Chimeric antigen receptor-natural killer (CAR-NK) cells are emerging as a promising platform for allogeneic, cell-based immunotherapy. Among available sources, NK cells derived from pluripotent stem cells (PSCs) provide a renewable and scalable option that overcomes the limitations of primary NK cells. Human epidermal growth factor receptor 2 (HER2), a membrane protein frequently overexpressed in many solid tumors, is an attractive target for cancer immunotherapy. In this study, we designed a green fluorescent protein (GFP)-linked anti-HER2 CAR construct and introduced it into PSCs via lentiviral transduction. Three stable PSC-derived clones (CAR-A, CAR-B, and CAR-C) were established, each co-expressing anti-HER2 CAR with GFP. After differentiation under xeno-free and feeder-free culture conditions, CAR expression was maintained in NK cells. The resulting PSC-derived CAR-NK cells displayed phenotypic and functional features comparable to wild-type PSC-derived NK cells, while showing markedly enhanced cytotoxicity against HER2-positive cancer cell lines. These findings demonstrated the potential of the use of PSC-derived anti-HER2 CAR-NK cells as a robust and scalable immunotherapy. In addition, this platform could be extended to produce CAR-NK cells directed against a wide range of tumorassociated antigens. [BMB Reports 2025; 58(11): 475-483].

Glucosamine (GlcN), a critical substrate in the hexosamine biosynthetic pathway, is known to modulate inflammatory responses in macrophages depending on extracellular glucose concentration. In hyperglycemic conditions (25 mM glucose), GlcN suppresses the production of nitric oxide (NO) and decreases the expression of inducible nitric oxide synthase (iNOS). Conversely, under normoglycemic conditions (5 mM glucose), GlcN paradoxically enhances lipopolysaccharide (LPS)-induced iNOS expression, NO production, and the upregulation of additional proinflammatory mediators. In this study, we examined the effect of alloxan, a known O-GlcNAc transferase (OGT) inhibitor, on GlcN- and/or LPS-mediated inflammatory responses in RAW264.7 macrophage cells. Under hyperglycemic conditions, alloxan exhibited little effect on the LPS-induced or LPS plus GlcN-induced expression of iNOS, cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). In contrast, under normoglycemic conditions, alloxan significantly inhibited the induction of these inflammatory genes in response to LPS plus GlcN. At the mechanistic level, alloxan reduced NF-κB DNA-binding activity and prevented its recruitment to the iNOS promoter. In addition, alloxan attenuated GlcN-induced increase in OGlcNAcylation of the NF-κB subunit p65. Collectively, these results indicate that OGT-mediated O-GlcNAcylation of NF-κB is critical for GlcN-induced proinflammatory signaling under normoglycemia. Our work highlights the glucose dependency of O-GlcNAc cycling in macrophage responses and provides new perspectives on the metabolic regulation of innate immune responses. [BMB Reports 2025; 58(11): 467-474].

The human genome contains sequences derived from endogenous retroviruses (HERVs), which constitute approximately 8% of chromosomal DNA. Most HERVs are currently inactive and noninfectious due to recombination, deletion, and mutation after integration into the host genome. However, recent studies have implicated HERVs as mutagens of intracellular genes, contributing to autoimmune diseases and tumors. Several studies have shown a significant association between HERVs and certain cancers. We focused on knocking out the HERV-R (ERV3-1) env gene in the DLD1 colon cancer cell line. A 208-bp deletion was confirmed by genomic PCR and DNA sequencing. As a result, HERV-R env gene expression was significantly lower in DLD1 HERV-R knockout (HERV-R KO) cells compared to control cells at both RNA and protein levels. Additionally, the invasion and migration abilities of HERV-R KO cells were significantly reduced. In vivo experiments on mice injected with HERV-R KO cells showed smaller tumor sizes compared to mice injected with control cells, suggesting that HERV-R env plays an important role in tumor growth. Further mRNA-seq analysis identified genes associated with cell invasion and migration. The STRING tool, which analyzes gene correlations, confirmed that HERV-R is linked to genes involved in cancer proliferation, migration, and invasion in colon cancer. This study suggests that the expression of the HERV-R env gene influences the tumorigenic properties of colon cancer, providing valuable evidence for potential clinical studies in colon cancer patients.

