Serendipity is to come across a nice coincidence or to discover something unexpected. Also, it is to look for something and happen to find something of value other than what you are looking for. In simple, it is to seize upon good fortune by a random chance. I described examples of serendipity in scientific discoveries in the glycoscience field and their background in the 2011 publication of MICC-3 under the title "Serendipity in scientific discoveries: some examples in glycosciences." We have learned that the progress in the scientific field has been remarkable, and many discoveries have been made, including some discoveries by serendipity. In this chapter, I filled the gaps in serendipitous discoveries in the biomedical sciences left by the MICC-3 as follows: (i) the discovery of intramolecular lactonization of sialic acids, (ii) the discovery of ancient Chinese script (), (iii) the discovery of oriental beauty oolong tea, and (iv) Yamanaka's Nobel Prize-winning discovery of induced pluripotent stem (iPS) cells. Finally, the planning for serendipity was discussed.

Induced pluripotent stem cells (iPSCs) have emerged as a powerful tool in biomedical research, enabling the study of cellular function and early disease mechanisms within patient-specific genetic contexts. Traditionally, iPSCs have been used to model monogenic diseases, where highly penetrant variants produce robust cellular phenotypes detectable in few cell lines. Recent advances in scalability and standardisation now enable systematic comparisons across many donors. This development is particularly relevant for complex diseases, which are driven by numerous genetic variants with small individual effects and therefore require population-scale designs to resolve genotype-phenotype relationships. However, several limitations of iPSC technology continue to challenge the reliability and reproducibility of such studies, constraining their translational relevance. Here, we review the challenges and opportunities of using iPSCs to model complex diseases, structured around three key themes: detecting subtle effects, modelling environmental context, and expanding genetic diversity.

Post-translational modifications (PTMs) of proteins represent central regulatory mechanisms within cells, enabling rapid and targeted modulation of protein functions. PTMs can directly influence protein activity, stability, or protein-protein interactions, while histone modifications also play a crucial role in gene expression regulation. To date, over 400 types of PTMs have been identified, with new types continually emerging. Among these, lysine lactylation (Kla), crotonylation (Kcr), and lysine 2-hydroxyisobutyrylation (Khib) have recently been recognized as novel PTMs with critical roles in plant growth, development, and stress responses. Unlike previous reviews that broadly summarize plant PTMs, this article provides a focused synthesis on these three newly characterized acylations, highlighting their distinct biochemical features, regulatory mechanisms, and functional relevance in plant growth, development, and stress adaptation. We summarize recent proteomic and functional studies that uncover (i) the role of histone and non-histone lactylation in metabolic reprogramming and stress resilience; (ii) the contribution of crotonylation to transcriptional regulation, enzyme activity, and abiotic stress tolerance; and (iii) the emerging function of 2-hydroxyisobutyrylation in photosynthesis, stem development, and plant pathogen interactions. Furthermore, we discuss cross-talk among Khib, Kcr, and Kac (lysine acetylation), revealing a coordinated acylation network that fine-tunes chromatin dynamics and metabolic homeostasis. By integrating findings across multiple species including rice, wheat, maize, pepper, and fungi this review proposes a comparative and mechanistic framework for understanding how these acylations bridge cellular metabolism with epigenetic and physiological regulation.

Oral mucosal ageing represents a fundamental reprogramming of the tissue microenvironment, a dynamic process that underlies the functional decline and heightened disease susceptibility observed in the elderly. This review synthesises current evidence to reconceptualise oral mucosal ageing as an active reprogramming of the tissue microenvironment, delineating the interplay between structural, molecular, and immunological changes, and exploring how these alterations drive functional decline and increase susceptibility to age-related oral diseases. Through a comprehensive analysis of experimental and clinical studies from human and animal models, we demonstrate that the ageing process fundamentally transforms the oral mucosa. Key findings include structural changes such as epithelial atrophy, extracellular matrix remodelling, and salivary gland degeneration, driven molecularly by genomic instability, accumulation of proinflammatory senescent cells, stem cell exhaustion, and dysregulated stress responses. These are compounded by an immunological state of 'inflammaging' and functional decline in innate and adaptive immunity, further exacerbated by shifts in the oral microbiome. Collectively, these deficits lead to impaired regeneration, diminished sensory function, and reduced salivary secretion, creating a permissive landscape for chronic oral diseases. In conclusion, oral mucosal ageing is a dynamic process of microenvironmental reprogramming driven by cellular senescence, immunosenescence, and structural decay. This actively underpins the heightened vulnerability to oral disease in the elderly, providing a mechanistic foundation for developing targeted interventions to preserve oral health in ageing populations.

