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Mapping the quality of Norwegian health information –Does it facilitate informed choices?

Background and aim Health literacy refers to the ability to use relevant information to make informed choices. However, the quality of the available information influences how well individuals can make those choices. Evidence-based recommendations for the development and design of health information have recently been published. In this study, we aimed to map the quality of Norwegian web-based health information across selected public health domains. Methods Using a multiple-cross-sectional design, we assessed information in 16 health domains relevant to infants, children, and youth. Convenience samples were drawn using structured Google searches. Three independent raters conducted the quality appraisal by applying the 19 criteria of the Mapping the quality of health information checklist. Inter-rater reliability was calculated using T-coefficients. Information quality was statistically described. To explain variance in quality, mean quality scores were compared across three independent variables: the type of the health problem, target group, and provider class. Results Across the surveys, 1,948 health information materials from 64 subdomains were assessed. Inter-rater reliability was excellent (mean T = .89/.90). On average, the materials complied with 22% (range: 0–73%, standard deviation = .09) of the current minimal standard. Differences between types of problems or target groups were marginal. No differences were found between information provided by health authorities, health services, or commercial entities. Conclusion Norwegian web-based health information is not of sufficient quality to facilitate informed health choices made by citizens. These findings apply across a wide range of public health domains relating to infants, children, and youth. In the absence of appropriate health information of acceptable quality, estimates of the public’s level of health literacy may need reconsideration. Further research is needed to appraise the quality of information in other health domains and countries.

Treatment of asymptomatic tuberculosis: Protocol for a systematic review of treatment strategies, regimens, and clinical outcomes

Introduction Asymptomatic tuberculosis (TB) is increasingly recognised through active case finding and prevalence surveys. However, treatment strategies for this patient group remain poorly defined, and there is no consensus on optimal regimens, duration, or outcomes. Methods and analysis We will conduct a systematic review of observational and interventional studies reporting anti-TB treatment in patients with asymptomatic TB. Databases including MEDLINE, Embase, Scopus, Web of Science, CINAHL, and the Cochrane Library will be searched without language restrictions. Outcomes of interest include favourable outcome rate, treatment coverage, success rate, relapse, mortality, loss to follow-up, adverse events, and patient-reported outcomes such as pill burden and treatment discontinuation. Study selection, data extraction, and quality assessment will be performed independently by two reviewers, following PRISMA guidelines. Where appropriate, meta-analyses will be conducted using a random-effects model. Discussion This review will provide a comprehensive synthesis of current evidence on the treatment of asymptomatic TB. It aims to inform future clinical and public health strategies, including the potential for simplified or shortened treatment regimens tailored to this population. By identifying gaps and inconsistencies in current practice, the findings will support evidence-based decision-making and contribute to global TB control efforts.

Resilient in adversity: Innovative treatment support interventions in facilitating ART adherence among young adults living with HIV in the informal settlements of Kibera, Nairobi

Background Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) poses significant health challenges. Despite ongoing efforts to scale up Antiretroviral therapy (ART) to save lives from AIDS-related morbidity and mortality,adherence among young adults remains low at 65% in sub-Saharan Africa. Aim Our study aimed to inform the development of youth-friendly, context-sensitive programs that are both scalable and sustainable in urban informal settlements. This paper presents findings on youth facilitators to ART adherence in Kibera informal settlement. Setting The study was conducted in Nairobi urban informal settlement of Kibra, Nairobi county, Kenya. Methods We utilized in-depth interviews (n = 25) and key informant interviews (n = 10) to collect data on faciliators to ART adherence among purposively selected eligible partcipants. Thematic analysis framework was employed to analyze the data. Results HIV adherence facilitators encompassed patient-related factors like self-acceptance and open disclosure, health system factors such as accessibility, provider relationships, and patient reminders, and socio-economic aspects including support groups, education awareness, family support, and economic empowerment. Conclusions The findings emphasize the need for tailored, age-appropriate, and context-specific interventions in informal settlements to enhance HIV adherence. Fostering self-acceptance, creating an enabling environment through youth friendly services, improving provider-patient relationships, and leveraging social support systems such as peer groups and educational initiatives are essential strategies. Integrating these elements into programmatic and policy frameworks will ensure that interventions resonate with the unique realities of this populationpromoting sustainable adherence outcomes. Contribution The findings will provide a foundation for developing context-sensitive interventions and programs to improve adherence in similar settings.