Senescence of mesenchymal stem cells in bone tissue (BMSCs), the primary progenitors of osteoblasts, is a key contributor to age-related osteopenia and osteoporosis. Aged cells exhibit elevated cellular stress and abnormal accumulation of stress granules (SGs), which contain G-quadruplex (G4) structured nucleic acids and G4-binding proteins. Dhx36, a helicase that unwinds G4 structure, may play a protective role in this context. In this study, we investigated the function of Dhx36 in BMSCs and bone homeostasis by silencing Dhx36 expression in vitro and in vivo. Dhx36 deficiency increased SG formation and impaired their resolution in BMSCs. This was accompanied by reduced expression of G4-containing autophagyrelated genes and diminished autophagic activity. Loss of Dhx36 also enhanced senescence features and impaired BMSC osteogenic differentiation. Dhx36 expression was significantly lower in bone tissue and BMSCs from aged mice, compared to young mice. Moreover, 8-week-old mice with BMSC-specific Dhx36 knockout exhibited reduced bone volume and trabecular number, indicating premature bone loss. Analysis of public singlecell RNA sequencing data further showed that stress induced by 5-fluorouracil in mice suppressed Dhx36 expression in BMSCs, and downregulated genes related to ossification and osteoblast differentiation. Collectively, our findings identify Dhx36 as a regulator of BMSC aging, linking SG dynamics and autophagy to bone homeostasis, and suggest Dhx36 as a potential therapeutic target to prevent age-related bone loss.

Colorectal cancer (CRC) is a major health concern and understanding its molecular characteristics is crucial for improving its diagnosis and treatment. Here, we present a comprehensive analysis utilizing RNA-sequencing (RNA-seq) data and clinical information from Korean patients with CRC. Differential gene expression analysis identified significant changes in gene expression between tumor and normal tissues. Gene Set Enrichment Analysis (GSEA) revealed dysregulated pathways associated with tumor progression. Furthermore, using CMScaller, we successfully stratified CRC tissues into distinct molecular subtypes. Upon reviewing the public consensus molecular subtype (CMS) signature, it was confirmed that it shares similar biological characteristics with the existing CRC. Additionally, biological characteristics of the group that could not be classified using CMScaller were found to resemble those of CMS2. Finally, distinguishing characteristics were observed between the tumor and normal groups when analyzed from an immunological perspective. Patients with CRC were checked for immunotherapy responsiveness, and those who clinically responded to immunotherapy were identified. Survival analysis confirmed that certain microsatellite stable (MSS) samples were responsive to immunotherapy and showed a relatively better prognosis. Furthermore, analysis of various immune cell types to identify genes involved in the response to immunotherapy revealed that RORC, NOS2, and KLRK1 are potential candidate genes. Our findings provide valuable insights into the molecular landscape of CRC in the Korean population and underscore the potential for integrating RNA-seq data with clinical information to improve cancer research and patient care. Immunotherapy was found to be effective in Korean patients with CRC.

This study examined therapeutic potential of mitochondrial transplantation using PN-101, a mitochondria preparation derived from human umbilical cord mesenchymal stem cells (UCMSCs), to address SSBP1-related mitochondrial DNA (mtDNA) depletion syndrome. Patient-derived fibroblasts harboring a heterozygous SSBP1 mutation (c.272G＞A:p.Arg91Gln) were treated with PN-101. Its successful uptake and integration into these cells were confirmed. Subsequent analyses revealed that PN-101 treatment significantly increased mtDNA copy numbers in a time- and dose-dependent manner, elevated the expression of key oxidative phosphorylation proteins, and enhanced overall mitochondrial bioenergetics. Taken together, these results provide strong evidence that mitochondrial transplantation holds promise as a therapeutic strategy for primary mitochondrial diseases, including those involving SSBP1 mutations.

As a disease with a high mortality rate, colorectal cancer (CRC) highlights the importance of comprehending its molecular mechanisms to develop effective therapies. In this study, we conducted RNA sequencing (RNA-seq) analysis on 476 samples consisting of fresh-frozen CRC tissues and adjacent normal tissues obtained from Samsung Medical Center (SMC) in South Korea. By analyzing gene expression differences, we identified that upregulated genes in tumor samples were significantly associated with pathways related to the cell cycle, extracellular matrix (ECM)-receptor interaction, and DNA damage response (DDR). Conversely, genes exhibiting high expression in normal samples were primarily related to metabolic pathways. Tumor samples were found to be enriched in various DDR pathways, prompting an investigation into the enrichment of related genes. Additionally, the analysis focused on the Homologous recombination (HR) pathway, for which the Homologous recombination deficiency (HRD) score was calculated. Furthermore, we categorized colorectal tumor samples into four subgroups using in silico methods to identify the biological and clinical characteristics of each subgroup and compared our results with those of the widely used existing subgrouping methods. Majority of our fibroblast and immune enriched/fibroblast samples aligned with CMS4, characterized by stromal invasion and mesenchymal differentiation, whereas the immune enriched subtype aligned with CMS1, known for its immune-centric profile. To investigate the clinical implications, the composition of the tumor microenvironment (TME) by cell type was examined across four subgroups, along with an immunological analysis. In particular, the calculated HRD score and the expression levels of immune-related genes associated with CRC were analyzed to provide evidence for personalized therapeutic strategies for each subgroup. Our findings provide valuable insights into the molecular mechanisms underlying CRC in Korean patients, particularly in the SMC patient group, and offer opportunities for personalized therapeutic strategies.

