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Pharmaceutical research and development has accumulated vast and heterogeneous archives of data. Much of this knowledge stems from discontinued programs, and reusing these archives is invaluable for reverse translation. However, in practice, such reuse is often infeasible. In this work, we introduce DiscoVerse, a multi-agent co-scientist designed to support pharmaceutical research and development at Roche. Designed as a human-in-the-loop assistant, DiscoVerse enables domain-specific queries by delivering evidence-based answers: it retrieves relevant data, links across documents, summarizes key findings and preserves institutional memory. We assess DiscoVerse through expert evaluation of source-linked outputs. Our evaluation spans a selected subset of 180 molecules from Roche's research and development repositories, encompassing over 0.87 billion Byte-Pair Encoding (BPE) tokens and more than four decades of research. To our knowledge, this represents the first agentic framework to be systematically assessed on real pharmaceutical data for reverse translation, enabled by authorized access to confidential archives covering the full lifecycle of drug development. Our contributions include: role-specialized agent designs aligned with scientist workflows; human-in-the-loop support for reverse translation; expert evaluation; and a large-scale demonstration showing promising decision-making insights. In brief, across seven benchmark questions, DiscoVerse achieved near-perfect recall (≥0.99) with moderate precision (0.71 - 0.91). Qualitative assessments and three real-world pharmaceutical use cases further showed faithful, source-linked synthesis across preclinical and clinical evidence.

Fluid activity in marine carbonate strata is commonly recorded by calcite veins, which are important archives of diagenesis and hydrocarbon charging. However, the origin and evolution of veins in subsalt carbonate reservoirs remain poorly constrained. This study investigates calcite veins from the subsalt Fourth Member of the Ordovician Majiagou Formation (O2m4) in the central-eastern Ordos Basin, China. Petrography, carbon and oxygen isotopes, in-situ trace elements, and fluid inclusion studies were integrated to constrain vein-forming fluids, vein evolution, and their relationship with hydrocarbon charging. The results show that the veins were predominantly formed during a single precipitation stage and that their parent fluids were mainly host-rock-buffered burial fluids, with limited contribution from adjacent strata. These veins were subsequently modified to a limited extent by later hydrocarbon-bearing fluids. Fluid inclusion assemblages and homogenization temperatures indicate that hydrocarbon activity recorded by the O2m4 vein system can be divided into three stages: (a) limited early hydrocarbon charging during shallow burial, (b) widespread oil charging during the Late Triassic to Early Jurassic, and (c) later cracking of previously accumulated oil to gas during the Early Cretaceous. The hydrocarbon records preserved in O2m4 therefore indicate mature-oil charging followed by later oil cracking. This study provides new constraints on the coupling among vein formation, fluid evolution, and hydrocarbon accumulation in subsalt marine carbonate reservoirs and offers implications for natural gas exploration in the Majiagou Formation.

