Biology and Life Sciences

Abstract: Medicinal plants grown outside their native forest habitat may produce phytochemical profiles that differ from wild-harvested material, yet the ecological mechanisms underlying these differences remain poorly synthesized across disciplines. This review proposes that the forest understory functions as a multi-signal elicitation system in which canopy light filtering, arbuscular mycorrhizal fungi (AMF), and above-ground biotic interactions collectively shape secondary metabolite profiles. AMF-mediated induced systemic resistance and above-ground biotic interactions operate through confirmed jasmonate-mediated pathways. Sunfleck-driven reactive oxygen species signaling is hypothesized but untested, and the red-to-far-red ratio modulated phytochrome B pathway characterized in Arabidopsis remains unconfirmed in shade-tolerant species. Using three saponin-rich herbs (Panax vietnamensis, P. ginseng/P. quinquefolius, and Paris polyphylla) as case studies, we formalize this as a testable chemical terroir hypothesis with three falsifiable predictions. We also translate it into an ecological co-cultivation design principle with three production levels and a two-step operational framework, and identify priority experiments, analytical methods, and implementation challenges needed for validation. These contributions bridge forest ecology and medicinal plant science while identifying critical evidence gaps requiring resolution before field implementation.

Abstract: Sweet potato (Ipomoea batatas L.) is a key food security crop in the developing world. Its production is, however, constrained by low-quality, virus-infected planting material derived from conventional vegetative propagation. In this study, we developed an efficient and reproducible in vitro micropropagation protocol for the orange-fleshed sweet potato cv. ‘Kulfo’. Nodal and apical shoot explants were cultured on Murashige and Skoog (MS) medium containing different combinations of 6-benzylaminopurine (BAP), naphthalene acetic acid (NAA), and gibberellic acid (GA₃) for shoot initiation and multiplication, and indole-3-butyric acid (IBA) and NAA for rooting. The maximum shoot regeneration was achieved (62% from nodal and 59% from apical explants) on MS medium supplemented with 0.5 mg L⁻¹ BAP and 0.1 mg L⁻¹ GA₃. MS medium supplemented with 1.0 mg L⁻¹ BAP and 0.1 mg L⁻¹ NAA produced a mean of 7.2 shoots per explant per subculture with vigorous growth during the shoot multiplication stage. Half-strength MS medium supplemented with 0.1 mg L⁻¹ IBA and 0.1 mg L⁻¹ NAA was the best rooting medium. The acclimatized plantlets from the optimal treatment showed a 98.2% survival rate in the greenhouse. The optimized cultivar-specific protocol provides a reliable system for the mass production of high-quality, orange-fleshed sweet potato planting material to support food security, genetic improvement, and germplasm conservation.

Abstract: Mineral waters represent unique limnological ecosystems with stable physicochemical conditions and specialised microbial communities adapted to extreme environments. Bulgarian mineral waters remain comparatively underexplored despite their considerable ecological and biotechnological significance. This review analyses current knowledge on the diversity, ecological functions, and biotechnological potential of microbial communities from Bulgarian mineral springs. A comprehensive literature survey covers studies published between 1990 and 2026. The study integrates hydrogeological, limnological, microbiological, and biotechnological data and encompasses both culture-dependent methods and molecular approaches. The available evidence demonstrates that microbial communities in Bulgarian mineral waters include diverse bacteria, archaea, cyanobacteria, microalgae that adapt to broad thermal and geochemical gradients. These microorganisms actively participate in element cycles, form complex biofilms, and show numerous physiological adaptations to oligotrophic and extreme conditions. Many taxa produce thermostable enzymes, antimicrobial compounds, exopolysaccharides with potential applications in medicine, industrial biotechnology, environmental remediation, and cosmeceutical technologies. The review identifies significant research gaps and emphasises the importance of integrated multi-omics approaches for future exploration of Bulgarian mineral water ecosystems.

