Abstract: Neural decoding has demonstrated that population activity contains behaviorally relevant information, yet predictive accuracy alone does not constitute mechanistic explanation. Decoding models establish statistical mappings between neural responses and task variables but leave the underlying computational processes underdetermined. We argue that neural computation is more appropriately framed within a dynamical state-space perspective, in which population activity reflects the evolution of latent states governed by structured transition operators. Across empirical and theoretical work, neural trajectories increasingly appear as low-dimensional, nonlinear flows shaped by recurrent circuit structure and contextual inputs. This shift reframes the central scientific objective: not merely extracting representations, but learning the evolution operator that governs state transitions. However, even accurate reconstruction of latent dynamics does not guarantee mechanistic validity. Observational data typically constrain only an equivalence class of admissible operators, rendering the inferred dynamics structurally non-identifiable. We therefore propose that causal neural dynamics must be defined through perturbation and experimental design. By introducing directional constraints on state transitions, targeted interventions collapse equivalence classes and enable identification of operators that remain valid under manipulation. In this framework, evolution operators are treated as falsifiable hypotheses whose mechanistic status depends on predictive stability under perturbation. This perspective recasts neural modeling as the search for perturbation-validated dynamical laws governing population activity, moving the field from decoding-based description toward causal dynamical explanation.

Abstract: Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. Its hallmarks are extracellular amyloid-beta (Aβ) plaques and intracellular hyperphosphorylated tau forming neurofibrillary tangles, leading to synaptic dysfunction and neuronal loss. Despite extensive research, the mechanisms driving these proteinopathies and the contribution of genetic, molecular, and environmental factors remain unclear. Objective: This review summarizes the molecular mechanisms underlying AD and the factors influencing its onset and progression. Methods: A narrative review of peer-reviewed studies from PubMed, Scopus, and Web of Science was conducted. Relevant articles on neuropathology, molecular pathways, genetic susceptibility, oxidative stress, mitochondrial dysfunction, neuroinflammation, and metabolic and lifestyle risk factors were analyzed. Results: AD is marked by Aβ accumulation and tau pathology, causing synaptic and neuronal loss. Key mechanisms include abnormal amyloid precursor protein processing, tau hyperphosphorylation, oxidative stress, mitochondrial dysfunction, neuroinflammation, and calcium dysregulation. Genetic variants (APP, PSEN1, PSEN2, APOE ε4) increase risk, while aging, cardiovascular disease, diabetes, and lifestyle factors further influence disease onset and progression. Conclusion: AD arises from complex interactions among molecular and environmental factors. Understanding these pathways is essential for developing preventive strategies and effective therapies, with personalized approaches offering future promise.

Abstract: The biosphere is undergoing an unprecedented transformation driven by global warming, habitat loss, and resource depletion, threatening biodiversity through widespread species extinctions and population declines. Although conservation and restoration remain essential, the risk of irreversible tipping points demands new strategies. Synthetic biology offers one such approach: engineering existing ecosystems by modifying functional traits of resident communities to enhance resilience and prevent abrupt shifts. Despite and because of public concern, advances in biosafety and control have been achieved, mainly on a cellular scale. However, after decades of bioremediation efforts, a central question emerges: not only can interventions be perfectly controlled, but also whether they can persist and sustain ecological function. Meeting this challenge requires a paradigm shift in design philosophy, from classical to emergent engineering, embracing adaptation, feedback, and multiscale complexity as the foundation of ecosystem design.

