Abstract: Background: Primary cells derived from connective tissues contain mesenchymal stem/stromal cell (MSC)–like progenitors with chondrogenic potential relevant for cartilage repair. However, donor‑ and tissue‑specific variability and the lack of robust, high‑throughput analytical methods limit their translational use. Objectives: This study aimed to develop and optimize a fast, reproducible high‑content imaging workflow for quantitative evaluation of chondrogenesis in three‑dimensional (3D) spheroids derived from primary cells. Methods: Primary human cells isolated from cartilage were chondrogenically differentiated in vitro. A systematic optimization of immunofluorescence staining parameters was performed, including staining platform, enzymatic matrix digestion, non‑specific site blocking, membrane permeabilization, and nuclear counterstaining. Type II collagen was detected using an Alexa Fluor 488–conjugated antibody, and spheroids were analyzed using high‑content non-confocal imaging. Fluorescence intensities were normalized to spheroid area to account for size‑dependent effects. Results: Staining directly in imaging plates enabled streamlined high‑content analysis. Controlled pepsin‑mediated matrix digestion markedly enhanced antibody penetration, while excessive digestion compromised spheroid integrity. Extended bovine serum albumin blocking improved type II collagen signal intensity and homogeneity. Triton X‑100 permeabilization increased detection sensitivity but occasionally induced structural disruption in weakly organized control spheroids. The optimized protocol enabled clear discrimination between chondrogenic spheroids and controls, with approximately threefold higher type II collagen signal in chondrogenic samples. Conclusions: This study establishes a standardized, high‑content imaging–based workflow for quantitative assessment of 3D chondrogenesis from primary cells. The approach provides a rapid, scalable platform with direct relevance for in vitro screening, potency testing, and quality control in cartilage‑oriented advanced therapy development.

Abstract: The energy balance model (EBM) and its operational form, calories-in-calories-out (CICO), have dominated obesity research and clinical practice for decades. While these frameworks have yielded valuable public health insights, they rely on indirect conversions between mass and energy and rest on misconceptions about thermodynamic principles. This Perspective argues that a mass balance model (MBM) provides a conceptually simpler, mathematically consistent, and biologically more faithful paradigm. By tracking macronutrient mass directly – without intermediate energy-unit conversions or misapplications of thermodynamic laws – the MBM aligns analysis with physiological reality and better predicts body composition dynamics. Clarifying that the first law of thermodynamics concerns only energy (not mass), that calories cannot be eaten or oxidized, and that E=mc² has no relevance to human metabolism paves the way for more precise translational interventions in metabolic medicine.

Abstract: Adipose tissue is a heterogenous organ with newly identified endocrine function, consisting of immune cells along with main populations of fat storing adipocytes and adipose precursor cells. Dysregulated immune cell function and infiltration cause low grade chronic inflammation in adipose tissue that leads to various metabolic disorders like obesity, insulin resistance, type2 diabetes and cardiovascular disease. Our research showed the role of P311 protein in adipogenesis, amoeboid migration, vascular wall homeostasis, and blood pressure regulation. Studies from our laboratory and other labs showed the potential involvement of P311 in wound healing and predicted immune function. Here we studied the role of P311 on inflammation mainly focusing on macrophage phenotypes and functions as macrophages are predominant immune cells in adipose tissue that switch the inflammatory micro-environment between pro- and anti-inflammatory conditions. For the first time, we show the expression of P311 in macrophages implicating its role in inflammation directly. Further, P311 expression in macrophages induced anti-inflammatory phenotype (M2 macrophages) through phosphorylation of STAT6 of canonical JAK/STAT signaling pathway. The human gastrointestinal (GI) system harbors high populations of both healthier and pathogenic microbial communities that provide immunity, inflammation, nutrients, and GI tract epithelial homeostasis. Given the roles of P311 in macrophage mediated inflammation and metabolic diseases, we verified whether lack of P311 in P311 knockout mice has any effects on GI microbiome compared to wildtype mice. Our studies demonstrate that lack of P311 led to changes in the intestinal microbial strains. Together, current studies implicate a larger role of P311 connecting inflammation and microbiome with obesity.

