搜索结果：integrity

The biological function of the cell membrane is significantly affected by a disrupted lipid bilayer. Maintaining the structural integrity of the lipid bilayer is hence crucial. In this work, a series of molecular dynamics (MD) simulations were carried out by varying ethanol and glucose concentrations to investigate the counteracting effects of glucose concentration on the ethanol-stressed disorganized hydrated model lipid bilayer, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Our work highlights that the ethanol's concentration-dependent disruptive role affects bilayer integrity, as evidenced by increased lateral diffusion, reduced bilayer thickness, and enhanced disorder in the structural arrangements of the lipids, including the surface curvature order parameter. We observed that the addition of glucose, to some extent, opposes such disorganization. Our investigation reveals that glucose forms substantial hydrogen bonds with lipid headgroups, thereby reducing ethanol-headgroup interaction and promoting tighter lipid packing. The minimum-distance distribution functions suggest that, while water is excluded from the lipid tail, ethanol is found all the way towards the lipid tails, and the terminal methyl groups interact significantly, causing the lipid tails to bend toward the polar regions of the bilayer. This phenomenon however was observed less in the presence of glucose. An inverse relationship between glucose concentration and translational mobility is consistently observed across all ethanol concentrations studied, while higher ethanol content facilitates glucose mobility, regardless of the glucose concentration. This suggests a complex interplay between glucose and ethanol that modulates the diffusive dynamics of the solvent and solute, affecting lipid diffusion and its structural integrity. The computation of the potential of mean force (PMF) using the umbrella sampling technique highlights that the ethanol penetration process is significantly less favored and energetically hindered in the presence of glucose; as a result, lipid diffusion is slowed down. Our findings provide insights into the molecular mechanisms and underscore the protective role of glucose in stabilizing lipid bilayers under alcohol-induced stress. The study is relevant to various pharmaceutical and biomedical applications, as well as the design of biopreservation strategies for cells and tissues.

Lectins are carbohydrate-binding proteins that recognize specific glycan patterns on cell surfaces and have been increasingly explored as analytical tools in reproductive biology. This study characterized the interaction of a lectin isolated from Abelmoschus esculentus seeds (AEL) with ovine spermatozoa and evaluated its compatibility with sperm functional parameters during short-term refrigeration. Eighteen ejaculates were diluted in a Tris-egg yolk extender supplemented with 0, 1, or 3 µg/mL AEL and stored at 5°C for 24 h. Sperm motility (CASA) and flow cytometry were used to assess plasma membrane integrity and fluidity, mitochondrial membrane potential, and reactive oxygen species production. Confocal microscopy was performed to determine the localization pattern of AEL binding. AEL labeling was predominantly restricted to the sperm midpiece region. Supplementation with AEL at the tested concentrations did not affect motility patterns, membrane integrity, mitochondrial membrane potential, or ROS levels after 24 h of storage (p > 0.05). These findings indicate that AEL exhibits a consistent midpiece-associated binding pattern and does not compromise sperm functional parameters under refrigerated conditions. The results support the use of AEL as a compatible probe for investigating glycan distribution in the midpiece region of ram spermatozoa.

The skin is far from a passive shield; it functions as a dynamic "living barrier" whose structural and immunological integrity is paramount in preventing atopic dermatitis (AD) and the subsequent progression of the atopic march toward food allergy (FA). While prophylactic emollient therapy has emerged as a promising strategy for primary prevention, recent large-scale randomized controlled trials have yielded conflicting results. In this review, we examine the complex interplay between emollient formulations, skin barrier biology, and immune responses in the context of AD and FA prevention. We discuss the functional roles of occlusives, humectants, and barrier-replenishing lipids, highlighting how their composition, ratios, and physicochemical properties determine their effects on barrier integrity. We further evaluate the impact of additional formulation components, including food-derived ingredients, haptens, irritants, and pH, as well as external factors such as product handling and application practices, which may inadvertently promote barrier disruption and transcutaneous sensitization. Collectively, current evidence supports a shift from generalized emollient use toward a precision-based, barrier-directed approach. Optimized formulations that restore physiological lipid composition, combined with early intervention and integration of objective biomarkers, may offer a more effective strategy to prevent AD and the atopic march.

