Abstract: The microRNA-548 (miR-548) family is a large primate-specific microRNA group characterized by extensive sequence diversification, but the relationship between sequence evolution and disease-associated organization remains unclear. We integrated 81 curated mature miR-548 sequences with 134 literature-derived disease-association records and applied sequence alignment, entropy profiling, maximum-likelihood phylogenetics, Jaccard-based disease-profile clustering, network and intersection analyses, and sequence-function matrix correlation. Disease associations spanned 54 curated identifiers across cancer, infectious, inflammatory, and autoimmune categories and were broadly distributed across the phylogeny. After exact mature-sequence matching and collapse of three nomenclature aliases, the primary sequence-resolved analysis included 44 unique mature sequences. Mature-sequence distance showed no significant association with disease-profile distance (Spearman rho = -0.1103, permutation p = 0.1002; 946 pairwise comparisons; 5000 permutations). Restricting the analysis to experimentally supported associations yielded a comparable result (43 sequences; rho = -0.1150, p = 0.1008). These findings indicate that mature-sequence similarity is not a strong predictor of broad disease-association profile similarity within the miR-548 family and support disease-associated convergence across evolutionarily distributed family members.

Abstract: The aim of this paper is to demonstrate the feasibility of applying immunohistochemical interrogation of cleared embryos to reveal three-dimensional distribution of protein expression related to facial skeletal development while preserving anatomic context. Here we show the development of a collagen 3 facial bone precursor involved in the formation of the embryonic mandible. Within the tissue volume occupied by the collagen 3 mandible form, collagen 1 is expressed. The process is dependent on developmental stage. This event is demonstrated in the e15.5 mouse embryo. In the e11.5 mouse embryo, collagen 3 expression is demonstrated surrounding early vessels but there is no evidence of mandible formation at that stage. We show that this acquisition method allows analysis of collagen 1, collagen 3, and others in the same specimen while maintaining congruency of the data sets.

