Search Results (81)

Porphyromonas gingivalis plays a key role in periodontal disease and has been associated with several serious systemic diseases. Its fimbriae are a major virulence factor. We recently demonstrated the formation of bundles of long FimA fimbriae in strain ATCC 33277. Transmission (TEM) and scanning electron microscopy (SEM) were used to examine a collection of P. gingivalis strains representing all seven known FimA types (I, Ib, IIa, IIb, III–V) and a P. gulae strain (type A). Additionally, two P. gingivalis strains (ATCC 49417 and OMI 1127) were investigated in dual-species approaches together with Fusobacterium nucleatum or Streptococcus oralis as well as in co-culture with human gingival fibroblasts (HGFs). To evaluate the role of fimbriae accessory proteins FimCDE, proteomic analysis of outer membrane vesicles (OMVs) was performed. Bundling was confirmed to occur regardless of FimA type but was impaired by strong capsule formation. Furthermore, tubular and chain-like outer membrane extensions (OMEs) were identified in most strains examined, including P. gulae. For the first time, fimbriae-associated OMVs (FAVs) were observed. REM images suggest that bundled fimbriae, OMEs and FAVs form connections with F. nucleatum and S. oralis. Proteome analysis of OMV content revealed the ratios of FimA to accessory proteins to be approximately 13:1 for FimC and FimD and approximately 7:1 for FimE. The results imply more accessory proteins per fimbriae or shorter FimA fimbriae in OMVs than in cells. Since FimCDE are known to be responsible for the adhesion properties and autoaggregation of FimA fimbriae, we propose that they could also mediate the stability of bundled fimbriae and the binding of OMVs. Full article

Fatty acid vesicles (FAVs) are promising nanocarriers, but their application is limited by a narrow, alkaline pH formation window that mismatches the weak acidity of physiological environments, such as skin. To overcome this, we developed composite vesicles using oleic acid (OA) and the non-ionic surfactant Tween 40 (TW40). pH titration confirmed that the OA/TW40 system successfully broadened the vesicle formation window from 8.2–10.08 to 3.1–7.2, aligning it with the physiological pH range. The bioactive flavonoid luteolin (LUT) was efficiently encapsulated into these OA/TW40-FAVs, achieving a high encapsulation efficiency (EE) of 87.13% and a drug loading capacity (DLC) of 9.58. The formulation demonstrated superior topical delivery performance: the cumulative transdermal flux (933.08 µg·cm⁻²) and skin retention (68.18 µg·cm⁻²) were both approximately double that of the free LUT solution. Furthermore, the OA/TW40/LUT-FAVs provided sustained drug release and exhibited synergistically enhanced antioxidant and antimicrobial activities compared to free LUT or blank vesicles. Collectively, these findings establish OA/TW40 composite vesicles as a robust and efficient nanoplatform for the topical delivery of bioactive compounds. Full article

This review examines a small interfering RNA (siRNA) designed for intrathecal (IT) injection, which reduces the formation of amyloid beta precursor protein (APP), a critical factor in the pathology of Alzheimer’s disease (AD). The siRNA, designated ALN-APP, incorporates a 16-carbon chain (C16-siRNA) to enhance its delivery to the central nervous system (CNS) while leveraging advancements in specificity and duration of action based on previously approved drugs by the Food and Drug Administration. The development of ALN-APP involved a comprehensive analysis of the optimal carbon chain length and its conjugation position to the siRNA. Preclinical studies conducted on male Sprague Dawley rats, mice, and non-human primates (NHPs) demonstrated the efficacy of ALN-APP. In rats, an IT injection of C16-siRNAs at a concentration of 30 mg/mL, delivering a dose of 0.9 mg, resulted in cranial distribution via cerebrospinal fluid and led to a 75% reduction in copper-zinc superoxide dismutase 1 (SOD1) mRNA levels. These effects were dose-dependent and persisted for three months across multiple brain regions. Furthermore, studies in NHPs indicated that soluble APP levels were reduced to below 25%, sustained for two months. In the cerebrovascular amyloid Nos2^−/− (CVN) mouse model of AD, administration of 120 µg of siRNA via the intracerebroventricular route produced reductions in APP expression, with mRNA levels remaining suppressed for 60 days in the ventral cortex. Indeed, ALN-APP controlled neuropathology in 5xFAD mice by significantly reducing amyloid levels and brain neuroinflammation, with improved behaviors in the elevated plus maze. Following these promising results in animal models, ALN-APP advanced to a Phase 1 trial, designated ALN-APP-001, which assessed its safety and efficacy in 12 participants with early-onset Alzheimer’s disease (EOAD). Initial findings revealed a 55% reduction in soluble APPα and a 69% reduction in APPβ by day 15. These exploratory findings require further validation with larger cohorts and proper statistical analysis. In a subsequent cohort of 36 patients, administration of the 75 mg dose via IT injection led to mean reductions of 61.3% in soluble APPα (sAPPα) and 73.5% in soluble APPβ (sAPPβ) after one month. These silencing effects persisted for six months and were associated with important decreases in Aβ42 and Aβ40 levels. These results highlight the potential of ALN-APPs to address Alzheimer’s pathology while maintaining a favorable safety profile. Whether ALN-APP succeeds in further clinical trials, key challenges include ensuring accessibility and affordability due to treatment costs, the need for specialized intrathecal administration, and establishing infrastructure for large-scale production of siRNAs. In conclusion, advancements in ALN-APP represent a promising strategy to reduce beta-amyloid formation in AD, with substantial biomarker reductions suggesting potential disease-modifying effects. Continued development may pave the way for innovative treatments for neurodegenerative diseases. Full article