Abstract: Dielectric surface loss from junction wiring represents a critical secondary limit for superconducting transmon coherence. We present a quasi-one-dimensional analytical framework to minimise this loss, enabling rapid optimisation without computationally expensive 3D simulations. We compare uniform strips (V1) against linear (V2–V3) and optimised hybrid tapers (V4–V5). We demonstrate that geometric tapering suppresses wiring participation by up to 99.6%, reducing it from 0.0756 ppm (V1) to 0.0003 ppm (V4). Crucially, however, a simple linear taper (T1 ≈ 127.306 μs) yields coherence virtually indistinguishable from theoretically optimal complex profiles (T1 ≈ 127.323 μs) in the current pad-dominated regime. We thus establish a definitive design rule: standard linear tapering is sufficient to eliminate wiring loss as a bottleneck, rendering fabrication-sensitive complex shapes unnecessary for next-generation, low-loss devices.

Abstract: Background: Lung cancer causes more deaths than any other malignancy worldwide, accounting for 2.2 million new cases and 1.8 million deaths in 2020. Extracting structured clinical knowledge from unstructured French-language oncology records remains methodologically unresolved in Tunisian and Francophone healthcare systems, where validated natural language processing tools do not yet exist. This study examined the effectiveness of transformer-based named entity recognition for automated clinical annotation of Tunisian lung cancer reports. Aim: The study aimed to (i) benchmark four transformer-based models on a publicly available thoracic radiology dataset, (ii) evaluate five models, including a French biomedical specialist, on a newly constructed Tunisian clinical corpus, and (iii) demonstrate prototype deployment feasibility for structured clinical decision support. Methods: A benchmarking study evaluated BERT, RoBERTa, BioClinicalBERT, and CamemBERT on the RadGraph dataset (600 annotated thoracic radiology reports). Five models were subsequently fine-tuned on 200 manually annotated initial diagnostic reports from Mami Pneumo-Phthisiology Hospital, Tunis. All models were trained for a maximum of 10 epochs, with a learning rate of 5x10-5, a batch size of 16, and an 80/10/10 train-validation-test split, and evaluated using precision, recall, and F1-score. Results: On RadGraph, RoBERTa achieved the highest F1-score of 0.873 (precision: 0.869, recall: 0.877), followed by BioClinicalBERT (F1: 0.868) and BERT (F1: 0.857). CamemBERT achieved an F1 score of 0.682 on this English dataset. On the Tunisian corpus, DrBERT outperformed all models with an F1-score of 0.811, compared to RoBERTa at 0.79. A prototype interface generated structured clinical summaries encompassing prior conditions, imaging modalities, and TNM staging. Conclusion: Language- and domain-adapted transformer models effectively extract structured clinical entities from French-language Tunisian lung cancer reports. DrBERT's precision advantage confirms that biomedical pretraining in the target language is the primary driver of performance in specialized French oncology text. This work establishes foundational infrastructure for NLP-driven oncology data management in Tunisia and comparable Francophone settings.

Abstract: Piper aduncum L. essential oil (PAEO) contains bioactive compounds with acknowledged insecticidal potential against various agricultural pests. Nevertheless, there is limited information about its long-term toxicological stability. In this sense, this study sought to assess the toxicological stability of PAEO after storage for 12 months at different temperatures (5 °C, 20 °C, and 35 °C) and light conditions (exposed to light or not), focusing on four insect pest species of stored grains: Sitophilus zeamais (Coleoptera: Curculionidae), Tribolium castaneum (Coleoptera: Tenebrionidae), Oryzaephilus surinamensis (Coleoptera: Silvanidae), and Cryptolestes ferrugineus (Coleoptera: Cucujidae). The toxicological stability of PAEO was evaluated every four months using concentration-mortality bioassays. Dillapiole was the predominant constituent, representing 70.34% of the identified compounds. At the conclusion of the 12-month evaluation, the PAEO demonstrated increased toxicity to the species S. zeamais, O. surinamensis, and C. ferrugineus. High temperature (35 °C) and light exposure significantly reduced the toxicity of PAEO to all four species. In conclusion, the efficacy of PAEO against insect pests is best preserved when kept in amber bottles, at temperatures not exceeding 20 °C, and shielded from light.