Tracheal diverticulum is frequently detected incidentally on cross-sectional imaging but may pose a significant intraoperative challenge when anticipated within or adjacent to the thyroid surgical field, particularly in close proximity to the recurrent laryngeal nerve (RLN) and during central compartment (level VI) dissection. Conventionally, surgeons use preoperative computed tomography (CT) to approximate diverticular anatomy and then rely on intraoperative experience and anatomic landmarks for dissection. Recognition is challenging because intraoperative localization relies on CT correlation and anatomic landmarks within the posterior capsular plane; limited exposure may obscure the diverticulum, and a non-aerated sac may collapse and become indistinguishable from surrounding soft tissue, increasing the risk of rupture and subsequent loss of tension with further obscured planes and potential operative-field contamination. However, a standardized intraoperative workflow to functionally localize the diverticulum (and confirm tracheal communication) before definitive posterior dissection, and to verify tracheal integrity after diverticulectomy and repair, is lacking. Here, we describe a stepwise surgical technique for planned thyroidectomy in which a cervical tracheal diverticulum has been identified preoperatively. The workflow integrates preoperative contrast-enhanced CT-based risk stratification with a ventilation-assisted functional visualization maneuver [standardized endotracheal tube (ETT) repositioning within recorded cuff-depth boundaries 'D_cuff, the ETT incisor depth at which the proximal cuff margin is visualized just distal to the vocal cords; D_cuff2, the deeper ETT incisor depth after advancement beyond the diverticular level to keep the cuff distal to the diverticular ostium'] to localize the diverticular sac at the CT-predicted region and confirm tracheal communication before definitive posterior dissection. After localization, posterior dissection proceeds with deliberate RLN identification and protection, followed by controlled diverticulectomy and submerged air-leak testing under gentle manual ventilation to verify tracheal wall integrity.

Intestinal barrier dysfunction is a key driver of septic liver injury (SLI). Dachaihu decoction (DCHD), a classic traditional Chinese medicine formula recorded in the Treatise on Cold Damage, is widely used to treat gastrointestinal and hepatic inflammatory conditions. The primary objective of our research was to elucidate the protective effects of DCHD against SLI and the underlying molecular mechanisms. In a murine model of sepsis induced by cecal ligation and puncture (CLP), we evaluated the therapeutic effects of DCHD on SLI by assessing serum liver enzymes, histopathology, oxidative stress, hepatocyte apoptosis, and inflammatory cytokines. Intestinal barrier integrity was examined via transmission electron microscopy, serum biomarkers (D-lactate, DAO, LPS), and tight junction proteins (ZO-1, Occludin, E-cadherin). Gut microbiota composition was analyzed using 16S rRNA sequencing. Chemical profiling of DCHD was performed via UPLC-Q-TOF-MS. Integrated network pharmacology, bioinformatics, and transcriptomic analyses identified the NF-κB/NLRP3/Caspase-1 axis as a potential mechanism, which was validated in vivo and in LPS-stimulated immortalized mouse Kupffer cells (ImKCs). Functional involvement of TLR4 and NLRP3 was further confirmed by genetic silencing of TLR4 with siRNA and pharmacological inhibition using TAK-242 (TLR4 inhibitor) and MCC950 (NLRP3 inhibitor). DCHD treatment attenuated liver injury in CLP-induced septic mice, as evidenced by improved liver function, attenuated histopathology, reduced oxidative stress, suppressed inflammation, and decreased hepatocyte apoptosis. These hepatoprotective effects were associated with reduced intestinal permeability and enhanced barrier integrity, alongside gut microbiota remodeling characterized by enrichment of beneficial bacteria and reduced abundance of gram-negative genera (e.g., Klebsiella, Enterobacter, Proteus), leading to decreased LPS production and translocation to the liver. Integrated network pharmacology and transcriptomics revealed the NF-κB/NLRP3/Caspase-1 axis as a central mechanism, with DCHD downregulating p-p65, p-IκBα, NLRP3, ASC, and Cleaved Caspase-1 in vivo and in LPS-stimulated ImKCs. Functional validation using TLR4 siRNA and the inhibitors TAK-242 and MCC950 confirmed that DCHD might attenuate liver inflammatory injury primarily through the NF-κB/NLRP3/Caspase-1 signaling pathway. DCHD may alleviate SLI by enhancing the intestinal barrier, potentially reducing the translocation of gut-derived LPS to the liver, and subsequently inhibiting the NF-κB/NLRP3/Caspase-1 axis, highlighting its considerable translational potential for SLI therapy.