Seafloor vegetation map of man-made boulders reef by underwater photogrammetry: Suggestions for site selections in macroalgal bed creations

Macroalgal beds play important roles in coastal ecosystems by supplying oxygen, providing food resources, and offering habitats for various marine animals. In recent years, macroalgal beds have significantly declined due to various factors, leading to efforts toward macroalgal bed restorations. Despite these efforts, suitable sites for macroalgal bed creations remain insufficiently understood. In this study, we investigated suitable location conditions for establishment of macroalgal beds by mapping the seafloor vegetation. In an 80 m × 20 m area at a depth of 4.5–9.2 meters in Himeshima Island, Fukuoka, Japan, man-made boulders reef was created by the local government in the fiscal year 2016 for macroalgal bed creation. A 3D model of the seafloor, with a resolution of 0.07 meters, was created using underwater photogrammetry, enabling the visualization of macroalgal vegetation on these artificial boulders through a detailed seafloor vegetation map. Rich macroalgal vegetation, including Sargassum spp. and Undaria pinnatifida was established on the boulders placed on sandy bottoms. In contrast, on the boulders placed on natural cobble/boulder reefs, only a short-lived seaweed Colpomenia sinuosa was observed, and almost all boulders showed no vegetation. Even on the sandy bottoms, boulders that were adjacent to or surrounded by natural cobble/boulder reefs, or those that were piled together, tended to have poor vegetation. For effective macroalgal beds creation, installation of boulders at a low density on sandy bottoms would be preferable, while avoiding the areas on or adjacent to natural cobble/boulder reefs.

Correction: Effect of perchlorate on biocementation capable bacteria and Martian bricks

The predictive value of the dynamic change slope of red blood cell distribution width to platelet ratio combined with clinical indicators for the mortality outcome of patients with sepsis

This retrospective study investigated the predictive value of the dynamic slope of the red blood cell distribution width to platelet ratio (RPR) for in-hospital mortality in patients with sepsis admitted to the intensive care unit (ICU). A total of 154 patients with sepsis admitted to the ICU of the Second Affiliated Hospital of Anhui Medical University between August 2023 and August 2024 were included and classified into non-survivors ( n  = 37) and survivors ( n  = 117) according to in-hospital outcome. Red blood cell distribution width (RDW) and platelet count (PLT) were recorded on days 1–5 after ICU admission, and RPR was calculated as RDW/PLT. Generalized estimating equations demonstrated significant differences in RPR between groups and over time, with a significant group-time interaction, indicating distinct temporal trends between survivors and non-survivors. The RPR in the survivors increased initially and then declined, whereas the RPR in the non-survivors showed a continuous upward trend. Receiver operating characteristic analysis showed that the slope of RPR change had good predictive performance for in-hospital mortality, with an area under the curve of 0.863 (95% CI 0.781–0.946). Optimal cutoff value of 0.017 yielded sensitivity of 86.5% and specificity of 83.8%. Multivariate logistic regression analysis identified high RPR slope (OR = 5.665, 95% CI 1.453–22.084), lactate level, Sequential Organ Failure Assessment (SOFA) score, and mechanical ventilation time as independent risk factors for in-hospital mortality. Furthermore, the combined model incorporating RPR slope, SOFA score, lactate, and mechanical ventilation time showed excellent predictive ability, with an area under the curve of 0.954 (95% CI 0.924–0.983). These findings suggest that dynamic monitoring of RPR provides valuable prognostic information and may improve early risk stratification in patients with sepsis.