Structural variants (SVs) are a major class of genomic variation that profoundly influences human genetic diversity, evolution, and disease. Historically underappreciated due to detection challenges, SVs are now recognized as key drivers of both constitutional disorders and cancer. Understanding their origins and consequences is fundamental to modern genomics and clinical medicine. SVs arise from the complex interplay between endogenous sources of DNA damage - such as reactive oxygen species, replication stress, and transcription-replication conflicts - and error-prone repair mechanisms including non-allelic homologous recombination, microhomology-mediated end joining, fork stalling and template switching, and break-induced replication. The formation and patterns of these variants are critically constrained by the three-dimensional architecture of the nucleus, particularly topologically associating domains, which determine the spatial proximity of potential translocation partners. Key insights into these processes are provided by genomic instability syndromes (e.g., Bloom syndrome, Fanconi anemia, Werner syndrome, Nijmegen breakage syndrome), where specific repair pathway defects result in characteristic SV signatures and clinical phenotypes. Similarly, cancer genomes serve as detailed molecular archives of repair failures, with distinct SV patterns now enabling prediction of underlying deficiencies such as BRCA loss. Thus, the pattern of SVs in a tumor genome can serve as a retrospective molecular archive of underlying repair failure, enabling 'signature-based' prediction of HR deficiency even when germline BRCA status is unknown. Emerging technologies, especially long-read sequencing, have revolutionized the field by achieving >95% sensitivity for SV detection and resolving previously intractable rearrangements. Furthermore, recent discoveries regarding biomolecular condensates in DNA repair (e.g., PARP1, MRNIP phase separation) reveal previously unrecognized regulatory layers governing repair pathway choice and SV formation. (i) SVs are generated by specific DNA lesions and error-prone repair processes, with their patterns shaped by nuclear architecture and three-dimensional genome organization. (ii) Genomic instability disorders and cancer genomes provide crucial mechanistic insights by linking specific repair pathway defects to characteristic SV signatures. (iii) Technological advances, particularly long-read sequencing, now enable comprehensive and sensitive detection of SVs, including those in complex repetitive regions. (iv) A unified framework for understanding SVs as products of DNA damage, cellular metabolism, and chromatin context has profound clinical implications for diagnostic reverse phenotyping, synthetic lethality strategies in oncology, and the development of targeted therapies.

Hypertension and frailty frequently coexist in older adults and jointly increase the risks of falls, hospitalization, disability, and mortality. However, bibliometric evidence mapping the knowledge structure, hotspots, and trends in this field remains limited. This study aimed to characterize the intellectual landscape of hypertension and frailty research using a multi-database bibliometric approach. English-language publications were retrieved from the Web of Science Core Collection (WoSCC), Scopus, and PubMed. Article and Review types were restricted in WoSCC and Scopus, while PubMed records were harmonized during preprocessing. Records were merged in R using bibliometrix and deduplicated mainly by DOI and title. Annual trends, countries/regions, institutions, authors, journals, and collaboration patterns were analyzed. VOSviewer and bibliometrix were used for keyword co-occurrence and institutional collaboration networks. CiteSpace, based on WoSCC data, was used for keyword clustering, citation bursts, and citation analyses. In total, 1,853 records were retrieved from WoSCC, 5,210 from Scopus, and 1,615 from PubMed; 4,954 publications were included after cleaning. Publications were sparse from 1973 to 2000, increased after 2000, accelerated after 2010, and rose sharply after 2015, approaching 1,000 in 2023. The United States contributed the most publications (1,086; 21.9%), followed by China (542; 10.9%) and Italy (379; 7.7%). Wang Y was the most productive author, Archives of Gerontology and Geriatrics was the leading journal, and Harvard University was the most productive institution. Keyword analyses highlighted hypertension management, frailty indices, body composition, grip strength, gait speed, physical activity, and successful aging. CiteSpace identified recent citation bursts for "frailty index" and "hypertension management." The PURE study ranked first in global citations, while the SPRINT trial in adults aged ≥75 years ranked first in local citations. Research on hypertension and frailty has grown rapidly, especially after 2015, forming a knowledge structure focused on hypertension management, frailty assessment, and functional outcomes. Future studies should address multimorbid populations, prioritize functional endpoints, and validate combined blood pressure control and function-oriented interventions in real-world settings.

