Search Results (630)

Artificial intelligence has advanced from merely predicting static protein structures to modeling equilibrium conformational ensembles. It now concurrently forecasts structure and binding affinity and actively participates in candidate selection during the initial stages of drug discovery. Foundation models introduced between 2024 and 2026, including BioEmu, AlphaFlow, DiG, Boltz-2, Chai-1, NeuralPLexer, and explicit-solvent prediction systems such as SuperWater, have begun to address issues previously identified as fundamental concerns in earlier critiques of AI in drug discovery. Nevertheless, many of these models are presently accessible only as preprints and require validation through independent peer review. Evidence indicates a shift in the primary bottleneck from representation challenges to validation difficulties. However, this transition remains incomplete and heavily dependent on context. The risks associated with AI-enabled drug discovery are increasingly not solely about the models’ capacity to accurately represent ensembles, but also about whether the evidentiary standards used to validate AI-derived predictions keep pace with the rapidity with which these predictions are generated and employed. This article introduces a four-tier validation framework designed to align the extent of computational and experimental evidence with the translational and regulatory risks associated with various artificial intelligence (AI) applications within the molecular sciences. These applications include machine learning (ML) models that analyze sequences, structures, conformational ensembles, protein–ligand complexes, and molecular dynamics trajectories. Tier 1 addresses the internal reproducibility of ML inference when applied to molecular inputs; Tier 2 pertains to the robustness of molecular-science benchmarks such as CASP, CASF-2016, PoseBusters, and OpenFE; Tier 3 involves prospective experimental validation against biophysical and biochemical measurements; and Tier 4 encompasses clinical and translational calibration within physiologically based pharmacokinetic (PBPK) and quantitative systems pharmacology (QSP) frameworks. This validation hierarchy functions as an explicit conceptual guide, serving as a framework rather than a regulatory requirement. It is firmly grounded in established principles derived from ICH Q8/Q9/Q10, the FDA model-informed drug development (MIDD) approach, the EMA reflection paper on AI in the medicinal product lifecycle, and the EU AI Act. The manuscript further incorporates recent evidence from ensemble-aware AI, prospective docking, free-energy campaigns, and clinical-stage AI-derived candidates. It concludes with specific recommendations pertaining to lifecycle governance, uncertainty reporting, and the adoption of harmonized evidentiary templates for AI/ML applications in the molecular sciences. Full article

Background/Objectives: Familial hyperaldosteronism type IV (FH-IV) is an extremely rare, clinically heterogeneous condition representing the least characterized familial subtype of primary aldosteronism (PA) caused by germline gain-of-function CACNA1H mutations. Despite growing molecular insights, optimal diagnostic and therapeutic strategies remain poorly defined. This systematic review aims to synthesize available evidence regarding the clinical, biochemical, and genetic characteristics of FH-IV, and to evaluate the efficacy of current pharmacological and surgical treatments. Methods: A systematic review was conducted in accordance with PRISMA guidelines and preregistered in PROSPERO (CRD420261324945). A comprehensive search of MEDLINE, Embase, and Web of Science identified studies reporting genetically confirmed FH-IV patients. Data concerning clinical phenotypes, diagnostic evaluations, treatment outcomes, and genetic backgrounds were extracted and analyzed. Results: The primary cohort included 31 fully characterized symptomatic patients, alongside 8 mutation-positive relatives (4 asymptomatic carriers and 4 symptomatic individuals). The genetic landscape was remarkably heterogeneous, encompassing 17 distinct CACNA1H mutations. Clinically, diagnosis was frequently delayed, often complicated by atypical normokalaemic presentations and misleading adrenal imaging. Surgical treatment was generally ineffective, frequently resulting in persistent or recurrent hypertension and biochemical dysregulation. Pharmacologically, patients often required multiple antihypertensive drugs, most frequently a combination of mineralocorticoid receptor antagonists (MRAs) and calcium channel blockers (CCBs). Conclusions: FH-IV is best conceptualized as a systemic adrenal channelopathy. While standard screening parameters are usually elevated, atypical biochemical profiles and misleading structural imaging can complicate the diagnostic process. Optimal management relies on multigene Next-Generation Sequencing (NGS) panels for definitive diagnosis and cascade screening of relatives. Finally, while the combination of MRAs and CCBs is commonly used in PA, it represents a valuable therapy for FH-IV, with dual L-/T-type CCBs emerging as a potential disease-specific option. Full article