Abstract: Mangrove wetlands are important coastal ecosystems and are increasingly vulnerable to heavy metal contamination. The accumulation of heavy metals in man-grove ecosystems is well studied; however, studies on the seasonal variations of heavy metals in mangrove wetlands are scarce. This study investigated heavy metal (Cd, Cr, Cu, As, Pb, and Zn) accumulation in surface sediments of six typical mangrove wet-lands (DZG, QLH, XCP, SYR, SBW, and XY) in Hainan Island, China, during wet and dry seasons. In addition, potential ecological concerns and relationships between sedimentary physicochemical parameters and metal accumulation were assessed. The findings demonstrated significant spatial differences in heavy metal accumulation, with higher concentrations in the northern localities and lower concentrations in the southern areas. There were notable seasonal fluctuations in heavy metal concentrations, with higher levels in the dry season. Risk assessment models exhibited that Cadmium (Cd) and Arsenic (As) were the principal contaminants of concern in most research sites with moderate levels of contamination and posed at least moderate ecological concerns in both wet and dry seasons. The overall ecological risk index indicated a moderate risk to the environment, especially in the dry season. The principal component analysis (PCA) and correlation analysis results indicated that the physicochemical properties of sediments, mainly total organic carbon (TOC), total phosphorus (TP), total nitrogen (TN), and salinity, had significant effects on the heavy metals accumulation in the mangrove sediments. The present study helps raise awareness of seasonal fluctuations in heavy metal pollutants and provides strategies for the prevention and monitoring of metal pollution in mangrove wetlands.

Abstract:

Caryocar coriaceum Wittm. (Caryocaraceae) is a native Brazilian species predominantly distributed in Cerrado areas and transitional regions with the Caatinga in Northeastern Brazil, whose fruits exhibit significant nutritional, technological, and biofunctional potential. This review systematizes and critically analyzes the available scientific evidence regarding the fixed oil extracted from its fruits, addressing extraction methods, chemical composition, physicochemical parameters, nutritional value, technological applications, and the main bioactivities described in experimental models. Chromatographic and bromatological studies demonstrate that the oil presents a lipid profile characterized by the predominance of monounsaturated and saturated fatty acids, especially oleic acid and palmitic acid, in addition to the presence of carotenoids, phenolic compounds, and other bioactive lipophilic constituents. Available preclinical evidence indicates antioxidants, anti-inflammatory, wound-healing, gastroprotective, respiratory, anticonvulsant, and microbial resistance-modulating properties, suggesting potential applications in the food, pharmaceutical, cosmetic, and biotechnological fields. From the perspective of Food Science, the oil demonstrates characteristics compatible with lipid matrices of functional interest, although aspects related to oxidative stability, compositional standardization, sensory acceptability, and industrial scale-up remain insufficiently explored. Additionally, important limitations persist regarding the scarcity of systematic toxicological studies, the absence of clinical trials in humans, and the limited elucidation of the molecular mechanisms involved in the observed bioactivities. Thus, although C. coriaceum presents promising biotechnological potential, the advancement of its translational application will depend on multidisciplinary approaches capable of integrating chemical standardization, toxicological safety, and applied technological development.

Abstract: Mechanistic models in radiobiology have proliferated across FLASH ultra-high dose-rate radiotherapy, spatially fractionated radiation therapy (SFRT), and stereotactic body radiotherapy (SBRT), yet the field has not converged on unified mechanistic explanations despite decades of model development. We propose that this proliferation partly reflects a structural property of the model-observation pairing itself: clinically accessible measurements may be insufficient to uniquely recover the parameters governing the underlying biological dynamics. Using generating-series structural identifiability analysis, we examine four representative models spanning the temporal, spatial, magnitude, and adaptive-state dimensions of radiobiological response: the Pratx-Kapp radiolytic oxygen depletion model (FLASH), the McMahon kinetic-bystander model (SFRT), the LQ-L extension (SBRT), and the Gupta phenotypic-plasticity model of adaptive resistance. The Pratx-Kapp and McMahon models exhibit intrinsic non-identifiability under conventional surviving-fraction observation, while the LQ-L and Gupta models exhibit observation-dependent identifiability conditional on dose-range coverage and marker-panel richness. These findings suggest that increasing radiobiological complexity progressively exposes the limitations of fixed-parameter mechanistic descriptions under partial observability. As a constructive response, we propose, as a hypothesis, that adaptive latent-state inference frameworks operating over a coupled multi-layer organizational state may provide a complementary operational paradigm for radiobiology under uncertainty.

