Biology subjects

Maity, S.

Publications and source records attributed to Maity, S..

At least 19 recordsLinked to original sources

bioRxiv2026

Model-based pupil deconvolution reveals latent attentional dynamics

Changes in pupil size have been widely used as an indirect measure of attention. However, attention engages on a faster timescale than the pupillary response. Therefore, the slow time course of the pupil response makes it difficult to distinguish attentional responses to stimuli presented in close temporal succession. Although signal deconvolution has been used in previous research to estimate latent attentional responses from the pupil signal, existing methods primarily model dilation without considering the visual stimulus evoked constriction phase of the pupil. Here, we introduce a dual-kernel deconvolution model that models constriction and dilation using separate impulse response functions. Using an RSVP paradigm with emotional faces as target stimuli, we demonstrate that the proposed model estimates latent attentional response despite substantial overlap in the measured pupil signal. Importantly, the recovered attentional response resembles the time course of attentional allocation previously predicted by several models of Attentional Blink. Together, these findings demonstrate that the dynamics of latent attentional episodes can be recovered from the pupil response with a temporal resolution previously obscured by the sluggishness of the pupillary response. The proposed method is also provided as a usable software package that serves as a general tool for investigating the temporal dynamics of attention in rapid visual paradigms.

neuroscience↗

bioRxiv2026

Reconstructing time-resolved inter-residue distance distributions in a protein ensemble during functional dynamics in solution

Reconstructing time-resolved inter-residue distance distributions during protein functional dynamics in the solution state is known to be a difficult and important problem. This article presents a technique for extracting spin-spin (as a proxy for residue-residue) distance distributions on doubly-spin-labeled proteins from rapid-scan time-resolved Gd-Gd electron paramagnetic resonance (rs-TiGGER) spectra recorded near room temperature in solution at 240 GHz. We use a best-fit technique that convolves a dipolar kernel matrix with an intrinsic, non-dipolar-broadened (single-labeled) spectrum. The kernel incorporates the effect of solution-state tumbling on the dipolar broadening using a correlation function that bridges the static and rapidly tumbling regimes. We apply the technique to AsLOV2, a protein domain with a dark-state crystal structure that is well-known from X-ray crystallography, but a less well-characterized and disordered tertiary structure that manifests after photoactivation at 450 nm. Informed by principal component analysis, we assume that the underlying distance distribution may be approximated by a sum of two Gaussian distributions. The fits returned time-resolved, light-activated populations with mean distances of [Formula] (dark) and [Formula] (lit) in the wild type, and [Formula] (dark) and [Formula] (lit) in an N414Q mutant, with nearly complete unfolding (within fit uncertainty) of the active, light-sensitive fraction. The extracted distance distributions and their accompanying uncertainties are consistent within uncertainty with molecular dynamics simulations of the equilibrated protein structure.

biophysics↗

bioRxiv2026

Quantum transduction from electron spin state to a signaling state in a wild-type LOV photoreceptor

1Whether coherent spin dynamics can control biological regulation remains an open question. Here we show that the electron spin state in the wild-type Avena sativa phototropin 1 Light-Oxygen-Voltage domain 2 (AsLOV2) modulates FMN-cysteine photoadduct formation, the covalent bond that defines its signaling state. Although AsLOV2 was thought magnetically inactive, we observe a magnetic field effect (MFE) on its fluorescence, emerging above ~100 mT and strengthening to 1300 mT. The MFE establishes a spin-correlated radical pair on the photoadduct pathway, one rendered inaccessible to direct spectroscopy by the same strong coupling that sets the high-field onset. It arises from g-factor asymmetry within the closely spaced FMN-cysteine radical pair overcoming its dipolar coupling to drive coherent singlet-triplet interconversion. We furthermore observe an MFE in UV-Vis absorption that, unlike fluorescence, shows the field modulates productive bond formation itself. LOV domains are ubiquitous biological regulators, suggesting that quantum transduction relying on radical pairs as molecular qubits may be a general property among natural and engineered photoreceptors.

biophysics↗

bioRxiv2026

The CYP27A1 - VDR Feedback Rheostat Controls Mitochondrial Protein Homeostasis and Preserves Hippocampal - Striatal Network Integrity to rescue Cognitive impairment in HD condition