Medical imaging data are an essential resource for research and teaching; however, regulations such as the Health Insurance Portability and Accountability Act require careful consideration of protected health information (PHI) contained within images and their metadata. De-identification, the removal of PHI to prevent subject re-identification, is often essential for regulatory compliance. In pathology, whole-slide imaging (WSI) files-high-resolution scans of entire glass slides-are essential for research and machine learning model training. Currently, many scanner vendors use proprietary WSI formats; some vendors offer de-identification tools, which are often manual and tedious to use. Alternatively, physical slides may be re-scanned with obfuscated labels, though this is resource intensive. Here, we describe an institutional-scale automated WSI de-identification pipeline, which utilizes an informatics-based approach to convert clinical WSI from 11 proprietary formats into de-identified WSI in multiple open formats. This approach minimizes manual processes and additional slide-scanning hardware, storage, and personnel. De-identification requests are submitted through a zero-footprint web portal following the Fast Healthcare Interoperability Resources ServiceRequest data model. De-identification is verified via a human-in-the-loop review, and archives are distributed using cloud-based storage. Since deployment in November 2024, our pipeline has de-identified 819 cases comprising 4322 WSI files generated by 7 scanner models in 4 formats. We demonstrate that the conversion process is predictable, linearly scalable, and reliable across de-identification request sizes (238× variation), image sizes (120× variation), and capture format. This pipeline eliminates the need for manual de-identification or re-scanning while achieving high throughput and reliability at an institutional scale.

oral health is a crucial yet frequently overlooked component of overall health. While global policies have made progress in reducing oral diseases, many developing countries, including Ethiopia, often do not adequately incorporate oral health into their health policy frameworks. This policy landscape review aimed to synthesize the existing policy documents for oral health in Ethiopia. the research employed a mixed-methods design; a desk review of policy documents and key informant interviews. Systematic searching retrieved relevant oral health policies from government websites and the Ministry of Health archives. The desk review used the Policy Triangle Framework for the analysis of the content, context, actors, and processes of currently operational policy documents. While key informant interviews explored challenges affecting oral health policymaking and implementation. six policy documents were analyzed, and fourteen key informants were interviewed. Ethiopia lacks a comprehensive oral health policy. Oral health was not among the priorities in the health policy. Key gaps identified include: poor integration into broader policies, lack of stakeholder engagement, no dedicated structures in the Ministry of Health, and limited capacity for promotion. this review highlights the lack of a comprehensive oral health policy and poor integration with general health policies. The development of a national oral health policy could improve its alignment with primary care.

'Publish or perish' is a grim reality for many academic surgeons and has led to authorship proliferation and internationalization of the cardiothoracic surgical literature. We sought to examine whether these trends are continuing today. We reviewed 17,267 articles from 2007-2022 in the archives of the three leading cardiothoracic journals (European Journal of Cardiothoracic Surgery, EJCTS; Journal of Thoracic and Cardiovascular Surgery, JTCVS; Annals of Thoracic Surgery, ATS). Data on the number of authors and geographic origin were collected. The mean number (&#xb1; standard error) of authors per article increased with time for all journals: from 6.5&#x2009;&#xb1;&#x2009;0.1 in 2007 to 9.0&#x2009;&#xb1;&#x2009;0.2 in 2022 for the EJCTS (p&#x2009;<&#x2009;0.001), from 7.4&#x2009;&#xb1;&#x2009;0.1 in 2007 to 8.2&#x2009;&#xb1;&#x2009;0.2 in 2022 for the JCTVS (p&#x2009;<&#x2009;0.001), and from 6.9&#x2009;&#xb1;&#x2009;0.1 in 2007 to 9.0&#x2009;&#xb1;&#x2009;0.2 in 2022 for the ATS(p&#x2009;<&#x2009;0.001). North American institutions increasingly dominate JTCVS/ATS, whilst European manuscripts decline in all journals. Only EJCTS showed increasing internationalization. Authorship proliferation continues in the three leading cardiothoracic surgical journals, reflecting the natural evolution of the demands of modern research and career progression.