Diffraction‐Enabled Operando Nanoscale Tracking of Li‐ion Dynamics of Solid Electrolyte and Inhomogeneous Diffusion in Composite Cathode

Abstract Li + diffusion has mostly been studied in cathode active materials (CAMs) in liquid batteries, whereas it remains rarely explored in solid‐state electrolytes (SSEs) and all‐solid‐state batteries. Herein, diffraction was established as an effective method for all‐solid‐state lithium batteries (ASSLBs) by focusing on SSE in composite cathodes. Operando synchrotron x‐ray diffraction presented diffraction angle shifts of certain Li 3 InCl 6 Bragg planes during the first ASSLB cycle due to lithiation/delithiation into its lattice, whose preferred Li + migration pathways were suggested by the partiality of these shifts, and the three‐phase evolution indicated the fundamental Li + diffusion kinetics factors. X‐ray nanodiffraction (XND) mapped nanoscale inhomogeneous Li + distributions and diffusion within individual Li 3 InCl 6 particles, revealing facilitated Li + conduction in high‐crystallinity regions and their role as pathways across SSE/CAM interfaces, and the most negatively strained regions were shown to be less susceptible to Li + insertion. XND from various electrochemical techniques inferred high transient charging rates to be the culprit of irreversible Li + diffusion instead of the overall charging depth. This study proved diffraction to be a potent tool to probe intricate Li + dynamics in ASSLBs and provide microscopic insights for optimal battery designs.

Navigating work, family, and society: Challenges facing Jordanian female journalists

The aim of this study is to explore the challenges encountered by Jordanian female journalists, focusing on their experiences in the journalistic work environment (including the workplace and the field) in addition to the challenges faced from society and family. Through using a qualitative and inductive approach by conducting in-depth interviews with Jordanian female journalists who are registered professionals working in a variety of media environments, including daily, weekly, and electronic media. The research findings explore a wide range of challenges female journalists face in Jordan, including workplace issues and external challenges from family and society. The following main themes were emerged in the study, at the workplace level: harassment and newsroom safety; pay inequalities, organizational culture and leadership this point leads to subthemes as bullying, framing female Journalists, and stigmatization, On the other hands challenges themes found at the level of the society and family security which emerged several subthemes as party affiliation, security harassment, and cultural beliefs, as well as family, parents and relatives perspectives. The findings highlight persistent gender‑based discrimination shaped by workplace practices and cultural expectations. Strengthening protections, ensuring fair pay and promotion, and shifting societal attitudes are essential to supporting female journalists. Further research is needed to better understand these challenges and inform effective solutions.

Comparative evaluation of otolith and fin ray as tools for assessing population differentiation in Atlantic sturgeon (Acipenser oxyrinchus)

Atlantic sturgeon ( Acipenser oxyrinchus Mitchill, 1815) is a long-lived, anadromous species known for its extensive migrations between freshwater and marine habitats throughout its life. Despite increased conservation efforts, there is only limited information on the early life stages and habitat use of the St. Lawrence River (SLR) and Saint John River (SJR) populations in Eastern Canada. This study explores the use of otolith and fin ray microchemistry to distinguish Atlantic sturgeon populations and investigate habitat use throughout their lives. The otoliths and fin rays of fish caught in both the SLR and SJR regions were analyzed using LA-ICP-MS procedures to determine their elemental signatures throughout their lifespan (coretoedge). Using a machine learning classification approach, both otolith and fin ray revealed strong potentials for differentiating individuals from the SLR and SJR populations. Fin ray microchemistry showed a higher reclassification success and produced more contrasted elemental signatures compared to otolith microchemistry. Our results also showed that the integration of elements is dependent on the structure (i.e., fin ray or otolith). A significant correlation between element concentrations at the core of fin rays and otoliths was observed for only three elements (Sr, Mn, and Li). This phenomenon should be further investigated and considered in future applications because it could lead to reclassification errors. These findings suggest that fin ray microchemistry is a powerful approach that can be used to discriminate population origin and infer life history patterns of Atlantic sturgeon. These results are especially relevant since we propose a cost-effective method to monitor population structure and habitat use without lethal sampling. This is an essential step toward careful management of this species in Eastern Canada.

