Search Results (356)

Background: Biological aging influences cancer outcomes, but its changes during chemotherapy and impact on chemotoxicity in colorectal cancer (CRC) remain underinvestigated. We examined (1) trajectories of biological aging (using Levine Phenotypic Age) during six months of chemotherapy, (2) sociodemographic and clinical risk factors for biological aging, and (3) links between biological aging and chemotoxicity. Methods: Using data from electronic health records (2013–2019) from 1129 adult CRC patients, we computed biological aging (raw Levine Phenotypic Age and its age acceleration [Levine Phenotypic Age–chronological age]) from routine blood tests (e.g., complete blood counts, hepatorenal/inflammatory markers). Chemotoxicity was identified primarily via International Classification of Diseases (ICD-9 and -10) codes. Results: Chemotherapy accelerated biological aging over time. Biological aging at baseline and changes over time predicted chemotoxicity. However, changes in biological aging over time showed stronger associations than baseline biological aging. Advanced cancer stages, higher comorbidity burden, and socioeconomic disadvantage (especially area-level deprivation) were associated with accelerated biological aging at baseline and over time. Biological aging occurred across both young and older adults. Conclusions: Levine Phenotypic Age, computed from routine blood tests in EHRs, offers a feasible clinical tool for aging-related chemotoxicity risk stratification. Validation in diverse cohorts and the development of predictive models are needed. Full article

Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry. Full article

Background: Bimekizumab, secukinumab, and ixekizumab are IL-17-targeting biologics approved for the treatment of moderate-to-severe plaque psoriasis. While secukinumab and ixekizumab selectively inhibit IL-17A, bimekizumab targets both IL-17A and IL-17F, potentially providing greater anti-inflammatory efficacy. This study aimed to compare the real-world effectiveness, safety, and tolerability of these agents in a Polish dermatology center between 2019 and 2024. Methods: We conducted a retrospective analysis of 98 patients meeting at least one of the following criteria: PASI ≥ 10, BSA ≥ 10, DLQI ≥ 10, or involvement of special areas with inadequate response or contraindications to ≥2 systemic therapies. Patients with prior exposure only to IL-17 inhibitors were excluded. PASI, BSA, and DLQI scores were recorded at baseline, week 4, and week 12. Due to differences in dosing schedules, outcomes were aligned using standardized timepoints and exponential modeling of continuous response trajectories. Mixed-effects ANOVA was used to assess the influence of baseline factors (age, BMI, PsA status) on treatment outcomes. Adverse events were documented at each monthly follow-up visit. Results: Bimekizumab showed the greatest effect size for PASI reduction (Hedges’ g = 3.662), followed by secukinumab (2.813) and ixekizumab (1.986). Exponential modeling revealed a steeper response trajectory with bimekizumab (intercept = 0.289), suggesting a more rapid PASI improvement. The efficacy of bimekizumab was particularly notable in patients who were previously treated with IL-23 inhibitors. All three agents demonstrated favorable safety profiles, with no serious adverse events or discontinuations. The most frequent adverse events were mild and included upper respiratory tract infections and oral candidiasis. Conclusions: This real-world analysis confirmed that IL-17 inhibitors effectively improved PASI, BSA, and DLQI scores in moderate-to-severe psoriasis. Bimekizumab demonstrated the most rapid early improvements and a higher modeled likelihood of complete clearance, without significant differences at week 12. All agents were well tolerated, underscoring the need for further individualized, large-scale studies. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder primarily characterized by memory loss, cognitive decline, and structural brain atrophy. Substantial sex differences have been observed in its incidence, clinical trajectory, and response to treatment. Women are disproportionately affected, exhibiting faster progression and more severe cognitive impairment. Exercise has emerged as a promising non-pharmacological intervention to mitigate AD-related decline, yet growing evidence reveals that its benefits vary by sex. This review synthesizes current findings from human and animal studies, focusing on how exercise impacts AD differently in males and females. In women, exercise is more strongly associated with improvements in cognitive function, neurotrophic support, and emotional regulation. In men, benefits tend to involve structural preservation and oxidative adaptations. Underlying mechanisms include differential hormonal profiles, inflammatory responses, and neuroplastic signaling pathways. These findings underscore the need to consider sex as a biological variable in AD research. Developing sex-specific exercise strategies may enhance therapeutic outcomes and support more individualized approaches in AD prevention and care. Full article