Large audio archives contain rich and diverse sonic material, yet they are seldom usable as controllable media in interactive contexts such as installations, live performance and adaptive sound environments. This paper presents a framework for interactive latent audio synthesis and technically continuous sound-space traversal and synthesis within a structured latent manifold rather than unconstrained audio generation. The framework first uses pretrained audio encoders, including AudioMAE, CLAP and related models, to organize a curated 120,000-clip AudioSet subset into a structured audio embedding space. A variational autoencoder then learns a smooth latent representation, which is further refined by a latent diffusion model to improve latent validity and traversal continuity. The refined latent codes are rendered into controllable waveforms through a DDSP-based synthesis stage, while Ambisonic spatialization provides Ambisonic spatial rendering coupled to traversal parameters. Gesture is used only at inference time as a control layer for traversal and spatial modulation, rather than as a training condition for the generator. The framework is evaluated against VAE-only and diffusion-only baselines using latent-structure analysis, interpolation behavior, synthesis quality and runtime performance. Results show that the proposed hybrid model achieves a CLAP similarity of 0.82, a mean F0 error of 245.3 Hz, a spectral convergence of 0.132 and an interactive latency of approximately 35 ms. These findings provide technical and proxy-based evidence for latent continuity, synthesis stability and real-time traversal feasibility. These findings provide technical and proxy-based evidence for latent continuity, synthesis stability and real-time traversal feasibility, while the human-centered pilot evaluation provides initial user-level evidence for perceived traversal smoothness, controllability, responsiveness and creative usefulness. Because the pilot evaluation is small-scale, these user-facing findings should be interpreted as preliminary rather than as statistically generalizable validation.

Conjunctival melanoma (CM) is a rare cancer with a potentially high recurrence rate. The mechanics of its progression, its relationship with neighboring tissues, and its molecular characteristics are largely unknown. Diagnosis currently requires a biopsy and the time and expertise of a pathologist. Archived human biopsies containing CM were submitted to Xenium spatial transcriptomic analysis. Regions were graded by disease progression through histopathology. Differential expression (DE) and composition analysis were performed across disease states. From three patients, 12 formalin-fixed paraffin-embedded (FFPE) tissue specimens were recovered. Composition analysis showed that melanoma depletes fibroblast and epithelial cells while melanocytes proliferate. DE signatures specific to each state show a clear pattern of progression from inflammation, to cellular restructuring, and then to tumor progression and malignancy. Spatial transcriptomics allows single-cell transcriptomics techniques to compare spatially relevant annotations that are difficult to separate by library. This study proposes disease progression biomarker candidates that may elucidate the mechanics of CM progression and function as objective diagnostic and prognostic tools in the future. Conjunctival melanoma is a rare cancer of the eye. Ideally, its diagnosis, prognosis, and treatment would be guided by measurable biomarkers. However, definitive markers are lacking, and no ancillary studies, such as immunohistochemical stains or molecular studies like bulk RNA-seq, can reliably distinguish benign from premalignant/malignant lesions, predict outcomes, or guide treatment. As a result, diagnosis frequently relies heavily on morphologic assessment by an experienced pathologist. To address this gap, biopsied tissues from three patients with conjunctival melanoma were obtained for this study. Regions of the tissue were manually labeled from normal, healthy tissue through three stages of increasing cancer severity. With thin tissue slices, new spatial transcriptomic technology measured the expression of genes across the tissue. Previous methods would have required the annotated tissue to be carefully physically separated before measuring expression. Comparing cells labeled as healthy to melanoma, there is a sharp change in the proportion of cell types present. The cell types that are present in the tumor also express genes differently compared to their counterparts outside of the tumor. Some of these genes only change during one portion of tumor progression. Measuring the levels of these severity-dependent genes may provide an alternative diagnostic method. Given the role of these genes, it is also possible to infer how conjunctival melanoma develops and becomes malignant to inform the development of future treatments.

