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Results for “Physiology”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 721 records · Page 40Linked to original sources

bioRxiv2026

An Ex Vivo Muscle Physiology Method for Robust Measurement of Supraspinatus Muscle Function in Mouse Models

The supraspinatus is the most frequently injured rotator cuff muscle, but its anatomical characteristics such as larger size, complex fiber architecture, and a single exposed tendon have limited the development of reproducible ex vivo contractility assays. In this study, we establish a robust method for ex vivo assessment of murine supraspinatus contractile function and characterize its physiological properties across age and injury conditions. We additionally adapt a barium chloride (BaCl2)-induced injury protocol for the supraspinatus, an approach not previously described, to evaluate how acute myofiber degeneration affects muscle performance. Male C57BL/6 mice (4 months) underwent 1.2% BaCl2 injection directly into the supraspinatus to induce controlled myofiber necrosis, allowing comparison of contractile behavior between injured and uninjured muscles. Using our injury ex vivo physiological testing protocol, we quantified optimal length (L0), twitch kinetics, force-frequency responses, peak tetanic force, and preliminary fatigue-recovery dynamics. Our protocol consistently generated fused tetanic contractions and reproducible force-frequency curves in the supraspinatus. We observed differences in supraspinatus contractility between young and old mice, consistent with well-established age-related changes in hindlimb muscle contractility. In addition, BaCl2 injury produced significant impairments in contractility 48 hours post-injection, demonstrating the sensitivity of this method to acute muscle damage. This study provides a novel and reliable method for evaluating the contractile function of the murine supraspinatus muscle ex vivo, overcoming previous anatomical challenges.

bioengineering↗

bioRxiv2026

Development of Physiologically Based Liver Distribution Model that Incorporates Intracellular Lipid Partitioning and Binding to Fatty Acid Binding Protein 1 (FABP1)

Steady-state volume of distribution (Vss) can be predicted using tissue-to-plasma partition coefficients (Kp) and tissue volumes. Kp values are important components of physiologically based pharmacokinetic (PBPK) models, allowing for estimation of distribution kinetics and simulation of concentration-time profiles. Many in silico approaches have been developed to predict tissue Kp values based on physicochemical processes that govern drug distribution. However, these methods frequently over- or under-predict tissue Kp values, highlighting the need to consider additional mechanisms that can impact drug distribution kinetics. Many drugs have been shown to bind to rat and human fatty acid binding proteins (FABPs) in vitro but the impact of this binding to drug distribution has not been incorporated into Kp predictions. We hypothesized that incorporating intracellular protein binding into tissue Kp predictions will improve Kp prediction accuracy. Using liver as a model organ, four physiologically based dynamic liver distribution models (LDMs) were developed to assess the role of distribution processes in Kp predictions. The developed LDMs incorporated known distribution mechanisms and intracellular drug binding to liver FABP (FABP1). The liver Kp values for drugs that bind to FABP1 were accurately predicted using the LDM that incorporates lipid partitioning, albumin distribution, and FABP1 binding but not using LDMs without FABP1 binding. Human FABP1 expression was quantified in 61 human livers and the interindividual variability in tissue FABP1 binding was incorporated into tissue Kp predictions. These simulations showed that intracellular FABP1 binding can cause interindividual variability in Kp values and result in concentration dependent tissue distribution. Significance StatementThis study shows that incorporating intracellular protein binding such as binding to FABP1 into tissue Kp predictions improves accuracy of the predictions. The novel dynamic LDM can be extrapolated to other organs of interest and integrated into full-body PBPK models to predict drug distribution kinetics. With dynamic and saturable distribution mechanisms incorporated into a PBPK model, nonlinear distribution kinetics can be simulated for various drugs.

pharmacology and toxicology↗

bioRxiv2026

A reproducible human brain tissue model to study physiological and disease-associated microglia phenotypes

