Biology and Life Sciences

Abstract: Bryophytes are important components of Antarctic terrestrial vegetation and provide habitats for diverse bacterial taxa. These bacteria may contribute to nitrogen, phosphorus, and sulfur transformations, processes important for nutrient availability in Antarctic terrestrial ecosystems. However, information on the occurrence and taxonomic affiliation of genes involved in these transformations in bryophyte-associated bacteria remains limited. We analyzed bacterial taxonomic composition and selected nitrogen-, phosphorus-, and sulfur-related genes in metagenomes from nine bryophyte samples collected on Livingston Island, Antarctica. Bacterial taxonomic composition differed significantly among the nine bryophyte samples (R² = 0.770, p < 0.001), without significant differences in multivariate dispersion. Despite these differences, 1,309 of the 2,257 detected bacterial genera were shared by all nine samples. The occurrence of nitrogen-related genes differed among samples, while most targeted phosphorus-related genes and all targeted sulfur-related genes were detected across all nine metagenomes. Nutrient-related genes were associated with several bacterial phyla, including Pseudomonadota, Actinomycetota, and Cyanobacteriota. These results provide a baseline for further investigation of bacterial diversity and nutrient-related genetic potential in Antarctic bryophyte microbiomes.

Abstract: Background/Objectives: Exercise can induce muscle damage, and human evidence on angiotensin-(1–7) supplementation for recovery remains limited. This study evaluated the effects of oral hydroxypropyl-β-cyclodextrin-complexed angiotensin-(1–7) (HPβCD–Ang-(1–7)) on muscle damage and recovery in trained amateur cyclists. Methods: Twelve male cyclists completed a randomized, double-blind, placebo-controlled crossover trial with a 15-day washout. Participants received HPβCD–Ang-(1–7) (2 mg) or placebo immediately after 10 sets of 10 squats at 75% of one-repetition maximum and again 24 h later. Outcomes included creatine kinase (CK), ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), cytokines, pressure pain threshold, and vastus lateralis thickness. Wingate performance and UBE2B and HSPA1A expression in peripheral blood mononuclear cells were assessed at 48 h. Results: Compared with placebo, HPβCD–Ang-(1–7) supplementation resulted in lower CK (p = 0.039) and higher ORAC (p = 0.009) at 48 h. FRAP was higher overall, but between-condition differences at individual time points were not significant after adjustment. TNF was lower at 24 h and 48 h, while IL-8 was lower and IL-10 higher at 48 h. UBE2B expression was lower (fold change = 0.33; p = 0.034), whereas HSPA1A expression did not differ significantly. No significant differences between conditions were detected in Wingate performance, pressure pain threshold, or muscle thickness. Conclusions: HPβCD–Ang-(1–7) supplementation reduced circulating CK, modified antioxidant and inflammatory responses, and lowered UBE2B expression in peripheral blood mononuclear cells, without detectable differences in Wingate performance, pressure pain threshold, or muscle thickness. Trial registration: RBR-5ftj2fy.

Abstract: Sedation, anesthesia, and analgesia are fundamental components of contemporary veterinary medicine, contributing to procedural safety, pain control, and animal welfare. This narrative review aimed to synthesize current evidence on pharmacological and clinical strategies for sedation, anesthesia, and analgesia in domestic and wild animals, with emphasis on individualized and species-specific ap-proaches. Recent literature addressing pre-anesthetic medication, sedation, balanced anesthesia, multimodal analgesia, pharmacological agents, routes of administration, anesthetic monitoring, recov-ery, and species-specific considerations was reviewed and critically integrated. The evidence indicates that effective anesthetic management requires consideration of physiological, metabolic, behavioral, and pharmacological characteristics, as well as the clinical condition and specific requirements of each patient. Multimodal approaches facilitate nociceptive control and may reduce the requirements for general anesthetic agents, while continuous monitoring supports the early recognition and manage-ment of cardiovascular, respiratory, and thermoregulatory alterations. Appropriate recovery is also essential for minimizing stress, pain, and physiological instability and for promoting a gradual return to normal physiological and behavioral states. Overall, the reviewed evidence supports individualized, multimodal, and continuously monitored anesthetic strategies as fundamental components of contem-porary veterinary practice. These approaches integrate procedural safety, effective pain management, physiological stability, and animal welfare across different species and clinical contexts.