Abstract: Hodge theory is a powerful framework for modeling and analyzing vector fields, as found in fluid and electro- dynamics. However, its full power and modern formulation, especially on manifolds, remain largely inaccessible to non-specialists due to the substantial prerequisite in modern mathematics. This article aims to fill this gap by providing a comprehensive, self-contained introduction to Hodge theory, specifically tailored for an audience versed in traditional vector/tensor calculus and seeking to understand the modern formulation of this theory. We choose orientable closed surfaces as our pedagogical setting, due to their conceptual simplicity, mathematical tractability, and physical relevance (as boundaries of three-dimensional regions). Crucially, this setting is perfect for elucidating the complete structure of Hodge theory, particularly its topological and geometric aspects---elements frequently absent or obscured in treatments rooted in classical physics. We accomplish this through a parallel development of the modern exterior calculus and a dedicated 2D vector calculus on surfaces, followed by a series of specifically designed analytical and numerical examples. Furthermore, recognizing the fragmented historical development of the subject---a primary source of the conceptual gap for modern readers---we include a concise historical synopsis to bridge this divide.

Abstract: Clinical outcomes after acute ischemic stroke remain highly heterogeneous, even among patients with comparable lesion characteristics and successful reperfusion, challenging traditional lesion-based models. Increasing evidence suggests that stroke should be conceptualized as a disorder of distributed brain networks, yet the mechanisms linking focal ischemia to large-scale dysfunction remain incompletely understood. In this review, we propose that diaschisis constitutes a central physiological mechanism underlying this transition from focal injury to network-level impairment. Building on advances in functional imaging, connectomics, and cerebellar physiology, we argue that diaschisis is best understood as a disruption of cerebello-cortical loop dynamics rather than a nonspecific remote effect. These closed, polysynaptic circuits linking cortex, cerebellum, and thalamus support the integration of motor and cognitive processes and are particularly vulnerable to perturbation. Focal ischemia may therefore induce a cascade of dysfunction that propagates across these loops, leading to widespread impairment despite limited structural damage. Within this framework, outcome variability emerges from the interaction of three key factors: lesion characteristics, brain reserve and network vulnerability, and the extent of diaschisis. We further highlight that functional suppression of cerebellar output, even in the absence of structural degeneration, may play a critical role in mediating network dysfunction. This circuit-based perspective provides a mechanistic explanation for inter-individual variability in stroke outcomes and shifts the focus from lesion localization to network dynamics. Understanding diaschisis as cerebello-cortical loop dysfunction opens new avenues for prognosis and therapeutic intervention, emphasizing the potential of targeting network-level restoration to improve recovery after stroke.

Abstract: Type 1 diabetes  is a chronic autoimmune disease marked by progressive destruction of pancreatic β cells and lifelong dependence on insulin. The transient honeymoon phase, a period of partial remission with improved metabolic control and reduced insulin needs, offers a critical therapeutic window to preserve residual β-cell function. This review highlights emerging strategies to prolong the honeymoon phase and modify disease progression. The anti-CD3 monoclonal antibody Teplizumab, the first FDA-approved disease-modifying therapy for T1D, delays clinical onset and preserves C-peptide secretion. Complementary immunomodulators such as baricitinib, rituximab, golimumab, verapamil, anti-thymocyte globulin, and DPP-4 inhibitors target distinct immune and metabolic pathways. Lifestyle interventions as optimized diet, vitamin D supplementation, and regular exercise further enhance insulin sensitivity and β-cell survival. Integrating these approaches through combination and personalized therapies may counteract immune dysregulation, oxidative stress, and viral triggers that accelerate β-cell loss. Collectively, these advances signal a paradigm shift from reactive insulin replacement toward proactive disease modification, offering renewed hope for extending remission and improving long-term outcomes in individuals with T1D.