Although cranial growth has been extensively explored, forensic and biological anthropology lack a formal incorporation of how cranial growth processes impact the adult phenotype and downstream biological profile estimations. Objectives: This research uses an ontogenetic framework to identify when interlandmark distances (ILDs) stabilize during growth to reach adult levels of variation and to evaluate patterns of cranial sexual size dimorphism. Methods: Multivariate adaptive regression splines (MARS) were conducted on standardized cranial ILDs for 595 individuals from the Subadult Virtual Anthropology Database (SVAD) and the Forensic Data Bank (FDB) aged between birth and 25 years. Cross-Validated R-squared (CVRSq) values evaluated ILD variation explained by age while knot placements identified meaningful changes in ILD growth trajectories. Results: Results reveal the ages at which males and females reach craniometric maturity across splanchnocranium, neurocranium, basicranium and cross-regional ILDs. Changes in growth patterns observed here largely align with growth milestones of integrated soft tissue and skeletal structures as well as developmental milestones like puberty. Conclusions: Our findings highlight the variability in growth by sex and cranial region and move forensic anthropologists towards recognizing cranial growth as a mosaic, continuous process with overlap between subadults and adults rather than consistently approaching subadult and adult research separately. Full article

Metformin, a long-established antidiabetic agent, is undergoing a renaissance as a prototype gerotherapeutic and immunometabolic oncology adjuvant. Mechanistic advances reveal that metformin modulates an integrated network of metabolic, immunological, microbiome-mediated, and epigenetic pathways that impact the hallmarks of aging and cancer biology. Clinical data now demonstrate its ability to reduce cancer incidence, enhance immunotherapy outcomes, delay multimorbidity, and reverse biological age markers. Landmark trials such as UKPDS, CAMERA, and the ongoing TAME study illustrate its broad clinical impact on metabolic health, cardiovascular risk, and age-related disease trajectories. In oncology, trials such as MA.32 and METTEN evaluate its influence on progression-free survival and tumor response, highlighting its evolving role in cancer therapy. This review critically synthesizes the molecular underpinnings of metformin’s polypharmacology, examines results from pivotal clinical trials, and compares its effectiveness with emerging gerotherapeutics and senolytics. We explore future directions, including optimized dosing, biomarker-driven personalization, rational combination therapies, and regulatory pathways, to expand indications for aging and oncology. Metformin stands poised to play a pivotal role in precision strategies that target the shared roots of aging and cancer, offering scalable global benefits across health systems. Full article

Chrysomya megacephala, as one of the common blowflies, displays biological characteristics, such as ovoviviparity and carrion-feeding adaptation. Thus, this species is generally considered of significant ecological, medical, and forensic importance. However, without a high-quality pseudo-chromosome genome for C. megacephala, elucidating its evolutionary trajectory proved difficult. Herein, we assembled and analyzed a high-quality chromosome-level genome assembly of the C. megacephala, combined with PacBio HiFi long reads, Hi-C data, and Illumina reads. The pseudo-chromosomes assembly of C. megacephala spans 629.44 Mb, with 97.05% anchored to five chromosomes. Final assembly includes 1056 contigs (N50 = 1.68 Mb), and 97 scaffolds (N50 = 121.37 Mb), achieving 98.90% BUSCO completeness (n = 1367). Gene annotation predicted 17,071 protein-coding genes (95.60% BUSCO completeness), while repeat masking identified 244.26 Mb (38.82%) as repetitive elements. Additionally, 3740 non-coding RNAs were characterized. Gene family analyses resulted in 10,579 gene families, containing 151 gene families that experienced rapid evolution. Comparative genomic analyses showed that the expanded genes are related to reproduction and necrophagous habits. In addition, we annotated the gene family P450s, CCEs, IRs, GRs, and ORs, all of which represent remarkable expansion, playing a crucial role in the mechanism of locating the hosts for forensic insects. Our research establishes a high-quality genome sequence to facilitate subsequent molecular investigations into significant species within forensic entomology. Full article

Accurate estimation of aboveground biomass (AGB) in tree–shrub communities is critical for quantifying forest ecosystem productivity and carbon sequestration potential. Although generalized allometric equations offer expediency in natural forest AGB estimation, their neglect of interspecific variability introduces methodological pitfalls. Precise AGB prediction necessitates resolving two biological constraints: phylogenetic conservation of allometric coefficients and ontogenetic regulation of scaling relationships. This study establishes an integrated framework combining the following: (1) phylogenetic signal detection (Blomberg’s K/Pagel’s λ) across 157 species’ allometric equations, revealing weak but significant evolutionary constraints (λ = 0.1249, p = 0.0027; K ≈ 0, p = 0.621); (2) hierarchical error decomposition of 9105 stems in a Mt. Wuyishan forest dynamics plot (15 species), identifying family-level error stratification (e.g., Theaceae vs. Myrtaceae, Δerror > 25%); (3) ontogenetic trajectory analysis of Castanopsis eyrei between Mt. Wuyishan and Mt. Huangshan, demonstrating significant biomass deviations in small trees (5–15 cm DBH, p < 0.05). Key findings resolve the following hypotheses: (1) absence of strong phylogenetic signals validates generalized models for phylogenetically diverse communities; (2) ontogenetic regulation dominates error magnitude, particularly in early developmental stages; (3) differential modeling is recommended: species-specific equations for pure forests/seedlings vs. generalized equations for mixed mature forests. This work establishes an error hierarchy: ontogeny > taxonomy > phylogeny, providing a mechanistic basis for optimizing forest carbon stock assessments. Full article

