Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with limited treatment options, where neuroinflammation and gut microbiota dysbiosis are emerging as interconnected therapeutic targets. This study evaluated the therapeutic potential of non-gene-edited human chemically induced pluripotent stem cell-derived neural stem cells (hCiPSC-NSCs) in a prenatal valproic acid (VPA)-induced rat model of ASD, using a dual-pathway administration strategy (intravenous systemic delivery combined with an intracerebroventricular boost). The treatment significantly ameliorated core ASD-like behaviors, including improved sociability (increased stranger interaction time, P < 0.0001), reduced repetitive behaviors (decreased marble-burying, P < 0.0001; and self-grooming, P < 0.05), and enhanced spatial memory (shorter escape latency in the Morris water maze, P < 0.01). At the mechanistic level, hCiPSC-NSCs attenuated neuroinflammation (suppressed IL-1β, IL-6, and TNF-α; elevated IL-10, all P < 0.0001), reduced oxidative stress (restored GSH and SOD, decreased MDA and NO), diminished microglial activation in the hippocampus and cortex, and restored synaptic ultrastructure by replenishing synaptic vesicles. Furthermore, 16S rRNA sequencing revealed a rebalancing of the gut microbiota, characterized by a reduced Firmicutes/Bacteroidota ratio, enrichment of beneficial taxa like Bacteroidota and Alloprevotella, suppression of pathobionts such as Desulfovibrionales, and partial restoration of microbial diversity. These findings demonstrate that non-gene-edited hCiPSC-NSCs can simultaneously address neural pathophysiology and gut ecosystem disruption in ASD, highlighting their potential as a gut-brain axis-targeting therapy for neurodevelopmental disorders.

Acute myeloid leukemia (AML) remains a highly heterogeneous hematologic malignancy in which therapeutic resistance and disease relapse are largely driven by leukemic stem cells (LSCs). These rare, self-renewing cells possess unique biological properties that enable them to survive conventional chemotherapy and targeted therapies, thereby sustaining minimal residual disease and promoting leukemia re-emergence. LSC persistence arises from a complex and multilayered network of resistance mechanisms, including intrinsic cellular programs, adaptive molecular plasticity, and protective interactions within the bone marrow microenvironment. Intrinsic mechanisms include cellular quiescence, enhanced multidrug efflux activity, resistance to apoptosis and senescence, and activation of stress-adaptive pathways such as autophagy. In addition, LSCs exhibit remarkable metabolic and epigenetic flexibility, allowing them to rewire signaling pathways and survive therapeutic pressure. Extrinsic cues from the bone marrow niche, including stromal interactions, cytokine signaling, and metabolic support, further reinforce the survival and drug tolerance of LSCs. Together, these interconnected mechanisms create a highly resilient cellular state that limits the efficacy of current therapies. In this review, we summarize the major biological pathways that sustain LSC-mediated resistance in AML and discuss emerging therapeutic strategies aimed at selectively targeting these cells. A deeper understanding of LSC biology will be critical for the development of combination therapies capable of eradicating minimal residual disease and achieving durable remission in patients with AML.

Androgenetic alopecia (AGA) is a common hair disorder in which limited follicular drug delivery and an inflammatory and oxidative follicular microenvironment reduce topical efficacy. Herein, we developed a fast-dissolving microneedle (MN) patch of chondroitin sulfate and carboxymethyl chitosan for localized codelivery of Platycladus orientalis leaf-derived extracellular vesicles (PO-EVs) and minoxidil nanoparticles (MXD NPs). PO-EVs were separated and characterized as nanoscale vesicles and were shown to possess antioxidant, anti-inflammatory, and pro-angiogenic activities relevant to hair follicle maintenance. MXD NPs were prepared by thin-film hydration to improve the minoxidil solubility and local retention. Both were loaded into microneedles with sufficient mechanical strength that could dissolve rapidly in the skin. In a mouse model of androgenic alopecia, repeated dual-loaded MN treatment accelerated the telogen-to-anagen transition, increased hair-covered area and shaft thickness, and restored follicular morphology. Mechanistic studies showed that hair follicle stem cells were activated and proliferated, perifollicular oxidative stress and inflammation were reduced, and microvessel density around hair follicles was increased. No evident skin irritation or systemic toxicity was observed. This MN codelivery strategy improves hair regrowth by combining efficient minoxidil delivery with PO-EV-mediated microenvironment restoration and may be extended to other inflammatory/oxidative skin disorders impairing regeneration.