Abstract: Background: Cervical insufficiency is associated with second-trimester pregnancy loss and spon-taneous preterm birth. A three-step cervical cerclage technique has been im-plemented at our center for prophylactic and emergency indications. This study evalu-ated its feasibility and ma-ternal, obstetric, and neonatal outcomes in a real-world ter-tiary-care cohort. Methods: We con-ducted a retrospective, single-center observational study including 142 pregnancies managed with a three-step cervical cerclage technique between Janu-ary 2015 and March 2026. Women were clas-sified according to cerclage indication as prophylactic (n=80) or emergency (n=62). Pregnancy-level outcomes included gesta-tional latency, gestational age at delivery, preterm birth, preterm prem-ature rupture of membranes before 34 weeks, chorioamnionitis, gestational loss, mode of delivery, and maternal complications. Neonatal outcomes were analyzed at the individual newborn level. Birth weight, Apgar scores, neonatal intensive care unit admission, neonatal sur-vival, and low and very low birth weight were evaluated using newborn-level denom-inators. Multivariable linear and logistic regression models were used to assess the in-dependent associations of gestational duration and cerclage indication with birth weight, low birth weight, neonatal intensive care unit admission, preterm delivery, and preterm premature rupture of membranes. Results: Prophylactic cerclage was placed earlier than emergency cerclage (mean ges-tational age at placement, 15.28 \pm 2.64 vs. 20.14 \pm 3.33 weeks; p<0.001), and pre-procedure cervical length was greater in the prophylactic group (31.33 \pm 9.98 vs. 14.58 \pm 9.02 mm; p<0.001). Gestational latency was longer after prophylactic cerclage (mean, 20.48 \pm 6.30 vs. 14.34 \pm 6.39 weeks; p<0.001); however, ges-ta-tional age at delivery did not differ significantly between groups (median, 263.5 vs. 263.0 days; p=0.306). Preterm birth before 37 weeks occurred in 33.8% and 43.5% of prophylactic and emergency cases, respectively (p=0.296), whereas preterm birth be-fore 34 weeks occurred in 21.2% and 30.6% (p=0.244). Preterm premature rupture of membranes before 34 weeks occurred in 23.8% of prophylactic cases and 17.7% of emergency cases (p=0.415). Chorioamnionitis was diagnosed in 6 prophylactic cases (7.5%) and 10 emergency cases (16.1%; p=0.118). Cervical cleisis was performed more frequently in emergency cases (25.8% vs. 3.8%; p<0.001). Cesarean delivery rates were similar between groups (26.2% vs. 27.4%; p=0.873). Six pregnancies ended in gestation-al loss before 22 weeks, including three cases in each group. Among 140 newborns with available birth-weight data, mean birth weight was lower after emergency cerclage than after prophylactic cerclage (2485.8 ± 958.8 vs. 2786.1 ± 823.4 g; p=0.049). Low birth weight occurred in 45.0% and 26.3% of newborns, respec-tively (OR 2.30, 95% CI 1.13–4.69; p=0.021). However, after adjustment for gestational age at delivery, cerclage indication was not independently associated with birth weight (β = 22.67 g; p=0.825) or low birth weight (adjusted OR 1.13, 95% CI 0.40–3.16; p=0.824). Each additional gesta-tional day was associated with a 20.10-g increase in birth weight and lower odds of low birth weight. Among 135 newborns with available neonatal in-tensive care data, 20.0% required admis-sion, with no significant difference between emergency and prophylactic groups (23.3% vs. 17.3%; p=0.516). No postnatal neonatal deaths were recorded among newborns with available follow-up. Conclusions: The three-step cervical cerclage technique was feasible in both prophylac-tic and emergency settings. Despite earlier placement and longer post-procedural la-tency in the prophy-lactic group, gestational age at delivery, prematurity rates, preterm premature rupture of mem-branes, chorioamnionitis, and mode of delivery were broad-ly comparable between groups. Emergency cerclage required cervical cleisis more fre-quently, reflecting a more advanced cervical presentation. Although emergency cer-clage was associated with lower birth weight and more frequent low birth weight in unadjusted analyses, these associations were not independent of gestational age at de-livery. Gestational duration was the principal determinant of birth weight and neona-tal intensive care unit admission. These findings support the feasibility of the three-step technique in selected patients but do not establish its superiority over conventional cerclage tech-niques. Prospective comparative studies with standardized pregnan-cy-level and newborn-level follow-up are warranted.

Abstract: With 60 years of research, knowledge-based system has travelled a long journey from early small-scale rule-based programs to modern super-large-scale knowledge graphs. Several multithreading technical stages can be broadly categorized: early history of rule-based system, knowledge engineering, semantic network, semantic web, ontology engineering, knowledge graph, and recent advances driven by machine learning. In the past couple years, the whole area of artificial intelligence including knowledge-based system has been significantly influenced by large language models, which dramatically increases the understanding and utilization of knowledge by increasing to an extremely large scale. Considering the long-standing intrinsic problems of large language models such as hallucination and lack of explainability, the challenge of how to build reliable large-scale knowledge-based systems in an effective and economical way still exists. From the overview of the developing history, we can see a promising research direction of combining large language models with those traditional knowledge-based frameworks.

Abstract: Correlation-based criteria are often used to select transformations that improve linear association on a transformed scale. This paper studies a structural limitation of such criteria in general parametric transformation families. We show that Pearson correlation is locally insensitive to the affine component of any infinitesimal perturbation of a transformed variable: the local derivative depends only on the residual component after projection onto the span of the constant function and the current transformed variable. We call this phenomenon affine invisibility. It provides a general mechanism for weak local discrimination and, when low visibility persists over parameter regions, for weak identification under correlation-based selection. The theory is developed for general smooth transformation paths and specialized to log-polynomial transformation classes. The Box–Cox transformation is reinterpreted as a one-dimensional path in function space whose tangent directions are combinations of log-polynomial components. Analytical illustrations quantify scale-free local visibility for log-polynomial directions and along the Box–Cox path, providing a concrete instance of the broader geometric framework. The results suggest that correlation maximization should be accompanied by local-visibility and near-optimality diagnostics before selected transformation parameters are interpreted as well identified.