Immunotherapy has revolutionized cancer treatment, offering durable responses across various malignancies. However, blood cancers present unique challenges due to significant heterogeneity, an immunosuppressive tumor microenvironment (TME), and potent mechanisms of immune evasion. This review synthesizes the current landscape of immune checkpoint blockade (ICB), evaluating both established agents and emerging targets (e.g., LAG-3, TIM-3, CD47) in hematologic malignancies. We critically examine the role of cancer stem cells (CSCs) in driving therapeutic resistance and recurrence, highlighting how aberrant signaling pathways (Wnt, Notch, m6A) fuel immune avoidance. Furthermore, we assess the transformative potential of cellular immunotherapies, specifically CAR-T and CAR-NK cells, proposing strategies to enhance their persistence and safety. By integrating insights from recent preclinical and clinical studies, this report provides a roadmap for developing rational, multi-pronged combination strategies that disrupt the “resistance ecosystem” of blood cancers, paving the way for personalized curative regimens.

Anticancer therapeutics have evolved from small-molecule drugs to monoclonal antibodies and, more recently, to cell and gene therapies (CGTs). This progress has been driven by the pursuit of greater drug specificity, potency, and safety. Recent breakthroughs in chimeric antigen receptor T-cell (CAR-T) therapy for B-cell hematologic malignancies have accelerated the development of CAR-X CGTs, including CAR-T, CAR-natural killer (CAR-NK), and CAR-macrophage approaches. In this article, we compare candidate CAR-X platforms for T-cell-related diseases, such as T-cell hematologic malignancies, and propose the most suitable modality. Therefore, we analyzed the advantages and limitations of CAR-T, CAR-NK, and CAR-macrophage therapies. In T-cell-related diseases, CAR-T therapy faces multiple challenges, including fratricide, T-cell aplasia, and substantial barriers to the generation of allogeneic CAR-T products. CAR-macrophage therapies, in contrast, are constrained by relatively limited efficacy. In contrast, CAR-NK cells do not cause fratricide or T-cell aplasia and can be manufactured efficiently as allogeneic, "off-the-shelf" products. Collectively, to sustain and extend the advances in CGT initiated by CAR-T cells in B-cell malignancies, prioritizing CAR-NK research infrastructure for T-cell-related diseases represents a rational and strategic approach.

Transcription factor acetylation is a critical yet often overlooked regulator of cell fate. Although traditionally studied in the context of histone modifications, many acetyltransferases and deacetylases also modify transcription factors directly, thereby controlling lineage-specific transcriptional programs. At the molecular level, acetylation fine-tunes transcription factor activity by modulating DNA binding, protein stability, cofactor interactions, and nucleo-cytoplasmic trafficking. These molecular effects frequently intersect with other post-translational modifications, establishing acetylation as a versatile molecular switch of transcriptional output. These molecular effects scale into cellular outcomes that determine identity and plasticity. In pluripotent stem cells, defined acetylation events on core regulators stabilize the pluripotency network and prime lineage-specific enhancers. In hematopoiesis, transcription factor acetylation modulates transitions from stem and progenitor states to committed lineages, while in myogenesis, it governs progenitor differentiation and regenerative capacity. Importantly, differential acetylation of distinct lysine residues can yield context-dependent outcomes, underscoring the precision and adaptability of this modification in controlling cell identity. Recognizing transcription factor acetylation as a central axis of epigenetic regulation reframes our understanding of lineage specification and cellular plasticity. Beyond developmental biology, it provides a mechanistic rationale for therapeutic strategies that target acetylation dynamics, not only altering chromatin states but also reprogramming transcription factor function. This review synthesizes current knowledge of transcription factor acetylation in hematopoietic and myogenic contexts, highlighting its significance as a bridge between molecular mechanisms and cellular identity, and as a promising target in disease intervention.

Male infertility is a rising problem globally with male factors contributing up to 50% of all couple infertility cases. The sperm quality decline raises serious concerns regarding future population sustainability and male reproductive health. Adipose-derived mesenchymal stem cell (AdMSC) secretome, defined as a cell-free product comprising paracrine factors secreted by these cells, has emerged as a promising cell-free regenerative therapy for testicular injury, offering advantages of accessibility and therapeutic potential. This systematic review aimed to evaluate the effectiveness of AdMSC secretome in chemically induced testicular injury models.