Abstract: The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) threatens the efficacy of this last-line antibiotic. The GraSR two component system is frequently mutated in VISA strains. Here, we demonstrate that the GraS(T136I) point mutation, identified in the clinical VISA isolate XN108, is a key determinant of reduced vancomycin susceptibility. Introducing this mutation into the susceptible strain Newman increased the vancomycin MIC from 1.5 to 4 mg/L, while its reversion in XN108 decreased the MIC from 12 to 8 mg/L. The mutation conferred common phenotypes, including thickened cell wall, decreased autolysis, and reduced cell surface negative charge via upregulation of the dltABCD operon and mprF. Notably, GraS(T136I) mutation also upregulated virulence genes (efb, hlb, sbi, hld) and enhanced hemolytic activity. Interestingly, despite this hypervirulence profile, the mutant showed impaired long term survival within macrophages. Our study reveals that a single GraSR mutation can co-regulate vancomycin resistance and virulence, offering new insights into the adaptation of S. aureus to antibiotic pressure.

Abstract: Background: Chronic low back pain (CLBP) is the leading cause of years lived with disability globally, affecting over 600 million individuals. Intervertebral disc degeneration (IVDD) is a principal structural contributor, yet conventional treatments, including pharmacotherapy, physical therapy, and surgical intervention, do not reverse the underlying degenerative pathology. Regenerative medicine has introduced a spectrum of biological therapies, ranging from cell-based mesenchymal stromal cells (MSCs) transplantation to cell-free modalities, including platelet-rich plasma (PRP), platelet lysate, MSC-derived extracellular vesicles (EVs), and MSC-derived secretomes. However, these approaches have largely been studied in isolation, without a unified framework to compare their respective advantages and limitations in CLBP secondary to IVDD. Accordingly, this narrative review aims to provide an integrated and comparative evaluation of these regenerative strategies within a single translational and clinical context. Methods: For this narrative review, PubMed, Scopus, and Web of Science were searched from January 2000 to January 2026 using terms combining regenerative modalities with intervertebral disc degeneration, and chronic low back pain. Randomized controlled trials (RCTs), prospective cohort studies, systematic reviews, and preclinical studies with translational relevance were included. Results: Intradiscal MSC therapy has demonstrated safety across multiple phase I–III trials, but two recent landmark RCTs (RESPINE and the Mesoblast phase III trial) failed to meet primary efficacy endpoints, highlighting the gap between preclinical promise and clinical outcomes. PRP has the largest clinical evidence base, with level II evidence supporting short- to medium-term pain relief for discogenic pain, although standardization remains a critical barrier. Platelet lysate, MSC-derived EVs, and MSC-derived secretomes show compelling preclinical data, including extracellular matrix restoration, anti-inflammatory modulation, and attenuation of nucleus pulposus cell apoptosis, but remain at early translational stages for spinal applications, with no completed RCTs. The hostile disc microenvironment (avascular, hypoxic, acidic, and nutrient-poor) poses unique challenges for all regenerative modalities, differing fundamentally from other musculoskeletal applications. Conclusions: The studies included in this narrative review suggest that no single regenerative modality has yet shown consistent and unequivocal efficacy for CLBP secondary to IVDD across clinical trials. Cell-free approaches offer manufacturing, scalability, and safety advantages over cell-based therapies, but lack clinical validation. Future progress requires standardized preparation protocols, disc-specific delivery systems, patient phenotyping strategies, and rigorously designed comparative clinical trials. This narrative review provides a framework for researchers and clinicians to evaluate these therapies in context rather than isolation.

Abstract: Avian metapneumovirus (aMPV) represents a serious respiratory pathogen of poultry and is associated with considerable economic losses in breeder flocks worldwide. Although horizontal transmission is well established, the contribution of vertical transmission remains poorly understood, especially under field conditions in chickens. In this study, we aimed to assess whether aMPV could be transmitted vertically in unvaccinated broiler breeder flocks that tested positive by PCR in Egypt. Therefore, 10 broiler breeder flocks (≥30 weeks) from seven Egyptian governorates were screened for aMPV subtypes A and B. From each flock, tracheal swabs were collected from breeder hens, along with 20 fertile eggs and 20 newly hatched chicks. All samples, including tracheal swabs, chicken tissues (trachea, lungs, reproductive tract, and spleen), eggshells, internal egg contents, and embryonic tissues were analyzed for aMPV RNA using subtype-specific RT-qPCR. All breeder flocks tested positive for aMPV subtype B, but not subtype A. No aMPV RNA was found in eggshells, internal egg contents, embryonic tissues, or tissues from newly hatched chicks. In conclusion, Despite PCR detection of aMPV in breeder hens, the absence of viral RNA in eggs and their progeny provides field evidence that vertical transmission of subtype B is unlikely to play a significant role in virus spread in commercial broiler breeder flocks. These results support horizontal transmission as the primary route of aMPV spread and highlight the need for further longitudinal and genomic studies to better elucidate aMPV transmission dynamics.

