a DMT. Conclusions: Integrating complementary therapies into oncology care requires attention to patient, clinic, and system-level factors. The BDS framework can guide the therapy/tool selection process by highlighting patient needs, potential barriers, and implementation challenges. Future work should focus on operationalizing the BDS into a practical decision-making tool for healthcare providers. Full article

Background and Objectives: In multiple sclerosis (MS), the Risk of Ambulatory Disability (RoAD) score is a validated prognostic tool based on demographic, clinical, and MRI variables assessed at treatment initiation and after one year. We aimed to assess the predictive value of the RoAD score for long-term irreversible disability in a large real-world MS cohort. Materials and Methods: A retrospective analysis was performed on relapsing–remitting MS patients (RRMS) followed for ≥5 years at the Bari MS Center. The RoAD score (0–8) was calculated and dichotomized (<4 vs. ≥4). Cox proportional hazards models were used to evaluate the risk of irreversible Expanded Disability Status Scale (EDSS) 6.0. Results: A total of 1051 RRMS patients (67.1% female) were included, with a median follow-up of 18.0 years. Most patients (97.5%) received moderate-efficacy DMTs as first-line therapy. During follow-up, 123 (11.7%) patients reached irreversible EDSS 6.0 after a median of 9.5 years. Patients with RoAD score ≥4 (16.8%) showed a threefold higher risk of irreversible disability (HR 3.16, 95% CI 2.19–4.56, p < 0.001). The predictive value of RoAD ≥4 was confirmed both in the adjusted multivariable model and in sensitivity analyses treating RoAD as a continuous variable. Conclusions: In this real-world cohort, the RoAD score demonstrated solid predictive validity for long-term ambulatory disability, supporting its role as a practical tool for early risk stratification in MS management. Full article

The dynamic response of soil bacterial communities to fertilization throughout the entire crop growth cycle remains inadequately characterized. To address this, we conducted a long-term field experiment in Jiangle County, Fujian Province, China, and collected soil samples across four rice growth stages (tillering, elongation, filling and maturity) under five fertilization regimes: no fertilization (CK); chemical fertilizer (NPK); and NPK supplemented with extra nitrogen (NPKN), extra phosphorus (NPKP) and rice straw (NPKS). Bacterial communities were analyzed by high-throughput sequencing. Our results revealed that soil bacterial diversity decreased progressively throughout the growth stages, with fertilization exerting only a minor influence. Structural equation modeling (SEM) identified daily mean temperature (DMT) as the factor with the strongest direct and total effects on the diversity. In contrast, fertilization regimes were the primary determinant of the community structure. Mantel test and redundancy analysis (RDA) indicated that soil pH was the most important factor shaping the community structure. Soil bacterial network attributes also varied mainly with fertilization: fertilizer addition reduced the complexity but enhanced stability, with NPK and NPKS showing the greatest stability. Regarding rice yields, all fertilized treatments were comparable but considerably higher than CK. In conclusion, rice growth stages primarily influenced soil bacterial diversity, while fertilization regimes predominantly shaped the community structure and network attributes. Further, we recommend NPK and NPKS as optimal strategies for balancing crop production, agroecosystem sustainability and environmental health. Full article

Tsetse flies are major vectors of trypanosomes in Sub-Saharan Africa, posing risks to livestock and human health. This study investigated the diversity, distribution, and infection rates of tsetse species, as well as the genetic diversity of drug resistance-associated trypanosome strains in Kenya. Flies were collected from Kwale, Taita-Taveta, Kajiado, Narok, and Turkana counties between November 2024 and February 2025. DNA analyses targeting rRNA and transporter genes (TbAT/P2, E6M6, DMT, TcoAde2) identified infections and resistance-associated mutations among 4693 sampled flies. Apparent density was highest in Kwale (101.52 flies/trap/day) and lowest in Turkana (1.18). Species distribution varied by county, with Kwale dominated by G. pallidipes, G. austeni, and G. brevipalpis; Taita-Taveta G. pallidipes, and G. brevipalpis; Kajiado G. pallidipes and G. longipennis; Narok G. pallidipes, G. brevipalpis, G. swynnertoni, and G. longipennis; and Turkana only G. pallidipes. Trypanosoma congolense was most prevalent, especially in Kwale, while T. brucei was common in Kajiado and Kwale. G. brevipalpis, G. austeni, and G. pallidipes showed higher infection risks. Drug resistance-associated T. congolense strains were found in Kwale and Taita-Taveta, with TcoAde2 and E6M6 gene diversity linked to Kenyan isolates. These findings highlight the need for targeted control of high-risk tsetse species and drug-resistant trypanosomes in Kenya. Full article