Habitat destruction, changing climate and other anthropogenic impacts have resulted in the recorded extinctions of hundreds of species, with many more undocumented extinctions being likely to have occurred. Approaches to conserving threatened species include protection or improvement of habitat, fenced conservation reserves, species translocations and reintroductions, elimination of environmental toxins, breeding programs in reserves or captivity, and genetic rescue and management. The latter includes storage of gametes, stem cells or embryos, to both conserve species and maintain or expand their genetic diversity. Many of these approaches require a basic knowledge of the reproductive biology of the species of interest. Such knowledge is difficult to achieve because of the astonishing diversity of species-specific reproductive strategies that have evolved. Unfortunately, for many species we simply do not have that knowledge. This report summarises key discussions from a workshop titled Reproductive Biology Research Needed for Saving our Wildlife held in Melbourne, Australia, and attended by stakeholders from zoos, wildlife organisations, universities, museums and government organisations. The workshop prioritised aspects of reproductive biology knowledge needed, how this knowledge might be obtained, and how it should be deployed. Using examples of planned and successful conservation strategies for individual species, the workshop participants considered environmental challenges, managing introduced species, captive breeding programs, challenges for assisted reproductive technologies, de-extinction science in conservation efforts, examination of reproductive steroid hormones across species, endocrine disruption, and cryopreservation of genomic diversity to assist the management of wild and captive populations. The workshop highlighted the magnitude of the issues involved and identified reproductive approaches to be used to direct future conservation efforts for saving threatened species.

The treatment of critical-size bone defect, particularly those with irregular shapes, presents a significant clinical challenge. Chitosan hydrogels, owing to their degradability, excellent biocompatibility and injectability, represent a promising carrier platform for bone tissue engineering (BTE). Bioavailable Mg2+ serves as a pivotal element in bone regeneration, promoting osteogenesis and angiogenesis to accelerate bone tissue repair. Furthermore, Gallic acid (GA) exhibits anti-inflammatory properties, modulating the immune microenvironment to create favorable conditions for bone regeneration. To control its release behavior, metal-organic frameworks (MOFs) may be constructed by leveraging the coordination interactions between Mg2+ and GA. This study constructed an injectable thermo-responsive hydrogel using chitosan and sericin as the matrix, functionalizing it by embedding Mg-GA MOF at varying loading capacities. This material system is termed CS-MOF. In vitro experiments confirmed that the Mg-GA MOF-functionalized hydrogel exerts multiple biological functions: promoting osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), inducing angiogenesis in human umbilical vein endothelial cells (HUVECs), and suppressing the inflammatory response of LPS-stimulated RAW264.7 macrophages. Using a rat critical-sized cranial defect model, we demonstrated that the 0.01% wt/vol Mg-GA MOF-functionalized hydrogel significantly enhanced new bone formation and angiogenesis compared to the MOF-free and 0.02% wt/vol MOF-loaded hydrogels. Collectively, this thermo-responsive Mg-GA MOF-functionalized hydrogel represents a promising candidate for clinical translation in bone defect repair.

