Vision-Based Digital Twin and AI Agent Framework for Low-Cost, Explainable Indoor Building Inspection and Safety Assessment.

Ischemic Stroke (IS), caused by cerebral artery occlusion leading to focal interruption of blood flow and subsequent ischemic necrosis of brain tissue, accounts for over 9.7 million new cases annually, imposing a heavy burden on global public health (). Endovascular therapies, represented by mechanical thrombectomy and pharmacological thrombolysis, have significantly improved recanalization rates in ischemic patients. However, nearly half of these patients still fail to achieve favorable functional outcomes even after successful recanalization of the occluded vessel, revealing a long-neglected clinical bottleneck—CIRI (). During blood reperfusion, cells within the ischemic penumbra undergo a “damage storm” driven by a complex interplay of reactive oxygen species (ROS) burst, calcium overload, mitochondrial dysfunction, inflammatory cytokine storm, and multiple forms of programmed cell death (apoptosis, ferroptosis, pyroptosis) (). Among these, microglia play an indispensable role in the inflammatory response following cerebral ischemic injury. They can switch their polarization states and secrete various cytokines, thereby modulating neuroinflammation through multiple pathways and participating in the repair process (). Of note, excessive activation or improper polarization of microglia may also promote the progression of inflammation, further exacerbating the adverse outcomes of brain injury. To treat CIRI, decades of research into neuroprotective agents targeting different pathological mechanisms (e.g., anti-oxidation, anti-inflammation, anti-apoptosis) have never ceased. In recent years, minocycline and other tetracycline antibiotics have been found to exert certain neuroprotective effects against cerebral ischemic injury, independent of their antimicrobial activity (). Minocycline, a semi-synthetic tetracycline, is characterized by its low cost and relatively few side effects, making it a promising candidate for stroke treatment. The protective effects of minocycline in acute ischemic stroke have been validated in multiple clinical trials (). Several systematic reviews and meta-analyses have been conducted to assess the efficacy of minocycline in treating acute ischemic stroke, and the results have confirmed its protective role in ischemic stroke (). Furthermore, animal studies have demonstrated the efficacy of minocycline in reducing cerebral infarct volume, improving neurobehavioral functions, and decreasing mortality in CIRI rat models (). Despite the promise shown by most drugs in animal models, they have repeatedly failed in clinical trials. The fundamental reason lies in the “delivery dilemma” commonly faced by these drug molecules: the physical barrier of the blood–brain barrier (BBB) and the highly heterogeneous, oxidative, and inflammatory pathological microenvironment following reperfusion result in low trans-barrier transport efficiency and rapid inactivation of the drugs (). Therefore, there is an urgent need to achieve precise, stable, and low-toxicity targeted delivery to improve the treatment of cerebral ischemia-reperfusion injury. In response to the complex pathological microenvironment of CIRI and the drug delivery bottleneck, engineered living cell delivery systems have attracted considerable attention due to their unique biological properties (). Neutrophils possess an innate chemotactic ability toward inflammation: the abundant chemokines (e.g., IL-8, LTB4) and damage-associated molecular patterns released in the lesioned area after CIRI can be actively recognized by neutrophils, enabling them to precisely home to the ischemic penumbra (). Leveraging the increased permeability of the BBB under inflammatory conditions and their own transendothelial migration mechanisms, neutrophils achieve highly efficient lesion-targeted delivery. Moreover, neutrophils can internalize or surface-conjugate therapeutic nanomedicines, which are then released in a spatiotemporally controlled manner upon reaching the inflammatory region, triggered by the local microenvironment (). Notably, neutrophils themselves are involved in amplifying inflammatory injury in CIRI (e.g., releasing ROS, NETs, and proteases); thus, improper engineering modifications may exacerbate secondary injury ().