Abstract: Retinoic acid receptors (RARs): RARα, RARβ, and RARγ, encoded by RARA, RARB, and RARG are ligand-regulated transcription factors that convert retinoid availability into cell-type-specific programs controlling development and tissue homeostasis. Disease-associated RAR alterations are usually reviewed separately as leukemia fusions, inherited developmental variants, treatment-resistance mutations, or pathway abnormalities. Here, these alteration classes are integrated within a common domain–mechanism–phenotype framework that links receptor architecture, chromatin regulation, and protein quality control to clinical presentation and therapeutic response. Attention is given to PML::RARA and variant RARA fusions in acute promyelocytic leukemia, germline RARB variants in neurodevelopmental and ocular disease, and RARG-rearranged acute myeloid leukemia. AF-1 and ligand-binding-domain variants, defective receptor turnover, and therapeutic strategies involving retinoids, arsenic trioxide, epigenetic modulation, and targeted protein degradation are also evaluated. The evidence indicates that disease phenotype and treatment response emerge from the interplay among the affected receptor domain, fusion partner, chromatin context, and capacity for protein degradation. Distinguishing established drivers from treatment-emergent lesions, biomarkers, and variants of uncertain significance is essential for accurate diagnosis and precision therapy.

Abstract: Twenty-plus papers in the mass-balance series have addressed metabolism, obesity, tissue clearance, and clinical nutrition. None has addressed biomechanics – the domain in which the geometric argument was first developed. This commentary fills that gap and, in doing so, makes an epistemological point that applies across the series. Mathematical and geometric truths do not require empirical confirmation. They are necessary. Physical laws are contingent but necessary within their domain. Biological applications are empirical and falsifiable. When these three levels of truth are conflated, two errors follow. The first is to treat geometric necessities as if they were empirical hypotheses awaiting confirmation. The second is to attribute to biology what geometry already entails. Both produce over-attribution to regulatory physiology. In metabolism, the result is inflated estimates of adaptive thermogenesis. In biomechanics, the result is inflated estimates of remodeling regulation. The geometric argument functions as a cutting tool: it separates what is necessary from what is empirical. What remains after the cut is the residual – the proper object of biological investigation. Biomechanics is the domain in which this cut is most visible, because the geometry is most explicit.

Abstract: Pig farming significantly supports livestock agriculture, food security, livelihoods, household income, and employment across developing countries, including Nigeria. This study characterized Gram-negative bacteria from pig production systems at Okada, Edo State, Nigeria, using a One Health approach of integrating animal, environmental and human-associated compartments. A total of 356 samples were collected and examined from the three compartments comprising, 132 pig-associated (37.08%), 124 environmental (34.83%), and 100 human-associated (28.09%). Cultural and biochemical examinations yielded 48 Gram-negative isolates, consisting of 22 isolates (45.83%) from pigs, 14 isolates (29.17%) from environmental sources, and 12 isolates (25.00%) from humans. The isolates comprised Proteus, Enterobacter, Pseudomonas, Escherichia, Klebsiella, Bordetella, Morganella, Providencia and Citrobacter, with Proteus predominating (13; 27.08%). Although bacterial genera varied numerically among compartments, Pearson’s chi-square test showed no significant association between bacterial genus and compartment (χ² = 11.25, p = 0.79). Whole-genome shotgun sequencing generated high-quality data, with mean reads exceeding 17 million and Q30 scores, with 95.50–96.50% of reads retained after filtering. Krona analysis showed predominance of Proteobacteria, Gammaproteobacteria and Enterobacterales across the compartments. Proteus spp (> 20%) and Bordetella trematum(16%), were prominent among pig-associated sequences; Proteus spp (>22%) and Escherichia coli(14%), predominated among human-associated sequences; environmental profiles were more heterogeneous, with E. coli, Citrobacter freundii, Klebsiella variicola each contributing approximately 9%. Seventeen species and a genus Halomonas were identified, with nine species shared across the three compartments. Cochran’s Q test showed no significant difference in species representation (Q = 1.14, p = 0.57). Jaccard similarity was highest between environmental and human-associated compartments (0.733), indicating substantial taxonomic connectivity. Overall, the findings support integrated One Health surveillance of Gram-negative bacteria in pig production.

