Xiang Li

Pathological remodeling of transverse tubules (T-tubules, TTs) is commonly observed in cardiac disease and may be promoted by sustained adrenergic stimulation. Although cholinergic signaling has been associated with cardioprotective effects, it remains unclear whether it directly modulates TT integrity in cardiomyocytes. Here, we examined how cholinergic receptor activation affects TT organization during acute β-adrenergic stimulation in isolated adult rat cardiomyocytes. Cells were exposed to isoproterenol (ISO), alone or in combination with acetylcholine (ACh) or nicotine (Nic). Confocal imaging showed that ISO disrupted TT organization and reduced the cellular length-to-width (L/W) ratio. ACh or Nic alone altered TT architecture, primarily by reducing TT power and increasing longitudinal tubule density; however, co-treatment with either agonist was associated with altered TT remodeling responses to ISO in TT structure and cell morphology. The muscarinic receptor agonist xanomeline (Xano) did not reproduce these effects. These results suggest a cardiomyocyte-autonomous role for nAChR signaling in limiting acute β-adrenergic stimulation-induced TT remodeling. Further studies are required to identify the nAChR subtype and downstream signaling mechanisms involved and to determine the relevance of these findings in vivo.

Background/Objectives: The blood–brain barrier (BBB) is compromised in many neurological disorders, yet in vitro models rarely reproduce graded inflammatory stimulation of brain endothelial cells in vivo. This study developed a detachable, modular BBB-on-a-chip for stepwise inflammation modeling with multi-marker readout, and compared the anti-inflammatory efficacy of quercetin (QUER) and kaempferol (KAE). Methods: The chip combines a Christmas-tree concentration gradient generator with a four-channel culture module, fabricated separately and assembled on demand for stepwise seeding, exposure, dosing, and sampling. hCMEC/D3 cells were exposed to a TNF-α gradient (0–30 ng/mL); extracellular ATP, ROS, NO, cytokines, ZO-1, and ICAM-1 were monitored over 48 h. Transcriptomics and network pharmacology were integrated with molecular docking and 100 ns molecular dynamics simulations; QUER and KAE were administered gradient-wise (0–20 μM), with dexamethasone as a control. Results: The TNF-α gradient induced time- and concentration-dependent injury, with ATP and IL-8 responding at 8 h, ROS and NO at 12 h, and IL-1β, IL-6, and tight-junction impairment later, yielding spatiotemporally resolved readouts across four parallel channels. Ten hub inflammatory genes, including ICAM1, were identified, and network pharmacology nominated QUER. QUER was predicted to bind ICAM-1 more strongly than KAE, its structural analog differing by one B-ring hydroxyl group; gradient administration confirmed QUER suppressed ICAM-1 expression and inflammatory mediator release at lower concentrations. Conclusions: The detachable modular design makes multi-step inflammation modeling and gradient-based anti-inflammatory evaluation convenient on a single chip; QUER’s consistent advantage over KAE across binding calculations and functional assays supports a structure-activity relationship consistent with ICAM-1 engagement.

Fusel oil is a by-product during the fermentation of alcoholic beverage, mainly including n-propanol, isobutanol, isopentanol, and others. Long-term or excessive intake of them may cause potential harm to human health. In the present work, we preliminarily evaluated the cytotoxicity of n-propanol and isobutanol, main components of fusel oil, in human fetal astrocytes (SVGp12), human microvascular endothelial cells (HMEC-1), and human microglial cells (HMC3). The results showed that both n-propanol and isobutanol exhibited cytotoxicity in all three types of cells, and the release of proinflammatory cytokines (IL-6 and IL-8) significantly increased in the cells exposed to fusel oil components. The transepithelial electrical resistance (TEER) values were decreased and the permeability was increased in HMEC-1 cells exposed to fusel oil components. These results indicate that fusel oil components may cause potential harm to human health.

Microorganism-based tumor therapy has attracted increasing interest due to the intrinsic tumor tropism and metabolic plasticity of certain bacterial species. However, their therapeutic efficacy is often hindered by insufficient metabolic activity within the tumor microenvironment and safety concerns associated with systemic administration. Here, we develop a biohybrid system, termed Ce6@PB@MR-1, to enhance the intrinsic tumor-targeting behavior of chlorin e6 (Ce6) and lactate-metabolizing capability of Shewanella oneidensis MR-1 (MR-1) through engineered material-microbe coupling. In this system, Prussian blue (PB) is metabolically precipitated onto the MR-1 surface during anaerobic respiration, forming an electron-mediating interface in which PB functions as an efficient exogenous electron acceptor to strengthen respiratory electron flux and accelerate the lactate metabolism of MR-1. The PB coating simultaneously attenuates bacterial immunogenicity, enabling the improved in vivo persistence and safety of MR-1. Furthermore, bioconjugated Ce6 enables 660 nm-triggered photodynamic therapy to induce immunogenic cell death and activate antitumor immune responses. In vivo, the biohybrid system achieves durable tumor eradication accompanied by a marked remodeling of the tumor microenvironment. This work establishes a metabolically assisted material-microbe hybridization framework that expands microbial functionality and offers a versatile strategy for developing safe and effective microbe-based cancer therapies.