Excessive generation of reactive oxygen species (ROS) and proinflammatory cytokines is a pivotal mechanism causing sensorineural hearing loss (SNHL) through damage to auditory hair cells. In particular, high expression levels of tumor necrosis factoralpha (TNF-α) were observed in SNHL. Alpha-lipoic acid (ALA) has demonstrated protective effects against cochlear hair cell damage and hearing deterioration. This study investigated the protective effect of ALA against TNF-α-triggered ototoxicity in auditory hair cells and in a noise-induced hearing loss mouse model. Cells were pretreated with ALA prior to TNF-α treatment, after which cell viability, ROS generation, and nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant activity were assessed. In addition, we observed the hearing levels, the number of outer hair cells (OHCs), and Nrf2-related protein expression in ALA-pretreated mice before noise exposure. ALA pretreatment significantly enhanced cell viability, suppressed ROS production, and activated Nrf2-mediated antioxidant activity compared with TNF-α treatment alone. In the animal model, noise-exposed mice exhibited elevated TNF-α expression in cochlear tissues. ALA pretreatment decreased the auditory brainstem response threshold and reduced OHCs damage. Furthermore, ALA administration upregulated Nrf2-related antioxidant protein expression in cochlear tissues. Taken together, these findings suggest that ALA pretreatment confers cytoprotective effects against TNF-α-triggered auditory hair cell damage through activation of the Nrf2 signaling- mediated antioxidant activity.

Hypoxia-inducible factors (HIFs) act as master regulators of hypoxia-induced pathological angiogenesis, a hallmark of various ischemic ocular diseases. Recent evidence highlights the pivotal role of HIF-2α among HIF isoforms in endothelial cells (ECs) undergoing pathological angiogenesis under hypoxic conditions. However, the regulatory mechanisms underlying endothelial HIF-2α expression during hypoxia remain incompletely understood. Here, we demonstrated that stem cell factor (SCF) and its receptor, cKIT, upregulate HIF-2α expression in hypoxic ECs. Using the oxygen-induced retinopathy (OIR) mouse model, we observed that HIF-2α was highly expressed in cKIT-positive pathological neovessels in the retina, and SCF was upregulated mainly at astrocytes in the inner retinal layer. Experiments using cKIT mutant mice and anti-SCF neutralizing antibody demonstrated that inhibition of SCF/cKIT signaling significantly reduced retinal HIF-2α expression and pathological angiogenesis in mice with OIR. Moreover, HIF-2α inhibition abolished the SCF-induced increase in the angiogenic activity of human umbilical vein ECs (HUVECs) under hypoxic conditions. Mechanistic studies in HUVECs revealed that SCF enhanced HIF-2α protein levels without affecting its mRNA levels, through AKT- and ERK1/2-dependent phosphorylation of ribosomal protein S6 kinase β-1 under hypoxia. These findings provide novel insights into the regulatory mechanisms controlling HIF-2α expression in angiogenic ECs during hypoxia and suggest that the SCF/cKIT/HIF-2 axis in hypoxic ECs represents a crucial pathway in the regulation of pathological angiogenesis in ischemic ocular diseases.

