Search Results (200)

The growing threat of infectious diseases requires novel therapeutics with different mechanisms of action. Antimicrobial peptides (AMPs), which are crucial for innate immunity, are a promising research area. The medicinal leech (Hirudo medicinalis) is a potential source of bioactive AMPs that are vital while interacting with microorganisms. This study aims to investigate the antimicrobial properties of peptides found in the H. medicinalis genome using a novel high-throughput screening method based on the expression of recombinant AMP genes in Escherichia coli. This approach enables the direct detection of AMP activity within cells, skipping the synthesis and purification steps, while allowing the simultaneous analysis of multiple peptides. The application of this method to the first identified candidate AMPs from H. medicinalis resulted in the discovery of three novel peptides: LBrHM1, NrlHM1 and NrlHM2. These peptides, which belong to the lumbricin and macin families, exhibit significant activity against E. coli. Two fragments of the new LBrHM1 homologue were synthesised and studied: a unique N-terminal fragment (residues 1–23) and a fragment (residues 27–55) coinciding with the active site of lumbricin I. Both fragments exhibited antimicrobial activity in a liquid medium against Bacillus subtilis. Notably, the N-terminal fragment lacks homologues among previously described AMPs. Full article

Wireworms are a major threat to potatoes. Agronomic prevention is always the first IPM strategy to be implemented. This work assesses whether a bioactive cover crop, sunn hemp (Crotalaria juncea L.), a tropical leguminous plant, reduces wireworm damage risk when cultivated as a crop preceding potatoes. The effects of Crotalaria plants (alive, chopped, and incorporated) on wireworms and tuber-damage prevention were studied in semi-natural (pots) and open-field conditions. The survival of a set number of reared wireworms feeding on Crotalaria plants or potato tubers in soil with incorporated Crotalaria chopped tissues was assessed. Wireworm damage on tubers was assessed in fields where Crotalaria had been cultivated, chopped, and incorporated the previous year. The tuber damage assessment involved counting all the erosions/scars caused by wireworm feeding. The prevalent wireworm species studied was Agriotes sordidus. Our research is the first to demonstrate that Crotalaria as a cover crop can significantly reduce potato damage by wireworms. A major role is likely played by the high pyrrolizidine alkaloid content in Crotalaria juncea tissues, but this has to be specifically proven. Crotalaria juncea may thus represent an effective means for use alone or with complementary ones to produce potatoes with low wireworm damage without using synthetic insecticides. Full article

Background/Objectives: Cervical Intraepithelial Neoplasia (CIN) is a significant risk factor for the development of invasive cancer, and the histological detection of High-Grade CIN (CIN2+) during screening generally indicates the need for surgical removal of the lesion; cervical conization is the current gold standard of treatment. The recurrence risk for disease is reported to be up to 30%, based on data in the literature. Follow-up protocols mainly rely on High-Risk Human Papillomavirus (hrHPV) detection at six months post-treatment; if negative, this is considered the test of cure. This approach assumes that all patients have an equal risk of disease recurrence, regardless of individual characteristics. The objective of this study was to evaluate the individual recurrence risk using a mathematical model, analyzing the weight of various parameters and their associations in terms of recurrence development. Methods: We retrospectively examined 428 patients treated for CIN2+ at San Raffaele Hospital in Milan between January 2010 and April 2019. Clinical and pathological data were recorded and correlated with disease recurrence; three different variables, known to behave as significant prognostic factors, were analyzed: hrHPV persistence, the surgical margin status, Neutrophil–Lymphocyte Ratio (NLR), along with their relative associations. Data were used to engineer a mathematical model for the identification of different risk classes, allowing for the risk stratification of cases. Results: Surgical margins status, hrHPV persistence, and a high NLR index were demonstrated to act as independent and significant risk factors for disease recurrence, and their different associations significantly correlated with different recurrence rates. The mathematical model identified eight classes of recurrence probability, with Odds Ratios (ORs) ranging from 7.48% to 69.4%. Conclusions: The developed mathematical model may allow risk stratification for recurrence in a hierarchical fashion, potentially supporting the tailored management of follow-up, and improving the current protocols. This study represents the first attempt to integrate these factors into a mathematical model for post-treatment risk stratification. Full article