Abstract: Allergic diseases are increasing globally, particularly among children, who are highly vulnerable due to critical windows of immune development. This review examines climate change as a key environmental determinant driving the rising burden of pediatric allergic diseases, including asthma, allergic rhinitis (AR), atopic dermatitis (AD), and food allergy (FA). Climate change influences disease risk through interconnected pathways, such as increased air pollution, altered aeroallergen patterns, and more frequent extreme weather events. Elevated carbon dioxide (CO₂) levels and rising temperatures prolong pollen seasons and enhance allergenicity, while pollutants such as ozone (O₃) and particulate matter (PM) exacerbate airway inflammation and immune dysregulation. Emerging evidence emphasizes the role of early-life exposure, particularly during prenatal and early postnatal periods, when environmental insults can induce long-term effects via epigenetic modifications and immune reprogramming. These mechanisms may increase susceptibility to allergic sensitization and subsequent disease development. Epidemiological studies consistently link exposure to air pollution, including PM₂.₅ (PM with aerodynamic diameter < 2.5 μm) and nitrogen dioxide (NO₂), with increased risk of allergic diseases in children. Additionally, climate change-related events such as wildfires, sand and dust storms, and thunderstorms further elevate exposure to allergens and pollutants, contributing to acute exacerbations and disease progression. Addressing this growing public health challenge requires integrated mitigation strategies to reduce greenhouse gas (GHG) emissions and improve air quality, alongside adaptive interventions to enhance resilience and reduce exposure. Understanding these mechanisms is essential for developing targeted prevention strategies and protecting child health in a changing climate.

Abstract: The construction (AEC) industry has consolidated Building Information Modelling (BIM) as the standard for producing and managing project information, yet its analytical exploitation in Business Intelligence (BI) environments remains manual, ad hoc and dependent on proprietary platforms. Existing literature addresses partial aspects of the problem —IFC extraction, dashboards, semantic approaches, data quality— without articulating a coherent architecture that integrates dimensional modelling, open-standard-based ETL, granular lineage and pre-ingestion validation. This work proposes BIM2BI, a BIM-BI integration architecture organised into four functional layers (data sources, transformation and orchestration, analytical storage and exploitation) that formalises a separation of responsibilities, explicit data contracts between layers and an extensibility-without-redesign principle. The architecture is grounded in the openBIM standards IFC, IDS and BCF, adopts the IfcGlobalId as a technical key for end-to-end lineage and uses IDS as a pre-ETL quality gate with a staged three-level validation strategy. The proposal is validated empirically through an open-source reference implementation (MIT licence) applied to ten representative use cases grouped in three complexity profiles. The results demonstrate the viability of the architecture in terms of data quality, traceability, reproducibility and scalability, and document empirical findings on the real behaviour of openBIM standards within automated analytical workflows.

Abstract: Caño Barro is a secondary tributary of the Ayapel wetland complex (Ramsar site), Córdoba, Colombia. Despite its role connecting the Cauca River to the wetland, no previous study has assessed its environmental condition. This work presents an integrated geo-environmental evaluation combining morphometric analysis, in-situ water quality measurements, and total mercury (Hg-T) analysis across ten stations. The watershed (632.78 km2, Kc = 2.09) has a very low channel slope (0.017%), limiting sediment transport. Dissolved oxygen fell below 4.0 mg/L at three stations (P1 = 3.55, P3 = 2.58, P6 = 3.27 mg/L), indicating localized oxygen depletion. Hg-T exceeded the US EPA chronic criterion (CCC = 0.77 µg/L) at six of seven quantifiable stations (range: 0.54–2.01 µg/L), with one outlier of 97.46 µg/L requiring confirmation. The Conesa impact assessment classified mercury ecotoxicity as severe (I = −66), ranking it as the highest management priority. Conservation proposals include riparian restoration, erosion control, and mercury monitoring. These results provide the first environmental baseline for this Ramsar tributary and underscore the impacts of illegal gold mining on protected wetland systems.