Abstract: Sleep fragmentation (SF) is associated with metabolic dysfunction, systemic inflammation, and altered gut homeostasis. However, its effects on the gut microbial composition and intestinal barrier remain unclear. This study assessed whether SF alters the gut microbiota and its association with intestinal barrier integrity and enteric nervous system (ENS)-related markers in mice. Fourteen 6-week-old male BALB/c mice were assigned to a home cage control (HC) or SF group. SF was induced for 8 weeks, with fecal samples and colon tissues collected for 16S ribosomal RNA gene sequencing and quantitative real-time polymerase chain reaction analyses. Although α-diversity did not differ significantly, β-diversity revealed distinct microbial community structures. The SF group exhibited enrichment of potentially dysbiotic taxa, including Bacteroides, Parasutterella, Sellimonas, Gordonibacter, Peptostreptococcaceae, and Enterococcaceae, whereas Oscillospira, Roseburia, Monoglobus, and Lachnoclostridium were more abundant in the HC group. SF significantly downregulated tight junction protein 1 and occludin, whereas claudin-1 and ENS-associated markers (glial fibrillary acidic protein and S100 calcium-binding protein beta) were unaltered. Interleukin-6 was downregulated, whereas tumor necrosis factor and interleukin-1 beta were unaltered. These findings indicate that SF is associated with altered gut microbial dysbiosis and intestinal barrier-related genes, with limited effects on ENS-associated markers under the present conditions.

Abstract: The FAIR Data Point specification provides a standards-based framework for publishing FAIR metadata usingsemantic web technologies and linked-data standards. While FDPs support rich metadata representation andsemantic querying through RDF and SPARQL, these technologies can present a barrier for users who are primarilyinterested in discovering relevant datasets through intuitive search interfaces. The Swiss Personalized HealthNetwork FAIR Data Point extends the reference FDP implementation with a user-centered discovery layerdesigned to improve metadata exploration across health research datasets and catalogs. The SPHN FAIR DataPoint preserves the underlying FAIR-compliant semantic metadata model while introducing a lightweight JSON-based indexing mechanism that transforms RDF metadata into a retrieval-optimized representation. This indexpowers responsive full-text search and faceted filtering within the web interface, enabling users to quickly identifyrelevant resources without requiring knowledge of RDF, ontologies, or SPARQL. At the same time, the originalsemantic metadata remain accessible through standard FDP interfaces, including machine-readable metadataexports, REST API, and SPARQL-based querying. By combining standards-compliant semantic interoperabilitywith a lightweight search index, the SPHN FAIR Data Point provides two complementary pathways for accessingthe same metadata: semantic querying for advanced and machine-driven use cases, and interactive search andfiltering for human-centered dataset discovery. This approach enhances the usability and discoverability of FAIRmetadata within the SPHN Metadata Catalog and demonstrates a practical strategy for supporting both technicaland non-technical users in large-scale health data ecosystems.

Abstract: Congenital heart defects (CHD) are among the most common birth defects and a leading cause of infant mortality. Pregestational diabetes mellitus increases risk of fetal CHD. However, this association and prevention implications have not been integrated across literature. This narrative review seeks to combine evidence of cardiac formation and biological mechanisms that frame maternal hyperglycemia as a teratogen of cardiogenesis, as well as preconception care (PCC) recommendations for diabetic women. Cardiac neural crest cells are vulnerable to glycemia-induced oxidative stress, apoptosis, and epigenetic abnormalities before cardiac septation is complete by the seventh week of gestation. CHD risk rises at maternal HbA1c levels starting from 5.6%, below the minimum for prediabetes. As the window for hyperglycemia’s teratogenic effect may close before pregnancy is confirmed, glycemic control during pregnancy is unlikely to reduce much risk of CHD, while PCC can have greater influence in reducing first-trimester HbA1c levels, lowering risk of congenital defects. Little evidence exists isolating risk of CHD from risk of fetal malformations. Disparities in access to clinical care limit the improvement it could bring to odds of CHD-free birth. Bridging gaps in evidence and implementation is crucial for bringing evidence into PCC for CHD prevention based on glycemic control.