Abstract: The severe acquired respiratory coronavirus–2 (SARS–CoV-2) infection has initiated both acute and chronic COVID–19 disease between 2020 and 2023, currently evolving with other homologous prior coronavirus strains of the Nidoviridae order, which encompasses other prevalent alpha/ beta coronaviruses, but also the Middle East Respiratory Syndrome (MERS-CoV) and SARS-CoV-1, with recent SARS–CoV–2 variants, increasing demands for effective immunogens and therapeutic approaches that will reduce global disease burden and further infection from SARS–CoV-2 affected individuals that may experience post acute sequelae (PASC) or “Long COVID”. Following a worldwide programme of prophylactic vaccination, there is still a dilemma in the efforts to find prophylactic and early therapeutic approaches that would treat novel SARS-CoV-2 variants and prevent future epidemics or pandemics within host human and animal populations, where zoonotic or cross species transfer naturally occurs. Concerns about viral immune escape intersect at a specific point; a gained evolutionary ability of several viruses to co–infect and compete against previous scientific advances since 1796 that remain undetected or asymptomatic during the early stages of infection progressing to symptomatic and severe disease via the double methylation of the 5' end of eukaryotic DNA or RNA-based viral genomes, the 7-MeGpppA2’-O-Me cap, and its double methylation capping process is performed by the activated viral 2’ - O - Methyltransferase (MTase) enzyme, a complex of two viral non-structural proteins (NSPs) joined together through an activation process (NSP10/16) and by N7-Methyltransferase (N7-MTase/NSP14), respectively. Moreover, it was discovered that polymorphic viruses translate NSP1, which prevents the activation of various Pattern Recognition Receptors (PRRs), and consequently, detection of Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs) alike. NSP1 also silences important interferon-encoding genes (INGs) and interferon-stimulated genes (ISGs), is signalled in a paracrine manner to neighbouring cells, and that induces the apoptosis of host cells, inducing an effect of “trace erase” effect and making the viral infection as immunologically “invisible” as possible during the initial, key stages of viral replication and distribution, all such mechanisms occurring independently of the viruses in cause. Another important viral NSP is NSP14, as it plays two functional roles that are independent of each other; to produce new viral genetic material for the purpose of maintaining the validity of the viral genome as well, and not just transfer a methyl group to the 5’ end of the viral genome. Other viral NSPs share a role with NSP1, 10, 14 and 16 in directly suppressing the activation of PRRs and ISGs, and all such viral proteins help the virus in its process of self-camouflaging against first- and second-line immunity, thereby often severely impacting the quality of the produced adaptive immune responses. The outcome of all such phenomena is the sharp decrease in the host Type I and Type III interferons' (IFNs) rate of synthesis by the host cells, that would usually occur and affect homeostatic cellular pathways, resulting in further viral replication and induced apoptosis. Nonetheless, effects of microbial immune evasion during the development of other viral or carcinogenic pathologies are not widely known. In short, polymorphic viruses developed a proportionate evolutionary response against developed adaptive immune responses, by currently relying on gaps mostly situated in the natural immune system in their process of molecular self-camouflaging. Scientists developed numerous approaches of early treatment that generally showed good success rates and fewer risks of adverse events, and the still early present stages of COVID-19 research should also be taken into consideration whilst filtering for the most appropriate solutions. For example, the administration of recombinant human interferons I and III into the nasal mucosa cellular layer, as key mediators of anti–viral activity, can simulate intracellular infection and stimulate cellular activity in a timely manner, training the innate and adaptive immune system cells to develop and appropriately stimulate an adequate immune response through B and T cells. Another example could involve the treatment of natural and adaptive lymphocytes with a low dose of IFNs I and possibly III, prior to their insertion into the host lymphatic system, possibly alongside additional recruitment of plasmacytoid dendritic cells (pDCs) as further interferon “factories”, all with the purpose of early infection management. It might be that focusing on directly offering the immune system the information about the genetics and protein structure of the pathogen, rather than training its first-line mechanisms to develop faster, excessively increases its specificity, making it reach a level that brings the virus the opportunity to evolve and escape previously-developed host immune mechanisms. With regards to efforts to delay the onset of malignant diseases, approaches of chrono-biological oncotherapies that include a combination of Type I and Type III Interferon-based “immune re-awakening” and low-dose SSRI or SNRI approaches, could display meaningful extents of efficacy, at least in effective delays in the onset of malignant diseases. Such overall approaches could also be considerably effective in efforts to delay and/or even prevent a number of acquired immunodeficiencies (i.e. HIV-1-induced AIDS) and diverse forms of malignant cancer, potentially helping to notably decrease the overall burden of disease worldwide in the long run. It is until the scientific community realises this potentially crucial aspect that large proportions of the world population will probably continue to face serious epidemics and pandemics of respiratory diseases over the coming several decades, evidenced with dengue fever and more recently, monkeypox and possibly avian flu. Of note, it has been indicated that IFN I and / or III display significant immunising, early therapeutic and clinical disease onset-attenuating effects for many other microbial evoked diseases, as well as for a number of oncological diseases. Microbial agents could undergo loss-of-function research upon genes responsible for inducing clinical illness whilst keeping genes responsible for microbial reproduction and transmission at least generally as functional, CRISPR-Cas9 genome editing to have genes encoding proteins suppressive of the host interferon system eliminated prior to human genes encoding Pattern Recognition Receptor activator or agonist proteins, such as outer membrane proteins of Neisseria meningitidis, as well as Type I, Type III and possibly even Type IV Interferons and various ISGs inserted into the microbial genome. Importantly, the present study is theoretical and conceptual in nature and does not advocate for any practical steps or deployment into any real-world context. Such an approach is imagined as a potential prophylactic and early therapeutic method based upon the model of editing genes of harmless bacteria to transform such them into “producers” and “distributors” of human insulin, and could turn several microbial agents into clinically harmless, transmissible “factories” for various key elements of the host interferon system, potentially placing such microbes into a reverse evolutionary path that would be deemed as “natural de-selection”, visibly reducing the average burden of disease and metabolic stresses, which in turn could gradually increase average human and animal lifespans worldwide.