Aluminum chloride (AlCl₃)-induced rat models are widely used to investigate Alzheimer-like neurodegeneration, yet substantial methodological variability limits cross-study comparability. A structured synthesis focused specifically on the methodological architecture of these models, including dose, exposure duration, route of administration, and behavioral assessment, remains lacking. This review aimed to synthesize the behavioral paradigms used to assess learning and memory in rat models of aluminum chloride-induced Alzheimer’s disease, with particular emphasis on dose, duration, and route of administration. A structured narrative review incorporating systematic elements was conducted following PRISMA-informed procedures using PubMed, Web of Science, and Scopus. The reviewed literature showed a predominance of oral administration, low-to-moderate AlCl₃ doses and subchronic exposure durations, most commonly 31–60 days. Behavioral assessment was dominated by hippocampal-dependent paradigms, particularly the Morris water maze and Y-maze. Across studies, AlCl₃ exposure was associated with multidomain behavioral impairment accompanied by consistent hippocampal and cortical histopathological abnormalities and convergent biochemical and molecular changes, including cholinergic dysfunction, oxidative stress, neuroinflammation, and amyloid- and tau-related alterations. Overall, the available literature does not support a standardized experimental protocol or a clear overall dose–effect or duration–effect relationship. Greater harmonization of study design is needed to improve reproducibility and translational relevance. Full article

Objectives: This study aimed to examine the structure of anthropometric characteristics, motor skills and specific motor skills in young football players. Methods: Study participants (427 male football players) were divided into pre-pioneers (11–13 y), n = 133; pioneers (13–15 y), n = 160; and cadets (15–17 y), n = 134. The entire sample of subjects was evaluated using 13 anthropometric and seven motor variables. The factor structure for each chronological age group was determined using Hotelling’s method. Results: Anthropometric characteristics showed three extracted factors in the pre-pioneers group, four factors in the pioneer group and two factors in the cadet group. Motor skills displayed three factors for the youngest group, two factors for the pioneers and three factors for the cadet group. Four factors were determined for specific motor skills in pre-pioneers, four in pioneers and three in cadet age. Conclusions: This study revealed structural variability and non-uniformity in the latent dimensions across age groups, with the total number of factors fluctuating between two and four. This study revealed two consistent latent dimensions in anthropometric data across all age groups: general morphological parameters and subcutaneous fat tissue. In motor skills, an initial universal factor is separated into central and energetic regulation of movements. Finally, specific motor skills demonstrated a transition from a highly differentiated four-factor structure in younger players toward a more integrated functional system in the oldest cohort, comprising intermuscular coordination, running speed with and without a ball; segmental speed of the lower extremities with a ball; and explosive force in hitting a ball with the foot and head. Full article

Non-arteritic anterior ischemic optic neuropathy (NAION) is a leading cause of sudden vision loss, yet no effective therapy exists to preserve retinal ganglion cells (RGCs) after ischemic injury. Nostoc commune (NC), an edible cyanobacterium with established antioxidant and anti-inflammatory activities, has emerged as a potential functional bioresource with relevance to ocular health. Here, we investigated the therapeutic effects of a crude aqueous extract of NC using a rodent model of anterior ischemic optic neuropathy (rAION). NC treatment significantly improved RGC survival, reduced apoptosis, attenuated macrophage and microglial activation (ED-1, Iba1), suppressed proinflammatory cytokine expression (IL-6), enhanced the reparative marker Ym1+2, and preserved optic-nerve myelination. Functionally, NC administration restored visual signaling as demonstrated by improved Flash Visual Evoked Potential amplitudes. Immunoblot analysis showed increased phosphorylation of PI3K/AKT/mTOR/p70S6K signaling components in retinal tissue following NC treatment. Proteomic profiling further demonstrated that NC extract comprises a coordinated repertoire of phycobiliproteins, antioxidant enzymes, and stress-response proteins that may collectively contribute to its biological effects. Together, these findings suggest that Nostoc commune extract may serve as a promising functional food-derived candidate for protecting RGCs and preserving visual function following ischemic optic neuropathy. Further studies are required to identify its active constituents, optimize formulation strategies, and evaluate its translational potential. Full article