Abstract: As cities emerge as the primary drivers of global consumption-based emissions, the need for greenhouse gas (GHG) accounting methods that model multisectoral urban interactions has become paramount. In this context, consumption-based (CB) urban GHG emission inventories have arisen as a useful tool for political decision-makers. This systematic literature review was carried out across three databases, covering al-most 20 years of publications strictly related to the elaboration of CB GHG emission inventories, reaching a total of 100 publications. More than a third of the articles ex-plored Life-Cycle Assessment (LCA), 34% used Environmentally-Extended In-put-Output Analysis (EEIOA), with only 10% delving into hybrid methodologies. A case study comparison was performed for cities that applied different methodologies, in terms of carbon footprint. The strengths and weaknesses of each framework were also assessed. The results showed that both EEIOA and LCA were useful to model complex carbon flows and accounted for the majority of emissions associated to urban activity. EEIOA excelled for its operational simplicity and speed in the calculation of carbon footprint when input-output matrices are available, but it was not as suitable for policy-making. LCA required a larger volume of information and its processing was more time-consuming, but it was also capable of identifying hotspots. Hybrid approaches obtained carbon footprint results similar to those of EEIOA or LCA, while covering certain weaknesses of these standalone methodologies.

Abstract: This note extends our earlier existence and uniqueness results in AIMS Mathematics, 10 (2025), 19280–19299. Using sharper estimates for the squared Green’s functions and Rus’s fixed point theorem with the unweighted L2 metric, we obtain conditions for the classical problem with 1 < α ≤ 2 and the sequential problem with 1/4 < θ ≤ 1. A weighted L2 metric covers the full sequential range 0 < θ ≤ 1 and gives a less restrictive condition than the Banach condition based on the maximum L1 integral. We also compare the Rus and Banach conditions and illustrate the improvements with examples.

Abstract: The process by which fascial membranes emerge during fetal development remains incompletely understood. Recent developmental anatomical studies suggest that recognizable fascial lamination appears as a late fetal event coinciding with extracellular matrix maturation, skeletal stiffening, and the emergence of a body-wide tension network. Within this developmental framework, Poisson-compression-driven syneresis may transform hydrated loose mesenchyme into dense fascial membranes through mechanical phase separation.We propose that aging represents the reverse rotation of this developmental process. In development, increasing tension fields generate orthogonal compression, fluid expulsion, collagen densification, and membrane formation. In aging, progressive decline of tension fields reduces Poisson compression, allowing Donnan osmotic swelling pressure to predominate. This shift promotes rehydration, re-expansion, loss of structural density, ligamentous creep, and eventual membrane failure.This framework provides a unified biomechanical explanation for several age-related disorders characterized by failure of tension-dependent supporting membranes, including pelvic organ prolapse, abdominal wall and inguinal hernia, and age-related spinal kyphosis. Rather than interpreting these conditions as isolated local diseases, we suggest they represent different anatomical manifestations of a common biomechanical cascade:

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Tension field decay

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Loss of Poisson compression

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Loss of syneresis

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Re-expansion

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Creep

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Membrane failure

We further propose a Two-Hit Framework in which systemic fascial decompression establishes vulnerability, while local trauma or shear loading determines the anatomical site of failure. This model connects developmental morphogenesis and age-related structural collapse through a single physical principle and offers a conceptual foundation for future investigation of connective tissue aging.