Abstract: Intestinal dysbiosis is common in people living with HIV/AIDS (PLWH), yet fungal communities of the gut microbiota (mycobiota) remain poorly characterized, especially in severely immunosuppressed patients. We analyzed the gut mycobiota of 33 PLWH and 20 healthy controls from a public hospital in central Argentina. Most PLWH presented severe immunosuppression (<200 CD4+ T cells/μL) and acute or chronic diarrhea, with or without antibiotic exposure or antiretroviral therapy. Fecal DNA was extracted and the ITS2 region was sequenced using next-generation sequencing. Beta-diversity analyses revealed significant segregation between PLWH and controls (PERMANOVA, Adonis: p = 0.001, R² = 0.0989). LEfSe analysis identified 17 fungal species enriched in PLWH, predominantly Candida albicans, Candida dubliniensis, and Nakaseomyces glabratus, whereas 31 species were more abundant in controls, including Penicillium spp., Candida sake, and Clavispora lusitaniae. Histoplasma capsulatum, an endemic pathogen in the region, was more prevalent in PLWH and associated with CD4+T-cell counts. Dirichlet multinomial mixture analysis revealed two mycobiotypes: M1, with a balanced fungal composition predominating in controls, and M2, dominated by Candida species and present in PLWH. These findings provide novel insights into gut mycobiota alterations in severely immunosuppressed PLWH in Argentina, highlighting Candida-driven dysbiosis and the regional relevance of H. capsulatum.

Abstract: Antimicrobial resistance is often framed as a problem acquired outside the patient through transmission of resistant strains and genes. This view is important, but it is incomplete for immunocompromised patients, where there is substantial evidence that drug-resistant bacteria can evolve within the host during therapy. In haematological malignancy, transplantation, and other states of impaired immunity, infections persist longer, immune clearance is reduced, and prolonged use of last-line antibiotics creates repeated selection events. These conditions favour stepwise evolution toward the hardest-to-treat phenotypes, including carbapenem resistance, tigecycline resistance, colistin resistance, and resistance to ceftazidime–avibactam, often alongside persistence in reservoirs such as the gastrointestinal tract. This essay argues that antibiotic escalation alone is therefore an incomplete strategy in these settings and that care should be explicitly evolution-aware. Adjunct and alternative approaches should be prioritised earlier to reduce bacterial burden, shorten time under selection, and limit reliance on prolonged sequential antibiotic regimens. Bacteriophages are highlighted as one promising adjunct because they are highly specific, generally well tolerated, can self-amplify at sites where susceptible bacteria are present, and can be iterated through approaches such as training and rational cocktails. Phage–antibiotic synergy is also discussed as a practical strategy to improve killing and reduce escape.