Mitochondria are crucial for energy metabolism and their dysfunction is implicated in the development of various human diseases. Direct mitochondrial transplantation has shown potential in reversing mitochondrial dysfunction in recipient cells. Mesenchymal stem cells (MSCs) present a promising approach as donor cells for such transplantation. We have previously demonstrated that tomatidine, a natural steroidal alkaloid, promotes the differentiation of human embryonic stem cells (hESCs) into mature cardiomyocytes by enhancing mitochondrial quantity and function. In this study, we assessed the capacity of hESCderived cardiomyocytes (hESC-CMs) and MSCs as donor cells for mitochondrial transplantation. Mitochondria were extracted from MSCs, immature hESC-CMs, and tomatidine-treated mature hESC-CMs. Treating MSCs with mitochondria derived from mature hESC-CMs led to a marked increase in mitochondrial protein levels, such as COX IV and MIC60, in the recipient MSCs, in comparison to those receiving mitochondria from immature hESC-CMs or MSCs. Transplantation of mature hESC-CM-derived mitochondria significantly enhanced the proliferation of recipient MSCs. These findings indicate that mature hESC-CMs are highly effective as donor cells for mitochondrial transplantation in addressing mitochondrial dysfunction.

Long double-stranded RNAs (dsRNAs) are recognized by innate immune response proteins, thereby initiating the integrated stress response. As these RNAs adopt an A-form helical structure, immune sensors recognize dsRNAs primarily based on their structural features, such as the length of the doublestranded stretch and the triphosphate at the 5' end, rather than on specific sequences. This structure-dependent, sequenceindependent mode of RNA recognition is also characteristic of many dsRNA-binding proteins (dsRBPs). Consequently, multiple dsRBPs share a common pool of dsRNA substrates, leading to a complex regulatory network in which proteins modulate each other's activation status and signaling activities. With the development of advanced analytical techniques capable of studying RNA sequences and structures at single-nucleotide resolution, research into dsRNA-protein interactions has advanced significantly. This review discusses the long dsRNAinteracting dsRBPs encoded in the human genome, their RNA substrates, recognition mechanisms, and the downstream effects of protein-RNA interactions, with the aim of deepening our understanding of dsRNA recognition and signaling. [BMB Reports 2025; 58(11): 451-466].

The gut microbiota plays a fundamental role in maintaining host homeostasis, and the aging process profoundly influences its composition and function. Accumulating evidence suggests that alterations in the gut microbiota are not just a consequence of aging, but also an active driver of age-related physiological decline. In particular, age-dependent gut microbiota dysbiosis has emerged as a critical factor contributing to host aging and aging-related diseases. This review systematically summarizes alterations in the gut microbiota (e.g., reduced alpha diversity, depletion of beneficial commensals, and enrichment of pathobionts) during the aging process, and discusses the spatiotemporal dynamics and causal relationships between microbial aging and host aging. The regulatory mechanisms by which the gut microbiota influences aging-related diseases, such as metabolic disorders (e.g., obesity, type 2 diabetes, and cardiovascular disease), immunosenescence, and neurodegenerative diseases (e.g., Alzheimer's disease and Parkinson's disease), are also elucidated. Finally, microbiota-targeted intervention strategies (e.g., probiotics, prebiotics, and postbiotics) are explored, together with advanced research strategies.

Lipocalin-2 (LCN2) is a protein secreted by activated astrocytes, and its signal peptide (SP) is essential for secretion and recruitment to the autophagic pathway. SP is a short sequence present at the N-terminus of secreted proteins, such as LCN2, which facilitates transport to the endoplasmic reticulum (ER). Although SP is cleaved during the initial stages of translation in the ER, it influences the subsequent pathways of mature proteins produced in the ER lumen. ER-generated proteins are secreted or recruited to the autophagic pathway. To explore this further, we sought to determine the functional role of SP from a novel perspective. In this study, we fused LCN2 SP to the N-terminus of ubiquitin (Ub), an intracellular protein used for the proteasomal degradation of misfolded proteins and autophagic degradation of protein aggregates. We demonstrated that SP enabled the secretion of free Ub and facilitated the targeting of Ub conjugates to the autophagic pathway. We also found that SP affected intracellular Ub conjugate levels by regulating their degradation via the autophagic pathway. Furthermore, the ER-generated Ub (UbE) showed increased participation in polyubiquitinating protein aggregates generated under proteotoxic stress conditions, promoting the formation of perinuclear aggresome-like structures, and recruitment to the autophagosome. It is highly likely that UbE shares a common route with protein aggregates before being recruited to autophagosomes. Thus, this study suggests that UbE confers an altered trafficking pathway compared with endogenous Ub, thereby facilitating protein aggregate clearance without altering Ub's intrinsic biochemical activity.