Abstract: Acyl-CoA thioesterase 9 (ACOT9), a member of the type II hot-dog fold thioesterase superfamily, play important roles in regulating the balance between intracellular acyl-CoA and free fatty acids. Although its functions have been extensively studied in vertebrates, its evolutionary diversification and physiological roles in Diptera, particularly in the economically important insect black soldier fly (Hermetia illucens), remain largely unclear. In this study, ACOT9 homologs were identified from 93 representative dipteran species, and H. illucens was used as a model to investigate phylogenetic re-lationships, synteny, domain architecture, expression profiles, and RNA interference (RNAi)-based functional analysis. The results showed that ACOT9 underwent lineage-specific duplications in the suborder Brachycera, giving rise to four paralogs (ACOT9.1–9.4), accompanied by lineage-specific gene losses. Synteny and conserved domain analyses suggested potential functional divergence among these paralogs. In contrast, the ancestral single-copy ACOT9 retained a catalytically con-served domain (e.g., d1lo7a) shared between vertebrates and insects. We cloned the full-length open reading frame (ORF) of H. illucens ACOT9. Transcript abundance peaked on day 12 of larval devel-opment (pre-pupation), with higher expression in males than in females, and predominant localiza-tion in the Malpighian tubules. RNAi-mediated knockdown in 6- to 7-day-old larvae significantly altered fatty acid composition: total saturated fatty acids increased by 13.35%, while monounsatu-rated and polyunsaturated fatty acids decreased by 5.39% and 14.27%, respectively, with relative abundances of lauric acid and linoleic acid changing by more than 10%. Transcriptomic analysis revealed that ACOT9 knockdown significantly upregulated genes involved in de novofatty acid synthesis (FAS1/2/3, ACC, MAT, KAS, ACP) and acyl-CoA activation (ACSM1/2, ACSL4/6), down-regulated the lipolysis gene LIP, and induced expression of the mitochondrial β-oxidation trans-porter genes CPT1/2. These findings indicate that ACOT9 deficiency triggers compensatory lipid synthesis and β-oxidation activation, ultimately leading to saturated fatty acid accumulation. In summary, this study elucidates the evolutionary diversification of ACOT9 in Diptera and demon-strates its pivotal role in lipid homeostasis in H. illucens, providing important insights into insect thioesterase function and endogenous lipid metabolic networks.

Abstract: Background: Exercise intolerance is frequently reported in patients with mitral valve prolapse (MVP) despite preserved left ventricular (LV) systolic function and non-severe mitral regurgitation, but its mechanisms remain incompletely understood. We investigated whether antero-posterior (A-P) thoracic diameter is associated with reduced functional capacity in symptomatic MVP and characterized exercise-related LV filling and forward-flow responses. Methods: In this prospective single-center study, 101 consecutive symptomatic individuals undergoing exercise stress echocardiography (ESE) were enrolled, including 58 with MVP and 43 symptomatic non-MVP controls. Resting and exercise assessment included indexed LV volumes, stroke volume index (SVi), cardiac index (CI), LV filling indices, and pulmonary pressures. Reduced functional capacity was prespecified as peak workload <100 W. Logistic regression and receiver-operating-characteristic analyses were performed to identify its determinants and evaluate A-P thoracic diameter. Results: Patients with MVP had a smaller A-P thoracic diameter and lower exercise capacity than controls, with more frequent exertional symptoms and greater exercise-induced ST-segment depression despite negative ESE for inducible wall-motion abnormalities. At rest, MVP patients exhibited smaller LV dimensions and volumes, lower LV mass and left atrial size, and lower SVi and CI despite comparable LVEF and E/e′. During exercise, LV contractile reserve and pulmonary pressure responses were comparable, whereas peak LVEDVi, LVESVi, SVi, CI, and E/e′ were lower in MVP patients. Exercise-induced increases in LVEDVi, SVi, CI, and E/e′ were also attenuated. After multivariable adjustment, female sex (adjusted OR 3.99, 95% CI 1.23–13.01; p=0.022) and A-P thoracic diameter (adjusted OR per 1-cm increase 0.32, 95% CI 0.17–0.58; p<0.001) remained independently associated with reduced functional capacity, whereas MVP did not. A-P thoracic diameter showed good discrimination (AUC 0.864), with an internally derived optimal cut-off ≤12.75 cm. Conclusions: Symptomatic MVP was characterized by reduced exercise capacity and a smaller, low-filling cardiac phenotype with limited forward-flow augmentation despite preserved LV contractile reserve. A smaller A-P thoracic diameter, rather than MVP status, remained independently associated with reduced functional capacity, supporting thoracic geometry as a component of a broader thoraco-cardiac functional phenotype. The identified threshold requires external validation.