Correction: Whole genome sequences of nine Taylorella equigenitalis strains isolated in the Czech Republic between 1982–2021: Molecular dating suggests a common ancestor at the time of Roman Empire

Genomic and phenotypic characterisation of Listeria monocytogenes strains isolated from pig feces on farm and from pork meat at retail in France

Listeria monocytogenes is an ubiquitous foodborne pathogen transmissible to humans through the consumption of contaminated products, including pork. In this study, we characterised the Listeria monocytogenes population circulating from the primary reservoir, pigs, to consumers in France. In 2008 and 2010, 147 strains from on-farm pig feces and 154 strains from retail pork meat were respectively isolated. Serogroups and clonal complexes (CC) were determined (n = 301), and 123 representative strains were further assessed for virulence, biofilm-forming ability, and resistance to Benzalkonium chloride (BC). Serogroup IIb, and CCs such as CC11, CC21, CC20, CC26, CC31, CC59, CC37, CC1 and CC77 strains predominated on farms, whereas serogroup IIc and IIa (respectively CC9 and CC121) were mainly recovered from retail meat. All 123 strains harbored the virulence-associated genes inlA , inlC, inlJ, plcA , prfA , actA , hlyA and iap. Overall virulence did not differ significantly between farm- and retail-derived strains; however, serogroup IVb strains were significantly more virulent, while serogroup IIc strains exhibited lower virulence. In our study, CC1 (mainly present in feces) and CC121 (present only on meat) showed the highest virulence level. Biofilm-forming ability was significantly higher in strains isolated from farm feces than in those from retail meat. Most meat strains, including CC121, CC9, CC14 and CC7, were more resistant to benzalkonium chloride than fecal strains. Our findings highlight the genetic and phenotypic evolution of the Listeria monocytogenes population along the pig-to-pork continuum. They suggest that strains persisting to the retail stage are more strongly associated with resistance to biocides than with robust biofilm formation in the food-processing environment. Contrary to expectations, our CC121 strains exhibited the highest level of virulence, even though this CC is reported hypovirulent.

Towards a cybersecure and privacy enhanced smart grid: A blockchain enabled federated learning framework

In smart grids, data collection is carried out through smart meters and devices of the Internet of Things, which are installed in the home, allowing to predict the demand for electricity and optimize the distribution of energy. Although the smart grids improve efficiency of operations for end users, they simultaneously present pronounced challenges regarding user privacy and security at the system level. In the context of conventional centralized machine learning, paradigms risk breaching the raw data of consumers, while decentralized paradigms often lack strong mechanisms for verifying identity or ensuring traceability. Existing federated learning systems often lack client level differential privacy, secure aggregation, and decentralized identity protection, leaving them vulnerable to privacy leakage and inference attacks. Blockchain based solutions typically expose model updates or use single layer identifiers. This paper introduces a secure and privacy preserving architecture that combines a dual layer blockchain architecture, federated learning (FL) and central differential privacy (DP) to thoroughly solve these challenges. The proposed system includes a dual layer blockchain system that ensures secure and tamper resistant logging of client interactions and protects client identities by storing salted cryptographic hashes. This design provides both traceability and anonymity, and thus maintains the integrity of participation while obfuscating sensitive identifiers. Privacy is guaranteed by storing raw data in client devices and sending only model updates for central aggregation. At the server side, Gaussian noise is added to the aggregated model parameters to achieve central DP, so as to reduce the risks of inference attacks on user data. Implementation of the proposed framework was performed based on Flower to test the PRECON (Pakistan Residential Electricity CONsumption) dataset, which consists of real-world household electricity consumption data. Multiple machine learning models were benchmarked and out of all the models, Random Forest performed best with the performance metrics of Mean Absolute Error (MAE) of 0.153, Mean Absolute Percentage Error (MAPE) of 0.085 and Mean Squared Error (MSE) of 0.143. The results showed that the proposed framework improved data privacy, preserved the forecasting accuracy and security in smart grid environments.

