A Unified Upstream Architecture for Human Tissue Reconstruction: Immediate Phase Transition and Parallel Immune–Regenerative Activation

This is a preprint and has not been peer-reviewed. Acute human injury has long been understood to proceed from inflammation to reconstruction, yet the upstream mechanism governing this transition has never been directly observed. In our previous work (Paper 1), we recorded a rapid biological response induced by localized mild mechanical stimulation (RE-regenerative acupuncture) using three independent layers of analysis: plasma proteomics, exosome cargo profiling, and flow cytometry. In this study (Paper 4), we reanalyzed this dataset with a specific focus on the immediate activation phase that occurs directly after threshold-level injury, thereby revealing the biological entity that initiates the transition. We found that at the very onset of the response (0 min), the entire physiological system undergoes an abrupt shift to a distinct stable state, forming a Systemic Biological Phase Transition (SBPT) in which four initial reactions—Immune Alert, Antiviral Shutdown, Limiter Release, and Pre-stored Activation—are launched synchronously. This coordinated activation simultaneously establishes optimized immune positioning, suppression of viral replication, release of structural and metabolic restraints, and mobilization of translation-independent repair resources, thereby creating all prerequisites for tissue reconstruction within the first moment of response. Following SBPT, from 0 to 120 minutes, we observed the parallel activation of the seven early regeneration templates conserved in highly regenerative organisms, together with a human-specific immune reconstruction module. The biphasic dynamics of TSP-1 and the synchronized peaks of MSCs and NK cells demonstrate that regeneration and immunity are jointly regulated by a unified upstream switch, referred to here as Factor X. Together, these findings show that human tissue reconstruction does not follow the classical sequential model in which regeneration begins only after inflammation resolves. Instead, humans operate via a threshold-dependent integrated architecture (ERDP) in which immunity, regeneration, and metabolism are switched together as a single system. Clarifying the conditions required for SBPT and identifying its upstream driver (Factor X) may provide a new conceptual framework for understanding acute injury responses, chronic inflammation, degenerative diseases, and aging.