Abstract: Background: Effective influenza molecular epidemiology depends on curated, temporally representative sequence datasets. The transition from raw GISAID or NCBI/GenBank batch downloads to analysis-ready FASTA often requires command-line pipeline configuration or custom scripting, which may be inaccessible to some field and clinical virologists. To our knowledge, a targeted, non-systematic comparison of widely used viral-genome tools did not identify a single browser-delivered workflow combining supported GISAID-style and NCBI/GenBank-compatible header parsing, interactive human-in-the-loop temporal subsampling, exact-sequence identity-group analysis, and six selectable language catalogues.Methods: We developed VirSift (Viral Sequence Intelligence and Filtering Toolkit), a seven-page Streamlit web application implementing: (1) a custom parser handling five supported GISAID-style and NCBI/GenBank-compatible FASTA header variants with host inference and species normalization; (2) vectorized quality filtering and MD5-based identification of exact-sequence redundancy; (3) six documented human-in-the-loop (HITL) temporal sampling strategies with an operational date-span recommendation, plus a separate multi-attribute diversity filter for balanced host/location/clade subsampling; (4) ten Plotly visualization types, including a configurable N-level Sankey flow diagram and an exact-sequence persistence matrix; and (5) structured export to FASTA, CSV, and segment-organized ZIP bundles. The interface exposes six structurally aligned 921-key language catalogues. English and Russian contain complete or near-complete native-language values (100% and 99.0% respectively); French, Spanish, Arabic, and Chinese now also contain predominantly native-language values (94.1%, 98.0%, 98.9%, and 98.6% respectively) following a subsequent full-catalogue translation pass, with a small residual of proper nouns, format names, and language-specific cognates remaining in English. This tool-description paper documents implemented functions and includes a limited H3N2 demonstration and multi-file round-trip check; comprehensive analytical, usability, performance, and multilingual validation is reserved for separate work.Results: Applied to 59 H3N2 haemagglutinin sequences from Novosibirsk, Russia, spanning October 2021 to April 2025, VirSift identified 12 records redundant by exact nucleotide identity (20.3% of records), retaining 47 unique sequences across 9 calendar months. The observed 1,279-day collection-date span was assigned to the software-defined long-span category (labelled "Endemic" in the version 1.0 interface), for which Custom Checkpoints was recommended. The Molecular Timeline reported 47 exact-sequence identity groups. Clade 3C.2a1b.2a.2a.3a.1 accounted for 69.5% of records. Multi-file ingestion and metadata-based split export were verified by reconciliation of record counts across five source files. All described operations were completed without programming.Conclusions: VirSift provides a reproducible and auditable browser-delivered workflow for pre-phylogenetic curation of influenza sequence datasets. Its six selectable language catalogues, supported parsing rules, HITL sampling options, visualization modules, and structured exports are described here as implemented capabilities. The H3N2 case study and count-reconciliation exercise demonstrate workflow operation but do not constitute comprehensive software validation. VirSift may support institutions seeking an accessible interface for documented sequence-data curation before downstream phylogenetic analysis.

Abstract: Despite advances in treating breast cancer with modern therapeutic approaches, it still causes significant morbidity and mortality in patients. Like many other diseases, oxidative stress has significant risk factor for initiation and progression of breast cancer. Redox-sensitive transcription factors, nuclear factor-kappa B (NF-κB), activator protein-1 (AP-1), and hypoxia-induced regulators promote chronic inflammation, proliferation, angiogenesis, and metabolic adaptation of cancer cells. Therefore, regulating oxidative stress is necessary to repair cellular damage and slow or inhibit cancer progression. However, current therapeutic approaches for treating breast cancer have limitations that necessitate the development of new treatment strategies. Cannabidiol (CBD), a non-psychoactive lipophilic phytocannabinoid, acts as a context-dependent redox modulator and selectively exploits oxidative vulnerabilities in breast malignancies. It demonstrates strong antioxidant capabilities, modulating redox balance and also disrupts multiple oncogenic pathways. There is also increasing interest in developing synthetic CBD derivatives with improved therapeutic potential for cancer treatment. Inhibiting the molecular targets of cancer cell development and progression by these derivatives may provide an effective therapeutic strategy. This review provides an understanding of CBD’s potential in reducing cancer cell proliferation, metastasis, inducing apoptosis and inhibiting angiogenesis. It also highlights novel approaches of CBD analogues on molecular targets in breast cancer cell lines.