Abstract: Cement manufacturing is one of the major sources of carbon dioxide (CO2) emissions globally. Cement replacement materials are increasingly used to minimize the environ-mental impact of concrete production. In the present study, the mechanical and envi-ronmental performance of concrete mixtures containing fly ash and recycled glass powder as partial cement replacements at levels of 10%, 20%, and 30% were investigated. Workability, unit weight, compressive strength, and water permeability tests were con-ducted to evaluate the effect of replacements on the behavior of concrete. Carbon emissions and performance-normalized indicators were applied to evaluate environmental performance. It was observed that as the replacement level increased, the carbon emis-sions decreased. The highest reduction was observed at the 30% replacement level, as 28.9%. Compressive strength varied between 21.9 and 27 MPa. This indicates that all mixtures met the targeted strength range. The mixture with 30% fly ash demonstrated the highest environmental efficiency, with a carbon intensity of 10.84 kg CO₂/MPa. This in-dicates a 19.2% reduction compared to the control mixture. The sensitivity analysis re-vealed that changes in emission factors did not alter the order of the mixture.

Abstract:

Bacillus thuringiensis subsp. israelensis (Bti) is the most widely used biological larvicide for mosquito control worldwide and a cornerstone of environmentally sustainable vector-management programs. Its long-term global deployment reflects a well-characterized balance between public-health benefit and manageable ecological tradeoffs within integrated vector management (IVM) frameworks. Bti combines high larvicidal efficacy, operational simplicity, and strong target specificity, resulting in an exceptional safety profile for humans and vertebrate wildlife. Decades of laboratory and field studies demonstrate that Bti is biologically selective rather than ecologically inert, with reproducible yet context-dependent effects confined to closely related non-target aquatic dipterans. This review links the molecular and toxicological foundations of Bti to its operational performance, ecological selectivity, resistance-mitigating properties, and sustained utility in mosquito-control programs. Beyond its established larvicidal function, Bti’s prokaryotic insect larvicidal organelle (PILO) represents an underexplored platform for heterologous intracellular protein assembly. Its dense packing, structural stability, and resistance to environmental and biochemical stress indicate an evolutionary specialization for high-capacity protein storage during sporulation. These properties support noncanonical applications in biomolecule storage and stabilization and motivate cautious exploration of environmentally responsive protein release strategies. Although significant mechanistic and translational challenges remain, particularly with respect to cargo trafficking, modularity, and purification, the architectural principles that have enabled effective mosquito control provide a strong foundation for extending PILO-based platforms beyond larvicidal applications.

Abstract: Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant widely detected in aquatic ecosystems, but its subcellular targets and the mechanisms by which it disrupts light resource utilization in photosynthetic protozoa remain poorly understood at environmentally relevant concentrations. Here, Euglena gracilis was exposed to environmentally relevant PFOS concentrations. Subcellular distribution, phototaxis, photosynthetic light reactions, and energy metabolism were investigated using isolated chloroplast assays, transcriptomics, and proteomics. PFOS accumulated prominently in the eyespot and chloroplasts. Eyespot accumulation impaired phototactic motility and increased the light perception threshold. PFOS did not acutely inhibit overall photosynthesis; instead, a transient upregulation of photosynthesis-related genes and a slight stimulation of oxygen evolution were observed, which weakened with prolonged exposure. PFOS significantly reduced ATP levels and the photosynthetic electron transport rate (ETR), while Fv/Fm remained unchanged and non photochemical quenching (NPQ) was elevated. Isolated chloroplast assays confirmed direct inhibition of Mg²⁺ ATP synthase and thylakoid electron transport. Transcriptomic and proteomic analyses revealed compensatory upregulation of photosynthesis pathways but suppression of ATP synthesis and redox homeostasis. Mechanistically, PFOS directly targets chloroplast ATP synthase, leading to proton gradient accumulation, feedback inhibition of electron transport, and increased NPQ. Together with eyespot mediated phototaxis impairment, PFOS dually disrupts light acquisition (behavioral) and light conversion (physiological). This dual impairment may compromise the ecological fitness of Euglena in PFOS contaminated environments, especially under prolonged exposure.