Background/Objectives: Aging is associated with physiological, biochemical, and psychosocial changes that can significantly affect nutritional status and overall health. In Sub-Saharan Africa (SSA), older adults face unique age-related challenges that may compromise healthy aging, yet evidence remains fragmented. This systematic review synthesized the existing literature on the nutritional status, age-related challenges, and strategies to promote healthy aging of older adults in SSA. Methods: A systematic literature search was conducted on PubMed, Scopus, ScienceDirect, and Cochrane Library to identify relevant studies published up to 10 December 2025. Results: Fifty-five studies met the inclusion criteria, with most of the studies coming from South Africa, Ghana, and Nigeria. Amongst community-dwelling populations, approximately 30–65% of the older adults were either malnourished or at risk of malnutrition, while hospital-based studies reported markedly higher burdens, with malnutrition prevalence exceeding 70% in some settings. Undernutrition, micronutrient deficiencies, and the coexistence of overweight and obesity were frequently observed, reflecting the region’s ongoing nutrition transition. Frailty emerged as the predominant age-related challenge, with prevalence ranging around 10–60%. Other common challenges included sarcopenia, reduced muscle strength, functional disability, cognitive impairment, and dysphagia, all of which were closely related to poor nutritional status, food insecurity, multimorbidity, and reduced quality of life. Few studies reported on healthy aging strategies, with the limited evidence suggesting that nutrition education, physical activity, and psychosocial interventions may enhance nutritional and functional outcomes. Conclusions: The need for context-specific, nutrition-sensitive interventions, and stronger health and social support systems is warranted to promote healthy aging in SSA older adults. Full article

The life sciences are currently undergoing a serious transition from the reductive biochemical analysis of dissociated tissues to non-destructive “spatial forensics”. In addition to discovering new molecules, we are moving towards finding out their precise tissue localization and performing in situ interrogation to uncover a biological logic within preserved cellular “neighborhoods”. Our perspective is focused on exploring the spatial imperative, including the structural logic and “neighborhood effects” of the tissue microenvironment, which is a prerequisite to understanding cellular function in normal and in pathological conditions. Beginning with a historical foundation of the origins of histochemistry, dating back to the 19th century with pioneer botanist François-Vincent Raspail, we emphasize the technological metamorphosis, transitioning from classical immunohistochemistry to modern multi- and high-plex spatial multi-omics. A critical evaluation of the current operational landscape has been made, addressing the engineering strategies behind multiplexed immunofluorescence (mIF), the challenges of experimental design in spatial transcriptomics, and the functional symbiosis between targeted and unbiased spatial proteomics. There are many layers of genomic and proteomic information we have to consider in order to unravel the mechanisms underlying body function. If we learn how to combine all this information together, we will be able to better understand how cells communicate with each other and what disrupts their communication, leading to cancer and many other pathologies. It is obvious that by implementing spatial biology tools, it becomes possible to develop new medicines and treat diseases in the most efficient ways. At the same time, we realize that there is an urgent need to learn how to put data pieces together so that they blend seamlessly into a meaningful output, further transitioning spatial biology over time into a routine tool to cure for both common and rare diseases and improve our lives and health. Full article