Emerging tobacco use patterns in the United States: Tobacco use behaviors associated with current use of nicotine pouches

Nicotine pouches (NPs) are non-combustible tobacco products marketed as alternatives to traditional tobacco. Recent studies suggest an increasing use of NPs in the United States. The primary goals of this study were to assess the associations between current use of each of the seven other tobacco products and current use of NPs among U.S. adults (18+), and to determine which other products are significantly associated with current use of NPs. The secondary goals were to describe the population of adults who currently use NPs in terms of their tobacco use behaviors and sociodemographic characteristics. Data from the 2022–2023 Tobacco Use Supplement (TUS) to the Current Population Survey (CPS), collected in the U.S., were used in this cross-sectional study to address the primary (n = 107,281) and secondary (n = 537) goals. The primary outcome was current NP use (yes/no). All analyses accounted for the TUS-CPS complex design. The prevalence of current NP use was 0.47% (SE = 0.03%), corresponding to an estimated 1,146,681 adults nationwide. Adults who currently used smokeless tobacco (aOR=12.03, 95% CI = 8.83-16.39) had the highest odds of current use of NPs, followed by those who used heated tobacco (aOR=4.84, 95% CI = 2.01-11.67), hookah tobacco (aOR=3.70, 95%CI = 1.55-8.82), e-cigarettes (aOR=2.90, 95% CI = 1.84-4.60), cigars (aOR=2.48, 95% CI = 1.71-3.58), and combustible cigarettes (aOR=1.84, 95% CI = 1.38-2.45). Among adults who currently use NPs, 61.00% (SE = 2.59%) used at least one other tobacco product and the most commonly used products were smokeless tobacco (27.39%), combustible cigarettes (21.74%), e-cigarettes (20.54%), and cigars (17.30%). The observed sociodemographic profile of adults who use NPs (e.g., 89.14% are men) suggests that NPs may be reaching subgroups that differ from those who typically use other tobacco products. The findings underscore the need for further research to determine whether use of NPs leads to product switching, cessation, or sustained poly-tobacco use.

Development of immortalized Callithrix jacchus kidney cell lines supporting infection with a panel of viruses

Common marmosets ( Callithrix jacchus ) are valuable non-human primate (NHP) animal models in biomedical research, including infectious diseases modelling. However, for in vitro studies only a few immortalized cell lines have been generated, and additional lines are needed to comply with the 3R principles of replacement, reduction and refinement. Here, we present the generation and characterization of three cell lines derived from kidney tissue, which were immortalized by transduction of SV40 large T antigen. The cell lines display an epithelioid morphology, show differential podoplanin expression and are likely of pericyte origin, as deduced from expression profiles of marker genes obtained by RNA sequencing analysis (RNA-seq). All cell lines had a functional interferon (IFN) system, as shown by responsiveness to human IFNβ and marmoset IFNα14 and the induction of interferon-stimulated genes (ISG). Infection with retroviral pseudotypes demonstrated susceptibility to entry driven by glycoproteins from a wide range of human pathogenic viruses. Finally, these cell lines are highly permissive for Zika virus, for which marmosets are a model organism, and Herpes simplex virus 1, which causes a deadly disease in marmosets. We believe that these cell lines are a valuable resource for in vitro studies on marmosets.