Emerging evidence links vitamin D (VD) deficiency to cognitive and motor dysfunction in Huntingtons disease (HD), yet the underlying mechanism remains unclear. Here, we combine in vitro genetic and 3-nitropropionic acid (3-NP)-induced in vivo models of HD to define the mechanistic basis of VD-mediated neuroprotection. We demonstrate that VD supplementation restores cognitive and motor deficits while improving mitochondrial function and cellular survival. Mechanistically, VD enhances mitochondrial fusion and rescues complex II expression, a key defect in HD pathology. We identify the mitochondrial enzyme CYP27A1 as a critical mediator of this effect, as its expression is reduced in HD models but restored upon VD treatment. Overexpression of CYP27A1 recapitulates the protective effects of VD, confirming its central role in maintaining mitochondrial integrity. Furthermore, VD promotes vitamin D receptor (VDR)-dependent transcriptional activation of CYP27A1 and additional nuclear- and mitochondrial-encoded genes, establishing a regulatory feedback loop that supports mitochondrial biogenesis and function. VD supplementation also improves proteostasis via attenuating endoplasmic reticulum stress. Together, our findings uncover a previously unrecognized VD-CYP27A1 axis that links mitochondrial dysfunction to HD pathology and highlight CYP27A1 as a potential therapeutic target.

neuroscience↗

bioRxiv2026

Patient-Specific Vascularized Lung Tumor Organoids for Tumor-Immune Profiling

The use of cellular systems to advance cancer therapeutics has expanded rapidly, spanning cell therapies to patient-specific tumor models. Platforms that recapitulate key features of the tumor microenvironment, including vascular and immune components, hold significant potential to improve the predictive power and translational relevance of preclinical models. Here, we report a vascularized tumor organoid platform that combines self-organizing microvascular networks with patient-derived tumor organoids and tumor-infiltrating lymphocytes. To minimize non-specific endothelial immunogenicity and enable broader compatibility across patient samples, we engineered the vasculature using {beta}2-microglobulin-knockout endothelial cells. Leveraging this system, we established patient-specific, lymphocyte-incorporated tumor models that enabled quantitative assessment of T cell infiltration. In conjunction with immune checkpoint blockade, this platform distinguishes responder and non-responder patient samples, consistent with the clinical observations. Single-cell RNA-sequencing revealed tumor-intrinsic and immune-associated programs underlying this stratification, identifying tumor-driven hyperangiogenic signaling as a barrier to T cell extravasation. Pharmacological co-targeting of PD1 and VEGF restored T cell infiltration in non-responder organoids, shifting them from an immune-excluded to an immune-inflamed state. Together, this vascularized tumor organoid platform provides a predictive and mechanistic framework for modeling patient-specific immunotherapy responses and design of combination therapies.

bioengineering↗

bioRxiv2026

Dimeric Alix nucleates ESCRT-III CHMP4 polymerization

Alix is a key adaptor protein of the endosomal sorting complex required for transport (ESCRT) membrane remodeling machinery. Although Alix-mediated recruitment of the ESCRT-III subunit CHMP4 is well established, the molecular mechanisms underlying Alix activation and ESCRT-III polymerization remain poorly understood. Here, we present the crystal structure of the dimeric Alix V-domain (Alix-V) in complex with a llama nanobody. Dimerization is mediated by domain swapping, generating an X-shaped flexible conformation. We demonstrate that Alix forms dimers in vivo and provide evidence for the recruitment of dimeric Alix to plasma membrane repair sites and the cytokinetic midbody. Notably, a mutation disrupting Alix dimerization impairs plasma membrane repair. Furthermore, high-speed AFM experiments reveal that dimeric Alix, but not the monomeric form, nucleates CHMP4B filament polymerization. Our data establish that dimeric Alix is the active form responsible for nucleating two ESCRT-III CHMP4 filaments, whose geometry creates a platform for the recruitment of downstream ESCRT-III components required to assemble the active membrane remodeling and fission machinery.