The Marburg virus (MARV) is an extremely contagious zoonotic virus that leads to severe hemorrhagic fever in humans, with a fatality rate as high as 90%. It is known for causing nosocomial outbreaks in hospitals and laboratories globally. The recent outbreak of MARV in Rwanda highlighted significant challenges to infection prevention and control (IPC) protocols in two major hospitals, leading to outbreaks in intensive care units (ICUs) where the majority of infections occurred among healthcare providers. In contrast, the Rwandan National Reference Laboratory (NRL) demonstrated remarkable preparedness and resilience due to systematic investments and capacity building, which resulted in zero contamination, exposure, or infection, despite handling thousands of samples from across the country. This stark difference in infection dynamics between laboratory personnel at the NRL and healthcare providers underscores the effectiveness of the strict biosafety and biosecurity measures in place. Consequently, this situation underscores the urgent need for cross-facility training, the sharing of best practices, and the role of the NRL in reinforcing IPC measures throughout the country. This report delves into the preparedness and resilience of the NRL by examining its exemplary laboratory biosafety and biosecurity practices, emphasizing the crucial need for ongoing training, supervision, adherence to safety protocols, and improvements in the structure and operations of healthcare settings to prevent future outbreaks. Full article

Among its various targets on restoring natural habitats and ecosystems in the EU, the recently adopted Nature Restoration Law (NRL) introduces ambitious targets for restoring surface water bodies (SWBs) as well. Simultaneously, the Italian CAP Strategic Plan for the implementation of the Common Agricultural Policy 2023–2027 has been designed to enhance sustainable agricultural practices, including water resource management. This paper provides a comparative analysis of the synergies, gaps, and challenges between these two regulatory frameworks, focusing on sustainable water use in Italian agriculture. A two-level comparative matrix methodology is employed to evaluate the alignment between the NRL’s objectives for freshwater ecosystems and the measures taken by the Italian CAP Strategic Plan on water resources. The results highlight key areas of convergence, existing shortcomings, and necessary steps for aligning Italian agricultural policies with the EU’s water restoration goals. The findings offer insights for policymakers, researchers, and stakeholders engaged in water governance, biodiversity conservation, and agricultural sustainability. Full article

This study explores using natural rubber latex (NRL) as a sustainable polymeric additive to improve the mechanical performance of cement-stabilized soil–crushed limestone waste (CLW) mixtures for pavement base applications. The experimental program involved varying cement contents (3%, 6%, and 9% by weight of soil) and NRL replacement levels (10%, 15%, 20%, and 25% of an 18% optimum water content, as determined by the standard Proctor test) under two target dry unit weights (16.6 and 17.6 kN/m³) and curing periods of 7 and 28 days. Unconfined compressive strength (UCS) tests and stiffness (Go) measurements were performed, while microstructural developments were examined using scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). The results indicate that an optimal NRL replacement exists for each cement content, enhancing interparticle bonding through the formation of polymeric films that reduce porosity and improve the ductility of the matrix. However, excessive NRL was found to retard cement hydration and ultimately decrease strength. On average, a 28-day curing period produced a 38% increase in UCS over 7-day values, independent of the NRL dosage. Comparisons with literature standards, including the ASTM D4609 threshold of 345 kPa for field strength, confirm that the optimized mixtures meet and exceed the minimum performance requirements. These findings underscore the potential of NRL as a viable alternative to conventional synthetic latexes in sustainable pavement base materials. Full article

The specificity of the life cycle of T. gondii, the causative agent of toxoplasmosis, determines its relevance in some patient groups; especially in women of childbearing age. The objective of this study was to ascertain the prevalence of this parasitic infection in Bulgaria between 2014 and 2023, focusing on pregnant women and those applying for an in vitro procedure or after an abortion. During the period, 115,053 individuals were tested for toxoplasmosis in the country, with an average seropositivity rate of 16.96%. At the NRL for the Diagnosis of Parasitic Diseases, ELISA tests were utilized to ascertain specific Toxoplasma IgG, IgM, and IgA antibodies, IgG avidity, and PCR to substantiate the DNA of the parasite. Between 2014 and 2023, the laboratory conducted tests on 631 pregnant women, and 161 women applying for in vitro fertilization or after an abortion. In 24.7% of pregnant women, data demonstrated the presence of IgG antibodies only, and Toxoplasma IgG and IgM or IgG, IgM, and IgA antibodies were found in 16.6% and 8% of women, respectively. In the subset of individuals examined after an abortion or for an in vitro procedure, IgG was detected in 28%, IgG and IgM in 13%, and IgG, IgM, and IgA antibodies in 3.7%. Seroprevalence rises with increasing age, but does not show any dynamic compared to our previous studies. Our results show a higher seropositivity for toxoplasmosis in pregnant women in Bulgaria than in neighboring countries. Full article