Stem-cell-based in vitro models offer promising potential to elucidate human brain cell functions and interactions under physiological and pathological conditions. However, harnessing this potential is impaired by low reproducibility, maturity, or cell-type diversity of existing models. Especially, prolonged incorporation of mature microglia and studies of neuroinflammation have proven challenging. Here, we developed a 3D cortical brain tissue model (3BTM) containing neurons, astrocytes, and microglia with high reproducibility, maturity, and viability. 3BTMs show morphological, functional, and proteomic maturation of all cell types, leading to high similarity to their in vivo counterparts. Incorporated microglia survive for over 6 months and display mature morphology, functions, and gene expression. Importantly, when engineered to model Alzheimers disease pathology, 3BTMs recapitulate key disease hallmarks including amyloid deposition, increased phospho-Tau levels, and neuroinflammation, with microglia shifting their transcriptional landscape to disease-relevant signatures. Together, our model offers unprecedented possibilities for studying physiological and pathological states of human brain tissue and translational applications.

neuroscience↗

bioRxiv2026

Baicalin ameliorates behavioral and physiological deficits in Gtf2i-duplication mice and modulates synaptic activity in 7q11.23 Duplication Syndrome patient-derived neurons

7q11.23 Duplication Syndrome (7Dup) is a type of syndromic autism spectrum disorder caused by duplication of a typically 1.5-1.8 Mb segment in section q11.23 of chromosome 7, including 25-27 genes. Previous work has highlighted the GTF2I gene as playing a major role in the phenotype of 7Dup patients. Accordingly, mice with Gtf2i duplication (Gtf2i+/dup) are commonly used as an animal model of 7Dup. We previously reported deficits in several behavioral and physiological modalities, which were associated with Gtf2i dosage in mice conducting a battery of social discrimination tests. Here, we report the effect of treating Gtf2i+/dup mice with Baicalin, a naturally occurring flavonoid added to the mices drinking water (0.15 mg/ml), on these deficits. We found that Baicalin treatment ameliorated the higher surface temperature observed in Gtf2i+/dup males and the lower tail temperature observed in Gtf2i+/dup females during the social behavior tests. It also prevented the increased defecation rate exhibited by Gtf2i+/dup mice during the social preference test. We further analyzed the effect of Baicalin treatment on cortical neurons differentiated from 7Dup patient-derived IPSCs. Using whole cell patch clamp and calcium imaging, we found an increased rate of excitatory postsynaptic currents in Baicalin-treated cells, without a change in their firing rate, indicating a stronger synaptic activity in the Baicalin-treated cells. Altogether, our results reveal that Baicalin administration alleviates some of the behavioral and physiological effects of Gtf2i duplication in mice, and affects neuronal activity in cultured 7Dup human neurons. Thus, Baicalin administration has the potential to serve as a treatment for 7Dup patients.

neuroscience↗

bioRxiv2026

Early sex-specific organ transcriptional divergence without physiological differences in a murine model of fecal-induced peritonitis

Sepsis is defined as a dysregulated response to infection, leading to life-threatening organ dysfunction that particularly affects parenchymal organs. Clinical studies remain inconclusive regarding the impact of biological sex on sepsis, and preclinical studies are predominantly performed in male animals. We examined early (8 h) septic responses in male and female mice using a fecal-induced peritonitis (FIP) model. Blood biochemical parameters, body temperature, and murine sepsis scores provided evidence of a septic response in animals randomized to FIP compared to controls, but showed no physiological differences between male and female mice. Transcriptomic analysis of the liver, kidney, and lung showed consistent inflammatory activation in response to sepsis as compared to controls. Notably, in the kidney and lung, female mice exhibited stronger immune activation and a heightened inflammatory response compared to males. Thus, biological sex differences in the septic response can be detected in early acute sepsis without apparent physiological differences.

pathology↗

bioRxiv2026

Extreme Heat as the New Normal: A Methodological Roadmap for Behavior, Physiology, and Species Distributions