Abstract: Microenergy acoustic pulse (MAP) therapy has been associated with functional and structural improvement after childbirth-related urethral injury, but its multicellular ef-fects remain incompletely defined. We explored treatment- and injury-associated dif-ferences in the urethral microenvironment using single-cell RNA sequencing. Eight female Sprague–Dawley rats were assigned to sham, vaginal balloon dilation plus ovariectomy (VBDO), VBDO plus beta-aminopropionitrile (BAPN), or VBDO plus BAPN and MAP (MAP) groups, with one 24-week-old and one 48-week-old rat per group. Urethral tissues were analyzed for cell composition, differential gene expression, Gene Ontology enrichment, stem/progenitor features, senescence-associated secretory phe-notype activity, and CellChat-inferred intercellular communication. A balanced sin-gle-cell dataset comprising 23,128 cells was used for downstream comparative analyses and resolved 19 annotated cell-type/state categories. Across the injury- and age-associated experimental conditions, epithelial, vascular, stromal, immune, and muscle compart-ments showed distinct transcriptional patterns, whereas MAP-treated samples showed a distinct cellular distribution; a separate histological cohort showed higher urethral muscle content. MAP-treated samples also showed differences in CellChat-inferred signaling activity in selected extracellular-matrix, adhesion, vascular, developmental, and neu-ral/neuromuscular pathways, including LAMININ, FN1, COLLAGEN, ANGPT, VEGF, WNT, NOTCH, RELN, SLIT, NCAM, and NRXN. Exploratory enrichment analysis identified treatment-associated differences in translation, oxidative metabolism, stress adaptation, synaptic-organization processes, progenitor-associated transcriptional states, and senescence-related programs. Overall, the findings are descriptive and hypothe-sis-generating and require validation in independently replicated cohorts.

Abstract: Membrane-bounded vesicles assembled from prebiotically plausible amphiphiles remain one of the most experimentally supported models of early compartmentalization. Mixed single-chain amphiphiles form vesicles over a wider pH and salinity range than early single-component fatty-acid systems; such vesicles can grow, divide by physically or chemically simple routes, and, in selected formulations, host limited nonenzymatic nucleic-acid chemistry. This article reviews those results, with emphasis on work since the 2018 syntheses of Joyce and Szostak and of Chen and Walde, and separates them from a second, independent question: whether modern microbial biofilms can be used as functional analogs when thinking about matrix-stabilized compartments.The two questions are independent in claim-type and must not be fused, but they are linked by an explicit translation rule. Extracellular polymeric substances, short-chain fatty acids, and other products of evolved metabolism are not demonstrated prebiotic building blocks. A publicly posted preprint by the present author coupled a vesicular framework to microbial-biofilm language [20]. Preliminary morphological observations of heat-treated probiotic biofilms after rehydration, developed in drafts leading to that preprint, do not establish a vesicle-to-cell transition, do not document sterility, and cannot be read as abiogenesis. Even a later, well-controlled demonstration of survival after autoclaving would concern persistence of pre-existing biological material, not the emergence of cells from nonliving chemistry. An informal coupling of pH gradients to zeta potential is retained only as a qualitative analogy that currently lacks defined variables, energy accounting, kinetics, and falsifying predictions.The recommended path is therefore split in its inferences and joined in its constraints: a microbiological study of matrix-protected survival, if pursued at all, should meet sterilization-validation standards and remain silent on origin-of-life claims; protocell experiments should start from abiotic amphiphile mixtures and specified geochemical boundary conditions, and should obey the same translation rules used to reject the biofilm reading. Within those limits, vesicular models continue to offer a coherent experimental program for the chemistry-to-biology transition.