Injectable biomaterials have emerged as a promising option for minimally invasive tissue repair, especially in cases with small and irregular lesions. In combination with electroconductivity and self-healing abilities, these materials provide unique benefits for neural tissue engineering. They promote adaptive defect filling, assist in post-injection structural repair, and improve bioelectrical signaling. The current study focuses on the synthesis and characterization of injectable, self-healing, electroconducting hydrogels, which are intended to serve as a potential platform for addressing small and irregular neural defects. Dynamic covalent hydrazone coupling between oxidized methacrylate sodium alginate-polypyrrole (OMA-PPy) and adipic acid dihydrazide-functionalized hyaluronic acid (HA-ADH) was employed to produce hydrogels. The hydrogels were subsequently reinforced with additional photopolymerization to ensure post-injection stability. Additionally, a laminin-derived peptide called IKVAV was covalently linked to generate biomimetic signals for enhancing neuronal cell adherence and differentiation. The hydrogels demonstrated adjustable mechanical properties (elastic modulus: 72.91 ± 10.84-103.94 ± 17.72 Pa; and compressive strength: 76.87 ± 25.06-153.60 ± 37.89 kPa) and pore size (44.86 ± 23.18-76.34 ± 59.28 μm), exceptional shear thinning behavior, and self-healing abilities (recovery up to 90.35% after six cycles), along with adequate electroconductive performance suitable for minimally invasive procedures and in-situ regeneration for neural applications. In vitro studies have shown that IKVAV-functionalized hydrogels enhance the adhesion, proliferation, and differentiation of neural stem cells (NSCs) with Tuj1 expression of 6.79 ± 0.71 in the OMA-PPy/HA-ADH/IKVAV group. In addition, the OMA-PPy/HA-ADH/IKVAV formulation demonstrated favorable biocompatibility in vivo (ISO 10993-6 reactivity score: 1.22), along with a well-regulated biodegradation profile (91.6% degradation by day 21), when tested in subcutaneous implantation models. The findings indicate that optimizing a single material characteristic is insufficient; achieving a balance among bioactive signaling, secondary network connections, and dynamic covalent bonding is essential for identifying an ideal candidate material. This versatile hydrogel platform offers an encouraging approach for future research focusing on the repair and regeneration of nerve tissues, particularly in addressing localized and small-sized nerve injuries.

Tooth extraction is a common dental procedure often accompanied by local tissue damage and alveolar bone resorption. The integration of hemostatic and regenerative materials can significantly enhance therapeutic efficacy and patient outcomes following tooth extraction. Herein, we developed dual-functional polyhedral oligomeric silsesquioxane (POSS)-functionalized carboxymethyl chitin microspheres (CMGP) via electron beam irradiation grafting. Both in vitro and in vivo studies demonstrated that CMGP possessed good biocompatibility and biodegradability. These microspheres promoted blood coagulation through robust platelet activation capacity. Notably, in a rat artery puncture model, clotting time was reduced from 555 s to 55 s, while blood loss decreased from 617 mg to 21 mg. Moreover, CMGP microspheres significantly induced M2 polarization of macrophages, demonstrating potent tissue repair-promoting properties. Furthermore, the microspheres accelerated osteogenic differentiation of mesenchymal stem cells, which is critical for bone regeneration. Therefore, POSS-functionalized radiation-grafted carboxymethyl chitin microspheres CMGP represent a promising biomaterial platform for post-extraction socket management, enabling enhanced hemostasis and tissue repair.

Mechanisms that maintain genome integrity are crucial for coordinating transcription that drives mammalian forebrain development. Neural progenitor cells and differentiating neurons in the developing forebrain sustain high transcriptional activity and metabolic demand and are therefore vulnerable to DNA damage. Transcription-coupled nucleotide excision repair is a specialized DNA repair pathway that helps to mitigate damage induced by 'bulky' adducts such as UV-induced pyrimidine dimers and monoadducts formed by reactive oxygen species. TC-NER factors, which include CSB/CSA, UVSSA-USP7, ELOF1, and STK19, coordinate and assemble the complex to initiate repair. Notably, TC-NER safeguards genome integrity and plays an essential role in neuronal differentiation, synaptogenesis, and neurogenesis. Impaired TC-NER pathway activity manifests in tissue-level pathologies, including neurodegeneration and increased susceptibility to neurological deficits. This is relevant to neurodevelopmental disorders that stem from TC-NER deficiency, such as Cockayne syndrome, Trichothiodystrophy, and Cerebro-Oculo-Facio-Skeletal syndrome. Although deficits in TC-NER have been well established as a contributor to a variety of neurodegenerative disorders, its roles in the developing forebrain across various cell types and neurodevelopmental windows remain poorly defined. In this review, we highlight recent studies investigating mechanisms linking TC-NER deficiency to forebrain developmental phenotypes and summarize knowledge gaps in the field regarding cell-type specificity, regional vulnerability, and therapeutic windows for intervention.