A defining feature of climate change is the increasing frequency, intensity, and severity of extreme weather events. Among them, extreme heat is recognized as a critical driver of ecological and evolutionary change. Intense heat episodes can exceed physiological limits, alter animal movement, restructure geographic ranges, and increase extinction risk more than gradual changes to mean temperatures. Yet links between extreme heat events and organismal biology remain limited, in part because definitions and metrics are not standardized, and user-friendly workflows and guides are lacking for many biologists. We present a methodological roadmap, with reproducible code, for integrating extreme heat into studies of behavior, physiology, biophysical ecology, species distribution models (SDMs), and population dynamics. First, we provide standardized computational approaches to define and quantify extreme heat. Second, we fit species distribution models for California quail (Callipepla californica) that include an extreme heat metric and showcase improved predictions of habitat suitability, particularly at range edges. Third, we compute biophysical simulations to quantify exposure to thermal stress in Sleepy lizards (Tiliqua rugosa) across distinct macro- and microclimates. Finally, accounting for temporal autocorrelation in temperature profiles in population simulation models, we show that clustered heat extremes--missed by averages--can increase the risk of population collapse. As extreme heat events become more common, incorporating their dynamics is essential for understanding ecological and evolutionary change, designing experiments across species geographic ranges, and supporting conservation in a rapidly warming world. Together, these case studies illustrate a reproducible, organism-informed roadmap to integrate extreme heat into predictions of ecological impacts and inference across levels of biological organization under ongoing climate change.

ecology↗

bioRxiv2026

Leaf age modulates physiological and metabolic responses to contrasting nitrogen forms in Chinese fir (Cunninghamia lanceolata (Lamb.) Hook)

Atmospheric nitrogen (N) deposition is increasingly affecting global ecosystems, with nitrate contributing a growing proportion alongside ammonium. However, the interaction between N forms and leaf developmental stage in shaping physiological and metabolic strategies in Chinese fir remains poorly understood. In this study, a field experiment was conducted to explore the physiological and metabolic responses of young and old leaves to ammonium and nitrate N addition. Our findings showed that N addition enhanced photosynthetic performance in young leaves, with a stronger effect from nitrate. In contrast, old leaves exhibited limited photosynthetic response but accumulated higher non-structural carbohydrates and showed elevated N assimilation enzyme activities, particularly under nitrate addition. Phytohormone profiles varied between leaf ages, with young leaves having higher auxin levels while old leaves exhibiting increased abscisic and salicylic acid contents under N addition. Additionally, N addition induced differential reprogramming of amino acid metabolism, with age-dependent accumulation patterns. Metabolomic analysis identified key amino acids involved in coordinating carbon-nitrogen metabolism. These results highlighted the complementary metabolic strategies by young and old leaves of Chinese fir under contrasting N forms addition and emphasized the importance of considering both N form and leaf age in optimizing N management for sustainable plantation practices. HighlightsO_LINitrate enhanced photosynthesis in young Chinese fir leaves more effectively than ammonium. C_LIO_LIOld leaves prioritized C storage and N assimilation under N addition, especially nitrate. C_LIO_LIComplementary metabolic strategies between leaf ages optimized resource use under different N forms addition. C_LI

plant biology↗

bioRxiv2026

Physiological re-replication during human stem cell differentiation

During defined developmental windows in Drosophila, controlled re-replication generates physiological gene amplification. Although gene amplification has also been observed during human stem cell differentiation, re-replication in human cells has largely been linked to tumor-associated genome instability. Here, we demonstrate that re-replication likewise operates as a physiological mechanism in human stem cells. Using Rerep-Seq and DNA fiber-combing, we identify distinct phases of re-replication during the differentiation of human myoblasts into myotubes and during the lineage commitment of mesenchymal stem cells toward adipogenic, osteogenic, chondrogenic, and neuronal fates. In all differentiation systems examined, re-replication occurred within defined temporal windows. FACS-isolated re-replicating cells exhibited elevated gene expression using RNA-Seq specifically within re-replicated genomic regions. Moreover, re-replicated DNA was detected as extranuclear DNA. These findings support a model in which cells that do not undergo re-replication, and thus avoid increased chromosomal instability, may nonetheless boost the expression of differentiation-relevant genes by acquiring re-replicated DNA released from neighboring re-replicating cells. We propose that human stem cells exploit an evolutionarily conserved re-replication mechanism to transiently increase gene copy number and thereby meet the heightened protein demands associated with differentiation.