Pneumothorax is a finding that is frequently missed in the emergency department, particularly in cases with subtle radiographic features, and can rapidly progress to tension pneumothorax when overlooked on the initial chest radiograph. Although artificial intelligence (AI)-assisted chest radiograph interpretation has been shown to improve diagnostic accuracy, its effect on the actual decision behaviour of emergency physicians - particularly on chest computed tomography (CT) ordering - remains insufficiently studied. This study evaluated the impact of AI-assisted chest radiograph interpretation on emergency physicians' pneumothorax diagnostic decisions and chest CT ordering behaviour, with a particular focus on the capacity of the AI alert to function as a second reader and capture diagnoses initially missed by the physician. This was a nationwide, online, cross-sectional simulation study conducted between 1 and 15 April 2026. Emergency physicians practising in T&#xfc;rkiye were asked to interpret 20 standardised posteroanterior chest radiographs presented in a randomised order (10 pneumothorax-positive [5 overt and 5 subtle] and 10 pneumothorax-negative cases, all confirmed by chest CT). For each case, participants first indicated whether they suspected pneumothorax on the unannotated radiograph, and then - after being shown the same image annotated by a CE-certified, deep learning-based chest radiograph interpretation system - indicated whether they would order a chest CT. The primary endpoint was the paired pre-AI versus post-AI change in simulated CT-ordering intent, derived from a predefined survey coding scheme and analysed using the McNemar exact test. As the pre- and post-AI items do not capture CT-ordering intent identically, this endpoint reflects simulated imaging intent rather than observed CT-ordering behaviour. A total of 231 physicians (51.5% general practitioners, 25.5% emergency medicine residents, 22.9% emergency medicine specialists) completed the survey, yielding 4,620 physician-case response pairs. Simulated CT-ordering intent rose from 8.1% before AI exposure to 26.7% after AI exposure (absolute difference&#x2009;+&#x2009;18.6% points; p&#x2009;<&#x2009;0.001). The increase was concentrated in pneumothorax-positive cases (+&#x2009;31.6 points; p&#x2009;<&#x2009;0.001) and remained limited in pneumothorax-negative cases (+&#x2009;5.7 points; p&#x2009;<&#x2009;0.001). In subtle pneumothorax cases, the integrated diagnostic capture rate rose from 54.8% to 85.0% (+&#x2009;30.2 points); among the 339 cases in which physicians had initially answered "no pneumothorax," 211 (62.2%) were converted into a CT order after the AI alert. The effect was statistically significant across all professional titles and seniority strata (p&#x2009;<&#x2009;0.001 for all). The mean perceived usability score of the system was 8.1 out of 10 (interquartile range 7-10). In this simulation, AI-assisted chest radiograph interpretation did not reduce simulated CT-ordering intent; rather, the increase in intent was concentrated in true positive cases, with only a limited effect on negative cases. These findings are hypothesis-generating and require prospective confirmation with real CT-ordering data. The principal clinical value of the system lies in capturing pneumothorax diagnoses initially missed by emergency physicians, supporting its positioning as a second reader rather than as a CT-reduction tool. Not applicable.

To report a complex cervicothoracic vascular-osseous phenotype detected on CTA and define its surgical and radiological relevance. Neck CTA of a 76-year-old woman was reviewed on multiplanar reconstructions for aortic arch branching, supraaortic courses, vertebral artery segments, collateral channels, cervical ribs, styloid processes, and pharyngeal carotid relationships. CTA showed a common origin of the brachiocephalic trunk and left common carotid artery (colloquially termed bovine aortic arch), bilateral rudimentary cervical ribs, high-riding pretracheal brachiocephalic trunk, and marked supraaortic tortuosity. The brachiocephalic trunk reached C7 and divided low in the neck below the right thyroid lobe. The right common carotid artery formed a proximal loop, and the right vertebral artery arose posteriorly from the right subclavian artery, passed anterior to the right cervical rib, and entered the C6 transverse foramen. On the left, the common carotid artery formed a 2.12-cm posterolateral arch loop. The left vertebral ostium, V1 segment, and proximal V2 segment were absent. A tortuous left deep cervical artery arose from the left subclavian artery, passed anterior to the left cervical rib, and reconstituted the distal V2 segment at the C3-C4 disc level; the distal artery continued as a PICA-type vertebral artery. Additional findings were a medial loop of the right external carotid artery, a 1.56-cm retropharyngeal/retrotonsillar loop of the right internal carotid artery, bilateral elongated styloid processes, and bilateral poor sternoclavicular joint articulations with the left brachiocephalic vein partly coursing in the resulting interclavicular space. The case illustrates interacting cervicothoracic variants that may affect anterior neck surgery, thyroid and pharyngeal procedures, tracheostomy, supraclavicular exposure, endovascular access, and CTA interpretation.