The extensive use of antiviral substances (SASs) during and after the COVID-19 pandemic has increased their release into wastewater systems, raising concerns regarding their persistence and potential ecotoxicological effects. The primary objective of this study was to isolate bacterial strains from activated sludge (AS) that possess the ability to biodegrade SASs. From the AS sample, three bacterial species, Comamonas testosteroni (I2), Bacillus amyloliquefaciens (I3) and Bacillus mycoides (I4), were successfully isolated and identified. These strains were subsequently applied in biodegradation experiments targeting seven SASs: daclatasvir (DCV), darunavir (DRV), favipiravir (FAV), lopinavir (LOP), remdesivir (REM), ritonavir (RIT), and umifenovir (UMI). During the experiments, residual SAS concentrations, microbial growth parameters, physicochemical indicators and ecotoxicity were monitored. All three strains demonstrated substantial biodegradation potential, achieving reductions exceeding 90% for most tested compounds, with particularly low toxicity observed in experiments conducted with AS and Bacillus amyloliquefaciens. These findings highlight the relevance of AS-derived bacteria as promising candidates for enhancing SAS removal in wastewater treatment processes. Full article

Chickpeas are a pulse crop that originated in Eurasia and are a source of protein for many people. The objective of this research is to select stable, high-yielding chickpea genotypes using uni- and multivariate methods of adaptability and stability analysis. Fifteen genotypes were tested in the 2020 and 2021 agricultural years. The experimental design was a completely randomized block design with three replications. The collected data were yield (kg/ha) values, and the stability analyses were performed using Eberhart and Russell’s, Lin and Binns’s modified by Carneiro’s, additive main effects and multiplicative interaction (AMMI), and weighted average of absolute scores (WAASB) methods. The average sum of ranks (ASR) was then calculated by ranking genotypes according to their yield and stability indices. The AMMI analysis of variance showed significant effects (p < 0.05) for environments, genotypes, and the interaction between genotypes and environments. From AMMI, the first three principal components (PCs) had significant effects, and the cumulative variance on the PC1 and PC2 axes was 86%. FLIP02-23C, FLIP03-109C, and Jamu 96 had the lowest ASR, indicating that these genotypes are the most stable and productive chickpea genotypes. According to AMMI2, genotypes FLIP03-109C, FLIP03-35C, FLIP02-23C, and FLIP06-155C could be adapted to irrigated environments. Full article