Star sensors, as the most precise attitude measurement devices currently available, play a crucial role in spacecraft attitude estimation. However, traditional frame-based cameras tend to suffer from target blur and loss under high-dynamic maneuvers, which severely limit the applicability of conventional star sensors in complex space environments. In contrast, event cameras—drawing inspiration from biological vision—can capture brightness changes at ultrahigh speeds and output a series of asynchronous events, thereby demonstrating enormous potential for space detection applications. Based on this, this paper proposes an event data extraction method for weak, high-dynamic space targets to enhance the performance of event cameras in detecting space targets under high-dynamic maneuvers. In the target denoising phase, we fully consider the characteristics of space targets’ motion trajectories and optimize a classical spatiotemporal correlation filter, thereby significantly improving the signal-to-noise ratio for weak targets. During the target extraction stage, we introduce the DBSCAN clustering algorithm to achieve the subpixel-level extraction of target centroids. Moreover, to address issues of target trajectory distortion and data discontinuity in certain ultrahigh-dynamic scenarios, we construct a camera motion model based on real-time motion data from an inertial measurement unit (IMU) and utilize it to effectively compensate for and correct the target’s trajectory. Finally, a ground-based simulation system is established to validate the applicability and superior performance of the proposed method in real-world scenarios. Full article

Consciousness remains one of the most critical yet least understood functions of the brain, not only in humans but also in certain highly organized animal species. In this review, we propose treating consciousness as an emergent, goal-directed informational system organized by the subjective “self” as an active system-forming factor. We present an integrative theoretical–systems framework in which subjectivity functions as system-forming factor of consciousness (SFF) throughout biological evolution. Beginning with proto-conscious invertebrates, we trace progressive elaborations of working and long-term memory, the refinement of behavioral programs, and the emergence of an internal arbiter capable of resolving competing drives. In endothermic vertebrates, subjectivity acquires distinct functional features—sensory filtering, causal reasoning, and adaptive arbitration—underpinned by increasingly complex neural architectures. This evolutionary trajectory culminates in humans, where subjectivity attains its highest level of organization through culturally mediated networks. Although the framework does not assume any specific neural substrate, it provides a testable roadmap linking evolutionary biology, information theory, and quantitative modeling. By clarifying why consciousness arose and how subjectivity shapes complex networks, this perspective also lays the groundwork for exploring possible nonbiological extensions of subjectivity. Full article

Postbiotics are defined as non-viable metabolites or compounds produced by probiotic microorganisms with significant impact on human health. The growing interest in postbiotics is supported by numerous studies due to their additional benefits over probiotics that show positive outcomes for specific conditions, as well as their application as biopreservatives in the food industry. Their potential in functional foods and therapeutic applications is increasingly recognized as they exhibit stability, safety, and diverse biological activities. As for their most important biological roles, postbiotics have been shown to have effective anti-inflammatory, antimicrobial, antioxidant, and anticancer properties, in addition to reducing food allergies. The application of postbiotics in functional foods contributes to improving intestinal health and reducing the risk of foodborne diseases. The concept of postbiotics is relatively new in the food industry. They offer a promising alternative to conventional food preservatives due to their ability to inhibit pathogenic bacteria and extend shelf life. Considering the diversity of postbiotic compounds and their significant biological activities, this review presents and discusses the mechanisms of action and future trends in their application in the food industry and their impact on human health. Increasing research and development in the production and formulation of postbiotics will play a key role in the upward trajectory of the market. Full article