Human cytomegalovirus (HCMV) reactivation is a common and significant complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT), causing potentially life-threatening disease. Antiviral therapy approaches for HCMV are often limited by toxicities and the risk of developing antiviral drug resistance. This review article (Part 2) provides an overview of current antiviral pharmacotherapies for HCMV and the application of virus-specific adoptive T cell therapies for the prevention or treatment of HCMV reactivation in allo-HSCT recipients. The number of available antiviral drugs for HCMV is expanding, and letermovir primary prophylaxis is increasingly being adopted due to its favourable safety profile. Treatment resistant/refractory infections, end-organ disease, and late HCMV reactivations after antiviral therapy withdrawal continue to pose challenges. Adoptive HCMV-specific T cell therapies are a promising strategy for promoting immune-mediated control of HCMV reactivation in allo-HSCT recipients. The administration of HCMV-specific T cell products, generated through ex vivo expansion of donor-derived or partially HLA matched, third party HCMV-specific T cells, have demonstrated efficacy in combatting clinically significant HCMV infection in clinical trials. Adoptive HCMV-specific T cell therapies represent a powerful alternative approach for managing drug resistant HCMV infections in allo-HSCT recipients and reducing the reliance on antiviral pharmacotherapies.

Umbilical cord mesenchymal stromal cells (UC-MSCs) are emerging as leading stem cells in regenerative medicine due to their high proliferative capacity, potent immunomodulatory effects, and non-invasive collection. However, the absence of standardized guidance on optimal passage number and tissue-specific characterization criteria limits clinical translation, raising concerns about variability in potency, genomic stability, and safety. This review synthesizes evidence on how in vitro passaging alters UC-MSC properties, including purity, proliferation, senescence, genomic integrity, differentiation, and immunomodulation. Preclinical data suggest that UC-MSCs tolerate extended passaging better than MSCs derived from other sources, with several functional attributes preserved up to later passages. Clinical evidence indicates that early to middle passages (P3-P5) achieve the best balance between scalability and therapeutic efficacy. We further propose an updated immunophenotypic framework incorporating tissue-specific positive and negative markers to enhance clinical-grade characterization. Establishing harmonized passage guidelines and potency assays is essential to maximize reproducibility, safety, and the translational potential of UC-MSC therapies.

SPEECHLESS (SPCH) is the earliest master regulator of the stomatal lineage, and in dicots, defines a transient, self-renewing stem cell state crucial for guard cell formation and environmental plasticity. Over the past decade, studies have revealed how the basic helix-loop-helix transcription factor coordinates a broad transcriptional network controlling cell-cell signaling, asymmetric division, cell-cycle progression, and environmental pathways, while itself subject to multilayered transcriptional and phospho-regulatory controls. These findings position SPCH as a model for understanding how master transcription factors orchestrate lineage progression and integrate intrinsic and environmental cues. Here, we synthesize recent advances in SPCH-mediated gene networks and the regulation of SPCH in the model plant Arabidopsis thaliana, highlighting how this single transcription factor establishes and shapes the stomatal stem cell state, with implications for plant adaptation and crop improvement.

Spinal cord injury (SCI) represents a devastating neurological condition characterized by immediate mechanical damage followed by secondary pathological processes, including acute and chronic inflammation, which exacerbate neuronal loss, axonal degeneration, and glial scar formation, ultimately leading to permanent functional deficits. Emerging research highlights the dual nature of inflammation, where timely modulation can shift from a detrimental M1-like phenotype to a regenerative M2-like state, thereby fostering neural stem cell (NSC) survival and neurogenesis. Strategies for reprogramming inflammation include pharmacological interventions like minocycline or resolvins to dampen excessive cytokine storms, biomaterial scaffolds impregnated with anti-inflammatory agents to create supportive niches, and gene therapies targeting NF-κB pathways to promote anti-inflammatory signaling. Additionally, stem cell-based approaches, such as mesenchymal stem cell transplantation, secrete immunomodulatory factors that enhance NSC migration and remyelination while reducing astrogliosis. Preclinical models demonstrate that these reprogramming tactics not only mitigate secondary injury but also amplify NSC-mediated repair, improving motor recovery and sensory function. Clinical translation faces challenges like timing of intervention and personalized immunomodulation, yet holds promise for novel therapeutics. The objective of this review is to synthesize current evidence on reprogramming inflammatory pathways to optimize NSC function in SCI and to propose integrated strategies for advancing regenerative therapies.