Abstract: We propose a theory in which consciousness is identified with the generation of subjective time flow by sufficiently complex structures. The theory is built on a small set of axioms concerning a primordial Void, that is an infinitely continuous entity whose examination at any finite resolution necessarily breaks an underlying symmetry, giving rise to structured reality with causal ordering. When structures exceed a critical complexity threshold, they develop non-trivial correlations across infinitesimally neighboring resolution scales, a process we term inter-scale sparking. We identify this sparking with the subjective experience of temporal flow, i.e., with consciousness. We examine the compatibility of this framework with quantum mechanics (particularly the renormalization group and Nottale’s scale relativity), general relativity (particularly Alexandrov’s chronogeometry and causal set theory), and existing theories of consciousness (particularly Integrated Information Theory, which we suggest may emerge as a consequence). The theory is background-independent, metric-invariant, and naturally incorporates the observer into the fundamental structure of physics.

Abstract: Background: Pubertal sucrose intake is a public health concern, but its effects on cholesterol metabolism and male reproductive endocrinology remain poorly understood. Rodent studies of this window have generally used 30% (w/v) sucrose or 20% (w/v) fructose solutions; beverage-like concentrations have been examined less often. Reported effects of dietary sugar on circulating testosterone are inconsistent; we hypothesized that differences in developmental stage might account for this discrepancy. Methods: Male ICR (Institute of Cancer Research) mice had free access to a 10% (w/v) sucrose solution from 4 to 8 weeks of age. We assessed hepatic and plasma lipids, testicular cholesterol and testosterone, hepatic acetyl-CoA carboxylase (ACC) and AMPK phosphorylation, and expression of cholesterol metabolism- and steroidogenesis-related genes. All measurements were performed after a 16-h fast, during which the sucrose solution was replaced with water. Results: Sucrose selectively elevated hepatic and plasma cholesterol without altering triglycerides, the circulating increase being confined to the non-high-density lipoprotein fraction. Phosphorylation of ACC1 and ACC2 rose while AMPK phosphorylation was unchanged. Peritesticular fat weight increased despite unchanged body weight and energy intake. In the testes, cholesterol content and several steroidogenic transcripts increased, whereas steroidogenic enzyme protein was unchanged. Plasma testosterone increased, whereas intratesticular testosterone did not. Conclusions: In male ICR mice, a 10% (w/v) sucrose solution during puberty supplied approximately 25% of total energy intake, with a comparable fall in solid-chow intake; it was associated with a cholesterol-predominant rather than triglyceride-predominant lipid response and higher circulating testosterone. Testicular cholesterol content and plasma testosterone were both higher while steroidogenic enzyme protein was unchanged, indicating an association between the two rather than a change in steroidogenic capacity.

Abstract: Current editorial guidelines from organizations such as the International Committee of Medical Journal Editors (ICMJE) treat generative artificial intelligence (AI) primarily as an administrative assistant or text manipulator, relegating its contributions to footnotes or acknowledgments. This policy framework misinterprets the operational reality of modern biomedical research, where advanced language models function as active intellectual partners capable of logical stress-testing, data synthesis, and hypothesis generation. Conflating operational cognitive contribution with legal and ethical accountability creates unnecessary opacity in scholarly publishing. To resolve this tension, this paper examines four structural credit frameworks—ranging from the institutional status quo to dual-track independent lists and expanded contributor taxonomies. We propose that medical publishing must evolve beyond obsolete binary definitions, establishing transparent attribution models that separate human regulatory liability from the recognition of machine-assisted scientific co-creation.