genomics↗

bioRxiv2026

Integrated physiological performance and Nax1-mediated sodium exclusion reveal mechanisms of salinity tolerance in spring wheat (Triticum aestivum L.)

Soil salinity is a rapidly intensifying abiotic stress that significantly limits wheat productivity, particularly in coastal and irrigated agroecosystems. Although sodium (Na+) ion exclusion has been recognized as a key tolerance mechanism, the integration of physiological performance with Nax1-mediated molecular regulation among regionally adapted wheat genotypes remains insufficiently characterized. The present study aimed to dissect salinity tolerance by combining hydroponic phenotyping, multivariate trait analysis, molecular marker profiling, and quantitative expression analysis of the Na+ ion transporter gene Nax1. Seventeen spring wheat genotypes were evaluated under four salinity levels (0.0, 10, 12, and 14 dS m-{superscript 1}). Germination and survival rate, shoot and root growth, and biomass accumulation were measured. Principal component analysis (PCA) and hierarchical clustering were performed to classify genotypes, while SSR (simple sequence repeat) and Nax-linked markers assessed genetic diversity. Relative Nax1 expression was quantified using qRT-PCR (quantitative real-time polymerase chain reaction). Salinity significantly reduced germination, survival, elongation, and biomass, with strong genotype-dependent variation. Multivariate analyses clearly separated tolerant and sensitive genotypes, with biomass retention and survival contributing most to total variation. Marker analysis revealed moderate genetic polymorphism. Notably, tolerant genotypes exhibited 3-6-fold induction of Nax1 under severe salinity, positively correlating with biomass maintenance. These findings demonstrate that salinity tolerance in wheat is associated with coordinated physiological resilience and enhanced Nax1-mediated Na ion exclusion, thereby advancing mechanistic understanding and supporting molecular-assisted breeding for salt-affected environments.

plant biology↗

bioRxiv2026

Physiological cerebrospinal fluid like medium reveals autophagy dependency of leukaemia in the central nervous system

Nutrient availability is a critical environmental factor that influences the metabolism and adaptability of cancer cells, including acute lymphoblastic leukaemia (ALL) cells, prone to relapse in the central nervous system (CNS). Currently available cell culture media contain supraphysiological nutrient levels and do not represent the restricted metabolic environment of CNS-ALL which resides in the leptomeninges surrounded by cerebrospinal fluid (CSF). Therefore, we formulated a novel physiological CSF-like cell culture medium (CSFmax) that recapitulates the unique metabolite composition of the CSF. Through in vitro and in vivo metabolic and functional studies, we demonstrate that ALL cells cultured in CSFmax rewire their metabolism, closely mimicking the metabolic phenotype of CNS-ALL, including their metabolic activity and redox state. Utilising CSFmax, in comparison to conventional nutrient-rich culture media, we identified an essential role for autophagy in ALL adaptation to the CNS niche. This was evident by increased autophagic activity and selective sensitisation of ALL cells to pharmacological inhibition of autophagy and genetic knockout of Unc-51 Like Autophagy Activating Kinase 1 (ULK1) or autophagy related 7 (ATG7). Importantly, using a robust preclinical in vivo model, mice xenografted with ULK1 and ATG7 deficient ALL cells exhibited reduced CNS disease burden when compared to mice xenografted with control cells. Overall, our findings provide strong evidence that physiological CSFmax is superior to current in vitro culture systems in recapitulating the metabolic signature of CNS resident ALL cells. By exploiting this system, we revealed for the first time autophagy as a targetable therapeutic vulnerability in CNS-ALL. Key PointsO_LICulturing ALL cells in bespoke CSF-like medium (CSFmax) recapitulates the metabolic adaptation of ALL cells in the CNS niche C_LIO_LIAutophagy is critical for metabolic adaptation and survival of CNS resident ALL cells C_LI

cancer biology↗

bioRxiv2026

Nanoscale Material Size Shapes Distinct Immune Transcriptional States Under Physiological Flow