Abstract: Background: Phenylketonuria (PKU) requires lifelong adherence to a strict low phenylalanine (Phe) diet. However, PKU friendly foods remain limited in variety and sensory appeal, contributing to poor dietary compliance, especially in children. Objective: This study aimed to develop innovative, personalized snacks using 3D food printing and casein glycomacropeptide (CGMP)—a naturally low Phe protein source—to improve dietary diversity and palatability for individuals with PKU. Methods: Two snack prototypes were formulated: (1) a short-crust pastry shell filled with a CGMP based gel, and (2) a 3D printed chocolate shell filled with a CGMP based mousse. Functional ingredients included tagatose (a low glycemic sweetener) and glucomannan (a hydrocolloid stabilizer). Sensory evaluation was conducted with 40 panelists using a five point hedonic scale assessing appearance, smell, taste, flavour, texture, and overall liking. Results: All prototypes contained very low phenylalanine levels (approximately 3 mg per serving), contributing to the expansion of available low‑Phe food options. Although the amino acid profile is not complete, the formulations provide relevant amounts of several essential amino acids—particularly threonine, isoleucine, and valine—and can be further optimized in future development. Sensory evaluation indicated high overall liking, with the peanut‑flavored mousse and the short‑crust pastry achieving the highest scores.. Conclusion: Combining CGMP based formulations with 3D food printing offers a promising strategy for developing safe, palatable, and customizable PKU snacks. Precise portioning, personalized shapes, and improved sensory quality may help address current market limitations and support long term dietary adherence.

Abstract: The present study aims to analyze the Effect of the political skill of employees, on Emotional Intelligence. Political skills may affect employees’ Mental Faculties as well as the close relationship between leaders and employees. In turn, the Qualities of the employee, Negotiation or manipulation will positively impact the organization as well as the Emotional Stance of the employee. This study used a questionnaire and was conducted in the Manufacturing sector of Gujarat India. questionnaires were properly filled and 40 respondents were considered fit to be used in the study. A level of significance was observed between the dimensions of political skills and dimensions of Emotional Intelligence. Regression equations were prepared to observe the impact of dimensions of political skills on the dimensions of Emotional Intelligence. The results showed that political skill positively affected dimensions of Emotional Intelligence.

Abstract: We develop a mathematical framework for integrating fractional calculus into the backpropagation learning algorithm. We present two complementary approaches: (i) fractional-order gradient descent (FOGD), which replaces the integer-order derivative in the optimizer with a Caputo or Grünwald–Letnikov fractional derivative, inducing power-law memory in weight updates; and (ii) fractional-order neural networks (FONN), which employ fractional derivatives within the network’s activation and chain rule. We prove the equivalence of the Grünwald–Letnikov and Riemann–Liouville definitions for α ∈ (0, 1) under explicit regularity conditions, and cite the finite-part interpretation for α ≥ 1 as a classical result rather than a new proof. We establish the Mittag-Leffler solution to fractional gradient flow and derive its power-law asymptotics via complete monotonicity and Hankel contour integration. We state a corrected fractional Taylor proposition valid only for functions that are not classically C1 at the expansion point, and we explicitly note the well-known counterexample for standard smooth functions. We prove a conditional convergence result for stochastic fractional gradient descent on non-convex objectives at rate O(T^(−1/2)) + O(T^(−α)), where the memory-control condition is stated as Assumption 7.4 and the O(T^(−α)) bias term is derived explicitly from that assumption under an additional regularity hypothesis (Assumption 7.5). We give an explicit failure example showing that Assumption 7.4 can fail for small α and large truncation K, and we exhibit an admissible fractional activation (the Mittag-Leffler activation) for which the fractional chain rule of Section 6.3 is valid. Numerical verification confirms the theoretical predictions where the assumptions hold, and is reported with the regime of validity made explicit. The framework specializes to SGD, momentum, and Nesterov acceleration as the case α = 1, connects heuristically to anomalous diffusion on loss landscapes, and yields an emergent power-law learning-rate schedule.