Intracerebral hemorrhage (ICH) is a devastating acute neurological condition with high mortality and disability. Induced pluripotent stem cell-derived neural progenitor cells (iPSCNPCs) have been shown to promote behavioral recovery by enhancing neural connectivity and providing trophic support. As the adenosine monophosphate-activated protein kinase (AMPK)/ mammalian target of rapamycin (mTOR) signaling pathway is a key regulator of autophagy in stroke, we investigated its role in the context of iPSCNPC transplantation for ICH.

The potential anti-obesity, anti-inflammatory, and anti-oxidative stress properties of ark shell-derived LLRLTDL (Bu1) and GYALPCDCL (Bu2) peptides were comprehensively investigated. In bone marrow-derived mesenchymal stem cells (BMMSCs), both peptides demonstrated significant anti-adipogenic effects by downregulating key adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer-binding protein alpha (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP-1) and their downstream adipocyte-specific genes including adipocyte fatty acid-binding protein 2 (aP2), fatty acid synthase (FAS), and lipoprotein lipase (LPL). Mechanistically, Bu1 and Bu2 promoted lipolysis through the activation of AMP-activated protein kinase (AMPK) and hormone-sensitive lipase (HSL). These peptides also exhibited potent anti-oxidative stress activity by suppressing reactive oxygen species generation and activating the HO-1/Nrf2 signaling pathway, as confirmed through HO-1 siRNA silencing. In addition, Bu1 and Bu2 demonstrated robust anti-inflammatory effects by reducing pro-inflammatory cytokine production and inhibiting MAPK signaling pathways. These findings were corroborated in a high-fat diet (HFD)-induced mouse model, where oral administration of Bu1 and Bu2 resulted in significant reductions in body weight, weight gain, and adipose tissue accumulation, along with decreased expression of adipogenic transcription factors and genes while improving serum cholesterol levels, and exhibited anti-oxidative stress effects via HO-1/Nrf2 activation. Collectively, these results underline the potential of Bu1 and Bu2 as multi-target therapeutic agents against obesity and related metabolic disorders.

Myocardial ischemia/reperfusion (I/R) injury is an unsolved medical issue that is caused by additional injuries derived from reperfusion therapy for patients with acute myocardial infarction, one of the leading causes of morbidity and mortality in the world. Myocardial I/R injury causes unpredictable complications evoked by oxidative stress, endothelial dysfunction, dysregulated autophagy, apoptosis, and an imbalanced inflammatory response. Microvesicles (MVs) derived from adipose stem cells (ADSC) and egg-derived exosomes (EXOs) may confer antioxidant, anti-inflammatory, anti-apoptotic and tissue repair potential, showing potential in cardiovascular therapy. This study aims to investigate the therapeutic effects and mechanisms of MVs and EXOs on myocardial I/R injury.

Bone homeostasis is maintained through a dynamic balance between bone-forming osteoblasts and bone-resorbing osteoclasts. Osteoblasts originate from mesenchymal/skeletal stem cells through commitment, proliferation, and differentiation, which are controlled by sequential activation of signaling molecules and transcriptional regulators. Among them, runt-related transcription factor 2 (RUNX2) and Osterix serve as master transcription factors driving osteoblast commitment, differentiation, and maturation. Emerging evidence highlights that posttranslational modifications (PTMs), including phosphorylation, ubiquitination, and acetylation, play indispensable roles in regulating activity, stability, and interactions of these transcription factors. Through reversible chemical modifications, PTMs integrate extracellular cues with transcriptional programs, leading to fine-tuning osteoblast lineage specification and bone formation. This review summarizes recent advances in understanding how PTMs modulate RUNX2 and Osterix during osteoblast development. We cover mechanistic insights from both in vitro and in vivo studies and highlight potential therapeutic implications of targeting PTM-mediated regulatory pathways in skeletal disorders.

How the cellular state of senescence manifests in hematopoietic stem cells (HSCs) is currently poorly understood and likely orchestrated by a complex interplay of intrinsic and extrinsic factors, such as genetic instability, epigenetic reprograming, alterations in the stem cell niche and metabolic dysregulation. Accumulating senescence may contribute to the age-related functional decline of HSCs, which manifests as reduced self-renewal, impaired differentiation, altered hematopoietic regenerative potential, expansion of dysfunctional HSC clones, and increased susceptibility to hematological disorders. Recent work has advanced our understanding of the molecular hallmarks and signaling pathways that contribute to HSC senescence, nominating promising therapeutic targets to ameliorate age-associated hematopoietic dysfunction and malignancy. Here, we review the intrinsic and extrinsic factors that likely contribute to HSC senescence during homeostasis and pathological conditions. We further summarize senescence targeting strategies that may be leveraged to mitigate HSC senescence and restore hematopoietic function during aging or hematologic disease.