Gold nanoparticles (AuNPs) have numerous applications in science and industry. Therefore, their potential phytotoxicity should be investigated. Garden cress (Lepidium sativum L.) is a useful model plant for assessing the effects of chemicals released into the environment. The aim of this study was to prepare alginate gels containing AuNPs for plant exposure experiments, evaluate their physicochemical properties, and determine their effects on selected biochemical parameters of garden cress seedlings. Gold nanoparticles were synthesized in sodium alginate at an initial concentration of 50 mg/L, using xylose and maltose as reducing agents. The gels were diluted with distilled water to obtain AuNP concentrations of 5 and 25 mg/L. Garden cress seeds were placed on filter paper soaked with the tested formulations, while distilled water and sodium alginate solutions without AuNPs served as controls. After 5 days of incubation at 20 °C under light conditions, the plant material was collected and selected bioactive compounds were determined. AuNP-containing gels significantly affected the biochemical status of the seedlings. In particular, AuNPs synthesized with xylose at 25 mg/L significantly increased the contents of photosynthetic pigments and total polyphenolic compounds. All tested AuNP formulations increased the antioxidant activity of seedlings, suggesting the activation of abiotic stress-related defense responses, however, direct markers of oxidative damage were not assessed in the present study. Overall, the results indicate that alginate-based AuNPs can modify selected biochemical parameters in garden cress seedlings, and these effects depend on nanoparticle concentration and reducing sugar used during synthesis, which may be relevant for the future development of plant-targeted nanomaterials for agricultural applications. Full article

Background/Objectives: Pediatric intussusception, a condition where part of the intestine telescopes into an adjacent segment, predominantly affects children aged 6–18 months. Prompt diagnosis and management are crucial to prevent serious complications such as ischemia or necrosis. This systematic review aims to comprehensively evaluate and synthesize existing research on predictive and prognostic biomarkers associated with pediatric intussusception that can aid in early diagnosis, severity assessment, outcome prediction, and treatment. Methods: A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science using specific MeSH and free-text terms related to intussusception, biomarkers, and the pediatric population. The review followed PRISMA guidelines, with independent screening, data extraction, and quality assessment using the Joanna Briggs Institute critical appraisal tools. A total of 47 studies, mostly retrospective cohorts from diverse countries, with over 20,000 patients, were included. Results: The studies identified numerous biomarkers associated with disease severity, including hematological markers and indices (e.g., WBC counts and neutrophil-to-lymphocyte ratio), inflammatory markers (CRP and cytokines), biochemical markers (serum lactate, D-dimer, and electrolytes), and novel molecular markers (I-FABP, MCP-1, and transfer RNA fragments). Elevated inflammatory markers and derived ratios consistently predicted bowel necrosis, ischemia, and need for surgery. Biochemical markers like serum lactate and D-dimer correlated with ischemic severity. Emerging molecular biomarkers show promise for early, non-invasive risk stratification. However, heterogeneity in study designs, assay methods, and cutoff values currently limits immediate clinical application. Conclusions: Biomarker research offers valuable tools for improving pediatric intussusception management, with the potential to enhance early diagnosis and outcome prediction. While traditional markers are useful, novel molecular and protein biomarkers hold promise for more specific and rapid assessment. Validation through multicenter, prospective studies and standardized protocols is essential before routine implementation. Integrating biomarkers with clinical and imaging data could refine decision-making, ultimately reducing morbidity and improving prognosis in affected children. Full article

