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Rab family proteins are GTPases and members of the Ras superfamily of monomeric G proteins. These membrane-associated proteins are involved in many aspects of vesicle-mediated transport, taking part in the initial vesicle formation, transport of vesicles along the cytoskeleton, and eventual fusion of vesicle and target membranes. Rab4 is localized at early endosomes/recycling endosomes and functions as a key regulator for sorting/recycling of membrane and proteins. Both Rab4A and Rab4B isoforms are localized to similar cellular compartments and are believed to have similar functions. Rab4 interacts with several Rab4 effectors in a complex on a special endosome site to promote membrane/protein recycling.

PTEN (phosphatase and tensin homologue deleted on chromosome ten), also referred to as MMAC (mutated in multiple advanced cancers) phosphatase, is a tumor suppressor implicated in a wide variety of human cancers. PTEN encodes a 403 amino acid polypeptide originally described as a dual-specificity protein phosphatase. The main substrates of PTEN are inositol phospholipids generated by the activation of the phosphoinositide 3-kinase (PI3K). PTEN is a major negative regulator of the PI3K/Akt signaling pathway. PTEN possesses a carboxy-terminal, noncatalytic regulatory domain with three phosphorylation sites (Ser380, Thr382, and Thr383) that regulate PTEN stability and may affect its biological activity. PTEN regulates p53 protein levels and activity and is involved in G protein-coupled signaling during chemotaxis.

Mitogen‑activated protein kinase (MAPK) signaling cascades represent a set of highly evolutionarily conserved signal transduction systems that exist across primitive prokaryotes and complex mammalian cells. Among all MAPK subfamilies, the MAPK‑ERK axis specializes in relaying extracellular stimuli from the cell surface deep into the cytoplasm and nucleus. After completing multi‑step kinase phosphorylation cascades, this pathway initiates a wide spectrum of cellular physiological outcomes, including cell cycle progression, clonal proliferation, cell lineage differentiation, malignant transformation, and programmed cell death (apoptosis). Its high conservation across species highlights its irreplaceable role in maintaining basic cellular homeostasis.

The mitogen‑activated protein kinase (MAPK) cascade refers to an evolutionarily conserved intracellular signaling module that governs multiple core cellular behaviors such as cell proliferation, differentiation and migratory movement. This signaling system consists of a wide array of functional protein molecules, among which ERK (extracellular signal‑regulated kinases) represents the initial identified subtype of MAPK family. It relays intracellular signals via sequential protein phosphorylation, acting as molecular switches to turn biological processes on or off.

The mammalian target of rapamycin (mTOR) signaling cascade receives and consolidates signals originating from both inside and outside cells, and exerts critical regulatory effects on a wide array of cellular activities, including metabolic balance, cell expansion, division, and cell survival.

Nuclear factor‑kappa B (NF‑κB) refers to a collective group of transcription factor proteins that exert biological effects in dimeric forms, controlling the expression of target genes associated with immune defense, inflammatory reactions and cellular survival status.

Oxidative phosphorylation, also called electron transport-coupled phosphorylation, refers to a core metabolic route that transforms chemical energy released during nutrient oxidation into ATP via the electron transport chain. It acts as a critical cellular energy conversion reaction and represents the final stage of aerobic respiration inside eukaryotic cells.

TP53 gene aberrations show strong pathological correlation with a wide range of human malignancies, including hepatocellular carcinoma, mammary carcinoma, bladder cancer, ovarian neoplasms, intracranial tumors, gastric carcinoma, colorectal cancer, esophageal carcinoma, lung carcinoma and hematological leukemia.

ALS is a fatal neurodegenerative disease. Traditional research has largely focused on limb paralysis symptoms caused by motor neuron damage; however, clinical data show that more than half of patients experience cognitive impairments beyond the motor system, with approximately 35% of patients exhibiting mild cognitive and behavioral abnormalities, primarily manifested as language deficits, executive dysfunction, and apathy. Some patients may further develop frontotemporal dementia (ALS-FTD). For a long time, the pathological mechanisms underlying the different cognitive subtypes of ALS have remained unclear, and it is not known whether the various cognitive decline phenotypes originate from a unified core pathological pathway or from specific molecular interaction abnormalities at the level of brain regions and cells. Moreover, conventional clinical diagnosis and treatment lack a refined cognitive assessment system, and existing studies cannot fully elucidate the pathological changes involving multicellular interactions in the ALS brain. TDP-43 proteinopathy, as a classic pathological hallmark of ALS, also cannot fully explain the individual differences in cognitive impairments among patients. Based on this, the study integrates clinical cognitive stratification phenotypes with multi-omics spatial mapping technology to systematically analyze cellular and molecular abnormalities in the prefrontal cortex of ALS patients, revealing specific cellular phenotypes and pathological mechanisms corresponding to different cognitive decline.

The essence of biochemical conjugation labeling lies in utilizing the specific affinity between biomolecules along with chemical conjugation reactions to covalently or non-covalently combine effector molecules with recognition capabilities with labels possessing detection, modification, and regulatory functions. Antibodies, functional proteins, peptides, nucleic acids, and small bioactive molecules serve as core effector carriers, playing a crucial role in target recognition and specific binding; various fluorescent agents, enzymes, and biofunctional modification materials serve as labels, responsible for signal output, performance optimization, and functional enhancement.