biochemistry↗

bioRxiv2026

A nested shell structure coordinates enzyme communication in pyruvate oxidation

The pyruvate dehydrogenase complex (PDHc)1 links glycolysis to the Krebs cycle by catalyzing the oxidative decarboxylation of pyruvate to acetyl-CoA and CO2, a process essential for life2,3. PDHc is formed by structural proteins (E3-binding protein, E3BP)4-7, enzymatic subunits (E1, E2, E3)4,6, and mobile lipoyl domains (LDs), the latter shuttling intermediates across active sites6,8. Although numerous details regarding pyruvate oxidation steps have been elucidated9, the precise organization of the entire PDHc remains unknown due to its large size and dynamic heterogeneity. Here, we employ in silico, in vitro, and in situ methods to propose a multi-scale model of PDHc that includes approximately one million atoms and to visualize multiple conformational states. This model reveals a [~]40-50 nm nested shell structure, formed by flexible linkers that spatially coordinate the E1 and E3 enzyme complexes around the E2-E3BP core scaffold. This structure acts as a molecular sieve, selectively guiding lipoyl arms while maintaining enzyme positioning with sub-nm precision. During catalysis, the nested shell structure expands and adopts a mechanically reinforced state comparable in magnitude to viral assemblies10. Our findings provide structural context for the textbook "link reaction"11, building on decades of biochemical knowledge, are transferable to functional aspects of other -ketoacid dehydrogenase complexes, and, ultimately, expand our understanding of primary metabolism as a whole. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=195 SRC="FIGDIR/small/724543v1_ufig1.gif" ALT="Figure 1"> View larger version (70K): org.highwire.dtl.DTLVardef@1615612org.highwire.dtl.DTLVardef@159bc8dorg.highwire.dtl.DTLVardef@69f8c1org.highwire.dtl.DTLVardef@14a83a3_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2026

Identification of Key Residues in Allosteric Signaling of Photoactivated Adenylyl Cyclase

Photoactivated adenylyl cyclases (PACs) convert ATP to cyclic AMP (cAMP) through long-range photoinduced allosteric communication between a BLUF domain and a distant adenylyl cyclase (AC) domain. Although photoactivation of the BLUF domain induces only minimal structural changes, it activates a chemical reaction about 4-5 nm away. Here, we combine molecular dynamics simulations, electronic structure calculations, network theory, and machine-learning approaches to investigate photoinduced allostery in the PAC from Beggiatoa sp. (bPAC). We observed that the photoexcitation enables electron transfer from a conserved tyrosine (Tyr7) to the flavin isoalloxazine ring, while the free energy of the electron transfer remains similar across active and inactive mutants. Therefore, photoinduced allosteric activity arises from conformational effects rather than changes in the electronic parameters. Using network theory and eigenvector centrality analysis, we identified residues relevant to allosteric pathways linking the BLUF and AC domains. Furthermore, we used machine-learning (ML) models to distinguish active and inactive conformational states without prior knowledge of functional residues. Remarkably, the ML models identified key regions known from network analysis. Together, these results provide a generalizable frame-work for understanding allosteric pathways in blue-light-sensitive proteins.

biophysics↗

bioRxiv2026

Excessive Ca2+-dependent ER-mitochondrial contact stabilization by EFHD1 drives liver injury

Metabolic-associated steatohepatitis (MASH) involves hepatocyte damage that cannot be explained solely by lipid accumulation. Here, to discover injury-specific pathways, we focused on a gene of uncertain function, EF-Hand Domain Family Member D1 (EFHD1), identified in human genome-wide association studies of liver injury but not liver fat. We show that EFHD1, a Ca2+-dependent actin crosslinker, stabilizes endoplasmic reticulum-mitochondria contact sites (ERMCS), detecting spatiotemporal coincidence of inter-organellar proximity and ER Ca2+ release. During MASH, EFHD1 upregulation drives pathological mitochondrial fragmentation via excessive contact persistence. This structural failure promotes mitochondrial double-stranded RNA escape and activation of a maladaptive antiviral PKR-dependent stress response, a causal relationship also supported by Mendelian randomization in humans. Consequently, inhibiting EFHD1 in human and mouse models blunts hepatocyte damage. These findings identify EFHD1 as a Ca2+-dependent ERMCS stabilizer, reveal a hepatocyte-intrinsic injury pathway, and suggest EFHD1 inhibition as a therapeutic strategy.

cell biology↗

bioRxiv2025

Dapagliflozin mitigates hypoxia-induced metabolic stress, kidney tubular cell death and fibrosis

Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) slow progression of kidney disease but therapeutic mechanisms remain elusive. Here we report the beneficial effect of dapagliflozin on hypoxia-mediated kidney tubular epithelial cell injury, a contributing factor to kidney disease progression, using a human pluripotent stem cell (hPSC)-derived hypoxic kidney organoid model. Hypoxic organoids showed increased expression of Hypoxia Inducible Factor (HIF)-associated transcriptional targets, decreased tricarboxylic acid (TCA) cycle metabolites and mitochondrial {beta}-oxidation protein expression, and activated unfolded protein response. A transcriptional signature derived from hypoxic organoids 1) identified a subgroup of individuals whose kidney disease subsequently progressed, and 2) correlated with worse tubular injury. Dapagliflozin enhanced mitochondrial stress response resulting in reversed hypoxia-induced tubular epithelial cell apoptosis, reactive oxygen species (ROS) accumulation, and organoid fibrosis. These results indicate that dapagliflozin may contribute to improved kidney disease outcomes by attenuating hypoxia-induced metabolic stress-mediated tubular epithelial cell injury.

cell biology↗

bioRxiv2025

PEX11β-mediated improvement of mitochondrial dysfunction restores behavioral defect and cellular viability in neuropathological conditions

Peroxisomal biogenesis factor 11 beta (Pex11{beta}) is a key regulator of peroxisome proliferation, functioning in coordination with mitochondrial fission proteins. Recent human proteome co-regulation mapping has revealed a distinctive co-expression pattern between Pex11{beta} and components of the mitochondrial respiratory chain complex at the peroxisome-mitochondria interface. In neurodegenerative disorders, such as Huntingtons disease (HD) and Alzheimers disease (AD), mitochondrial dysfunction is primarily associated with impairments in the respiratory chain complexes, particularly Complex II. However, the role of Pex11{beta} in maintaining mitochondrial homeostasis in these two disease conditions remains largely unexplored. In this study, using both in vitro and in vivo models, we identify Pex11{beta} as a critical modulator of mitochondrial dynamics, influencing the balance between fission and fusion. Through targeted knockdown and overexpression experiments, we demonstrate a direct link between Pex11{beta} level and mitochondrial dysfunction, mediated by transcriptional dysregulation of nuclear-encoded Complex II and mitochondrial fusion genes. Restoration of Pex11{beta} expression, along with Complex II and fusion gene level in striatal brain via a peroxisome proliferator & chemical chaperone, significantly alleviates motor and cognitive deficits in 3-NP-induced HD mouse model indicating better mitochondrial health in striatal brain. Furthermore, in silico analysis and ChIP-qPCR reveal Yin Yang 1 (YY1) is a critical transcription factor governing the co-expression of Pex11{beta} and Complex II genes. This establishes a novel transcriptional axis that orchestrates inter-organellar communication. Collectively, our findings position Pex11{beta} as a pivotal mediator of mitochondrial fission-fusion dynamics, linking mitochondrial morphology and oxidative phosphorylation (OXPHOS) to behavioural outcomes, and offering mechanistic insights relevant to amyloid-associated neurodegenerative diseases.

neuroscience↗

bioRxiv2025

Ultra-High-Throughput LC-MS Method for Targeted Protein Degradation Compound Screening Using the Orbitrap Astral Mass Spectrometer

High-throughput proteomics analysis is crucial for targeted protein degradation (TPD) compound screening. Here, we developed a 300 sample per day (SPD) LC-MS method using the Orbitrap Astral mass spectrometer for ultra-high-throughput TPD compound screening. We identified close to 8,000 protein groups from a single cell line with a coefficient of variance (CV) of less than 10%, highlighting the deep proteome coverage and method reproducibility even at 300 SPD. This high degree of precision provides the statistical confidence to detect subtle, yet significant, changes in protein abundance that were previously challenging to quantify in high-throughput workflows. To evaluate the quantitation accuracy of this method, we further mixed the digests from two or three species at different ratios. Our three-proteome mixture results demonstrated highly accurate quantitation for proteins with both small and large fold changes. Moreover, our two-proteome mixture experiment, where 20 to 160 ng of yeast digest was spiked into 200 ng of HeLa digest, showed an R2 of 0.999 for the yeast proteome, underscoring the quantitation accuracy of the method. Utilizing this workflow, we studied dose-dependent protein degradation patterns induced by pomalidomide, iberdomide, and mezigdomide. Our results indicate that mezigdomide may possess enhanced efficacy in T cells by degrading additional proteins such as IKZF2, thereby boosting anti-cancer immunity. Together, we developed an ultra-high-throughput LC-MS method with excellent proteome coverage and quantitation accuracy that is highly suitable for chemoproteomics screening of drug libraries.