Personalized transdermal drug delivery systems (TDDS) represent a transformative approach in precision medicine by enabling patient-specific, non-invasive, and controlled therapeutic administration. Conventional transdermal patches are limited by fixed dosing, passive diffusion, and interindividual variability in skin permeability and metabolism, often leading to suboptimal therapeutic outcomes. Recent advances in materials science, nanotechnology, microneedle engineering, and digital health have enabled the development of next-generation personalized TDDS capable of programmable, adaptive, and feedback-controlled drug release. Smart wearable patches integrating biosensors, microfluidics, microneedles, and wireless connectivity allow real-time monitoring of physiological and biochemical parameters, enabling closed-loop drug delivery tailored to individual metabolic profiles. Nanocarriers such as lipid nanoparticles, polymeric nanoparticles, and stimuli-responsive hydrogels further enhance drug stability, penetration, and controlled release, while 3D-printing technologies facilitate patient-specific customization of patch geometry, drug loading, and release kinetics. Artificial intelligence (AI) and machine learning tools are increasingly being employed to predict drug permeation behavior, optimize enhancer combinations, and personalize dosing regimens based on pharmacogenomic and pharmacokinetic data. Despite these advances, regulatory complexity, manufacturing standardization, long-term biocompatibility, and cybersecurity considerations remain critical challenges for clinical translation. This review highlights recent innovations in personalized TDDS, discusses their clinical potential, and examines regulatory and technological barriers. Collectively, these emerging smart transdermal platforms offer a promising pathway toward adaptive, patient-centered therapeutics that can significantly improve treatment efficacy, safety, and compliance. Future research should focus on integrating multimodal biosensing, advanced biomaterials, scalable manufacturing strategies, and robust regulatory frameworks to enable clinically validated, fully autonomous transdermal systems that can dynamically adapt to real-time patient needs in diverse therapeutic settings. Full article

Waste-to-energy technology plays a crucial role in advancing the circular economy framework, a strategy that contributes to achieving the United Nations Sustainable Development Goals on responsible consumption and production, as well as the provision of affordable and clean energy. Hydrothermal co-liquefaction has emerged as a promising technology for addressing waste material challenges by converting them into valuable biofuels. This review focuses on biomass feedstock classification and provides an overview of hydrothermal co-liquefaction for sustainable waste management and improved energy production. Moreover, the article provides details on integrating other waste treatment methods with hydrothermal liquefaction to promote the circular economy. Research publications from 2015 to 2025 were obtained from Web of Science and Scopus to identify research trends and output across countries and map out future research directions. The retrieved data from Web of Science was analysed for mapping research, keyword occurrence, and network analysis using VOSviewer software. The study highlighted that waste treatment techniques not only mitigate environmental pollution but also provide a sustainable pathway for energy production and contribute to global carbon neutrality. The review shows that biocrude yield varies with blending ratio because of differences in the biochemical composition of feedstocks, which affect reaction pathways and lead to synergistic or antagonistic interactions during co-processing. Therefore, careful selection of biomass feedstock is essential to achieve optimal results. Full article

Background/Objectives: Celiac disease (CD) is a chronic, immune-mediated enteropathy induced by dietary gluten exposure in genetically predisposed individuals. Along with non-celiac gluten sensitivity (NCGS), these disorders present with multiple intestinal and extra-intestinal symptoms leading to multisystemic involvement, with complications documented in the oral cavity as well. Persistent immune activation and dysregulation, chronic inflammation, nutrient deficiencies, xerostomia, and microbial dysbiosis found in CD and NCGS constitute shared pathological findings, providing biological plausibility for an association with periodontitis. Methods: A narrative literature review was conducted based on a systematic search of four databases (PubMed, Scopus, Web of Science, Cochrane Library) and the gray literature through January 2026. A comprehensive set of clinical, radiographic, biochemical and immunological parameters was assessed. Two reviewers independently screened and selected studies, with disagreements resolved by consensus. Results: A total of 15 studies met the eligibility criteria and were included in the review. Available evidence, mainly derived from cross-sectional observational studies, remains limited, methodologically heterogeneous, and largely inconclusive. Across adult and pediatric populations, findings do not consistently demonstrate a clinically meaningful association between CD or NCGS and periodontal inflammation, irrespective of gluten-free diet (GFD) adherence. Observed differences, when reported, are modest and inconsistent, and can be mainly attributed to oral hygiene behaviors and dental visit patterns. Conclusions: Despite considerable biological plausibility linking gluten-related disorders with periodontal inflammation, current evidence does not support a definitive conclusion regarding the impact of CD or NCGS on periodontal health. Full article