Abstract: Background: An estimated 28,900 deaths around the world in 2021 were attributed to unintentional CO poisoning. Following inhalation, CO binds to hemoglobin with an affinity 220–240 times greater than that of oxygen to form carboxyhemoglobin (COHb). While the constituents of CO exposure are known to determine CO uptake in the blood, much less is understood regarding individual variability of the response to a given CO stimulus. Thus, the purpose of this paper was to explore the relationship between hemoglobin mass (HbM, a proxy for blood hemoglobin content) and the magnitude of the ensuing carboxyhemoglobinemia. Methods: This is a theoretical work based solely on considerations and published data. Discussion: Currently considered the gold standard for HbM assessment, the CO-rebreathing technique relies on the dilution principle i.e. the lower the HbM values the higher the ΔCOHb following a standardized CO bolus administration or an outdoors exposure. Accordingly, previously published prediction equations with HbM and ΔCOHb as the predictor and outcome variables, respectively, are reviewed with particular reference to the (confounding) factor of pulmonary ventilation. As far as treatment to CO poisoning is concerned, dynamic exercise emerges as a supplement to oxygen therapy to facilitate CO removal from human body. Screening procedures aiming to identify individuals susceptible to CO poisoning should henceforth include HbM assessments.

Abstract: Coronary heart disease (CHD) is a leading cause of morbidity and mortality, driven by metabolic remodeling, vascular inflammation, and perivascular adipose tissue (PVAT) dysfunction. We integrated bulk transcriptomic datasets to develop a machine learning–based diagnostic model, evaluated 113 algorithms, and identified a seven-gene signature (PYGL, PTGS2, PFKFB3, MMP9, CYP1B1, CXCR1, ABCB1) with robust predictive performance. Single-cell RNA sequencing of coronary PVAT revealed substantial cellular heterogeneity and prioritized PFKFB3 as a hub linking glycolytic activity to NF-κB regulon activity. Macrophage-centered communication via SPP1, MIF, and other pathways was enhanced in disease conditions. Virtual knockout of PFKFB3 induced transcriptional changes enriched in immune activation, phagocytosis, and oxidative stress, while molecular dynamics simulations indicated stable salidroside binding within PFKFB3. Together, these analyses provide a multi-layered framework connecting glycolytic remodeling, inflammatory transcriptional activity, and intercellular signaling in CHD. The findings support PFKFB3 as a potential biomarker and mechanistic hub, and suggest that salidroside may modulate its activity. This study offers an integrative computational foundation for future experimental validation and mechanistic exploration of PVAT dysfunction in CHD.

Abstract: Retroviruses induce immunosuppression in their infected hosts. This phenomenon is well described for the immunodeficiency viruses, with human immunodeficiency virus type 1 (HIV-1) representing the best-studied example, but it also occurs in other retroviral infec-tions. Immunosuppressive properties were first characterized in murine leukemia viruses (MuLV). Additional well-studied examples include feline leukemia virus (FeLV) and koala retrovirus (KoRV). Investigations into the mechanisms underlying retrovirus-induced immunosuppression revealed that not only inactivated viral particles, but also their purified transmembrane envelope (TM) proteins exhibit immunosuppressive activity. However, in certain retroviral infections, additional viral proteins contribute to the immunosup-pression in vivo. Within the TM proteins, a highly conserved region, designated the immunosuppressive (isu) domain, was identified. Synthetic peptides corresponding to this domain suppress a wide range of in vitro immune responses by regulating Ras-Raf-MEK-MAPK and PI3K-AKT-mTOR pathways. They modulate cytokine release and alter gene expression in immune cells, mirroring the activity of the corresponding TM protein. Mutations in the sequence abrogate the effect. Numerous TM proteins have demonstrated immunosuppressive activity in vivo, in a tumor rejection model, and muta-tions within the isu domain also abrogate this function. These studies have important implications for reproduction, particularly through the immunosuppressive syncytins in the placenta; for tumor development, where similar mechanisms may protect cancer cells from the host immune system; as well as for vaccine development and xenotransplantation. Notably, immunization with TM proteins carrying mutations in the isu domain elic-its stronger immune responses compared with the wild-type proteins. Finally, the potential of retroviral TM proteins to protect xenotransplants from immune rejection will be discussed.