This study presents a comprehensive investigation into the effects of nonlinear vibrational regimes on the structural and functional integrity of reduced graphene oxide- hydroxyapatite (rGO-HA) scaffolds fabricated via extrusion-based 3D-printing. A coupled Van der Pol-Duffing oscillator model was developed to simulate vibrational dynamics during deposition, and its influence was experimentally validated using MEMS accelerometry and scaffold characterization. rGO-HA composite powders were synthesized via hydrothermal methods and formulated into inks with varying HA content. Scaffolds printed under vibrational excitation exhibited pronounced morphological defects, including anisotropic pore geometry, surface cracking, and disrupted layer alignment. Elemental mapping revealed compositional heterogeneity, while pore size analysis indicated increased defect density. Mechanical testing showed a ∼17% reduction in compressive strength, and electrical conductivity declined by ∼78% under vibrational conditions, attributed to disrupted graphene networks and poor interfacial bonding. Comparative analyses confirmed the detrimental impact of dynamic perturbations on scaffold fidelity. These findings underscore the critical importance of vibration control in biofabrication and offer a predictive framework for optimizing scaffold performance in tissue engineering and smart biomaterial applications.

This study investigated the effects of polishing duration (15-120 s) in a laboratory abrasive rice polisher on milling quality, grain characteristics, and kernel surface microstructure. The results revealed that the degree of polishing (DOP) increased significantly from 2.38% (15 s) to 15.29% (120 s), which was accompanied by a higher broken content (from 6.35% to 18.45%) and a reduced head rice yield (from 93.6% to 80.3%). The complete removal of bran streaks required a DOP >13.05%, but this threshold also coincided with over-milling and yield loss. Scanning electron microscopy (SEM) images revealed the progressive abrasion of the protuberances and bran layers, with uniform polishing achieved only after 90 s. These findings clearly indicate the trade-off between bran removal and grain integrity, underscoring the need to optimize the polishing time for balanced quality, yield, and sustainability in rice processing. Therefore, this study highlights how optimizing rice polishing through abrasive milling can reduce grain breakage, increase head rice yield, and improve grain uniformity, thereby minimizing postharvest losses. By balancing whiteness, transparency, and surface structure, this research supports more efficient use of harvested rice, promoting food security and sustainability in grain processing.

Prostate-specific membrane antigen (PSMA) is a validated target for prostate cancer imaging and radiotherapy, with most high-affinity ligands incorporating the lysine-urea-glutamate (KuE) pharmacophore. Despite emerging triphosgene-free approaches, current synthetic strategies still largely rely on hypertoxic triphosgene for asymmetric urea formation. Herein, we report a comparative evaluation of triphosgene-free acyl-transfer reagents for on-resin KuE formation under solid-phase peptide synthesis (SPPS) conditions. Among the reagents examined, 1,1'-carbonyldiimidazole (CDI) emerged as the most effective, enabling near-quantitative urea formation under mild, SPPS-compatible conditions. Application of the optimised CDI-mediated protocol on TentaGel® resin bearing an HMPB linker enabled efficient fully solid-phase assembly of PSMA-617 in >80% crude purity and 31% isolated yield. Purified PSMA-617 was radiolabelled with 68Ga in >99% radiochemical purity, confirming chemical integrity. Additionally, the PSMA-I&T backbone and four PSMA-617 analogues were synthesised in high crude purities, demonstrating rapid on-resin ligand construction for structure-activity relationship (SAR) studies.

As part of a programme of work developing human-relevant New Approach Methodologies (NAMs) for next-generation risk assessment (NGRA), use of a human air-liquid interface (ALI) bronchial epithelial model (MucilAir™) to investigate the impact of exposure to protease was assessed. To guide in vitro dosing, scenarios representing low-high risk of sensitisation after 8 h of protease exposure in an occupational setting were modelled by performing simulations with the Multiple Path Particle Dosimetry (MPPD) model with refinement of the outputs using a tracheobronchial/alveolar clearance model, to estimate tracheobronchial tissue doses. With no effects seen at these concentrations, higher concentrations were subsequently tested to identify thresholds for biological effects. Repeated apical liquid exposures over 8 h were applied using a wide concentration range of protease (0.00125-7812 μg protease protein/mL) or phosphate-buffered saline (PBS) control. Effects on epithelial barrier integrity, cytokine production, and extracellular vesicle (EV) dynamics were measured. Reduced transepithelial electrical resistance (TEER), increased EV and IL-8 secretion were observed using a PBS control reflecting the impact of liquid dosing alone. No significant protease-related adverse effects were observed at concentrations of 0.5 μg protease protein/mL or lower when compared to the PBS control. At concentrations of 75 μg protease protein/mL or more, however, TEER was significantly reduced and mucin and tetraspanin expression on EVs was degraded. Here, we show the impact of liquid dosing when investigating the effects of materials on bronchial epithelia, and challenges encountered when working with proteases. This work provides a foundation for developing in vitro methodology for generation of data for use in risk assessment of inhalation of enzymes and other materials. It is hypothesised that nebulised protease delivery could be a more suitable alternative and better replicate in vivo (human) inhalation dynamics.