Nanoplastics interact continuously with circulating immune cells, yet how particle size and exposure complexity shape immune transcriptional organization under physiological flow conditions remains poorly understood. Here, controlled microfluidic exposure was combined with single-cell RNA sequencing to investigate the effects of size-defined polystyrene nanoplastics (PSNPs; 40 nm, 200 nm, and 40 + 200 nm) on primary human peripheral blood mononuclear cells (PBMCs) under dynamic flow conditions. Across immune populations, PSNP exposure induced a conserved ribosome-associated and RNA-regulatory transcriptional program, indicating a shared intracellular adaptive response. Monocytes displayed the strongest transcriptional remodeling, characterized by coordinated modulation of ribosome-associated, metabolic, and inflammatory signaling pathways in a size-dependent manner. Exposure to 40 nm PSNPs negatively enriched (suppressed) mitochondrial metabolic pathways, whereas 200 nm PSNPs enriched inflammatory signaling programs. Combined exposure induced concurrent metabolic and inflammatory pathway engagement without evidence of major immune topology disruption or discrete inflammatory state transitions. In contrast, adaptive immune cells exhibited comparatively modest and lineage-preserving transcriptional modulation. Together, these findings demonstrate that nanoplastic size and exposure complexity shape coordinated immunometabolic adaptation in human immune cells under physiologically relevant flow conditions and establish a framework for studying dynamic material-immune interactions at single-cell resolution.

bioinformatics↗

bioRxiv2026

Deep-learning-assisted simulation of a cortical circuit: integrating anatomy, physiology and function

Mechanistic understanding of the brain requires models constrained by anatomy, physiology, and functional activity. We present a differentiable simulator and a ~67,000-neuron model of mouse primary visual cortex that integrates multimodal data, including electron-microscopy connectomics, multipatch synaptic physiology, cell-type-resolved intrinsic electrophysiology, and large-scale Neuropixels recordings from diverse cell types. End-to-end training completes on a single GPU in ~6.5 hours while preserving biological constraints. Networks trained only on brief drifting-grating responses reproduce cell-type-specific benchmarks and generalize to new contrasts and natural scenes. We uncover heterogeneous cell-type- and tuning-dependent synaptic organization and show that training preferentially sculpts inhibitory connectivity into distinct cohorts that exert outsized control over network activity. Targeted ablations show that removing biological priors on synaptic weight distributions can preserve functional activity yet disrupt emergent wiring rules. The freely shared models and code facilitate differentiable simulations as a computationally practical framework for studying brain circuit function and mechanisms under biological constraints.

neuroscience↗

bioRxiv2026

Physiologically relevant media are associated with overlapping metabolic responses in primary human hepatocytes and Huh7 cells

BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is challenging to study in vivo in humans and in vitro models are limited. Although primary human hepatocytes (PHHs) are considered the gold-standard, immortalized hepatic cell lines are utilised due to scalability. This study compared the metabolic responses of PHHs with our Huh7-based model cultured in physiologically-relevant fatty acid (FA) mixtures. MethodsPHH and Huh7 cells were treated with 2% human serum, sugars and FAs enriched in either unsaturated (OPLA) or saturated (POLA) FAs for 4 or 7 days, respectively. Stable isotope tracers investigated basal metabolic changes in response to treatment. Cell viability, media biochemistry, intracellular metabolism, lipid droplet morphology and gene expression were quantified. ResultsHuh7 cells had greater viability than PHHs, while NEFA uptake and triglyceride secretion were similar. OPLA and POLA increased large lipid droplets in Huh7 cells, whereas only OPLA produced comparable effects in PHHs. Despite higher baseline TG in PHHs, both models showed similar lipid composition, de novo lipogenic responses, and glycogen levels. Compared to Huh7 cells, PHHs exhibited higher 3-hydroxybutyrate, lower lactate, reduced glucose uptake, and donor-dependent transcriptomic variability. ConclusionsHuh7 cells are metabolically adaptable and when cultured in physiologically-relevant media, produce metabolic readouts similar PHH cells.