Abstract: Objective: The study investigates the effects of modeling liquids (MLs) on the staining of composite resins, with a focus on unichromatic resins. Materials and methods: The research was carried out by subjecting samples of monochromatic resin (2mm height x 6mm internal diameter) to the immersion protocol in coffee solution (Nescafé Tradição Forte), with color evaluation after 21 days. Results: Statistics showed that the adhesive group presented greater color change when compared to the modeling group (p = .000). There was no statistically significant difference between water and experimental staining (= 0.104). Among the staining group factors, there was a difference for ∆E in the interactions mC-mE (p = 0.004), mC-aC (p < 0.001), mC-aE (p < 0.001), cE-aC (p = 0.015), cE-aE (p = 0.007), cC-aC (p = 0.033) and cC-aE (p = 0.017). Conclusion: These results indicate the need for further clinical studies on the applicability of modeling liquids to support decision-making in clinical practice.

Abstract: This ethnobotanical study documents medicinal plant diversity and traditional healing practices in Barguna District, a coastal region of Bangladesh. Twenty-seven traditional healers (kabiraj) were interviewed using semi-structured questionnaires during April-June 2025. A total of 68 medicinal plant species representing 34 botanical families were documented. Fabaceae emerged as the most represented family (10.3%), followed by Lamiaceae (8.8%). Trees constituted the dominant growth form (35.3%), with leaves being the most frequently utilized plant part (32.4%). The documented species treat twelve major ailment categories, with gastrointestinal disorders (22.8%) being most prevalent. Informant Consensus Factor (FIC) values ranged from 0.62 to 0.89, with gastrointestinal disorders showing highest consensus (FIC = 0.89), followed by respiratory ailments (FIC = 0.85) and diabetes (FIC = 0.82). Citation Frequency (Cf) analysis revealed Azadirachta indica (Cf = 0.89), Ocimum sanctum (Cf = 0.81), and Curcuma longa (Cf = 0.78) as culturally most significant species. Decoction (34.6%) and paste application (23.4%) were predominant preparation methods, with oral administration (61.2%) being most common. The demographic profile indicated that 81.5% of healers acquired knowledge through family inheritance, highlighting intergenerational transmission patterns. However, this traditional knowledge faces erosion threats from modernization, with 44.4% of practitioners lacking formal education and 18.5% aged above 60 years. The study reveals substantial ethnomedicinal diversity in coastal ecosystems, emphasizing the urgent need for conservation strategies, sustainable harvesting protocols, and systematic pharmacological validation to preserve indigenous knowledge while supporting rural healthcare and drug discovery initiatives.

Abstract: Background: Hematopoietic stem cell transplantation (HSCT) is a widely utilized subtype of transplantation employed in various malignant and non-malignant diseases, particularly when conventional treatments or therapeutics prove ineffective. Despite the frequent occurrence of post-transplantation lymphoproliferative disease (PTLD) in patients undergoing HSCT, no comprehensive global prevalence rate has been established to date. Methodology: In this study, we selected 39 studies from 941 studies from three databases (i.e., PubMed, ScienceDirect, and Google Scholar) to identify the global prevalence rate of PTLD in HSCT patients. Results: The pooled prevalence was determined as 5.6% (95% CI: 5.0 to 6.3) and increased to 12.4% (95% CI: 10.2 to 14.7) after excluding outlier studies. The quality of the studies was also high. The prevalence of death cases among HSCT patients was determined as 0.6% (95% CI: 0.4 to 0.9). PTLD was most prevalent in allogenic HSCT (i.e., 5.6% (95% CI: 4.9 to 6.3)) and within the European region (i.e., 27.1% (95% CI: 21.4 to 32.8)). Among risk factors, HLA mismatch was reported in most of the studies. Conclusion: This study assessed and discussed the overall global prevalence of PTLD in HSCT patients, continent-based prevalence, and risk factors that can be helpful in finding the possible prevention mechanism of PTLD and implementing individualized treatment approaches based on the treatment availability during HSCT.