Hematopoietic stem cells (HSCs) maintain lifelong production of blood by balancing self-renewal and differentiation. However, certain aspects of their divisional dynamics, namely the role of quiescence and the intrinsic heterogeneity of the HSC pool, are not completely understood. High-resolution clonal tracking provides a powerful resource to investigate such dynamics as the data captures patterns of clonal persistence, dilution and late clonal emergence. Here, we apply mechanistic mathematical modeling to longitudinal clonal data from non-human primates to explore structural requirements that underlie the observed dynamical patterns. We show that models treating HSCs as a single, homogeneous population can explain the gradual loss of clonal diversity, but fail to reproduce clone size distributions and the long-term persistence of small and late-appearing clones. To address this, we propose a stochastic, two-compartment model in which HSCs transition reversibly between an actively cycling state and a quiescent, potentially niche-bound state. Compared to the simpler one-compartment model, this advanced framework provides a substantially improved fit for different metrics, consistently captures clone size distributions and explains the delayed activation and sustained coexistence of small and large clones. These results provide quantitative evidence that heterogeneity within the HSC pool, particularly the existence of a reversible quiescent state, is critical to account for clonal aspects of long-term hematopoiesis. Our findings highlight how clonal data can uncover underlying regulatory mechanisms and supports a central role for niche-mediated HSC quiescence in maintaining stable and diverse blood production over time.

This study aimed to produce a high-quality mesenchymal stem cell-derived secretome (MSC-sec) using a three-dimensional culture system to enhance its therapeutic potential for skin wounds. Human umbilical cord-derived MSCs were cultured on optimally modified gelatin sponge (GS) scaffolds (ethanol-plus-polylysine), which maintained high cell viability. The secretome from these GS-cultured MSCs (GS-MSC-sec) contained significantly higher concentrations of key growth factors (KGF, VEGF, PDGF) compared to conventional 2D culture. In vitro, GS-MSC-sec enhanced fibroblast proliferation, migration, and angiogenesis. In a rat full-thickness skin wound model, concentrated GS-MSC-Section (5 ×) not only accelerated wound healing but also promoted wound-induced hair neogenesis. This enhanced regeneration was associated with upregulation of Wnt/β-catenin and TLR3/STAT3 signaling and downregulation of BMP/Smad signaling. These findings demonstrate that GS-MSC-sec possesses significant therapeutic potential for promoting skin wound healing and regeneration, with implications for treating alopecia.

To investigate the key research hotspots and trends related to exosomes in premature ovarian insufficiency (POI) using bibliometric visualization analysis, and to provide a data-driven framework for future scientific and clinical development.

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, characterized by poor prognosis, high intratumoral heterogeneity, and pronounced therapy resistance, primarily driven by glioma stem cells (GSCs). SUMOylation, a reversible post-translational modification, has emerged as a critical regulator of GBM progression and therapeutic response. By modifying transcription factors, SUMOylation enhances oncogenic transcriptional programs, contributing to chemoresistance and retinoid resistance. RNA-binding proteins are also affected, influencing exosomal microRNA sorting, invasion, and vasculogenic mimicry. Additionally, SUMOylation of metabolic and cell cycle regulators supports glycolysis, proliferation, and GSC maintenance, highlighting its role in metabolic rewiring. Dysregulation of tumor suppressors through small ubiquitin-like modifier (SUMO)-mediated mechanisms, such as SENP1-dependent deSUMOylation of HIF-1α and β-catenin, promotes stemness and immune evasion. SUMOylation further intersects with angiogenesis, immune regulation, and epigenetic modifiers, including histone deacetylases and zeste homolog 2, shaping tumor plasticity and therapy resistance. Preclinical studies indicate that pharmacological inhibition of SUMOylation with agents like TAK-981, topotecan, or Paromomycin reduces tumor growth, reverses therapy resistance, and enhances radiosensitivity. Moreover, SUMO-related enzymes, such as UBA2, SENP1, and SUMO2/3, may serve as prognostic biomarkers. Understanding SUMOylation in GBM offers insights into tumor biology and identifies potential therapeutic targets to improve patient outcomes.