Objective: The neutrophil–lymphocyte ratio (NLR) is an inexpensive and easily available inflammatory marker for cardiovascular disease. The aim of the present study is to evaluate a possible association between preoperative NLR value and popliteal artery aneurysm (PAA) repair outcomes. Methods: A single-center retrospective study on all patients, who underwent urgent or elective PAA repair from June 2010 to October 2022, was performed. Study outcomes were immediate technical success, 30-day and mid-term primary patency, reintervention, limb salvage, and mortality rates. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count, and, according to the literature, a cut-off of five has been considered as a possible threshold for the analysis. Results: Eighty-two patients (80 male) with a total of 97 popliteal artery aneurysms were enrolled in this study. The mean preoperative NLR was 2.9 ± 2.4. In 10 (10.3%) PAAs, the NRL was >5 (High-NLR group), and, in the remaining 87 (89.7%), the NLR was <5 (Low-NLR group). The preoperative NLR for urgent procedures was higher than elective cases (4.37 vs. 2.30; p < 0.001). However, no significant differences were found as far as immediate 24 h technical success (p = 0.48) and 30-day primary patency (p = 39). At mean follow-up, the primary patency rate was significantly higher in the Low-NLR group (p = 0.0044), without statistical differences for re-operation (p = 0.27), limb salvage (p = 0.09), and mortality rates (p = 0.51). The Kaplan–Mayer analysis showed a significant difference in freedom from major amputation in patients with an NLR > 5 compared to the ones with an NLR < 5 (p = 0.038), without any differences in terms of survival, primary patency, and the need for reintervention rates. The multivariable Cox regression analysis identified the NLR value as an independent predictor of better outcomes regarding freedom from the amputation rate (p = 0.25). Conclusions: Our experience indicates that a preoperative NLR value > 5 can identify high-risk patients affected by a PAA and may negatively influence the surgery’s long-term outcomes. Therefore, this selected group of patients could need a more tailored approach and closer monitoring over time. Full article

NRL (NPH3/RPT2-Like) proteins, which are exclusive to plants, serve as critical mediators in phototropic signaling by dynamically regulating light-dependent cellular processes. We identified 24 NRL genes (VvNRL) in the Vitis vinifera L. genome, which were unevenly distributed on 11 chromosomes. Phylogenetic analysis showed that these family members were divided into six groups, and promoter analysis revealed ubiquitous light-responsive cis-elements across all 24 members, suggesting conserved regulatory mechanisms. Sequence alignment and structural similarity analysis showed that VvNRL4 and VvNRL6 were highly similar to NPH3 and NPR2. Experiments with different light qualities showed that VvNRL6 was induced by blue and red light, while VvNRL4 was not affected by light spectra, similar to NPH3 in Arabidopsis. Molecular docking prediction suggested that VvNRL4 and VvNRL6 may, respectively, interact with the LOV domain in VvPHO1 and VvPHO2, through their C-terminal coiled-coil domain and N-terminal BTB domain, to further regulate the activity of VvPHO1 and VvPHO2. In addition, 10 of the 24 VvNRLs, including VvNRL4 and VvNRL6, possessed the conserved RxS motif in their conserved C-terminal consensus sequences. This study provides a reference for further studies on the function and regulation of VvNRL family members in fruit vine plants. Full article

Drug resistance is the main challenge in treating parasitic diseases, including cystic echinococcosis (CE). Hence, the current study aims to investigate the effect of nanocapsules containing albendazole (ABZ), mebendazole (MBZ), and praziquantel (PZQ) on treating hydatid cysts in mice using these high-potency drugs. A total of 78 female white laboratory mice (BALB/C mice), 8 weeks old and weighing 25 g, were intraperitoneally injected with 1500 live protoscoleces of Echinococcus granulosus. The first group received ABZ nanocapsules, group 2 received MBZ nanocapsules, group 3 received PZQ nanocapsules, group 4 received ABZ + MBZ nanocapsules, group 5 received ABZ + PZQ nanocapsules, and group 6 received MBZ + PZQ nanocapsules. Each group also had a control group, which received the non-nanocapsulated drugs (group 7–12). Group 13 received no treatment and served as the negative control, just receiving phosphate-buffered saline (PBS). A thorough examination of the cysts’ physical properties, including size, quantity, and weight, was carried out. According to our results, the polymeric nanocapsules are sphere-like and of different sizes. The total number of cysts in all nanocapsule groups significantly decreased compared to the control group. In the total weight of the cysts, ABZ + MBZ nanocapsules, ABZ + PZQ nanocapsules, and MBZ + PZQ nanocapsules had the least total cyst weight, showing that the use of the medicinal combination had a better effect on the penetration and weight reduction of the cysts. In conclusion, the findings showed that ABZ, MBZ, and PZQ significantly reduced the size, weight, and number of hydatid cysts in the mouse model used in this study. Full article