Abstract: We study federated reinforcement learning in which multiple agents interact with a common Markov decision process and communicate through a central server to collaboratively learn the optimal stateaction value function. Our goal is to understand whether the sample-efficiency benefits of collaboration can be retained when a fraction of the agents behave adversarially and transmit arbitrarily corrupted information. To address this problem, we introduce Robust Async-Fed-Q, an epoch-based federated learning algorithm that combines variance-reduced estimation of the Bellman optimality operator at the agents with robust aggregation at the server. We establish high-probability finite-time guarantees showing that the proposed method preserves the statistical gains of collaboration among the honest agents while tolerating adversarial corruption. In particular, the effect of the adversarial agents decreases as the amount of data collected by each honest agent grows and eventually vanishes in the infinite-sample limit. We complement these guarantees with information-theoretic lower bounds that characterize the unavoidable statistical cost of adversarial corruption, leading to the first nearly matching upper and lower bounds for adversarially robust federated reinforcement learning. We further extend our framework to accommodate single-trajectory Markovian sampling and heterogeneous partial coverage, where different agents may explore different regions of the state-action space and learning relies on their collective coverage. Finally, our epoch-based design substantially improves the best known communication complexity for federated Q-learning under asynchronous sampling.

Abstract: The proliferation of fraudulent university rankings presents a growing challenge to academic integrity and scholarly communication worldwide. This study examines the cross-border and systemic penetration of fake Webometrics domains (webometrics.org, webometricsranking.com, and webometrics.online), which emerged in 2025, into official scientific discourse. Utilizing advanced search tools in Google Scholar as of September - October 2026, the research identifies numerous instances of erroneous data and methodology citations across national peer-reviewed journal articles, doctoral dissertations, and master's theses. Evidence reveals that researchers from multiple countries—including Algeria, Argentina, Brazil, Ecuador, Egypt, Indonesia, Malaysia, Moldova, Poland, Spain, Turkey, Uzbekistan, and Ukraine—have mistakenly utilized these fraudulent platforms as official sources. The findings demonstrate how blind trust in unverified scientometric metrics leads to severe distortions in institutional performance assessments and creates administrative and reputational risks for higher education entities. The paper emphasizes the urgent need to enhance the scientometric literacy of researchers, peer reviewers, and dissertation councils, and stresses that critical source verification of global rankings must become a mandatory element of academic quality control.