The interfacial mechanisms governing stem cell adhesion on wettability-patterned microstructures remain insufficiently understood, particularly regarding how initial fluid dynamics dictate subsequent protein distribution and cellular organization. Herein, we fabricate three distinct laser-textured surface architectures on Ti6Al4V─periodic microgrooves, microdimple arrays, and disordered porous structures─and investigate their physicochemical properties, protein adsorption behavior, and mesenchymal stem cell responses. Surface characterization reveals that laser texturing induces complete surface oxidation and generates pronounced time-dependent, anisotropic wettability, driven by capillary infiltration and plastron destabilization. Notably, cell adhesion exhibits strong topographical dependency: on deep microgrooves (depth > 20 μm), mesenchymal stem cells predominantly anchor at groove-ridge junctions rather than spreading within grooves, displaying either "spanning" or "guided" cytoskeletal architectures. Protein adsorption experiments demonstrate a consistent "high-seeking, low-avoiding" distribution pattern, where fetal bovine serum preferentially enriches on ridges and planar regions while being virtually excluded from pits and porous interiors. Using phase-field simulations of droplet dynamics on topology-mimetic models, we reveal that hydrophilic ridges generate moderate, positive interfacial pressure, serving as fluid-anchoring points, whereas grooves produce repulsive, high-pressure zones. This interfacial pressure gradient provides a physical rationale for the spatially selective fluid retention that precedes and likely directs protein patterning and subsequent cell adhesion.

Idiopathic nephrotic syndrome is the most common glomerulopathy in children, and minimal change disease (MCD) is the most common histological pattern. First-line treatment involves glucocorticosteroids, but frequent relapses and steroid dependence may lead to steroid-related complications. Rituximab (RTX) is recommended in cases of lack of response or treatment side effects, reducing relapse rates and limiting the need for other medications. The mechanism of RTX involves B-cell depletion through various cytotoxic mechanisms. Its efficacy in nephrotic syndrome (NS) may stem from its influence on cytokines produced by B cells and a further effect on the podocyte cytoskeleton has been postulated. The present case describes a 19-year-old male with NS resulting from MCD, with a frequently relapsing, steroid-dependent, multidrug-resistant disease. He experienced a hypersensitivity reaction to RTX after the third dose, which contraindicated therapy continuation with traditional infusion. Due to the limited therapeutic options, a 12-step RTX desensitization protocol was adopted, allowing for safe administration of subsequent doses, achievement of remission, and gradual discontinuation of glucocorticosteroids.

Osteoarthritis is fundamentally a whole-joint disease, and a critical pathological feature is the limited capacity of articular cartilage for self-regeneration, leading to accelerated joint degeneration once breakdown begins. Current therapeutic strategies are primarily palliative, and conventional marrow stimulation procedures such as microfracture often yield suboptimal, short-lived outcomes. Stem cell-based biologic augmentation using mesenchymal stem cells has emerged as a promising approach through direct chondrocyte differentiation, paracrine stimulation, and immunomodulation. Umbilical cord-derived mesenchymal stem cells offer robust proliferative capacity, enhanced biological potency, and lower immunogenicity than adult mesenchymal stem cells, and can be obtained with minimal ethical concerns. Clinical trials of human umbilical cord blood-derived mesenchymal stem cells combined with hyaluronic acid hydrogel (CARTISTEM®) have demonstrated excellent safety, improved patient-reported outcomes, and durable hyaline-like cartilage regeneration. Emerging evidence further suggests that combining high tibial osteotomy with human umbilical cord blood-derived mesenchymal stem cells-based cartilage regeneration for medial compartment osteoarthritis with varus malalignment creates a synergistic biological and mechanical environment that promotes structural cartilage repair. In conclusion, surgically transplanted human umbilical cord blood-derived mesenchymal stem cells show therapeutic potential in arthritic knees, although the role of intra-articular injections and the optimal indications for combined high tibial osteotomy remain to be clarified.