Abstract: Osmosis has lacked a satisfactory mechanistic explanation for over a century. Pollack and colleagues showed that hydrophilic surfaces release protons into adjacent water, and that the resulting pH and potential gradients across a membrane can account for the direction of osmotic flow. That account, however, is incomplete: a pure proton flux across a membrane would acidify one side indefinitely, and would not by itself constitute the transfer of water. The missing step is redox. Osmosis is the same chemistry as in the demonstrated acid–base battery with oxygen electrodes, in which water is broken down on the alkaline side (4 OH⁻ → O₂ + 2 H₂O + 4 e⁻), electrons cross to the acidic side, and water is reconstituted there (4 H⁺ + O₂ + 4 e⁻ → 2 H₂O). Dioxygen is consumed and produced in the cycle and is therefore required. This redox interpretation has a direct anatomical consequence: any biological system sustaining osmosis at scale must continuously supply dioxygen to the acidic side. The loop of Henle in the mammalian kidney is shown to be precisely such a recirculation system, with the vasa recta returning dioxygen released in the descending limb back to where it is needed. The anatomy of the nephron is what the redox mechanism predicts.

Abstract: The extant body of evidence pertaining to the acceptance of cultured meat in Sub-Saharan Africa remains limited. The present study examined the determinants of intention to adopt cultured meat among a sample of young, urban, meat-eating adults in Chad (n = 290, from a recruited sample of 304). This was achieved using a cross-sectional online survey. Hierarchical OLS with HC3-robust inference was estimated across five hypothesis blocks, complemented by dominance analysis, binary-outcome sensitivity, and exploratory triangulation (Bayesian, elastic net, conditional random forest). Approximately half of the respondents expressed a willingness to try cultured meat (52.4%). The final model accounted for 30.6% of the intention variance (adjusted R² = 0.188). Following Holm's correction for multiple comparisons, the conventional-meat and knowledge blocks did not demonstrate a significant difference. The product beliefs (ΔR² = 0.056, p = 0.022), affective-risk barriers (ΔR² = 0.086, p = 0.004), and value-fit (ΔR² = 0.039, p = 0.048) were found to be significant, with affective-risk ranking first in dominance analysis (22.8%). Binary sensitivity analysis demonstrated acceptable discrimination (AUC = 0.744), although no block remained significant after correction. Exploratory analyses yielded convergent results, including notably robust Bayesian support for excluding the conventional-meat block (BF01 = 1.66 × 10^12). Sensitivity power analysis confirmed adequate power (≥ 0.80) for the significant blocks, but indicated that the conventional-meat non-significance may partly reflect limited power (estimated power = 0.47). Cultured-meat adoption intention was more strongly associated with affective-risk and value-fit appraisals than with conventional meat-purchase priorities. This suggests that acceptance strategies should prioritise risk reduction, trust-building, and perceived value. Findings should be interpreted as applying to a digitally connected, young, urban, meat-eating, predominantly tertiary-educated early-adopter-like segment (90.5% with university-level education; 72.7% residing in cities of more than 500,000 inhabitants), rather than to the general Chadian population.