Current biodegradable polymers for absorbable tissue ligation clips suffer from not possessing rigidity and toughness simultaneously compared with polyoxymethylene (POM) clips. To overcome the limitations, two series of biodegradable copolymers of poly(ε-caprolactone) and poly(L-lactide) with random and block architectures were designed and synthesized. Compared with random copolymer P(CL-r-LLA), diblock copolymer PCL-b-PLLA exhibited higher crystallinity and superior mechanical strength. The copolymers with 15 mol% CL composition were selected for further study, denoted as RP15 (random) and BP15 (block). The BP15 clips achieved a closure force of 27.9 ± 1.4 N, comparable to commercial POM clips (29.0 ± 2.4 N), while also offering biodegradability. The degradation studies showed that BP15 clips degraded slowly, maintaining structural integrity and sustained closure functionality for up to two weeks, which was essential for safe tissue ligation. Subcutaneous implantation in rats further confirmed that BP15 clips exhibited favorable performances, demonstrating their potential as a promising biodegradable alternative to POM for use as an absorbable tissue ligation clip.

To systematically evaluate the morphology, temporal evolution and musculoskeletal adaptations associated with semitendinosus tendon (ST) and muscle (SM) regeneration after isolated ST autograft harvest for primary anterior cruciate ligament reconstruction (ACLR). A systematic review was conducted according to PRISMA 2020 guidelines. PubMed, Embase, Scopus and Web of Science were searched from inception to 20 December 2025. Eligible studies included primary ACLR with isolated ST autografts and objective post-operative assessment of ST or SM regeneration using imaging (ultrasound, magnetic resonance imaging and computed tomography) or histology. Methodological quality was evaluated using the JBI checklist for randomized controlled trials and the Methodological Index for Non-Randomized Studies instrument for non-randomized studies. Due to heterogeneity in surgical techniques, imaging protocols, follow-up intervals and regeneration definitions, results were synthesized narratively according to synthesis without meta-analysis principles, with regeneration frequencies reported by modality and predefined time windows. Sixteen studies comprising 376 patients (mean age 25.5 years) were included. Across studies, tendon-like continuity was frequently detected between 6 and 12 months post-operatively, although reported regeneration rates varied depending on imaging modality and definitional criteria. The regenerated neotendon (NT) typically demonstrated non-anatomical distal attachment or fusion patterns, accompanied by proximal migration of the musculotendinous junction, permanent shortening and atrophy of the SM. The ST and SM exhibit robust biological potential for regeneration after isolated harvest, typically forming a viable NT within the first post-operative year. However, regeneration does not restore native anatomy; significant muscle shortening, atrophy and proximal insertion shifts are consistent findings. Despite these morphological deficits, the high rate of tissue continuity supports the isolated ST graft as a low-morbidity option that preserves overall hamstring complex integrity. Level IV.

TMS-007 is a member of the SMTP congeners for the treatment of acute ischemic stroke. To support its preclinical study, LC-MS/MS methods for the quantification of TMS-007 in rat plasma and brain were developed. The samples were prepared by protein precipitation. A UPLC HSS T3 column (2.1 mm × 50 mm, 1.8 µm) was used to achieve chromatographic separation. An acetonitrile-water mixture containing ammonium acetate was used as the mobile phase. The methods were validated with regard to selectivity, calibration curve and lower limit of quantitation, accuracy and precision, matrix effect, extraction recovery, carryover, dilution integrity, and stability. The calibration ranges of TMS-007 in rat plasma and brain homogenate were 10.0-10 000 ng mL-1. There was no endogenous or cross interference in the biological matrices. Across these matrices, the intra- and inter-batch coefficients of variation and accuracy deviations for all QC samples met the acceptance criteria. The inter-batch coefficients of variation of the QC samples were ≤11.7% for plasma and ≤15.0% for brain. The inter-batch accuracy ranged from 97.8% to 104.1% for plasma and 97.1% to 102.3% for brain. No significant matrix effect was observed from the matrices (from 102.9% to 111.0% for plasma and from 114.3% to 118.9% for brain). The extraction recoveries of the methods at different concentrations were consistent and reproducible. For plasma, the coefficients of variation were ≤9.9%, and for brain, the coefficients of variation were ≤4.6%. The analyte was stable in different matrices under various storage conditions (room temperature for 8 h, 4 °C in the autosampler for 3 days, 3 freeze-thaw cycles and 7 days at -70 °C). The methods were successfully applied to a preclinical study in a transient middle cerebral artery occlusion rat model after single dose administration. The pharmacokinetic results of the study drug laid a foundation for its further development.