Objective: To explore the value of multimodal molecular imaging in diagnosing and differentiating dementia with Lewy bodies (DLB). Methods: A retrospective analysis was conducted on clinical data and multimodal molecular imaging of 40 probable DLB patients treated at Peking Union Medical College Hospital (August 2017–December 2024). All 40 had ¹⁸F-FDG PET/CT; 15 had ¹³¹I-MIBG imaging; 11 had ¹⁸F-FP-CIT PET/CT. A total of 12 patients with poor cognition or atypical ¹⁸F-FDG PET/CT underwent ¹⁸F-AV45 PET/CT (2 also had ¹⁸F-PM-PBB3 imaging). A sex- and age-matched control group (cognitively normal, same-period health checkup ¹⁸F-FDG PET/CT) was included. ¹⁸F-FDG PET/CT images were visually and semi-quantitatively analyzed (ROI, SPM). ¹⁸F-AV45 PET/CT was assessed both visually and semi-quantitatively; ¹³¹I-MIBG imaging and ¹⁸F-FP-CIT PET/CT were visually evaluated. Results: The 40 DLB patients (29 males, 11 females; mean age 72 years) had distinct initial symptoms: 8 (20%) presented with cognitive decline as the first symptom, 23 (57.5%) with parkinsonian symptoms as the first symptom, and 9 (22.5%) with both symptoms occurring simultaneously. Mean intervals: 16.25 months from initial cognitive decline to parkinsonian symptoms, and 24.43 months from initial parkinsonian symptoms to cognitive decline. All had parkinsonian symptoms and cognitive impairment; 38 (95%) had visual hallucinations; and 26 (65%) had REM sleep behavior disorder. ¹⁸F-FDG PET/CT: 30(75%) showed typical occipital hypometabolism and posterior cingulate island sign; 10 (25%) had atypical findings. ¹³¹I-MIBG (15/15, 100%): cardiac sympathetic denervation. ¹⁸F-FP-CIT (10/11, 90.9%): basal ganglia dopaminergic damage. ¹⁸F-AV45 (9/12, 81.8%): positive. Semi-quantitative ¹⁸F-FDG analysis revealed parietal, occipital, and lateral temporal hypometabolism in DLB (left more severe than right). Conclusions: Dementia with Lewy bodies (DLB) presents with pre-onset parkinsonism and cognitive impairment, plus high rates of visual hallucinations and sleep disorders. Key imaging features—occipital hypometabolism/island sign on ¹⁸F-FDG PET/CT, cardiac sympathetic denervation on ¹³¹I-MIBG, and basal ganglia dopaminergic damage on ¹⁸F-FP-CIT—aid DLB diagnosis. ¹⁸F-AV45 PET/CT detects Aβ pathology in severely cognitively impaired patients, suggesting these DLB patients may have underlying AD pathology beyond DLB. Full article

Industrial bio-inputs can improve commodity farming by replacing the use of agrochemicals. To assess the potential of agricultural bio-inputs to contribute to Brazil’s agro-industrial growth, we analyzed the market share held by domestic companies and the local market created by farmers who adopt bio-inputs. The results revealed that Brazilian companies accounted for 82.8% of the 221 companies with agricultural bio-inputs registered in Brazil by 2024. These domestic companies used technologies available to local investors and developed in collaboration with public innovation centers. Adoption levels among interviewed farmers ranged from 41.7% for biosolubilizers to 88.9% for bionematicides, revealing a large domestic market potential for bio-inputs in Brazil. We conclude that industrial agricultural bio-inputs represent an area of opportunity for Brazilian neo-industrialization based on local competitive advantages, low entry barriers, and domestic and foreign investments that can benefit from the local market for bio-inputs. Full article

The given paper proposes a new statistical framework based on the combination of the Fav-Jerry distribution (FJD) and a joint type-II censoring scheme (JT-II-CS) to examine heterogeneous and censored data. The FJD offers tractability in analysis by using its closed form of the quantile function, whereas with missing or incomplete data, the JT-II-CS offers multi-sample comparisons. Bayesian estimation is based on Markov chain Monte Carlo procedures, while the maximum likelihood estimation is obtained via a Newton–Raphson method. Both estimation strategies provide estimates of the parameters along with corresponding measures of uncertainty. The proposed methodology is also used on coded survey data on the knowledge of autism in both Hong Kong and Canada, which illustrates its potential in the measurement of cultural variance. In addition to this use, the framework highlights the potential for integrating more complex distributional modeling with censoring methods for general applications in engineering, natural sciences, and social sciences. Full article