Abstract: Background: Whooping cough (pertussis), caused by Bordetella pertussis, remains a major public health concern worldwide despite high vaccination coverage. Resurgent outbreaks underscore the need for continued epidemiological and immunological monitoring to evaluate population immunity. To assess the humoral immune protection in children aged 1–14 years vaccinated with DTP/Hib/HB between January and December 2022 in Duque de Caxias, Rio de Janeiro, Brazil. Methods: A total of 220 serum samples were analyzed using commercial ELISA kits to detect circulating IgG antibodies against pertussis toxin (PTx) and B. pertussis antigens. Antibody levels were compared across age groups using the Kruskal–Wallis test followed by Dunn’s multiple comparisons. Results: Anti-PTx antibody levels were low across all age groups, with only 2.17% of children showing seropositive levels (>40 IU/mL). Broader reactivity to B. pertussis antigens (PTx + FHA) was detected in 36.7% of samples, but antibody titers declined significantly with increasing age (p < 0.05). These findings indicate waning vaccine-induced immunity and potential susceptibility to reinfection. Conclusions: The study reveals low levels of circulating IgG antibodies against pertussis among vaccinated children, emphasizing the need to reassess the current immunization schedule. Introduction of adolescent booster doses and expanded access to acellular pertussis vaccines are recommended to enhance long-term protection.

Abstract: Glucose and ascorbate transport and their opposite effects on the physiological processes, explain the pathophysiology of the Ebola virus. The virus impairs intracellularly the interferon (IFN) signalling. The present article will focus on the viral factors (VP24, VP35, VP40 proteins, nucleoprotein NP) that operate in the inner of the cell, subsequently to the viral entry. The haemorrhagic fever syndrome could be understood as a state of oxidative stress, driven by hyperglycaemia and the activation of NF-kB pathway and inflammatory cytokines. High glucose levels in plasma contributes to oxidative stress. It has also an inhibitory effect on Interferon (IFN) signalling. Conversely, ascorbate can counteract the IFN blocking exerted by the virus and interfere virus budding. A treatment strategy would focus on the administration of ascorbate and glutathione, glucose or insulin at convenience, in order to maintain constant and normal levels of glucose in plasma, to combat the oxidative and inflammatory stress.

Abstract: Excess sodium intake is a growing public health concern in Malaysia. Reformulation using potassium chloride (KCl) and monosodium glutamate (MSG) offers a potential strategy to reduce sodium while maintaining palatability, although consumer responses to these ingredients remain mixed. This study examined young adults’ preferences for sodium-reduced canned soup and evaluated how flavour, sodium information, price, and additive-related cues influence stated choice, alongside sensory evaluation of sodium-reduced formulations. A cross-sectional mixed-method study was conducted among 211 Malaysian young adults. Participants completed a choice-based conjoint (CBC) experiment comprising six hypothetical purchase tasks that varied across seven product attributes. Multinomial logit models estimated part worth utilities and attribute importance. Sensory evaluation was conducted in a controlled environment using the generalised Labelled Magnitude Scale (gLMS) and Labelled Affective Magnitude (LAM) scale to assess saltiness intensity and pleasantness across soup formulations. Sodium-related attributes accounted for approximately 36% of stated decision weight, with sodium reduction percentage and flavour emerging as the strongest drivers of stated choice. Moderately sodium-reduced formulations incorporating KCl and MSG achieved favourable sensory ratings. Young adults’ acceptance of sodium-reduced soup is shaped primarily by flavour, sodium cues, and affordability. Sensory findings support the feasibility of sodium reduction using KCl and MSG without compromising palatability.