Abstract: Microplastics (MPs) are widespread pollutants in aquatic environments, but their impacts throughout the life cycle remains of organisms are still not well understood. This systematic review integrates recent experimental results on the developmental, physiological, and neurobehavioral effects of MPs exposure on zebrafish (Danio rerio), a popular model organism for ecotoxicology research. A PRISMA-guided search using Web of Science (WoS) and Scopus as databases generated 371 articles, which was screened to 60 eligible articles. The collated results showed that MP toxicity strongly related to concentration, size, and extent of weathering or aging at various life stages of zebrafish. For developmental toxicity, a concentration-dependent yielded peer-reviewed publications assessing specific MPs properties, such as polymer identity, size, concentration, shape, and aging status. At various life stages, the toxicity of MPs was most affected by concentration, size, and aging. The developmental toxicity showed a concentration-dependent decrease in the rate of hatching, growth inhibition, and cardiac dysfunction, while, an increase in malformations, especially at concentrations of ≥100 µg/L or ≥10 mg/L has been reported. Non-monotonic and threshold effects have also been observed, the complexity of particle-based versus mass-based concentrations. Weathered and photo-aged MPs were found to exhibit higher embryotoxicity and neurodevelopmental toxicity, including changes in gene expression of neurons, decreased integrity of motor neurons, and impaired retinal development, compared with virgin MPs. Furthermore, physiological endpoints showed that oxidative imbalance was a key mechanistic process, which included changes in the activity of antioxidant enzymes (SOD, CAT, GPx), lipid peroxidation, inflammation, and disruption of tight junctions. Chronic MP exposures caused changes in the gut microbiota, hepatic metabolism, endocrine disruption, reproductive damage, thyroid function disruption, and genotoxicity in zebrafish. Neurobehavioral alterations, such as changes in locomotor activity, anxiety response, neurotransmitter homeostasis, and acetylcholinesterase function, occurred in both larvae and adults, with a potentiation effect in aged MP exposure. Previous, experimental data have also shown that zebrafish are very sensitive to MPs exposure in various biological systems, with toxicity being a function of physicochemical properties and exposure conditions. Finally, this review found major limitations for inter-study comparisons because of inconsistencies and differences in methodology related to MP concentration, simulation of MP aging, and MP dose measurements.

Abstract: We report a cross-station replication of endogenous circadian rhythms in plant bioelectric voltage, recorded continuously for 42 days at three independent sensor stations within a public science exhibition (Phänomena, Dietikon, Switzerland; March–April 2026). Three primrose (Primula vulgaris) stations were equipped with custom Biolingo bioelectric sensors (ESP32 + AD8232) and recorded autonomously through approximately 21,000 visitor interactions. We extracted DC-invariant spectral features from 5–10 second volt-age windows (n = 78,431 quality-filtered files) and fitted two-stage cosinor models with bootstrap 95% confidence intervals. All three stations show a robust 24-hour rhythm in the 1–5 Hz band power (bp1–5), with peak-to-trough amplitudes between 0.35× and 1.19× of mesor (R²med 0.72–0.87). Acrophase varies across stations from 05:00 to 11:00 local time. Critically, the rhythm survives an overnight-only restriction (18:00–09:00, no visitors) at all three stations, ruling out visitor presence as the rhythm driver. The most visi-tor-intensive station (faces of museum visitors triggering an emotion-recognition instal-lation) additionally shows a sharp daytime amplitude collapse coincident with exhibition opening at 09:00, consistent with the cardiovascular-mechanosensory coupling demon-strated in a companion study [20]. We argue that bp1–5—the spectral band most directly related to plant action-potential activity—carries an endogenous circadian signal in Primula vulgaris, and that this signal is modulated by sustained nearby human cardio-vascular activity in a manner consistent with frequency-selective mechanosensory transduction. From a biomimetic perspective, this demonstrates that the plant’s evolved bioelectric sensing apparatus can be leveraged as a live ambient biosensor for nearby human activity, complementing the more common biomimetic approach of replicating plant sensing in synthetic devices.

Abstract: Adulteration of beef (Bos indicus) with buffalo meat (Bubalus bubalis) is a common form of food fraud with economic and religious implications, but quantitatively detecting its presence in ground beef products is difficult. Ten replicates of each of six binary mixtures (100:0 to 0:100 % w/w) of ground beef and buffalo meat were characterized using untargeted ¹H NMR metabolomics (43 metabolites after QC filtering), physicochemical measurements (pH, CIE L*a*b* color, water activity, and electronic nose), and proximate composition. Fifteen pairwise OPLS-DA models and a 1000-fold permutation test were performed for discrimination and biomarker identification. PCA explained 54.2% of the total variance, and the adulteration groups separated along the PC1 axis. All OPLS-DA models were statistically valid (R²Y = 0.738–0.981; Q² = 0.532–0.961; pQ² < 0.001), with no evidence of overfitting. Three metabolites met all three criteria (VIP > 1.0, FDR < 0.05, < FC > 2 or < 0.5) and had AUC = 1.00 in the internal data set: betaine (−82.6% in buffalo vs. beef), glycerol (+154.7%), and malonate (+656%). No individual biomarker exceeded the multi-criterion threshold at buffalo substitution levels less than10%. The selection of external discovery-phase candidates for beef authentication using NMR includes betaine, glycerol, and malonate.