Evolving threats: Leveraging C. elegans to decode the virulence profiles of highly related environmental Salmonella Newport isolates

Salmonella enterica subspecies enterica , particularly serovar Newport, remains a leading cause of foodborne illnesses in the United States, implicated in numerous outbreaks associated with a diverse array of food products. This study systematically investigates the virulence of five distinct S . Newport isolates, characterized by varying patterns of pulse-field gel electrophoresis (PFGE) molecular-diagnostic subtyping, using the nematode Caenorhabditis elegans as a host model organism. We conducted viability assays on C. elegans to evaluate how these isolates affect nematode survival. The selected bacterial strains, chosen for their historical significance in foodborne outbreaks yet isolated form environmental sources, were previously sequenced to provide a comprehensive genomic framework. A notable focus of our research was on the nearly genetically identical PFGE types Newport-61 and the Newport-1015 isolates, which differ by a 1.7 Mb genomic inversion. C. elegans survival assays in response to pathogenic-strain infections revealed that one Newport-1015 and the Newport-61 isolates were particularly more virulent compared to other isolates tested. These findings enhance our understanding of the pathogenic potential of environmental S . Newport and highlight the need to understand the regulatory mechanisms that contribute to virulence capacity.

Development and psychometric validation of caring leadership scale in nursing

Background Caring leadership plays a pivotal role in supporting nurses’ well-being, fostering patient recovery, and advancing organizational performance. Despite its recognized importance, a validated instrument for measuring caring leadership has been lacking in the literature. Objective This study aimed to develop a Caring Leadership Scale and evaluate its validity, reliability, and practical applicability. Methods Guided by a conceptual framework of caring leadership, scale items were initially generated through qualitative interviews, open-ended questionnaires, and a comprehensive literature review. The Delphi technique was used to refine these items. A pilot survey informed further modifications before a large-scale survey was conducted with 2,125 frontline nurses from six tertiary hospitals across China. Item screening was carried out using classical test theory, including assessments of item discrimination, item-total correlations, and internal consistency (Cronbach’s alpha). Content validity, factor structure, internal reliability, and acceptability were investigated using content validity indices, exploratory and confirmatory factor analyses, correlation coefficients, and descriptive statistics. Results An initial pool of 40 items across five dimensions was developed. Following two Delphi rounds and preliminary testing, 39 items were retained. Item analysis led to the elimination of 12 items that did not meet predetermined criteria. The final scale consisted of 27 items across five dimensions, rated on a 5-point Likert scale. The content validity indices were strong, with item-level CVIs ranging from 0.90 to 1.00, a scale-level content validity index universal agreement (S-CVI/UA) of 0.89, and a scale-level content validity index average (S-CVI/Ave) of 0.99. Exploratory factor analysis (EFA) supported a well-defined five-factor structure, with common factor variances ranging from 0.849 to 0.949. Confirmatory factor analysis demonstrated good model fit (RMSEA = 0.078, CFI = 0.964, NFI = 0.958, TLI = 0.959, IFI = 0.964). The average variance extracted (AVE) ranged from 0.834 to 0.925, and composite reliability (CR) ranged from 0.965 to 0.989. The scale showed moderate correlations with job satisfaction (r = 0.463–0.484, p  < 0.001). Internal consistency was high, with Cronbach’s alpha values between 0.962 and 0.993, and split-half reliability coefficients ranging from 0.955 to 0.982. Conclusion This study presents the first validated instrument for measuring caring leadership in nursing. The final 27-item scale demonstrates robust psychometric properties, including excellent validity, reliability, and user acceptability. It offers a scientifically sound and practical tool for assessing caring leadership among nurse leaders.