Abstract: Pseudogenes have traditionally been interpreted as nonfunctional remnants of protein-coding genes and therefore occupy a marginal position in genomic interpretation. This project proposes a novel conceptual perspective in which pseudogenes are reconsidered as potential components of a latent genomic layer associated with biological time and regulatory history. Rather than contributing primarily through immediate gene expression, certain pseudogenes may reflect accumulated biological trajectories and long-term regulatory constraints within genomic systems. By reframing pseudogenes through a temporal lens, this work explores the possibility that non-executing genomic elements may encode traces of past regulatory states that shape future biological responses. The project aims to develop a conceptual framework that integrates genomic persistence, biological memory, and temporal constraint in understanding genome organization and disease trajectories.

Abstract: Background/Objectives: Imidazole dipeptides (IDPs), carnosine and anserine, are endogenous antioxidants. The metabolism and functions of IDPs have mainly been investigated in rodents. However, the blood of primates, such as humans, contains carnosinase (CN1), which hydrolyzes IDPs. In non-primates, CN1 is absent, allowing IDPs to be distributed throughout tissues. There are concerns about whether the results of animal experiments can be directly applied to humans. Therefore, we aimed to investigate the blood kinetics and tissue distribution of IDPs following their oral administration to golden hamsters, the only non-primates known to possess CN1. Methods: Plasma CN1 activity was compared between hamsters and humans. Hamsters were administered IDPs (an anserine/carnosine mixture) purified from chicken meat at a dose of 1,000 mg/kg. Blood samples were collected at time points up to 6 h after administration. Tissue samples were collected at 6 h after administration to measure the concentrations of IDPs and related substances. Additionally, IDP levels in human and mice tissues from previous studies were compared with that of hamster tissues in this study. Results: Hamster plasma CN1 activity was more than 10 times higher than that in humans. Although IDPs were not detected in IDP-treated hamster plasma, constituent amino acids of IDPs increased up to 1–2 h and Nπ-methyl-histidine (m-His) remained at high levels up to 6 h after administration. IDP levels in control tissues (vehicle) were similar to those in human tissues. In the IDP group, tissue IDPs were higher than those in the vehicle and m-His increased in all tissues. Conclusions: This study suggests that IDPs and m-His levels increase in human tissues following a single oral administration of IDPs, and that m-His may serve as a substitute for IDPs.

Abstract: Background/Objectives: Bacterial biofilms are structured communities of sessile cells embedded in a self-produced extracellular matrix that protects against environmental stress, host immune responses and antimicrobial treatments. In response to specific cues, biofilm cells can revert to a planktonic free-swimming lifestyle through a process termed biofilm dispersal. When dispersed cells escape the biofilm matrix, they lose bio-film-associated antibiotic tolerance, a major barrier to treating medical biofilms. As such, dispersal-inducing compounds like nitric oxide (NO) are actively investigated as adjuvants to potentiate the biofilm eradicating activity of existing antibiotics. We recently characterised the transcriptomic responses elicited during spontaneous biofilm dispersal in closed culture-grown Pseudomonas aeruginosa biofilms. Here, we evaluated the tran-scriptional profile of P. aeruginosa biofilms treated with the NO donor Spermine-NONOate (SP-NONO) and the nitroxide C-TEMPO, an NO analogue to determine potential pathways involved in NO-mediated dispersal. Methods: Dispersal activity on P. aeruginosa PAO1 biofilms by SP-NONOate and C-TEMPO was quantified by crystal violet staining. Cellular responses to each compound were profiled by RNA-seq on treated and untreated cells. Results: While both compounds disrupted the transcription of ANR-regulated energy metabolism pathways, only SP-NONO activated canonical NO-regulated responses. Considering that only SP-NONO showed biofilm dispersal activity in this culture system, we investigated shared transcriptional shifts in SP-NONO-treated and spontaneously dispersed biofilms to identify pathways likely involved in central dispersal responses. These mostly included genes participating in the catabolism of leucine, valine, isoleucine and lysine, as well as 9 of 14 genes previously defined as transcriptional biomarkers of spontaneous biofilm dispersal. Conclusions: This study suggests that NO disrupts biofilm maturation by prematurely stimulating central pathways of spontaneous biofilm dispersal and highlights this set of biomarkers as robust indicators of dispersal responses.