Effective management of IBD necessitates ongoing evaluation of disease activity. Molecular imaging of neutrophil elastase (NE) could address this urgent need as it mechanistically targets the early event of intestinal inflammation. In this study, based on macrocyclic peptide POL6014, [68Ga]Ga-POL6014 was developed for noninvasive assessment of colitis activity and treatment response through targeting of NE. [68Ga]Ga-POL6014 exhibited high specificity and affinity for NE with the KD of 14.81 nM and IC50 of 3.02 nM. In PET imaging, [68Ga]Ga-POL6014 could quickly visualize inflammation sites with colon uptake of 3.15 ± 0.63%ID/g and colon/muscle ratio of 4.92 ± 0.74 at 30 min p.i.. The specificity of [68Ga]Ga-POL6014 was demonstrated by the dose-response blocking studies with POL6014. Furthermore, [68Ga]Ga-POL6014 PET was used to evaluate treatment response to 5-ASA. The treatment significantly inhibited colon uptake of [68Ga]Ga-POL6014 (1.71 ± 0.21 %ID/g), accompanied by a decrease in imaging contrast (2.81 ± 0.26). Immunofluorescence revealed the preservation of mucosal barrier integrity and a remarkable decrease in NE positive cells after 5-ASA treatment. Moreover, there were good correlations between PET quantification with NE expression and DAI score, indicating the reliability of [68Ga]Ga-POL6014. Additionally, [68Ga]Ga-POL6014 was widely distributed and cleared rapidly from nonspecific organs and blood pool, and was excreted through urinary system, suggesting its favorable pharmacokinetics. In conclusion, [68Ga]Ga-POL6014 is a promising tracer that enables in vivo globally mapping of neutrophil-mediated inflammation in the entire gastrointestinal tract for early diagnosis, assessment of disease activity and evaluation of anti-inflammatory treatment response.

Native long-read DNA sequencing simultaneously captures genetic variants and epigenetic modifications from single molecules, but preserving molecular length and base modifications currently depends on cold-chain infrastructure that limits access to well-resourced settings. We demonstrate that ensilication, the encapsulation of DNA within silica matrices, preserves DNA at ambient temperature for 30 days with sequencing performance equivalent to conventional - 80 °C freezing. Across three Genome-in-a-Bottle reference genomes, ensilicated and frozen samples show no significant differences in read length (N50 ~ 8,000-11,000 bp), variant-calling accuracy, or genome-wide CpG methylation. Single-read methylation calls benchmarked against an independent bisulfite-sequencing reference confirm that ensilication introduces no detectable bias, with per-read accuracy differing by less than 0.4% between preservation conditions. Ensilicated DNA tolerates repeated handling better than frozen samples and maintains fragment integrity under accelerated weathering. In two patients with rare genetic disorders, ambient-preserved DNA resolves a de novo variant in the segmentally duplicated GTF2I locus and detects methylation patterns consistent with KDM2A-related disorder. Ensilication enables diagnostic-quality native long-read sequencing without cold-chain infrastructure, supporting ambient storage and transport while preserving both sequence and methylation information.

The cellular DNA damage response (DDR) is essential for maintaining genome integrity in the face of exogenous assault, as well as errors and breaks introduced during DNA replication. The DDR is a complex network of cellular processes that detects the type and severity of DNA damage and coordinates downstream actions. These include activating specific DNA repair pathways, including cell cycle arrest to allow time for repair, and-if the damage is irreparable-triggering apoptosis to eliminate cells with compromised genomes. DNA viruses have evolved multiple strategies to evade, suppress, or even hijack host DDR factors to promote their own replication. In the absence of such countermeasures, the activation of the host DDR may rapidly detect viral genomes as aberrant DNA, and restrict viral infection. Paradoxically, many DNA viruses depend on many aspects of the host DDR to ensure efficient replication of their genomes. Here, we focus on human cytomegalovirus (HCMV), a beta-herpesvirus with a large complex double-stranded DNA genome, and its relationship with host DDR. Although HCMV infects most of the human population, fundamental gaps remain in understanding how viral replication modulates a robust cellular DDR or recruits it for its own replication. Moreover, the roles of DDR in restricting viral DNA (vDNA) replication, promoting entry into latency, stabilizing latent genomes during cellular proliferation, and promoting vDNA synthesis following infection or reactivation from latency remain poorly understood.