Oral Squamous Cell Carcinoma (OSCC) is considered a highly immunosuppressive malignancy largely mediated by the Programmed Cell Death 1/Programmed Cell Death Ligand 1(PD-1/PD-L1) axis. The interaction between PD-L1 expressed on tumor cells and PD-1 receptors on T-cells results in T-cell dysfunction, exhaustion, and immune evasion within the tumor microenvironment. This study aimed to evaluate PD-L1 expression in primary non-metastatic OSCC, primary metastatic OSCC, and nodal metastatic OSCC, as well as to investigate its association with different available clinicopathological parameters. Immunohistochemical staining was performed to retrospectively evaluate PD-L1 expression in 30 archival paraffin-embedded OSCC specimens retrieved from the Department of Oral Pathology, Faculty of Dentistry, and the Oncology Center, Faculty of Medicine, Mansoura University. PD-L1 immunoreactivity was evaluated using a semi-quantitative scoring system based on both the staining intensity and the percentage of positively stained cells. The percentage of immunopositive cells was scored as stated: 0 (0%); 1 (<&#x2009;25%); 2 (25-50%); 3 (50-75%); and 4 (>&#x2009;75%). Staining intensity was graded as follows: (0&#x2009;=&#x2009;negative); (1&#x2009;=&#x2009;weak); (2&#x2009;=&#x2009;moderate); and (3&#x2009;=&#x2009;strong). A combined immunoreactivity score was calculated by adding the percentage and the intensity for each case (range 0-7). The final score was categorized as follows: 0 (negative); 1-3 (weak); 4-7 (strong). Statistical analysis was conducted to determine significant differences and correlations between PD-L1 expression and clinicopathological parameters using the Chi-square test, Monte Carlo test, one-way ANOVA, Student's t-test, and Fisher's exact test. The p-value&#x2009;<&#x2009;0.05 was considered statistically significant. PD-L1 immunopositivity was detected in all OSCC cases (100%). A statistically significant difference was observed among the different studied groups (p&#x2009;<&#x2009;0.001), with the strongest PD-L1 expression detected in both primary metastatic and nodal metastatic OSCC. Strong PD-L1 expression showed a significant association with patient age (p&#x2009;=&#x2009;0.024). Additionally, a significant correlation was identified between PD-L1 expression and the depth of tumor invasion (p&#x2009;<&#x2009;0.001). PD-L1 expression may have a potential role in tumor progression of OSCC.