Canephora coffee genotypes developed in other growing regions, with traits of interest such as drought tolerance and high coffee bean yield, need to be introduced and characterized in other locations to check adaptability. The aim of this study was to check the agronomic performance and determine the genetic parameters of the clonal canephora coffee cultivar Marilândia ES 8143, composed by twelve genotypes, developed by the Capixaba Institute of Research, Technical Assistance and Rural Extension (Instituto Capixaba de Pesquisa, Assistência Técnica e Extensão Rural—Incaper), in an irrigated system of the Central Cerrado region of Brazil. The study was conducted in the experimental areas of Embrapa Cerrados at 1050 m altitude in a center pivot irrigation system using a management system with water stress controlled for around 65 days. A randomized block experimental design was used with three replications, and each plot consisted of eight plants. The clones were planted in February 2019 and in 2021 and 2022. Phenotyping was carried out to evaluate the following traits: coffee bean yields, sieve retention percentages, plant height, canopy projection, number of pairs of plagiotropic branches, and frost damage using a scoring scale. Clone 5 stood out in mean value in the two years evaluated for bean yield. Clones 5, 6, 7, 8, and 9 had higher mean values for flat-type coffee beans in both years. Clones 1 and 5 exhibited mean values indicating good vegetative development. Clones 5 and 12 showed no visible symptoms for low air temperatures and frost effects. Highly significant differences were observed among the genotypes for all the morphoagronomic traits evaluated, and high values of heritability, genetic coefficients of variation, and selective accuracy showed conditions favorable to the selection of clones for the agronomic traits analyzed. Clones 1, 2 and 6 have values in lower groups for chlorogenic acids and caffeine, and in higher groups for protein and soluble solids, thus showing greater potential for obtaining quality beverages. Full article

Nitrogen-modified atmosphere technology, due to its effectiveness in pest control, is widely used in grain storage as an eco-friendly preservation method. This study compared the quality changes in unhulled rough rice (paddy) stored under nitrogen-modified atmosphere and conventional conditions. Fatty acid value (FAV), reactive oxygen species (ROS) content, coenzyme levels, antioxidant enzyme activities, and concentrations of central carbon metabolism-related metabolites of paddy were monitored during storage under different storage conditions. The results revealed that compared to conventional storage, nitrogen-modified atmosphere resulted in lower FAV and ROS levels, as well as higher pyridine nucleotides contents and antioxidant enzyme activities, including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione reductase (GR). Metabolomic profiling demonstrated that N₂-MAS induced metabolic changes characterized by the down-regulation of 2-hydroxyglutaric acid and the up-regulation of fructose 6-phosphate, glucose 1-phosphate, glycerol 3-phosphate, gluconic acid, fumaric acid, and malic acid, which collectively contribute to reduced oxidative damage and enhanced preservation quality. These findings elucidated the mechanism of N₂-MAS-delayed quality deterioration and revealed the regulatory role of the antioxidant system and central carbon metabolism. Full article

Background: The Derotational femoral osteotomy (DFO) is an effective surgical treatment for patients with disabling anterior knee pain associated with pathological Femoral anteversion (FAV). However, the complexity in determining the precise origin of the deformity has put limits on its use. This study aims to review the literature to learn how the authors study the origin of the deformity and then provide a new methodology using 3D technology to assess the origin of FAV. Methods: A search of the literature was conducted on PubMed utilizing the following search string: “anteversion” and “femur” or “origin” or “CT” or “MRI” or “3D”. In addition, an observational study was conducted on CT scans of six femurs from three female patients with unilateral pathological FAV. This work represents a pilot study and should be considered preliminary. Using the 3DSlicer (version 4.11.20210226), MeshMixer (version3.5), and 3DBuilder software (Microsoft.com), 3D biomodels were generated. A mirrored healthy femur served as a reference. The CloudCompare software (software version 2.13.0) was used to compare volumetric structures and analyze torsional deformities. Torsion at each level was quantified using MATLAB (software version 23.2). Results: The 3D technology identified three torsional patterns: 1. FAV predominantly originating at the femoral head (distance between the centroids = maximum deformity in the last discs, which coincides with the proximal region of the femur; heat maps = red in the proximal femur); 2. FAV primarily affects the mid-distal diaphysis (distance between the centroids = maximum deformity in the first discs, which coincides with mid-distal third of the femur; heat maps = red in the diaphyseal level); 3. a pan-diaphyseal deformity involving the entire femur (distance between the centroids = both the first and last discs, means deformity along the entire femur; heat maps = red along the entire femoral diaphysis). Conclusions: All femoral segments contributed to the total FAV, but the location and severity varied among the cases. Pathological FAV is a multifactorial deformity that can arise in different femoral regions. Individualized correction strategies are essential to improving DFO outcomes and preventing secondary deformities. It is important to note that the pilot data is intended to be purely illustrative and, as such, should not be utilized for the purposes of guiding clinical decision-making. Full article