Shifting human subjects research from research sites to participants' homes removes barriers to participation. Previously, we developed homeRNA, a kit for stabilization of RNA in self-collected blood using a custom-engineered tube containing RNA stabilizer fluid. The stabilized RNA is extracted and used for downstream gene expression analysis. Here, we introduce homeRNAmax, which improves our original design by interfacing with a commercially available blood collection tube (BD Microtainer), allowing homeRNAmax to be used with any blood collection method that uses this tube and doubling the possible sample volume that can be collected and stabilized compared to the original homeRNA. Through a pilot study (n = 19 participants), we show that homeRNAmax (with the Tasso+ blood collection device) produces RNA samples of sufficient quality (mean RIN = 7.8) and yield (mean yield = 1.93 μg) for downstream analysis and can reach participants across the United States, who generally (n = 17/19) found the homeRNAmax kit easy to use. We also present RNA integrity data from an ongoing longitudinal clinical study using homeRNAmax in rheumatology (mean RIN = 7.1). A key aspect of the homeRNA and homeRNAmax platforms is a fluidic feature that prevents the RNA stabilizer from spilling, for which we developed a theoretical model. In brief, fluid in the tube is suspended due to a balance of pressures; an increase in air volume within the tube reduces the air pressure above the fluid, creating a small vacuum, and preventing fluid leakage. Overall, we show that homeRNAmax is a user-friendly, effective tool for remote blood RNA stabilization.

The mechanical mismatch between rigid clinical electrodes and soft biological tissues remains a primary bottleneck restricting the stability of long-term electrophysiological monitoring. Printable flexible thin-film electrodes offer a compelling solution by enabling additive, high-throughput patterning on flexible and stretchable substrates, thereby circumventing the reliance on vacuum environments and high-temperature processing typical of conventional microfabrication. This review synthesizes recent advances in functional inks, ranging from metals and carbon nanomaterials to conductive polymers and ionogels, together with high-resolution printing techniques. Addressing the critical challenge of interfacial failure in flexible devices, we explore engineering strategies to enhance adhesion at both electrode-substrate and electrode-tissue interfaces. Specifically, we analyze the pivotal roles of physical interlocking and chemical anchoring mechanisms in suppressing dynamic delamination and maintaining device integrity. Finally, the review highlights representative applications in wearable electronics, implantable systems, and emerging organoid interfaces, and outlines key translational challenges, including long-term stability and manufacturing reproducibility.

Bile salts are key regulators of intestinal homeostasis and host-microbe interactions in the intestine. While bile salt hydrolase (BSH) activity is known to modulate host metabolism, the direct interplay between bile salt signaling, microbial BSH activity, bile acid signaling, and epithelial responses in colorectal cancer remains poorly understood. Here, we established a controlled in vitro co-culture platform using isogenic murine healthy and tumor-derived colon organoids to dissect bile salt-driven epithelial-microbe responses at cellular resolution. We investigated the dynamics between the host and an engineered BSH-expressing Escherichia coli strain (EcAZ-2LsBSH) compared to its native counterpart (EcAZ-2). We found that while bile salts broadly impaired bacterial colonization, EcAZ-2LsBSH preferentially colonized tumor organoids over healthy controls. Crucially, microbial BSH activity functionally rescued host signaling in healthy organoids, driving a robust 1.5-fold upregulation of the farnesoid X receptor (FXR) protein and activating downstream cell lineage pathways. In contrast, tumor organoids exhibited an intrinsic resistance to this FXR-mediated metabolic rescue. Furthermore, we identified the epithelial surface attachment factor Hspg2 (Perlecan) as a dynamically regulated target at the host-microbe interface. While bile salt exposure increased Hspg2 expression, bacterial colonization triggered significant transcriptional suppression, revealing opposing regulatory mechanisms that govern bacterial adhesion. Together, this study demonstrates that microbial metabolism of bile acids exerts profound, context-dependent effects on epithelial signaling and barrier integrity, providing a mechanistic foundation for the development of engineered bacterial therapeutics in colorectal cancer.