Abstract: We explore the hypothesis that the observed FLRW cosmology admits a finite global completion and ask how this changes the prospects for testing quantum gravity. A finite overdense region embedded in a larger background can undergo gravitational collapse, providing a possible prehistory for the observed expansion. If the collapse approaches a finite quantum-supported density \( \rho_G \), positive spatial curvature permits a nonsingular bounce connecting contraction to expansion. In one realization, the late-time de Sitter horizon of the FLRW interior is identified with the Schwarzschild horizon of the exterior, providing a finite global completion without modifying the local FLRW dynamics. The central proposal of this review is that such a finite bouncing cosmology can act as a laboratory for quantum gravity. We use quadratic gravity and PT-symmetric quantum theory as concrete realizations while emphasizing that the observational strategy is more general. Within scalaron inflation, the measured CMB amplitude constrains the \( R^2 \) coupling \( \alpha \) once the primordial state, reheating history and pivot-scale mapping are specified. Large-angle CMB parity statistics can similarly be related, within a specified primordial-state model, to an effective PT-breaking amplitude \( A_{\rm PT} \). PT completion also suggests a possible connection between the arrow of time and quantum information: information inaccessible within one semiclassical branch may remain encoded in a unitary PT-complete quantum state, potentially reformulating aspects of both the Past Hypothesis and apparent information loss. The contracting phase provides a possible second source of structure, distinct from inflationary quantum fluctuations. Nonlinear structures may form before the bounce. If such relics survive, their evolved abundance and mass function could be constrained by dark matter, early supermassive black holes, lensing and gravitational-wave observations. Strong-gravity measurements provide complementary tests of candidate microscopic completions through black-hole perturbations, horizon absorption and extreme-mass-ratio inspirals whenever the relevant additional degrees of freedom lie in an observationally accessible regime. The resulting framework is therefore best regarded as a network of cross-consistency and falsification tests. Relations among \( A_s \), \( \alpha \), \( A_{\rm PT} \), \( Y_B \), \( \rho_G \), spatial curvature, relic populations and strong-gravity observables range from established model-specific results to phenomenological hypotheses that still require microscopic derivation. If these relations can be sufficiently specified, otherwise unrelated observations could over-constrain a common quantum-gravitational history. Cosmological maps, black holes and gravitational waves can be regarded as experiments performed by Nature in regimes inaccessible to terrestrial laboratories, providing an observational approach to quantum gravity complementary to microscopic theory building. A finite Universe may preserve measurable information about both its pre-Big-Bang evolution and its high-density quantum state, turning otherwise inaccessible quantum-gravitational dynamics into a potentially falsifiable observational programme.

Abstract: Background: Tissue hypoxia and dysregulated hypoxia-inducible factor-1α (HIF-1α) signaling recur across diabetic complications, yet a circulating determinant linking chronic hyperglycemia to organ oxygen stress remains incompletely defined. Glycohypoxia proposes that impaired erythrocyte oxygen unloading constitutes an additional systemic pressure superimposed on tissue-specific microvascular and metabolic vulnerability. Evidence synthesis: In T2DM, increasing HbA1c was associated with lower P₅₀ (27.0 ± 0.5 to 26.2 ± 0.7 mmHg) and 2,3-bisphosphoglycerate (2,3-BPG; 4.8 ± 0.4 to 4.2 ± 0.5 μmol/g Hb) despite preserved arterial PO₂, while modeling predicted a 1.5–3.9% cumulative unloading deficit across HbA1c 6–9%. Independent mechanistic models demonstrate that ADORA2B–AMPK–BPGM, SphK1–S1P–Band 3/glycolytic, and ENT1–AMPD3–purine/redox signaling dynamically regulate erythrocyte 2,3-BPG/P₅₀ and tissue oxygenation. During hypoxia, SphK1-dependent adaptation increased P₅₀ by approximately 20% in humans; genetic failure of erythrocyte unloading increased renal and myocardial hypoxia, whereas AMPK activation restored BPGM/2,3-BPG signaling and reduced tissue hypoxia. Downstream, oxygen availability interfaces with PHD–VHL/FIH–HIF signaling, but diabetes can uncouple hypoxia from effective adaptation. Methylglyoxal promotes HIF-1α degradation through Hsp40/Hsp70–CHIP and disrupts HIF-1α–p300 transcriptional competence, while diabetic myocardial fatty-acid metabolism limits succinate-dependent PHD inhibition. Accordingly, diabetic kidney, retina, myocardium, peripheral nerve, and wounds exhibit distinct combinations of tissue hypoxia, HIF dysregulation, VEGF signaling, metabolic remodeling, fibrosis, and defective repair. Conclusions: Glycohypoxia is therefore best considered a mechanistically grounded but unproven systemic oxygen-delivery modifier whose expression depends on organ-specific reserve. Definitive validation requires within-subject linkage of P₅₀/2,3-BPG to directly measured tissue oxygenation, PHD/FIH–HIF state, and organ dysfunction independently of glycemia, hemoglobin concentration, arterial oxygenation, and perfusion.