In recent years, with the rapid development of materials science, there has been a significant increase in the focus on nanozymes. Metal–organic framework (MOF)-based nanozymes are a class of porous organic–inorganic coordination materials capable of mimicking the catalytic activity center of natural enzymes. The properties of MOF-based nanozymes include high specific surface area and porosity, structural diversity and customizability, and excellent catalytic activity and stability. Through rational design, the activity of MOF-based nanozymes can be further enhanced to promote their application in biosensing and other fields. This paper systematically investigates the intrinsic relationship between the structure of MOFs and their catalytic performance, with a focus on the diverse catalytic activities of MOF-based nanozymes, including peroxidase, oxidase, catalase, superoxide dismutase, and hydrolase. It reviews optimization strategies for the key parameters, such as selectivity and stability, summarizing the advances in synthesis strategies. Furthermore, the application progress of MOF-based nanozymes in the field of biosensing is reviewed, covering areas such as biomarker detection, virus recognition, and the screening of pathogenic microorganisms, among others. This review provides a systematic discussion of the opportunities and challenges in the development of MOF-based nanozymes, identifies the key scientific issues that are driving the field forward, and offers important references for optimizing MOFs’ structural designs and developing high-efficiency biochemical sensors. Full article

Electron transfer is one of the most essential processes in biological systems. Redox reactions, either directly or indirectly, drive the main ATP-synthesizing pathways, especially those relying on a chemiosmotic mechanism, and as such, they are fundamental to photosynthesis and respiration. During biochemical redox reactions, electrons are transferred from a low-potential donor to a high-potential acceptor, mainly affecting the oxidation state of carbon atoms. The mechanism of electron transfer remains an intriguing enigma because of the wave-particle duality of subatomic particles. According to the biophysical conditions, electrons can be transferred by quantum tunneling or hopping from one redox site to another. While the driving force is always the electrochemical potential, a particularly interesting case is reversible electron bifurcation, where downhill (exergonic) redox reactions are coupled with uphill (endergonic) reactions by splitting the electrons of a two-electron donor. Here, we aim to discuss these different mechanisms in a comprehensive review accessible to students, teachers, and researchers in biological sciences. Full article

Background: Vitamin B12 deficiency is a recognized but frequently under-integrated cause of global developmental delay (GDD) in infancy and early childhood. Early diagnosis is critical because neurological impairment may be partially or completely reversible with timely treatment. Objective: This narrative review aims to synthesize current evidence on the role of vitamin B12 deficiency in the diagnostic evaluation of GDD, with a focus on clinical phenotype, risk factors, biomarkers, treatment outcomes, and practical integration into contemporary diagnostic algorithms. Methods: A structured, non-systematic search of PubMed/MEDLINE, Embase, and Web of Science was performed to identify clinical studies, case series, reviews, and guideline documents addressing pediatric vitamin B12 deficiency and neurodevelopmental delay. Results: Vitamin B12 deficiency in early childhood is most commonly associated with maternal deficiency and exclusive breastfeeding without adequate supplementation. Evidence from recent clinical and observational studies indicates that vitamin B12 deficiency may present with nonspecific neurological symptoms, including developmental regression, hypotonia, and feeding difficulties. Incorporating vitamin B12 assessment—using serum vitamin B12, holotranscobalamin, methylmalonic acid, and homocysteine—into early diagnostic algorithms for GDD may facilitate timely identification of a treatable cause of neurodevelopmental impairment. The proposed diagnostic framework emphasizes early biochemical evaluation in infants with unexplained developmental delay, thereby supporting prompt treatment during a critical window of neurological reversibility. Conclusions: Targeted assessment of vitamin B12 status in children with GDD, together with evaluation of maternal status, represents a clinically relevant approach to identifying a potentially preventable and treatable cause of neurodevelopmental impairment. Integration of functional biomarkers into diagnostic pathways and the development of pediatric-specific reference standards are key priorities for future research and clinical practice. Full article