Abstract: Racing homing pigeons (Columba livia) have been selectively bred for centuries for superior flight capacity. Yet, the quantitative structure of flight performance traits and the extent to which sex influences these parameters remain poorly characterized, par-ticularly in Turkish populations. This study aimed to evaluate flight performance in racing pigeons raised in the South Marmara region of Turkiye using three key kine-matic traits (flight duration, speed, and distance) and to explore the multivariate structure and individual variation of these parameters through an integrative machine learning framework. Data were compiled from 166 individually registered pigeons (77 females, 89 males), totaling 781 race records used for pattern analysis. A composite Flight Performance Score (FPS) was constructed using min–max normalized compo-nent variables, and its internal consistency was assessed via Cronbach's alpha and principal component analysis. Univariate comparisons revealed no statistically signif-icant sex-related differences in any of the three flight parameters (P > 0.05 for all traits). Principal component analysis confirmed substantial overlap between male and female individuals in multivariate trait space, and Random Forest classification failed to dis-criminate between sexes above chance level (accuracy = 0.490; ROC-AUC = 0.500), col-lectively indicating that sex is not a dominant determinant of flight performance in this population. Internal consistency analysis revealed that flight duration, speed, and dis-tance are functionally independent dimensions (Cronbach's α = 0.135; r = −0.749 be-tween duration and speed), with their variance structure being effectively two-dimensional (PC1: 60.1%; PC2: 39.7%), supporting the equal-weighting scheme applied in FPS construction. Pattern analysis of race records identified four biologically distinct flight performance profiles, characterized by differential trade-offs among flight duration, speed, and distance, suggesting that individual-level performance strategy, rather than sex, is the primary axis of variation in this dataset. These findings challenge common breeder assumptions about sex-based differences in performance and highlight the multidimensional, individual-specific nature of flight performance in racing pigeons.

Abstract: NK cells are crucial for innate immunity and rapidly target abnormal cells through ligand-receptor signaling, without prior sensitization. Vitamin C is a bioenhancer of NK cells; however, its susceptibility to oxidation limits its efficacy in NK cell activation. This study evaluated the efficacy of Aptamin C, a stable conjugate of vitamin C and an aptamer, in enhancing NK cell activation. In in vivo study, 109 participants were ad-ministered either Aptamin C (36.057 mg/day) or placebo for 4 weeks. The results showed significant increases in NK cell cytotoxicity after 2 and 4 weeks in the Aptamin C group. Additionally, cytokine and granule levels associated with NK cell activity peaked in the serum 4 weeks after Aptamin C intake. In in vitro study, NK-92 cells treated with Aptamin C were compared to NK-92 cells treated with vitamin C. The results showed enhanced proliferation, survival, cytotoxicity, and cytotoxic granule production in NK-92 cells treated with Aptamin C compared to cells treated with vitamin C. These findings indicated that Aptamin C effectively promoted NK cell ac-tivation, suggesting its potential as an immunomodulatory supplement in NK cell therapy.

Abstract: The number of human genetic variants cataloged in dbSNP has plateaued since 2021, with over ~1.1 billion variants housed. Since the human pangenome reference has enabled the precise identification of even structurally complex variants, capturing the entire spectrum of human genetic variants is almost achievable. However, the clinical impacts of most genetic variants still remain elusive. This is due to limitations in genome-wide association study (GWAS), the standard framework for variant interpretation, which relies solely on statistical assumptions. GWAS cannot interpret low‐frequency alleles and capture molecular interactions between variants, hindering its ability to explain complex traits and diseases. Recently, large language models (LLMs) enabled accurate inference of human genetic variants’ pathogenicity even without requiring a large sample size or prior annotations by modeling the biological principles encoded within the genome. For instance, Evolutionary Scale Modeling (ESM1b) successfully predicted missense variants in ClinVar, achieving an auROC of up to 0.905. In addition, Evo 2 classified non-coding pathogenic variants in ClinVar with an auROC of 0.987 for single nucleotide variants (SNVs) and 0.971 for non-SNVs. These results suggest that although yet limited to pathogenicity prediction, integrating multiomic and clinical data through LLM will enable the complete clinical interpretation of human genetic variants.