Coffee beverage quality is determined by a complex interaction of genetic and environmental factors, including specific biochemical characteristics. In this context, the present study aimed to estimate the genetic parameters of elite irrigated Conilon coffee genotypes in the Cerrado over two consecutive years based on the biochemical characteristics of the beans, assessed by near-infrared spectroscopy (NIRS). The research was conducted at the Embrapa Cerrados experimental field, using the unit’s elite collection. Levels of chlorogenic acid (5-ACQ), caffeine, sucrose, citric acid and trigonelline were analyzed in the raw beans of 18 genotypes harvested in two consecutive years. Data were subjected to analysis of variance in a time-subdivided plot design, considering genotypes as plots and years as subplots, with means grouped by the Scott-Knott test at 5% significance. Results showed significant genetic variability for caffeine, sucrose and trigonelline, while chlorogenic and citric acid levels did not differ significantly among genotypes. A significant genotype × year interaction was observed for caffeine, sucrose, and 5-ACQ. Estimated heritabilities were high for caffeine (85.5%), trigonelline (80.1%), sucrose (62%) and citric acid (60%). Selection gains were positive for sucrose (5.58%), citric acid (10.01%) and trigonelline (8.27%), and negative for caffeine (−6.87%) and 5-ACQ (−0.47%). It is concluded that among the compounds evaluated, caffeine shows the greatest potential for selection, enabling effective gains in raw bean composition, while sucrose and trigonelline present moderate potential for genetic improvement. Full article

This paper presents a cloud-based architecture for the acquisition, transmission, and processing of acoustic data from hydrophone arrays, designed to enable the detection and monitoring of both surface and underwater vehicles. The proposed system offers a modular and scalable cloud infrastructure that supports real-time and distributed processing of hydrophone data collected in diverse aquatic environments. Acoustic signals captured by heterogeneous hydrophones—featuring varying sensitivity and bandwidth—are streamed to the cloud, where several machine learning algorithms can be deployed to extract distinguishing acoustic signatures from vessel engines and propellers in interaction with water. The architecture leverages cloud-based services for data ingestion, processing, and storage, facilitating robust vehicle detection and localization through propagation modeling and multi-array geometric configurations. Experimental validation demonstrates the system’s effectiveness in handling high-volume acoustic data streams while maintaining low-latency processing. The proposed approach highlights the potential of cloud technologies to deliver scalable, resilient, and adaptive acoustic sensing platforms for applications in maritime traffic monitoring, harbor security, and environmental surveillance. Full article

Stevia rebaudiana Bertoni, a semi-perennial herb from the Asteraceae family, is native to the Paraguay–Brazil border region. The growing industrial interest in this species is due to its natural sweetening properties, such as steviol and its derivatives, which offer sweetness without adding calories. Morphological traits are crucial for assessing genetic variability and ensuring distinctness, homogeneity, and stability (DHS) for cultivar protection. This study characterized 19 elite Stevia genotypes from Embrapa Cerrados’ Active Germplasm Bank (BAG) using 21 morphological descriptors from Brazil’s Ministry of Agriculture, Livestock, and Supply (MAPA). Genetic distances were calculated using the simple coincidence index complement method, and clustering was performed via the Unweighted Pair-Group Method with Arithmetic Mean (UPGMA). The results showed that 17 of the 21 descriptors (>80%) effectively differentiated the genotypes, revealing significant genetic variability. Dendrogram analysis identified at least four major similarity groups, highlighting the potential of these genotypes for Stevia breeding programs. These findings underscore the suitability of these elite genotypes for developing superior varieties adapted to Cerrado conditions, supporting future cultivation and genetic improvement efforts. Full article

Genome editing technologies have revolutionized the production of microorganisms, plants, and animals with phenotypes of interest to agriculture. Editing previously sequenced genomes allows for the punctual, discreet, precise, and accurate alteration of DNA for genetic analysis, genotyping, and phenotyping, as well as the production of edited organisms for academic and industrial purposes, among many other objectives. In this context, genome editing technologies have been causing a revolution in Brazilian agriculture. Thanks to the publication of Normative Resolution No. 16 (in Portuguese Resolução Normativa No. 16-RN16) in 2018, Brazilian regulatory authorities have adapted to the new genetic manipulation technologies available to the scientific community. This review aims to describe the effects of updates to the regulatory framework for edited organisms in Brazil and to point out their impacts on research and development of emerging technologies in the Brazilian agricultural sector. The implementation of RN16 rationalized the regulatory aspects regarding the production, manipulation, exploration and commercial release of edited organisms and led to the faster, cheaper and safer obtaining of edited technologies, which are more productive and better adapted to different environmental conditions in Brazil. Full article