biochemistry↗

bioRxiv2025

A sex hormone-BDNF-TrkB axis directs sympathetic innervation in the mouse mammary gland

Stromal-epithelial interactions underlie fundamental tissue morphogenesis in normal development, tissue regeneration and cancer. Peripheral nerves are increasingly implicated as important stromal drivers of normal and malignant epithelial tissue biology. In the mammary gland, epithelial cell fate is highly dependent on stromal cues during distinct stages of postnatal growth which are triggered by ovarian sex hormones estrogen and progesterone. However, the effects of sex hormones on peripheral nerves in the postnatal mammary gland is largely unknown. Here, we uncover extensive changes in peripheral sympathetic innervation in the mammary stromal microenvironment during puberty and pregnancy which are periods of active postnatal mammary epithelial growth. We find that sex hormones induce sympathetic axonal branching through an intricate hormone-epithelial-nerve cross-talk. Specifically, estrogen and progesterone stimulate the expression of brain-derived neurotrophic factor (BDNF) in mammary hormone receptor- expressing luminal epithelial cells which acts on Tropomyosin receptor kinase B (TrkB)- expressing sympathetic nerves to activate BDNF-TrkB signaling. Our findings illustrate a previously unrecognized capacity of hormone-sensing epithelial cells to modulate sympathetic innervation, providing a framework for understanding nerve dynamics during tissue regeneration and cancer.

molecular biology↗

bioRxiv2025

Cellular and Spatial Drivers of Unresolved Injury and Functional Decline in the Human Kidney

Building upon a foundational Human Kidney resource, we present a comprehensive multi-modal atlas that defines spatially resolved versus unresolved repair states and mechanisms in human kidney disease. Homeostatic interactions between injured kidney epithelium and its surrounding milieu determine successful repair outcomes, while pathogenic signaling promotes unresolved inflammation and fibrosis leading to chronic disease. We integrated multiple single-cell and spatial modalities across [~]700 samples from >350 patients ([~]250 research biopsies), analyzing [~]1.7 million cells alongside complementary mouse multi-omic profiles spanning acute-to-chronic injury and aging (>300,000 cells) and spatial transcriptomic analysis of >150 human biopsies. This cross-species atlas delineates functional pathways and druggable targets across the nephron and defines gene regulatory networks and chromatin landscapes governing tubular, fibroblast, and immune cell transitions from injury to either recovery or failed repair states. We identified distinct cellular states associated with specific pathological features that show dynamic distributions between acute kidney injury (AKI) and chronic kidney disease (CKD), organized within unique spatial niches that reveal progression mechanisms from early injury to unresolved disease. Gene regulatory analyses prioritized key transcription factor activities (SOX4, SOX9, NFKB1, REL, KLFs) and their target networks establishing disease states and tissue microenvironments. These regulatory programs were directly linked to clinical outcomes, identifying molecular signatures of recovery and secreted biomarkers predictive of AKI-to-CKD progression, providing a key resource for therapeutic development and precision medicine approaches in kidney disease.

molecular biology↗

bioRxiv2025

Hydraulic Activation of the AsLOV2 photoreceptor

How proteins transduce light into mechanical energy remains a central question in biology. This study tests the hypothesis that blue light activation of the LOV2 (light, oxygen, voltage sensitive) domain of Avena sativa phototropin 1 (AsLOV2), gives rise to concerted water movement that induces protein conformational extensions. Using electron and nuclear magnetic resonance spectroscopy, along with molecular dynamics simulations at high pressure, we find AsLOV2 activation can be initiated by blue light or high pressure, followed by selective and concerted expulsion of low-entropy, tetrahedrally coordinated "wrap" water from the protein hydration shell. These findings suggest that interfacial water serves as constituents to reshape the proteins free energy landscape during activation. Our study highlights hydration water as an active hydraulic fluid that can drive long-range conformational changes underlying protein mechanics upon light activation and offers a new concept for engineering externally controllable protein actuators. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=70 SRC="FIGDIR/small/660617v2_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1a35f9dorg.highwire.dtl.DTLVardef@da4991org.highwire.dtl.DTLVardef@113e9b2org.highwire.dtl.DTLVardef@53d9fc_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2025