cell biology↗

bioRxiv2026

Adaptive immunity shapes baseline physiology of M. tuberculosis in high-dose versus low-dose infection BALB/c mouse drug treatment models

Preclinical tuberculosis (TB) drug evaluation relies heavily on mouse infection models. Drug efficacy varies depending on inoculum and the timing of treatment initiation. These differences reflect, in part, physiological adaptations of Mycobacterium tuberculosis (Mtb) to host immune pressure. We used novel molecular markers of pathogen health (RS ratio and SEARCH-TB) to contrast Mtb phenotypes in the BALB/c high dose aerosol (HDA) subacute TB and low dose aerosol (LDA) chronic TB infection models, focusing on the transition from innate to adaptive immunity. We found that the onset of adaptive immunity coincided with a rapid reprogramming of Mtb physiology, characterized by suppressed respiration, metabolism, and biosynthesis, together with induction of stress and nutrient acquisition pathways. Changes in key Mtb processes were concordant with changes in host expression of canonical features of adaptive immunity. Our results also explain key model-specific differences in drug efficacy: when used for drug evaluation, the HDA model begins treatment during the innate immune phase when Mtb are metabolically active, whereas the LDA model initiates therapy after host adaptive immunity has already activated and the bacterial population is immune-constrained. The HDA model is shown to be a mixed model, spanning immune phases with initial treatment acting on replicating bacteria and later treatment acting on immune-constrained populations. Together, the two models offer complementary perspectives on therapeutic activity across the spectrum of bacterial states and provide a framework for designing regimens that are effective against both active and immune-constrained Mtb.

genomics↗

bioRxiv2026

Cardiac Calsequestrin is a Physiological Dimer that Polymerizes through a Ca2+-Triggered Cooperative Switch

Cardiac Calsequestrin (CASQ2) polymerizes within the junctional sarcoplasmic reticulum to buffer Ca{superscript 2} and regulate ryanodine receptor 2 (RyR2) gating, yet the molecular mechanism governing this process remains poorly understood. Using an integrated set of complementary approaches spanning single-particle biophysics, bulk solution measurements, and polymer chemistry, we demonstrate that CASQ2 is an intrinsic dimer at nanomolar concentrations and under physiological ionic conditions, independently of Ca{superscript 2}. In addition, Ca{superscript 2}-dependent polymerization operates as a highly cooperative switch between a stable oligomeric phase and a high-order polymeric state. Physiological amounts of K ions modulate this switch through a biphasic electrostatic mechanism, supporting polymerization at low concentrations and inhibiting it beyond charge neutralization ([~]194 mM). These findings redefine CASQ2 as an intrinsic dimer with polymerization-switch properties, and provide a mechanistic framework for understanding how catecholaminergic polymorphic ventricular tachycardia type 2 mutations, distributed evenly across the CASQ2 surface, cause disease through two distinct pathological trajectories.

biochemistry↗

bioRxiv2026

Lack of effect of physiological oxidative stress on N-terminal cysteine dependent proteolysis