Resistance to amitraz in Varroa destructor mites poses a significant challenge to global beekeeping, leading to the declining efficacy of treatments and increased colony losses. This study aims to comprehensively map, characterize, and analyze the status of amitraz efficacy and resistance in Varroa and other parasitic mites such as Tropilaelaps spp. and Acarapis woodi. A systematic review, following PRISMA 2020 guidelines, examined 74 studies, revealing substantial variability in experimental protocols, mite origins, and environmental factors, all of which impacted toxicity assessments. These findings highlight the urgent need for standardized methodologies to ensure consistency and reliability. Resistance ratios (RR) and indices (RI) showed significant geographical variation, reflecting localized resistance development. Laboratory studies highlighted inconsistencies in detecting resistance, underscoring the importance of combining bioassays, molecular diagnostics, and field efficacy tests. Understanding the genetic and physiological mechanisms driving amitraz resistance, as well as their prevalence, is vital to devising sustainable management strategies. Establishing national monitoring programs and revising testing protocols are pivotal steps toward ensuring the continued effectiveness of acaricides. These measures, combined with coordinated efforts by researchers, beekeepers, and policymakers, are essential to safeguarding global honey bee populations and supporting the long-term sustainability of apiculture. Full article

To enhance the speed-control performance of a permanent magnet synchronous motor (PMSM) drive system, an improved sliding-mode anti-interference control strategy is presented. Firstly, to tackle the speed fluctuation issue caused by cogging torque (a periodic disturbance) and time-varying disturbances at low set speeds in PMSM, an improved sliding-mode control (ISMC) is proposed. It consists of a continuous adaptive fast terminal sliding-mode surface (CAFTSMS) and a new reaching law (NRL). The CAFTSMS boosts the system’s immunity to interference, while the NRL, improved via an adaptive function, enhances the fast transient response and notably reduces speed fluctuations. Secondly, a quasi-proportional resonant (QPR) controller is introduced. It suppresses specific-order system harmonics, significantly reducing the harmonic amplitude and strengthening the system’s ability to handle periodic disturbances. Finally, a cascaded extended state observer (CESO) with a special cascade structure is proposed to solve the observation-delay problem in the traditional cascade structure. Experimental results show that the proposed sliding-mode anti-disturbance control strategy performs excellently in overcoming disturbances. Full article

Herein, we investigate the performance and safety of four of the early-stage, commercial Na-ion batteries available in 2024, representing the most popular cathode types across research and commercialization: polyanion (Na-VPF), layered metal oxide (Na-NMF), and a Prussian blue analog (Na-tmCN). The cells deliver a wide range of energy density with Na-tmCN delivering the least (23 Wh/kg) and Na-NMF delivering the most (127 Wh/kg). The Na-VPF cell was in between (47 Wg/kg). Capacity retention under specified cycling conditions and with periodic 0 V excursions was the most robust for the Na-tmCN cells in both cases. Accelerating rate calorimetry (ARC) and nail penetration testing finds that Na-NMF cells do undergo thermal runaway in response to abuse, while the Na-VPF and Na-tmCN exhibit only low self-heating rates (<1 °C/min). During these safety tests, all cells exhibited off-gassing, so we conducted in-line FTIR equipped with a heated gas cell to detect CO, CO₂, CH₄, toxic acid gases (HCN, HF, NH₃), and typical electrolyte components (carbonate ester solvents). Gases similar to those detected during Li-ion failures were found in addition to HCN for the Na-tmCN cell. Our work compares different types of commercial Na-ion batteries for the first time, allowing for a more holistic comparison of the safety and performance tradeoffs for different Na-ion cathode types emerging in 2024. Full article

Photoreceptor/retinal degeneration is the major cause of blindness. Induced and inherited mouse models of retinal degeneration are valuable tools for investigating disease mechanisms and developing therapeutic interventions. This study investigated the potential of the antioxidant resveratrol to relieve photoreceptor degeneration using mouse models. Clinical studies have shown a potential association between thyroid hormone (TH) signaling and age-related retinal degeneration. Excessive TH signaling induces oxidative stress/damage and photoreceptor death in mice. C57BL/6 (rod-dominant) and Nrl^−/− (cone-dominant) mice at postnatal day 30 (P30) received triiodothyronine (T3) via drinking water (20 µg/mL) with or without concomitant treatment with resveratrol via drinking water (120 µg/mL) for 30 days, followed by evaluation of photoreceptor degeneration, oxidative damage, and retinal stress responses. In experiments using Leber congenital amaurosis model mice, mother Rpe65^−/− and Rpe65^−/−/Nrl^−/− mice received resveratrol via drinking water (120 µg/mL) for 20 days and 10–13 days, respectively, beginning on the day when the pups were at P5, and pups were then evaluated for cone degeneration. Treatment with resveratrol significantly diminished the photoreceptor degeneration induced by T3 and preserved photoreceptors in Rpe65-deficient mice, manifested as preserved retinal morphology/outer nuclear layer thickness, increased cone density, reduced photoreceptor oxidative stress/damage and apoptosis, reduced upregulation of genes involved in cell death/inflammatory responses, and reduced macroglial cell activation. These findings demonstrate the role of oxidative stress in photoreceptor degeneration, associated with TH signaling and Rpe65 deficiency, and support the therapeutic potential of resveratrol/antioxidants in the management of retinal degeneration. Full article