Successful full-arch rehabilitation depends not only on implant survival but also on long-term prosthetic stability and biomechanical harmony. Despite advancements in implant dentistry, prosthetic complications remain a significant challenge in full-arch fixed implant-supported prostheses. Implant positioning parameters, such as implant angulation, anteroposterior spread, and cantilever extension, may influence the stress distribution and contribute to prosthetic failure. This study aimed to evaluate the association between implant positioning parameters and prosthetic failure in full-arch fixed implant-supported prostheses. This retrospective matched case-control study was conducted in the Department of Prosthodontics and Crown and Bridge, using archived patient records from January 2020 to December 2024. Ninety participants were included, comprising 30 patients with prosthetic failure and 60 matched controls without complications. Cone-beam computed tomography (CBCT) records were evaluated to assess the mesiodistal angulation, buccolingual angulation, vertical implant position, anteroposterior spread, distal cantilever length, cantilever-to-anteroposterior spread ratio, and inter-implant distance. Statistical analysis was performed, with a p-value less than 0.05, which was considered statistically significant. Repeated screw loosening was the most common prosthetic complication and was observed in 13 (43.3%) patients, followed by framework fracture in 11 (36.7%) patients and catastrophic veneering material fracture in 6 (20.0%) patients. The case group demonstrated significantly greater mesiodistal angulation (18.4 &#xb1; 4.2&#xb0;&#xa0;versus 12.1 &#xb1; 3.8&#xb0;), buccolingual angulation (15.7 &#xb1; 5.1&#xb0;&#xa0;versus 10.3 &#xb1; 3.6&#xb0;), vertical implant position (3.8 &#xb1; 1.4 mm versus 2.9 &#xb1; 0.9 mm), distal cantilever length (14.2 &#xb1; 3.1 mm versus 10.4 &#xb1; 2.6 mm), and cantilever-to-anteroposterior spread ratio (1.42 &#xb1; 0.31 versus 0.89 &#xb1; 0.22) compared with controls (p < 0.001). Greater anteroposterior spread and inter-implant distance demonstrated protective effects against prosthetic failure. Implant positioning parameters significantly influence prosthetic outcomes in full-arch fixed implant-supported prostheses. Increased implant angulation and cantilever extension are associated with a higher prosthetic failure risk, whereas greater anteroposterior spread and inter-implant distance improve biomechanical stability. Accurate prosthetically driven implant placement may reduce technical complications and improve the long-term prosthetic success.

Symbiotic partnerships have opened new ecological niches and contributed to the remarkable diversification of insects. The leafhopper Scaphoideus titanus, a phloem-feeding insect known to be the primary vector of Flavescence dor&#xe9;e phytoplasma, harbours two primary endosymbionts: the bacterium 'Candidatus Karelsulcia muelleri' and a yeast-like symbiont (YLS). While most studies on insect-associated microorganisms have focused on obligate bacterial symbionts, fungal endosymbionts, although documented for almost a century, are only now gaining renewed attention for their evolutionary and ecological significance. In this study, we integrated genomic and proteomic data with phylogenetic analyses to elucidate the functional and evolutionary features of the YLS associated with S. titanus. Using a data-independent proteomic approach supported by a newly sequenced symbiont genome, we defined the proteins expressed by the YLS that may contribute to host physiology. Comparative analyses across the five currently available YLS genomes enabled a proteome-wide phylogenetic reconstruction within the genus Ophiocordyceps, refining the evolutionary placement of these symbioses. Finally, large-scale mining of NCBI transcriptomic Sequence Read Archive datasets using a novel computational workflow, combined with an extensive literature survey, identified several new candidate insect hosts and provided a comprehensive inventory of species harbouring these fungal partners.

The increasing prevalence of antifungal resistance necessitates the exploration of novel therapeutic agents from natural reservoirs. Bacteria derived from medicinal plants serve as an underexploited repository of biologically active secondary metabolites. This study investigated the chemical profile and antifungal potential of the cell-free supernatant (CFS) derived from Lactiplantibacillus plantarum (L. plantarum) strain isolated from the medicinal plant Pulicaria jaubertii (P. jaubertii) (Asteraceae) in Yemen. L. plantarum was isolated from surface-sterilized leaves of P. jaubertii and cultured to obtain CFSs. The chemical composition of the CFS was characterized using Fourier-transform infrared (FT-IR) spectroscopy. Antifungal efficacy was evaluated against clinically significant isolates of Aspergillus fumigatus (A. fumigatus) and Candida albicans (C. albicans) using agar incorporation and agar well-diffusion methods, respectively. FT-IR spectroscopy indicated that the CFS is a complex mixture containing functional groups of organic acids, peptides, and carbohydrates. It exhibited dose-dependent antifungal activity, achieving 71.9% and 90.0% growth inhibition against A. fumigatus and C. albicans, respectively, at 30% (v/v). Notably, a sharp increase in efficacy occurred between 20 and 25% (v/v). We hypothesize that this threshold effect may reflect a multi-mechanistic mode of action, potentially driven by the interplay between the acidic and peptidic constituents. These findings underscore the potential of L. plantarum CFS as a promising, sustainable source of multicomponent antifungal agents. This study highlights the value of integrating plant biodiversity with microbial chemistry to develop postbiotic interventions that address critical fungal challenges.