Abstract: This study evaluated the seasonal variation (July vs. September) in the chemical and flavonoid composition of Mediterranean natural pasture used for grazing Cilentana goats and assessed its impact on fresh goat cheese quality. A total of 36 pasture samples and 60 cheese samples were analyzed for proximate composition, fiber fractions, minerals, and flavonoids (HPLC). July pastures showed higher dry matter (95.4%), ash (8.74%), and lower fiber (28.7%), whereas September pastures had higher crude protein (17.7%), fiber (43.7%), and kaempferol (36.4 mg/kg DM). Cheese produced in July had higher fat (46.8% DM), ash (8.36%), NaCl (4.78%), and dry matter, while September cheeses showed slightly lower fat (42.2%), higher moisture, and a more acidic pH (5.90). Seasonal increases in kaempferol, lutein, quercetin, and CMG suggest enhanced antioxidant potential in late‐season forage. These findings highlight the importance of seasonal pasture monitoring to optimize feed quality and dairy product characteristics in extensive Mediterranean goat systems.

Abstract: Despite numerous studies on carbohydrate metabolism in gestational diabetes mellitus (GDM), the role of amino acid metabolic disturbances in the mother-fetus system remains insufficiently characterized, even though amino acids play a critical role in the develop-ment of fetal macrosomia (FM) and the programming of offspring metabolic health. This study included 62 mother–newborn dyads, stratified into clinical groups based on the presence of GDM and FM. Quantitative amino acid analysis was performed in maternal serum, umbilical cord serum, and amniotic fluid samples. Statistical analysis included Kruskal–Wallis, Mann–Whitney, chi-square tests, Spearman's correlation, and machine learning methods (Random Forest) with SHAP value calculation. Metabolic pathway analysis was conducted using MetaboAnalyst. Specific amino acid markers were identi-fied for each biological compartment. In maternal serum, GDM markers included glycine, 1-methylhistidine, γ-aminobutyric acid, lysine, and tryptophan, all showing significantly decreased levels. In cord blood, 11 amino acids exhibited reduced concentrations in GDM, including glutamine, glycine, asparagine, methionine, and proline. In amniotic fluid, GDM was associated with increased levels of lysine and 1-methylhistidine. In GDM complicated by FM, cord blood showed elevated lysine, proline, leucine, and al-lo-isoleucine, whereas amniotic fluid in this group was characterized by low homocitrul-line, asparagine, and lysine alongside high histidine levels. Correlation analysis revealed multiple associations between amino acids and clinical parameters, including an inverse correlation of fetal weight with homocitrulline and positive correlations with lysine and isoleucine. Metabolic pathway analysis indicated that GDM markers in maternal serum are associated with disturbances in biotin, glutamate, and carnitine metabolism, whereas cord blood markers implicated a broader spectrum of processes, including amino acid and purine metabolism. In amniotic fluid from GDM with FM, the methylhistidine me-tabolism pathway was additionally enriched, potentially reflecting specific alterations in neonatal muscle metabolism. GDM is accompanied by differential alterations in the amino acid profile across all investigated biological compartments, with the combination of GDM and FM characterized by unique metabolic signatures. The identified amino ac-ids may serve as potential biomarkers for early prediction of GDM and its complications, and offer prospects for targeted correction of metabolic disturbances.