Abstract: Phaseolus vulgaris L. is one of the food legumes of greatest functional relevance in Andean agricultural systems; however, the combined influence of genotype and extraction system on its phenolic profile and antioxidant behaviour remains poorly characterised for Ecuadorian varieties. The present study evaluated four Andean bean varieties (brown, black, panamito and UEB-Bombolín) under extraction with methanol, ethanol and acetonitrile using a 4 × 3 factorial design with three replicates (n = 36). Total polyphenols, flavonoids and anthocyanins were quantified using the Folin-Ciocalteu, Kumazawa and differential pH methods, respectively, while antioxidant capacity was determined using ABTS, DPPH and FRAP. The two-way ANOVA showed highly significant effects of variety, solvent and their interaction on all variables (p < 0.0001), with η²p values of up to 0.994. Principal component analysis explained 78.4% of the total variance and differentiated treatments according to seed-coat pigmentation and extraction efficiency. Brown + ACN showed the highest antioxidant activity by ABTS (73.49 µmol TE/g) and DPPH (37.38 µmol TE/g), whereas Black + ACN recorded the highest anthocyanin content (507.91 mg CY3GE/g) and the highest FRAP response (38.48 µmol TE/g). Multiple regression models showed that polyphenols and anthocyanins accounted for up to 92.1% of the antioxidant variability. The brown variety yielded a protein isolate with 70.81% protein and 76.9% extraction efficiency, demonstrating potential for the development of plant-based functional ingredients.

Abstract: A detector records an event through a succession of physical changes, from its initial response to the recovery of its working state. We construct a complete finite cycle on the local physical--observation phase space of PODA. An incoming carrier traverses fixed interaction regions, with its arrival, speed, and energy transfer governed by an autonomous Hamiltonian bounded below. Six canonical gates write a smooth event profile, amplify the pointer separation, export the record, reverse the working displacement, and exchange the remaining pointer state with a prepared blank. Their exact reference map identifies the selector and mechanical recoil left by record export. The retained core returns on the event-cell plateaus; narrow transition strips contribute a bounded probability of failure and a recoil that depends on the resolution. With a positive free Hamiltonian present throughout the passage, energy conservation and a finite-time perturbation estimate establish faithful writing, finite retention, and return within prescribed tolerances. An explicit binary realization admits nonzero preparation errors, and independent trajectory integrations check the equations and the endpoint map. These results complete the single cycle for the specified local model and incoming family. The calculation follows the archive, carrier, and waste through the output section, making explicit the resources consumed by reset. Preparation of fresh blanks, replenishment of those resources, and storage beyond the proven holding interval remain physical requirements of continued operation.

Abstract: Building on the generalized microon gas model and its equations of motion proposed in our previous work, this paper derives the four fundamental laws governing material interactions, namely Newton's law of universal gravitation, Coulomb's law, Faraday's law of electromagnetic induction, and the Biot–Savart law. Within this theoretical framework, the origins of mass and electric charge, as well as the fundamental nature of material interactions, are revealed, and the four fundamental interactions—strong, weak, electromagnetic, and gravitational—are unified under a single equation. As applications of the theory, we explain the origin of the anomalous rotational velocities of stars in galactic outskirts, analyze the mechanisms underlying nuclear decay and stability, derive an analytical formula for the β-stability line, and discuss the physical basis of the mass–velocity relation.