Medicinal plants play an important role in the prevention and treatment of several diseases in Africa. They are the first resort for patients with Prostate Diseases (PD) as soon as the first symptoms appear in Benin; PD, particularly prostate cancer, are the leading cause of cancer-related deaths worldwide and in Benin. This study aims to document the medicinal plants used by populations in southern Benin in the prevention and treatment of prostate diseases and to carry out chemical screening and larval toxicity testing on the most commonly used plants. Using a structured questionnaire, 41 herbalists and 27 traditional healers who agreed to participate in the study were interviewed on plants they use in the prevention and treatment of PD. The parts of these plants, their methods of use, and their route of administration were recorded. A triangulation was conducted on medicinal plants cited by herbalists and traditional healers in order to identify their pharmacological properties. Qualitative phytochemical screening based on colour and/or precipitation reactions and the larval toxicity test evaluating the survival of brine shrimp larvae in the presence of different extracts were carried out on the eight most commonly used plants. A total of 28 medicinal plants species belonging to 28 families and 29 genus were collected and identified. All plants were administered orally. The dominant family was Annonaceae (11%). The main species according to frequency of citation (FC&#x2009;=&#x2009;percentage of informants who cited the plant) were Caesalpinia bonduc (FC&#x2009;=&#x2009;36%), Bambusa vulgaris (FC&#x2009;=&#x2009;29%), and Annona muricata (FC&#x2009;=&#x2009;21%). Decoctions were the preferred method of preparation, and roots were the most commonly used part of the plant. The plants, rich in flavonoids, tannins, and coumarins, were non-toxic. Data analysis showed that Caesalpinia bonduc was the most widely used plant in southern Benin for treating prostate diseases. This study revealed a significant diversity of medicinal plants traditionally used to treat PD in southern Benin. The predominance of Annonaceae families, the preferential use of roots in decoctions, and the richness in non-toxic bioactive metabolites support these traditional practices. Further pharmacological studies are needed to validate their therapeutic efficacy.

This study aims to investigate the inhibitory effect of Fat mass and&#xa0;obesity-associated&#xa0;protein (FTO) overexpression on glycolysis in glomerular mesangial cells (GMCs) and its potential therapeutic impact on chronic glomerulonephritis (CGN). An adeno-associated virus (AAV9-FTO) was constructed to explore the protective role of FTO overexpression in CGN mice in vivo. Renal tissue pathology was assessed through haematoxylin and eosin (HE) staining, Masson's trichrome staining, and TUNEL staining. The expression of proliferation markers were analyzed by Western blot. GMCs proliferation was evaluated via EdU assay, and m&#x2076;A modification of ADP Dependent Glucokinase (ADPGK) was quantified using methylated RNA immunoprecipitation followed by qPCR (MeRIP-qPCR). The impact of FTO overexpression on ADPGK mRNA stability was assessed through Actinomycin D assay. Additionally, real-time quantitative PCR (RT-qPCR) was used to assess ADPGK mRNA expression before and after mutation of the m&#x2076;A site. Tissue staining results demonstrated that FTO overexpression ameliorates renal pathological progression in CGN mice. Both in vivo and in vitro experiments confirmed that FTO overexpression can reduce the expression levels of proliferation markers and also inhibit the expression of glycolysis markers. Mechanistic studies revealed that FTO overexpression suppresses the glycolytic process by downregulating ADPGK expression, thereby inhibiting abnormal proliferation of GMCs. Collectively, these findings demonstrate that FTO overexpression ameliorates CGN by inhibiting glycolysis in GMCs.