Decoding Breast Cancer in X-ray Mammograms: A Multi-Parameter Approach Using Fractals, Multifractals, and Structural Disorder Analysis

We explored the fractal and multifractal characteristics of breast mammogram micrographs to identify quantitative biomarkers associated with breast cancer progression. In addition to conventional fractal and multifractal analyses, we employed a recently developed fractal-functional distribution method, which transforms fractal measures into Gaussian distributions for more robust statistical interpretation. Given the sparsity of mammogram intensity data, we also analyzed how variations in intensity thresholds, used for binary transformations of the fractal dimension, follow unique trajectories that may serve as novel indicators of disease progression. Our findings demonstrate that fractal, multifractal, and fractal-functional parameters effectively differentiate between benign and cancerous tissue. Furthermore, the threshold-dependent behavior of intensity-based fractal measures presents distinct patterns in cancer cases. To complement these analyses, we applied the Inverse Participation Ratio (IPR) light localization technique to quantify structural disorder at the microscopic level. This multi-parametric approach, integrating spatial complexity and structural disorder metrics, offers a promising framework for enhancing the sensitivity and specificity of breast cancer detection.

cancer biology↗

bioRxiv2025

Modeling Immunosenescence on-a-chip: a platform for cancer vaccine efficacy assessment

Immunosenescence dramatically reduces cancer vaccine efficacy in elderly patients, who represent the majority of cancer cases. Despite this clinical reality, age-related immune decline is rarely considered in preclinical testing. Therefore, novel in vitro models to test cancer vaccine efficacy, considering immunosenescence, are needed. Our novel lymph node paracortex on-a-chip (LNPoC) platform addresses this gap by recapitulating age-dependent immune responses against cancer vaccines, specifically antigen presentation, antigen-specific T cell activation, and antitumoral responses. Using this platform, we demonstrated that bone marrow-derived antigen-presenting cells (APCs) from young mice (6-7 weeks) displayed significantly enhanced ovalbumin (OVA) peptide presentation compared to APCs from older mice (35-36 weeks). This age-dependent difference translated to significantly greater OVA-specific CD8+ T cell activation and increased cytotoxicity against B16-OVA cancer cells. These age-dependent differences are unique to our LNPoC and undetectable in traditional 2D cultures, confirming that our LNPoC was more effective than 2D cultures at recapitulating immunosenescence-mediated immune responses against cancer vaccines in vitro. The in vivo validation confirms these findings, as young mice demonstrated higher OVA-specific CD8+ T cell responses and smaller tumors than older mice. Our LNPoC is a valuable tool for assessing immunosenescences impact on cancer vaccines, potentially guiding more effective therapies for older adults.

bioengineering↗

bioRxiv2025

Embolization-on-a-chip: Novel Vascularized Liver Tumor Model for Evaluation of Cellular and Cytokine Response to Embolic Agents

BackgroundEmbolization is a well-established treatment modality for liver cancer. However, traditional embolization agents are limited by inefficient delivery and aggregation in blood vessels. Novel shear-thinning hydrogels (STH) have been developed to address the need for safer and more effective local delivery of embolic agents and therapeutics. ObjectiveWe aim to evaluate the efficacy of novel embolic agents such as STH using a human-relevant in vitro model that recapitulates human hepatocellular carcinoma capillary networks. MethodsA vascularized human liver-tumor-on-a-chip model was developed to assess embolic agent performance. The effects of drug-eluting STH (DESTH) on tumor cell viability, surface marker expression, vasculature morphology, and cytokine responses were evaluated. To study the effects of embolization on microvasculature morphology independent of the chemotherapy compound, we assessed the effect of different drug-free embolic agents on the vascular tumor microenvironment under flow conditions. ResultsDESTH treatment induced tumor cell death, downregulated the expression of Epithelial Cell Adhesion Molecules (EpCAM) in HepG2, increased levels of cytokines such as Interleukin-4 (IL-4), Granulocyte-macrophage colony-stimulating factor (GM-CSF), and Vascular Endothelial Growth Factor (VEGF), and decreased albumin secretion. Furthermore, different embolic agents exert distinct effects on microvascular morphology, with STH causing complete regression of the microvascular networks. ConclusionThis vascularized liver tumor-on-a-chip model enables human-relevant, real-time assessment of embolic agent efficacy and vascular response, paving the way for the development of innovative and effective embolization therapies for liver cancer.

bioengineering↗