Dairy farm profitability in the European Union has become increasingly volatile following market deregulation, complicating farm operations and undermining food security amid geopolitical tensions. To address the need for a streamlined analytical tool, this study develops a simulation model of milk production profitability tailored to small, open economies, using Poland as a case study. The model defines a profitability coefficient as the ratio of sector-level milk revenues to feed costs and decomposes it into three dynamic components: production efficiency (milk yield per feed unit), the price spread between milk and feed, and the net effect of policy interventions on revenues and costs. Exogenous variables (milk prices, feed prices, and policy support indices) are projected under baseline, optimistic, and pessimistic scenarios, while endogenous variables (profitability, herd size, and yield) evolve recursively based on estimated lags reflecting biological and economic responses. Simulation results for 2023–2027 indicate that profitability trajectories hinge primarily on price spreads, with policy measures playing a stabilizing but secondary role. Optimistic scenarios yield significant increases in profitability, whereas pessimistic assumptions lead to significant declines. These findings highlight the need to balance key market drivers—such as the relationship between milk prices and feed costs—with appropriately designed support instruments for milk producers. The model provides policymakers with a tool to adjust interventions so that support instruments are effective but do not lead to excessive reliance on public assistance. Full article

Seed germination is the initial step in a plant’s life cycle; it is precisely regulated by many factors at the molecular and biological levels. Reversible protein phosphorylation, which is regulated by protein kinases and protein phosphatases, plays a key role in hormone signal transduction, energy metabolism, stress response, and plant growth and development, including seed germination. This review provides a comprehensive elucidation of the coordinated regulatory mechanisms mediated by kinases and phosphatases during seed germination, with particular emphasis on their dynamic interplay and reciprocal modulation within biological signaling networks. Through the systematic integration of current research findings, we mechanistically dissect the sophisticated phosphorylation–dephosphorylation circuitry that governs metabolic activation, hormonal signaling transduction, and cellular homeostasis in germinating seeds. Furthermore, we propose a novel conceptual framework that delineates the spatiotemporal cooperation between these opposing enzymatic activities in regulating dormancy release and developmental transitions. The current challenges in the field of seed germination research are critically examined, and potential future investigative trajectories are outlined, aiming to establish a robust theoretical framework for elucidating the molecular mechanisms underlying seed dormancy regulation, as well as translating these findings into innovative agricultural production practices. Full article

Human migration has driven transformative shifts in agricultural systems by reshaping how communities relate biologically and culturally to the land. Migration demands the reconfiguration of preexisting human–environment relationships, a process central to agricultural history. Understanding adaptation strategies is essential for land studies as it highlights the impact of cultural persistence on agricultural practices and the potential challenges in integrating migrant rural knowledge with local ecological systems. In the late 19th century, a significant migration wave occurred from the Veneto region in northeastern Italy to southern Brazil, significantly impacting Brazilian agri-food production. This study investigates the biocultural adaptation strategies employed by the first Veneto communities in their new Brazilian environment. Data for this research were derived from the letters sent by Veneto migrants from Brazil in the initial wave of Italian migration (1877–1894). Utilising Critical Discourse Analysis and Sentiment Analysis of migrants’ letters, we explored the Veneto settlers’ perceptions of the Brazilian landscape, agri-food production practices, and culinary traditions. Our findings show that the Brazilian environment was perceived as predominantly negative, particularly in the wilderness areas. The initial Venetian migrant settlement exhibited no genuine biocultural adaptation strategies. Instead, they deliberately resisted Brazilian influences, striving to reproduce Veneto’s agricultural model verbatim in their new surroundings. The study also opens a new trajectory in historical ethnobiology, thus suggesting new potential applications of the analysis of migrants’ letters. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of upper and lower motor neurons. One of its major genetic causes is C9ORF72, where mutations lead to hexanucleotide repeat expansions in the C9ORF72 gene. These expansions drive disease progression through mechanisms, including the formation of toxic RNAs and the accumulation of damaged proteins such as dipeptide repeats (DPRs). This review highlights these pathogenic mechanisms, focusing on RNA foci formation and the accumulation of toxic DPRs, which contribute to neuronal damage. It also discusses promising targeted therapies, including small molecules and biological drugs, designed to counteract these specific molecular events. Small molecules such as G-quadruplex stabilizers, proteasome and autophagy modulators, and RNase-targeting chimeras show potential in reducing RNA foci and DPR accumulation. Furthermore, targeting enzymes involved in repeat-associated non-AUG (RAN) translation and nucleocytoplasmic transport, which are crucial for disease pathogenesis, opens new therapeutic avenues. Even some anti-viral drugs show encouraging results in preclinical studies. Biological drugs, such as antisense oligonucleotides and gene-editing technologies like CRISPR-Cas, were explored for their potential to specifically target C9ORF72 mutations and modify the disease’s molecular foundations. While preclinical and early clinical data show promise, challenges remain in optimizing delivery methods, ensuring long-term safety, and improving efficacy. This review concludes by emphasizing the importance of continued research and the potential for these therapies to alter the disease trajectory and improve patient outcomes. Full article