Abstract:

Rust, caused by Puccinia arachidis, is one among the most destructive fungal diseases constraining global groundnut (Arachis hypogaea L.) production. While the development of disease-resistant varieties stands as the most effective approach to preventing substantial yield losses, the genetic mechanisms underlying resistance to rust is not yet well understood, emphasizing the necessity for further detailed research. In this study, 184 accessions from the ICRISAT groundnut mini-core collection were evaluated for rust resistance at Dharwad, India, across multiple seasons, as well as in Vietnam for one season. Whole-genome resequencing-based genome-wide association study (GWAS) identified five highly significant marker trait associations (MTAs) for rust resistance (p = 5.22 × 10-13 to 7.21 × 10-08). Among these, two robust rust-associated kompetitive allele specific PCR (KASP) markers, snpAH00607 at chromosome Ah01 and snpAH00609 at chromosome Ah17, were validated across diverse set of breeding and pre-breeding lines. These markers were linked to candidate genes encoding sterol C4-methyl oxidase 1-2, implicated in brassinosteroid-mediated salicylic acid signalling, and MYB transcription factor known to be associated with defense responses. The identified SNPs, validated markers, and candidate genes will serve as important resources for marker-assisted breeding of rust disease resistant groundnut varieties.

Abstract: Chronic kidney disease (CKD) represents an escalating global health burden, fundamentally altering morbidity and mortality trajectories across the world, particularly as it advances into end-stage renal disease (ESRD). Beyond the primary decline in renal filtration and excretion, a wide spectrum of endocrine and metabolic derangements frequently accompanies kidney failure, with thyroid dysfunction emerging as a critical complication. The current study was designed to rigorously evaluate the nuanced association between thyroid hormone dynamics—specifically thyrotropin (TSH), triiodothyronine (T3), and thyroxine (T4)—and renal status in three distinct cohorts: individuals with suspected thyroid issues but normal renal function (NP), non-dialysis kidney patients (NDKP), and patients undergoing maintenance hemodialysis (DP). Data were collected from a clinical setting in Bangladesh, involving 161 subjects. The results demonstrated that patients in the DP cohort exhibited slightly elevated thyroid hormone levels relative to those in the NDKP cohort. Specifically, within the subgroups of patients exhibiting normal or sub-reference hormonal levels, dialysis patients maintained higher concentrations than their non-dialysis counterparts. Demographic stratification further revealed that males, females, and individuals younger than 45 years were more likely to demonstrate restorative hormonal profiles in the DP group than in the NDKP group. These collective outcomes suggest that renal replacement therapy, specifically hemodialysis, may serve to stabilize or improve thyroid function in ESRD patients by potentially mitigating the suppressive effects of uremic toxins and normalizing homeostatic feedback loops.

Abstract: The alignment between neural dynamics and environmental structures constitutes a fundamental challenge in neuroscience. While Georg Northoff's Temporo-Spatial Theory of Consciousness (TTC) posits a "common currency" of temporo-spatial dynamics, the mechanistic operationalization of this alignment remains unspecified. This report integrates the TTC with the Affective Criticality Hypo proposed by Tucker, Luu, and Friston (2025). We propose that consciousness and optimal brain-world alignment emerge when the neural system operates in a regime of Excitatory-Inhibitory (E/I) precision balance. Specifically, we identify the affective qualities of elation and anxiety not as epiphenomenal accompaniments, but as constitutive control parameters regulating precision weighting in active inference. Elation corresponds to excitatory precision (E), enhancing prior confidence, while anxiety corresponds to inhibitory precision (I), enhancing sensory vigilance. This balance is homeostatically regulated through sleep-wake cycles, where NREM and REM sleep serve as subcritical and supercritical excursions, respectively. We provide a formalization of this process within the variational free energy framework and compare its explanatory power against alternative theories (e.g., Binding by Synchrony, Population Clocks). We conclude that affective criticality offers a neurobiologically grounded mechanism for the brain-world alignment, transforming the "hard problem" of consciousness into a problem of precision-regulated inference.