Stakeholder priorities and conceptualization of One Health: Insights from fuzzy cognitive mapping and grounded theory

One Health (OH) has gained global recognition as a framework and practice for addressing interconnected health and sustainability challenges, such as emerging infectious diseases, food insecurity and climate change. Yet its operationalization remains limited, in part due to persistent differences in how OH is conceptualized across sectors and knowledge systems, including Indigenous knowledge holders and environmental actors. To address these gaps, we applied a mixed methods approach that combined fuzzy cognitive mapping (FCM) with grounded theory (GT) to examine stakeholder priorities and conceptualization of OH in Turkana County, Kenya. Thirty-six fuzzy cognitive maps were co-developed with community members, frontline workers, health, veterinary, and NGO stakeholders, then aggregated by group and analyzed using network metrics including normalized degree centrality and Jaccard similarity. Results revealed areas of alignment and convergence in OH conceptualization and perspective. Conceptually, the environment group map was the most distinct, while the health and NGO maps were the most similar. Environmental actors emphasized human-driven degradation, while community members described a pluralistic health system and the importance of wild foods, both absent from other group narratives. Shared priorities such as human and livestock health, nutrition, and water resources represent potential entry points for cross-sectoral integration. These findings demonstrate that barriers to OH operationalization are not only structural, but also shaped by differences in knowledge, experience, and problem framing across sectors and society within the socioecological system. Embedding ecosystem services, biodiversity, and traditional knowledge at the core of OH can enhance inclusivity and contextual relevance. Our integrated FCM-GT approach offers a transferable framework for participatory systems research, providing actionable insights for more inclusive and ecologically grounded OH implementation.

Reimagining <i>o</i> ‐Carborane‐Based Fluorophores: Charge‐Transfer from Boron Substituents Triggers Aggregation‐ and Crystallization‐Induced Emission

Abstract o ‐Carborane‐based fluorophores are widely recognized for their aggregation‐induced and crystallization‐induced emission (AIE and CIE) properties, making them valuable building blocks for materials used in fluorescence applications such as bioimaging or optoelectronics. Until now, observing AIE/CIE required the fluorophore to be attached via the carbon atom of the carborane, inherently limiting further functionalization possibilities. Herein, we report for the first time that boron‐substituted carboranes (substituent is at position 9) exhibit AIE/CIE activity, which originates from photoexcitation‐induced electron‐transfer from the substituents linked to the carborane cage via its boron vertices. Furthermore, the solid state emission can be tailored by the proper selection of the substituents. This finding not only significantly broadens the scope of AIE‐active compounds but also offers new design strategies for the development of luminescent carborane‐based materials.

Correction: Factors associated with death from COVID-19 in traditional peoples and communities in Brazil

Cheminformatics-driven discovery of natural isoquinoline alkaloid inhibitors of Beta-secretase I for Alzheimer’s management

Alzheimer’s disease (AD) is characterized by the gradual deterioration of cognitive functions, speech impairment, and memory loss. It can potentially be treated by targeting the beta-site amyloid precursor protein cleavage enzyme 1 (BACE1), which plays a key role in amyloid plaque formation, neurofibrillary tangles, and hyperphosphorylated tau protein. Current drugs have limitations in terms of safety, efficacy, and blood-brain barrier permeability. In view of this, this study was designed to determine the potential inhibitors of the BACE1 enzyme by virtual screening using a curated library of 415 natural products including terpenoids, phenolic compounds, and alkaloids from different medicinal plants. Based on the docking score and interaction analysis, 50 compounds were selected for the downstream analysis, such as ligand binding interactions, pharmacokinetics, druglikness and physicochemical parameters. Among the lead compounds, Palmatine (compound 45) and Berberine (compound 49), demonstrated optimal drug-likeness and blood-brain barrier permeability among the top compounds. 2-[(9Z,12Z)-heptadeca-9,12-dienyl]-6-hydroxybenzoic acid (compound 4) was inactive in most toxicity parameters. Pharmacophore analysis revealed that Palmatine and Berberine share similar features with the standard, highlighting their potential as effective compounds. Furthermore, structural chemistry analysis provided insights on their shared isoquinoline alkaloid framework, illustrating their structural similarities. Molecular dynamics simulations confirmed the stability of the Palmatine-BACE1 and Berberine-BACE1 complexes during a 50 ns production run. Overall, these findings highlighted the potential of Palmatine and Berberine as promising candidates for the experimental validation and the development of the drugs for the treatment of AD.