Abstract: Melanoma adjuvant therapy has substantially improved recurrence-free and distant metastasis-free survival in patients with resected high-risk disease, and more recently these advances have extended to earlier stages. However, important unmet needs remain, including the management of stage IIIA disease, the optimal treatment strategy after relapse on adjuvant therapy, and the identification of biomarkers capable of refining patient selection. This review summarizes recent advances and unresolved questions in the adjuvant and neoadjuvant treatment of melanoma. We discuss novel systemic strategies, including immune checkpoint inhibitor combinations and personalized neoantigen mRNA vaccines, together with the expanding role of neoadjuvant approaches. We also examine prognostic and predictive tools - such as clinicopathologic models, circulating tumor DNA, serum biomarkers, tumor microenvironment features, and gene expression profiling – that may help better define recurrence risk and therapeutic benefit. Current evidence suggests that although modern therapies have changed the natural history of resected melanoma, a substantial proportion of patients are still overtreated or undertreated when treatment decisions are based on stage alone. Future progress will depend on integrating biological risk stratification with clinical staging and on optimizing treatment sequencing across adjuvant and neoadjuvant settings.

Abstract:

The Koide relation \( Q = (\sum m_\ell)/(\sum \sqrt{m_\ell})^2 = 2/3 \) for the charged leptons has held to one part in \( 10^5 \) for over forty years without an accepted derivation and is widely regarded as numerology. This paper takes the relation as a clue rather than an endpoint. Treating lepton mass square roots as Descartes-circle curvatures, the outer root of the Descartes quadratic equals the closed form \( \mathcal{F} = e_1 - \sqrt{p_2} \) when Koide holds exactly (Proposition 1); equivalently, \( \mathcal{F}^2 = \alpha_K^2\,\mu_\star \) with \( \alpha_K^2 = 5/2 - \sqrt{6} \) and \( \mu_\star = \sum_\ell m_\ell \) the lepton-sum scale. The three-input symmetric-polynomial identity thus collapses to one dimensionless Koide-determined constant times the lepton-sum scale. Kocik [1] first observed a Descartes-like reading of Koide; our mutually-tangent variant is mathematically distinct but follows the same geometric spirit. The four-curvature completion carries a testable consequence absent from the bare three-mass relation: evaluating the squared fourth curvature numerically, \( \mathcal{F}^2 = 95.113 \) MeV, and comparing against the strange-quark \( \bar{MS} \) mass at \( \mu_\star \) within current lattice precision yields a residual of \( +0.04 \) MeV against \( \pm 0.69 \) MeV, about \( +0.06\sigma \). The lepton-side quantity is fixed to better than \( 0.01\% \); future lattice improvements will sharpen or refute the present numerical agreement. To our knowledge this paper implements the first Monte Carlo null test of the Koide relation under a random-spectrum prior; a Koide-conditioned null-model calibration across four prior shapes pre-registered for the analysis gives hit fractions at the sub-percent level — model-conditional frequencies, not \( p \)-values. Scale, input, prior, and filter sensitivities, together with the error budget, are reported; full Monte Carlo protocols, numerical output, and pre-registration are in a companion methods note [2].

Abstract: Exploring a possibility of β-myrcene (MY) incorporation in propene copolymerization has been studied in the presence of phenoxide-modified half-titanocene, Cp’TiCl₂(O-2,6-ⁱPr₂-4-C₆H₃) (Cp’ = Cp*, Me₃SiC₅H₄), and ketimide-modified half-titanicene, Cp’TiCl₂(N=C^tBu₂) (Cp’ = Cp*, Cp), catalysts. The permethylated Cp* catalysts exhibited good catalytic activities in the copolymerizations but afforded the copolymers up to 3 mol% MY incorporation; the other catalysts showed the negligible activities. The resulting copolymers were amorphous and exhibited glass transition temperatures (T_g) that de-creased with increasing the comonomer (MY) content, reaching values as low as −17 °C.