Chronic viral infections and cancer challenge immune control by enforcing sustained antigen exposure, which profoundly alters the fate and function of CD8+ T cells. In contrast to acute infections, which induce robust effector differentiation and durable immune memory, persistent infections and tumors drive CD8+ T cells into distinct states of functional adaptation. The best studied chronic adaptation is T cell exhaustion, which is characterized by impaired effector functions, reduced proliferative capacity, sustained expression of inhibitory receptors, and stable transcriptional and epigenetic reprogramming. T cell exhaustion is not a uniform or terminal condition but comprises heterogeneous and dynamic cellular states, including stem-like/precursor populations that retain self-renewal capacity and therapeutic responsiveness. These insights have reshaped our understanding of immune regulation in chronic disease and underpin the success of immune checkpoint blockade therapies. However, heterogeneous and often transient clinical responses highlight critical gaps in our mechanistic understanding of exhausted T cell biology. This review synthesizes recent advances in the cellular and molecular profiling of chronically stimulated CD8+ T cells across chronic viral infection and cancer, focusing on regulatory networks, defining factors, and tissue-specific cues that govern functional adaptation and exploring emerging therapeutic reprogramming strategies.

Cellular senescence compromises pulp vitality and may negatively affect vital pulp therapy and regenerative endodontics. Exposure to dental materials may accelerate this process, highlighting the need for safer biomaterials and novel therapeutic strategies.

Exosomes, tiny extracellular vesicles (EVs) from different cell types, are gaining attention in dermatology due to their unique properties. They enhance cell communication, transport bioactive substances, and influence immune responses, making them valuable for skin regeneration, wound healing, and addressing skin conditions.

Primary mitochondrial disorders (PMDs) are inherited metabolic diseases that most often present with neurological symptoms in infancy or adolescence, underscoring the central importance of mitochondrial function to brain health. Historically, the field has emphasized neurodegeneration-consistent with the high energetic demands of postmitotic neurons. However, neurodevelopmental manifestations are now recognized as common early phenotypes, frequently preceding clinical regression in many PMDs. Given the pivotal role of mitochondria in neural stem/progenitor cell maintenance and cell fate decisions, defects in the respiratory chain are poised to disrupt neurogenesis and gliogenesis. Evidence for such developmental vulnerabilities is reviewed here. Likewise, because mitochondrial metabolism and dynamics shift across the oligodendrocyte lineage-from oligodendrocyte precursor cell expansion to differentiation and the energetically intensive phase of myelin synthesis-callosal atrophy in mitochondrial leukoencephalopathies may, at least in part, reflect developmental shortcomings in oligodendrogenesis and myelination. This possibility warrants focused investigation in cellular and in vivo models.

A plant's indeterminate growth requires constant cell proliferation and stem cell maintenance to support its developmental plasticity. The root meristem is an excellent system to study the developmental control of plant cell cycles due to the organ's accessibility and the tight link between cell cycle and developmental regulation. Studies have uncovered diverse pathways that shape root tissue patterning and cell identity, but how these mechanistically connect to cell cycle components remains unclear. Recent work and new approaches are starting to bridge this gap. In this review, we synthesize recent findings on the developmental regulation of cell cycle progression across distinct cell types and developmental zones in the Arabidopsis thaliana root apical meristem, highlighting cells and regions of the root where these processes have been thoroughly studied, and others where we know little. These discoveries reveal a nuanced relationship between cell identity and cell cycle regulation that implies an active role for cell cycle modulation in the patterning and developmental plasticity that are integral to plant growth.

The progressive decline in physiological processes with aging is a complex biological process that increases susceptibility to age-related diseases. Cellular senescence is a primary contributor to this process, a state of sustained cell cycle arrest accompanied by a distinctive secretory profile known as the Senescence-Associated Secretory Phenotype (SASP). In recent years, extracellular vesicles (EVs), including exosomes and microvesicles (MVs), have emerged as key mediators of intercellular communication by carrying bioactive molecules, such as proteins, lipids, and nucleic acids. In this review, we describe how EVs are important SASP vectors that transmit senescent signals to nearby cells, driving immunosenescence, persistent inflammation (inflammaging), and other aging characteristics, such as stem cell exhaustion and genomic instability. Furthermore, we highlight the dual function of EVs as both pathogenic drivers of aging-related dysfunctions and promising therapeutic agents. In addition, we emphasize their potential as diagnostic biomarkers for age-related diseases, including cardiovascular disease, osteoporosis, and Alzheimer's disease. Finally, we explore the emerging therapeutic uses of EVs, particularly those derived from mesenchymal stem cells (MSCs), to promote tissue repair, reduce aging phenotypes, and serve as engineered drug-delivery systems. This study highlights the critical role of EVs in aging mechanisms and establishes them as potent diagnostic and therapeutic tools for anti-aging.