Unmanned Aerial Vehicles (UAVs) are widely used in Internet of Things (IoT) scenarios, but factors like circuit malfunctions and network issues can lead to data loss, disconnections, and service interruptions, causing UAVs to go offline and fail to meet user needs. This problem can be effectively solved using UAV resource migration techniques. However, traditional methods lead to resource redundancy and cannot ensure effective migration decisions or the continuity of services. Therefore, we proposed a new UAV framework with a high-availability migration strategy to improve UAV swarm resource utilization. By combining Software Defined Network and Mobile Edge Computing technologies, we designed a UAV collaboration architecture model and introduced large language model agents in the edge layer for better task execution. Additionally, we created a two-tier collaborative UAV high-availability mechanism for handling failures in edge scenarios during UAV collaborative tasks. Our experiments on the container cloud platform showed a 42% reduction in failure recovery time and higher overall resource utilization compared to baseline algorithms. While our focus is on UAVs, our findings can potentially be applied to broader IoT and mobile edge computing scenarios such as traffic management systems and healthcare IoT systems.

We developed an advanced bionic breathing-type airway exposure platform to address the anatomical and physiological limitations of conventional inhalation toxicology models. This system integrates four key technological innovations: a biomimetic respiratory structure with a 3D-bioprinted, anatomically realistic tracheobronchial tree that includes integrated oral/nasal conduits and compliance modules, enabling spatially resolved simulation of aerosol deposition; an intelligent multi-mode breathing control system that reproduces clinical and tobacco-related inhalation patterns at a 0.1-second resolution via triple-route switching; programmable CO₂control to simulate both normal and pathological respiratory gas exchange; and modular sub-regional exposure interfaces for compartment-specific toxicological analysis. Validation studies demonstrated that the platform accurately replicates smoking-related aerosol deposition patterns and detects dose-dependent cytotoxic and pro-inflammatory responses in air-liquid interface cultured human bronchial epithelia. By offering a physiologically realistic model for investigating inhalation toxicity mechanisms and particle dynamics, this platform effectively bridges the gap between in vitro systems and human respiratory responses.

The blood-brain barrier (BBB) is a vital defense interface of the central nervous system that selectively regulates molecular transport into the brain and maintains brain homeostasis. Disruption of BBB integrity contributes to various neurological diseases and represents a key target for therapeutic compounds. However, traditional in vitro models are hard to recreate BBB’s complex structure and dynamic functions. Recent advances in microfluidics and three-dimensional bioprinting have enabled the construction of high-fidelity BBB in vitro models that imitate the brain’s vascular microenvironment. By integrating principles from materials science, microfabrication, and cell biology, these “BBB‑on‑a‑chip” platforms support physiologically relevant shear stress, cell–cell interactions, and barrier properties, making them powerful tools for compound screening and mechanistic research. This review summarizes the advance in BBB in vitro model and the application of bioprinting and microfluidic technology for compound evaluation.

Formaldehyde poses a significant threat to human health, yet its toxicity assessment is limited by current detection methods. This study developed a modular biomimetic lung chip which consists of gas concentration gradient generator module and cell culture module, assembled using alignment holes and micropillars. This design enables stepwise experimental procedures, including cell loading, gas concentration gradient exposure, and cell sample collection, through the assembly and disassembly of the modules. Using this chip to investigate the formaldehyde-induced cellular ferroptosis, BEAS-2B cells were exposed to formaldehyde under a concentration gradient. Transcriptomic sequencing revealed the effects of different formaldehyde concentrations on the expression of ferroptosis-related genes in cells, identifying 12 ferroptosis-related genes (FRGS) and an enhancement of oxidative stress. The ferroptosis inhibitor (deferoxamine mesylate) significantly reduced cell death and reactive oxygen species levels, confirming the involvement of ferroptosis in formaldehyde-induced toxicity. Furthermore, deferoxamine mesylate modulated the expression of hub genes of FRGS, including PTGS2, ATF3, CDKN1A, PLIN2, and DUOX1, at both transcript and protein levels. These findings provide novel insights into the molecular mechanisms underlying formaldehyde-induced respiratory damage and establish the modular biomimetic lung chip as a powerful platform for studying environmental toxicants.