Memory consolidation transforms newly acquired experiences into stable long-term memories essential for learning and cognition. This process involves systems consolidation, where memory traces are reorganized across brain regions, and synaptic consolidation, which fine-tunes local neural connections. Sleep plays a critical role in both, coordinating memory reactivation, synaptic remodeling, and long-range neural communication. Systems consolidation is supported by stagespecific brain oscillations: during NREM sleep, the coupling of slow-oscillations, spindles, and sharp-wave ripples facilitates hippocampal-cortical transfer of memory representations, while REM sleep theta oscillations contribute to memory integration, abstraction, and emotional tagging. Complementary neuromodulatory dynamics, particularly involving norepinephrine and dopamine, regulate the timing and prioritization of memory processing. At the synaptic level, sleep balances strengthening and weakening of connections through a coordinated interplay of NREM and REM activity. Recent findings also suggest that dreaming may reflect the subjective correlate of these processes, particularly through the integration of recent and remote memory fragments. Although the precise relationship between systems-level reorganization and local synaptic refinement remains unclear-partly due to current technical limitations-emerging approaches are beginning to bridge these scales. Together, these findings underscore the integrative role of sleep in optimizing memory consolidation and offer promising avenues for clinical and translational research. [BMB Reports 2025; 58(10): 425-436].

Several individual bioactive compounds isolated from Hericium erinaceus exhibit various physiological and biochemical activities, including neuroprotective, neurotrophic, gastrointestinal protective, immunoregulatory, and anti-inflammatory effects. However, the specific anti-inflammatory effects of H. erinaceus extracts, which can vary significantly depending on the extraction solvent, require further investigation. In this study, we aimed to investigate the anti-inflammatory effects of H. erinaceus hot water extract (HWE). Therefore, we evaluated nitric oxide (NO) production, the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the expression and release of pro- and anti-inflammatory cytokines, and changes in inflammation-related signaling pathways in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. HWE effectively suppressed NO production and iNOS expression; however, COX-2 expression exhibited a biphasic response, increasing at 1.25 mg/ml and decreasing at 2.5 mg/ml. Additionally, HWE reduced the expression and release of the proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and increased the expression and release of the anti-inflammatory cytokine IL-10. Furthermore, HWE attenuated the phosphorylation of IKK-α/β and NF-κB p65 and ameliorated LPS-induced inflammation by inhibiting the phosphorylation of JAK1 and STAT3. These findings suggest that HWE may serve as a valuable source for anti-inflammatory agents or health functional food ingredients.

Modern genomic sequencing techniques have advanced rapidly, thereby improving data production rates and dimensionality. With this accelerated growth, machine learning, especially deep learning, has been leveraged to analyze complex data and complement conventional bioinformatics methods. Deep learning approaches have been successfully applied in genomics, leading to the development of state-of-the-art models and significantly improved interpretation of genomic data. Here, we review deep learning models in four genomic domains: variant calling, gene expression regulation, motif finding, and 3D chromatin interactions. We summarize the key aspects of model development, such as training and generalization, that enable the efficient application of deep learning models in genomic research. Real-world applications have demonstrated the reliability and efficiency of these models for predicting genomic profiles. Finally, we highlight the future directions of deep learning approaches in genomics by discussing the challenges related to genome tokenization and multi-omics data integration.

Left-right determination factor 2 (Lefty2) is a transforming growth factor-β (TGF-β) receptor ligand that is critical for organ asymmetry and cell proliferation. More broadly, the TGF-β superfamily plays indispensable roles in development and gene regulation, and TGF-β family ligands are instrumental in osteoclast differentiation and bone resorption. In the present study, we show that Lefty2 dramatically inhibits receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation. We found that this effect was associated with inhibition of early intracellular signaling pathways activated by RANKL, which are important for osteoclast differentiation. Furthermore, administration of exogenous Lefty2 prevented RANKL-induced bone loss in mice. Interestingly, transgenic mice expressing Lefty2 controlled by the Mx-1 promoter did not show a distinct bone phenotype, even though transgenic mouse-derived bone marrow macrophages exhibited reduced osteoclast formation compared to controls in vitro.