Abstract: Avian eggshell membrane (ESM) is a protein-rich fibrous biomaterial from egg-processing waste. It contains collagens, glycosaminoglycans, hyaluronic acid, chondroitin sulfate, and bioactive peptides, supporting joint homeostasis. This narrative review evaluates ESM as a multi-functional platform for joint health. ESM reduces IL-1β, TNF-α, and IL-6, modulates NF-κB and Keap1/Nrf2/HO-1 antioxidant pathways, and inhibits cartilage-degrading enzymes MMP-3, MMP-13, and ADAMTS-5. Clinical trials indicate 300–500 mg/day improves pain, stiffness, and physical function in knee osteoarthritis, with benefits within 7–10 days. At 500 mg/day, pain decreased by 72.5% at day 30 in an open-label study, while a randomized trial reduced WOMAC pain by 15.9% and stiffness by 12.8% versus placebo at day 10. A crossover trial reported improvements of 14.9% in WOMAC, 12.3% in pain, 18.2% in stiffness, and 15.2% in function at day 30. A dose-response trial showed reduced knee pain and improved quadriceps strength with 300 and 500 mg/day. Meta-analyses confirmed improvements over placebo. Processing method influences bioactivity and bioavailability, yet no head-to-head trial has established clinical equivalence. Structural joint outcomes in humans remain undemonstrated. ESM is well tolerated, but long-term and disease-modifying evidence is still needed. Preclinical evidence suggests potential canine joint-health applications, while animal studies indicate bone effects.

Abstract: This Opinion proposes that research assessment should be understood as both a measurement system and an incentive system. It further argues that scientific contribution is contextual and temporally dynamic. The significance of a discovery may not be apparent when it is produced and may depend on subsequent scientific developments. The central proposition is therefore that research assessment should evaluate scientific contribution in context and over time, recognizing that current visibility is not necessarily equivalent to scientific significance.

Abstract: Background/Objectives: Cisplatin induced hearing loss (CIHL) is a major global health sequela of chemotherapy, affecting over half a million cancer patients annually. We previously reported that honokiol, a multifunctional molecule compatible with cisplatin, protects against CIHL and upregulates sirtuin 3. Sirtuin family is composed of seven highly conserved while differentially expressed members which are critical enzymes for oxidative stress regulation in different cellular compartments. Therefore, this study aims to further verify the expression and upregulation of the entire sirtuin family during honokiol-mediated hearing protection against CIHL in a tumor-bearing mouse model. Methods: Adult female mice carrying mouse mammary tumor virus polyomavirus middle T agent oncogene were used. These mice developed palpable tumors automatically at the age of 70.8±10.3 days. CIHL was induced using a three-cycle (14 days/cycle) low-dose (4 mg/kg/day for 4 days per cycle, intraperitoneal injection) cisplatin treatment mimicking chemotherapy regimens. Honokiol (5-20 mg/kg) was administered one hour before cisplatin. Cochlear function was evaluated by auditory brainstem response threshold shifts and synaptic changes. Immunostaining and RT-qPCR were performed to verify the upregulation of sirtuin family members (1, 2, 3, 5, and 7) during these processes. Results: CIHL was observed at high-frequency range (24-32 kHz), which was mitigated by honokiol treatment. The optimal dose of honokiol for oto-protection and animal survival was 10 mg/kg. Fluorescence signals of sirtuins 1, 2, 3, 5, and 7 increased in cochleae from honokiol-treated mice. RT-qPCR confirmed a significant upregulation of sirtuin 3 mRNA with honokiol treatment. Conclusions: Sirtuin family upregulation was involved in honokiol-mediated hearing protection against CIHL. The dose-response curve of honokiol lays the foundation for potential translational applications for human studies.

Abstract: Artificial intelligence is changing how cancer biology is read, searched, modeled, and turned into hypotheses. But scientific AI does not meet biology directly. Much of what it learns has already passed through English, abstracts, pathway labels, database entries, and text-mined relations. New foundation models create a second translation problem. They can learn from molecular structures, single-cell profiles, perturbation data, and clinical trajectories without first converting those relations into human-readable explanations. This could expand biological and biomedical discovery, but it also changes the burden of proof. If a model proposes a target, biomarker, stratification, or perturbation that is reproducible but only partly interpretable, what evidence should be required before researchers or clinicians act on it? We argue that interpretability is not only an engineering problem. It is a translation problem. When the internal language of a model is difficult to read, the external evidence must become stronger: clear provenance, experimental challenge, cross-population validation, reproducibility, and accountable human judgment.