Abstract: Background: Tuberculosis remains a leading cause of infectious disease mortality, with over 10 million new cases annually. The standard first-line regimen—isoniazid, rifampicin, pyrazinamide, and ethambutol—has dramatically improved survival, yet drug-induced micronutrient depletion, particularly zinc, is an underappreciated complication that may contribute to treatment-related morbidity. Ethambutol-induced optic neuropathy (EON) affects 1–5% of treated patients, and accumulating evidence implicates zinc chelation as its central mechanism. We hypothesize that anti-TB therapy creates a “multi-hit” zinc depletion state through convergent drug- and disease-mediated pathways.Methods: We conducted a systematic search of PubMed, Scopus, Web of Science, and Cochrane databases from 1944 (discovery of streptomycin) through March 2026. Search terms combined anti-TB drug names with zinc, copper, micronutrient, optic neuropathy, and visual loss. We included randomized controlled trials, cohort studies, case-control studies, case series, in vitro investigations, and animal models. PRISMA 2020 guidelines were followed. Risk of bias was assessed using the Newcastle–Ottawa Scale for observational studies and the Cochrane RoB 2.0 tool for trials.Results: From 2,847 initial records, 186 studies met inclusion criteria. Serum zinc was significantly lower in TB patients versus controls (pooled mean difference: −12.1 μmol/L; 95% CI: −14.5 to −9.7; I² = 68%). Ethambutol directly chelates zinc and copper in retinal ganglion cells via its metabolite EDBA, causing lysosomal membrane permeabilization and mitochondrial dysfunction. Isoniazid depletes pyridoxine, impairing zinc-dependent enzymatic cascades. Rifampicin induces CYP3A4 via PXR activation, accelerating retinol catabolism and functionally coupling zinc deficiency to vitamin A insufficiency through impaired retinol-binding protein synthesis. The zinc–vitamin A axis demonstrates a strong positive correlation (r = 0.86, p < 0.01) in TB cohorts. Zinc supplementation (50 mg elemental zinc/day) improved sputum conversion rates and reduced hepatotoxicity markers in three randomized trials.Conclusions: Anti-TB drugs collectively create a “multi-hit” zinc depletion syndrome that extends beyond simple ethambutol chelation. We propose a clinical algorithm for baseline zinc assessment, risk stratification, and prophylactic supplementation during TB therapy. Persistent visual loss despite ethambutol discontinuation should prompt evaluation of concurrent zinc depletion from isoniazid, rifampicin, and the underlying TB disease itself.

Abstract: Rice (Oryza sativa L.) is an important staple crop in Mozambique, and understanding its genetic diversity is essential for crop improvement, genetic resources management and conservation. However, molecular characterization of Mozambican rice germplasm remains limited. This study assessed genetic diversity and population structure of 40 lowland rainfed rice genotypes using 3473 high-quality single nucleotide polymorphism (SNP) markers generated through DArTseq™ genotyping-by-sequencing platform. Results revealed moderate genetic diversity with a mean polymorphism information content of 0.25, indicating moderate marker informativeness. Unbiased expected heterozygosity (uHe = 0.314) was higher than observed heterozygosity (Ho = 0.125), reflecting the inbreeding nature of rice (FIS = 0.357). Model-based admixture analysis identified four subpopulations, with 20% of genotypes classified as admixed. Substantial genetic differentiation was observed among these subpopulations (FST = 0.267), which was broadly consistent with the principal coordinate analysis and the neighbor-joining tree. Furthermore, a high mean Manhattan dissimilarity index (0.70), indicated strong genetic divergence across the panel. Analysis of molecular variance revealed significant variation among subpopulations (32.90%) and within subpopulations (67.10%). These findings provide foundational genetic insights to guide Mozambican rice breeding programs and support the long-term conservation of local germplasm.