To advance the development of novel therapies for lung cancer, we investigated tumor-associated molecules implicated in tumorigenesis. RNA-seq data were generated from paired tumors and adjacent normal tissues of four patients with lung squamous cell carcinoma (LUSC) and five patients with lung adenocarcinoma (LUAD). Additional analyses utilized RNA-seq data from The Cancer Genome Atlas (TCGA), including paired tumor and adjacent normal samples (51 LUSC, 57 LUAD) and tumor-only samples (450 LUSC, 461 LUAD). Adjacent normal tissues served as controls. Our RNA-seq results showed strong concordance with TCGA data. Ion channels Aqp1, Aqp4, and Clic5 were significantly downregulated in lung tumors, whereas enzymes involved in membrane lipid metabolism, including phosphatidylcholine (PC), sphingomyelin (SM), and cholesterol (Cho), were upregulated in lung tumors. Cardiolipin (CL), a mitochondrial inner membrane lipid, was downregulated in lung tumors. These changes might have impaired oxygen permeability and mitochondrial function, promoting hypoxia and reactive oxygen species (ROS) production. Hif1α expression was elevated in both LUSC and LUAD, along with a hypoxiaresponsive protein kinase Csnk2a1 and its downstream targets Hdac1 and Hdac2. ROS-responsive transcription factors Yy1, Foxm1, E2f1, and E2f8 were also significantly upregulated in both LUSC and LUAD. Notably, the master epigenetic regulator Uhrf1 activated by these transcription factors showed marked overexpression in tumors compared to that in normal tissues. TCGA data corroborated these findings. Our study identified tumor cell membrane-associated molecules, including ion channels (Aqp1, Aqp4, Clic5) and membrane lipid metabolism enzymes (PC, SM, Cho, and CL), as critical contributors to lung tumorigenesis. These molecules represent promising targets for developing innovative anti-cancer therapies.

Flavonoids are plant-derived polyphenols that influence nematode behavior, yet their neuronal and molecular targets remain poorly understood. Here, we show that the free-living nematode Caenorhabditis elegans detects and avoids a green tea catechin epigallocatechin gallate (EGCG) via the SRXA-7 Gprotein coupled receptor (GPCR) in the ASH nociceptive neurons. EGCG and epicatechin gallate (ECG), both containing a galloyl group, trigger strong avoidance, unlike other green tea catechins lacking this moiety. EGCG avoidance behavior displays species- and strain-specific differences among Caenorhabditis species and wild C. elegans isolates. Moreover, it is dynamically modulated by prior experience and feeding state. The ASH chemosensory neurons are required for EGCG detection, with avoidance mediated through canonical GPCR signaling components including GRK-2, GPA-3, ODR-3, and TRPV channels OCR-2 and OSM-9. A targeted GPCR screen revealed that srxa-7 mutants exhibited specific defects in EGCG avoidance. EGCG-evoked calcium responses in ASH are reduced in srxa-7 mutants and restored by ASH-specific expression of srxa-7 cDNA. These findings indicate that SRXA-7 is a sensory receptor for galloylated polyphenols, uncovering the neuronal and molecular basis of adaptive aversive responses to dietary plant compounds in nematodes.

Both ethical imperatives and scientific limitations increasingly challenge the traditional reliance on animal models for toxicity testing and drug evaluation, particularly in the era of precision medicine. In response, a paradigm shift is underway, marked by the development of advanced in vitro and in silico technologies that can offer human-relevant and mechanistically informed alternatives. This review examines well-established alternatives, such as receptor binding assays, the monocyte activation test, and enzyme-linked immunosorbent assays, highlighting their applications, mechanisms, and limitations. We further explore emerging human-relevant technologies that include organoids, organ-on-a-chip systems, microphysiological systems, and artificial intelligence-powered modeling platforms. Special emphasis is placed on immune-integrated microphysiological systems as next-generation platforms to evaluate immunotherapy, vaccine responses, and immune toxicities. These models recapitulate dynamic human physiological processes, such as hematopoiesis and germinal center reactions, beyond the capabilities of traditional animal systems. Collectively, these technologies represent scientifically superior and ethically progressive trajectories for preclinical testing. Their integration into regulatory and industrial workflows requires continued refinement, cross-sector collaboration, and standardization.

[Erratum to: BMB Reports 2025; 58(8): 325-339, PMID: 40635200, PMCID: PMC12402691] BMB Reports recently published the article "Decoding tau acetylation in Alzheimer's disease and tauopathies: from site-specific mechanisms to therapeutic horizons" (BMB Rep. 2025; Vol. 58, No.8, pp.325-339) by Yoonah R. Oh et al. The original publication inadvertently omitted the ACKNOWLEDGEMENTS section. This section has now been added to the online version. ACKNOWLEDGEMENTS This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (RS-2023-00209597). All figures were created using BioRender. The authors and editorial office apologize for any inconvenience or confusion this omission may have caused to the authors and readers.