Oxidative post-translational modifications on the sulfhydryl group of cysteines can occur spontaneously or enzymatically. The dioxygenation of N-terminal cysteines has emerged as a new oxygen sensing paradigm, catalysed by 2-aminoethanethiol dioxygenase (ADO) in mammals. Conflicting evidence has been reported in recent years on whether this reaction can occur in the absence of ADO. Here we sought to address whether physiological oxidative stress can interfere with ADO-catalysed N-terminal dioxygenation. Using a system to produce titratable intracellular levels of H2O2, we demonstrate that the stability of RGS4 and 5 is not affected by oxidative stress, whether ADO is present or not. However, cytotoxic levels of oxidative stress did induce an increase in RGS4/5 protein levels that occurred independently of the Cys N-degron pathway. This effect of tBHP was reduced by Fe2+ chelation and perturbations of lysosomal function, suggesting the possible involvement of ferroptosis. We conclude that N-terminal cysteine dependent proteolysis of RGS4/5 is not sensitive to physiological oxidative stress, but these proteins can be stabilised during the process of oxidative stress-induced cell death through an N-terminal cysteine independent mechanism.

cell biology↗

bioRxiv2026

Microfluidic bioprinting of a physiologically relevant thyroid three-dimensional in vitro model

Endocrine disruptors (EDs) are an exogenous group of compounds associated with thyroid malfunctioning in the human body. Nonetheless, there are currently no adequate in vivo or in vitro models for the preclinical testing of these compounds since both animal and two-dimensional (2D) cell-based models are not able to mimic thyroid physiological conditions from both functional and three-dimensional (3D) organization perspective. Recently, bioprinting technologies emerged as an innovative tool in the field of regenerative medicine and advanced 3D in vitro models that allow the creation of 3D well-organized structures able to mirror physiologically relevant tissue and organ architectures. In this study, we evaluated microfluidic bioprinting as a biofabrication technology to develop a 3D in vitro model of the thyroid gland. We studied the fundamental parameters to obtain a fine control over the bioprinted fibres for different biomaterials. Then, we assessed the possibility to bioprint single thyroid cells, thyroid spheroids and finally mouse embryonic stem cell-derived thyroid follicles. The different cell types maintained high viability and metabolic activity. The bioprinted thyroid model showed high expression of different early and late functional markers and to be responsive to ED exposure. These bioprinted thyroid constructs could provide a new set of advanced 3D in vitro models to test potential EDs and possible adverse outcomes that may be associated with their administration or exposure.

bioengineering↗

bioRxiv2026

Oral and gut microbiomes reveal latent physiological constraints on release readiness in rehabilitating Javan slow lorises

Illegal wildlife trade and habitat degradation displace thousands of animals annually in Southeast Asia, with many confiscated primates housed in rehabilitation centers that increasingly function as long-term holding environments. In slow lorises, dental clipping associated with the pet trade may generate persistent disruption along the oral-gut axis, potentially undermining physiological readiness for release in ways not captured by conventional screening. Here, we evaluated whether microbiome structure provides an integrative marker of release readiness in rehabilitating Javan slow lorises (Nycticebus javanicus). From June to October 2024, we collected fecal (n = 26) and saliva (n = 18) samples from 19 adults housed at YIARI, including 10 release candidates and 9 non-candidates classified primarily based on tooth loss, medical history, and possibility of release. Bacterial communities were characterized using 16S rRNA (V3-V4) amplicon sequencing, with alpha and beta diversity, taxonomic enrichment (LEfSe), and predicted functional profiles (PICRUSt2) assessed. Microbiome composition was strongly compartmentalized by body site, with higher alpha diversity in the gut. Release candidacy was associated with modest gut compositional differences, whereas oral microbiomes showed pronounced divergence between candidates and non-candidates. Non-candidates were enriched in dysbiosis-associated taxa and degradation-oriented functional pathways, while candidates showed enrichment of biosynthetic and central energy metabolism pathways. Gut microbiome structure was stable across pre-release and soft-release phases. These findings indicate that oral and gut microbiomes represent distinct physiological niches and that persistent oral microbiome alteration is a sensitive marker of long-term dental perturbation. Integrating microbiome-informed metrics may improve multidimensional assessment of release readiness.

microbiology↗